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Chronic hypoparathyroidism is characterized by low serum calcium, increased serum phosphorus, and inappropriately low or decreased serum parathyroid hormone. This rare disorder is associated with a variety of complications. The prevalence, incidence, mortality, financial burden, and epidemiology of complications of this disorder are not well understood. This narrative review summarizes current information on the epidemiology and complications of chronic hypoparathyroidism. The reported prevalence of chronic hypoparathyroidism ranges from 6.4-37/100,000, and the incidence is reported to be 0.8-2.3/100,000/year. Mortality is not increased in studies from Denmark or South Korea but was increased in studies from Scotland and Sweden. The financial burden of this disorder is substantial because of increased health care resource utilization in two studies but not well quantitated. Recognized complications include hypercalciuria, nephrocalcinosis, kidney stones, and chronic kidney disease; low bone turnover and possibly upper extremity fractures; cardiac and vascular calcifications; basal ganglia calcifications, cataracts, infections, neuropsychiatric complications, and difficulties with pregnancy. This review concludes that chronic hypoparathyroidism is a rare disorder associated with significant morbidity that may not increase overall mortality but is associated with a substantial financial burden. © 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

Hypoparathyroidism (HypoPT) and pseudohypoparathyroidism (PHP) are diseases with abnormal calcium and phosphate homeostasis and low and high PTH levels, respectively. It has been hypothesized that this could dispose to vascular calcifications and thereby perhaps also cardiovascular morbidity. The aim of this study was to assess lower leg arterial calcifications (LLAC) in patients with HypoPT or PHP. Using a cross-sectional design, we measured the LLAC using a high-resolution peripheral quantitative computed tomography (HR-pQCT) scanner in 72 patients with HypoPT and 25 patients with PHP and compared them with findings in 61 controls. LLAC were found in only two (3%) of the controls. Compared to the controls, LLAC were significantly more prevalent in patients with HypoPT (N = 12, [17%], p < 0.01) and PHP (N = 4, [16%], p < 0.04). Compared to the patients without calcifications, patients with calcifications had higher plasma calcium levels and a lower eGFR, as well as they were older and more often males. Plasma phosphate levels and the calcium-phosphate product were not associated with LLAC. In conclusion, we found that HypoPT and PHP are associated with an increased prevalence of vascular calcifications.

Background Pseudohypoparathyroidism (PHP) is a rare and inherited disease caused by mutations in the GNAS-gene or upstream of the GNAS complex locus. It is characterized by end-organ resistance to PTH, resulting in hypocalcemia and hyperphosphatemia. We aimed to investigate the dental anomalies according to tooth types and the orthodontic characteristics of patients with PHP. Methods Using a cross-sectional design, 29 patients (23 females) with PHP, living in Denmark, were included, and their clinical intraoral photos and radiographs were examined. Results Pulp calcification was found in 76% of the patients. Blunting of root apex was present in 55% and shortening of root in 48% of the examined patients. Blunting and shortening of roots were seen more often in premolars than in other tooth types (pboth Conclusion In the present study population, the teeth were frequently affected by pulp calcification and/or deviation of the root morphology. Blunting and shortening of root(s) were more often seen in premolars than in other tooth types. Class III malocclusion was relatively prevalent. It is important to pay attention to dental anomalies and occlusion in order to provide adequate care for patients with PHP.

Introduction In our clinical experience, need for doses of active vitamin D and calcium supplements changes during the period following a diagnosis of postsurgical hypoparathyroidism (HypoPT), but only sparse data are available. In the present study, we aimed to investigate the magnitude of changes in need for activated vitamin D (alfacalcidol) and calcium supplements during initiation of therapy as well as time to be expected until a stable phase was achieved. Furthermore, we determined the frequency of (unexpected) episodes of hypo‐ and hypercalcaemia after reaching a steady state for alfacalcidol and calcium. Methods Retrospective study of twenty‐four patients with chronic postsurgical HypoPT (>6 months) diagnosed from 2016 to 2018. Data were extracted from medical records on doses of alfacalcidol and calcium as well as ionized plasma calcium levels (P‐Ca2+) from time of diagnosis and until 86 weeks after surgery. Results Patients were treated with alfacalcidol and calcium in order to maintain a stable concentration of P‐Ca2+. Our data demonstrated a great variation in treatment needs until 11 weeks after surgery, where the mean doses of alfacalcidol stabilize, while calcium doses stabilized a bit earlier. After the stable phase had emerged, 21 out of 24 patients continued to have one or more episodes of spontaneous hypo‐ or hypercalcaemia. Conclusions Patients with chronic HypoPT attain a steady state for alfacalcidol 11 weeks after the diagnosis. Continuous monitoring of P‐Ca2+ is of continued importance after reaching steady state due to a high frequency of spontaneous hypo‐ or hypercalcaemia., BLURB FOR ETOCA retrospective review of medical records on 24 patients with chronic postoperative hypoparathyroidism lead to the finding of a steady state for treatment with activated vitamin D 11 weeks after the diagnosis.

