Ectopic calcifications (ECs) and heterotopic ossifications (HOs) form in non-mineralized tissues, most often in subcutaneous and muscular areas. Local and systemic complications can cause severe disability. Systemic administration of sodium thiosulfate (STS) gives promising results but is difficult to use in clinical practice.
Evaluation of the efficacy and safety of topical STS in ECs and HOs.
Retrospective analysis of the CATSS-O registry that included patients receiving topical STS 25 % prepared by the pharmacy of Limoges hospital during 2014-2020. The efficacy of STS was assessed by imaging (radiography or CT) after at least 6 months\' treatment.
Among 126 patients who received STS 25 %, 35 had complete clinical and radiographic data for analysis (28 with ECs and 7 with HOs; 18 children [mean age 8.9 years, range 1.5-16], 17 adults [mean age 52.4 years, range 24-90]). Calcifications or ossifications were due to dermatomyositis (8 children, 6 adults), systemic scleroderma (6 adults) or pseudo-hypoparathyroidism 1A (7 children). They were single (37.1 %) or multiple (62.9 %). Treated regions were in the lower limbs (31.4 %), upper limbs (37.1 %) or both (28.6 %) and the axial region (2.9 %). Topical STS was clinically effective in 9/28 (32.1 %) patients with ECs and 2/7 (28.6 %) children with HOs. Three patients experienced complete disappearance of their calcifications. Response for ECs was better in children than adults (54.5% vs 17.6 %, p = 0.035). Topical STS was well tolerated.
Local STS seems effective for ossifications, particularly pediatric calcifications or ossifications. Randomized and experimental studies are needed to confirm this observation and to identify the underlying mechanisms.

Hypoparathyroidism (HypoPT) or pseudo-hypoparathyroidism (pseudo-HypoPT) during pregnancy may cause maternal and fetal/neonatal complications. In this regard, only a few case reports or case series of pregnant or lactating women have been published. The purpose of this study was to describe clinical and biochemical course, pharmacological management, and potential adverse events during pregnancy and post-partum in pregnant women with HypoPT or pseudo-HypoPT. This was a retrospective, observational, multicenter, study involving nine Italian referral centers for endocrine diseases affiliated with the Italian Society of Endocrinology and involved in \"Hypoparathyroidism Working Group\".
This study identified a cohort of 28 women (followed between 2005 and 2018) with HypoPT (n = 25, 84% postsurgical, 16% idiopathic/autoimmune) and pseudo-HypoPT (n = 3). In HypoPT women, the mean calcium carbonate dose tended to increase gradually from the first to third trimester (+ 12.6%) in pregnancy. This average increase in the third trimester was significantly greater compared to the pre-pregnancy period (p value = 0.03). However, analyzing the individual cases, in 44% the mean calcium dosage remained unchanged throughout gestation. Mean calcitriol doses tended to increase during pregnancy, with a statistically significant increase between the third trimester and the pre-pregnancy period (p value = 0.02). Nevertheless, analyzing the individual cases, in the third trimester most women with HypoPT (64%) maintained the same dosage of calcitriol compared to the first trimester. Both mean calcium carbonate and calcitriol doses tended to decrease from the third trimester to the post-partum six months. Most identified women (~ 70%) did not display maternal complications and (~ 90%) maintained mean serum albumin-corrected total calcium levels within the low-to-mid normal reference range (8.5 ± 0.8 mg/dl) during pregnancy. The main complications related to pregnancy period included: preterm birth (n = 3 HypoPT women), and history of miscarriages (n = 6 HypoPT women and n = 2 pseudo-HypoPT women).
This study shows that mean serum albumin-corrected total calcium levels were carefully monitored during pregnancy and post-pregnancy, with limited evaluation of other biochemical parameters, such as serum phosphate, 24 h urinary calcium, 25-OH vitamin D, and creatinine clearance. To avoid complications in mothers affected by (HypoPT) or (pseudo-HypoPT) and offspring, intense biochemical, clinical and pharmacological monitoring during pregnancy and breastfeeding is highly recommended.

BACKGROUND: Cardiac damage triggered by severe hypocalcemia is well known. However, the role of chronic hypoparathyroidism (HP) and pseudohypoparathyroidism (PHP) in cardiac health is still unclear. We investigated the effect of chronic HP and PHP on cardiac structure and conductive function in patients compiling with treatment.
METHODS: The study included 18 patients with HP and eight with PHP aged 45.4 ± 15.4 and 22.1 ± 6.4 years, respectively with a previously regular follow-up. In addition, 26 age- and sex-matched healthy controls were included. General characteristics and biochemical indices were recorded. Cardiac function and structure were assessed by estimation of myocardial enzymes, B-type natriuretic peptide (BNP), and echocardiography. The 12-lead electrocardiogram and 24-h Holter electrocardiography were performed to evaluate the conductive function.
RESULTS: Levels of serum calcium in HP and PHP were 2.05 ± 0.16 mmol/L and 2.25 ± 0.19 mmol/L, respectively. The levels of myocardial enzyme and BNP were within the normal range. Adjusting for age at evaluation and body mass index, all M-mode measurements, left ventricular mass (LVM), LVM index (LVMI) and relative wall thickness (RWT) were comparable between patients and controls. Prolongation of corrected QT (QTc) intervals occurred in 52.6% (10/19) of patients, and 6.7% (1/15) of patients manifested more than 100 episodes of supraventricular and ventricular extrasystoles, as well as supraventricular tachycardia. None of the above arrhythmias was related to a severe clinical event.
CONCLUSIONS: From this pilot study, patients diagnosed with HP and PHP and well-controlled serum calcium levels manifested normal cardiac morphology and ventricular function, except for prolonged QTc intervals, and a small percentage of mild arrhythmias needing further investigation.

