Hormone Testing

Hormone Testing, General Health & Wellness

The combination of the serum T4and T3uptake (THBR) as an indirect assessment of TBG, helps to determine whether an abnormal T4value is due to alterations in serum thyroxine-binding globulin or to changes of thyroid hormone levels. Deviations of both tests in the same direction usually indicate that an abnormal T4is due to abnormalities in thyroid hormone. Deviations of the two tests in opposite directions provide evidence that an abnormal T4may relate to alterations in TBG.Causes of increased TBG bindinginclude neonatal state, molar and conventional pregnancy, estrogens, oral contraceptives, heroin, methadone, 5-fluorouracil, clofibrate, infectious hepatitis, chronic active hepatitis, and primary biliary cirrhosis, acute intermittent porphyria, lymphoma, and hereditary TBG increase.Amphetamines, iopanoic acid, ipodate, and amiodarone increase thyroxine.5,6High dose propranolol may elevate T4and FTI levels.7Causes of decreased TBG bindinginclude abnormal protein states especially nephrotic syndrome, androgens, anabolic steroids, prednisone, acromegaly, liver or other systemic illness, severe stress or hereditary TBG deficiency. Salicylates and diphenylhydantoin may lower T4significantly. Amiodarone may cause increased thyroxine levels and can cause hypothyroidism or hyperthyroidism.Lithium carbonate may cause goiter with or without hypothyroidism.Carbamazepine (Tegretol®) is reported to cause decreased values in thyroid function tests.

Hormone Testing, General Health & Wellness

The consequences of subclinical thyroid disease (serum TSH 0.1−0.45 μIU/mL or 4.5−10.0 μIU/mL) are minimal and current guidelines recommend against routine treatment of patients with TSH levels in these ranges, but thyroid function tests should be repeated at 6- to 12-month intervals to monitor TSH levels;8however, treatment of subclinical hypothyroidism is indicated in patients with TSH levels >10.0 μIU/mL or in patients with TSH levels <10.0 μIU/mL in conjunction with goiter or positive for antithyroid peroxidase antibodies (or both).9In patients who are receiving replacement therapy, the dose should be adjusted so serum TSH values range from 0.3−3.0 μIU/mL. An exception is thyroid hormone replacement treatment after thyroidectomy for differentiated thyroid cancer, in which case, a mildly to moderately suppressed TSH level is generally desirable.10It is reasonable to consider serum TSH measurement for pregnant women or women planning to become pregnant with a family history of thyroid disease, prior thyroid dysfunction, symptoms or physical findings suggestive of hypo- or hyperthyroidism, an abnormal thyroid gland on examination, type 1 diabetes mellitus, or a personal history of autoimmune disorder.11Suggested upper limit for the TSH reference range for pregnant women and preconception is: first trimester − <2.5 μIU/mL, and 3.0 μIU/mL in the second and third trimesters.10Unsuspected increase in the level of serum TSH is not uncommon in elderly subjects. A study by Sawin et al found that 22 of 344 (5.9%) healthy persons older than age 60 had a TSH level >10 μIU/mL; 10 of the 22 had low T4and FT4index. Elderly hypothyroid individuals may have minimal recognizable clinical symptoms of thyroid deficiency.11TSH is the single most sensitive test for primary hypothyroidism. If there is clear evidence for hypothyroidism and the TSH is not elevated, hypopituitarism should be considered (secondary hypothyroidism).TSH levels have been elevated or inappropriately detectable for high thyroid hormone levels in some patients with thyrotropin-secreting pituitary adenomas. Delay in diagnosis of these tumors may lead to visual compromise. The effects of such neoplasms can be misdiagnosed as those of primary hyperthyroidism.Until the late 1980s, TSH assays were not sufficiently sensitive to distinguish hyperthyroidism from euthyroid (normal) subjects. The new generation of ultrasensitive TSH immunoassays have provided a far more effective diagnostic separation of thyrotoxicosis from euthyroidism.This assay has a sensitivity of 0.004 μIU/mL and meets all criteria as a third-generation TSH assay.

Hormone Testing, General Health & Wellness

Offered as part of multiple lab tests

Hormone Testing, General Health & Wellness

Triiodothyronine (T3) normally represents only approximately 5% of the thyroid hormone and like thyroxine is almost entirely bound to the carrier proteins, with only 0.25% of the total being in the free state. Measurement of free triiodothyronine is of value in confirming the diagnosis of hyperthyroidism, when an elevated free or total thyroxine level is found. Abnormal total and free triiodothyronine concentrations may appear in T3toxicosis, in the presence of normal thyroxine levels. Free T3levels are unaffected by carrier protein variation.

Hormone Testing, General Health & Wellness

Offered as part of multiple lab tests

Hormone Testing, General Health & Wellness

Increased T3often occurs in hyperthyroidism, but in approximately 5% of cases only T3is elevated, “T3toxicosis.” Do not confuse T3with T3uptake; these are two different tests. The latter is done very commonly as part of the usual thyroid profile. Less than 1% of T3is unbound.

Autoimmune & Inflammation, Hormone Testing

Thyroglobulin antibody (TgAb) measurement is typically used in two clinical scenarios, in the assessment of autoimmunity and in the follow-up of patients treated for differentiated thyroid carcinoma (DTC).1-8In thyroid autoimmunity, TgAb level can be increased. However, the presence of TgAb is not always pathogenic nor diagnostic, especially at very low levels. Because changes in TgAb levels can reflect changes in thyroid tissue mass, TgAb concentrations can also serve as a surrogate tumor marker for DTC recurrence and for monitoring changes in tumor mass in certain patients.1A rising, or de novo appearance of TgAb may indicate recurrence, whereas a progressive decline suggests successful treatment.3When present, TgAb interferes with thyroglobulin (Tg) measurement, causing falsely low or undetectable Tg immunometric assay values that can mask disease. Guidelines mandate that every Tg test have TgAb measured simultaneously and quantitatively by immunoassay. The propensity and magnitude of TgAb-Tg interference relates to both Tg and TgAb concentrations and the class of Tg method used.The United States NHANES III survey reported a TgAb prevalence of approximately 10% for the general population, measured by competitive immunoassay.1This study reported that 3% of subjects with no risk factors for thyroid disease had detectable TgAb without associated presence of thyroid peroxidase (TPO) antibodies.1TgAb prevalence has been shown to be approximately twofold higher than normal for patients diagnosed with disseminated thyroid carcinoma (~20%).2,3It has been suggested that low levels may represent "natural" antibody in healthy individuals or, alternatively, may represent underlying silent autoimmune thyroid disease.4There is some debate over the clinical utility of serum TgAb measurement for assessing the presence of thyroid autoimmunity in areas of iodide sufficiency.4,5In iodide-deficient areas, however, TgAb is believed to be useful for detecting autoimmune thyroid disease, especially for patients with a nodular goiter. TgAb measurements are also useful for monitoring iodide therapy for endemic goiter, since iodinated Tg molecules are more immunogenic. Sera samples were obtained in the United States for males <30 years of age following the criteria outlined by the National Academy of Clinical Biochemists (NACB) for establishing a normal reference range for thyroid tests.6,7The screening criteria included serum TSH levels between 0.5 and 2.0 mIU/L, no personal or family history of thyroid disease, and absence of nonthyroid autoimmune disease. One hundred thirty-seven screened samples were tested, generating a 95% nonparametric upper reference limit below 4 IU/mL. Additionally, 519 samples were collected in the United States for both males and females ranging from 18 to 74 years of age. The screening criteria included serum TSH levels between 0.5 and 2.0 mIU/L, no personal or family history of thyroid disease, and absence of nonthyroid autoimmune disease. Of the 519 samples tested, 96% fell below 4 IU/mL.Labcorp reports TgAb results above the limit of detection as elevated. The decision to employ this threshold is based on the fact that the presence of TgAb above the limit of detection is suggestive of the presence of thyroid tissue and can be a negative prognostic in patients treated for DTC. Also, the presence of any level of TgAb in cases where Tg testing is ordered causes the lab to employ an alternate method for that measurement; one that is not confounded by TgAb.

Diabetes & Blood Sugar, Hormone Testing

Insulin is a peptide hormone with a molecular weight of approximately 6000 daltons. Serum insulin determinations may be performed on patients with symptoms of hypoglycemia4,5where insulinoma is a possible etiology. Patterns of secretion by insulinomas may be sporadic or constant. Insulinoma is a rare functional tumor of pancreatic origin that secretes insulin inappropriately, causing hypoglycemia. Whipple originally described the tumor and classic diagnostic criteria called "Whipple's Triad". The criteria included:1) neurologic symptoms of hypoglycemia2) low glucose (<50 mg/dL) which are corrected immediately by giving glucose or carbohydrate.Today, as described above, we would add inappropriately elevated insulin levels during an episode of hypoglycemia. Usually hypoglycemia is induced with a fast or exercise, and the diagnostic criteria may include a 48 to 72 hour fast with insulin levels greater than 5 μU/mL during a hypoglycemic episode.4Hypoglycemia can, however, also be facilitated intentionally or unintentionally (factitious hypoglycemia),4,5C-peptide levels along with insulin levels may be helpful in ruling out factitious insulin use, however note the limited reactivity of various insulin analogs. Accordingly, one use of the insulin test is to screen patients with low glucose for insulinoma if other factors such as glucose-lowering drugs or reactive hypoglycemia are excluded.Insulin levels can be also useful in predicting susceptibility to the development of type II diabetes.4However, the American Diabetes Association recommendations for the diagnosis of diabetes do not include the measurement of insulin levels.6Insulin levels may also be measured to estimate the patient's capacity for insulin secretion (eg, glucagon test) or in the evaluation of insulin sensitivity (eg, oral glucose tolerance test). Although the adequacy of pancreatic insulin synthesis is frequently assessed via the determination of C-peptide, fasting insulin is also measured to assess insulin resistance.In treated patients therapeutic administration of insulin can lead to the formation of insulin binding antibodies. Insulin binding antibodies invariably interfere with insulin measurement methods and results are unreliable. For patients with known autoantibodies to insulin should measure free and total insulin to assess biologically active fraction of insulin (free insulin) and total insulin. Measurements of free and total insulin, C-peptide, insulin antibodies and hemoglobin A1C are often tested in conjunction to clarify the contribution of endogenous and exogenous insulin to overall diabetic management. See Test501561for Free and Total Insulin.

Hormone Testing, Women's Health

Levels rise during pregnancy and are elevated during lactation, in postpartum subjects, and following bilateral oophorectomy. Destructive pituitary diseases cause low levels. Hypothalamic lesions may be associated with increased values. Many pituitary tumors which previously were called chromophobe adenomas are now recognizable as prolactinomas.Patients with hyperprolactinemia may have the multiple endocrine neoplasia syndrome, MEN-1.6Provocative tests used in work-up of hyperprolactinemia include metyrapone stimulation of ACTH-2 and TRH provocative test.7Antipsychotic drugs may elevate serum prolactin. Antipsychotics block dopamine, thereby elevating serum prolactin levels. Hyperprolactinemia is present in many patients receiving neuroleptics with an occasional patient developing amenorrhea, galactorrhea, and/or decreased libido. Amoxapine, a dibenzoxazepine type of tricyclic with antidepressant and antipsychotic characteristics, has been found to cause galactorrhea and oligomenorrhea with hyperprolactinemia. Amoxapine may have a dopamine blocking action.8The prolactin level may rise significantly but only briefly. Point prolactin level determinations during therapy may be within normal range while total integrated 24-hour secretion is significantly increased. It has been recommended that patients who develop amenorrhea and/or galactorrhea during neuroleptic therapy should be observed regularly for possible emergence of a pituitary tumor.Persistent elevations of plasma prolactin levels may be observed with, and after withdrawal from, chronic cocaine abuse, and may reflect a cocaine-induced derangement in the neural dopaminergic regulatory systems.9