Objective: 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. Methods: 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). Results: 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 (P both = 0.01). PWV was significantly higher among patients with Ns-HypoPT (P crude = 0.02), even after adjustment for mean arterial pressure, body mass index, age and gender (P adjusted 0.05). Conclusion: 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.

Objective: Hypercalciuria, impaired kidney function and renal calcifications are common in chronic hypoparathyroidism (HypoPT). We aimed to study associations between indices of known importance to the kidney in HypoPT by hypothesizing adverse effects of hypercalciuria on renal outcomes. Design: We used cross-sectional design. Patients: We identified all patients followed for chronic HypoPT at our department and who had been examined by a 24-h urine collection for measurement of renal calcium excretion (24 h U-Ca). Measurements: By chart review, we identified additional biochemistry measured in close connection with the collection of urine, as well as demographic, treatments and anthropometrics. Results: The 166 included patients (79.5% females) had a high prevalence of hypercalciuria (65.7%). In multiple adjusted analyses, hypercalciuria was in an independent manner inversely associated with (residual) levels of plasma PTH and positively associated with levels of 1,25-dihydroxyvitamin D and ionized calcium as well as 24 h U-phosphate, gender, and etiology (surgical vs. non-surgical). Overall, this model explained 54% (p

OBJECTIVE: As only sparse data are available, we aimed to investigate whether needs for activated vitamin D and calcium supplements change in women with hypoparathyroidism during pregnancy and lactation and risk of pregnancy-related complications.DESIGN: Retrospective review of medical records.PATIENTS: Twelve Danish and Canadian patients with chronic hypoparathyroidism who completed 17 pregnancies.MEASUREMENTS: Data were extracted on plasma levels of ionized calcium (P-Ca2+ ) and doses of active vitamin D and calcium supplements during pregnancy (N = 14) and breastfeeding (N = 10). Data on pregnancy complications were available from all 17 pregnancies.RESULTS: Although average doses of active vitamin D (P = .91) and calcium supplements (P = .43) did not change during pregnancies, a more than 20% increase or decrease in dose of active vitamin D was needed in more than half of the pregnancies in order to maintain normocalcemia. Five women (36%) developed hypercalcaemia by the end of pregnancy or start of lactation. Median levels of P-Ca2+ increased from 1.20 mmol/L in third trimester to 1.32 mmol/L in the post-partum period (P < .03). Accordingly, the average dose of active vitamin D was significantly reduced (P = .01) during lactation compared to 3rd trimester. One woman developed severe pre-eclampsia (6%). Further four pregnancies (24%) were complicated by polyhydramnios, dystocia and/or perinatal hypoxia. Ten pregnancies required caesarean delivery (59%) with four (24%) being performed as an emergency.CONCLUSION: In chronic hypoparathyroidism, close medical monitoring of the mother with frequent adjustments in the dose of calcium and active vitamin D is required during pregnancy and lactation in order to maintain normocalcemia. Patients should be offered close obstetric care to handle potential perinatal complications. We recommend evaluating the neonate immediately after birth and notifying the paediatrician of the risks of hypocalcaemia as well as hypercalcaemia in the neonate.

