Chapter 0: Introduction to the Consensus on Primary Hyperparathyroidism from the French Society of Endocrinology, French Association of Endocrine Surgery and French Society of Nuclear Medicine.

This consensus on primary hyperparathyroidism, drawn up under the aegises of the French Society of Endocrinology (SFE), French Association of Endocrine Surgery (AFCE) and French Society of Nuclear Medicine (SFMN), provides an update on positive, etiological and differential diagnosis and treatment in primary hyperparathyroidism. These recommendations take account of recent increase in the prevalence of primary hyperparathyroidism, due to 1. more systematic routine measurement of blood calcium and improved quality of parathyroid hormone assays, 2.

Chapter 4: Differential diagnosis of primary hyperparathyroidism.

The differential diagnosis of primary hyperparathyroidism can be considered clinically, biologically and radiologically. Clinically, primary hyperparathyroidism should be suspected in case of diffuse pain, renal lithiasis, osteoporosis, repeated fracture, cognitive or psychiatric disorder, or disturbance of consciousness. Nevertheless, the differential diagnosis of primary hyperparathyroidism is mainly biological, particularly in atypical forms, which must be differentiated from hypercalcemia with hypocalciuria or non-elevated PTH on the one hand, and from normo-calcemia with elevated PTH, hypophosphatemia or hypercalciuria on the other.

Chapter 12: PREPARATION FOR PARATHYROID SURGERY.

Preoperative treatment of PHPT aims to 1) manage severe and/or symptomatic hypercalcemia and 2) prevent postoperative hypocalcemia. Severe hypercalcemia, defined as a blood calcium level ≥ 3.5 mmol/L, requires admission to hospital in a conventional or critical care unit, depending on clinical symptoms and comorbidities.

Clinical practice recommendations for the diagnosis and management of X-linked hypophosphataemia.

X-linked hypophosphataemia (XLH) is a rare metabolic bone disorder caused by pathogenic variants in the PHEX gene, which is predominantly expressed in osteoblasts, osteocytes and odontoblasts. XLH is characterized by increased synthesis of the bone-derived phosphaturic hormone fibroblast growth factor 23 (FGF23), which results in renal phosphate wasting with consecutive hypophosphataemia, rickets, osteomalacia, disproportionate short stature, oral manifestations, pseudofractures, craniosynostosis, enthesopathies and osteoarthritis. Patients with XLH should be provided with multidisciplinary care organized by a metabolic bone expert.

Mineralocorticoid axis activity and cardiac remodeling in patients with ACTH dependent Cushing's syndrome.

Background: Arterial hypertension and left ventricular hypertrophy and remodeling are independent cardiovascular risk factors in patients with Cushing's syndrome. Changes in the renin-angiotensin system and in the mineralocorticoid axis activity could be involved as potential mechanisms in their pathogenesis, in addition to cortisol excess.

Methods: In this ancillary study of our previous study prospectively investigating patients with ACTH-dependent Cushing's syndrome by cardiac magnetic resonance imaging (NCT02202902), 11 patients without any interfering medication were cross-sectionally compared to 20 control subjects matched for age, sex and body mass index.

PDE11A is a phenotype modulator of Primary Bilateral Macronodular Adrenal Hyperplasia: results of a 334 patients' series.

Purpose: Primary bilateral macronodular adrenal hyperplasia (PBMAH), the most common cause of Cushing's 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.

Methods: Leukocyte DNA of 354 PBMAH index cases was sequenced for ARMC5 and PDE11A genes by Next generation sequencing (NGS).

Aberrant hormone receptors regulate a wide spectrum of endocrine tumors.

Aberrant G-protein coupled receptor (GPCR) expression is highly prevalent in cortisol-secreting primary bilateral macronodular adrenal hyperplasia (PBMAH) and unilateral adenomas. The aberrant expression of diverse GPCRs and their ligands play an important role in the over-function of various endocrine tumours. Examples include aberrant expression of MC2R, 5-HT4R, AVPR1A, LHCGR, and GnRHR in primary aldosteronism; GCGR, LHCGR, and 5-HT4R in phaeochromocytomas and paragangliomas; TRHR, GnRHR, GIPR, and GRP101 in pituitary somatotroph tumours; AVPR2, D2DR, and SSTR5 in pituitary corticotroph tumours; GLP1R, GIPR, and somatostatin receptors in medullary thyroid carcinoma; and SSTRs, GLP1R, and GIPR in other neuroendocrine tumours.

X-linked hypophosphataemia.

X-linked hypophosphataemia is a genetic disease caused by defects in the phosphate regulating endopeptidase homolog X-linked (PHEX) gene and is characterised by X-linked dominant inheritance. The main consequence of PHEX deficiency is increased production of the phosphaturic hormone fibroblast growth factor 23 (FGF23) in osteoblasts and osteocytes. Chronic exposure to circulating FGF23 is responsible for renal phosphate wasting and decreased synthesis of calcitriol, which decreases intestinal phosphate absorption.

