AIP mutations, of which nine new mutations have been described here, occur in approximately 15% of FIPA families. Although pituitary tumors occurring in association with AIP mutations are predominantly somatotropinomas, other tumor types are also seen. Further study of the impact of AIP mutations on protein expression and activity is necessary to elucidate their role in pituitary tumorigenesis in FIPA.

Transcription factor SOX10 plays a role in the maintenance of progenitor cell multipotency, lineage specification, and cell differentiation and is a major actor in the development of the neural crest. It has been implicated in Waardenburg syndrome (WS), a rare disorder characterized by the association between pigmentation abnormalities and deafness, but SOX10 mutations cause a variable phenotype that spreads over the initial limits of the syndrome definition. On the basis of recent findings of olfactory-bulb agenesis in WS individuals, we suspected SOX10 was also involved in Kallmann syndrome (KS). KS is defined by the association between anosmia and hypogonadotropic hypogonadism due to incomplete migration of neuroendocrine gonadotropin-releasing hormone (GnRH) cells along the olfactory, vomeronasal, and terminal nerves. Mutations in any of the nine genes identified to date account for only 30% of the KS cases. KS can be either isolated or associated with a variety of other symptoms, including deafness. This study reports SOX10 loss-of-function mutations in approximately one-third of KS individuals with deafness, indicating a substantial involvement in this clinical condition. Study of SOX10-null mutant mice revealed a developmental role of SOX10 in a subpopulation of glial cells called olfactory ensheathing cells. These mice indeed showed an almost complete absence of these cells along the olfactory nerve pathway, as well as defasciculation and misrouting of the nerve fibers, impaired migration of GnRH cells, and disorganization of the olfactory nerve layer of the olfactory bulbs.

SummaryThe thyroid is the organ with the highest selenium content per gram of tissue because it expresses specific selenoproteins. Since the discovery of myxoedematous cretinism and thyroid destruction following selenium repletion in iodine-and seleniumdeficient children, data on links between thyroid metabolism and selenium have multiplied. Although very minor amounts of selenium appear sufficient for adequate activity of deiodinases, thus limiting the impact of its potential deficiency on synthesis of thyroid hormones, selenium status appears to have an impact on the development of thyroid pathologies. The value of selenium supplementation in autoimmune thyroid disorders has been emphasized. Most authors attribute the effect of supplementation on the immune system to the regulation of the production of reactive oxygen species and their metabolites. In patients with Hashimoto's disease and in pregnant women with anti-TPO antibodies, selenium supplementation decreases anti-thyroid antibody levels and improves the ultrasound structure of the thyroid gland. Although clinical applications still need to be defined for Hashimoto's disease, they are very interesting for pregnant women given that supplementation significantly decreases the percentage of postpartum thyroiditis and definitive hypothyroidism. In Graves' disease, selenium supplementation results in euthyroidism being achieved more rapidly and appears to have a beneficial effect on mild inflammatory orbitopathy. A risk of diabetes has been reported following long-term selenium supplementation, but few data are available on the side effects associated with such supplementation and further studies are required.

Homogeneous and heterogeneous expression of prolactinomas, somatotropinomas, NS, and Cushing's disease can occur within families in the absence of MEN1/CNC. FIPA and sporadic cases have differing clinical characteristics. FIPA may represent a novel endocrine neoplasia classification that requires further genetic characterization.

The management of cancer patients has changed due to the considerably more frequent use of immune checkpoint inhibitors (ICPIs). However, the use of ICPI has a risk of side effects, particularly endocrine toxicity. Since the indications for ICPI are constantly expanding due to their efficacy, it is important that endocrinologists and oncologists know how to look for this type of toxicity and how to treat it when it arises. In view of this, the French Endocrine Society initiated the formulation of a consensus document on ICPI-related endocrine toxicity. In this paper, we will introduce data on the general pathophysiology of endocrine toxicity, and we will then outline expert opinion focusing primarily on methods for screening, management and monitoring for endocrine side effects in patients treated by ICPI. We will then look in turn at endocrinopathies that are induced by ICPI including dysthyroidism, hypophysitis, primary adrenal insufficiency and fulminant diabetes. In each chapter, expert opinion will be given on the diagnosis, management and monitoring for each complication. These expert opinions will also discuss the methodology for categorizing these side effects in oncology using ‘common terminology criteria for adverse events’ (CTCAE) and the difficulties in applying this to endocrine side effects in the case of these anti-cancer therapies. This is shown in particular by certain recommendations that are used for other side effects (high-dose corticosteroids, contraindicated in ICPI for example) and that cannot be considered as appropriate in the management of endocrine toxicity, as it usually does not require ICPI withdrawal or high-dose glucocorticoid intake.