SHBG Clinical Significance
02-01-2003 02:42 PM
SHBG Clinical Significance
Not sure where this info. came from, but Mosaman posted it at BB4Life and its a good one......
SHBG Clinical Significance:
Sex hormone binding globulin (SHBG) is a ß-globulin that transports testosterone, dihydrotestosterone (DHT), and estradiol in plasma. It tightly binds approximately 60% of plasma testosterone and DHT. Neither steroid is metabolically active in the bound form.
The measurement of SHBG in serum can be useful in interpreting blood levels of testosterone. Alterations in SHBG levels in certain disease states can result in measurements of testosterone that do not accurately reflect bioavailable levels. SHBG levels may be decreased in obesity, hypothyroidism, androgen use, nephrotic syndrome, Cushing's disease, and acromegaly. Levels may be increased in hepatic cirrhosis, hyperthyroidism, and estrogen use. Free testosterone levels are often more useful in these situations.
Testosterone, Bioavailable and Sex Hormone Binding Globulin; Free and Total:
Free testosterone is calculated using measurements for total testosterone and sex hormone-binding globulin, while the bioavailable testosterone is calculated using measured total testosterone, sex hormone-binding globulin, and albumin. Calculated values for free and bioavailable testosterone compare well with dialysis methods of measuring unbound testosterone.
Testosterone and dihydrotestosterone (DHT) circulate in plasma either unbound, free (approximately 2-3%), or bound to plasma proteins. The binding proteins include the specific sex hormone-binding globulin (SHBG) and nonspecific proteins such as albumin. SHBG is a ß-globulin that has low capacity for steroids, but binds with very high affinity (Ka = 1 x 108 to 1 x 109). SHBG has the highest affinity for DHT and the lowest for estradiol. In men, circulating testosterone is bound 44-65% to SHBG and 33-54% to albumin, whereas in women, testosterone is bound 66-78% to SHBG and 20-32% to albumin.
Blood testosterone levels are dependent on rates of production, interconversion, metabolic clearance, and binding protein concentrations. Because SHBG levels are altered by medications, disease, aging, sex steroids, and insulin, measurement of free testosterone or bioavailable testosterone more accurately reflects the level of bioactive testosterone than does the measurement of total serum testosterone. In aging men, total serum testosterone is often normal, while free testosterone or bioavailable testosterone is low. Because SHBG is often low in women with hirsutism, free testosterone is elevated while the total testosterone concentration is normal.
Testosterone levels are helpful in the assessment of androgen status in male hypogonadism, hirsutism, virilization, acne, and amenorrhea.
Testosterone levels are increased with:
• Polycystic ovarian syndrome,
• Congenital adrenal hyperplasia,
• Androgen resistance, and
• Women with Cushing's syndrome, hirsutism, or adrenal or ovarian androgen secreting tumors.
Testosterone levels are decreased with:
• Male hypogonadism and
• Men with Cushing's disease or those receiving glucocorticoid therapy.
Testosterone is the primary androgen produced by the Leydig cells of the testes. In adult males, testosterone levels show a diurnal variation with the highest levels detected in the early morning and the lowest in the evening. Levels also increase after exercise and gradually decrease with advancing age. In women, levels are 5- 10% of that in males.
Testosterone circulates primarily as a protein-bound steroid (60% bound to sex hormone-binding globulin, 40% to albumin). Only 2-3% exists in the free, biologically active form. The conventional radioimmunoassays for testosterone are too insensitive to quantitate the free form. It is generally expected that the concentration of free testosterone in circulation increases if the testosterone level (T) increases or if the sex hormone-binding globulin (SHBG) level decreases. The T/ SHGB ratio is sometimes referred to as the testosterone free index (TFI).
Serum concentrations of free testosterone in prepubertal children range from less than 0.2-1.5 pg/mL. Levels increase during puberty to adult values, and are related to pubertal stage rather than chronological age. Serum concentrations of testosterone in both sexes during the first week of life average about 25 ng/dL. In male infants, values increase sharply in the second week to a maximum (mean about 175 ng/dL) at approximately two months, which lasts until about six months of age. In female infants, values decrease in the first week and remain low throughout early childhood. Levels increase during puberty to adult values, and are related to pubertal stage rather than chronological age.
Clinical syndromes in which serum testosterone is increased include gonadal and adrenal tumors, adrenal hyperplasia, and polycystic ovaries (Stein-Leventhal syndrome). Conditions such as hypogonadism, hypopituitarism, orchiectomy, estrogen therapy, and some cases of Klinefelter's syndrome are associated with decreased levels of testosterone. Clinical applications of serum testosterone tests in pediatrics include detection of precocious puberty, hypogonadism in adolescent boys, pituitary or hypothalamic disease, where both testosterone and gonadotropin concentrations are low, and virilization in girls.
Urine testosterone measurements are useful clinically for the same purpose as serum measurements, reflecting total daily testosterone output. The advantage of urine measurements are that the levels are unaffected by the serum binding proteins. Disadvantages are that approximately half of the hydrolyzed urine testosterone is from conjugates produced in the liver from testosterone or precursors that are of little physiological consequence, and the typical sample collection difficulties involved in a 24-hour collection.
The TFI is often increased in severe acne, male androgenic alopecia (balding), hirsutism, and other conditions. A low SHBG level, often in combination with a normal total testosterone level, is a common finding in these conditions. An increase in the testosterone production rate typically induces a decrease in the SHBG level. This stimulates cellular uptake and metabolism of testosterone, by making more available in the free form. The result is that the total testosterone level is often normal, because the increased production rate is offset by an increased rate of clearance.
Total testosterone measurements have traditionally been used to help screen for hirsutism. In view of the mechanism just described, it is natural to expect free testosterone levels, measured directly or indexed by the T/SHBG ratio, to correlate better with hirsutism.
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