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Acromegaly is a rare disease with prevalence of approximately 60 cases per million, slight female predominance and peak onset in adults in the fourth decade. Clinical diagnosis is often delayed by several years due to the slowly progressive onset of symptoms. There are multiple clinical criteria that define acromegaly: dysmorphic syndrome of insidious onset, symptoms related to the pituitary tumor (headaches, visual disorders), general signs (sweating, carpal tunnel syndrome, joint pain, etc.), complications of the disease (musculoskeletal, cardiovascular, pneumological, dental, metabolic comorbidities, thyroid nodules, colonic polyps, etc.) or sometimes clinical signs of associated prolactin hypersecretion (erectile dysfunction in men or cycle disorder in women) or concomitant mass-induced hypopituitarism (fatigue and other symptoms related to pituitary hormone deficiencies). Biological confirmation is based initially on elevated IGF-I and lack of GH suppression on oral glucose tolerance test or an elevated mean GH on repeated measurements. In confirmed cases, imaging by pituitary MRI identifies the causal tumor, to best determine management. In a minority of cases, acromegaly can be linked to a genetic predisposition, especially when it occurs at a young age or in a familial context. The first-line treatment is most often surgical removal of the somatotroph pituitary tumor, either immediately or after transient medical treatment. Medical treatments are most often proposed in patients not controlled by surgical removal. Conformal or stereotactic radiotherapy may be discussed on a case-by-case basis, especially in case of drug inefficacy or poor tolerance. Acromegaly should be managed by a multidisciplinary team, preferably within an expert center such as a reference or skill center for rare pituitary diseases.

Patients with germline SDHDpathogenic variants (encoding succinate dehydrogenase subunit D; ie, paraganglioma 1 syndrome) are predominantly affected by head and neck paragangliomas, which, in almost 20% of patients, might coexist with paragangliomas arising from other locations (eg, adrenal medulla, para-aortic, cardiac or thoracic, and pelvic). Given the higher risk of tumour multifocality and bilaterality for phaeochromocytomas and paragangliomas (PPGLs) because of SDHDpathogenic variants than for their sporadic and other genotypic counterparts, the management of patients with SDHDPPGLs is clinically complex in terms of imaging, treatment, and management options. Furthermore, locally aggressive disease can be discovered at a young age or late in the disease course, which presents challenges in balancing surgical intervention with various medical and radiotherapeutic approaches. The axiom—first, do no harm—should always be considered and an initial period of observation (ie, watchful waiting) is often appropriate to characterise tumour behaviour in patients with these pathogenic variants. These patients should be referred to specialised high-volume medical centres. This consensus guideline aims to help physicians with the clinical decision-making process when caring for patients with SDHDPPGLs.

•Hypophysitis is a common IRAE in patients undergoing anti-CTLA-4 and combination treatment and appears to be dose-dependent.•PAI is a rare IRAE, which occurs especially in patients with nivolumab or ipilimumab in monotherapy or combination treatment.•Clinical and hormonal monitoring before and during immunotherapy is necessary for early diagnosis of hypophysitis or PAI, especially in the first months of treatment, with special attention paid to TSH level in hypophysitis (TSH decrease may precede hypophysitis).•If hypophysitis or PAI is suspected, the corticotropin replacement is an emergency.•ACTH assay is useful to distinguish PAI from SAI, and thus add mineralocorticoid therapy in PAI, and examine the other endocrine axes in cases of SAI.•Imaging must be performed if hypophysitis (MRI) or a PAI (adrenal CT) is suspected, with monitoring for the first 3 months for hypophysitis, especially to rule out differential diagnosis of cerebral or bilateral adrenal metastasis.•Diabetes insipidus and visual disorder are rare in immunotherapy-induced hypophysitis.•In case of hypophysitis or PAI, high-dose GCs should not be administered systematically, but only in case of major tumour syndrome (severe resistant headache or visual disorder) in hypophysitis.•Immunotherapy should not be stopped (can sometimes be delayed) in case of ICI-induced hypophysitis or PAI.•Adrenal insufficiency in PAI and corticotropin deficiency in hypophysitis are usually definitive and require education of patients and oncologists on adaptation and injection of hydrocortisone.•Multidisciplinary long-term follow-up with an endocrinologist and an oncologist is needed in such endocrine IRAEs.

