Anti-Aging

Anti-Aging

Offered as part of multiple lab tests

Anti-Aging

Offered as part of multiple lab tests

Anti-Aging

Offered as part of multiple lab tests

Anti-Aging

Offered as part of multiple lab tests

Anti-Aging

Offered as part of multiple lab tests

Anti-Aging

DHEA-S is a steroid hormone which is produced from the precursor cholesterol in the zona reticularis and broad fascia of the adrenal cortex.1The determination of elevated DHEA-S values is an important aid in the diagnosis of hirsutism and virilism.2,4In addition to a differential diagnosis of hirsutism and virilism, further indications for this parameter are all forms of androgenization, hyperprolactinemia, polycystic ovarian syndrome, and the exclusion of an androgen-producing tumor of the adrenal cortex.2DHEA-S exhibits only a weak androgenic activity but can be metabolized to more active androgens, such as androstenedione and testosterone, which can indirectly cause hirsutism and virilism.2,5From 7 years of age onwards, an increase in DHEA-S levels is observed which then gradually after the age of 30 begins to fall again.6Only elevated DHEA-S concentrations are of clinical importance; other factors which can be responsible for DHEA-S excess production are genetic enzyme defects of the adrenal cortex (adrenogenital syndrome),7hyperplasia of the adrenal cortex, as well as androgen-producing tumors.2The rate of secretion of DHEA-S into the blood stream is only slightly more than the rate observed for DHEA. As a consequence of the DHEA-S half-life of approximately one day, the DHEA-S level is, however, about a thousand-fold greater.8DHEA-S is relatively strongly bound to albumin, only a small portion is nonprotein bound, and none appears to be bound to sex hormone-binding globulin (SHBG).9Due to its high concentration and low inter- and intra-day variability, DHEA-S is an excellent indicator of adrenal cortex androgen production.8,10Together with testosterone, DHEA-S assays represent the assay of choice for initial screening tests to determine whether androgen values are elevated in hirsutism. Approximately 84% of the women suffering from hirsutism exhibit elevated androgen levels.11The main purpose of this is to exclude the presence of androgen-producing tumors (from the adrenal cortex or the ovaries).7

Anti-Aging

The concentration of free testosterone is very low, typically <2% of the total testosterone concentration. In most men and women, >50% of total circulating testosterone is bound to sex hormone-binding globulin, SHBG, and most of the rest is bound to albumin.1,2Routinely available assay methods used to measure total testosterone are not sensitive enough to accurately quantitate the free testosterone fraction directly. Free testosterone is estimated in this test by a direct, analogue immunoassay method. This assay uses a labeled testosterone analogue that has a low binding affinity for both SHBG and albumin but is bound by antitestosterone antibody used in the assay. Since the analogue is unbound in the plasma, it competes with free testosterone for binding sites on an antitestosterone antibody that is immobilized on the surface of the microtiter plate well.Several authors have found that the analogue method has good correlation with equilibrium dialysis,1-4but have found that the analogue results were only about one-fourth as high. Another group found that the analogue method produced results directly comparable to equilibrium dialysis without multiplication by a factor.5More recently, Winters and coworkers have found the analogue method to correlates better with total testosterone levels than with bioavailable testosterone determined by the ammonium sulfate precipitation method.6They suggested that the analogue-free testosterone results might be misleading in men with low SHBG concentration.6Ooi suggested that the problems observed by Winters6might, in large part, be resolved by simply using a more appropriate population-based reference interval.7Vermeulen and coworkers found that the analogue-free testosterone method correlated well with free testosterone by equilibrium dialysis, but did not agree well with a free testosterone calculated from total testosterone and SHBG.3

