Hyperthyroidism Acutely Increases Sex Hormone-Binding Globulin (SHBG) Levels
Yes, high thyroid hormone levels (hyperthyroidism) can acutely raise SHBG levels in the body. This relationship is well-established in clinical guidelines and research.
Mechanism and Evidence
According to the European Association of Urology guidelines (2025), hyperthyroidism is specifically listed as a factor that increases SHBG circulating levels 1. This relationship is direct and clinically significant enough to be included in their official guidelines on male sexual and reproductive health.
The mechanism behind this relationship has been elucidated in research:
- Thyroid hormones (T3 and T4) increase SHBG production in the liver by:
- Increasing hepatocyte nuclear factor-4alpha (HNF-4alpha) gene expression
- Reducing cellular palmitate levels that further contribute to increased HNF-4alpha levels in hepatocytes 2
- Acting indirectly through metabolic pathways rather than through direct thyroid hormone response elements
Clinical Observations
Multiple studies confirm this relationship:
- In patients with hyperthyroidism due to Graves' disease or autonomous thyroid adenomas, elevated SHBG levels were found in 69% of cases 3
- The highest SHBG elevations correlate with the highest serum T4 concentrations 3
- When hyperthyroid patients are treated and become euthyroid, SHBG levels normalize 4
- Interestingly, SHBG and corticosteroid-binding globulin (CBG) show opposite responses to thyroid status - SHBG increases with hyperthyroidism while CBG decreases 4
Timing of SHBG Response
The acute nature of this response is demonstrated by:
- In a study of male hyperthyroid patients receiving antithyroid drug treatment, SHBG levels were significantly elevated at baseline and began decreasing as thyroid hormone levels normalized 5
- However, in subacute thyroiditis (a shorter duration form of hyperthyroidism), only 1 of 12 patients had elevated SHBG, suggesting that the duration of exposure to increased thyroid hormone affects SHBG elevation 3
Clinical Applications
This relationship has practical applications:
- SHBG measurement can serve as an in vitro test for end-organ sensitivity to thyroid hormones 6
- In patients with chronic liver disease, SHBG levels are also elevated but may ultimately decline with progression from compensated to decompensated cirrhosis 1
- When evaluating abnormal sex hormone levels, thyroid status should be considered as a potential confounding factor
Important Caveats
- SHBG levels are also affected by other factors including sex (higher in women), age (increases with aging), liver disease, and medications 1
- When interpreting SHBG levels, these confounding factors must be considered
- In subacute thyroiditis, SHBG may not be elevated despite hyperthyroidism, likely due to the shorter duration of thyroid hormone elevation 3
This relationship between thyroid hormones and SHBG is clinically significant when evaluating hormonal status in patients with suspected thyroid dysfunction or when interpreting sex hormone abnormalities.