Hormone Testing, Men's Health

This immunoassay is intended for the in vitro quantitative determination of testosterone in human serum and plasma.Testosterone is the principal androgen in men.3,4The production of testosterone by the male testes isstimulatedby luteinizing hormone (LH), which is produced by the pituitary. LH secretion is, in turn, inhibited through a negative feedback loop by increased concentrations of testosterone and its metabolites. Most of the testosterone in males is produced by the Leydig cells of the testes and is secreted into the seminiferous tubule, where it is complexed to a protein made by the Sertoli cells. This results in the high local levels of testosterone that are required for normal sperm production.Diminished testosterone production is one of many potential causes of infertility in males.4,5Low testosterone concentrations can be caused by testicular failure (primary hypogonadism) or inadequate stimulation by pituitary gonadotropins (secondary hypogonadism). Since men with hypogonadism often have high SHBG levels, the measurement of free or bioavailable testosterone has been advocated when total testosterone levels are normal in men with symptoms of androgen deficiency.6Significant physiological changes occur in men as they age, in part due to a gradual decline in testosterone levels.7,8It is generally accepted that the principal cause of this age-related decrease in testosterone production is testicular failure, although diminished gonadotropin production may play a role.6By 75 years of age, the average male testosterone drops to 65% of average level in young adults. “Andropause” is a term that has been used to refer to the constellation of symptoms associated with the age-related decline in testosterone production in men.6,9The adult male reference range for testosterone was established by Travison and coworkers through an epidemiologic study that included men from different geographic regions of the United States and Europe.2Testosterone measurment was harmonized to the Center for Disease Control reference method.2The reference population included only men younger than 40 years of age who had a BMI less than 30. Much smaller amounts of testosterone and dihydrotestosterone are produced in women than in men.3,4Weaker adrenal androgens and ovarian precursor molecules including androstenedione, DHEA, and DHEA sulfate can have significant androgenic effects in women. The ovary and adrenal glands produce some testosterone, but the majority of the testosterone in women is derived from the peripheral conversion of other steroids. Often, the first sign of testosterone excess in women is the development of male pattern hair growth, which is referred to as hirsutism.1,4,5,10It should be noted that some women experience hair growth similar to that caused by increased testosterone due to racial or genetic causes and not due to excessive androgens. Measurement of the testosterone may help to distinguish racial or genetic causes of hirsutism from the abnormal pathology, particularly in women with mixed ethnic backgrounds. Women with more excessive testosterone levels may also experience virilization, with symptoms including increased muscle mass, redistribution of body fat, enlargement of the clitoris, deepening of the voice, and acne and increased perspiration. These women can also suffer from androgenic alopecia, the female equivalent of male pattern baldness.Many women with slowly progressive androgenic symptoms are diagnosed as having polycystic ovary syndrome (PCOS).10-12PCOS is relatively common, affecting approximately 6% of women of reproductive age.7Women with this complex syndrome experience symptoms of androgen excess associated with menstrual abnormalities and infertility. Most women with the syndrome have polycystic ovaries that can be detected by ultrasonography, although this finding is not essential for diagnosis.4,5,13Chronic anovulation experienced by patients with PCOS increases their risk of developing endometrial cancer. Women with PCOS are often overweight and are likely to suffer from insulin resistance putting them at increased risk for developing type 2 diabetes mellitus.3,11Obesity and insulin resistance can result in acanthosis nigricans, a skin condition that is characterized by hyperpigmented, velvety plaques of body folds.3Lipid abnormalities, including decreased high-density lipoprotein cholesterol levels and elevated triglyceride levels as well as impaired fibrinolysis, are seen in women with PCOS.11Cardiovascular disease is more prevalent, and women with PCOS have a significantly increased risk for myocardial infarction.11

Stress & Fatigue, Hormone Testing

Cortisol (hydrocortisone) is the most prominent glucocorticosteroid, and it is essential for the maintenance of several body functions. Like other glucocorticosteroids, cortisol is synthesized from the common precursor cholesterol in the zona fasciculata of the cortex of the adrenal gland. For the transport of cortisol in blood, about 90% of cortisol is bound to corticosteroid-binding globulin (CBG) and to albumin. Only a small amount of cortisol circulates unbound in blood and is free to interact with its receptors.3The most important physiological effects of cortisol are the increase of blood glucose levels (enhancement of gluconeogenesis, catabolic action) and its anti-inflammatory and immunosuppressive action.3Synthesis and secretion of cortisol by the adrenal gland are controlled by a negative feedback mechanism within the hypothalamus-pituitary-adrenal cortex-axis. If the cortisol level is low, corticotropin-releasing hormone (CRH) is secreted by the hypothalamus, which causes the pituitary to release adrenocorticotropic hormone (ACTH). This stimulates the synthesis and secretion of cortisol by the adrenal gland. Cortisol itself acts in a negative feedback mechanism on the pituitary gland and the hypothalamus. In addition, stress is followed by increased cortisol secretion.3Serum cortisol concentrations normally show a diurnal variation.3Maximum concentrations are usually reached early in the morning and then concentrations decline throughout the day to an evening level that is about half of the morning concentration; therefore, for interpretation of results, it is important to know the collection time of the serum sample.The cortisol status of a patient is used to diagnose the function or malfunction of the adrenal gland, the pituitary, and the hypothalamus.4,5Thereby, cortisol serum concentrations are used for monitoring several diseases with an overproduction (eg, Cushing syndrome)6,7or underproduction (eg, Addison disease) of cortisol and for monitoring several therapeutic approaches (eg, dexamethasone suppression therapy in Cushing syndrome and hormone replacement therapy in Addison disease).

Women's Health, Hormone Testing

Estradiol is responsible for the regulation of the estrous and menstrual female reproductive cycles and for the development and maintenance of female secondary sex characteristics.3,4Estradiol plays a key role in germ cell maturation and numerous other, non−gender-specific processes, including growth, bone metabolism, nervous system maturation, and endothelial responsiveness. Estrogens are crucial for the normal development and maintenance of the breasts and the uterus.5However, excessive estrogen levels can promote cell proliferation and may increase the risk of developing breast and uterine cancer as well as uterine endometriosis.5The three major naturally occurring estrogens in women are estrone (E1), estradiol (E2), and estriol (E3). E2 is the predominant estrogen during reproductive years, both in terms of absolute serum levels as well as in terms of estrogenic activity.3During menopause, a dramatic drop in E2 production leaves estrone as the predominant circulating estrogen. Estriol is the main pregnancy estrogen, but it does not play a significant role in nonpregnant women or men.3The concentration of E2 in men is much lower than in women of reproductive age. All estrogens are synthesized from androgen precursors by the enzyme aromatase.3,5Aromatase converts the androgenic substrates androstenedione, testosterone, and 16-hydroxytestosterone to the corresponding estrogens: estrone, estradiol, and estriol.5E2 is produced primarily in ovaries and testes by aromatization of testosterone.3A lesser amount of E2 is produced in the adrenal glands and some peripheral sites, most notably adipose tissue. Most of the circulating estrone is derived from peripheral aromatization of androstenedione (mainly in the adrenal gland). E2 and E1 can be converted to each other, and both are inactivated via hydroxylation and conjugation. E2 demonstrates two to five times the biological potency of E1.3The importance of E2 testing and the need for reliable and accurate estradiol measurements throughout the analytic range are emphasized in several recent publications.6-8LabCorp offers a sensitive estradiol by LC/MS(140244). Measurement of serum E2 serves an integral role in the assessment of reproductive function in females and in the assessment of infertility, oligomenorrhea, and menopausal status. E2 is commonly measured for monitoring ovulation induction, as well as during preparation for in vitro fertilization. Because of the relatively high serum concentrations of E2 in these patients, readily available automated immunoassay methods with modest sensitivity meet the clinical requirements.Adult female.In premenopausal women, E2 levels, along with luteinizing hormone (LH) and follicle-stimulating hormone (FSH) levels, delineate the stage of the menstrual cycle.3E2 levels are lowest during the early follicular phase and rise gradually. Two to three days before ovulation, estradiol levels start to increase much more rapidly to a peak just before ovulation. This dramatic increase in circulating E2 levels induces a surge in LH and FSH. E2 levels decline modestly during the ovulatory phase and then increase again gradually until the midpoint of the luteal phase and ultimately decline back to early follicular levels.Assessment of E2 levels is useful for the evaluation of hypogonadism and oligomenorrhea in women. Decreased ovarian estrogen production is classified as hypergonadotropic or hypogonadotropic, depending on whether the disease is of gonadal or pituitary/hypothalamic origin.9-11Measurement of gonadotropins (LH and FSH) is fundamental in differentiating these two low estradiol states. The main causes of primary gonadal failure (hypergonadotropic) are genetic (Turner syndrome, familial premature ovarian failure), autoimmune (autoimmune ovarian failure, autoimmune polyglandular endocrine failure syndrome type II), and toxic (related to chemotherapy or radiation therapy for malignant disease).Low E2 with low or inappropriately "normal" LH and/or FSH in young adult females is consistent with hypogonadotrophic hypogonadism.11-13This can be caused by hypothalamic or pituitary failure due to conditions including multiple pituitary hormone deficiency and Kallmann syndrome. Diagnostic workup includes the measurement of E2, along with pituitary gonadotropins and prolactin and, possibly, imaging. This endocrine presentation can be caused by starvation, overexercise, severe physical or emotional stress, and drug/alcohol abuse. While early studies suggested that E2 levels could be used to predict ovarian reserve in women of reproductive age undergoing assisted reproduction procedures, more recent studies have found the marker less useful.14Estradiol measurement is useful in assessing the status of ovulation induction in women with hypogonadotropic hypogonadism,15and for the prediction and prevention of ovarian hyperstimulation syndrome in patients undergoing assisted reproduction.16Normal or high E2 with irregular or absent menstrual periods is suggestive of possible polycystic ovarian syndrome, androgen producing tumors, or estrogen producing tumors. In these cases, measurement of total and bioavailable androstenedione, dehydroepiandrosterone (sulfate), and sex hormone-binding globulin can aid in differential diagnosis.The main site of estrogen biosynthesis in the nonpregnant premenopausal woman is the ovarian granulosa cells; however, the adipose tissue becomes a major source of circulating estradiol in postmenopausal women.3After menopause, androstenedione, secreted by the adrenal gland, is converted into estrone in the adipose tissue.3The conversion of plasma androstenedione to estrone increases with excess body weight in both pre- and postmenopausal women.3Estrone is then eventually converted to estradiol by 17-β-hydroxysteroid dehydrogenase enzymes present in peripheral tissues.3Measurement of E2 level, together with FSH and/or anti-Müllerian hormone (AMH) can be useful in predicting the timing of the transition into menopause.17,18A large population study (Randolph) found that the mean E2 level started to decline approximately two years prior to the final menstrual period (FMP) and exhibited a maximal rate of change at the FMP. The mean E2 level stabilized a menopausal level approximately two years after FMP.17A sensitive estradiol assay is required to measure E2 levels accurately in postmenopausal women. The current recommendations for postmenopausal female hormone replacement are to administer therapy in the smallest beneficial doses for as briefly as possible. Estrogen replacement in reproductive-age women should aim to mimic natural estrogen levels as closely as possible, while levels in menopausal women should be held near the lower limit of the premenopausal female reference range. Postmenopausal women with lower E2 levels are at increased risk of osteoporotic fractures, while higher estradiol levels are associated with increased risk of malignancy and cardiovascular disease.19,20Accurate measurement of E2 in women receiving hormone replacement may play a role in optimizing therapy.Gonadotropin receptor hormone (GNRH) analogues are used therapeutically to reduce the ovarian production of estradiol in sex hormone-dependent disorders, including endometriosis and uterine fibroids.21Aromatase inhibitors are also used therapeutically to reduce circulating estrogens (E2 and E1) levels in hyperestrogenic conditions (ie, endometriosis in women and gynecomastia in men) and in estrogen-sensitive malignancies.22-26The complete or near complete suppression of estradiol production induced by these treatments produces low serum levels that can only be accurately measured by sensitive methods.27SeeEstradiol, Sensitive (LC/MS) [140244].Adult male.The use of a sensitive, LC/MS assay for serum E2 measurement in males is preferred over direct immunoassays because of its greater sensitivity and lesser interference by other steroids.28See LabCorp testEstradiol, Sensitive (LC/MS) [140244]. In males, estradiol is present at low concentrations in blood, but it is extraordinarily high in semen.3Estradiol plays an important role in epididymal function and sperm maturation and is essential for normal spermatogenesis and sperm motility.3Gynecomastia refers to a syndrome of abnormal feminization with swelling of the breast tissue in boys or men, caused by an imbalance of the hormones estrogen and testosterone.29Gynecomastia is common during puberty in boys and can be seen in older males due to increased estrogen levels related to obesity (increased aromatase activity), decreased hepatic clearance, estrogen ingestion, and estrogen-producing tumors. Asymptomatic gynecomastia is common in older men, but individuals who present with gynecomastia of recent onset (associated with pain and tenderness) may require clinical workup.29Gynecomastia and other signs of male feminization may be caused by an absolute increase in E2 and/or E1. The testes may directly secrete too much estradiol due to a Leydig-cell or Sertoli-cell tumor. They may also secrete estradiol indirectly through the stimulatory effect of a human chorionic gonadotropin-secreting tumor of gonadal or extragonadal germ-cell origin.29Alternatively, men with normal estrogen levels can develop gynecomastia, if testosterone levels are low due to primary/secondary testicular failure, resulting in an abnormally elevated estrogen:androgen ratio. Feminization may also occur in men treated with antiandrogen therapy or drugs with antiandrogenic effects (eg, spironolactone, digitalis). Conversely, individuals with elevated androgen levels will often exhibit gynecomastia caused by aromatase-catalyzed estrogen production.Estrogens (and androgens) play an important role in the normal physiology of the skeleton in both sexes.3Males with diminished estrogen levels (due to congenital aromatase deficiency) or insensitivity to estrogens (due to estrogen receptor deficiency) have a characteristic phenotype with regard to bone development.3,25These males exhibit significant increased overall height due to lack of estrogen-induced epiphyseal closure.25The importance of estradiol in bone health is further supported by the fact that estradiol levels correlate better with bone mineral density than do testosterone levels in aging men.25The Endocrine Society has recently reported that low estradiol levels are associated with increased fracture risk and accelerated bone loss in older men.30Children and adolescents.A sensitive method is required to measure accurately the E2 concentrations found in boys and prepubertal girls. See LabCorp testEstradiol, Sensitive (LC/MS) [140244]. Levels in boys and heavier girls are generally lower than in girls of normal weight.31,32Adrenal steroids tend to increase prior to gonadal steroids at the beginning of the pubertal transition.31In girls, E2 concentrations increase just before breast development.31In precocious puberty (PP), estradiol and the gonadotropins, LH and FSH, tend to be above the prepubertal range.33E2 measurement in children suspected of having PP is performed to support the diagnosis and to determine the origin of the condition or disease. The source of increased estradiol can be exogenous estrogens or an ovarian cyst that has produced transient estrogens. Elevation of E1 or E2 alone suggests pseudoprecocious puberty, possibly due to a steroid-producing tumor.It is not normal for an adolescent to be amenorrheic for greater than three months, even in the early gynecologic years,34and menstrual cycle duration persistently outside 21 to 45 days in adolescents is unusual.35Since estrogen deficiency is a risk factor for later development of osteoporosis and cardiovascular disease, a workup including sensitive E2 measurement is recommended for adolescent girls and women with potentially disordered hypothalamic-pituitary-gonadal function.11,34Persistently low estrogens and elevated gonadotropins in children with delayed puberty suggest primary ovarian failure, while low gonadotropins suggest hypogonadotrophic hypogonadism. In this latter case, Kallmann syndrome (or related disorders) or hypothalamic/pituitary tumors should be excluded in well-nourished children.36Both E2 and E1 levels are very low or undetectable in children with aromatase deficiency.35Affected girls have hypergonadotropic hypogonadism, fail to develop secondary sexual characteristics, and exhibit progressive virilization.35The affected boys exhibit normal male sexual differentiation and pubertal maturation. However, boys with aromatase deficiency are typically extremely tall with eunuchoid proportions and continued linear growth into adulthood, severely delayed epiphyseal closure, and osteoporosis due to estrogen deficiency. Highly sensitive E2 measurement can be of value in the assessment of therapeutic efficacy of estrogen replacement in hypogonadal girls.32