Anti-Aging

Adrenocorticotropic hormone (ACTH), or corticotropin, is a peptide hormone consisting of 39 amino acids. It is produced in the anterior pituitary of the brain as part of the precursor molecule pro-opiomelanocortin (POMC). Tissue-specific cleavage results in ACTH and a range of related peptides.1,4ACTH stimulates formation and secretion of glucocorticoids (especially cortisol) by the adrenal cortex. The glucocorticoid production is regulated by various factors.5-8After stimulation (eg, by physical effort or by the internal body clock), the hypothalamus secretes CRH (corticotropin-releasing hormone). CRH acts on the pituitary, which in turn synthesizes and secretes ACTH. Finally, ACTH stimulates secretion of the glucocorticoids by the adrenals. High concentrations of glucocorticoids in the blood inhibit secretion of CRH and ACTH via a negative feedback mechanism.ACTH concentrations show a diurnal variation with high levels in the morning and low levels in the evening; therefore, as with cortisol, it is important to know the collection time of the plasma sample for interpretation of the results.Plasma ACTH measurements are useful in the differential diagnosis of pituitary Cushing's disease (ACTH hypersecretion), autonomous ACTH-producing pituitary tumors (eg, Nelson's syndrome), hypopituitarism with ACTH deficiency, and ectopic ACTH syndrome.9,10In addition to cortisol measurements, ACTH determinations can be used together with functional or stimulation tests to diagnose the origin of glucocorticoid overproduction. Similarly, ACTH measurements can be employed to facilitate differential diagnosis of adrenocortical insufficiency (Addison's disease).ACTH not produced by the pituitary gland is known as ectopic ACTH;11this is often associated with small cell carcinoma of the lung. In rare cases, ectopic ACTH can be caused by thymic tumors, pancreatic adenocarcinomas, or bronchial carcinoids. These tumors often secrete ACTH precursors (POMC and pro-ACTH).

Anti-Aging

The renin-angiotensin system and potassium ion are the major regulators of aldosterone secretion, whereas ACTH and other POMC peptides, sodium ion, vasopressin, dopamine, ANP, α-adrenergic agents, serotonin, and somatostatin are minor modulators.1,2Renin cleaves angiotensinogen, which is synthesized by the liver to produce angiotensin I. Angiotensin I is, in turn, rapidly cleaved by angiotensin-converting enzyme (ACE) in the lung and other tissues to form, angiotensin II. Angiotensin II stimulates aldosterone secretion and vasoconstriction. Factors that decrease renal blood flow, such as hemorrhage, dehydration, salt restriction, upright posture, and renal artery narrowing, increase renin levels which, in turn, raise aldosterone levels. In contrast, factors that increase blood pressure, such as high salt intake, peripheral vasoconstrictors, and supine posture, decrease renin and aldosterone levels.3Aldosterone promotes active sodium transport and excretion of potassium.Hypokalemia increases and hyperkalemia decreases renin release.1Potassium also directly increases aldosterone secretion by the adrenal cortex and aldosterone then lowers serum potassium by stimulating its excretion by the kidney. High dietary potassium intake increases plasma aldosterone and enhances the aldosterone response to a subsequent potassium or angiotensin II infusion.3Aldosterone deficiency conditions typically present with electrolyte abnormalities, including a variable degree of hyponatremia, hyperkalemia, and metabolic acidosis.1,2,4Congenital aldosterone deficiency is characterized by poor growth in childhood and minimal symptoms in adults. Infants typically suffer recurrent dehydration, salt wasting, and failure to thrive. These symptoms are present generally within the first three months of life. A modest uremia with a normal creatinine level reflects dehydration in the presence of intrinsically normal renal function. Plasma renin activity is invariably elevated.Hypoaldosteronism can occur in any condition that causes destruction or dysfunction of the adrenal gland.1,2,4These conditions include primary adrenal insufficiency, congenital adrenal hypoplasia, isolated mineralocorticoid deficiency, acquired secondary aldosterone deficiency (hyporeninemic hypoaldosteronism), and acquired primary aldosterone deficiency. Hyporeninemic hypoaldosteronism is the most common form of isolated hypoaldosteronism and is caused by impaired renin release from the kidney. Congenital hypoaldosteronism caused by inherited enzymatic defects in aldosterone biosynthesis are rare. Corticosterone methyloxidase I (CMO I) deficiency is associated with elevated serum levels of corticosterone and low levels of 18-hydroxy-corticosterone and aldosterone. Corticosterone methyloxidase II (CMO II) deficiency produces high levels of 18-hydroxy-corticosterone, the immediate precursor of aldosterone. Acquired primary hypoaldosteronism can be caused by the administration of heparin. Also, persistently hypotensive, critically ill patients with sepsis, pneumonia, peritonitis, cholangitis, and liver failure can have inappropriately low plasma aldosterone concentrations in relation to elevated plasma renin activity.Primary hyperaldosteronism, also referred to as Conn syndrome, is caused by the overproduction of aldosterone by one or both of the adrenal glands.1,2Historically, primary aldosteronism was considered to be an uncommon cause of hypertension; however, recent studies indicate that 10% to 15% of cases are associated with primary hyperaldosteronism.5Secondary hyperaldosteronism is relatively common and can occur as the result of any condition that decreases blood flow to the kidneys (ie, renal artery stenosis), decreases blood pressure, or lowers plasma sodium levels. Secondary hyperaldosteronism may also be seen with cirrhosis, congestive heart failure. and toxemia of pregnancy.Hyperaldosteronism increases reabsorption of sodium and loss of potassium by the kidneys, resulting in an electrolyte imbalance.1,6The condition can be asymptomatic, although muscle weakness can occur if potassium levels are very low. Several studies have suggested that high-normal aldosterone levels predict development of high blood pressure in normotensive subjects7and that increased aldosterone action contributes to hypertension, cardiovascular fibrosis, and cardiac hypertrophy.6-8

