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Summary Autoimmune polyglandular syndrome type 1 (APS-1) is a very rare autoimmune entity, accounting for about 400 cases reported worldwide. It is characterized by the presence of at least two of three cardinal components: chronic mucocutaneous candidiasis (CMC), hypoparathyroidism and Addison’s disease. It typically manifests in childhood with CMC and years later with hypoparathyroidism. A 50-year-old man was referred to the Endocrinology outpatient clinic due to irregular follow-up of primary hypoparathyroidism diagnosed at age 7. Previous analysis reported frequent fluctuations of calcium and phosphate levels and persistent hypercalciuria. He presented several comorbidities, including bilateral cataracts, other ocular disorders, transient alopecia and chronic gastritis. Due to weight loss, fatigue, gastrointestinal complaints and the findings at objective examination, Addison’s disease and CMC were investigated and confirmed. Antifungal therapy and hormonal replacement were started with evident clinical improvement. Regarding hypoparathyroidism, calcium-phosphate product decreased and other extraskeletal calcifications were diagnosed, such as nephrolithiasis and in basal ganglia. Further evaluation by genetic analysis revealed homozygosity for a frameshift mutation considered to be a pathogenic variant. It was reported only in two Asian siblings in compound heterozygosity. This case highlights the broad phenotypic spectrum of APS-1 and the significative intra-familial phenotype variability. A complete clinical history taking and high index of suspicion allowed the diagnosis of this rare entity. This case clarifies the need for regular long-term follow-up. In the specific case of hypoparathyroidism and Addison’s disease in combination, the management of APS-1 can be complex. Learning points: Autoimmune polyglandular syndrome type 1 (APS-1) is a deeply heterogeneous genetic entity with a broad spectrum of clinical manifestations and a significant intra-family phenotypic variability. Early diagnosis of APS-1 is challenging but clinically relevant, as endocrine and non-endocrine manifestations may occur during its natural history. APS-1 should be considered in cases of acquired hypoparathyroidism, and even more so with manifestations with early onset, family history and consanguinity. APS-1 diagnosis needs a high index of suspicion. Key information such as all the comorbidities and family aspects would never be valued in the absence of a complete clinical history taking. Especially in hypoparathyroidism and Addison’s disease in combination, the management of APS-1 can be complex and is not a matter of simply approaching individually each condition. Regular long-term monitoring of APS-1 is essential. Intercalary contact by phone calls benefits the control of the disease and the management of complications.

Hypocalcaemic cardiomyopathy is a rare form of dilated cardiomyopathy. The authors here present two cases in which symptomatic dilated cardiomyopathy was the result of severe hypocalcaemia. First, we report about a 26‐year‐old woman with primary hypoparathyroidism and then about a 74‐year‐old man with secondary hypoparathyroidism following a thyroidectomy. In both cases, the left ventricular systolic function improved after calcium supplementation. In the first case, a lack of compliance led to a repeated decrease of both serum calcium level and left ventricular systolic function. The authors also present a comprehensive summary of all cases of hypocalcaemic dilated cardiomyopathy that have been described in literature to date. The mean age of the affected patients was 48.3 years, of which 62% were female patients. The most common causes of hypocalcaemic cardiomyopathy are primary hypoparathyroidism (50%) and post‐thyroidectomy hypoparathyroidism (26%). In the post‐thyroidectomy subgroup, the median time for the development of hypocalcaemic cardiomyopathy is 10 years (range: 1.5 months to 36 years). Hypocalcaemic cardiomyopathy leads to heart failure with reduced ejection fraction in 87% of patients. Generally, the most common complications of hypoparathyroidism and/or hypocalcaemia are cerebral calcifications, cognitive deficit, and cataracts. Once calcium supplementation is administered, the disease has a good prognosis and, in most individuals, a significant improvement (21%) or even normalization (74%) of the left ventricular systolic function occurs.