Albright\'s hereditary osteodystrophy is a rare disease, characterized by phosphocalcic balance abnormalities related to peripheral resistance to parathyroid hormone. It is an hereditary affection with autosomal dominant inheritance pattern caused by mutation in GNAS gene1. It combines specific morphotype, subcutaneous calcifications, bone and renal resistance to parathyroid hormone. We report a new case of Albright\'s hereditary osteodystrophy in a 9-month old infant followed up for significant hypocalcaemia which occurred at 10 days of life. The purpose of this study was to remind clinicians of the clinical, biological, genetic and therapeutic features of this disease.

As only sparse data are available on indices of cardiovascular health among patients with nonsurgical hypoparathyroidism (Ns-HypoPT) and pseudohypoparathyroidism (PHP), we aimed to compare the cardiovascular profile between these groups of patients.
A total of 56 patients with Ns-HypoPT and 30 with PHP were included and underwent a clinical examination including blood sampling and measurements of arterial stiffness, pulse wave velocity (PWV) and blood pressure (BP). Arterial stiffness and PWV were measured using AtCor SphygmoCor-XCEL (Atcor Medical Pty Ltd, Sydney, NSW, Australia).
Patients with Ns-HypoPT had an average age of 47 ± 17 years (68% females) and PHP patients 36 ± 13 years (80% females). Over 70% in both groups were genetically screened. Groups did not differ in terms of a history of cardiovascular disease, smoking status, use of calcium and vitamin D supplements or treatment with cholesterol-lowering or antihypertensive drugs. Compared with Ns-HypoPT, PHP patients had significantly lower levels of high-density lipoproteins (HDL) cholesterol and average glucose from HbA1c (Pboth  = 0.01). PWV was significantly higher among patients with Ns-HypoPT (Pcrude  = 0.02), even after adjustment for mean arterial pressure, body mass index, age and gender (Padjusted  < 0.01). Heart rate was significantly higher in Ns-HypoPT compared with PHP (P = 0.03). Office BP and 24-hour ambulatory BP did not differ between groups (P > 0.05).
Patients with Ns-HypoPT have compared with PHP a higher arterial stiffness and heart rate. This has been associated with an increased risk of cardiovascular disease. Our data suggest that resistance to PTH is present in the cardiovascular system in PHP.

Nonsurgical hypoparathyroidism (Ns-HypoPT) and pseudohypoparathyroidism (PHP) are both rare diseases, characterized by hypocalcemia. In Ns-HypoPT, PTH levels are low, whereas patients with PHP often have very high levels due to receptor-insensitivity to PTH (PTH-resistance). Accordingly, we hypothesized that indices of bone turnover and bone mineralization/architecture are similar in Ns-HypoPT and PHP despite marked differences in PTH levels. We studied 62 patients with Ns-HypoPT and 31 with PHP as well as a group of age- and sex-matched healthy controls. We found a significantly higher areal BMD (aBMD) by DXA among patients with Ns-HypoPT, both compared with PHP and the background population. Compared with Ns-HypoPT, PHP patients had significantly lower total and trabecular volumetric BMD (vBMD) assessed by quantitative computed tomography (QCT) scans at the spine and hip. High-resolution peripheral quantitative computed tomography (HRpQCT) scans showed a lower trabecular area and vBMD as well as a lower trabecular number at the tibia in PHP compared to Ns-HypoPT and matched controls. In PHP, PTH levels correlated with levels of markers of bone formation (osteocalcin, bone-specific alkaline phosphatase, P1NP), and bone resorption (CTx). In adult males, levels of bone markers were significantly higher in PHP compared with Ns-HypoPT. Levels of procalcitonin and calcitonin were significantly higher in PHP compared with Ns-HypoPT. In conclusion, indices of bone turnover, density, and microarchitecture differ between patients with Ns-HypoPT and PHP. Our data suggest that patients with PHP do not have a complete skeletal resistance to PTH and that the effects of chronically high PTH levels in PHP are mostly confined to the trabecular tissue. © 2017 American Society for Bone and Mineral Research.

