DISCUSSION AND CONCLUSIONS • • • • • •

GTD with thyrotoxicosis is a rare clinical scenario, but thyroid hyperstimulation by hCG can have severe clinical consequences. Complete hydatidiform mole most commonly presents with vaginal bleeding, occurring at 6 to 16 weeks of gestation in 80% to 90% of cases (1). The clinical signs and symptoms, such as hyperemesis, have occurred less frequently in more recent years because of earlier diagnosis resulting from widespread use of ultrasonography and accurate tests for hCG. In the past, approximately 55% to 60% of women with trophoblastic disease had clinically evident hyperthyroidism that could be severe at the time of diagnosis. However, in a review of 196 patients from the United Kingdom treated for gestational trophoblastic disease between 2005 and 2010, biochemical hyperthyroidism was present in 7% and clinical hyperthyroidism in only 2% (2). Hydatidiform moles are commonly associated with hCG levels markedly elevated above those of normal pregnancy, as can be seen in our patient, who had an hCG level close to 2 million mIU/ml. Approximately 50% of patients with molar pregnancy have preevacuation hCG levels >100,000 mIU/ml (3).

Tisne et al. reported the first case of clinical hyperthyroidism in a patient with hydatidiform mole in 1955 (4). The glycoprotein hormone hCG is a specific tumor marker for trophoblastic diseases. The analogy in the structure between hCG and TSH can cause cross-reactivity with their receptors. It has been shown that the homology in the hCG and TSH molecules, as well as in their receptors, is likely to be responsible for the cross-reactivity of hCG with the TSH receptor (5). Glinoer has estimated that ”for every 10,000 mU/mL increase in serum hCG, FT4 increases by 0.1 ng/dL and TSH decreases by 0.1 mIU/mL” (6). Molecular variants of hCG found in molar pregnancies have increased thyrotropic potency (7). When gestational trophoblastic disease causes a significant rise in hCG levels, it may induce hyperthyroidism that requires treatment. As expected, thyrotoxicosis resolves with treatment of GTD and normalization of hCG levels. The development of hyperthyroidism is largely influenced by the level of hCG and usually resolves with treatment of GTD. The consideration of this cause of hyperthyroidism in pregnancy should be diagnosed early and managed efficaciously before imminent dilatation and curettage is required for definitive management of the hydatidiform mole.

*Endocrinology Division, UCLA School of Medicine, Los Angeles, CA

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