A 7-year-old mixed breed spayed bitch (body weight: 10.6 kg) was presented with a history of intermittent episodes of seizures and untreated limb fracture. Appetite loss, nervousness, lateral recumbency, fasciculations, ataxia and poor nutritional condition were found. Venous blood gas analysis highlighted normal acid-base balance and severe low ionized calcium (0.58 mEq/L [range 1.13-1.32 mEq/L]). Marked total hypocalcaemia (6.4 mg/dL [range 8-10] or 1.6 mM [range: 2-2.5]) associated with hyperphosphoraemia (9.3 mg/dl [range 3.5-6.5 mg/dl]) displayed inverted ratio between minerals. ECG showed sinus arrhythmias. Circulating levels of Mg and Cu were within physiological range (1.97 mg/dl and 128 μg/dl respectively) and effects from interactions were excluded. Oral administration of calcitriol at 40 ng/kg/day led to clinical improvement within 48 hours, but circulating iCa levels were still below the lower limit of the reference range. Baseline levels of circulating parathormone (PTH) were 3 pg/ml, along with normal values of circulating vitamin D. Primary hypoparathyroidism was diagnosed as a chronic underlying condition triggered by pelvic fracture.

A cataract in the young age group is uncommon and it is usually secondary to eye trauma, intraocular inflammation, uncontrolled diabetes mellitus, and hypoparathyroidism. We report a case of a rapidly developing cataract over two years in a 21-year-old female with extensive intracranial calcification due to primary hypoparathyroidism. Chronic hypocalcemia due to underlying hypoparathyroidism results in cataract. Extensive bilateral intracranial calcification involving basal ganglia and white matter has been rarely reported in the literature. It occurs due to the chronic deposition of calcium-phosphorus complexes. We would like to highlight that cataract in young patients is always a matter for further evaluation. Clinicians and ophthalmologists should be aware of hypoparathyroidism as a cause of bilateral cataracts. Early diagnosis of primary hypoparathyroidism can save patients from many complications.

The standard treatment of primary hypoparathyroidism (hypoPT) with oral calcium supplementation and calcitriol (or an analog), intended to control hypocalcemia and hyperphosphatemia and avoid hypercalciuria, remains challenging for both patients and clinicians. In 2015, human parathyroid hormone (hPTH) (1‐84) administered as a daily subcutaneous injection was approved as an adjunctive treatment in patients who cannot be well controlled on the standard treatments alone. This open‐label study aimed to assess the safety and efficacy of an oral hPTH(1‐34) formulation as an adjunct to standard treatment in adult subjects with hypoparathyroidism. Oral hPTH(1‐34) tablets (0.75 mg human hPTH(1‐34) acetate) were administered four times daily for 16 consecutive weeks, and changes in calcium supplementation and alfacalcidol use, albumin‐adjusted serum calcium (ACa), serum phosphate, urinary calcium excretion, and quality of life throughout the study were monitored. Of the 19 enrolled subjects, 15 completed the trial per protocol. A median 42% reduction from baseline in exogenous calcium dose was recorded (p = .001), whereas median serum ACa levels remained above the lower target ACa levels for hypoPT patients (>7.5 mg/dL) throughout the study. Median serum phosphate levels rapidly decreased (23%, p = .0003) 2 hours after the first dose and were maintained within the normal range for the duration of the study. A notable, but not statistically significant, median decrease (21%, p = .07) in 24‐hour urine calcium excretion was observed between the first and last treatment days. Only four possible drug‐related, non‐serious adverse events were reported over the 16‐week study, all by the same patient. A small but statistically significant increase from baseline quality of life (5%, p = .03) was reported by the end of the treatment period. Oral hPTH(1‐34) treatment was generally safe and well tolerated and allowed for a reduction in exogenous calcium supplementation, while maintaining normocalcemia in adult patients with hypoparathyroidism. © 2021 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

