Case In Point
Gynecomastia in a Patient With Hyperthyroidism
Kim A. Carmichael, MD
Professor of Medicine, Department of Internal Medicine, Division of Endocrinology, Diabetes, and Lipid Research, Washington University School of Medicine, St. Louis, Missouri
Carmichael KA. Gynecomastia in a patient with hyperthyroidism. Consultant. Published online October 14, 2021. doi:10.25270/con.2021.10.00003
The authors report no relevant financial relationships.
Kim A. Carmichael, MD, Professor of Medicine, John T. Milliken Department of Medicine, Washington University School of Medicine, 660 S Euclid Ave, St Louis, MO 63110-1010 (email@example.com)
A 26-year-old man presented to the emergency department with traumatic fractures of the left radius and ulna. He had no significant medical history, was a nonsmoker, and was not taking medication at the time of presentation.
An evaluation revealed symptomatic hyperthyroidism, a hyperdynamic heart with tachycardia, a precordial scratch, and incidental bilateral gynecomastia. No galactorrhea or testicular atrophy was noted.
Diagnostic testing. Results of laboratory studies revealed elevated levels of T3 and T4 (both more than twice the upper limit of normal), suppressed level of thyroid-stimulating hormone, and elevated levels of normal calcium (10.9 mg/dL) and alkaline phosphatase (240 U/L). The level of antithyroid microsomal antibodies was 50 times the upper limit of normal; this evaluation was performed before thyroid-stimulating immunoglobulin and thyroid peroxidase antibody tests had been developed.
The patient’s 24-hour thyroid radioactive iodine uptake was 85% (reference range, < 20%) with a diffusely enlarged and hyperactive gland. His total testosterone level was 1760 ng/dL (reference range, < 800), dihydrotestosterone level was 224 ng/dL (reference range, < 75), and total estradiol level was 78 pg/mL (reference range, < 42). A β-hCG level was unmeasurable. The patient’s free testosterone and free estradiol levels were not available at the time of evaluation. His follicle-stimulating hormone and luteinizing hormone levels were also markedly elevated at 32.2 IU/L (reference range, < 12) and 67 IU/L (reference range, < 20), respectively.
Treatment. He was initially given propranolol and thionamide therapy. Upon return for follow-up after an 8-month absence, the patient still had hyperthyroidism with bilateral gynecomastia and elevated testosterone and luteinizing hormone levels. A semen analysis showed a low level with immotile sperm. He was again lost to follow-up because of accidental death soon after his last visit.
Discussion. Although there were some gaps in his evaluation compared with current technology, our patient illustrates the unusual complication of gynecomastia in the setting of hyperthyroidism. He also had a precordial scratch, originally described by Lerman and Means in 1932.1
Gynecomastia in patients with hyperthyroidism has been described for more than 40 years2 and was thought to be present in up to 10% to 40% of male patients.3 More recently, researchers have speculated that it is much more uncommon because of earlier screening and treatment of hyperthyroidism. It is even more rarely the presenting feature.4 Indeed, the physiological investigation of this complication is limited to studies conducted and published more than 30 years ago1,5-7 and isolated case reports since then.3,8
Total and unbound estradiol, luteinizing hormone, and follicle-stimulating hormone levels are commonly elevated in men with hyperthyroidism.4-6 Although mean total testosterone and dihydrotestosterone levels may be markedly elevated, unbound testosterone levels are not different from those of men with normal thyroid function because of increased sex-hormone-binding globulin (SHBG).4,5 The mechanism for this is thought to be due to up-regulation of the hepatocyte nuclear factor-4α.8 With this, the ratio of unbound estradiol to unbound testosterone is markedly elevated in men with gynecomastia, associated with increased relative binding of testosterone (compared with estradiol) to SHBG. There is also increased peripheral aromatase activity in patients with hyperthyroidism, converting androgens into higher levels of estrogens.8
The elevated luteinizing hormone level could possibly be related to effects on hypothalamic luteinizing hormone-releasing hormone, but there are no data to confirm this theory.5 Another possibility is that there may be decreased secretion of testosterone in response to luteinizing hormone. Elevation of luteinizing hormone is not always present in men with hyperthyroidism.8 It is notable, however, that luteinizing hormone levels may also be elevated in women with hyperthyroidism, as well as in patients taking excessive exogenous levothyroxine therapy.5
Estradiol levels gradually return to normal with effective treatment of hyperthyroidism.6 In the most recently published case report, the free testosterone and SHBG levels improved dramatically after 2 months, and the gynecomastia resolved within 3 months.8
1. Lerman J, Means JH. Cardiovascular symptomatology in exophthalmic goiter. Am Heart J. 1932;8(1):55-65. https://doi.org/10.1016/S0002-8703(32)90027-1
2. Becker KL, Winnacker JL, Matthews MJ, Higgins GA Jr. Gynecomastia and hyperthyroidism. An endocrine and histological investigation. J Clin Endocrinol Metab. 1968;28(2):277-285. https://doi.org/10.1210/jcem-28-2-277
3. Prabhakaran P, Miskiewicz S. Gynecomastia as the initial presentation of thyrotoxicosis – a case report. Internet J Endocrinol. 2010;6(2). https://ispub.com/IJEN/6/2/11413
4. Sanyal T, Dutta D, Shivprasad K, Ghosh S, Mukhopadhyay S, Chowdhury S. Gynaecomastia as the initial presentation of thyrotoxicosis. Indian J Endocrinol Metab. 2012;16(Suppl 2):S352-S353. https://doi.org/10.4103/2230-8210.104089
5. Chopra IJ, Tulchinsky D. Status of estrogen-androgen balance in hyperthyroid men with Graves' disease. J Clin Endocrinol Metab. 1974;38(2):269-277. https://doi.org/10.1210/jcem-38-2-269
6. Chopra IJ, Abraham GE, Chopra U, Solomon DH, Odell WD. Alterations in circulating estradiol 17β in male patients with Graves’s Disease. N Engl J Med. 1972;286(3):124-129. doi:10.1056/NEJM197201202860303
7. Ashkar FS, Smoak WM 3rd, Gilson AJ, Miller R. Gynecomastia and mastoplasia in Graves' disease. Metabolism. 1970;19(11):946-951. https://doi.org/10.1016/0026-0495(70)90041-7
8. Mohammadnia N, Simsek S, Stam F. Gynecomastia as a presenting symptom of Graves' disease in a 49-year-old man. Endocrinol Diabetes Metab Case Rep. Published online April 1, 2021. https://doi.org/10.1530/edm-20-0181