French expert consensus statement on diagnosis and MANAGEMENT of PRIMARY HYPERPARATHYROIDISM.

In 2024, the French Society of Endocrinology, the French speaking association of endocrine surgery, and the French society of nuclear medicine have elaborated a joint consensus statement on primary hyperparathyroidism, which was presented at the last congress of the French Society of Endocrinology, in October 2024, and subsequently published as 15 individual chapters in the Annals of Endocrinology. This consensus statement is a fruit of a joint effort by over 80 French-speaking experts in the field, including adult and pediatric endocrinologists, endocrine and pediatric surgeons, radiologists, nuclear medicine specialists, biologists and geneticists, and has been endorsed by the Belgian and Swiss endocrine societies. This document summarizes the recommendations, subdivided into 15 sections each preceded by a brief introduction.

A recurrent splice variant sheds light on 11beta-hydroxylase deficiency in a unique large cohort.

Context: Congenital adrenal hyperplasia (CAH) can be due to 11β-hydroxylase deficiency (11βOHD). Sporadic reports of 11βOHD are frequent but overviews on molecular landscape in some populations are lacking.

Objective: The aim of this research was to compile a genetic landscape from a 11βOHD cohort, and to report a novel yet recurrent splice variant.

Performance of afternoon (16:00 h) serum cortisol for the diagnosis of Cushing's syndrome.

Introduction: Late-night salivary cortisol (LNSC), which assesses the loss of the circadian rhythm of cortisol, is one of the first-line tests performed to diagnose Cushing's syndrome (CS). Unfortunately, access to LNSC is still limited in some institutions. Alternatively, midnight serum cortisol can be measured, often combined with additional cortisol sampling over 24 h.

Bone, a double victim in metastatic catecholamine secreting tumors.

Introduction: Benign catecholamine-secreting pheochromocytoma and paraganglioma (PPGL) can cause secondary osteoporosis. Metastatic PPGLs, often presenting with bone metastases, elevated catecholamine levels and persistent disease, may lead to more severe bone impact. We investigated bone density and quality in three cases of metastatic PPGL over long-term follow-up.

Surgery for the treatment of arterial hypertension in patients with unilateral adrenal incidentalomas and mild autonomous cortisol secretion (CHIRACIC): a multicentre, open-label, superiority randomised controlled trial.

Background: Adrenal incidentalomas are found in 3-10% of adults undergoing abdominal imaging. Of these, 30-50% are responsible for mild autonomous cortisol secretion (MACS), which is frequently associated with hypertension. The impact of adrenalectomy on hypertension in patients with unilateral incidentalomas and MACS remains uncertain.

Identification of metabolite biomarkers for pancreatic neuroendocrine tumours using a metabolomic approach.

Importance: Metabolic flexibility, a key hallmark of cancer, reflects aberrant tumour changes associated with metabolites. The metabolic plasticity of pancreatic neuroendocrine tumours (pNETs) remains largely unexplored. Notably, the heterogeneity of pNETs complicates their diagnosis, prognosis, and therapeutic management.

KDM1A genetic alterations, a rare cause of primary bilateral macronodular adrenal hyperplasia, strongly associated with food-dependent Cushing's syndrome: results of its systematic germline screening in 301 index cases and genotype/phenotype correlation.

Objective: ARMC5 is the most prevalent gene predisposing to primary bilateral macronodular adrenal hyperplasia (PBMAH), but germline KDM1A variants have been identified in the rare PBMAH associated with food-dependent Cushing's syndrome (FDCS). The purpose of this work was to assess the frequency of KDM1A variants in a large series of PBMAH patients.

Design: A total of 301 consecutive PBMAH index cases from 8 international endocrinology departments were included.

The mutational landscape of ARMC5 in Primary Bilateral Macronodular Adrenal Hyperplasia: an update.

Background: Primary Bilateral Macronodular Adrenal Hyperplasia (PBMAH) is a rare cause of Cushing's syndrome due to bilateral adrenocortical macronodules. Germline inactivating variants of the tumor suppressor gene ARMC5 are responsible for 20-25% of apparently sporadic PBMAH cases and 80% of familial presentations. ARMC5 screening is now routinely performed for PBMAH patients and families.

Chapter 11: Treatment modalities.

Treatment modalities for primary hyperparathyroidism must take account of the expected benefits and risks of each treatment envisaged, before choosing the definitive option to be proposed to the patient. In this section, a Foreword puts in perspective the difficulties involved in choosing the criteria for a particular treatment method. Treatments are then considered one after the other: surgery, local destruction and medical management.

PDE11A Is a Phenotype Modulator of Primary Bilateral Macronodular Adrenal Hyperplasia: Results of a 334-Patient Series.