Background Muscle cramps (MCs) are prolonged, involuntary, painful muscle contractions characterized by an acute onset and short duration, caused by peripheral nerve hyperactivity. Objectives To provide a detailed description of the clinical features and diagnostic findings in dogs affected by MCs. Animals Fourteen dogs. Methods Multicenter retrospective case series. Cases were recruited by a call to veterinary neurologists working in referral practices. Medical records and videotapes were searched for dogs showing MCs. The follow-up was obtained by telephone communication with the owner and the referring veterinarian. Results Three patterns of presentation were identified depending on the number of affected limbs and presence/absence of migration of MCs to other limbs. In 9/14 (64%) of dogs, MCs were triggered by prompting the dogs to move. 8/14 (58%) dogs were overtly painful with 6/14 (42%) showing mild discomfort. The cause of MCs was hypocalcemia in 11/14 (79%) dogs: 9 dogs were affected by primary hypoparathyrodism, 1 dog by intestinal lymphoma and 1 dog by protein losing enteropathy. In 3/14 cases (21%) the cause was not identified, and all 3 dogs were German Shepherds. Conclusions and clinical importance Muscle cramps can manifest in 1 of 3 clinical patterns. Muscle cramps are elicited when dogs are encouraged to move and do not always appear as painful events, showing in some cases only discomfort. The main cause of MCs in this study was hypocalcemia consequent to primary hypoparathyroidism. In dogs having MCs of unknown etiology, idiopathic disease or paroxysmal dyskinesia could not be ruled out.

Background. Common variable immunodeficiency (CVID) is a rare disease characterized by humoral immunodeficiency, often causing sinopulmonary and gastrointestinal infections, and may cause enteropathy in some patients, which leads to severe malnutrition and electrolyte deficiencies. Although many autoimmune diseases are seen with increased frequency in CVID patients, primary hypoparathyroidism is extremely rare. Case presentation. A 50-year-old man with CVID presented with diarrhea. The patient had complaints for 2 years and was cachectic. He had severe electrolyte and vitamin deficiencies that did not respond to oral treatment. The diarrhea causes such as celiac, inflammatory bowel diseases, and gastrointestinal infections were excluded and the endoscopy showed enteropathic changes in the duodenum and colon. Concomitant hypoparathyroidism was also detected in the patient with hypocalcemia despite adequate replacement. Conclusion. Parenteral therapy should be considered in the management of CVID enteropathy cases that do not respond to oral replacement. Although very rare, hypoparathyroidism should be considered in the differential diagnosis of CVID patients with treatment-resistant hypocalcemia.

Focal seizures in neonates presenting to the emergency department can be potentially dangerous and life-threatening. Hypoparathyroidism is an exceedingly rare but treatable cause of focal neonatal seizures. Due to its weak association with neonatal seizures, hypoparathyroidism often remains undetected as a potential cause. We hereby elucidate a rare case of idiopathic hypoparathyroidism presenting as right-sided focal seizures in a 12-day-old female neonate with an uneventful birth history. Despite the administration of antibiotics and phenobarbitone, the seizures remained unabated. Laboratory workup revealed the diagnosis of late-onset hypocalcemia with severe hypoparathyroidism. The patient was subsequently treated with calcium supplements and alfacalcidol. Thereafter, the frequency of seizures gradually decreased and the same treatment regimen was continued until the patient was seizure-free. The patient continues to do well to date with complete remission of his clinical symptoms.

