Familial hypocalciuric hypercalcaemia type 1 caused by a novel heterozygous missense variant in the CaSR gene, p(His41Arg): two case reports.

BACKGROUND: Familial hypocalciuric hypercalcaemia (FHH) is a rare, inherited disorder of extracellular calcium sensing. It is clinically characterised by mild to moderate parathyroid hormone dependent hypercalcaemia, an autosomal dominant pattern of inheritance, and a normal to reduced urinary calcium excretion in spite of high serum calcium. CASE PRESENTATION: We report two cases of FHH in a family caused by a novel pathogenic missense variant in the CaSR gene, p. His41Arg. Case 1, describes a 17 year old female with no significant past medical history, admitted with acute appendicitis requiring laparoscopic appendectomy and reporting a six month history of polydipsia. Routine investigations were significant for hypercalcaemia, corrected calcium 3.19 mmol/L (2.21-2.52mmol/L), elevated parathyroid hormone of 84pg/ml (15-65pg/ml) and a low 24-hour urine calcium of 0.75mmol/24 (2.50-7.50mmol/24). She was initially managed with intravenous fluids and Zolendronic acid with temporary normalisation of calcium though ultimately required commencement of Cinacalcet 30 mg daily for persistent symptomatic hypercalcaemia. Genetic analysis was subsequently positive for the above variant. Case 2, a 50-year-old female, was referred to the endocrine outpatient clinic for the management of type 2 diabetes and reported a longstanding history of asymptomatic hypercalcaemia which had not been investigated previously. Investigation revealed hypercalcaemia; corrected calcium of 2.6 mmol/L (reference range: 2.21-2.52 mmol/L); PTH of 53.7ng/L (reference range: 15-65 ng/L) and an elevated 24-hour urine calcium of 10 mmol/24 (2.50-7.50 mmol/24hr) with positive genetic analysis and is managed conservatively. Despite sharing this novel mutation, these cases have different phenotypes and their natural history is yet to be determined. Two further relatives are currently undergoing investigation for hypercalcaemia and the family have been referred for genetic counselling. CONCLUSION: Accurate diagnosis of FHH and differentiation from classic primary hyperparathyroidism can be challenging, however it is essential to avoid unnecessary investigations and parathyroid surgery. Genetic analysis may be helpful in establishing a diagnosis of FHH in light of the biochemical heterogeneity in this population and overlap with other causes of hypercalcaemia.

Bilateral Lymphadenopathy After COVID Vaccine in 18F-Choline PET/MRI Performed for Hyperparathyroidism.

ABSTRACT: We describe a case of a 56-year-old woman with primary hyperparathyroidism. 18F-Choline PET/MRI revealed incidental bilateral axillary lymphadenopathy with mild-moderate increased 18F-choline uptake. The patient had her first and third doses of COVID-19 vaccines from the left arm and second dose of vaccine from the right arm before PET examination.

Association between calcium and vitamin D in geriatric patients hospitalized for Covid-19: Results from the GERIA-COVID study (preprint)

The deficiency of 25OH vitamin D (25[OH]D) is common in the older population. It physiologically triggers secondary hyperparathyroidism resulting in normal circulating calcium levels. Adjusted calcium (CaA) is estimated by the PAYNE method and several studies report a misclassification of calcium status by corrected calcium compared to ionized calcium (CaI) in older patients. Hypocalcemia is common in older COVID-19 patients. Blunted secondary hyperparathyroidism explain this high prevalence of hypocalcemia in COVID-19. However, no studies have focused on patients older than 75 years despite the high mortality rate in this population. In the present study, the association between the different types of calcium (CaI, CaA, and total calcium [CaT]) and 25(OH)D deficiency (below 50 nmol/L) was investigated. The study of the correlation between each type of calcium was performed secondarily. Observational monocentric study focused on the GERIA-COVID database during the second wave of COVID-19 in France from October 2020 to March 2021. COVID-19 was diagnosed with RT-PCR and/or chest CT-scan. A population of 181 older COVID-19 patients (86.4 years {+/-} 5.7) was analyzed. Sixty-three patients (34.8%) were deficient in 25(OH)D. The prevalence of total and ionized hypocalcemia was 44.1% and 39.2%, respectively. A negative association was reported in linear regression between 25(OH)D deficiency and CaA ({beta} =-0.052 [-0.093; -0.010], p = 0.015) as well as with CaT ({beta} = -0.05 [-0.09; -0.01], p =0.034) in the multivariate model. No association was found between vitamin D deficiency and CaI. In the multivariate models, there was no association between each type of calcium and PTH. CaI was correlated with CaT (r = 0.39, p < 0.001) and with CaA (r = 0.15, p = 0.043). Secondary hyperparathyroidism was not activated in the context of COVID-19 in this study. After reviewing the literature, this appears to be the first study in older patients to expose such results.

