Sex Hormone Binding Globulin (SHBG)

Additional Information:


EPIC Test Name: SEX HORMONE BINDING GLOBULIN

CPT Code(s):

84270

Collection Procedure:


Collect specimen in SST tube. Allow to clot. Centrifuge and store refrigerated. Transport to lab.

Specimen Requirements:


Specimen Type: Serum
Container/Tube: SST
Sample Volume: 1 mL
Minimum Volume: 0.2 mL (Repeat testing is not possible with this specimen volume.)
Storage: Refrigerate
Stability (collection to time of analysis/testing):

  • Refrigerated: 7 days
  • Frozen: 2 months

Use:

Sex hormone binding globulin (SHBG) is a ~100 kDa homodimeric plasma protein where its 373 amino acid monomeric form is ~50 kDa. The gene for SHBG is located on chromosome 17p1.

SHBG serves as the plasma transport protein for testosterone and dihydrotestosterone (DHT). Estrogen is also carried on SHBG whereas the affinity of SHBG for estrogen is lower than for testosterone or dihydrotestosterone. Estrogens and thyroid hormone increase SHBG concentrations, whereas insulin, growth hormone, glucocorticoids, androgens, and progestins lower SHBG concentrations. SHBG concentrations are higher in children than in adults. SHBG concentrations are generally higher in women than in men although their reference intervals overlap substantially. SHBG levels may decline in persons with the metabolic syndrome. With increasing age SHBG levels rise in men.

Testosterone exists in 3 pools: free, loosely (a.k.a. – weakly) bound to albumin and tightly bound to SHBG. Both free and weakly bound testosterone are considered to be biologically active (e.g., “bioactive” or “bioavailable”). Various sources report that the percent free testosterone (as a proportion of the total testosterone) is 0.5 – 3.0% or 1.0 – 4.0%. In men, albumin-bound testosterone is 50 – 68% of the total testosterone and SHBG-bound testosterone is 30 – 45% of the total testosterone. In women, albumin-bound testosterone is ~25% of the total testosterone and SHBG-bound testosterone is ~70% of the total testosterone.

Free or bioavailable testosterone can be measured using a variety of methods: calculated from the total testosterone and SHBG measurements, ultracentrifugation, dialysis equilibrium, precipitation of SHBG-bound testosterone, direct immunoassay and mass spectroscopy. What constitutes the “best method” for measuring free or bioavailable testosterone is controversial; however, many experts believe that in the setting of the routine clinical laboratory, the calculation of the free testosterone based upon the total testosterone and SHBG levels is the superior approach (see: http://www.issam.ch/freetesuit.htm) . Note that in women and children, total testosterone is best measured by mass spectroscopy.

General References

  1. Diver MJ. Laboratory measurement of testosterone. Front Horm Res. 2009;37:21-31.
  2. Elin RJ, Winters SJ. Current controversies in testosterone testing: aging and obesity. Clin Lab Med. 2004 Mar;24(1):119-39.
  3. Grundy SM, Brewer HB Jr, Cleeman JI, Smith SC Jr, Lenfant C; American Heart Association; National Heart, Lung, and Blood Institute. Definition of metabolic syndrome: Report of the National Heart, Lung, and Blood Institute/American Heart Association conference on scientific issues related to definition. Circulation. 2004 Jan 27;109(3):433-8.
  4. Morales A, Collier CP, Clark AF. A critical appraisal of accuracy and cost of laboratory methodologies for the diagnosis of hypogonadism: the role of free testosterone assays. Can J Urol. 2012 Jun;19(3):6314-8.
  5. Patel SM, Nestler JE. Fertility in polycystic ovary syndrome. Endocrinol Metab Clin North Am. 2006 Mar;35(1):137-55, vii.
  6. Rachon D. Differential diagnosis of hyperandrogenism in women with polycystic ovary syndrome. Exp Clin Endocrinol Diabetes. 2012 Apr;120(4):205-9.
  7. Rosenfield RL. Ovarian and adrenal function in polycystic ovary syndrome. Endocrinol Metab Clin North Am. 1999 Jun;28(2):265-93.
  8. Wheeler MJ. Measurement of androgens. Methods Mol Biol. 2006;324:197-211.

Methodology:


Solid-phase, two-site chemiluminescent immunometric assay

Reported:


1-3 business days

Reference Values:

  • Non-pregnant females: 18 – 144 nmol/L
  • Males: 10 – 57 nmol/L