Roux-en-Y gastric bypass (RYGB) is thought to reduce calcium absorption from the gut. Here, we report the case of a patient with a RYGB, who developed primary hypoparathyroidism after a total thyroidectomy, leading to recalcitrant hypocalcaemia. Despite aggressive oral calcium and calcitriol supplementation, she remained hypocalcaemic and required intravenous (IV) calcium supplementation to control her symptoms, and to keep calcium serum levels within an acceptable range. Teriparatide treatment improved calcium levels marginally. This treatment, however, was poorly tolerated and ultimately stopped by the patient. As a last resort, reversal of RYGB was performed to improve calcium absorption from the gut. Unfortunately, IV calcium supplementation remained necessary. This case illustrates that the reversal of RYGB is not always a guarantee for success in managing recalcitrant hypocalcaemia. ispartof: OBESITY SURGERY vol:30 issue:12 pages:5150-5152 ispartof: location:United States status: published

Dilated cardiomyopathy (DCM) is characterized by dilation and impaired contraction of one or both ventricles. Affected patients have impaired systolic function and may or may not develop overt heart failure (HF). Prognosis is generally poor without heart transplantation. We experienced a case of a 10-year-old child with dilated cardiomyopathy (DCM) accompanied by undiagnosed primary hypoparathyroidism. In our case,aggressive management of hypoparathyroidism significantly improved the manifestations of DCM. The case presentation highlights the importance of considering hypoparathyroidism as a cause of reversible myocardial dysfunction.

The role of the calcium-sensing receptor (CaSR) as a regulator of parathyroid hormone secretion is well established, but its function in bone is less well defined. In an effort to elucidate the CaSR's skeletal role, bone tissue and material characteristics from patients with autosomal dominant hypocalcemia (ADH), a genetic form of primary hypoparathyroidism caused by CASR gain-of-function mutations, were compared to patients with postsurgical hypoparathyroidism (PSH). Bone structure and formation/resorption indices and mineralization density distribution (BMDD), were examined in transiliac biopsy samples from PSH (n = 13) and ADH (n = 6) patients by histomorphometry and quantitative backscatter electron imaging, respectively. Bone mineral density (BMD by DXA) and biochemical characteristics were measured at the time of the biopsy. Because both study groups comprised children and adults, all measured biopsy parameters and BMD outcomes were converted to Z-scores for comparison. Histomorphometric indices were normal and not different between ADH and PSH, with the exception of mineral apposition rate Z-score, which was higher in the ADH group. Similarly, average BMD Z-scores were normal and not different between ADH and PSH. Significant differences were observed for the BMDD: average Z-scores of mean and typical degree of mineralization (CaMean, CaPeak, respectively) were lower (p = 0.02 and p = 0.03, respectively), whereas the heterogeneity of mineralization (CaWidth) and percentage of lower mineralized areas (CaLow) were increased in ADH versus PSH (p = 0.01 and p = 0.002, respectively). The BMDD outcomes point toward a direct, PTH-independent role of the CaSR in the regulation of bone mineralization. © 2018 American Society for Bone and Mineral Research.

Background Patients with hypoparathyroidism are at risk of both hypocalcemic and hypercalcemic crisis. Patients report that health professionals do not always respond adequately in an acute situation. The extent and handling of severe hypo- and hypercalcemia in hypoparathyroidism is unknown. Aims To outline the need for a medical emergency card for primary hypoparathyroidism. Method Postal survey amongst Norwegian and Swedish patients with chronic hypoparathyroidism of all causes. Altogether 455 invitations were sent (333 from Norway and 122 from Sweden). Results Three hundred and thirty-six of 455 (74%) patients responded (253 from Norway and 83 from Sweden). The majority were women (79%), and the main cause was postsurgical hypoparathyroidism (66%). Overall 44% and 16% had been hospitalized at least once for hypo- or hypercalcemia, respectively. Eighty-seven per cent felt that an emergency card would be highly needed or useful. Amongst those hospitalized for hypocalcemia, 95% felt a card was needed compared to 90% amongst those hospitalized for hypercalcemia. Five per cent believed that a card would not be useful. Conclusions The majority answered that an acute card is highly needed or useful. Hospitalization for acute hypocalcemia was more common (44%) than for acute hypercalcemia (16%). As a result of this survey, an emergency card will be distributed in three European countries to test its utility.