Hormone Testing, General Health & Wellness

Offered as part of multiple lab tests

Hormone Testing, General Health & Wellness

Offered as part of multiple lab tests

Hormone Testing

Congenital adrenal hyperplasia (CAH), is an autosomal recessive disorder affecting one of the enzymes required to synthesize cortisol from cholesterol in the adrenal gland.1-4Diminished production of cortisol leads to increased pituitary secretion of ACTH via the negative feedback mechanism, which in turn causes hyperplasia of the adrenal cortex. Excess production of hormones proximal to the enzymatic defect gives rise to various clinical phenotypes. The clinical symptoms of CAH directly result from either the deficiencies in mineralocorticoid or glucocorticoid production or from the overproduction of precursors that are converted to androgens.1-4There is a wide spectrum of clinical presentations, including a severely affected, "salt-wasting" form, a simple virilizing form with normal aldosterone production, and a mild "nonclassic" form that may be asymptomatic or may be associated with symptoms that may not be discovered until adulthood.1-5The incidence of classic CAH ranges from 1:10,000 to 1:20,000 births1but is more prevalent in some ethnic groups, particularly in remote geographic regions. The most common form of CAH occurs as the result of mutations in theCYP21A2gene, which results in 21-hydroxylase deficiency (21-OHD).1This enzyme converts 17-hydroxyprogesterone (17-OHP) to 11-deoxycortisol and progesterone to deoxycorticosterone, respective precursors for cortisol and aldosterone. In Caucasians, 21-OHD accounts for more than 90% of all cases, whereas 5% are caused by 11-hydroxylase deficiency and other enzyme deficiencies and clinical phenotypes are less common.1,4In 21-OHD, reduced production of glucocorticoids can lead to adrenal crises with hypoglycemia and hypotension in the setting of an illness or physiological stress.2Approximately 75% of classic CAH cases also suffer aldosterone deficiency with clinical symptoms that can include poor feeding and failure to thrive, vomiting, hyperkalemia, hyponatremia, dehydration, metabolic acidosis, and apathy.1-4The excess 17-OHP and other unblocked precursors, pregnenolone and progesterone, are diverted in the adrenals to the production of dehydroepiandrosterone and androstenedione, which are then peripherally converted to testosterone.1,2A key manifestation of this androgen overproduction is in utero virilization resulting in genital ambiguity in newborn females.1-4In fact, 21-OHD is the most common cause of ambiguous genitalia in females.8Males with 21-OHD appear normal at birth so the age at diagnosis in untreated boys varies according to the severity of disease.1-4If unrecognized and left untreated, both girls and boys undergo rapid postnatal growth and sexual precocity as well as premature maturation of the growth plates, ultimately resulting in reduced final height.1-4Neonatal screening and diagnosis of CAH is typically accomplished through the measurement of 17-OHP by immunoassay from filter paper (Guthrie) cards with subsequent confirmation in serum by liquid chromatography/tandem mass spectrometry (LC/MS-MS).5In order to reduce the potential of false-negative results, the cutoff levels of neonatal 17-OHP screening assays are typically set so that approximately 1% of all tests are reported as positive. Given the low prevalence of CAH, only approximately one in every 100 neonates with a positive screening test will have CAH as confirmed by LC/MS-MS.1-5Standard medical treatment of CAH consists of oral glucocorticoid and mineralocorticoid administration in order to suppress adrenal androgens and to compensate for adrenal steroid deficiencies.1-5Levels of 17-OHP, androstenedione, and plasma renin activity can be used to evaluate adequacy of therapy in conjunction with clinical signs and symptoms.8A recent clinical practice guideline recommends monitoring treatment by measuring 17-OHP levels early in the morning and before medication.1This guideline states that 17-OHP should not be completely normalized because of risk of iatrogenic Cushing's syndrome.1,8The target 17-hydroxyprogesterone range suggested for children with CAH is 400−1200 ng/dL.8Clinical factors dictate management of individual adults.8In addition to the classic salt-wasting and simple virilizing forms of CAH, there is also a mild "nonclassic" form of CAH (NC-CAH), which may show variable degrees of postnatal androgen excess but is sometimes asymptomatic.1,2,8NC-CAH is much more common than classic CAH, occurring in approximately 0.1% to 0.2% in the general Caucasian population but in as much as 2% in some populations, such as Ashkenazi Jews.1NC-CAH presents with a wide spectrum of phenotypes due to the complexity of gene duplications, deletions, rearrangements, and compound heterozygotes that cause the condition.1Like more severe forms of CAH, NC-CAH can present as salt-wasting and simple virilizing disease with growth acceleration, premature adrenarche, or menstrual abnormalities.2NC-CAH is a relatively common cause of hyperandrogenic symptoms in women and has been implicated in between 2% and 5% of cases studied.9-11The diagnosis of nonclassic CAH after infancy is accomplished by measuring an early morning baseline serum 17-OHP in symptomatic individuals.1-5,8Measurement of other steroids after a cosyntropin stimulation can be used to differentiate 21-OHD from 11-hydroxylase and P450 oxidoreductase deficiencies and to make the diagnosis in borderline cases.1-5,8

Women's Health, Hormone Testing

Progesterone is a steroid hormone with a molecular weight of 314.5 daltons.2Progesterone is mainly formed in the cells of the corpus luteum and during pregnancy in the placenta. Progesterone is increased in congenital adrenal hyperplasia due to 21-hydroxylase, 17-hydroxylase, and 11-β-hydroxylase deficiency. Progesterone is decreased in primary or secondary hypogonadism and short luteal phase syndrome.The progesterone concentration correlates with the development and regression of the corpus luteum. Whereas progesterone is barely detectable in the follicular phase of the female cycle, a rise in the progesterone level is observed one day prior to ovulation. Increased progesterone synthesis occurs during the luteal phase. In the second half of the cycle pregnanediol is excreted in urine as the main degradation product of progesterone.Progesterone brings about the conversion of the uterine mucosa into a tissue rich in glands (secretion phase), in order to prepare for the intrauterine implantation of the fertilized ovum. During pregnancy, progesterone inhibits the contraction of the myometrium. In the mammary gland, progesterone (together with estrogens) promotes the proliferation and secretion disposition of the alveoli.2,3The determination of progesterone is utilized in fertility diagnosis for the detection of ovulation and assessment of the luteal phase.3,4

Diabetes & Blood Sugar, Hormone Testing

For diagnosis and monitoring of diabetes and insulin-secreting tumors.

Hormone Testing

For diagnosis of hypothyroidism and hyperthyroidism.

Hormone Testing

Offered as part of multiple lab tests

Hormone Testing, General Health & Wellness

Sex hormone-binding globulin (SHBG) is the blood transport protein for testosterone and estradiol. It is a large glycoprotein with a molecular weight of about 95 kD and exists as a homodimer composed of two identical subunits. Each subunit contains two disulfide bridges.2Planar C18and C19steroids with a 17α-hydroxyl group bind particularly well,3,4whereas C1917-ketosteroids, such as dehydroepiandrosterone (DHEA) and androstenedione, do not bind so easily. SHBG has a high binding affinity to dihydrotestosterone (DHT), medium affinity to testosterone and estradiol, and only a low affinity to estrone, DHEA, androstenedione, and estriol.SHBG binds reversibly to sexual steroids. Albumin, which exists in far higher concentrations than SHBG, also binds to sexual steroids−although with a clearly lower binding affinity (eg, about 100 times lower for testosterone).SHBG has a half-life of about seven days and is produced mainly by the liver. Its synthesis and secretion are regulated by estrogen.5,6SHBG serum concentrations depend on the extent, duration, and the kind of estrogen applied, and how regulation takes place. Androgens and gestagens with androgenic residual action have the opposite effect.In serum, SHBG mainly takes over the transportation of steroids and the reduction/regulation of the effect of androgen.7,8Decreased SHBG serum levels are associated with conditions in which elevated androgen levels are present or in which the effect of androgen on its target organs is excessive. This explains the gender-related differences seen between men and women, especially during puberty.Measurement of SHBG can be an important indicator of an excessive/chronic androgenic action where androgen levels are normal, but where clinical symptoms would seem to indicate androgen in excess. SHBG is a useful supplementary parameter in the determination of androgen where a relatively high concentration of free androgen (eg, testosterone) is suspected.9By calculating the free androgen index (FAI), also called free testosterone index (FTI), from the ratio of total testosterone (TT) to SHBG [% FAI or FTI = (TT / SHBG) x 100], it is possible to calculate the approximate amount of free testosterone (FTc), as there is a direct correlation between FAI and FT. Only free testosterone is biologically active, and it best indicates the clinical situation of the patient. Free testosterone is also referred to as non-SHBG-bound testosterone and can be obtained by precipitation of the SHBG-bound-testosterone with ammonium sulfate, and by equilibrium dialysis.10,11Elevated SHBG levels can be seen in elderly men, and are often found in patients with hyperthyroidism and cirrhosis of the liver. SHBG levels also increase when oral contraceptives or antiepileptic drugs are taken. Pregnant women have markedly higher SHBG serum concentrations due to their increased estrogen production. Decreased SHBG concentrations are often seen with hypothyroidism, polycystic ovarian syndrome (PCOS), obesity, hirsutism, elevated androgen levels, alopecia, and acromegaly.