Context: Primary bilateral macronodular adrenal hyperplasia (PBMAH), the most common cause of Cushing syndrome due to bilateral nodules, is a heterogeneous disease at the clinical, hormonal, and morphological levels. ARMC5-inactivating pathogenic variants are causative of PBMAH, and rare variants of PDE11A have been associated with PBMAH.

Objective: The aim of this study, on a large cohort of individuals with PBMAH from Europe and America, was to study the ARMC5 and PDE11A genotype to determine the genotype/phenotype correlation and to investigate the hypothesis that PDE11A could be a modifying gene of the adrenal phenotype.

Impact of therapeutic doses of prednisolone and other glucocorticoids on insulin secretion from human islets.

Introduction: Glucocorticoid-induced diabetes (GCID) is a prevalent health issue, generally attributed to insulin resistance. High doses of dexamethasone (DEX) are known to inhibit glucose-stimulated insulin secretion (GSIS), but the effects of lower doses, commonly used in chronic therapy, and equipotent doses of other glucocorticoids (GCs) such as hydrocortisone (HC) and prednisone (PRED) remain underexplored. This study aimed to investigate these effects in vitro, and explore variations between patients.

Beyond MEN1, When to Think About MEN4? Retrospective Study on 5600 Patients in the French Population and Literature Review.

Context: Germline CDKN1B variants predispose patients to multiple endocrine neoplasia type 4 (MEN4), a rare MEN1-like syndrome, with <100 reported cases since its discovery in 2006. Although CDKN1B mutations are frequently suggested to explain cases of genetically negative MEN1, the prevalence and phenotype of MEN4 patients is poorly known, and genetic counseling is unclear.

Objective: To evaluate the prevalence of MEN4 in MEN1-suspected patients and characterize the phenotype of MEN4 patients.

Consensus statement by the French Society of Endocrinology (SFE) and French Society of Pediatric Endocrinology & Diabetology (SFEDP) for the diagnosis of Cushing's syndrome: Genetics of Cushing's syndrome.

Cushing's syndrome is due to overproduction of cortisol, leading to abnormal and prolonged exposure to cortisol. The most common etiology is Cushing disease, while adrenal causes are rarer. Knowledge of the genetics of Cushing's syndrome, and particularly the adrenal causes, has improved considerably over the last 10 years, thanks in particular to technical advances in high-throughput sequencing.

Carney complex predisposes to breast cancer: prospective study of 50 women.

Objective: Carney complex (CNC) is a rare genetic syndrome, mostly due to germline loss-of-function pathogenic variants in PRKAR1A. Carney complex includes pigmented skin lesions, cardiac myxomas, primary pigmented nodular adrenocortical dysplasia, and various breast benign tumors.

Design: The present study was designed to describe the characteristics of breast lesions in CNC patients and their association with other manifestations of CNC and PRKAR1A genotype.

Steroid hormones in systemic sclerosis: associations with disease characteristics and modifications during scleroderma renal crisis.

Objective: The renin-angiotensin-aldosterone system (RAAS) and glucocorticoids (GCs) are involved in vascular remodeling and fibrosis but have not been extensively studied in systemic sclerosis (SSc). Our aim was to investigate the RAAS and GC hormones in SSc patients.

Methods: Serum levels of renin (dosage and activity), aldosterone and its precursors (DOC, B, 18-OH-DOC, 18-OH-B), and GCs (cortisol, cortisone, 11-deoxycortisol, 18-OH-F) were assessed in 122 SSc patients and 52 healthy controls.

Complete pathological response following chemotherapy and radiotherapy in two cases of advanced anaplastic thyroid carcinoma.

Introduction: Anaplastic thyroid carcinoma (ATC) is the most aggressive form of thyroid cancer with a bleak prognosis. Favorable outcomes are rare but help decipher molecular pathophysiology, investigate prognosis factors, and discover new therapeutic targets.

Case Presentation: Two patients were diagnosed with locally advanced nonresectable ATC, one with metastatic extension.

Pituitary adenoma & nuclear medicine: Recent outcomes and ongoing developments.

In order to explore pituitary adenoma (PA), magnetic resonance imaging (MRI) remains the cornerstone. However, there are some limitations and MRI can be non-conclusive. The development of additional imaging modalities like nuclear medicine explorations may help to confirm PA diagnosis, guide management and follow up.

Consensus statement by the French Society of Endocrinology (SFE) and French Society of Pediatric Endocrinology & Diabetology (SFEDP) on diagnosis of Cushing's syndrome.

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.

Multiple symmetric and multiple familial lipomatosis.

Lipomas are the most common soft tissue tumors and are malignant in only 1% of cases. Lipomatosis is defined as the presence of multiple benign lipomas on the body, without lipoatrophy. Their impact on quality of life is significant.