Background: Anterior neck surgery is the leading cause of acquired hypoparathyroidism. Renal failure is the most common complication of treatment for hypoparathyroidism with active vitamin D and calcium supplements. However, the contribution of hypoparathyroidism to development of CKD in the absence of treatment is not well studied. Clinical Case: A 70-year old woman was brought to ED after she was found on the floor at home. Medical history was significant only for a partial thyroidectomy over 20 years prior, without reported post-operative complications. She was not taking any medications. Pertinent physical findings included altered mental status, hand tremors, involuntary contractions of left arm, and ashen skin. Laboratory tests upon presentation were significant for profoundly low albumin-corrected calcium of 3.68 mg/dL (n 8.6–10.2 mg/dL); low PTH 9.9 pg/dL (n 15–65 pg/dL); elevated phosphorous 8.5 mg/dL (n 2.7–4.5 mg/dL), elevated BUN 36 mg/dL (n 8–22 mg/dL), creatinine 2.76 mg/dL (n 0.5–1.3 mg/dL) and elevated CK of 4787 U/L (n 10–225 U/L). EKG showed QT interval prolongation. Head CT revealed periventricular and basal ganglia calcifications. Renal US was normal. The patient was treated with IV and PO calcium acetate and active vitamin D with resolution of the symptoms while calcium level improved. Post hospital follow-ups were significant for persistent hyperphosphatemia, which gradually improved with calcium and non-calcium phosphate binders as well as active vitamin D. Although this patient presented with acute hypocalcemia, she had chronic hypoparathyroidism as evidenced by basal ganglia calcifications. In the absence of other medical conditions, including negative PTH antibodies, or treatment for chronic hypoparathyrodism, the most likely cause of the CKD was chronic hypoparathyroidism itself. Conclusion: Post-surgical hypoparathyroidism may develop many years after surgery and can be asymptomatic. It is essential to diagnose this condition early to avoid late complications of the disease. The kidneys are particularly affected. Conventional treatment with calcium and vitamin D analogues is associated with ectopic mineralization and can lead to CKD. Untreated hypoparathyroidism on the other hand, can also lead to CKD, posing therapeutic challenges on finding the most appropriate and balanced treatment regimen in order to prevent further renal complications. Close monitoring and optimizing therapy plays critical role in preserving renal function of patients with hypoparathyroidism.

There are very few reports on the epidemiology of chronic hypoparathyroidism. A population-based study was undertaken to describe the prevalence and incidence of hypoparathyroidism in Tayside, Scotland. Data on biochemistry, hospital admissions, prescribing, and death records in Tayside, Scotland, from 1988 to 2015 were linked electronically. Patients with at least three serum albumin-corrected calcium concentrations below the reference range that were taken in an outpatient setting were included in the study. Patients with severe chronic kidney disease before low calcium were excluded from the study. Patients with hypocalcemia were included if they had either previous neck surgery/irradiation, a low serum parathyroid hormone (PTH), or were treated with vitamin D. Patients were identified as having either a postsurgical or a nonsurgical cause or had secondary hypoparathyroidism, eg, hypomagnesemia. Overall, 18,955 patients were identified with hypocalcemia. Of these, 222 patients had primary hypoparathyroidism, 116 with postsurgical and 106 with nonsurgical chronic hypoparathyroidism. In 2015, the prevalence of primary hypoparathyroidism was 40 per 100,000, with a rate of 23 and 17 per 100,000, respectively, for postsurgical and nonsurgical. Eighty percent of the former and 64% of the latter were female. The mean serum calcium at diagnosis was 1.82 mmol/L (SD ± 0.24) and the annual incidence varied from 1-4 per 100,000. Overall, 71% of patients were prescribed vitamin D and/or calcium, whereas activated vitamin D was used in 48% of postsurgical cases and 43% of nonsurgical cases. Thyroxine and/or hydrocortisone were prescribed in more than 90% of postsurgical and 64% of nonsurgical cases. In conclusion, the prevalence of nonsurgical chronic hypoparathyroidism was greater than previously reported using this population-based approach. Many had mild hypocalcemia and did not receive any treatment. © 2017 American Society for Bone and Mineral Research.