Stress & Fatigue, Hormone Testing

Offered as part of multiple lab tests

Hormone Testing, General Health & Wellness

Offered as part of multiple lab tests

Bone Health, Hormone Testing

Offered as part of multiple lab tests

Diabetes & Blood Sugar, Hormone Testing

Offered as part of multiple lab tests

Hormone Testing, General Health & Wellness

For differential diagnosis of primary, secondary, and tertiary hypothyroidism. Also useful in screening for hyperthyroidism. This assay allows adjustment of exogenous thyroxine dosage in hypothyroid patients and in patients on suppressive thyroxine therapy for thyroid neoplasia.

Hormone Testing

Offered as part of multiple lab tests

Men's Health, Hormone Testing

Testosterone circulates almost entirely bound to transport proteins: Normally less than 1-2% is free. The principal transport protein for testosterone is known as sex hormone binding globulin (SHBG) or testosterone-estradiol binding globulin (TeBG). Testosterone measurements are used to assess erectile dysfunction, infertility, gynecomastia, and osteoporosis and to assess hormone replacement therapy.

Hormone Testing, Anti-Aging

Human growth hormone (hGH) is a polypeptide hormone secreted from the acidophil cells of the anterior pituitary gland. Secretion is episodic and is associated with exercise, the onset of deep sleep or postprandially in response to falling glucose levels. Synthesis and release are under the control of hypothalamic releasing peptides and inhibitory peptides such as somatostatin. More recently, a gastric peptide, ghrelin, has been shown to also stimulate HGH secretion. The mediator of many hGH actions in the periphery, insulin-like growth-factor I (IGF-I) exerts an inhibitory effect through negative feedback mechanisms.1hGH in circulation consists of several molecular isoforms, with 22,000 Dalton hGH being the most abundant, followed by a 20,000 Dalton hGH variant produced by alternative splicing. Approximately 50% of circulating hGH is bound to a high affinity binding protein.2hGH is physiologically important in two main areas. Firstly, it has an integral role in skeletal growth which is well demonstrated in either excess or deficiency in childhood. The action of hGH in part is mediated through IGF-I as well as promoting protein synthesis and the uptake of amino acids into cells. Secondly, hGH influences intermediary metabolism by stimulating lipolysis and is antagonistic to the insulin-mediated uptake of glucose.3hGH secretion is stimulated by hypoglycemia and suppressed by hyperglycemia.In childhood, symptoms of hGH deficiency are retarded growth and dwarfism. Etiology is often unknown and an absolute or relative deficiency usually becomes apparent at about two years of age. Diagnosis can be confirmed by demonstrating low serum hGH which does not respond to stimulation tests. hGH deficiency is a major cause of severe short stature and diagnosis at an early stage is essential for successful therapy.4Hyposecretion in adults usually becomes apparent during the laboratory investigation of hypopituitarism.5,6Hypersecretion, commonly due to adenoma of the acidophil cells, is characterized by two conditions depending on whether it becomes apparent before or after fusion of the bony epiphyses. In childhood, excess hGH is characterized by gigantism. Heights of eight feet may be achieved and may also be associated with hypogonadism. In adults, acromegaly results, a condition characterized by progressive thickening of bone and soft tissue. Diagnosis is usually confirmed by dynamic function testing, which demonstrates a raised serum hGH level that does not fall in response to an oral glucose load.7In conditions where there are nutritional disturbances, such as anorexia, starvation, renal failure, and hepatic cirrhosis, increased basal hGH levels may be found.Recombinant hGH is available for treatment of hGH deficiency in both children and adults.4-6hGH excess is treated by surgery, irradiation therapy, or somatostatin analogues.8,9More recently, pegvisomant, a hGH receptor antagonist, which shares structural homology to hGH and competes with hGH for binding to the hGH receptor, has been developed.10The IDS iSYS hGH assay conforms to the recommendations outlined in the recently published consensus statement on the standardization and evaluation of growth hormone assays.11The assay is calibrated to the WHO International Standard for Somatropin from NIBSC, code 98/574.12The assay is 100% specific for the 22 kDalton form of hGH and has no cross-reactivity with pegvisomant.13

Stress & Fatigue, Hormone Testing

Cortisol is increased in Cushing's Disease and decreased in Addison's Disease (adrenal insufficiency).

Stress & Fatigue, Hormone Testing

Cortisol is increased in Cushing's Disease and decreased in Addison's Disease (adrenal insufficiency).

Stress & Fatigue, Hormone Testing

Cortisol is increased in Cushing's Disease and decreased in Addison's Disease (adrenal insufficiency).

Hormone Testing, General Health & Wellness

Total T3measurements are used to diagnose and monitor treatment of hyperthyroidism and are essential for recognizing T3toxicosis.

Women's Health, Hormone Testing

FSH and LH are secreted by the anterior pituitary in response to gonadotropin-releasing hormone (GNRH) secreted by the hypothalamus. In both males and females, FSH and LH secretion is regulated by a balance of positive and negative feedback mechanisms involving the hypothalamic-pituitary axis, the reproductive organs, and the pituitary and sex steroid hormones. FSH and LH play a critical role in maintaining the normal function of the male and female reproductive systems. Abnormal FSH levels with corresponding increased or decreased levels of LH, estrogens, progesterone, and testosterone are associated with a number of pathological conditions. Increased FSH levels are associated with menopause and primary ovarian hypofunction in females and primary hypogonadism in males. Decreased levels of FSH are associated with primary ovarian hyper-function in females and primary hypergonadism in males. Normal or decreased levels of FSH are associated with polycystic ovary disease in females. In males, LH is also called interstitial cell-stimulating hormone (ICSH). Abnormal LH levels with corresponding increased or decreased levels of FSH, estrogens, progesterone, and testosterone are associated with a number of pathological conditions. Increased LH levels are associated with menopause, primary ovarian hypofunction, and polycystic ovary disease in females and primary hypo-gonadism in males. Decreased LH levels are associated with primary ovarian hyperfunction in females and primary hyper-gonadism in males.

Hormone Testing

The T4 Free (FT4) test measures serum thyroxine (T4) that is not bound to thyroid hormone-binding proteins (thyroid hormone-binding globulin [TBG], transthyretin, albumin) and is thus readily available to target cells. This test is used with thyroid-stimulating hormone measurement (TSH, test code 899) in the diagnosis of hyperthyroidism (usually displaying elevated FT4) and hypothyroidism (low FT4), including congenital and acquired hypothyroidism.The FT4 test is used to assess thyroid function, monitor thyroid conditions, and assess treatment effectiveness. It has largely replaced the total T4 test (test code 867), which measures both bound and free T4, because the FT4 test is less affected by levels of thyroid hormone-binding proteins.This test uses a T4 analog, rather than equilibrium dialysis, to determine the amount of free T4. It therefore differs from the T4 Free, Direct Dialysis test (test code 35167). In the general population, the analog FT4 test is most useful as a follow-up test when TSH results are abnormal. It may also be used instead of TSH testing to assess thyroid function in patients with (1) known pituitary abnormalities; (2) chronically suppressed TSH, as often seen in patients for months after successful treatment for Graves disease [1]; or (3) a need to assess thyroid hormone dose changes sooner than the 6-8 weeks required for TSH to reach a new stable level. When the levels of thyroid hormone-binding proteins are very abnormal (eg, congenital TBG deficiency or excess; preterm infants [2]) or the affinity of binding proteins is altered [3] (eg, familial dysalbuminemic hyperthyroxinemia), the T4 Free, Direct Dialysis test will provide more accurate results.References1. Ross DS.N Engl J Med2011;364:542-550.2. Deming DD et al.J Pediatr.2007;151:404-408.3. Refetoff S. Abnormal Thyroid Hormone Transport. [Updated 2015 Jul 15]. In: Feingold KR, Anawalt B, Boyce A, et al, editors. Endotext [Internet]. South Dartmouth (MA): MDText.com, Inc.; 2000.

Women's Health, Hormone Testing

This test is useful in the differential diagnosis of pituitary and gonadal insufficiency and in children with precocious puberty.

Hormone Testing, Women's Health

Gonadotropin releasing hormone (Gn RH or LH RH) is a ten amino acid peptide produced mainly in the hypothalamus. It stimulates pituitary for the production of LH and FSH. The stimulation is predominantly on LH secretion and hence it is called LH RH. LH and FSH stimulate the production of gonadal hormones (e.g testosterone in males and estrogens in females). These steroid hormones have a feedback control on Gn RH secretion. Increased secretion occurs during puberty leading to the raise in concentration of LH and FSH for the stimulation of gonads. LH RH levels are high when there is secondary hypogonadism with decreased level of LH and FSH. LH RH levels are low in tertiary (hypothalamic) hypogonadism and also individuals with high stress levels with elevated dopamine and prolactin. LH RH and its agonists are routinely used in IVF settings to induce ovulation.

Diabetes & Blood Sugar, Hormone Testing

Offered as part of multiple lab tests

Stress & Fatigue, Hormone Testing

Offered as part of multiple lab tests

Hormone Testing, Cancer Screening

Serotonin measurement is used in conjunction with urinary 5-hydroxyindoleacetic acid (5-HIAA) and/or serum chromogranin A in the diagnosis of carcinoid syndrome. Carcinoid tumors are slow-growing neuroendocrine tumors derived from enterochromaffin cells that are widely distributed throughout the body.1-4Approximately 65% of carcinoid tumors are found in the gastrointestinal tract from the foregut, midgut, and hindgut and another 25% originate in the bronchopulmonary tract.2,4About a quarter of cases present with distant metastases, half of which have unknown primary tumor location.2Carcinoid tumors secrete a variety of peptides and small molecules.1,4,5,6Midgut carcinoid tumors frequently produce serotonin. Serotonin-secreting carcinoids from other locations are less common. Serotonin (5-hydroxy-tryptamine) is synthesized from the essential amino acid tryptophan via the intermediate 5-hydroxytryptophan (5-HTP). Serotonin secretion in the gut causes an increase in gastrointestinal blood flow, motility, and fluid secretion. In healthy individuals, the great majority of serotonin made by the gut is converted by the liver and lungs to 5-hydroxy-indoleacetic acid (5-HIAA) via first pass metabolism prior to entering the general circulation.Serotonin secreting carcinoid tumors are relatively slow growing, and in most cases, asymptomatic.1,4,5The local, paracrine effect of increased serotonin on the gut intestine can cause diarrhea, malabsorption, and tumor mass producing discomfort.4,7Since most serotonin produced by carcinoid tumors is metabolized prior to reaching the circulation, the metabolic product, 5-HIAA in a 24-hour urine collection is usually the most important marker for diagnosing and monitoring treatment of the carcinoid syndrome.4,8The severity of carcinoid syndrome symptoms correlates with the level of 5-HIAA in urine. Urine 5-HIAA has been shown to have a sensitivity of 73% and specificity of 100% for diagnosing well-differentiated functional gastroenterohepatic neuroendocrine tumors.9Compared with patients having normal urinary 5-HIAA levels, patients with elevated levels, whether symptomatic or not, tend to have poorer prognosis.10-12In cases where a larger amount of serotonin reached the systemic circulation (advanced disease with liver metastases bypassing first pass metabolism), patients can present with a constellation of symptoms referred to as the carcinoid syndrome. The carcinoid syndrome can also occur in the absence of liver metastases in cases where tumor pathology causes direct venous drainage of serotonin bypassing first pass liver metabolism.6,13Carcinoid syndrome is relatively rare and is most commonly associated with midgut carcinoid tumors.3,4Carcinoid syndrome occurs in 20% of cases of well-differentiated endocrine tumors of the jejunum or ileum.6,13Carcinoid syndrome occurs less often with neuroendocrine tumors of other origins and is very rare in association with rectal neuroendocrine tumors.6,13Carcinoid syndrome is characterized by one or more symptoms, including diarrhea, dry flushing without sweating with or without palpitations, and intermittent abdominal pain.6Some patients also experience lacrimation and rhinorrhea.6,13Advanced or long-standing carcinoid syndrome can lead to carcinoid heart disease involving the tricuspid and pulmonary valves of the heart.7Significant elevations in urine 5-HIAA have been associated with carcinoid heart disease.14-16Other cardiovascular complications include bowel ischemia and hypertension.7Approximately one in five patients with carcinoid syndrome present with heart disease at diagnosis.6,13Carcinoid tumors are classified similarly, whether they produce symptoms of the carcinoid syndrome or not.17In healthy individuals, approximately 99% of dietary tryptophan is metabolized by the oxidative pathway into nicotinic acid (vitamin B3).4In carcinoid tumors, excessive conversion of tryptophan to serotonin can cause result in vitamin B3deficiency referred to as pellagra, a condition that is characterized by a triad of symptoms: diarrhea, dementia, and dermatitis.18

