Spontaneous ovarian hyperstimulation syndrome is a rare event, in contrast to iatrogenic ovarian hyperstimulation syndrome, which is induced with the use of gonadotropins in assisted reproductive medicine. The pathological features of the syndrome, whether spontaneous or iatrogenic, include the presence of multiple serous and hemorrhagic follicular cysts lined by luteinized cells, a condition called hyperreactio luteinalis.¹ The pathogenesis of the syndrome and its systemic manifestations are poorly understood.^2-6 We describe a familial case of recurrent spontaneous ovarian hyperstimulation syndrome. The affected women were heterozygous for a mutation in the transmembrane domain of the gene encoding the follicle-stimulating hormone receptor. In vitro characterization of the mutated receptor revealed that its specificity had decreased, allowing human chorionic gonadotropin as well as follicle-stimulating hormone to stimulate it.

Differentiated thyroid cancers are more frequent in women than in men. These different frequencies may depend on differences in patient’s behavior and in thyroid investigations. However, an impact on sexual hormones is likely, although this has been insufficiently elucidated. Estrogens may increase the production of mutagenic molecules in the thyroid cell and favor the proliferation and invasion of tumoral cells by regulating both the thyrocyte enzymatic machinery and the inflammatory process associated with tumor growth. On the other hand, the worse prognosis of thyroid cancer associated with the male gender is poorly explained.

Impaired sensitivity to thyroid hormones encompasses disorders with defective transport of hormones into cells, reduced hormone metabolism, and resistance to hormone action. Mediated by heritable single-gene defects, these rare conditions exhibit different patterns of discordant thyroid function associated with multisystem phenotypes. In this context, challenges include ruling out other causes of biochemical discordance, making a diagnosis using clinical features together with the identification of pathogenic variants in causal genes, and managing these rare disorders with a limited evidence base. For each condition, the present guidelines aim to inform clinical practice by summarizing key clinical features and useful investigations, criteria for molecular genetic diagnosis, and pathways for management and therapy. Specific, key recommendations were developed by combining the best research evidence available with the knowledge and clinical experience of panel members, to achieve a consensus.

Pregnancy induces physiological alterations in thyroid function which may make difficult the interpretation of results of thyroid hormone measurement. A state of hyperstimulation of the thyroid gland is common in early pregnancy. In a few cases, thyroid hormone values will deviate from the normal range, which corresponds to the gestational transient thyrotoxicosis. This syndrome is closely associated with hyperemesis gravidarum. The relationship between the two syndromes, demonstrated by epidemiological studies, has been illustrated by an exceptional case of familial recurrent gestational thyrotoxicosis presenting as hyperemesis gravidarum due to hypersensitivity of the thyrotrophin receptor to hCG. However, the exact mechanisms of hyperemesis gravidarum have not yet been identified. Gestational transient thyrotoxicosis has to be distinguished from Graves’ disease, because the latter is associated with potential maternal and fetal complications when thyrotoxicosis is not controlled, whereas the former has usually a favourable outcome. The existence of other cases of thyroid hypersensitivity or hCG endowed with abnormal thyrotrophic activity is suspected. They may be identified only by assessment of the thyroid function in cases of hyperemesis gravidarum. The identification of these cases would be helpful to understand the mechanisms of specificity of glycoprotein hormone receptors.