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

Anti-Aging

This panel measures serum cholesterol and triglyceride (TG) levels. It includes evaluation of the LDL/HDL ratio (calculated), cholesterol/HDL-C ratio (calculated), HDL-C, LDL-C (calculated), non-HDL-C (calculated), total cholesterol, and TG. Comprehensive lipid assessment aids in evaluating cardiovascular disease (CVD) risk and the likelihood of an ischemic event. It is also useful for the prevention and management of atherosclerotic disease and diagnosis of metabolic syndrome [1].CVD is the leading cause of death in the United States. Individuals with high LDL-C and TG levels are at elevated risk for developing CVD and having an ischemic event [2,3]. The American Heart Association recommends that Americans aged 20 and above have their lipid levels tested every 4 to 6 years. Children should have their cholesterol tested for the first time between ages 9 and 11 and again between ages 17 and 21. Testing should start earlier if there is a family history of high cholesterol [4].This panel reports a calculated LDL/HDL ratio in addition to all the components included in Lipid Panel, Standard (test code 7600). High LDL/HDL ratio may be a stronger predictor of coronary heart disease than LDL and HDL alone in patients with hypertriglyceridemia [5].Treatment with N-acetyl cysteine for acetaminophen overdose may generate a falsely low result for cholesterol [6]. Venipuncture immediately after or during administration of the painkiller metamizole (dipyrone) may also lead to falsely low results for cholesterol [7].Note:Any or all individual tests from a panel can be ordered separately.The results of this test should be interpreted in the context of pertinent clinical and family history as well as physical examination findings.References1. Stone NJ, et al.Circulation. 2014;129(25 Suppl 2):S1-S45.2. CDC. Heart disease facts. Accessed January 3, 2022.https://www.cdc.gov/heartdisease/facts.htm3. Arbel Y, et al.Card Diabetol. 2016;15:11.4. Grundy SM, et al.Circulation. 2019;139(25):e1082-e1143.5. Manninen V, et al.Circulation. 1992;85(1):37-45.6. Cholesterol. Instructions for use. Beckman Coulter Inc; 2015.7. Gascon N, et al.Clin Chem. 1993;39(6):1033-1036.