OBJECTIVE: Nonsurgical hypoparathyroidism (NS-HypoPT) and pseudohypoparathyroidism (PHP) are rare diseases, with a prevalence of 2/100.000 and 1/100.000, respectively. Only few studies on Quality of Life (QoL) among patients with Ns-HypoPT and PHP are available. We aimed to investigate the QoL among patients with Ns-HypoPT and PHP including information about education.DESIGN: A cohort study with patients identified from a previously epidemiological study.PATIENTS: Fifty seven patients with Ns-HypoPT and 30 patients with PHP.MEASUREMENTS: The well-validated questionnaires SF-36v2 and WHO-5 Well Being Index. Results compared to norm-based material, disease-specific norm-based material and patients with postsurgical HypoPT RESULTS: SF36v2 showed a significantly reduced score in all eight subdomains in patients with NS-HypoPT compared with a norm-based population. PHP patients scored lower in five subdomains. Females were more affected than males. Compared with postsurgical HypoPT, Ns-HypoPT and PHP are compatible at most domains. At the domains Physical Function, Social Function and Mental Health, Ns-HypoPT and PHP patients scored significantly lower (Pall < .05). At the Mental Component Score, patients with Ns-HypoPT had a lower score compared with postsurgical HypoPT (P < .01). The overall WHO-5 Well Being Index score was comparable between groups (P = .45). No differences were seen comparing patients with postsurgical HypoPT and Ns-HypoPT (P = .68) or postsurgical HypoPT and PHP (P = .67). A WHO-5 score below 28 indicates depression (NS-HypoPT=7; PHP=3, P = .71), whereas a score between 28-50 suggesting poor emotional well-being (NS-HypoPT=19; PHP=5, P = .13). The remaining patients scored above 50 suggesting well-being.CONCLUSION: QoL is impaired equally among patients with Ns-HypoPT and PHP.

Hypoparathyroidism (HypoPT) is associated with an increased risk of various complications, but only few data are available on risk factors. Using a case-control design, we assessed associations between biochemical findings and risk of different complications within a subpopulation of our previously identified Danish patients. We retrieved all biochemical data available on 431 (81% women) patients from the Central Region of Denmark, covering approximately 20% of the Danish population. Average age of patients was 41 years at time of diagnosis. Most patients (88%) had HypoPT due to surgery, mainly due to atoxic goiter and more than 95% were on treatment with calcium supplements and activated vitamin D. On average, time-weighted (tw) plasma levels of ionized calcium (Ca2+tw ) was 1.17 mmol/L (interquartile range [IQR], 1.14 to 1.21 mmol/L) and the calcium-phosphate (CaxPtw ) product was 2.80 mmol2 /L2 (IQR, 2.51 to 3.03 mmol2 /L2 ). High phosphatetw levels were associated with increased mortality and risk of any infections, including infections in the upper airways. A high CaxPtw product was associated with an increased mortality and risk of renal disease. Compared to levels around the lower part of the reference interval, lower Ca2+tw levels were associated with an increased risk of cardiovascular diseases. Mortality and risk of infections, cardiovascular diseases, and renal diseases increased with number of episodes of hypercalcemia and with increased disease duration. Treatment with a relatively high dose of active vitamin D was associated with a decreased mortality and risk of renal diseases and infections. In conclusion, risk of complications in HypoPT is closely associated with disturbances in calcium-phosphate homeostasis. © 2018 American Society for Bone and Mineral Research.

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: Standard treatment of hypophosphatemic rickets (HR) is oral phosphate tablets plus vitamin D. Due to the rapid absorption of phosphate tablets, frequent daily doses are necessary, which is cumbersome and may cause fluctuations in plasma phosphate and risk of secondary hyperparathyroidism. It was hypothesized that phosphate from milk or cheese is less rapidly absorbed, and reduces fluctuations in plasma phosphate. Objectives: The current randomized, multiple crossover study aimed at investigating if an equivalent phosphate dose given as milk or cheese is comparable to phosphate tablets in patients with HR. Methods: Seven females with HR were included. They went through three different four-day treatment sessions of either oral phosphate tablets consisting of 800 mg elemental phosphorus divided into five doses over the day or an equivalent phosphorus dose ingested as skimmed milk or cheese divided over five daily doses. Blood and urine samples were taken from patients after each treatment session. Except the usual doses of vitamin D, no phosphate or calcium-modifying treatments were allowed. Statistical analyses were performed using mixed models. Results: Treatment feasibility was independent of the phosphorus source. The study demonstrated reduced plasma levels of parathyroid hormone (PTH), reduced fluctuations in plasma phosphate and plasma PTH, and reduced renal phosphate excretion when ingesting phosphorus supplementation as milk compared to phosphate tablets. The same trend was observed when administering phosphorus as cheese, though not statistically significant. Conclusions: Phosphorus supplements can be administered as phosphate tablets, milk or cheese when given in equimolar doses. The current study findings indicated that milk may be superior to phosphate tablets as the phosphate source in patients with HR.