Cushing's syndrome is defined by prolonged exposure to glucocorticoids, leading to excess morbidity and mortality. Diagnosis of this rare pathology is difficult due to the low specificity of the clinical signs, the variable severity of the clinical presentation, and the difficulties of interpretation associated with the diagnostic methods. The present consensus paper by 38 experts of the French Society of Endocrinology and the French Society of Pediatric Endocrinology and Diabetology aimed firstly to detail the circumstances suggesting diagnosis and the biologic diagnosis tools and their interpretation for positive diagnosis and for etiologic diagnosis according to ACTH-independent and -dependent mechanisms. Secondly, situations making diagnosis complex (pregnancy, intense hypercortisolism, fluctuating Cushing's syndrome, pediatric forms and genetically determined forms) were detailed. Lastly, methods of surveillance and diagnosis of recurrence were dealt with in the final section.

Although usually benign, anterior pituitary tumours occasionally exhibit aggressive behaviour, with invasion of surrounding tissues, rapid growth, resistance to conventional treatments and multiple recurrences. In very rare cases, they metastasize and are termed pituitary carcinomas. The time between a ‘classical’ pituitary tumour and a pituitary carcinoma can be years, which means that monitoring should be performed regularly in patients with clinical (invasion and/or tumour growth) or pathological (Ki67 index, mitotic count and/or p53 detection) markers suggesting aggressiveness. However, although both invasion and proliferation have prognostic value, such parameters cannot predict outcome or malignancy without metastasis. Future research should focus on the biology of both tumour cells and their microenvironment, hopefully with improved therapeutic outcomes. Currently, the initial therapeutic approach for aggressive pituitary tumours is generally to repeat surgery or radiotherapy in expert centres. Standard medical treatments usually have no effect on tumour progression but they can be maintained on a long-term basis to, at least partly, control hypersecretion. In cases where standard treatments prove ineffective, temozolomide, the sole formally recommended treatment, is effective in only one-third of patients. Personalized use of emerging therapies, including peptide receptor radionuclide therapy, angiogenesis-targeted therapy and immunotherapy, will hopefully improve the outcomes of patients with this severe condition.

Cushing's syndrome is defined by an endogenous or exogenous hypercortisolism. Increased cortisol, as well as increased androgens will have a negative impact on the pulsatile secretion of GnRH, thus leading to an increased risk of infertility. However, pregnancy can occur in a woman with Cushing's syndrome: it is a challenging situation, because of the numerous consequences which can be observed in the mother (increased risk of gestational diabetes, hypertension, eclampsia… in addition to the specific complications of hypercortisolism) and in the fetus (intrauterine growth retardation, prematurity). In contrast, Cushing's syndrome can also appear during pregnancy. It is a very rare situation: the diagnosis is challenging because of the numerous hormonal changes induced by pregnancy on cortisol levels. The objective of this brief review will be to detail the mechanisms of infertility due to hypercortisolism, the diagnostic methods of Cushing's syndrome during pregnancy, the maternal and fetal consequences of hypercortisolism during pregnancy, and finally the potential means of contraception that can be proposed.

The aim of this study was to describe endocrinological outcome in patients operated on for acromegaly.

Pancreatic neuroendocrine tumors (PNETs) occur in more than 80% of patients with multiple endocrine neoplasia type 1 (MEN1) syndrome, with predominance of small (<1cm) non-functioning tumors, followed by gastrinomas and insulinomas. Due to their small size, the diagnostic performance of conventional MRI and CT imaging is highly variable, with a real risk of false-negatives. Functional imaging on 111In-DTPA-Octreotide SPECT somatostatin receptor scintigraphy (Octreoscan®) is the modality of choice, but shows only 80% sensitivity. Alternatively, 18F-fluorodihydroxyphenylalanine (FDOPA) and, more recently, 68Ga-Dotatate PET/CT imaging are valuable options in case of negative Octreoscan®.