Anti-Aging

Offered as part of multiple lab tests

Anti-Aging

Estradiol is responsible for the regulation of the estrous and female menstrual reproductive cycles and for the development and maintenance of female secondary sex characteristics.2,3Estradiol 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.4Excessive estrogen levels, however, can promote cell proliferation and may increase the risk of developing breast and uterine cancers as well as uterine endometriosis.4The 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 estrogenic activity.2During 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.2The 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.2,4Aromatase converts the androgenic substrates androstenedione, testosterone, and 16-hydroxytestosterone to the corresponding estrogens: estrone, estradiol, and estriol.4E2 is produced primarily in ovaries and testes by aromatization of testosterone.2A 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 glands). E2 and E1 can be converted into each other, and both are inactivated via hydroxylation and conjugation. E2 demonstrates two to five times the biological potency of E1.2The importance of E2 testing and the need for reliable and accurate estradiol measurements throughout the analytic range are emphasized in several recent publications.1,5,6Measurement of serum E2 serves an integral role in the assessment of reproductive function in females and in the assessment of infertility, oligo-amenorrhea, 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 immunoassays methods with modest sensitivity meet the clinical requirements. E2 levels in children, postmenopausal women and men and are much lower than in women of reproductive age. The increased sensitivity and specificity that are achieved by LC/MS-MS are the more appropriate choice for these clinical situations.7,8LC/MS-MS offers superior analytical sensitivity, specificity and a larger dynamic range than immunoassays.7The clinical applications benefiting from highly sensitive E2 measurement include the assessment of congenital defects in sex steroid metabolism and disorders of puberty. This sensitive assay also has application in the evaluation of estrogen deficiency in men menopausal women, fracture risk assessment in these populations, and increasingly, in therapeutic drug monitoring of low-dose female hormone replacement therapy or anti-estrogen treatment.Adult Women.In premenopausal women, E2 levels, along with luteinizing hormone (LH) and follicle-stimulating hormone (FSH) levels, delineate the stage of the menstrual cycle.2E2 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 the 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 oligo-amenorrhea 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, over-exercise, 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 hypogonadism15and 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 testosterone, 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.4After menopause, androstenedione, secreted by the adrenal gland, is converted into estrone in the adipose tissue.4The conversion of plasma androstenedione to estrone increases with excess body weight in both pre- and postmenopausal women.4Estrone is then eventually converted to estradiol by 17 β-hydroxysteroid dehydrogenase enzymes present in peripheral tissues.4Measurement of E2 level, together with FSH and/or anti-Müllerian hormone, 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 the treatments produce serum low levels that can only be accurately measured by sensitive methods.27Adult Men.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.28In males, estradiol is present at low concentrations in blood, but it is extraordinarily high in semen.4Estradiol plays an important role in epididymal function and sperm maturation and is essential for normal spermatogenesis and sperm motility.4Gynecomastia 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 level-related obesity (increase 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 Leydif-cell or Sertoli-cell tumor. They may also secrete estradiol indirectly through the stimulatory effects 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-to-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.4Males 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.4,25,30These 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.31Children and Adolescents.A sensitive method is required to measure accurately the E2 concentrations found in boys and prepubertal girls. Levels in boys and heavier girls are generally lower than in girls of normal weight.32,33Adrenal steroids tend to increase prior to gonadal steroids at the beginning of the pubertal transition.32In girls, E2 concentrations increase just before breast development.32In precocious puberty (PP), estradiol and the gonadotropins, LH and FSH, tend to be above the prepubertal range.34E2 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 pseudo-precocious 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,35and menstrual cycle duration persistently outside 21 to 45 days in adolescents is unusual.36Since 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.11,35Persistently 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.37Both E2 and E1 levels are very low or undetectable in children with aromatase deficiency.36Affected girls have hypergonadotropic hypogonadism, fail to develop secondary sexual characteristics, and exhibit progressive virilization.36The affected boys exhibit normal male sexual differentiation and pubertal maturation. Boys with aromatase deficiency, however, 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.33

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.

Anti-Aging

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.

Anti-Aging

This test may aid in the diagnosis of hypogonadism in men, especially when total testosterone level is near the lower limit of the normal range or when sex hormone-binding globulin (SHBG) concentrations are affected by certain conditions. This test may also aid in the diagnosis of hyperandrogenemia in women [1-3].Testosterone circulates in 3 major forms: unbound (free), weakly bound to albumin, and tightly bound to SHBG. Free testosterone comprises 2% to 4% of total testosterone and is biologically active. In this panel, free testosterone concentration is calculated based on measurements of total testosterone, SHBG, and albumin.In men, fasting total testosterone concentrations measured in the morning are recommended for screening for hypogonadism [2]. Free testosterone level generally correlates well with total testosterone level except in individuals with conditions affecting SHBG concentrations, such as obesity, diabetes mellitus, nephrotic syndrome, aging, acromegaly, HIV disease, liver diseases, thyroid diseases, use of steroids and anticonvulsants, and polymorphisms in the SHBG gene. In these individuals and individuals whose total testosterone levels are at the lower limit, free testosterone levels are more sensitive than total testosterone levels for assessing androgen status. When the total testosterone level is low or total testosterone is normal but free testosterone is low, the fasting total testosterone level should be confirmed on another morning [2].In women with normal total testosterone levels but strong clinical suspicion of hyperandrogenemia or moderate to severe sexual hair growth, morning total and free testosterone may be measured [3]. Free testosterone levels correlate well with clinical presentations of hyperandrogenism and may serve as a more sensitive marker than total testosterone levels for diagnosing and monitoring the progress of hyperandrogenism [1].This test uses a calculation based on measurements of total testosterone, SHBG, and albumin to derive the free testosterone level. Equilibrium dialysis is considered more accurate for measuring free T [1].The results of this test should be interpreted in the context of pertinent clinical and family history and physical examination findings.References1. Rosner W, et al. J Clin Endocrinol Metab. 2007;92(2):405-413.2. Bhasin S, et al. J Clin Endocrinol Metab. 2018;103(5):1715-1744.3. Martin KA, et al. J Clin Endocrinol Metab. 2018;103(4):1233-1257.