Total thyroidectomy causes postsurgical hypothyroidism (HypoT). Besides HypoT, as a complication patients may also develop hypoparathyroidism (HypoPT). The aim of this study was to assess quality of life (QoL), muscle function, and postural stability in patients with postsurgical hypothyroidism and hypoparathyroidism (HypoT+PT) as compared to patients with postsurgical HypoT and healthy controls. Age- and gender-matched patients on treatment for HypoT+PT and HypoT were recruited from our outpatient clinic. Matched healthy controls were recruited from the general background population. Compared with controls, HypoT was associated with a significantly lower mental summary score, whereas patients with HypoT+PT had a significantly lower physical summary score (Short Form 36 Health Survey questionnaire version 2). Moreover, the physical component score was significantly lower in patients with HypoT+PT compared with HypoT. WHO-5 well-being index was significantly lower in both groups of patients compared with controls, but did not differ between groups of patients. Compared with controls, muscle strength and maximal force production was significantly reduced in HypoT+PT, but not in HypoT. In HypoT+PT, the time spent on the Timed Up & Go test and the Repeated Chair Stands test were significantly longer than in the HypoT group and the control group. Postsurgical HypoT+PT is associated with a more severe impairment of QoL, in particular regarding physical functioning, than HypoT. HypoT+PT patients are also hampered by impaired muscle function. Studies on how to improve well-being and muscle function in HypoT+PT patients are warranted. © 2016 American Society for Bone and Mineral Research.

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. © 2015 American Society for Bone and Mineral Research.

Hypoparathyroidism (HypoPT) is associated with an increased risk of various complications, but only few data are available on risk factors. Using a case-control design, we assessed associations between biochemical findings and risk of different complications within a subpopulation of our previously identified Danish patients. We retrieved all biochemical data available on 431 (81% women) patients from the Central Region of Denmark, covering approximately 20% of the Danish population. Average age of patients was 41 years at time of diagnosis. Most patients (88%) had HypoPT due to surgery, mainly due to atoxic goiter and more than 95% were on treatment with calcium supplements and activated vitamin D. On average, time-weighted (tw) plasma levels of ionized calcium (Ca

Objective: Both non-surgical hypoparathyroidism (NS-HypoPT) and pseudohypoparathyroidism (Ps-HypoPT) are rare diseases. As patients with NS-HypoPT lack PTH they have an elevated BMD compared to normal background population. Patients with Ps-HypoPT on the other hand have despite peripheral resistance against PTH and a constant elevated level of PTH which may decrease their bone strength. Methods: 52 patients with NS-HypoPT and 20 with Ps-HypoPT were scanned by DXA and high-resolution pQCT scanner (XtremeCT, Scanco Medical AG, Switzerland). Bone mineral density in the lumbar spine, hip and ultra-distal forearm were measured by DXA, whereas cortical and trabecular architecture were measured by HRpQCT in the distal radius and tibia. All calculations were perform with an independent t-test. Results: Patients with Ps-HypoPT have a significantly increased BMI compared with patients with NS-HypoPT. Nevertheless, they have a significantly reduced BMD in the neck of the hip (p=0.02), whereas the groups were compatible in the lumbar spine, total hip, ultra-distal forearm and whole body (pall>0.05). There are a significant difference between groups when investigation the HRpQCT data. Patients with Ps-HypoPT a significant higher cortical volumetric density at the distal radius (p=0,02) borderline significant in the distal tibia (p=0.07). However, patients with NS-HypoPT have an increased trabecular microarchitecture with significant increased trabecular bone density (pradius=0.02; ptibia=0.03), trabecular number(pradius=0.05; ptibia=

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- (± 2 yr) and gender-matched controls from the general background population. Compared with controls, patients did not have an increased risk of cataract (p = 0.52), spinal stenosis (p = 0.59), or any fracture (p = 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.

Hypoparathyroidism (HypoPT) is a state of hypocalcemia due to inappropriate low levels of parathyroid hormone (PTH). HypoPT is normally treated by calcium supplements and activated vitamin D analogues. Although plasma calcium is normalized in response to conventional therapy, quality of life (QoL) seems impaired and patients are at increased risk of renal complications. A number of studies have suggested subcutaneous injections with PTH as an alternative therapy. By replacement with the missing hormone, urinary calcium may be lowered and QoL may improve. PTH replacement therapy (PTH-RT) possesses, nevertheless, a number of challenges. If PTH is injected only once a day, fluctuations in calcium levels may occur resulting in hypercalcemia in the hours following an injection. Twice-a-day injections seem to cause less fluctuation in plasma calcium but do stimulate bone turnover to above normal. Most recently, continuous delivery of PTH by pump has appeared as a feasible alternative to injections. Plasma calcium levels do not fluctuate, urinary calcium is lowered, and bone turnover is only stimulated modestly (into the normal range). Further studies are needed to assess the long-term effects. If beneficial, it seems likely that standard treatment of HypoPT in the future will change into replacement therapy with the missing hormone.

