Why Hyperthyroidism Causes Gynecomastia
Mechanism of Gynecomastia in Hyperthyroidism
Hyperthyroidism causes gynecomastia through increased sex hormone-binding globulin (SHBG) production, which creates an imbalance favoring estrogen over testosterone at the tissue level, combined with increased peripheral conversion of androgens to estrogens. 1, 2
Hormonal Alterations in Hyperthyroid Men
The pathophysiology involves several interconnected hormonal changes:
Elevated SHBG levels are the central mechanism—thyrotoxicosis upregulates hepatocyte nuclear factor-4α (HNF4A) in liver cells, which subsequently increases SHBG expression 2
Total testosterone levels are elevated in hyperthyroid men, but this is misleading because the testosterone is bound to the increased SHBG 1
Free (unbound) testosterone remains normal or low despite high total testosterone, because most is bound to SHBG and unavailable to tissues 1
Total estradiol-17β levels are supranormal, and critically, free estradiol-17β is also elevated (unlike testosterone, where only total is high) 1
This creates a favorable hormonal environment for gynecomastia development—normal free testosterone with elevated free estradiol shifts the androgen-to-estrogen ratio toward estrogen dominance at the tissue level 1
Additional Contributing Factors
Increased peripheral aromatization of androgens to estrogens appears to be a major factor responsible for the elevated estradiol levels in hyperthyroidism 1
Increased glandular secretion of estradiol-17β may also contribute to the elevated estrogen levels 1
Luteinizing hormone (LH) levels are also supranormal in hyperthyroid men, though the clinical significance of this for gynecomastia development is less clear 1
Clinical Prevalence and Presentation
Gynecomastia occurs in 20-40% of men with hyperthyroidism on physical examination, making it a common finding 1, 2
However, gynecomastia as the initial or presenting complaint is extremely rare in undiagnosed hyperthyroidism 3, 4, 2
When present, the gynecomastia can be unilateral or bilateral and is often tender or painful 3, 4
Clinical Management Implications
Treatment of the underlying hyperthyroidism resolves the gynecomastia in most cases—breast pain typically disappears and breast enlargement either completely resolves or significantly decreases after achieving euthyroidism 3, 4, 2
Resolution typically occurs within 3 months of achieving euthyroid status 2
Because gynecomastia rarely presents as the initial complaint, thyroid function tests are not routinely indicated in the standard workup of patients whose primary complaint is gynecomastia 3
When to Consider Hyperthyroidism
Despite the above recommendation, thyroid function testing should be considered when:
Physical examination reveals signs of hyperthyroidism such as warm and moist peripheries, resting tachycardia, or goiter 4
History reveals symptoms of thyrotoxicosis including nervousness, irritability, palpitations, fatigue, or weight loss (even if the patient considers these "normal") 3
The patient has risk factors for thyroid disease including family history, autoimmune conditions, or previous thyroid disorders 5
Common Pitfalls to Avoid
Failing to examine for other signs of hyperthyroidism when evaluating gynecomastia—a focused breast examination alone may miss the underlying diagnosis 3, 4
Dismissing patient-reported symptoms of thyrotoxicosis that the patient has normalized or attributed to stress or aging 3
Unnecessary imaging in clear cases of gynecomastia can lead to additional unnecessary benign biopsies without improving outcomes 6