Anti-Aging

Testosterone is the principal androgen in men.2,3The production of testosterone by the male testes is stimulated by 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.3,4Low testosterone concentrations can be caused by testicular failure (primary hypogonadism) or inadequate stimulation by pituitary gonadotropins (secondary hypogonadism). Several congenital conditions (ie, Klinefelter syndrome, Kallmann syndrome, Prader-Willi syndrome) can result in decreased testosterone production. Testosterone can also be diminished as the result of testicular damage caused by alcoholism, physical injury, viral diseases (eg, mumps), and in certain malignancies.The 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.5Testosterone measurment was harmonized to the Center for Disease Control reference method.5The reference population included only men younger than 40 years of age who had a BMI less than 30.Significant physiological changes occur in men as they age, in part due to a gradual decline in testosterone levels.6,7It 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.8By 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 age-related decline in testosterone production in men.8.9Since 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.4Much 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.3,10,11It 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 testosterone may help to distinguish racial or genetic causes of hirsutism from abnormal pathology, particularly in women with mixed ethnic backgrounds. Women with more excessive testosterone levels may also experience virilization with symptoms that include 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).11-14PCOS is relatively common, affecting approximately 6% of women of reproductive age.2Women with this complex syndrome experience symptoms of androgen excess associated with menstrual abnormalities and infertility. Chronic 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.2,12Obesity and insulin resistance can result in acanthosis nigricans, a skin condition that is characterized by hyperpigmented, velvety plaques of body folds.2Lipid abnormalities, including decreased high-density lipoprotein cholesterol levels and elevated triglyceride levels, as well as impaired fibrinolysis, are seen in women with PCOS.12,14Cardiovascular disease is more prevalent, and women with PCOS have a significantly increased risk for myocardial infarction.12,14

Anti-Aging

Estrogens are secreted by the gonads, adrenal glands, and placenta. Total estrogens provide an overall picture of estrogen status for men and women.

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.

