Anne-Lise Lecoq

Objectives: Acromegaly is frequently associated with disturbances in calcium–phosphate metabolism, including mild hypercalcemia. Hypercalcemia may also reflect primary hyperparathyroidism (PHPT), which can occur with or without variants in MEN1 or the related genes. Distinguishing PHPT from insulin-like growth factor I (IGF-I)–related alterations in mineral metabolism remains challenging. We aimed to assess the prevalence and characteristics of PHPT in patients with acromegaly and explore biochemical approaches for identifying parathyroid autonomy. Design: We conducted a retrospective study at 2 French university hospitals, including adults with acromegaly who had at least 1 serum calcium measurement obtained during uncontrolled disease. Three diagnostic approaches based on serum calcium and phosphate levels were evaluated: a threshold-based decision rule, logistic regression, and a support vector machine model. Results: Among 393 patients (54% women; median age 43 years [interquatile range 33-55]), 23 (5.9%) had concomitant PHPT. In isolated acromegaly, hyperphosphatemia occurred in 37.3% and mild hypercalcemia in 3.2% of patients; both resolved after acromegaly treatment. Patients with PHPT had persistent mild hypercalcemia (median calcium 2.72 mmol/L [interquatile range 2.66-2.86]), elevated PTH, and low-to-normal phosphate levels, these abnormalities resolved after parathyroid surgery in the 10 operated patients. No pathogenic variants were identified in the tested genes. A threshold-based rule combining calcium >2.60 mmol/L and phosphate <1.46 mmol/L showed excellent diagnostic performance for identifying parathyroid autonomy, with bootstrap 0.632+ corrected sensitivity and specificity of 0.940 and 0.993, respectively, and was preferred because of its simplicity. Conclusions: PHPT may be more frequent in acromegaly than in the general population. In patients with acromegaly and hypercalcemia, a nonelevated phosphate level strongly suggests concomitant PHPT, whereas an elevated phosphate level favors IGF-I–related mineral disturbances.

Objective: PTH(1-34), used off-label, effectively controls serum calcium in patients with chronic hypoparathyroidism inadequately managed by standard-of-care therapy. PTH(1-34) also strongly stimulates bone remodeling and often raises bone turnover markers above normal levels. This study aimed to visually assess the risk of excessive bone stimulation associated with prolonged PTH(1-34) replacement therapy. Design: An observational study (N°20201026100318) was conducted in adults with chronic hypoparathyroidism treated with PTH(1-34) for over 2 years at 3 referral centers. Methods: Patients underwent whole-body 99mTc-methylenediphosphonate scintigraphy, biochemical evaluation, and bone mineral density assessment. The primary endpoint was the proportion of patients with pathological increases in bone tracer uptake. Results: Forty-one patients received a mean daily dose of 29.9 µg [Q1; Q3 22.5; 39.9] of PTH(1-34) for a duration of 57 months [40; 70], representing an exposure of 218.3 patient-years. Median age at imaging was 44 years [30; 55]; 31 (75.6%) were women. Pathological bone uptake was observed in 25 (61%) patients despite serum calcium predominantly in the target therapeutic values. Osteoarticular pain did not differentiate affected individuals. These patients had higher weight-adjusted PTH(1-34) doses (0.44 µg/kg [0.32; 0.56] vs 0.34 µg/kg [0.24;0.40], P = .045), elevated bone remodeling markers, lower serum magnesium, and increased urinary calcium excretion. A score combining serum C-telopeptides of collagen I, osteocalcin, and magnesium correctly classified 97% of patients (95% CI: 91%-100%). Conclusion: Long-term PTH(1-34) therapy in chronic hypoparathyroidism is frequently associated with excessive bone remodeling despite adequate calcemic control. Careful monitoring is therefore essential, especially in patients with elevated bone remodeling markers and hypomagnesemia.

