Can hyperthyroidism cause elevated Sex Hormone-Binding Globulin (SHBG) levels?

Hyperthyroidism Can Cause Elevated SHBG Levels

Yes, hyperthyroidism can cause elevated Sex Hormone-Binding Globulin (SHBG) levels, including values as high as 99 nmol/L. This is a well-documented relationship supported by multiple clinical studies and guidelines.

Relationship Between Thyroid Function and SHBG

Mechanism

• Thyroid hormones directly stimulate hepatic production of SHBG
• In hyperthyroidism, increased circulating thyroid hormones lead to increased SHBG synthesis in the liver 1
• This effect is opposite to what happens with corticosteroid-binding globulin (CBG), which decreases in hyperthyroidism 1

Evidence from Clinical Studies

• Multiple studies confirm elevated SHBG levels in hyperthyroid patients:
  • SHBG levels are significantly higher in hyperthyroid patients compared to euthyroid controls 1
  • SHBG concentrations correlate positively with free thyroid hormone concentrations 1
  • In a study of male hyperthyroid patients, SHBG levels were markedly elevated (mean 146±111 nmol/L) before treatment 2
  • SHBG levels normalize when hyperthyroidism is successfully treated 2, 1

Clinical Significance

Diagnostic Value

• SHBG measurement can serve as a metabolic marker of thyroid function 3
• It can be particularly useful in distinguishing between different forms of inappropriate TSH secretion 4
• SHBG shows better correlation with T3 levels (r=0.76) than with T4 levels (r=0.65), making it a good indicator of metabolic severity of thyrotoxicosis 3

Impact on Sex Hormones

• Elevated SHBG in hyperthyroidism affects bioavailable sex hormone levels:
  • In men with hyperthyroidism, despite increased total testosterone, free testosterone levels may decrease due to increased SHBG binding 2
  • This can contribute to sexual dysfunction in patients with chronic liver disease and thyroid disorders 5

Special Considerations

Duration of Hyperthyroidism

• The cause of hyperthyroidism may affect SHBG elevation:
  • In subacute thyroiditis, SHBG levels may remain normal despite hyperthyroidism, likely due to the shorter duration of thyroid hormone elevation 6
  • In Graves' disease and autonomous thyroid adenomas, SHBG elevation is more common (69% of patients) 6
  • The degree of SHBG elevation correlates with the severity of hyperthyroidism, with higher rates in patients with T4 >15.0 μg/dL (82%) compared to those with T4 between 11.0-15.0 μg/dL (77%) 6

Monitoring Treatment

• SHBG levels normalize when patients become euthyroid following treatment 6, 1
• This makes SHBG potentially useful for monitoring treatment response

Pitfalls and Caveats

• SHBG elevation is not specific to hyperthyroidism and can occur in other conditions
• Liver disease itself can affect SHBG levels, as SHBG is produced in the liver 5
• Overlooking the possibility of pituitary dysfunction affecting both TSH and FSH is a potential pitfall in management 7
• Age and sex influence baseline SHBG levels, with women typically having higher levels than men 1

In conclusion, an SHBG level of 99 nmol/L could certainly be caused by hyperthyroidism, and thyroid function tests should be performed to confirm this association.