Anti-Aging

CK-MB is found in much higher concentrations in cardiac muscle than in ordinary skeletal muscle.CK-MB is usually not elevatedin exercise (total CK elevated); myxedema (total CK elevated in about half of cases); injections into muscle (total CK elevated); strokes, CVA, and other brain disorders in which total CK may be increased; pericarditis; pneumonias or other lung diseases; pulmonary embolus; seizures (CK may be very high but no great MB increase, if any). Although CK-MB is not usually increased in angina, some CK-MB elevations are recognized in angina patients, depending partly on laboratory methodology.Atypical forms of CK occur. Macro CK type 1 is usually a complex of CK-BB and IgG (or rarely CK-MM with IgA) and created via an antigen-antibody reaction. It can lead to the false-positive diagnosis of acute myocardial infarction by CK-MB interference in some immunoassay techniques. In quantitative total CK assays, macro CK is indistinguishable from normal CK and can cause an elevation of the total CK, although total CK may also be normal. Macroenzymes should be suspected when enzyme levels are persistently raised with relatively constant levels and there is no obvious clinical explanation or other laboratory abnormality. The clinical relevance of macro CK type 1 is not clearly established. It is not associated with a particular type of disease and has been observed in patients with various diseases, as well as in apparently healthy individuals. Occurring more often in women than men and in patients older than 70 years than in the 20 to 69 year age group, it is likely a marker or consequence of cellular damage in a minority of predisposed individuals, predominantly women and elderly people. There are several reported disease associations, including hypothyroidism, neoplasia, autoimmune disease, myositis, and cardiovascular disease. The last two have the strongest reported associations and may support the diagnosis of an autoimmune process, but this may in part be explained by a higher frequency of requests for CK levels in these groups of patients.5Myositis, including autoimmune myositis, polymyositis, malignancy-associated dermatomyositis, and drug-induced myositis, has been diagnosed in >50% of the patients with macro CK type 1.6Macro CK type 2 is an oligomeric mitochondrial CK complex that migrates cathodically, or close to CK-MM. It is found primarily in adults who are severely ill with malignancies or liver disease or in children who have myocardial disease. It occurs transiently in about 1% of hospitalized patients and indicates a poor prognosis, except in children.6Characteristic Findings in Patients With Macro CK*Type 1Type 2*Adapted from Lee KN, Csako G, Bernhardt P, Elin RJ. Relevance of macro creatine kinase type 1 and type 2 isoenzymes to laboratory and clinical data.Clin Chem.1994 Jul; 40(7 Pt 1):1278-1283.Total CKUsually high (>500 U/L)~ 2/3 of casesUsually low (<100 U/L)~3/4 of casesCK-BBRarely detectable:~1/30 of casesPresent relatively often:~1/3 of casesCK-MBOften present (>4/5 of cases)Increased (>1/2 of cases)May be present (~1/4 of cases)Increased (~1/10 of cases)Macro CK~10% of total~25% of totalMyositisVery commonUncommonMalignancyUncommonVery common

Anti-Aging

This test measures creatine kinase (CK), an enzyme found primarily in striated muscle and heart tissue, and may be useful in assessing muscle damage. Total CK and fractions of CK isoenzymes are reported.CK is a dimeric enzyme composed of either 2 B subunits (CK-BB), 2 M subunits (CK-MM), or an M and a B subunit (CK-MB). CK-MM is the primary isoenzyme found in the skeletal muscle and heart tissue. CK-BB is mainly found in the brain and smooth muscle of gastrointestinal tract and urinary bladder. CK-MB is mainly found in the heart with a small amount in skeletal muscle [1].An increase in the CK level is often observed in inflammatory myopathy (eg, viral myositis, polymyositis, and immune-mediated myopathies), muscular dystrophy (eg, Duchenne sex-linked muscular dystrophy), rhabdomyolysis, or malignant hyperthermia [1]. In patients with neuromuscular disorders, an increased CK level may be the only initial manifestation [1]. Other causes of elevated CK levels include hypothyroidism, direct muscle trauma (eg, surgery and intramuscular injection), excessive exercise, and certain medications (eg, statins, fibrates, antiretrovirals, and angiotensin II receptor antagonists) [1].The quantitation of CK-MB levels in serum was widely used to diagnose acute myocardial infarction but has been replaced by troponin I and T levels, which are more cardiac-specific [2,3]. CK-MB measurement, preferably expressed as CK-MB relative to the total CK level, is only indicated in patients with suspected acute coronary syndrome or reinfarction when troponin T and I testing are not available [2]. In individuals with chronic muscle damage/disease or chronic renal failure, CK-MB may account for the elevation of CK levels owing to the phenomenon of "fetal reversion" [1].CK-BB levels may be increased in newborns with brain damage or very low birth weight, although healthy newborns can also have increased CK-BB levels as a result of birth-related muscle trauma [1].The results of this test should be interpreted in the context of pertinent clinical and family history and physical examination findings.References1. Panteghini M, et al. Serum enzymes. In: Rifai N, et al. eds.Tietz Textbook of Laboratory Medicine. 7th ed. Elservier Inc; 2022:4149-4299.2. CKMB: optimal testing recommendations. AACC. Accessed October 11, 2022.https://www.aacc.org/advocacy-and-outreach/optimal-testing-guide-to-lab-test-utilization/a-f/ckmb3. Gulati M, et al.Circulation. 2021;144(22):e368-e454.

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.

