Hyperthyroidism and human chorionic gonadotrophin production in gestational trophoblastic disease

Abstract

Background:Gestational trophoblastic disease (GTD) is a rare complication of pregnancy, ranging from molar pregnancy to choriocarcinoma. Patients with persistent disease require treatment with chemotherapy. For the vast majority, prognosis is excellent. Occasionally, GTD is complicated by hyperthyroidism, which may require treatment. This is thought to occur due to molecular mimicry between human chorionic gonadotrophin (HCG) and thyroid-stimulating hormone (TSH), and hence cross-reactivity with the TSH receptor. Hyperthyroidism usually resolves as the GTD is successfully treated and correspondingly HCG levels normalise.Methods:This paper reviews cases of GTD treated over a 5-year period at one of the three UK centres and identifies the prevalence of hyperthyroidism in this population. Four cases with clinical hyperthyroidism are discussed.Results:On review of the 196 patients with gestational trophoblastic neoplasia treated with chemotherapy in Sheffield since 2005, 14 (7%) had biochemical hyperthyroidism. Of these, four had evidence of clinical hyperthyroidism.Conclusion:Concomitant biochemical thyroid disease in patients with GTD is relatively common, and measurement of thyroid function in patients with persistent GTD is, therefore, important. The development of hyperthyroidism is largely influenced by the level of HCG and disease burden, and usually settles with treatment of the persistent GTD. However, rarely the thyroid stimulation can have potentially life-threatening consequences.

Trophoblastic Hyperthyroidism and Its Perioperative Concerns

“…TSH and hCG thus share a molecular mimicry and have similar effects on the thyroid [29]. Nonetheless, hCG receptors share 45% homology with the TSH receptors [3].…”

“…It also activates the TSH receptor. But the relative potency of hCG for the TSH receptor is 4000 times less than TSH [3]. It has been calculated that hCG contains approximately 1/4000 th of the thyrotropic activity of human TSH.…”

“…Extremely high levels are required for the development of clinical hyperthyroidism. Case studies have indicated that, serum levels of hCG of >100,000 mIUL -1 are usually needed to produce clinical evidence of thyrotoxicosis [3]. Such high levels are seen in conditions like hyperplacentosis, hyperemesis gravidarum, gestational trophoblastic disease, multiple pregnancy and hyper reaction-luteinalis [7].…”

“…Gestational trophoblastic disease is a family of diseases that includes complete and partial molar pregnancy also known as hydatidiform mole, locally invasive or Disseminated choriocarcinoma and placental site trophoblastic tumour [3]. Placental site trophoblastic tumour, invasive mole and choriocarcinoma are termed Gestational Trophoblastic Tumours.…”

“…The alpha subunit is identical to that found in TSH. It consists of a 92 aminoacid chain containing two nitrogen linked oligosaccharide side chains [3]. The beta subunit of hCG consists of 145 aminoacid residues with two N linked and four O linked oligosaccharides.…”