Metabolically healthy obesity in adults with X-linked hypophosphatemia.

Objectives: X-linked hypophosphatemia (XLH) is characterized by increased concentrations of circulating fibroblast growth factor 23 (FGF-23) resulting in phosphate wasting, hypophosphatemia, atypical growth plate and bone matrix mineralization. Epidemiologic studies suggest a relationship between FGF-23, obesity, and metabolic dysfunction. The prevalence of overweight and obesity is high in children with XLH.

Improved Oral Health in Adults with X-Linked Hypophosphatemia Treated with Burosumab.

Context: X-linked hypophosphatemia (XLH) is a rare genetic bone disease affecting both children and adults, with oral manifestations such as spontaneous dental infections. The main treatments for XLH are conventional treatment (CT) with oral phosphate salts and active vitamin D supplementation, and burosumab, an antibody targeting Fibroblast Growth Factor 23 (FGF23). While the beneficial effect of CT on oral manifestations is established, the effect of burosumab on oral health is unknown, especially in adults.

A novel mutation in the NR3C1 gene associated with reversible glucocorticoid resistance.

Objective: Glucocorticoid resistance is a rare endocrine disease caused by variants of the NR3C1 gene encoding the glucocorticoid receptor (GR). We identified a novel heterozygous variant (GRR569Q) in a patient with uncommon reversible glucocorticoid resistance syndrome.

Methods: We performed ex vivo functional characterization of the variant in patient fibroblasts and in vitro through transient transfection in undifferentiated HEK 293T cells to assess transcriptional activity, affinity, and nuclear translocation.

Anatomy of the medial wall of the cavernous sinus: A systematic review of the literature.

The existence, composition, and continuity of the medial wall of the cavernous sinus (MWCS) have been extensively studied and debated. However, the precise nature of this membrane remains unknown. Understanding the anatomical characteristics of the MWCS is crucial, notably in relation to pituitary adenomas, which often invade the cavernous sinus.

An Open-label Phase 2 Study of Eneboparatide, a Novel PTH Receptor 1 Agonist, in Hypoparathyroidism.

Context: Hypoparathyroidism is a rare disorder characterized by a deficiency in PTH resulting in hypocalcemia, hyperphosphatemia, and hypercalciuria. Eneboparatide is an investigational peptide agonist of the PTH1 receptor for the treatment of chronic hypoparathyroidism (HP).

Objective: To evaluate the efficacy, safety, and tolerability of eneboparatide in HP patients.

Anti-Müllerian hormone induces autophagy to preserve the primordial follicle pool in mice.

The reserve pool of primordial follicles (PMFs) is finely regulated by molecules implicated in follicular growth or PMF survival. Anti-Müllerian hormone (AMH), produced by granulosa cells of growing follicles, is known for its inhibitory role in the initiation of PMF growth. We observed in a recent in vivo study that injection of AMH into mice seemed to induce an activation of autophagy.

KDM1A genotyping and expression in 146 sporadic somatotroph pituitary adenomas.

Importance: A paradoxical increase of growth hormone (GH) following oral glucose load has been described in ∼30% of patients with acromegaly and has been related to the ectopic expression of the glucose-dependent insulinotropic polypeptide (GIP) receptor (GIPR) in somatotropinomas. Recently, we identified germline pathogenic variants and somatic loss of heterozygosity of lysine demethylase 1A (KDM1A) in patients with GIP-dependent primary bilateral macronodular adrenal hyperplasia with Cushing's syndrome. The ectopic expression of GIPR in both adrenal and pituitary lesions suggests a common molecular mechanism.

Acromegalic Cardiomyopathy: An Entity on its own? The Effects of GH and IGF-I Excess and Treatment on Cardiovascular Risk Factors.

Acromegaly is a chronic disease resulting from constantly elevated concentrations of growth hormone (GH) and insulin-like growth factor I (IGF-I). If not adequately treated, GH and IGF-I excess is associated with various cardiovascular risk factors. These symptoms mainly include hypertension and impaired glucose metabolism, which can be observed in approximately one-third of patients.

Differentiating pathologic parathyroid glands from thyroid nodules on neck ultrasound: the PARATH-US cross-sectional study.

Background: Neck ultrasound (US) is a widely used and accessible operator-dependent technique that helps characterize thyroid nodules and pathologic parathyroid glands (PPGs). However, thyroid nodules may sometimes be confused with PPGs. PARATH-US study aims at identifying US characteristics to differentiate PPGs from thyroid nodules, as there is no study, at present, which directly compares the US features of these two common neoplasms.

Pituitary surgery outcome in patients 75 years and older: a retrospective study.

Background: As the population ages, the number of elderly patients with an indication for pituitary surgery is rising. Information on the outcome of patients aged over 75 is limited. This study reports a large series assessing the feasibility of surgical resection in this specific age range, focusing on surgical complications and postoperative results.