Context: Chronic hypoparathyroidism (cHP) is a rare endocrine disorder characterized by hypocalcemia secondary to the insufficient secretion of the parathyroid hormone. Despite the good observance of oral treatment with calcium salts and active vitamin D analogs, and even after adding intermittent subcutaneous injections of teriparatide (IST), some patients are still uncontrolled. Previous studies have suggested that continuous subcutaneous administration of teriparatide (CSAT) may be an option in such cases. Objective: The aim of this study was to assess the evolution of biological parameters with CSAT in comparison to previous treatment. Design: Retrospective observational study including all patients who received CSAT from 3 tertiary care centers of the Epi-Hypo study. Methods: Blood calcium, phosphate, bone remodeling markers, urine calcium, and the evolution of oral treatment were captured from electronic medical records. Quality of life (QoL) was assessed using the Hypoparathyroid Patient Questionnaire (HPQ28). Results: Twenty patients were included, 85% were women, and 75% had post-surgery cHP. Total calcium concentration was significantly higher with CSAT than with IST for 73% patients. HPQ28 showed an improvement in three out of the five patients for whom it was assessed. Osteocalcin increased significantly with IST (P = .003), but no difference was observed after initiating CSAT. Conclusion: CSAT may be an option for patients with uncontrolled cHP. Further studies need to investigate bone consequences and better characterize the improvement of QoL among these patients.

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. We aimed to evaluate the prevalence of obesity and metabolic complications in adults with XLH. We conducted a prospective cohort study in adult XLH patients from a single tertiary referral center. The proportion of patients with a BMI >25 kg/m² was the main outcome measure. Body fat mass percentage (FM%) and adipose tissue surfaces were secondary outcome measures. Glucose homeostasis (plasma glucose and insulin concentrations after fasting and 2 hours after an oral glucose tolerance test) was explored in a subgroup of patients and compared with age-, sex-, and BMI-matched healthy controls. Among 113 evaluated patients, 85 (75%) were female and 110 (97%) carried a PHEX mutation. Sixty-three (56%) patients were overweight or obese, with a median BMI of 25.3 [IQR, 22.7; 29.2] kg/m². BMI was correlated with FM%, abdominal and thigh subcutaneous and intra-abdominal adipose tissue surfaces. The prevalence of impaired fasting glucose, impaired glucose tolerance, and diabetes was not different between XLH patients and matched controls. The prevalence of overweight and obesity is high among XLH patients and is associated with excess fat mass. However, the prevalence of glucose homeostasis abnormalities is not increased in patients compared to healthy controls, suggesting that metabolically healthy overweight or obesity predominates.

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. While the beneficial effect of CT on oral manifestations is established, the effect of burosumab on oral health is unknown, especially in adults. Objective: We aimed to compare the oral health (number of missing or endodontically treated teeth and presence of periodontal disease) and incidence of endodontic infections of adult patients with XLH according to their treatment's modalities (no treatment, CT, or burosumab). Methods: This was achieved through a single-center, retrospective analysis of oral health data from 44 patients who had undergone dental monitoring for at least 6 months. Results: Oral health varied according to the proportion of their adult life spent under treatment for XLH, and the incidence of dental infections during follow-up was influenced by the type of treatment received. There was a 55.9% reduction of infections during CT and an 86.4% reduction during burosumab treatment compared to periods with no treatment (P < .0001). Comparing treatment and nontreatment periods within the same patient showed a strong association between burosumab treatment and decreased infection incidence (.006 vs .09 infection per month, P < .01). Conclusion: We observed that adults with XLH treated with burosumab developed fewer endodontic infections during dental follow-up than patients who were untreated or received CT.

Infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the coronavirus disease 2019 (COVID-19) pandemic that has resulted in millions of deaths and a major strain on health systems worldwide. Medical treatments for COVID-19 (anticoagulants, corticosteroids, anti-inflammatory drugs, oxygenation therapy and ventilation) and vaccination have improved patient outcomes. The majority of patients will recover spontaneously or after acute-phase management, but clinicians are now faced with long-term complications of COVID-19 including a large variety of symptoms, defined as “post-acute COVID-19 syndrome”. Most studies have focused on patients hospitalised for severe COVID-19, but acute COVID-19 syndrome is not restricted to these patients and exists in outpatients. Given the diversity of symptoms and the high prevalence of persistent symptoms, the management of these patients requires a multidisciplinary team approach, which will result in the consumption of large amounts of health resources in the coming months. In this review, we discuss the presentation, prevalence, pathophysiology and evolution of respiratory complications and other organ-related injuries associated with post-acute COVID-19 syndrome.