Women's Health, Hormone Testing

Estriol, E3, is synthesized in the placenta from 16-α-hydroxydehydroepiandrosterone of fetal origin. Thus, normal production can serve as a measure of the integrity of the fetoplacental unit. Sequential monitoring of estriol in high-risk pregnancy has made possible early intervention and fetal salvage. Chronically low estriol values are found in intrauterine growth retardation but also are sometimes seen in normal pregnancy. A decreasing trend is indicative of fetal distress. The sensitivity and specificity of this test for detecting fetal distress are very poor;thus its use for this purpose has been largely abandoned.Combined evaluation of unconjugated serum estriol, maternal serum hCG, maternal serum AFP, and maternal age has value in predicting risk for fetal chromosomal abnormalities during pregnancy. The use of maternal serum AFP, hCG, and estriol predicts 65% of Down syndrome, as opposed to 28% if only serum AFP is used.3-5

Stress & Fatigue, Hormone Testing

Offered as part of multiple lab tests

Hormone Testing, General Health & Wellness

This panel provides an assessment of thyroid function and includes tests for thyroid stimulating hormone (TSH), total thyroxine (T4), triiodothyronine (T3) uptake (T3 resin uptake), and free T4 index. This panel may be useful for evaluating thyroid function when pituitary disease is not suspected. The results of the panel may help in the diagnosis of hyperthyroidism and hypothyroidism [1].T3 and T4 are hormones derived from the thyroid and released into the blood to regulate metabolism. Both T3 and T4 are produced in response to TSH from the pituitary gland. T4 circulates mostly bound to plasma proteins, with a small amount unbound and available for biological activity. To estimate free T4 concentration, a total T4 test and T3 uptake test are used to calculate the free T4 index [1].A normal TSH result excludes most cases of primary overt thyroid disease. Therefore, a cascaded testing approach (test code 15102) may be preferable for evaluating and monitoring thyroid function. This panel does not identify T3 thyrotoxicosis, which requires measurement of free T3 [2,3].Note:Interference due to heterophile antibodies has been known to occur [1].The results of this panel should be interpreted in the context of pertinent clinical and family history and physical examination findings.References1. Demers LM, et al. The thyroid: pathophysiology and thyroid function testing. In: Burtis CA, et al. eds.Tietz Textbook of Clinical Chemistry and Molecular Diagnostics. 4th ed. Elsevier; 2006:2053-2095.2. Ross DS, et al.Thyroid. 2016;26(10):1343-1421.3. Vasileiou M, et al; Guideline Committee.BMJ. 2020;368:m41.

Hormone Testing, General Health & Wellness

Testosterone, dihydrotestosterone and estrogens circulate in serum bound to Sex Hormone Binding Globulin (SHBG). SHBG concentrations are increased in pregnancy, hyperthyroidism, cirrhosis, oral estrogen administration and by certain drugs. Concentrations are decreased by testosterone, hypothyroidism, Cushings syndrome, acromegaly and obesity.

Women's Health, Hormone Testing

Levels increase sharply during the luteal phase of the menstrual cycle. The level increases from 9 to 32 weeks of pregnancy.

Hormone Testing, Men's Health

Offered as part of multiple lab tests

Hormone Testing, Women's Health

Offered as part of multiple lab tests

Hormone Testing, General Health & Wellness

Reverse triiodothyronine (rT3) is an isomer of triiodothyronine (T3) with no demonstrated biological activity.1,2The majority of rT3is produced through peripheral enzymatic monodeiodination of T4at the 5 position of the inner ring of the iodothyronine nucleus of thyroxine (T4). A lesser amount of rT3is secreted directly by the thyroid gland. Reverse T3is biologically inactive and does not stimulate thyroid hormone receptors.Multiple changes in serum thyroid hormone levels are commonly observed secondary to acute (eg, septic shock, myocardial infarction) or chronic (eg, cancer, advanced acquired immunodeficiency syndrome) systemic nonthyroidal illnesses.1-3The hallmark features of this "nonthyroidal illness syndrome" are a low serum T3level accompanied by an increase in serum rT3level. Diminished serum T3levels (the most biologically-active thyroid hormone) are thought to reflect altered thyroid homeostasis as a mechanism of adapting to severe illness.1"Low T3syndrome" affects the majority of critically ill patients and many outpatients suffering less acute illness.1,2Thyroid-stimulating hormone (TSH), thyroxine (T4), free T4(FT4), and free T4index (FTI) can also be affected to variable degrees depending on the severity and duration of the illness.1-3This constellation of abnormal thyroid hormone levels has historically been referred to as the euthyroid sick syndrome (ESS), because these patients are considered to be clinically euthyroid and typically have no hypothalamic, pituitary, or thyroid gland dysfunction, and thyroid hormone levels generally normalize on resolution of the underlying illness.1,2The conversion of T4to rT3is increased in ESS in large part because of increased 5'-deiodinase activity in the periphery.1,2This is often referred to as the "thyroid hormone inactivating pathway" because it reduces the amount of T4available for conversion to biologically active T3.1,2Also, the conversion of rT3to diiodothyronine (T2) is reduced in nonthyroidal illness because of inhibition of the 5'-monodeiodinase activity.1A number of studies have revealed that the expression of these deiodinases is modified by illness in a highly organ-specific manner resulting in tissue-specific modifications to thyroid status.2In acutely ill patients (after acute myocardial infarction or other patients in intensive care), an elevated rT3level has been found to independently predict increased mortality.4-8Significant changes in rT3occur rapidly in acute illness with maximal changes 24 to 36 hours after the onset of symptoms.6,7Reverse T3increase also appears to correlate with the degree of myocardial function impairment in patients with heart failure.8Reverse T3is often increased in nonacutely ill elderly people.3,9,10The Alsanut study, an epidemiological study conducted in the late 1980s, was designed to determine the prevalence of thyroid dysfunction in an independently living population of 440 elderly individuals.9This study revealed a significant relationship between increased rT3and shorter survival while taking into consideration other critical confounders such as age, gender, medical history, nutritional parameters, and energy intake. In this study, rT3was the only thyroid hormone associated with shorter survival.9van den Beld found that elderly persons with isolated increased rT3had lower physical performance and that elevated rT3may be associated with a poor global health status.10Forestier found a strong association between rT3and survival in a population of independently living elderly subjects regardless of other confounding factors.3

Hormone Testing, Women's Health

Offered as part of multiple lab tests

Hormone Testing

IGF-1 is a relatively small peptide (molecular weight 7647) that is tightly bound in serum to one of several high affinity binding proteins.1IGF-1 has approximately 50% sequence homology with proinsulin and has a number of biological activities similar to insulin. IGF-1 is a hormone that serves as the major effector of GH-stimulated somatic growth, as well as GH-independent anabolic responses in numerous tissues. IGF-1 has numerous growth-promoting effects, including mitogenic effects and the promotion of cartilage sulfation. Measurement of serum IGF-1 has been widely used in the diagnosis of disorders of GH secretion,2-6management of disorders that lead to nutritional insufficiency, or catabolism,7-9and monitoring both GH and IGF-1 replacement therapy. IGF-1 measurement may also have a role in the physiology of malignant disease.10,11The IDS iSYS IGF-1 assay conforms to the recommendations outlined in the recently published consensus statement on the standardization and evaluation of IGF-1 assays.12The assay is calibrated to the WHO recombinant reference standard 02/254 for IGF-1.13Reference intervals for IGF-I using the IDS IGF-I were determined in a clinical routine study population from the United States.13,14The cohort included 778,173 males and 710,752 females, aged from 0 to 90 years, who were representative of the overall United States population in terms of gender, race and ethnicity. Reference intervals were adjusted for age and sex using a modified Hoffman approach.15

Hormone Testing, Pediatric Testing

IGF-1 is a relatively small peptide (molecular weight 7647) that is tightly bound in serum to one of several high-affinity binding proteins.1IGF-1 has approximately 50% sequence homology with proinsulin and has a number of biological activities similar to insulin. IGF-1 is a hormone that serves as the major effector of GH-stimulated somatic growth, as well as GH-independent anabolic responses in numerous tissues. IGF-1 has numerous growth-promoting effects, including mitogenic effects and the promotion of cartilage sulfation. Measurement of serum IGF-1 has been widely used in the diagnosis of disorders of GH secretion,2-6management of disorders that lead to nutritional insufficiency or catabolism,7-9and monitoring both GH and IGF-1 replacement therapy. IGF-I measurement may also have a role in the physiology of malignant disease.10,11The IDS iSYS IGF-1 assay conforms to the recommendations outlined in the recently published consensus statement on the standardization and evaluation of IGF-1 assays.12The assay is calibrated to the WHO recombinant reference standard 02/254 for IGF-1.13Reference intervals for IGF-I using the IDS IGF-I were determined in a clinical routine study population from the United States.13,14The cohort included 778,173 males and 710,752 females, aged from 0 to 90 years, who were representative of the overall United States population in terms of gender, race and ethnicity. Reference intervals were adjusted for age and sex using a modified Hoffman approach.15

Hormone Testing, Anti-Aging

DHEA-S is the sulfated form of DHEA and is the major androgen produced by the adrenal glands. This test is used in the differential diagnosis of hirsute or virilized female patients and for the diagnosis of isolated premature adrenarche and adrenal tumors. About 10% of hirsute women with Polycystic Ovarian Syndrome (PCOS) have elevated DHEA-S but normal levels of other androgens.

Hormone Testing, Women's Health

During pregnancy and postpartum lactation, serum prolactin can increase 10- to 20-fold. Exercise, stress, and sleep also cause transient increases in prolactin levels. Consistently elevated serum prolactin levels (>30 ng/mL), in the absence of pregnancy and postpartum lactation, are indicative of hyperprolactinemia. Hypersecretion of prolactin can be caused by pituitary adenomas, hypothalamic disease, breast or chest wall stimulation, renal failure or hypothyroidism. A number of drugs, including many antidepressants, are also common causes of abnormally elevated prolactin levels. Hyperprolactinemia often results in galactorrhea, amenorrhea, and infertility in females, and in impotence and hypogonadism in males. Renal failure, hypothyroidism, and prolactin-secreting pituitary adenomas are also common causes of abnormally elevated prolactin levels.

Women's Health, Hormone Testing

Measuring the circulating levels of estradiol is important for assessing the ovarian function and monitoring follicular development for assisted reproduction protocols. Estradiol plays an essential role throughout the human menstrual cycle. Elevated estradiol levels in females may also result from primary or secondary ovarian hyperfunction. Very high estradiol levels are found during the induction of ovulation for assisted reproduction therapy or in pregnancy. Decreased estradiol levels in females may result from either lack of ovarian synthesis (primary ovarian hypofunction and menopause) or a lesion in the hypothalamus-pituitary axis (secondary ovarian hypofunction). Elevated estradiol levels in males may be due to increased aromatization of androgens, resulting in gynecomastia.

Hormone Testing, Stress & Fatigue

Determination of ACTH is useful in differentiating between primary and secondary adrenocortical hypo- and hyperfunctional disorders: Addison's Disease, Cushing's Syndrome, Adrenal Carcinoma, Ectopic ACTH Syndrome, Nodular Hyperplasia.

Diabetes & Blood Sugar, Hormone Testing

Insulin is a key hormone involved in the control of blood glucose and regulation of fatty acid metabolism. Insulin measurement is primarily used to evaluate the cause of hypoglycemia. Inappropriately elevated insulin in blood (hyperinsulinemia) is associated with hypoglycemia(1) or in disorders linked to hyperglycemia, such as metabolic syndrome(2). Causes of hyperinsulinemia include insulinoma, insulin resistance, noninsulinoma pancreatogenous hypoglycemia syndrome, insulin antibodies, surreptitious insulin administration or other drug-induced hyperinsulinism (e.g., sulfonyl urea), incretin effects after bariatric surgery, and congenital hyperinsulinism. Insulin (test code 561) immunoassay can be used to evaluate the etiology of hypo- or hyperglycemia but is not equivalent to the LC/MS/MS test. Combined with LC/MS/MS measurement of C-peptide in the Cardio IQ Insulin Resistance Panel with Score (test code 36509), the assay can also help evaluate the likelihood that an individual has clinically significant insulin resistance or help in differential diagnosis (e.g., insulinoma versus exogenous insulin administration(3). The results of this test should be interpreted in the context of pertinent clinical history and physical examination findings.References1. Cryer PE, Axelrod L, Grossman AB, et al. Evaluation and management of adult hypoglycemic disorders: an Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab. 2009;94(3):709-728. doi:10.1210/jc.2008-14102. Kelly CT, Mansoor J, Dohm GL, et al. Hyperinsulinemic syndrome: the metabolic syndrome is broader than you think. Surgery. 2014;156(2):405-411. doi:10.1016/j.surg.2014.04.0283. Abbasi F, Shiffman D, Tong CH, et al. Insulin resistance probability scores for apparently healthy individuals. J Endocr Soc. 2018;2(9):1050-1057. doi:10.1210/js.2018-00107

Women's Health, Hormone Testing

This test is useful in the differential diagnosis of pituitary and gonadal insufficiency and in children with precocious puberty.