BACKGROUND: Children with pseudohypoparathyroidism type 1a (PHP-1a) develop early-onset obesity. These children have decreased resting energy expenditure but it is unknown if hyperphagia contributes to their obesity.
METHODS: We conducted a survey assessment of patients 2 to 12 years old with PHP-1a and matched controls using the Hyperphagia Questionnaire (HQ) and Children\'s Eating Behavior Questionnaire (CEBQ). Results of the PHP-1a group were also compared with an obese control group and normal weight sibling group.
RESULTS: We enrolled 10 patients with PHP-1a and 9 matched controls. There was not a significant difference between the PHP-1a group and matched controls for total HQ score (p = 0.72), Behavior (p = 0.91), Drive (p = 0.48) or Severity (p = 0.73) subset scores. There was also no difference between the PHP-1a group and matched controls on the CEBQ. In a secondary analysis, the PHP-1a group was compared with obese controls (n = 30) and normal weight siblings (n = 6). Caregivers reported an increased interest in food before age 2 years in 6 of 10 PHP-1a patients (60%), 9 of 30 obese controls (30%) and none of the siblings (p = 0.04). The sibling group had a significantly lower Positive Eating Behavior score than the PHP-1a group (2.6 [2.4, 2.9] vs. 3.5 [3.1, 4.0], p < 0.01) and obese controls (2.6 [2.4, 2.9] vs. 3.4 [2.6, 3.8], p = 0.04), but there was not a significant difference between the PHP-1a and obese controls (p = 0.35). The sibling group had a lower Desire to Drink score than both the PHP-1a group (1.8 [1.6, 2.7] vs. 4.3 [3.3, 5.0], p < 0.01) and obese controls (1.8 [1.6, 2.7] vs. 3.3 [3.0, 4.0], p < 0.01) but there was not a significant difference between the PHP-1a and obese control Desire to Drink scores (p = 0.11).
CONCLUSIONS: Patients with PHP-1a demonstrate hyperphagic symptoms similar to matched obese controls.

Pseudohypoparathyroidism is a rare endocrine disorder that can be caused by genetic (mainly maternally inherited inactivating point mutations, although intragenic and gross deletions have rarely been reported) or epigenetic alterations at GNAS locus. Clinical and molecular characterization of this disease is not that easy because of phenotypic, biochemical and molecular overlapping features between both subtypes of the disease. The European Consortium for the study of PHP (EuroPHP) designed the present work with the intention of generating the standards of diagnostic clinical molecular (epi)genetic testing in PHP patients. With this aim, DNA samples of eight independent PHP patients carrying GNAS genetic and/or epigenetic defects (three patients with GNAS deletions, two with 20q uniparental disomy and three with a methylation defect of unknown origin) without GNAS point mutations were anonymized and sent to the five participant laboratories for their routine genetic analysis (methylation-specific (MS)-MLPA, pyrosequencing and EpiTYPER) and interpretations. All laboratories were able to detect methylation defects and, after the data analysis, the Consortium compared the results to define technical advantages and disadvantages of different techniques. To conclude, we propose as first-level investigation in PHP patients copy number and methylation analysis by MS-MLPA. Then, in patients with partial methylation defect, the result should be confirmed by single CpG bisulphite-based methods (ie pyrosequencing), whereas in case of a complete methylation defect without detectable deletion, microsatellites or SNP genotyping should be performed to exclude uniparental disomy 20.

We report three children with pseudohypoparathyroidism aged 13-16 years who presented with seizures and tetany. CT scan revealed striatopallidal calcification in two. MRI revealed wide-spread involvement showing T1 hyperintensity in striatopallidodentate distribution in all three and midbrain in one patient. T2 and FLAIR images were normal. T1 hyperintensity could represent early stage of calcification in whom MRI is more sensitive.

BACKGROUND: Since the identification of GH deficiency due to resistance to GHRH in patients with pseudohypoparathyroidism type Ia (PHP-Ia), no study investigated the effects of recombinant human GH (rhGH) therapy on height velocity (HV) in these patients.
OBJECTIVE: To address this question, eight prepubertal PHP-Ia children with GH deficiency (seven girls and one boy, aged 5.8-12 yr) underwent a 3- to 8-yr treatment with rhGH. Height and HV were measured before and at 6-month intervals during therapy. Nine sex- and age-matched children with idiopathic GH deficiency were monitored during rhGH therapy for comparison.
RESULTS: In PHP-Ia children, height sd scores increased from -2.4 ± 0.58 to -1.8 ± 0.47 (P = 0.04) after 12 months, this increase being maintained after the second (-1.6 ± 0.6) and third (-1.15 ± 0.6) year of therapy, similarly to what recorded in children with idiopathic GH deficiency. The HV and HV sd scores after 3 yr maintained a significant increase from 3.5 ± 0.6 to 7.0 ± 0.9 cm/yr (P < 0.0001) and from -2.8 ± 0.8 to +2.2 ± 1.0 (P < 0.0001), respectively. Six patients treated for 4-8 yr had a reduced pubertal spurt and did not improve their near-adult height, with the only exception of one patient in whom estrogen production was blocked by GnRH analogs.
CONCLUSIONS: We report the first study on the efficacy of rhGH replacement therapy in prepubertal children with PHP-Ia and provide indication that treatment of GH deficiency should be started soon due to the rather limited time window for a potentially effective therapy.