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 (± 2 years) and gender-matched 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. © 2013 American Society for Bone and Mineral Research.

Total thyroidectomy causes postsurgical hypothyroidism (HypoT). Besides HypoT, as a complication patients may also develop hypoparathyroidism (HypoPT). The aim of this study was to assess quality of life (QoL), muscle function, and postural stability in patients with postsurgical hypothyroidism and hypoparathyroidism (HypoT+PT) as compared to patients with postsurgical HypoT and healthy controls. Age- and gender-matched patients on treatment for HypoT+PT and HypoT were recruited from our outpatient clinic. Matched healthy controls were recruited from the general background population. Compared with controls, HypoT was associated with a significantly lower mental summary score, whereas patients with HypoT+PT had a significantly lower physical summary score (Short Form 36 Health Survey questionnaire version 2). Moreover, the physical component score was significantly lower in patients with HypoT+PT compared with HypoT. WHO-5 well-being index was significantly lower in both groups of patients compared with controls, but did not differ between groups of patients. Compared with controls, muscle strength and maximal force production was significantly reduced in HypoT+PT, but not in HypoT. In HypoT+PT, the time spent on the Timed UpGo test and the Repeated Chair Stands test were significantly longer than in the HypoT group and the control group. Postsurgical HypoT+PT is associated with a more severe impairment of QoL, in particular regarding physical functioning, than HypoT. HypoT+PT patients are also hampered by impaired muscle function. Studies on how to improve well-being and muscle function in HypoT+PT patients are warranted. © 2016 American Society for Bone and Mineral Research.

Hypoparathyroidism is characterized by hypocalcemia with inappropriately low parathyroid hormone (PTH) levels. Bone turnover is abnormally low and bone mineral density (BMD) is typically increased. Plasma calcium levels can be normalized by treatment with calcium supplements and vitamin D analogs, but bone turnover remains low and patients complain of a reduced quality of life (QoL). During recent years, a number of studies have shown that PTH replacement therapy (PTH-RT) may maintain calcium levels within the normal range, while the need for calcium and vitamin D supplements is reduced. In the initial response to subcutaneous PTH injections once or twice daily, bone turnover is overstimulated. BMD increases in cancellous bone, but decreases in cortical bone due to an increased porosity. Microcomputed tomography scans and histomorphometric studies on bone biopsies have shown changes similar to the well-known bone anabolic effects of PTH treatment in osteoporosis rather than a normalization of bone remodeling balancing the anabolic and catabolic effects of PTH. Most recently, continuous PTH delivery by pump was shown to increase the levels of bone markers into the normal range (without overstimulation of bone turnover) and with a normalization of renal calcium excretion. As PTH has a short plasma half-life, these findings indicate that exposure to PTH once or twice daily is not sufficient to reestablish a calcium homeostasis and bone metabolism that resembles normal physiology. Further studies should assess the effects of continuous PTH exposure by pump delivery (or multiple daily injections) on BMD and bone histology, as well as the effects of PTH-RT on indices of QoL.

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 (± 2 years) and gender-matched 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.

Hypoparathyroidism (HypoPT) is characterized by low serum calcium levels caused by an insufficient secretion of parathyroid hormone (PTH). Despite normalization of serum calcium levels by treatment with activated vitamin D analogues and calcium supplementation, patients are suffering from impaired quality of life and are at increased risk of a number of comorbidities. Thus, despite normalization of calcium levels in response to conventional therapy, this should only be considered as an apparent normalization, as patients are suffering from a number of complications and calcium-phosphate homeostasis is not normalized in a physiological manner. In a number of recent studies, replacement therapy with recombinant human intact PTH (rhPTH(1-84)) as well as therapy with the N-terminal PTH fragment (rhPTH(1-34)) have been investigated. Both drugs have been shown to normalize serum calcium while reducing needs for activated vitamin D and calcium supplements. However, once-a-day injections cause large fluctuations in serum calcium. Twice-a-day injections diminish fluctuations, but don't restore the normal physiology of calcium homeostasis. Recent studies using pump-delivery have shown promising results on maintaining normocalcemia with minimal fluctuations in calcium levels. Further studies are needed to determine whether this may improve quality of life and lower risk of complications. Such data are needed before replacement with the missing hormone can be recommended as standard therapy.