Hyperthyroidism due to gestational trophoblastic tumor

Simón Frapolli, Víctor José; López Montalbán, Ángel; Molina Vega, María

doi:10.1016/j.medcle.2022.08.025

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In addition to the more common aetiologies, such as Graves' disease, toxic multinodular goitre, toxic adenoma, and subacute thyroiditis, there are less common causes, such as hyperthyroidism due to excessive production of human chorionic gonadotropin (hCG) that occurs in gestational trophoblastic disease (GTD).<a class="elsevierStyleCrossRef" href="#bib0005">1</a>We report the case of a 50-year-old woman, with an obstetric record of two full-term pregnancies and no miscarriages, with a personal history of hypertension, type 2 diabetes and morbid obesity, referred from primary care due to an incidental finding of primary hyperthyroidism during an outpatient study of dyspepsia and abdominal pain. Without substance abuse or surgical interventions. Usual treatment: valsartan 160mg/hydrochlorothiazide 25mg/24h, sitagliptin 100mg/24h, metformin 1000mg/empagliflozin 10mg/12h, doxazosin 8mg/24hy carvedilol 25mg/24h. She reported unquantified weight loss in recent months and nervousness. No distal tremor, palpitations, or anterior cervical symptoms. Date of last menstrual period 4months before. Physical examination: height 156cm, weight 115kg, BMI 47.2kg/m2.Supplementary tests: GPT 15 (7−40U/l), GGT 76 (5−55U/l), TSH 0.03 (0.4−5μUI/ml), FT4 22.85 (11−22pmol/l), FT3 7.82 (3.10–6.80pmol/l), TSI 0.92 (<2IU/ml), TPO 41.7 (<60IU/ml). Thyroid ultrasound: slightly enlarged thyroid at the expense of the isthmus, with homogeneous echostructure and globally increased vascularity. No pathological nodules or lymphadenopathies are visible.Given the diagnosis of frank hyperthyroidism, thiamazole 5mg 1 tablet/12h was prescribed and a thyroid scintigraphy was requested, which showed increased and diffuse uptake in both thyroid lobes compatible with the clinical suspicion of diffuse goitre.Two months later, she went to the emergency department for metrorrhagia, fever, and abdominal pain. Abdominopelvic ultrasound: large 14×12cm hypervascularised endometrial mass invading the myometrium, with no other findings of interest. Endometrial biopsy: chorionic decidual tissue finding, hCG 154,059 (<2.0IU/l). Abdominopelvic CT: greatly enlarged anteverted uterus reaching the periumbilical region with heterogeneous content inside related to endometrial thickening with a neoplastic appearance. Bilateral parauterine vascular dilatations. Nodes in bilateral external iliac chain of up to 7mm. No free fluid in the abdominal cavity.Given the suspicion of GTD, a total hysterectomy plus double adnexectomy was performed. Pathological examination of the surgical specimen: invasive complete mole-type gestational trophoblastic tumor.One-month follow-up with clinical improvement and return to normal thyroid function: TSH 6.52, FT4 and FT3 normal, TSI negative, hCG decreasing but still positive, reducing thiamazole 5mg to 1tablet/day. On the next visit, TSH 4.51 and the rest was normal, thiamazole was discontinued. Two months later, TSH 1.88. Last three hCG measurements with undetectable levels.Hyperthyroidism due to excessive hCG production in GTD is a rare aetiology resulting from the structural similarity between hCG and TSH, acquiring the ability to stimulate the same receptors, particularly when high concentrations of TSH are present. GTD comprises a set of interrelated entities whose common features include hyperplasia of the trophoblastic epithelium (cytotrophoblast, syncytiotrophoblast) and a sharp increase in hCG (usually >200IU/ml). The most common symptom is metrorrhagia, followed by menstrual cycle abnormalities, vomiting, anaemia, early pre-eclampsia, hyperthyroidism and uterine overgrowth in advanced cases. In the absence of metastatic disease, the curative treatment for GTD is tumor removal, which will also result in progressive return to normal thyroid function. Hysterectomy is often considered in women who have completed their reproductive desire, to reduce the risk of disease persistence.<a class="elsevierStyleCrossRefs" href="#bib0010">2–4</a>Antithyroid drugs are the treatment of choice to restore thyroid function prior to the surgical approach. In addition, beta-blockers (propranolol is the preferred choice)<a class="elsevierStyleCrossRef" href="#bib0020">4</a> can be administered in patients with severe hyperthyroidism and no systolic dysfunction.This clinical case serves as a context to insist on the importance of a broad differential diagnosis of hyperthyroidism. Although hyperthyroidism associated with hCG production is generally uncommon, it is very important to be aware of it, especially if there is a history of previous pregnancy. A subgroup corresponds to transient hyperthyroidism with spontaneous regression; however, those associated with GTD must be diagnosed and treated appropriately, as the patient’s prognosis depends on it." 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