Vitamin D deficiency, secondary hyperparathyroidism and respiratory insufficiency in hospitalized patients with COVID-19.

PURPOSE: Hypovitaminosis D has emerged as potential risk factor for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in the general population with variable effects on the outcome of the coronavirus disease-19 (COVID-19). The aim of this retrospective single-center study was to investigate the impact of hypovitaminosis D and secondary hyperparathyroidism on respiratory outcomes of COVID-19. METHODS: Three-hundred-forty-eight consecutive patients hospitalized for COVID-19 at the IRCCS Humanitas Research Hospital, Rozzano, Milan (Italy) were evaluated for arterial partial pressure oxygen (PaO2)/fraction of inspired oxygen (FiO2) ratio, serum 25hydroxy-vitamin D [25(OH)D], parathyroid hormone (PTH) and inflammatory parameters at study entry and need of ventilation during the hospital stay. RESULTS: In the entire population, vitamin D deficiency (i.e., 25(OH)D values < 12 ng/mL) was significantly associated with acute hypoxemic respiratory failure at the study entry [adjusted odds ratio (OR) 2.48, 95% confidence interval 1.29-4.74; P = 0.006], independently of age and sex of subjects, serum calcium and inflammatory parameters. In patients evaluated for serum PTH (97 cases), secondary hyperparathyroidism combined with vitamin D deficiency was significantly associated with acute hypoxemic respiratory failure at study entry (P = 0.001) and need of ventilation during the hospital stay (P = 0.031). CONCLUSION: This study provides evidence that vitamin D deficiency, when associated with secondary hyperparathyroidism, may negatively impact the clinical outcome of SARS-CoV-2-related pneumonia.

Endocrine surgery during COVID-19 pandemic: do we need an update of indications in Italy?

The ongoing spread of the coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) poses a significant threat to global health. As the coronavirus outbreak began spreading, hospitals were forced to relocate resources to treat the growing number of COVID-19 patients. As a consequence, doctors across the country canceled tens of thousands of nonurgent surgeries. However, recognizing that the COVID-19 situation may be highly variable and fluid in different communities across the country, elective surgery could be still allowed in some centers for patients included in the high-priority class. The majority of endocrine disorders requiring surgical treatment in patients identifiable as first-priority class, or needing hospitalization within 30 days, are generally represented by malignant thyroid tumors, hyperthyroidism, hyperparathyroidism, and some adrenal disorders. The need for urgent intervention is evaluated on a case-by-case basis according to the severity of the symptoms, the likelihood of progression, and global clinical judgment. On the basis of the above indications, during the last 4 weeks, we performed 18 planned surgical treatments in patients with thyroid cancer (total thyroidectomies, plus lymph node dissection if needed) or multinodular toxic goiter. In no case, postoperative ventilatory support was needed, and the average hospital stay was 3 days. The negative COVID-19 status for all the treated patients was appropriately evaluated beforehand. Nobody knows how long the current COVID-19 pandemic will be lasting. Certainly, we will be requested in the next future to incrementally offer surgical services for endocrine disorders that have been deferred for the COVID-19 pandemic.