Diabetes & Blood Sugar, Hormone Testing

Offered as part of multiple lab tests

Hormone Testing, Anti-Aging

Measurement of GH is primarily of interest in the diagnosis and treatment of various forms of inappropriate growth hormone secretion. Growth hormone measurements in children are used in the evaluation of short stature and help differentiate low GH production from other sources of growth failure. Stimulation and suppression tests are often more meaningful than random measurements.

Hormone Testing

Offered as part of multiple lab tests

Stress & Fatigue, Hormone Testing

Offered as part of multiple lab tests

Hormone Testing, Men's Health

Helpful in assessing testicular function in male and managing hirsutism, virilization in females.

Hormone Testing, Men's Health

Helpful in assessing testicular function in prepubescent hypogonadal males and in managing hirsutism, virilization in females.

Hormone Testing

3,3',5'-Triiodothyronine (reverse T3, rT3) is, along with 3,3,5'-Triiodothyronine (T3) a deiodinated metabolite of thyroxine (T4), the major secretory product of the thyroid gland and is secreted into the bloodstream. Unlike T3, however, rT3 is thought to be metabolically inert.The process of 5'-monodeiodination that converts T4 to T3, and rT3 to diiodothyronine (DTT) is inhibited in a wide variety of conditions, collectively referred to as nonthyroidal illnesses (NTI) or the 'euthyroid sick' state. These conditions include fasting, malnutrition, poorly controlled diabetes mellitus, trauma, surgery, and systemic illness. Consequently, in patients with NTI the serum T3 level typically decreases, and the rT3 often, but not always, increases.

Hormone Testing, General Health & Wellness

The T3, Free (FT3) test measures serum triiodothyronine (T3) not bound to thyroid hormone-binding proteins (thyroid hormone-binding globulin [TBG], transthyretin, albumin). It is used, primarily in concert with measurement of thyroid-stimulating hormone (TSH, test code 899) and free T4 (FT4, test code 866), in the diagnosis and management of hyperthyroidism and to clarify thyroid hormone status in the presence of a possible thyroid hormone-binding protein abnormality.The FT3 (or total T3) test is usually ordered following an abnormally low TSH result and/or a clinical picture suggestive of hyperthyroidism, particularly if the free T4 test (FT4, test code 899) result is not elevated. Up to 10% of patients with proven hyperthyroidism (due to Graves disease or an autonomously secreting thyroid nodule) may have an elevated FT3 but normal FT4 (T3 toxicosis), particularly early in the course of disease or as an early sign of relapse after treatment [1]. In contrast, there is limited utility for FT3 testing for suspected hypothyroidism as FT3 levels may not drop until well after both TSH and FT4 rise [2].References1. Carle A, et al.Eur J Endocrinol.2013;169:537-545.2. Garber JR, et al.Endocrine Pract.2012;18:988-1028.

Women's Health, Hormone Testing

Estrone (E1) is a steroid, a weak estrogen, and a minor female sex hormone.3,4Estrone is one of three major endogenous estrogens, the others being estradiol and estriol.3,4Like the other estrogens, estrone is synthesized from cholesterol and secreted mainly from the gonads, though they can also be formed from adrenal androgens in adipose tissue. Estrone is primarily derived from metabolism of androstenedione in peripheral tissues, especially adipose tissues. Individuals with obesity have increased conversion of androstenedione to estrone, leading to higher concentrations. Estrone can be converted into estradiol and serves mainly as a precursor or metabolic intermediate of estradiol. In addition, an increase in the ratio of estrone to estradiol may be useful in assessing menopause in women.

Hormone Testing

Measurement of thyroglobulin antibodies and thyroid peroxidase antibodies is useful in the diagnosis and management of a variety of thyroid disorders including autoimmune thyroiditis, Hashimoto's Disease, Graves Disease and certain types of goiter.

Women's Health, Hormone Testing

Offered as part of multiple lab tests

Hormone Testing, Weight Management

Leptin is an adipocyte-derived hormone that is essential for normal body weight regulation. Leptin production is under neuroendocrine control so that serum concentrations vary directly with the amount of triglycerides stored in adipose tissue depots.

Hormone Testing

This quantitative test, performed with a random urine specimen, may help screen for hypercalciuria, one of the established risk factors for kidney stone formation [1-3]. This test may also help assess metabolic disorders of calcium metabolism, such as hyperparathyroidism, bone disease, and idiopathic hypercalciuria. To adjust for the concentration differences in random urine specimens, calcium to creatinine ratio is included in the results. In general, 24-hour urine specimens are preferred to random urine specimens when measuring calcium for diagnostic evaluation of hypercalciuria [1].Calcium is essential for bone formation and nerve, muscle, and heart functions. Calcium metabolism is jointly regulated by parathyroid hormone and vitamin D metabolites. Urinary calcium excretion is the major route of calcium elimination and reflects kidney tubular filtration and reabsorption of calcium in addition to dietary intake, intestinal absorption, and bone resorption [2].Urinary calcium levels may be elevated in patients with idiopathic hypercalciuria, chronic kidney disease, hyperparathyroidism, vitamin D intoxication, Paget disease of bone, sarcoidosis, or conditions that infiltrate and destroy bones (eg, multiple myeloma and a variety of metastatic cancers) [2,3]. Urinary calcium levels may be decreased in patients with hypoparathyroidism, vitamin D deficiency rickets, osteomalacia, or familial hypocalciuric hypercalcemia [2,3].Note that use of calcium supplements and loop diuretics may cause increased urinary calcium levels; thiazide diuretics may cause decreased urinary calcium levels [3].The results of this test should be interpreted in the context of pertinent clinical and family history and physical examination findings.References1. Williams JC Jr, et al.Urolithiasis. 2021;49(1):1-16.2. Rifai N, et al. eds.Tietz Textbook of Laboratory Medicine. 7th ed. Elservier Inc; 20223. MedlinePlus [Internet]. Calcium-urine. Accessed September 1, 2022.https://medlineplus.gov/ency/article/003603.htm

Hormone Testing, Anti-Aging

Insulin-like Growth Factor 1 (IGF-1, or Somatomedin C), a protein involved in stimulating somatic growth, is regulated principally by Growth Hormone (GH) and nutritional intake. IGF-1 is transported in serum by several proteins; this helps maintain relatively high IGF-1 plasma levels and minimizes fluctuations in serum IGF-1 concentrations.Measuring IGF-1 is useful in several growth-related disorders. Dwarfism caused by deficiency of growth hormone (Hypopituitarism) results in decreased serum levels of IGF-1, while acromegaly (growth hormone excess) results in elevated levels of IGF-1. IGF-1 measurements are also helpful in assessing nutritional status; levels are reduced in undernutrition and restored with a proper diet

Hormone Testing, Anti-Aging

DHEA is a weakly androgenic steroid that is useful when congenital adrenal hyperplasia is suspected. It is also useful in determining the source of androgens in hyperandrogenic conditions, such as polycystic ovarian syndrome and adrenal tumors.

Women's Health, Hormone Testing

Estrone is primarily derived from metabolism of androstenedione in peripheral tissues, especially adipose tissues. Individuals with obesity have increased conversion of androstenedione to Estrone leading to higher concentrations. In addition, an increase in the ratio of Estrone to Estradiol may be useful in assessing menopause in women.

Digestive Health, Hormone Testing

For the diagnosis and monitoring of gastrin-secreting tumors, gastric ulcer, Zollinger-Ellison syndrome. Increased in pernicious anemia.

Hormone Testing, Heart Health & Cardiovascular

Approximately 1-2% of individuals with primary hypertension have primary hyperaldosteronism characterized by hypokalemia (low potassium) and low direct renin. Because serum aldosterone concentrations vary due to dietary sodium intake and body positions, some physicians prefer measurement of 24-hour urine concentrations for aldosterone.

Hormone Testing

Thyroxine-binding globulin (TBG), a glycoprotein produced in the liver, binds both thyroxine (T4) and triiodothyronine (T3) with high affinity. Because TBG accounts for 76% of plasma protein thyroxine-binding activity, an increase or decrease in its circulating level alters total concentrations of T4 and T3 in blood, leading to potential confusion with true thyroid gland dysfunction. A number of diseases and medications, as well as inherited alterations in TBG gene expression, can change the serum TBG concentration. Measurement of TBG is useful in distinguishing quantitative TBG derangements from thyroid dysfunction. This analyte is elevated with estrogen therapy (especially oral contraceptive agents), during pregnancy and or hepatitis. Serum TBG may be decreased in cirrhosis, in the nephritic syndrome and by androgens.

Hormone Testing, Anti-Aging

Insulin-like growth factor binding proteins bind IGF-I and IGF-II with high affinity but do not bind insulin. Of the 6 distinct IGF binding proteins structurally characterized at this time, IGFBP-3 has been shown to be the major carrier of the IGFs, transporting approximately 95% of circulating IGF-I and IGF-II.IGFBP-3 is growth hormone (GH) responsive. Thus, levels are high in acromegaly and low in hypopituitarism, and levels increase in GH-deficient children after GH administration. Other causes of short stature that result in reduced IGFBP-3 levels include poorly controlled diabetes. The IGFBP-3 assay is useful in assessing nutritional status, since IGFBP-3 decreases during both caloric and protein restriction.

Women's Health, Hormone Testing

Diagnostic applications of estradiol assays include assessment of ovarian function in a wide variety of situations (menstrual disorders, precocious or delayed puberty, assisted reproduction protocols). For men, estradiol measurement may be useful in the evaluation of gynecomastia.

Hormone Testing, Men's Health

Offered as part of multiple lab tests

Stress & Fatigue, Hormone Testing

Offered as part of multiple lab tests

Stress & Fatigue, Hormone Testing

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Hormone Testing, Heart Health & Cardiovascular

Measurement of the Plasma Renin activity is useful in evaluating hypertension.