Au cours des dix dernières années, la prise en charge des cancers a été modifiée par l’utilisation de plus en plus fréquente de l’immunothérapie. Cependant, ces molécules exposent à des effets secondaires, parmi lesquels des toxicités endocriniennes. Les indications de ces molécules étant en constante augmentation du fait de leur efficacité, il est important que les endocrinologues et les oncologues sachent dépister, prendre en charge et surveiller ce type de toxicité. Dans cette optique, la Société française d’endocrinologie a initié la rédaction d’un consensus d’experts sur les toxicités endocriniennes de l’immunothérapie. Le texte présenté ici est une synthèse pour l’oncologue de ces avis d’experts : il est en particulier souligné le bilan initial à effectuer, la surveillance, les situations d’urgence pour lesquelles la prise en charge oncologique immédiate est cruciale, et la place de l’interaction entre l’oncologue référent et l’endocrinologue (que ce soit pour le diagnostic, le suivi ou la prise en charge). Ces points seront abordés pour chacune des quatre endocrinopathies induites, à savoir la thyroïdite, l’hypophysite, le diabète sucré et l’insuffisance surrénale. Enfin, une mise en perspective de la prise en charge de ces endocrinopathies et des recommandations globales du CTCAE (Common terminology criteria for adverse events) sera également effectuée.

The authors reported 2 cases of functioning gonadotroph pituitary adenoma (FGPA) revealed by an ovarian hyperstimulation syndrome (OHSS) in young women. In the first case, OHSS was observed after GnRH analog injection. Pelvic echography revealed multiple voluminous ovarian cysts. Dopamine agonist posology failed in estradiol hypersecretion control, which necessitated endoscopic endonasal transsphenoidal surgery. The patient experienced improvement in pelvic pain as estradiol hypersecretion decreased during the first few postoperative days. Outcome was favorable, and her menstrual cycle was normal after two months. The second case was a young girl with spontaneous pelvic pain and elevated plasma FSH and estradiol levels. FGPA was confirmed on cerebral MRI. Dopamine agonists were introduced, and surgical removal of the pituitary tumor was scheduled for 7 days later. In the meantime, the patient was admitted and underwent surgery for bilateral adnexal torsion related to OHSS. The pituitary tumor was removed one week later. Outcome was favorable, and estradiol and FSH plasma levels were normal after 3 months. The ovarian cysts were no longer visible on echography after 3 months. Given the lack of efficacy of the current standard medical therapy, surgical removal of pituitary adenomas is the reference treatment for FGPA. The authors suggest that severe OHSS related to FGPA should be considered as a relative surgical emergency and that surgery should not be unduly delayed, given the unpredictable risk of adnexal torsion, particularly in case of voluminous ovarian cysts. The authors performed a literature review on this topic.

The present final consensus statement of the French Society of Endocrinology lays out the assessments that are to be systematically performed before and during anticancer treatment by immunotherapy, tyrosine kinase inhibitors or mTOR inhibitors, even without onset of any endocrinopathy. It also discusses the CTCAE adverse event grading system in oncology and the difficulty of implementing it for endocrine side-effects of these anticancer treatments. Notably, this is why certain treatment steps applied in other side-effects (e.g., high-dose corticosteroids, contraindications to immunotherapy, etc.) need to be discussed before implementation for endocrine side-effects.

MYC-associated factor X (MAX) has been recently described as a new susceptibility pheochromocytoma (PHEO) gene with a total of ~40 reported cases. At present, no study has specifically described the functional imaging phenotype of MAX-related PHEO.

