(22.02) The triangle of hyperthyroidism, methimazole and gynecomastia!

Gynecomastia (GC) is a known complication of hyperthyroidism (HT), thyrotoxicosis (TC) and there have been some reported associations with hypothyroidism as well. We present an interesting case where we believe treatment of hyperthyroidism (HT) with methimazole (MM) led to unilateral gynecomastia which resolved with dose adjustment.

Case(s) Description :

45-year-old male was evaluated by endocrinology after he was noted to have weight loss and outpatient work up led to the diagnosis of Graves’ disease which was confirmed through ultrasound and thyroid function tests. Initial TSH was 0 and free T4 (FT4) was 4.81, reference ranges (RR) are 0.55-4.78 and 0.89-1.76, respectively.  Patient had already been started on MM 10 mg twice daily which he had taken for approximately one month. Repeat results indicated TSH 0, FT4 2.95 and TSI 411 (RR < 140) (which were prior to his visit with endocrinology and led to up titration of dose to MM 30 mg daily). On follow up in 2 months patient mentioned he noticed GC which had progressively been increasing. This was attributed initially to HT. Estradiol, LH, FSH, PRL and HCG levels were all within normal range. FT4 was 0.57 and TSH 0.01. The dose of MM was decreased to 25 mg daily and in a few days to 20 mg daily. Over the next few months patient’s GC was noted to resolve completely. Patient was continued on MM and over the year’s dose was tapered to 5 mg based on thyroid function tests.

Discussion :

GC is hyperplasia of breast tissue that occurs due to hormonal imbalance in men. It has been associated with HT in up to 40% of patients as thyroid hormone can increase estrogen levels. GC resolves with treatment of HT, however, there have been few case reports where it was noted after initiation of treatment regimens such as methimazole. In our patient. GC occurred after the MM dose was increased and was not an initial manifestation of HT or during initiation.  There have been cases where GC resolved with continued dosing of MM as the primary etiology was considered to be HT, which when treated resulted in resolution of GC. In our case interestingly with dose adjustment the condition worsened with complete resolution after MM dose was reduced. Possible mechanism of GC after initiation of treatment which have been reported in literature could be decreased total cholesterol and LDL, both of which increased after treatment with methimazole. As cholesterol is precursor to several hormones it may have led to increased levels of estradiol which leads to GC. In our patient however these levels were normal which makes this hypothesis less likely. We question if the GC was a primary side effect of MM. There have been cases of bilateral GC, but we present a unique case of unilateral GC. It is possible that over time the GC would have corrected however as it can lead to significant psychological distress in men, we believe a slower dose titration in our patient regardless who was not in over thyrotoxicosis was more reasonable approach.