Context There are concerns about the long-term safety of conventional therapy on renal health in patients with hypoparathyroidism. Careful audit of these would help comparisons with upcoming parathyroid hormone therapy. Objective We investigated nephrocalcinosis, renal dysfunction, and calculi, their predictors and progression over long-term follow-up in patients with primary hypoparathyroidism (PH). Design and Setting An observational study at a tertiary care center was conducted. Participants and Methods A total of 165 PH patients receiving conventional therapy were evaluated by radiographs, ultrasonography, and computed tomography. Their glomerular filtration rate (GFR) was measured by Tc-99m-diethylenetriamine penta-acetic acid clearance. Clinical characteristics, serum total calcium, phosphorus, creatinine, hypercalciuria, and fractional excretion of phosphorus (FEPh) at presentation and during follow-up were analyzed as possible predictors of renal complications. Controls were 165 apparently healthy individuals. Results Nephrocalcinosis was present in 6.7% of PH patients but not in controls. Patients younger than 15 years at presentation and with higher serum calcium-phosphorus product were at higher risk. Nephrocalcinosis showed no significant association with cataract and intracranial calcification. Prevalence of renal calculi was comparable between hypoparathyroid patients and controls (5% vs 3.6%, P = .58). Fourteen percent of patients had a GFR less than 60 mL/min/1.73 m2. Increased FEPh during follow-up was the significant predictor of low GFR. Nephrocalcinosis developed in 9% of patients over 10 years of conventional therapy. Conclusion A total of 6.7% of PH patients had nephrocalcinosis, and 14% showed renal dysfunction. Prevalence of renal calculi was similar in patients and controls. Nine percent of patients developed nephrocalcinosis over 10 years of conventional therapy.

Hypoparathyroidism is an uncommon endocrine disorder in the horse characterized by a transient or permanent parathyroid hormone insufficiency. Hypoparathyroidism is associated with hypocalcemia and hyperphosphatemia, primarily presenting with clinical signs consistent with hypocalcemia. This case report describes clinical presentation and treatment of a horse with severe hypocalcemia due to primary hypoparathyroidism. A 17-year-old, 542 kg Quarter Horse gelding presented for shaking and tremors. Significant findings include generalized muscle fasciculations, synchronous diaphragmatic flutter, and a markedly hypermetric hindlimb gait. Hematology revealed a moderate hyperkalemia, hyperphosphatemia, hypomagnesemia, and severe hypocalcemia. Initial treatment consisted of oral and intravenous calcium supplementation and fluid therapy. Thirty-six hours after presentation, clinical signs resolved, and treatment was discontinued. Clinical signs reoccurred after the discontinuation of treatment. A presumptive diagnosis of primary hypoparathyroidism was made based on low parathyroid hormone in the presence of low ionized calcium. The patient was maintained on oral calcium carbonate (feed grade lime) and vitamin AED supplementation. Hypoparathyroidism is rare but oral supplementation of calcium with calcium carbonate resulted in a favorable outcome with no apparent decrease in performance. Long-term supplementation may be required to prevent disease recurrence.

Primary hypoparathyroidism should be considered in dogs with vague signs, including tremors, facial rubbing, and seizures. Ionized hypocalcemia should be considered in dogs with protein-losing enteropathy, especially lymphangiectasia caused by hypovitaminosis D. Ionized hypocalcemia typically occurs only in advanced chronic kidney disease.

