Multicenter Retro-Prospective Observational Study on Chronic Hypoparathyroidism and rhPTH (1-84) Treatment

The use of recombinant human PTH (1-84) [rhPTH(1-84)] is approved as hormonal replacement therapy in patients with hypoparathyroidism not adequately controlled with conventional therapy. The objective of this study was to investigate the effects of 12 months of rhPTH (1-84) treatment in a cohort of patients selected according to the indications of recent hypoparathyroidism guidelines. It is a multicenter, observational, retro-prospective, open label study. Eleven Italian Endocrinological centers were involved. Fourteen adult subjects with chronic hypoparathyroidism treated with rhPTH (1-84) for 12 months were enrolled. Main outcome measures included serum and urinary parameters of mineral metabolism, renal function, oral calcium and vitamin D doses, and clinical manifestations. At 12 months, 61.5% of patients discontinued calcium supplement and 69.2% calcitriol. Mean serum calcium levels quickly normalized after initiation of rhPTH (1-84) treatment compared to baseline (p=0.009). Rare hypo-hypercalcemia episodes were reported. Renal function was maintained normal and no renal complications were reported. Serum and urinary phosphate and urinary calcium were maintained in the normal range. Mean phosphatemia levels linearly decreased from 3 months up to 12 months compared to baseline (p= 0.014). No severe adverse events were described. In conclusion, this study confirm the efficacy and safety of rhPTH (1-84) therapy.

Practice patterns for chronic hypoparathyroidism: data from patients and physicians in France

Context. Recent guidelines have provided recommendations for the care of patients with chronic hypoparathyroidism. Very little is known about actual physicians’ practices or their adherence to such guidelines. Objective. To describe the practice patterns and their compliance with international guidelines. Design. Cohort studies: Épi-Hypo (118 Physicians and 107 patients, from 09/2016 to 12/2019) and ePatients (110 patients, November 2019). Methods. Internet-based cohorts involving all settings at a nationwide level (France). Participants were i) physicians treating patients with chronic hypoparathyroidism and patients with chronic hypoparathyroidism either participating in the ii) Épi-Hypo study (Épi-Hypo 2019 patients) or iii) Hypoparathyroidism France, the national representative association (ePatients). Results. The physicians’ specialties were mainly endocrinology (61%), nephrology (28%), family medicine (2.5%), pediatrics (2.5%), rheumatology (2%) or miscellaneous (4%). Forty-five percent were practicing in public universities. The median number of pharmaceutical drug classes prescribed was 3 per patient. The combination of active vitamin D and calcium salt was given to 59% and 58% of ePatients and Épi-Hypo 2019 patients, respectively. Eighty-five percent of ePatients and 87% of physicians reported monitoring plasma calcium concentrations at a steady state at least twice a year. In 32% and 26% of cases, respectively, ePatients and physicians reported being fully in accordance with international guidelines that recommend targeting symptoms, plasma calcium and phosphate values, and urine calcium excretion. Conclusions. The care of patients with chronic hypoparathyroidism involves physicians with very different practices, so guidelines should include and target not only endocrinologists. Full adherence to the guidelines is low in France.

The PARADIGHM (physicians advancing disease knowledge in hypoparathyroidism) registry for patients with chronic hypoparathyroidism: study protocol and interim baseline patient characteristics

Background The PARADIGHM registry of adult and pediatric patients with chronic hypoparathyroidism evaluates the long-term safety and effectiveness of treatment with recombinant human parathyroid hormone, rhPTH(1-84), and describes the clinical disease course under conditions of routine clinical practice. In this first report, we detail the registry protocol and describe the baseline characteristics of two adult patient cohorts from an interim database analysis. One cohort after study entry were prescribed rhPTH(1-84), and the other cohort received conventional therapy of calcium and active vitamin D. Methods An observational study of patients with chronic hypoparathyroidism in North America and Europe, collecting data for ≥10 years per patient. Main outcome measures were baseline patient demographics, clinical characteristics, medications, and disease outcome variables of symptoms, biochemical parameters, and health assessments. Baseline is the enrollment assessment for all variables except biochemical measurements in patients treated with rhPTH(1-84); those measurements were the most recent value before the first rhPTH(1-84) dose. Exclusion criteria applied to the analysis of specified outcomes included pediatric patients, patients who initiated rhPTH(1-84) prior to enrollment, and those who received rhPTH(1-34). Clinically implausible biochemical outlier data were excluded. Results As of 30 June 2019, data of 737 patients were analyzed from 64 centers; 587 (80%) were women, mean ± SD age 49.1±16.45 years. At enrollment, symptoms reported for patients later prescribed rhPTH(1-84) (n=60) and those who received conventional therapy (n=571), respectively, included fatigue (51.7%, 40.1%), paresthesia (51.7%, 29.6%), muscle twitching (48.3%, 21.9%), and muscle cramping (41.7%, 33.8%). Mean serum total calcium, serum phosphate, creatinine, and estimated glomerular filtration rate were similar between cohorts. Health-related quality of life (HRQoL) 36-item Short Form Health Survey questionnaire scores for those later prescribed rhPTH(1-84) were generally lower than those for patients in the conventional therapy cohort. Conclusions At enrollment, based on symptoms and HRQoL, a greater percentage of patients subsequently prescribed rhPTH(1-84) appeared to have an increased burden of disease than those who received conventional therapy despite having normal biochemistry measurements. PARADIGHM will provide valuable real-world insights on the clinical course of hypoparathyroidism in patients treated with rhPTH(1-84) or conventional therapy in routine clinical practice. Trial registration EUPAS16927, NCT01922440

