Objective Data on pituitary neuroendocrine tumours (PitNETs) surgically treated during pregnancy are limited, and no studies have compared these cases to those treated in non-pregnant women. This study aimed to describe the clinical, radiological, and histological profiles of patients treated surgically for PitNETs during pregnancy and evaluate long-term prognosis.Design This study was multicentric, observational, and retrospective.Methods We included 10 patients from 5 university hospitals who underwent surgical treatment for PitNETs during pregnancy or within 12 months postpartum, along with 30 matched non-pregnant controls treated surgically for PitNETs. Clinical and histological data, as well as progression-free survival without additional treatment, were compared between pregnant and non-pregnant patients.Results and conclusions Among the 10 PitNETs, 4 were corticotropic, 2 gonadotropic, 2 lactotropic, and 2 somatotropic. The primary surgical indication (tumour syndrome with or without failure of medical treatment) was similar between the two groups: 7/10 vs 19/30 (P = 1.00). There was no statistically significant difference in volume (P = .072) or radiological invasion markers (optic chiasm compression, P = .059, and cavernous sinus invasion, P = .274). However, PitNETs in pregnant women showed higher mitotic activity (P = .038) and were more frequently classified as grade 2b (Trouillas clinicopathological classification; P = .049). The need for second-line treatment was also more frequent (P = .005). PitNETs requiring surgical treatment during pregnancy are characterized by increased proliferative activity and progression after surgery. Despite this, the long-term prognosis remains favourable. These results need confirmation in a larger study.

BACKGROUND:RET variants affecting codon 804 are part of the low-to-moderate risk group in the ATA classification, with indications for prophylactic thyroidectomy beyond age of 5years. However, aggressiveness seems to be variable. The objective of this study was to report a large cohort of French carriers of a pathogenic variant at codon 804 in the RET proto-oncogene. METHODS:Patients from 12 university hospitals with a RET 804 variant were recruited in this retrospective non-interventional French national study, from the French GTE-ENDOCAN-RENATEN database. Incidence and severity (TNM stage and calcitonin levels) of medullary thyroid carcinoma (MTC), phenotype-genotype correlation and clinical outcome were assessed. RESULTS:A total of 322 patients were analyzed. Index cases (n=65) had a median age at diagnosis of 57years (range: 46-66), and relatives (n=257) a median age of 37years (range: 18-51). Median first calcitonin measurement was 240ng/L (range: 79-1344) in index cases, and 6.7ng/L (range: 0-22) in relatives. In index cases, the pathogenic variant c.2410G>A (p.Val804Met) in RET was more frequent (80% of cases) than c.2410G>C or c.2410G>T (p.Val804Leu). MTC was multifocal, node-positive and metastatic in 64%, 51% and 20% of cases respectively. TNM stage, preoperative calcitonin level and male gender were predictive of persistent disease (defined by postoperative calcitonin>5ng/L) (P<0.001). Ten-year disease-free survival (DFS) was 61%. In total, 113 relatives were operated on: 62% with MTC and 34% with isolated C-cell hyperplasia (CCH); the youngest patients were aged 20 for MTC and 4years for CCH. Ten-year DFS was 90%. CONCLUSION:The RET pathogenic variants affecting the codon 804 mainly led to low aggressiveness disease, with late presentation and prolonged DFS. We suggest surgery in relatives if calcitonin values are above 6ng/L, instead of 10ng/L. Long-term surveillance is mandatory, since recurrence remains possible several years after surgery.

Abstract:Apalutamide, a selective androgen receptor antagonist, is a new treatment for prostate cancer. Among the side effects observed during apalutamide treatment, an increased risk of hypothyroidism has been reported, particularly in patients previously treated with levothyroxine compared with untreated patients. Apalutamide is thought to stimulate hepatic UDP-glucuronosyltransferase activity, resulting in increased clearance and stimulation of the thyroxine enterohepatic cycle. A 65-year-old man on 150 μg/day levothyroxine treatment after total thyroidectomy for Graves' disease was euthyroid. Treatment with apalutamide (240 mg/day) was started for metastatic prostate neoplasia. After 1 month, the TSH level was 47.9 μIU/mL, and the dose of levothyroxine was gradually increased. In the presence of refractory hypothyroidism (TSH 38 μIU/mL) despite 275 μg/day of levothyroxine (3.25 μg/kg/d), a levothyroxine absorption test was performed: the basal concentration of total T4 was 5.8 μg/dL; after oral absorption of 1,000 μg of levothyroxine, total T4 concentration increased, peaking at 8.1 μg/dL after 2 h. The percentage absorption of levothyroxine was 27.1% (normal: >60%). After 14 h, total T4 concentration fell to 5.7 μg/dL before rising again to 8.5 μg/dL at 20 h. In the absence of further levothyroxine intake, the second peak of total T4 concentration may be related to stimulation of UDP-glucuronosyltransferase activity, with increased T4 solubility in the bile, released into the small intestine, and finally absorbed, with increased T4 concentration at 20 h in the patient, attesting to the stimulated T4 enterohepatic cycle during apalutamide treatment. Overall, the result of this clinical study suggests that apalutamide reduces the digestive absorption of levothyroxine, in addition to stimulating the activity of hepatic UDP-glucuronosyltransferase, explaining the higher prevalence of hypothyroidism during apalutamide treatment in patients previously treated with levothyroxine.

