Sex Hormone-Binding Globulin (SHBG), Serum
Overview
Specimen
Clinical and Interpretive
Performance
Fees and Coding
LIS Resources
Setup Information:
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Sample Report
Abnormal Report
Setup Reference Guide
Useful For
Diagnosis and follow-up of women with symptoms or signs of androgen excess (eg, polycystic ovarian syndrome and idiopathic hirsutism)
An adjunct in monitoring sex-steroid and anti-androgen therapy
An adjunct in the diagnosis of disorders of puberty
An adjunct in the diagnosis and follow-up of anorexia nervosa
An adjunct in the diagnosis of thyrotoxicosis (tissue marker of thyroid hormone excess)
A possible adjunct in diagnosis and follow-up of insulin resistance and cardiovascular and type 2 diabetes risk assessment, particularly in women
In laboratories without access to bioavailable testosterone or equilibrium dialysis-based "true" free testosterone assays, sex hormone-binding globulin measurement is crucial in cases when assessment of the free testosterone fraction (aka free androgen index or calculated free testosterone) is required. At Mayo Medical Laboratories, both bioavailable testosterone (TTBS / Testosterone, Total and Bioavailable, Serum) and free testosterone (TGRP / Testosterone, Total and Free, Serum) measurements are available. Free testosterone (TGRP) is measured by equilibrium dialysis, obviating the need for sex hormone-binding globulin measurements to calculate free androgen fractions.
Clinical Information
Sex hormone-binding globulin (SHBG), a homodimeric 90,000 to 100,000 molecular weight glycoprotein, is synthesized in the liver. Metabolic clearance of SHBG is biphasic, with a fast initial distribution from vascular compartment into extracellular space (half-life of a few hours), followed by a slower degradation phase (half-life of several days).
SHBG binds sex steroids with high affinity (KD approximately 10[-10]M), dihydrotestosterone (DHT) ->testosterone (T) ->estrone/estradiol (E). Although each monomeric subunit contains 1 steroid binding site, the dimer tends to bind only a single sex-steroid molecule. The main function of SHBG is sex-steroid transport within the blood stream and to extravascular target tissues. SHBG also plays a key role in regulating bioavailable sex-steroid concentrations through competition of sex steroids for available binding sites and fluctuations in SHBG concentrations. Because of the higher affinity of SHBG for DHT and T, compared to E, SHBG also has profound effects on the balance between bioavailable androgens and estrogens. Increased SHBG levels may be associated with symptoms and signs of hypogonadism in men, while decreased levels can result in androgenization in women.
SHBG levels in prepubertal children are higher than in adults. With the increase in fat mass during early puberty they begin to fall, a process that accelerates as androgen levels rise. Men have lower levels compared with women and nutritional status is inversely correlated with SHBG levels throughout life, possibly mediated by insulin resistance. Insulin resistance, even without obesity, results in lower SHBG levels. This is associated with increased intra-abdominal fat deposition and an unfavorable cardiovascular risk profile. In postmenopausal women, it may also predict the future development of type 2 diabetes mellitus. Androgens and norethisterone-related synthetic progesterones also decrease SHBG in women.
Endogenous or exogenous thyroid hormones or estrogens increase SHBG levels. In men, there is also an age-related gradual rise, possibly secondary to the mild age-related fall in testosterone production. This process can result in bioavailable testosterone levels that are much lower than would be expected based on total testosterone measurements alone.
Reference Values
CHILDREN
Males
Tanner Stages*
Mean Age
Reference Range (nmol/L)
Stage I
7.1
31-167
Stage II
11.5
49-179
Stage III
13.6
5.8-182
Stage IV
15.1
14-98
Stage V
18.0
10-57
*Puberty onset (transitio