Hormone Testing, Heart Health & Cardiovascular

Metanephrine and normetanephrine (together referred to as metanephrines) are the 3-methoxy metabolites of the catecholamines, epinephrine and norepinephrine, respectively. The methylation of catecholamines is accomplished by catecholamine O-methyltransferase, a membrane-bound enzyme of chromaffin cells.1,5,13-18Levels of these metabolites can be increased in both plasma and urine in patients with catecholamine-producing tumors such as pheochromocytomas, paragangliomas and neuroblastomas. Pheochromocytomas, intra-adrenal paraganglioma, and extra-adrenal sympathetic and para-sympathetic paragangliomas (PPGLs) are rare neuroendocrine tumors derived from neural crest progenitor cells, including adrenal chromaffin cells and similar cells in extra-adrenal sympathetic and para-sympathetic paraganglia. Approximately 10% of pheochromocytomas and 35% of paragangliomas are malignant. About a third of these tumors are associated with three specific syndromes: von Hippel-Lindau syndrome, multiple endocrine neoplasia type 2 (MEN 2), and neurofibromatosis type 1. A number of germline mutations responsible for PPGLs have been identified.19,20Neuroblastomas are derived from immature embryonic neuroblast cells that also form tumors at adrenal and extra-adrenal locations, but present almost exclusively in childhood.21Patients with PPGLs can present with episodic hypertension related to excessive catecholamine synthesis and variety of other symptoms that can include tachycardia, headache, palpitations, profuse diaphoresis, and pallor.5,22Less frequently, these tumors can manifest as nausea, vomiting, flushing, and weight loss. In young patients with normal body weight, hypertension with diabetes mellitus may suggest PPGL.23Many patients present with an unidentified mass lesion and no specific clinical symptoms associated with PPGL. Given the relative non-specificity of symptoms and the low prevalence of the condition (less than one per 100,000 individuals in the general population),24it is not unusualfor the diagnosis of PPGL to be delayed. The critical first step for diagnosis is to recognize the possibility of the tumor.2,25,26The consequences of delayed detection can be severe as excessive catecholamine secretion can precipitate life-threatening hypertension, intracerebral hemorrhage, and cardiac arrhythmias.27,28When detected early, these tumors are potentially curable.29Diagnosis of pheochromocytoma and paraganglioma relies on biochemical evidence of catecholamine production by the tumor. Guidelines suggest that measurement of plasma-free metanephrines or urinary fractionated metanephrines should be performed in symptomatic patients,2,30patients with an adrenal incidentaloma,31and in individuals who have a hereditary risk for developing a pheochromocytoma or paraganglioma.20Metanephrines are produced continuously by the normal adrenal and by tumors via a process that is independent of catecholamine release, which for some tumors occurs at low rates or is episodic in nature.2,16-18While non-chromaffin cells of the sympathetic nervous system are the major sites of norepinephrine metabolism, they do not convert catecholamines to metanephrines because they lack the catecholamine O-methyltransferase enzyme. Consequently, plasma levels of free metanephrines reflect functional chromaffin cell quantity and become elevated in patients with catecholamine-producing chromaffin tumors.13,16Since many PPGLs produce and metabolize catecholamines but do not secrete the amines continuously or in amounts sufficient to produce a diagnostic signal, the metanephrines are superior to the parent catecholamines as diagnostic biomarkers.32,33The high diagnostic accuracy of measurements of urine fractionated metanephrines and plasma-free metanephrines has been confirmed by a large number of studies.2,10-12,16-18,34To ensure optimal diagnostic accuracy, samples for plasma metanephrine testing should be collected with the patient in a fully recumbent, supine position (for at least 30 minutes before sampling) and reference intervals established in the same position should be used.2Numerous studies have confirmed that lying supine at rest prior to blood collection prevents false-positive results due to postural-related stimulus of norepinephrine secretion.2,3,10,32,33,35,36Applying reference ranges established from samples collected in a supine position, the sensitivity of plasma metanephrines approaches 100%, such that a finding of normal levels has a very high negative predictive value for ruling out catecholamine secreting tumor.2,36Normetanephrine or metanephrine elevated three-fold or more above upper cutoffs are rarely false positives and should be followed up in most cases by imaging to locate the tumor.2,6,33In cases of borderline elevation (less than three-fold the upper limit of the reference interval) repeat testing with sampling in a supine position and/or second-line tests such as the measurement of fractionated 24-hour urinary metanephrines and performance of a clonidine suppression test with measurements of plasma normetanephrine can be performed prior to proceeding to imaging studies.2,37Chromogranin A levels are elevated in most patients with PPGLs and have been associated with risk of malignancy.37-39However, the test is not specific and is seen in other disorders such as carcinoid.

Hormone Testing, Men's Health

DHT is a potent androgen derived from testosterone via 5-Alpha-Reductase activity. 5-Alpha-Reductase deficiency results in incompletely virilized males (phenotypic females). This diagnosis is supported by an elevated ratio of testosterone to DHT.

Hormone Testing, Men's Health

Offered as part of multiple lab tests

Hormone Testing, Men's Health

Helpful in assessing testicular function in males and managing hirsutism, virilization in females.

Hormone Testing, Heart Health & Cardiovascular

Aldosterone is a hormone produced by the adrenal glands. Patients with primary hyperaldosteronism exhibit hypokalemia, hypertension, and low direct renin concentrations.

Women's Health, Hormone Testing

17-Hydroxyprogesterone is elevated in patients with Congenital Adrenal Hyperplasia (CAH). CAH is a group of autosomal recessive diseases characterized by a deficiency of cortisol and an excess of ACTH concentration. 17-Hydroxyprogesterone is also useful in monitoring cortisol replacement therapy and in evaluating infertility and adrenal and ovarian neoplasms.

Mental Health & Neurological, Hormone Testing

Measurement of dopamine levels in urine or blood in addition to urinary vanillylmandelic acid (VMA) and homovanillic acid (HVA) levels may aid in the biochemical diagnosis and monitoring of neuroblastomas [1]. This test may also be useful in evaluating dopamine-secreting pheochromocytomas and paragangliomas (PPGLs) [2].Neuroblastomas occur predominantly in children and are the most common malignancy under 1 year old. Neuroblastomas are catecholamine-metabolizing tumors, and thus catecholamine metabolites (including VMA and HVA) are more reliable than catecholamines as biochemical markers for neuroblastomas [1]. However, urinary VMA and HVA levels may have limited accuracy for diagnosis of neuroblastomas with high-risk metastatic biology [1]. Because poor prognosis is associated with immaturity of catecholamine metabolism, dopamine levels in urine or blood have been proposed as an additional marker to aid in diagnosis and monitoring of neuroblastomas [3].Most PPGLs secrete catecholamines, but the relative amount of dopamine, norepinephrine, and epinephrine varies widely. Measurements of plasma free or urinary fractionated metanephrines (ie, the O-methylated catecholamine metabolites) are recommended by the Endocrine Society for the initial biochemical testing of PPGLs [4]. In patients with high clinical suspicion but normal blood pressure and normal levels of metanephrines, measurement of dopamine and its metabolites (HVA and methoxytyramine) may help diagnose PPGLs that predominantly secrete dopamine [2].The results of this test should be interpreted in the context of pertinent clinical and family history and physical examination findings.References1. Eisenhofer G. Monoamine-producing tumors. In: Rifai R, et al. eds.Tietz Textbook of Laboratory Medicine. 7th ed. Elsevier Inc; 2022.2. Jain A, et al.Pediatr Nephrol. 2020;35(4):581-594.3. Brodeur GM, et al.J Clin Oncol. 1993;11(8):1466-1477.4. Lenders JW, et al.J Clin Endocrinol Metab. 2014;99(6):1915-1942

Hormone Testing, General Health & Wellness

Antidiuretic Hormone (ADH), also known as Arginine Vasopressin (AVP), is a neuropeptide that is secreted from the hypothalamus in response to hypovolemia and elevated plasma osmolality.4-6ADH has two primary functions: to retain water in the body and to constrict blood vessels.5The measurement of ADH has been employed in the differential diagnosis of a variety of disorders related to the physiologic response to changes in plasma osmolality and non-osmotic stress.1,7ADH measurement can aid in the differential diagnosis of conditions including diabetes insipidus (DI) and primary polydipsia.Diabetes insipidus (DI) is a rare disorder of water homeostasis characterized by the excretion of abnormally large volumes of hypotonic urine due to the inability to appropriately concentrate urine in response to volume and osmolar stimuli.8,9The primary causes for DI are decreased ADH production (central DI) or decreased renal response to ADH (nephrogenic DI), both of which lead to hypotonic polyuria which is usually accompanied by polydipsia. Along with these etiologies, the differential diagnosis of hypotonic polyuria includes primary polydipsia.9-11In primary polydipsia, there is no initial compromise in ADH secretion or renal action and instead, excessive fluid intake leads to a drop in plasma osmolality and a suppression of ADH synthesis. Primary polydipsia can be caused by an abnormality in the thirst center (dipsogenic polydipsia) or, more commonly, as the result of one of a number of psychiatric disorders (psychogenic polydipsia).9Historically, the primary diagnostic test for the evaluation of polyuria-polydipsia syndrome has been the standard water deprivation test.12-14In healthy subjects, water deprivation causes the plasma osmolality to rise, leading to the release of ADH into the circulation. In this test, insufficient ADH secretion or effect is revealed by insufficient concentration capacity of the kidneys on osmotic stimulation, which is achieved by a prolonged period of thirsting and followed by assessment of the response to exogenous ADH administration (Desmopressin). Recent studies aimed at validating the classical water deprivation revealed a diagnostic accuracy of only around 70%, with an even lower diagnostic accuracy in patients with primary polydipsia.3,12Direct measurement of ADH upon osmotic stimulation has been proposed as an alternative to measuring 24-hour urine osmolality.15

Diabetes & Blood Sugar, Hormone Testing

Offered as part of multiple lab tests

Women's Health, Hormone Testing

Much of Estradiol is bound to proteins. The unbound portion and Estradiol bound to proteins with low affinity reflect the free concentration. The Free Estradiol may better correlate with medical conditions than the Total Estradiol concentrations.

Hormone Testing, Women's Health

Androstenedione may be useful in evaluating patients with androgen excess and managing patients with congenital adrenal hyperplasia (CAH).

Mental Health & Neurological, Hormone Testing

Serotonin concentrations are greatly increased in patients with carcinoid syndrome. Carcinoid tumors are associated with Multiple Endocrine Neoplasia (MEN) Types I and II. These tumors are associated with flushing, diarrhea, pain, and other symptoms.

Diabetes & Blood Sugar, Hormone Testing

The glucagon assay is useful primarily when considering a glucagon-secreting tumor of the pancreas. Glucagonomas cause an unusual but characteristic syndrome consisting of a rash, mild diabetes, weight loss and hypoamninoacidemia. Measurement of plasma glucagon confirms the diagnosis; glucagon levels are very high in the setting of glucagonoma.

Hormone Testing

In humans, steroid hormones are produced by the adrenal glands and the gonads.1,2The formation of pregnenolone from cholesterol is the first step in steroidogenesis and is mediated by the proteolytic enzyme, single cholesterol side-chain cleavage enzyme (P450 scc). Steroidogenesis continues along two paths from pregnenolone. 17-Hydroxypregnenolone is produced from pregnenolone through the enzymatic action of 17α-hydroxylase (17α-H). Alternatively, pregnenolone is converted to progesterone through the enzymatic action of 3β-hydroxysteroid dehydrogenase (3β-HSD).Pregnenolone levels have been shown to remain in the normal range in patients with Cushing syndrome and hyperaldosteronism.3,4Levels can be suppressed with dexamethasone inhibition and increased with exogenous ACTH stimulation.3Pregnenolone levels have been shown to be elevated in patients with idiopathic hirsutism.4Since the various forms of congenital adrenal hyperplasia (CAH) result from enzymatic defects in the adrenal steroidogenic pathways, measurement of pregnenolone levels can be useful in diagnosis. Pregnenolone levels tend to be elevated in several forms of CAH, particularly in 17α-H deficiency and 3β-HSD deficiency since these enzymes catalyze steps immediately after pregnenolone in the steroidogenic pathways.2

Drug & Alcohol Testing, Hormone Testing

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Drug & Alcohol Testing, Hormone Testing

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Women's Health, Hormone Testing

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Hormone Testing, Heart Health & Cardiovascular

The three catecholamines (norepinephrine, epinephrine and dopamine) are the principal secretory products of neural tissue. Clinically, the measurement of circulating catecholamines is valuable in the diagnosis of catecholamine secreting tumors associated chiefly with hypertension (pheochromocytomas, neuroblastomas and gangliomas) and with the evaluation of orthostatic hypotension.

Hormone Testing

Total cortisol concentrations are decreased in Addison's Disease and increased in Cushing's Disease and in other conditions of glucocorticoid excess.

Hormone Testing

Free and weakly bound (bioavailable) testosterone measurement involves the selective precipitation of SHBG with ammonium sulfate. Tritiated testosterone is added to serum, which is then allowed to come to equilibrium at physiologic temperature. Testosterone bound to SHBG is then selectively precipitated with 50% ammonium sulfate, leaving free and albumin-bound testosterone in solution. The percentage of tritiated label not bound to SHBG is multiplied by the total testosterone to produce the bioavailable testosterone.Elevated levels of FWBT are observed in female hirsutism.2The measurement of free and weakly bound testosterone in women, when used in conjunction with the assay of the DHEA-S and SHBG, can be used to establish etiology of hirsutism. In males, decreased serum concentrations are associated with hypogonadism. FWBT levels tend to increase during pregnancy but have been found to remain below the upper limit of the reference interval.3Total testosterone levels in women decrease by approximately 30% after menopause.4Administration of exogenous estrogens has the physiologic effect of increasing SHBG concentrations and suppressing the production of androgens by the ovary.4This results in a net decrease in FWBT. Decreased FWBT levels have been associated with diminished libido4and loss of bone density.5FWBT levels in males fall with age6at a rate that exceeds that of total testosterone and parallels the drop in DHEA sulfate. This decrease is thought to be caused by diminished testicular production and not due to hypothalamic/pituitary insufficiency.7Decreased FWBT was not, however, found to correlate with diminished potency.8Since SHBG has been found to increase with age, the FWBT level may be a more reliable indicator of testosterone production than total testosterone.