Objective: The objective of this article is to present a case report of autoimmune polyendocrine syndrome type 1 (APS-1) diagnosed at a tertiary level hospital.Methods: This report summarizes the clinical presentations, laboratory values, treatments, and follow-up of a patient with APS-1. The diagnosis of APS-1 was based on clinical features and laboratory criteria.Results: The study patient with APS-1 was a 9-year-old girl that presented with recurrent seizure as a consequence of hypocalcemia due to primary hypoparathyroidism; an important component of this syndrome. A computerized tomography scan showed diffuse calcification of both basal ganglia and subcortical structures of the brain. Biochemical study showed features of primary hypothyroidism (free thyroxine = 0.31 ng/dL, free triiodothyronine = 1.0 pg/mL, thyroid-stimulating hormone >150 μIU/mL), primary hypoparathyroidism (serum calcium = 6.2 mg/dL, serum magnesium = 1.8 mg/dL, serum inorganic phosphate = 7.9 mg/dL, serum parathyroid hormone 1,000 IU/mL), which was highly suggestive of autoimmune hypothyroidism. The patient was managed with supplemental calcium, activated vitamin D, glucocorticoid, levothyroxine, antifungal medications, and anticonvulsants.Conclusion: Physician awareness of this rare autoimmune polyendocrine disorder can increase its early recognition and treatment, potentially preventing associated fatalities.Abbreviations: APS-1 = autoimmune polyendocrine syndrome type 1; AIRE = autoimmune regulator gene

Hypocalcaemia causes neuromuscular and myocardial symptoms, including QT interval prolongation, and cardiac arrhythmias. Prompt detection and calcium replacement may reverse the pathology, following which the underlying cause should be diagnosed and treated to prevent recurrence. I present the case of a young man presenting with collapse who was found to have sinus rhythm with significant QT interval prolongation on admission electrocardiogram (ECG) associated with profound hypocalcaemia secondary to primary hypoparathyroidism.

Clinically relevant hypocalcemia is a well-documented complication of glucocorticoid administration in people with hypoparathyroidism. The current report describes the phenomenon in a dog. A 7 yr old neutered male Pomeranian was diagnosed with immune-mediated thrombocytopenia, immune-mediated hemolytic anemia, and primary hypoparathyroidism. This dog required long-term parenteral calcium gluconate to prevent clinical hypocalcemia despite appropriate doses of oral calcitriol and calcium carbonate. This is the first description of clinically significant presumptive glucocorticoid induced hypocalcemia in a dog with primary hypoparathyroidism.

We report the case of a 54-year-old Caucasian female who presented with a two-year history of persistent hypocalcemia requiring multiple hospitalizations. Her medical history was significant for HIV diagnosed four years ago. She denied any history of prior neck surgery or radiation. Her vital signs were stable with an unremarkable physical exam. Pertinent medications included calcium carbonate, vitamin D3, calcitriol, efavirenz, emtricitabine, tenofovir disoproxil, hydrochlorothiazide, and inhaled budesonide/formoterol. Laboratory testing showed total calcium of 5.7 mg/dL (normal range: 8.4-10.2 mg/dL), ionized calcium of 2.7 mg/dL (normal range: 4.5-5.5 mg/dL), serum phosphate of 6.3 mg/dL (normal range: 2.7-4.5 mg/dL), and intact PTH of 7.6 pg/mL (normal range: 15-65 pg/mL). She was diagnosed with primary hypoparathyroidism. Anti-calcium-sensing receptor antibodies and NALP5 antibodies were tested and found to be negative. During subsequent clinic visits, doses of calcium supplements and calcitriol were titrated. Last corrected serum calcium level was 9.18 mg/dL. She was subsequently lost to follow-up. This case gives insight into severe symptomatic hypocalcemia from primary hypoparathyroidism attributed to HIV infection. We suggest that calcium levels should be closely monitored in patients with HIV infection.