Anti-Aging

Offered as part of multiple lab tests

Anti-Aging

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

Anti-Aging

Hyperviscosity most frequent (33% of cases)1with IgM monoclonal gammopathy (Waldenström macroglobulinemia); next with IgA myeloma. When IgG myeloma leads to hyperviscosity, IgG levels are usually very significantly elevated. A relative viscosity of 6−7 usually results in symptoms of the hyperviscosity syndrome, they have however been described with lower levels of relative viscosity (ie, 4).2Neonatal hyperviscosity, usually but not always associated with polycythemia, may be accompanied by a fairly typical clinical picture. Plethora, hypoglycemia, lethargy, and jitteriness/seizures (CNS symptoms) occur. There may be symptoms and findings suggesting congenital heart disease (CHD) (ie, respiratory distress, cardiac enlargement, and cyanosis). False diagnoses of CHD have been made in such cases. About 50% of such infants have modest hyperbilirubinemia (bilirubin >12 mg/dL).

Anti-Aging

This test may be useful in differentiating among different types of congenital adrenal hyperplasia (CAH). This test may also be used to monitor progress and treatment after diagnosis [1].CAH is a group of autosomal recessive diseases characterized by deficiencies of enzymes in steroid hormone production. These deficiencies cause imbalances of steroid intermediates and hormones. Clinical manifestations of CAH vary and depend upon the type of defect and severity of the impairment. Therefore, measurement of different steroid hormones can help in diagnosing CAH [1,2].Pregnenolone is a precursor to all steroid hormones. It can be elevated in some rare types of CAH, including deficiencies of 3-beta-hydroxysteroid dehydrogenase, 17-alpha-hydroxylase, and P450 oxidoreductase. Levels of pregnenolone (and all other steroids) can be low in lipoid adrenal hyperplasia [2].This test is generally ordered after evaluation of 17-hydroxyprogesterone (test code 17180). 17-hydroxyprogesterone testing, included in newborn screening, is used to detect 21-hydroxylase deficiency (the cause of 95% of CAH). When symptoms and signs suggest CAH, but 21-hydroxylase deficiency and 11-beta-hydroxylase deficiency are ruled out, pregnenolone can be measured to assist in diagnosing other types of CAH [1,2].Pregnenolone degrades rapidly at refrigerator temperature. Specimens should be frozen immediately after collection and remain frozen until analysis [3].This test should be interpreted in the context of pertinent clinical and family history as well as physical examination findings.References1. Speiser PW, et al.J Clin Endocrinol Metab. 2018;103(11):4043-4088.2. El-Maouche D, et al.Lancet. 2017;390(10108):2194-2210.3. Kushnir MM, et al.Clin Chem. 2006;52(8):1559-1567.

Anti-Aging

HLA-B27 is strongly associated with ankylosing spondylitis (Marie-Strumpell disease). HLA-B27 shares homology with aKlebsiellaprotein and may imply a bacterial pathogenesis to ankylosing spondylitis. A patient with consistent clinical and radiographic findings who is B27-positive has a greater chance of having or developing ankylosing spondylitis than a negative patient. The antigen is not causative, however, and 10% of normal subjects are B27-positive. This test should not be considered a screening procedure for ankylosing spondylitis. The antigen is less strongly associated with Reiter syndrome and other arthritides than with ankylosing spondylitis. It has been linked with congenital deficiency of C4and C2, and with adrenal hyperplasia.

Anti-Aging

The NMR LipoProfile® test is a blood test that directly measures the amount of LDL circulating in the body. “LDL” is low-density lipoprotein and has long been recognized as a major causal factor in the development of heart disease. Although the relationship of increased LDL particle number and plaque buildup in the artery wall has been known since the 1950s, a diagnostic test did not exist to measure LDL particle number (LDL-P). Historically, LDL cholesterol, or LDL-C, has been used to estimate LDL levels to assess a patient’s LDL-related cardiovascular risk and judge an individual’s response to LDL-lowering therapy. The NMR LipoProfile® test reports results for LDL-P, a more reliable measure of LDL that directly counts the number of LDL particles a patient has using NMR technology.

Hormone Testing, Anti-Aging

Offered as part of multiple lab tests

Hormone Testing, Anti-Aging

Offered as part of multiple lab tests