Due to its rarity, few studies have attempted to determine the incidence of hyperthyroidism in GTD. Here we explored the incidence of GTD-induced hyperthyroidism in various settings, and a summary is provided in Table 1.

Epidemiology of hyperthyroidism in GTD across various settings

aThere was no distinction between biochemical and clinical hypothyroidism in the study

GTD Gestational trophoblastic disease

GTN Gestational trophoblastic neoplasia

CM Complete hydatidiform mole

PM Partial hydatidiform mole

A study based in a dedicated GTD centre in Sheffield (United Kingdom) reviewed 196 patients who were treated with chemotherapy. Of these 196 patients, 14 (7.2%) had biochemical hyperthyroidism (based on TSH, FT3 and FT4), and four (2%) had clinical hyperthyroidism [11]. Given that the management of GTN in the UK is highly centralised and patients usually present early in gestation, the rates of hyperthyroidism in this study may be lower than other less-resourced healthcare settings.

A US study analysed one of the largest gestational trophoblastic cancer registries in the United States [12]. The authors identified 194 women with histopathologically confirmed complete mole (CM) and 172 with partial mole (PM). More women with CM developed biochemical hyperthyroidism compared to PM (16% vs 4.7%; p < 0.001). However, only 4/194 (2.1%) and 4/172 (2.3%) of women from the CM and PM had clinical hyperthyroidism, respectively. Overall, the incidence of hyperthyroidism in this cohort was approximately similar to the previously-described Sheffield cohort.

A 1981 South African study reported higher rates of hyperthyroidism in their cohort of GTD patients [13], with 15/27 (56%) developing biochemical hyperthyroidism. Clinical hyperthyroidism was seen in 9/27 (33%). The higher incidence of hyperthyroidism in this study compared to the previous two is most likely explained by later detection of GTD in women, compared to the other studies. Being a significantly older study, it is plausible that early detection techniques were either less developed or had lower uptake/implementation compared to the newer studies, resulting in later presentation of GTD and higher rates of GTD-related complications such as hyperthyroidism. The higher rates of hyperthyroidism in this study may also reflect differences in healthcare systems and resources, as well as socioeconomic disparities.

Two studies examined the frequency of GTD-induced hyperthyroidism in a Middle-Eastern population. An Iraqi study found rates of biochemical hyperthyroidism to be as high as 25% (10/40) [14]. An Iranian study found rates of clinical hyperthyroidism to be similar to that shown in the UK and US study. Of 230 patients with a pathologically confirmed CM or PM, 10 were diagnosed with clinical hyperthyroidism (4.3%), all of whom had a complete mole [15].

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