We aimed to identify all patients with postsurgical hypoparathyroidism (HypoPT) and to evaluate their risks of renal complications and cardiovascular disease in relation to their disease and its treatment. We identified possible patients through the Danish National Patient Registry and a prescription database. Case status was adjudicated by review of individual patients' hospital records. For each patient with postsurgical HypoPT due to surgery for nonmalignant diseases between 1988 and 2012, three age-matched (AE 2 years) and gendermatched controls were selected from the general background population. The prevalence of postsurgical HypoPT was 22 per 100,000 inhabitants. We identified 688 patients who had undergone neck surgery since 1988 with subsequent hypocalcaemia and inappropriate low parathyroid hormone (PTH) levels that necessitated treatment with calcium and/or vitamin D supplementation for more than 6 months. The average age at diagnosis was 49 years (range, 17-87 years), and 88% were women. Sixteen percent of all patients had had neck surgery prior to the operation causing HypoPT. Compared with controls, patients with HypoPT had an increased risk of renal complications (hazard ratio [HR], 3.67; 95% confidence interval [CI], 2.41-5.59) and hospitalization due to seizures (HR, 3.82; 95% CI, 2.15-6.79), whereas there was no increased risk of cardiac arrhythmias (HR, 1.11; 95% CI, 0.79-1.57) or cardiovascular disease or death (HR, 0.89; 95% CI, 0.73-1.09). In conclusion, although risk of seizures and renal complications is increased, mortality and risk of cardiovascular diseases or arrhythmias is not increased in patients with HypoPT. Further study should try to determine how to reduce the risk of seizures and renal complications in HypoPT.

Nonsurgical hypoparathyroidism (HypoPT) is a rare disorder most often caused by mutations in different genes. It is characterized by hypocalcaemia with inappropriately low PTH levels. Knowledge about this group of patients, including their mortality and morbidity, is very sparse. The aim was to identify all patients diagnosed with nonsurgical HypoPT in Denmark and assess their mortality and risk of complications. Through registers and review of individual patient hospital charts we identified all patients diagnosed with nonsurgical HypoPT in Denmark between 1977 and 2012. We assessed their mortality and morbidity by comparing them with a group of age- and gender-matched population-based controls. We identified a total of 180 patients with nonsurgical HypoPT among whom 123 (68%) were alive at the date of follow-up (prevalence of 2.3/100,000 inhabitants). Compared with controls, mortality was not increased, but patients had a significantly increased risk of renal insufficiency (hazard ratio [HR] 6.01), cardiovascular diseases (HR 1.91), neuropsychiatric complications (HR 2.45), infections (HR 1.94), seizures (HR 10.05), cataract (HR 4.21), and fractures at the upper extremities (HR 1.93). In contrast patients had significantly reduced risk of malignant diseases (HR 0.44). In conclusion, nonsurgical HypoPT is a rare disease associated with a number of complications that should be considered when taking care of these patients.