Hormone Testing, Heart Health & Cardiovascular

The Aldosterone-renin ratio is used to screen for primary aldosteronism.

Stress & Fatigue, Hormone Testing

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Stress & Fatigue, Hormone Testing

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Hormone Testing

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Hormone Testing, Men's Health

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Hormone Testing, Men's Health

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Hormone Testing

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Hormone Testing

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Hormone Testing

Alpha MSH is a 13 amino acid peptide (1665 kD) with serine at the N terminal end and amidated valine at the C terminal end. Alpha MSH is derived from pro-opiomelanocorticotropin, a precursor protein which contains within its structure, the sequence of ACTH, beta MSH and gamma MSH. The amino acid sequence of alpha MSH is identical to ACTH 1-13 in humans. Alpha MSH stimulates melanosome dispersion within dermal melanocytes and melanin biosynthesis within epidermal melanocytes. It also stimulates aldosterone synthesis. Plasma alpha MSH increases in humans with high fever due to endotoxin. Average plasma alpha MSH has been found higher in AIDS patients and also in obese men with insulin resistance.

Hormone Testing

In humans, the adrenal glands and the gonads produce steroid hormones.1,2The formation of pregnenolone from cholesterol is the first step in steroidogenesis. Steroidogenesis continues along two paths from pregnenolone. 17-Hydroxypregnenolone is produced from pregnenolone through the enzymatic action of 17-α-hydroxylase (17α-H). 3-β-hydroxysteroid dehydrogenase (3β-HSD) mediates the conversion of 17-hydroxypregnenolone to 17-hydroxyprogesterone. Alternatively, the enzyme 17,20 lyase can convert 17-hydroxypregnenolone to dehydroepiandrosterone (DHEA). 17α-H and 17,20 lyase activity are both mediated by a single microsomal cytochrome P450 complex.17-hydroxypregnenelone levels have been shown to remain in the normal range in patients with Cushing.3Levels can be suppressed with dexamethasone inhibition and increased with exogenous ACTH stimulation.3Levels during the follicular phase of the menstrual cycle tend to be higher than during the luteal phase.317-hydroxypregnenelone levels have been shown to be elevated in patients with idiopathic hirsutism.4

Hormone Testing

In humans, the adrenal glands and the gonads produce steroid hormones.1,2The formation of pregnenolone from cholesterol is the first step in steroidogenesis. Steroidogenesis continues along two paths from pregnenolone. 17-Hydroxypregnenolone is produced from pregnenolone through the enzymatic action of 17-α-hydroxylase (17α-H). 3-β-hydroxysteroid dehydrogenase (3β-HSD) mediates the conversion of 17-hydroxypregnenolone to 17-hydroxyprogesterone. Alternatively, the enzyme 17,20 lyase can convert 17-hydroxypregnenolone to dehydroepiandrosterone (DHEA). 17α-H and 17,20 lyase activity are both mediated by a single microsomal cytochrome P450 complex.17-hydroxypregnenelone levels have been shown to remain in the normal range in patients with Cushing.3Levels can be suppressed with dexamethasone inhibition and increased with exogenous ACTH stimulation.3Levels during the follicular phase of the menstrual cycle tend to be higher than during the luteal phase.317-hydroxypregnenelone levels have been shown to be elevated in patients with idiopathic hirsutism.4

Stress & Fatigue, Hormone Testing

Urinary free cortisol is useful in the detection of patients with Cushing's syndrome for whom free cortisol concentrations are elevated

Stress & Fatigue, Hormone Testing

Cortisol stimulates gluconeogenesis in the liver and reduces insulin secretion while increasing glucagon release by the pancreas. This increases blood glucose levels. Cortisol is also involved in inhibiting inflammatory responses and maintaining blood pressure by potentiating effects on norepinephrine.Most of circulating cortisol is bound to protein, primarily transcortin (corticosteroid-binding globulin [CBG]) and albumin. The free hormone hypothesis suggests that the unbound, or free, cortisol is the active fraction, and that this fraction is the most important clinically. Total serum cortisol may be an adequate measure of cortisol activity except when the levels of the binding proteins are abnormal such as in liver disease or acute illness.A study published in theNew England Journal of Medicinedemonstrates the utility of measurements of free cortisol in critically ill patients. Patients with critical illness increase cortisol secretion; however, this is best observed when free cortisol levels are measured. In the study, 40% of patients with hypoproteinemia had low levels of total cortisol even though their adrenal function was adequate as demonstrated by robust response to ACTH. Similar results were obtained when salivary cortisol was used as a marker for adrenal sufficiency during illness.A number of tests to determine free cortisol have been devised. The free fraction depends on the concentrations of the binding proteins and cortisol, and, thus, may be calculated based on these factors. Free cortisol is best measured by equilibrium dialysis. Structure-function observations favor a direct measure of free cortisol. There are polymorphic forms of transcortin that affect cortisol binding, and glycosylation affects cortisol binding to transcortin. TheCortisol, Free, Equilibrium Dialysis and LC/MS-MSassay provides a specific direct test.

Stress & Fatigue, Hormone Testing

Cortisol stimulates gluconeogenesis in the liver and reduces insulin secretion while increasing glucagon release by the pancreas. This increases blood glucose levels. Cortisol is also involved in inhibiting inflammatory responses and maintaining blood pressure by potentiating effects on norepinephrine.Most of circulating cortisol is bound to protein, primarily transcortin (corticosteroid-binding globulin [CBG]) and albumin. The free hormone hypothesis suggests that the unbound, or free, cortisol is the active fraction, and that this fraction is the most important clinically. Total serum cortisol may be an adequate measure of cortisol activity except when the levels of the binding proteins are abnormal such as in liver disease or acute illness.A study published in theNew England Journal of Medicinedemonstrates the utility of measurements of free cortisol in critically ill patients. Patients with critical illness increase cortisol secretion; however, this is best observed when free cortisol levels are measured. In the study, 40% of patients with hypoproteinemia had low levels of total cortisol even though their adrenal function was adequate as demonstrated by robust response to ACTH. Similar results were obtained when salivary cortisol was used as a marker for adrenal sufficiency during illness.A number of tests to determine free cortisol have been devised. The free fraction depends on the concentrations of the binding proteins and cortisol, and, thus, may be calculated based on these factors. Free cortisol is best measured by equilibrium dialysis. Structure-function observations favor a direct measure of free cortisol. There are polymorphic forms of transcortin that affect cortisol binding, and glycosylation affects cortisol binding to transcortin. TheCortisol, Free, Equilibrium Dialysis and LC/MS-MSassay provides a specific direct test.

Hormone Testing, Cancer Screening

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Hormone Testing, Cancer Screening

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Hormone Testing, Stress & Fatigue

11-Deoxycortisol is the immediate precursor of cortisol and follows the same catabolic pathways as cortisol. The conversion of 11-deoxycortisol to cortisol is inhibited by metyrapone, which acts on 11-β-hydroxylase. The metyrapone test (see the online Endocrine Appendix: ACTH Stimulation) serves as a reliable and sensitive indicator of pituitary ACTH secretory reserve. The 11-deoxycortisol levels normally increase to 100 times the control value following metyrapone administration. Reduced response occurs in patients with hypoadrenalism or with hypopituitarism and in some patients with diseases of the hypothalamus. Patients with myxedema, some pregnant patients, and those on oral contraceptives respond poorly.

Hormone Testing, Stress & Fatigue

Offered as part of multiple lab tests

Hormone Testing, Stress & Fatigue

11-Deoxycortisol is the immediate precursor of cortisol and follows the same catabolic pathways as cortisol. The conversion of 11-deoxycortisol to cortisol is inhibited by metyrapone, which acts on 11-β-hydroxylase. The metyrapone test (see the online Endocrine Appendix: ACTH Stimulation) serves as a reliable and sensitive indicator of pituitary ACTH secretory reserve. The 11-deoxycortisol levels normally increase to 100 times the control value following metyrapone administration. Reduced response occurs in patients with hypoadrenalism or with hypopituitarism and in some patients with diseases of the hypothalamus. Patients with myxedema, some pregnant patients, and those on oral contraceptives respond poorly.

Hormone Testing, Stress & Fatigue

11-Deoxycortisol is the immediate precursor of cortisol and follows the same catabolic pathways as cortisol. The conversion of 11-deoxycortisol to cortisol is inhibited by metyrapone, which acts on 11-β-hydroxylase. The metyrapone test (see the online Endocrine Appendix: ACTH Stimulation) serves as a reliable and sensitive indicator of pituitary ACTH secretory reserve. The 11-deoxycortisol levels normally increase to 100 times the control value following metyrapone administration. Reduced response occurs in patients with hypoadrenalism or with hypopituitarism and in some patients with diseases of the hypothalamus. Patients with myxedema, some pregnant patients, and those on oral contraceptives respond poorly.

Hormone Testing, Stress & Fatigue

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Stress & Fatigue, Hormone Testing

Free cortisol is useful in the detection of patients with Cushing's syndrome for whom free cortisol concentrations are elevated.

Hormone Testing

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Stress & Fatigue, Hormone Testing

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Hormone Testing

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Hormone Testing, Autoimmune & Inflammation

Offered as part of multiple lab tests

Bone Health, Hormone Testing

Fibroblast growth factor 23 (FGF-23), a member of the fibroblast growth factor (FGF) family of proteins, is a phosphaturic hormone predominantly produced by bone osteocytes.2-7Plasma FGF-23 exerts its actions by binding to the FGF receptors on cell membranes. Effective FGF-23 binding to these cell surface receptors requires that the cell membrane also contain the transmembrane protein, Klotho.2,8-11FGF-23 inhibits phosphate reabsorption by suppressing Na/Pi cotransporter activity in the proximal convoluted tubule of the kidney. In addition, FGF-23 suppresses intestinal phosphate absorption by inhibiting 1-α-hydroxylase, the enzyme responsible for the conversion of calcifediol to calcitriol, the biologically active form of vitamin D.2-4FGF-23 also possibly inhibits parathyroid hormone (PTH) synthesis and secretion.1-9In healthy individuals, low levels of FGF-23 are detected in the circulation, and FGF-23 secretion rises with increased phosphorus intake and increased calcitriol levels.12Elevated plasma FGF-23 activity has been associated with several hypophosphatemic diseases characterized by impaired renal phosphate reabsorption and rickets/osteomalacia.5,6,9Mutations in FGF-23 that render the protein resistant to proteolytic cleavage lead to increased FGF-23 activity and the renal phosphate loss found in autosomal-dominant hypophosphatemic rickets (ADHR). X-linked hypophosphatemic rickets (XLH)5,6,9and autosomal-recessive hypophosphatemic rickets (ARHR) are due to mutations in PHEX and dentin matrix protein 1, respectively. Both disorders are characterized by overproduction of FGF-23 by bone osteocytes. In tumor-induced osteomalacia (TIO), an acquired disorder of renal phosphate wasting associated with tumors, typically of mesenchymal origin; phosphatonins produced by the tumor promote renal phosphate wasting. FGF-23 is the most common phosphatonin found in patients with TIO.5Patients with TIO share similar biochemical and skeletal phenotypes with patients who have ADHR, ARHR, and XLH.5FGF-23 levels increase dramatically as renal function declines in chronic kidney disease (CKD) as the body attempts to overcome persistent phosphate retention.2,4FGF-23 elevation is thought to play a role in causing the disordered bone and mineral metabolism seen in CKD patients.2,4FGF-23 levels increase in parallel with the decline in renal function well before a significant increase in serum phosphate concentration or PTH occur.2,4Increased FGF-23 levels lead to reduced renal production of 1,25-dihydroxyvitamin D and to hypersecretion of parathyroid hormone.3Prospective studies have demonstrated that elevated FGF-23 levels predict faster disease progression in CKD patients not on dialysis and increased mortality in patients undergoing maintenance hemodialysis and patients with renal transplants.2,13FGF-23 may predict future development of refractory hyperparathyroidism and cardiovascular events in CKD patients3,14and is thought to play a central role in the pathogenesis of post-transplant hypophosphatemia in kidney transplant recipients.3

Hormone Testing, Anti-Aging

Offered as part of multiple lab tests

Hormone Testing, Anti-Aging

Offered as part of multiple lab tests

Hormone Testing

Offered as part of multiple lab tests

Hormone Testing

Offered as part of multiple lab tests

Hormone Testing, Men's Health

Offered as part of multiple lab tests

Hormone Testing, Men's Health

Offered as part of multiple lab tests

Diabetes & Blood Sugar, Hormone Testing

Offered as part of multiple lab tests