BACKGROUND:Endocrine science remains underrepresented in European Union research programs despite the fundamental role of hormone health in human well-being. Analysis of the CORDIS database reveals a persistent gap between the societal impact of endocrine disorders and their research prioritization. At national funding level, endocrine societies report limited or little attention of national research funding toward endocrinology. The EndoCompass project-a joint initiative between the European Society of Endocrinology and the European Society of Paediatric Endocrinology, aimed to identify and promote strategic research priorities in endocrine science to address critical hormone-related health challenges. METHODS:Research priorities were established through comprehensive analysis of the EU CORDIS database covering the Horizon 2020 framework period (2014-2020). Expert consultation in thyroid endocrinology was conducted to identify key research priorities, followed by broader stakeholder engagement including society members and patient advocacy groups. RESULTS:For thyroid disorders, research priorities encompass neoplastic and nonneoplastic conditions, focusing on disease mechanisms, improved diagnostics and treatments, and the impact of environmental and metabolic factors. Key areas include personalized medicine approaches, artificial intelligence applications, and the establishment of pan-European registries to advance understanding of rare thyroid conditions. CONCLUSIONS:The thyroid component of the EndoCompass project provides an evidence-based roadmap for strategic research investment. This framework identifies crucial investigation areas into thyroid disease pathophysiology, prevention, and treatment strategies, ultimately aimed at reducing the burden of thyroid disorders on individuals and society. The findings support the broader EndoCompass objective of aligning research funding with areas of highest potential impact in endocrine health.

Craniopharyngiomas are rare hypothalamic-pituitary tumors found in young children, adolescents and adults, and their multidisciplinary management required, calls for consistent practices for practicioners, patients and families. The French Endocrine Society and French Society for Pediatric Endocrinology & Diabetes enlisted and coordinated adult and paediatric endocrinologists, neurosurgeons, pathologists, radiotherapists as well as psychologists, dieticians and a patient association, to draft a reference document on this severe disease. The management of craniopharyngiomas remains complex due to their aggressive nature, invasive behavior, and propensity for recurrence, requiring a sequential and measured therapeutic approach and follow-up in expert centers. Although patient survival rates are high, the consequences of both the tumor and its treatment can lead to serious comorbidities and impaired quality of life, particularly in those patients with lesional hypothalamic syndrome. Recent advances have allowed the two described tumor types - papillary and adamantinomatous - to be associated with distinct molecular signatures, specific pathophysiological mechanisms and ipso facto, distinct therapeutic approaches, including innovative medications for hyperphagia, that will continue to evolve. This consensus statement covers all stages in the management of patients with craniopharyngioma, from diagnosis to therapeutic strategies including the long-term follow-up.

Hypothyroidism is a frequent disease, and oral levothyroxine is the mainstay of its treatment. However, more than 15% of levothyroxine-treated patients fail to achieve the recommended serum TSH level, and "refractory hypothyroidism" is due to either malabsorption, increased metabolism of thyroxine, or nonadherence to treatment. A levothyroxine absorption test must be used to differentiate true malabsorption from nonadherence or pseudo-malabsorption. We analyzed 166 levothyroxine absorption tests in 143 hypothyroid patients (109 women, mean age 43 ± 1 years) treated with oral levothyroxine. Despite a daily dose of 3.26 ± 0.09 g/kg/day, mean serum TSH concentration was 25.7 ± 3.7 mU/L. "Refractory hypothyroidism" was in the context of gastritis (24%), Helicobacter pylori infection (18%), drug interference with levothyroxine absorption (15.6%), nonadherence to treatment (10%), celiac disease (2.5%), or bariatric surgery (1.2%). After an overnight fast, patients orally took their daily dose of levothyroxine (220 ± 6 g), and blood samples were drawn before levothyroxine intake and every 2 hours for 24 hours. After levothyroxine intake, the mean total (basal = 7.64 ± 0.26 g/dL, peak 9.41 ± 0.28 g/dL), and free (basal = 12.58 ± 0.42 pg/mL, peak 15.77 ± 0.51 pg/mL) T4 levels increased (P < .001), total and free T4 peaks were observed at 4.2 ± 0.23 and 4.30 ± 9.27 hours, respectively. Levothyroxine absorption tests were well tolerated. In conclusion, in most patients with "refractory hypothyroidism," this clinical study revealed that the levothyroxine absorption test can be achieved via the absorption of the daily dosage of levothyroxine, and the evaluation of total or free T4 concentrations over 4- or 6-hour follow-up. The test is well tolerated without cardiovascular adverse events.