Differential Diagnosis for Low Free T and Bioavailable T with Elevated SHBG

• Single most likely diagnosis:
  • Hyperthyroidism: Elevated SHBG can be seen in hyperthyroidism, which can lead to an increase in total testosterone but a decrease in free and bioavailable testosterone due to the increased binding of testosterone to SHBG.
• Other Likely diagnoses:
  • Obesity: Obesity is associated with increased SHBG levels, which can lead to decreased free and bioavailable testosterone.
  • Liver disease: Certain liver diseases, such as cirrhosis, can cause an increase in SHBG production, leading to decreased free and bioavailable testosterone.
  • Aging: As men age, SHBG levels tend to increase, which can lead to decreased free and bioavailable testosterone.
  • Hypothyroidism: Some cases of hypothyroidism can lead to increased SHBG levels, although this is less common than hyperthyroidism.
• Do Not Miss diagnoses:
  • Androgen resistance syndromes: Although rare, these syndromes can present with elevated total testosterone but low free and bioavailable testosterone due to impaired androgen receptor function.
  • Testicular cancer: Some testicular cancers can produce human chorionic gonadotropin (hCG), which can stimulate testosterone production but also increase SHBG, leading to decreased free and bioavailable testosterone.
• Rare diagnoses:
  • Thyroid hormone resistance: A rare condition where the body is resistant to thyroid hormone, leading to increased SHBG production.
  • Idiopathic hypogonadotropic hypogonadism: A rare condition characterized by low gonadotropin levels, which can lead to decreased free and bioavailable testosterone.
  • Genetic disorders affecting SHBG or androgen receptors: Rare genetic disorders that can affect SHBG production or androgen receptor function, leading to abnormal testosterone levels.