In hypoparathyroidism, plasma parathyroid hormone (PTH) levels are inadequate to maintain plasma calcium concentration within the reference range. On conventional treatment with calcium supplements and active vitamin D analogues, bone turnover is abnormally low, and BMD is markedly increased. We aimed to study the effects of PTH-replacement therapy (PTH-RT) on calciumphosphate homeostasis and BMD. In a double-blind design, we randomized 62 patients with hypoparathyroidism to daily treatment with PTH(1-84) 100 mg or similar placebo for 24 weeks as add-on therapy to conventional treatment. Compared with placebo, patients on PTH(1-84) reduced their daily dose of calcium and active vitamin D significantly by 75% and 73%, respectively, without developing hypocalcemia. However, hypercalcemia occurred frequently during the downtitration of calcium and active vitamin D. Plasma phosphate and renal calcium and phosphate excretion did not change. Compared with placebo, PTH(1-84) treatment significantly increased plasma levels of bone-specific alkaline phosphatase (þ226% AE 36%), osteocalcin (þ807% AE 186%), N-terminal propeptide of procollagen 1 (P1NP; þ1315% AE 330%), cross-linked C-telopeptide of type 1 collagen (CTX; þ1209% AE 459%), and urinary cross-linked N-telopeptide of type 1 collagen (NTX; (þ830% AE 165%), whereas BMD decreased at the hip (À1.59% AE 0.57%), lumbar spine (À1.76% AE 1.03%), and whole body (À1.26% AE 0.49%) but not at the forearm. In conclusion, the need for calcium and active vitamin D is reduced significantly during PTH-RT, whereas plasma calcium and phosphate levels are maintained within the physiologic range. In contrast to the effect of PTH(1-84) treatment in patients with osteoporosis, PTH-RT in hypoparathyroidism causes a decrease in BMD. This is most likely due to the marked increased bone turnover. Accordingly, PTH-RT counteracts the state of overmineralized bone and, during long-term treatment, may cause a more physiologic bone metabolism. ß

Data on co-morbidity in patients with postsurgical hypoparathyroidism (HypoPT) are sparse. We aimed to assess risk of fractures, spinal stenosis, cataract, neuropsychiatric diseases, cancer, and infections within the historic cohort of patients with postsurgical HypoPT due to non-malignant causes that we previously have characterized. Patients were identified through the Danish National Patient Registry and regional prescription databases, with subsequent validation of their individual hospital records. Identified cases were matched with three age-(AE 2 yr) and gender-matched controls from the general background population. Compared with controls, patients did not have an increased risk of cataract (p ¼ 0.52), spinal stenosis (p ¼ 0.59), or any fracture (p ¼ 0.98). However, the risk of fractures at the upper extremities was significantly decreased in patients (HR 0.69, 95% CI 0.49-0.97). Compared with controls, patients had a significantly increased risk of hospitalization due to infections (HR 1.42, 95% CI 1.20-1.67) and depression/ bipolar affective disorders (HR 1.99, 95% CI 1.14-3.46). The risk of malignant diseases did not differ between groups although the risk of gastrointestinal cancers was significantly lower in patients compared with controls (HR 0.63, 95% CI 0.44-0.93). In conclusion, HypoPT is associated with an increased risk of depression and other types of neuropsychiatric diseases as well as infections, whereas patients seem to be protected against fractures at the upper extremities and gastrointestinal malignancies.

This European expert consensus statement provides recommendations for the diagnosis and management of primary hyperparathyroidism (PHPT), chronic hypoparathyroidism in adults (HypoPT), and parathyroid disorders in relation to pregnancy and lactation. Specified areas of interest and unmet needs identified by experts at the second ESE Educational Program of Parathyroid Disorders (PARAT) in 2019, were discussed during two virtual workshops in 2021, and subsequently developed by working groups with interest in the specified areas. PHPT is a common endocrine disease. However, its differential diagnosing to familial hypocalciuric hypercalcemia (FHH), the definition and clinical course of normocalcemic PHPT, and the optimal management of its recurrence after surgery represent areas of uncertainty requiring clarifications. HypoPT is an orphan disease characterized by low calcium concentrations due to insufficient PTH secretion, most often secondary to neck surgery. Prevention and prediction of surgical injury to the parathyroid glands are essential to limit the disease-related burden. Long-term treatment modalities including the place for PTH replacement therapy and the optimal biochemical monitoring and imaging surveillance for complications to treatment in chronic HypoPT, need to be refined. The physiological changes in calcium metabolism occurring during pregnancy and lactation modify the clinical presentation and management of parathyroid disorders in these periods of life. Modern interdisciplinary approaches to PHPT and HypoPT in pregnant and lactating women and their newborns children are proposed. The recommendations on clinical management presented here will serve as background for further educational material aimed for a broader clinical audience, and were developed with focus on endocrinologists in training.