The French endocrinology society (SFE) and the French pediatric endocrinology society (DFSDP) have drawn up recommendations for the management of primary and secondary adrenal insufficiency in the adult and child, based on an analysis of the literature by 19 experts in 6 work-groups. A diagnosis of adrenal insufficiency should be suspected in the presence of a number of non-specific symptoms except hyperpigmentation which is observed in primary adrenal insufficiency. Diagnosis rely on plasma cortisol and ACTH measurement at 8am and/or the cortisol increase after synacthen administration. When there is a persistant doubt of secondary adrenal insufficiency, insulin hypoglycemia test should be carried out in adults, adolescents and children older than 2 years. For determining the cause of primary adrenal insufficiency, measurement of anti-21-hydroxylase antibodies is the initial testing. An adrenal CT scan should be performed if auto-antibody tests are negative, then assay for very long chain fatty acids is recommended in young males. In children, a genetic anomaly is generally found, most often congenital adrenal hyperplasia. In the case of isolated corticotropin (ACTH) insufficiency, it is recommended to first eliminate corticosteroid-induced adrenal insufficiency, then perform an hypothalamic-pituitary MRI. Acute adrenal insufficiency is a serious condition, a gastrointestinal infection being the most frequently reported initiating factor. After blood sampling for cortisol and ACTH assay, treatment should be commenced by parenteral hydrocortisone hemisuccinate together with the correction of hypoglycemia and hypovolemia. Prevention of acute adrenal crisis requires an education of the patient and/or parent in the case of pediatric patients and the development of educational programs. Treatment of adrenal insufficiency is based on the use of hydrocortisone given at the lowest possible dose, administered several times per day. Mineralocorticoid replacement is often necessary for primary adrenal insufficiency but not for corticotroph deficiency. Androgen replacement by DHEA may be offered in certain conditions. Monitoring is based on the detection of signs of under- and over-dosage and on the diagnosis of associated auto-immune disorders.

Management of macroprolactinomas has dramatically changed in recent decades, from surgical to medical treatment as first-line therapy, with the development of dopamine agonists (DA). But few data exist on the long-term outcome of these patients.

Clinically NFPA is currently the preferred term for designing all the pituitary adenomas which are not hormonally active (in other words, not associated with clinical syndromes such as amenorrhea-galactorrhea in the context of prolactinomas, acromegaly, Cushing's disease or hyperthyroidism secondary to TSH-secreting adenomas). They account for 15–30% of pituitary adenomas. Diagnosis is usually made either in the context of mass effect due to a macroadenoma or, increasingly, fortuitously during imaging performed for some unrelated purpose; the latter case is known as pituitary incidentaloma. Surgery is indisputably indicated in case of tumoral syndrome, but other aspects of NFPA (hormonal work-up, follow-up, and especially postoperative follow-up, management of remnant or recurrence, the special case of incidentaloma, or apoplexy) remain controversial. The French Endocrinology Society (SFE) therefore set up an expert working group of endocrinologists, neurosurgeons, ophthalmologists, neuroradiologists, pathologists and biologists to draw up guidelines, at the 2012 SFE Congress in Toulouse, France. The present article presents the guidelines suggested by this group of French-speaking experts.

Through the multicentric international GENHYPOPIT network, 10 transcription factor genes involved in pituitary development have been screened in more than 1200 patients with constitutional hypopituitarism over the past two decades. The present report summarizes the main lessons learned from this phenotype-based genetic screening: (1) genetically determined hypopituitarism does not necessarily present during childhood; (2) constitutional hypopituitarism may be characterized by a pure endocrine phenotype or by various combinations of endocrine deficits and visceral malformations; (3) syndromic hypopituitarism may also be observed in patients with POU1F1 or PROP1 mutations; (4) in cases of idiopathic hypopituitarism, extensive genetic screening identifies gene alterations in a minority of patients; (5) functional studies are imperfect in determining the involvement of an allelic variant in a specific pituitary phenotype.

To describe the results of growth hormone (GH) therapy in adult GH-deficient patients treated in a tertiary referral center, with a focus on quality of life and adherence.