The Russian registry of chronic hypoparathyroidism and clinical decision support system integration

According to available research, chronic hypoparathyroidism is a relatively rare disease characterized by low serum calcium levels and the absence or deficiency of parathyroid hormone. The chronic course of the disease is associated with the multicomponent medical therapy, careful dynamic monitoring to reduce the risks of various complications in different organs and systems as well as disability and mortality.The Russian registry of patients with chronic postsurgical and nonsurgical hypoparathyroidism has started its work in 2020, based on data of the Endocrinology Research Centre. The main goals of the Registry are the assessment of the actual prevalence, incidence of hypoparathyroidism, the key epidemiological characteristics, the analysis of the clinical features and medical therapy of chronic hypoparathyroidism in Russian Federation.This article covers all objectives of this project, the methodology for maintaining the registry of chronic postsurgical and nonsurgical hypoparathyroidism, the analytical possibilities of its use, including the integration of a decision support system designed to help specialists in real clinical practice follow the algorithms for diagnosis and treatment of the disease, approved by clinical guidelines.The registry of chronic postsurgical and nonsurgical hypoparathyroidism is located on a single platform for the registers of endocrinopathies, regulated by the Endocrinology Research Centre (http://gipopt.clin-reg.ru/).

Daily calcium profile in diagnosis of hypo- and hypercalcemia in patients with chronic hypoparathyroidism. clinical case series

Hypoparathyroidism is a rare endocrine disorder characterized by hypocalcemia and hyperphosphatemia, due to absent or inappropriately low serum parathyroid hormone (PTH) levels. The chronic postoperative hypoparathyroidism accounts approximately 75% of patients; the genetic, autoimmune or idiopathic forms are significantly less common. Today, chronic hypoparathyroidism remains the last major endocrine deficiency, for which hormonal replacement therapy has not found widespread use. Achieving the target levels of phosphorus-calcium metabolism is an important factor of the disease control, required for the prevention of short- and long-term complications. The standard therapy with active metabolites/analogues of vitamin D (­alfacalcidol, calcitriol) and calcium supplements does not always allow to achieve the target treatment goals. Despite high doses of calcium and active vitamin D, some patients suffer from unstable calcium levels and associated symptoms.The measurement of serum calcium and phosphorus in the early morning hours remains the main laboratory tests for such patients, but in sometimes this diagnostic approach does not really reflect the true picture.The presented clinical cases describe the changes of both hyper- and hypocalcemia within one day in patients with chronic postsurgical hypoparathyroidism managed by standard therapy.

Women with chronic hypoparathyroidism have low risk of adverse pregnancy outcomes

Objective The aim of this study was to evaluate pregnancy outcome and total number of births in chronic hypoparathyroidism (hypoPT). Patients The Swedish National Patient Register, The Swedish Prescribed Drug Register, Swedish Medical Birth Register and the Total Population Register were used to identify 97 women with chronic hypoPT and 1030 age-matched controls who delivered 139 and 1577 singleton infants, respectively, following diagnosis between 1997 and 2017. Results Women in the chronic hypoPT group had more frequent diabetes (DM) and chronic kidney disease (CKD) compared to women in the control group (p=0.043 and p<0.001, respectively). After adjusting for DM, CKD, maternal age at delivery and calendar year of delivery, chronic hypoPT cases were associated with increased risk of induction of labor (OR 1.82; 95% CI 1.13-2.94) and giving birth to infants with lower birth weight (β-coefficient -188 g; 95% CI -312.2- -63.8) compared to controls. No difference was found in infant length, small for gestational age or head circumference after adjustments. Mean gestational age at delivery after controlling for DM, CKD and pre-eclampsia, was not significantly younger (p=0.119). There was no difference in congenital malformations or perinatal death. There was no difference in the total number of infants born to women with chronic hypoPT and controls (p=0.518). Conclusion The majority of women with chronic hypoPT had normal pregnancy outcomes, and the overall risks appear to be low. Maternal chronic hypoPT, is however, associated with a higher risk of induction of labor and slightly lower infant birth weight.