A 3 yr old, spayed, female miniature mchnauzer was presented for rhythmic, spontaneous contractions of the abdominal wall and across the costal arches. The rate of contractions coincided with the heart rate and increased during exercise. The dog was diagnosed with primary hypoparathyroidism based on low plasma ionized calcium and serum parathyroid hormone (PTH) concentrations. Fluoroscopic exam confirmed the diagnosis of a synchronous diaphragmatic flutter. Treatment of the hypocalcemia led to resolution of the diaphragmatic flutter.

SummaryContext Hypoparathyroidism is characterised by hypocalcaemia, hyperphosphataemia, and low or inappropriately normal parathyroid hormone (PTH) levels. Idiopathic or genetic drivers are the predominant causes of hypoparathyroidism in paediatric-age patients. Objective This study investigated the aetiology and clinical course of primary hypoparathyroidism in infancy and childhood. Subjects and measurements This study included 37 patients (23 males, 14 females) with primary hypoparathyroidism diagnosed prior to 18 years of age. We analysed aetiologies, initial presentation, age at diagnosis, endocrine and radiological findings, and outcomes. Results The median age at presentation was 1.7 months (range 1 day–17 years), and the mean follow-up duration was 7.0 ± 5.3 years (range 0.5–16.8 years). Our cohort included 22 cases (59.5%) of 22q11.2 microdeletion syndrome. Other aetiologies included hypoparathyroidism-deafness-renal dysplasia syndrome (5/37, 13.5%) and one patient each with autoimmune polyglandular syndrome type 1, Kearns–Sayre syndrome, and Kenny–Caffey syndrome. The remaining 7 (18.9%) patients were classified as idiopathic hypoparathyroidism cases. Among the 15 patients who underwent brain imaging, 5 (33.3%) had basal ganglia calcification. Among the 26 patients examined by renal imaging, 5 (19.2%) had either nephrocalcinosis or a renal stone. After 11 months of calcium or calcitriol supplementation, 16 patients (43.2%) discontinued medication. The final PTH levels were significantly higher in patients with transient hypoparathyroidism than those with permanent hypoparathyroidism. Conclusions Identification of the genetic aetiologies of hypoparathyroidism makes it possible to predict patient outcomes and provide appropriate genetic counselling. Long-term treatment with calcium and calcitriol necessitates monitoring for renal complications. This article is protected by copyright. All rights reserved.

A 2-year-old, castrated, male, domestic ferret weighing 1.125kg (2.48lb) was presented with a history of vomiting, diarrhea, anorexia, and lethargy of sudden onset. Physical examination revealed dehydration, tachypnea, bradychardia, hypotension, and moderate abdominal pain. As reference values for intact parathyroid hormone in ferrets were not available, samples from 3 clinically healthy males were analyzed. Low ionized calcium in conjunction with low intact parathyroid hormone concentrations are diagnostic for hypoparathyroidism. Based on diagnostic testing, the ferret described in this article was diagnosed with spontaneous primary hypoparathyroidism. Regular oral administration of dihydrotachysterol resulted in a therapeutic regimen to adequately control the hypoparathyroid condition of this ferret patient.

Primary hypoparathyroidism is an uncommon endocrinopathy in dogs, resulting from absolute or relative deficiency in the secretion of parathormone (PTH). The dog presented signs of hypocalcemia, including muscular spasms, tetany and cramps, evolving to tonic-clonic seizures and fever. Emergency therapy for hypocalcemia included glucose physiological solution at 0.45% and calcium gluconate administered intravenously. Diagnosis was confirmed by the presence of hypocalcemia, hyperphosphatemia and a decrease in parathormone (PTH).

Summary Chromosome 22q11.2 deletion syndrome (22q11.2DS) is a genetic syndrome that may present with hypocalcemia due to primary hypoparathyroidism (PH) at any age. We report a new diagnosis of 22q11.2DS in a 57-year-old man who presented with symptomatic hypocalcemia. It is important to consider genetic causes of hypocalcemia due to PH regardless of age. Learning points: It is important to discard genetic cause of primary hypoparathyroidism in a patient without autoimmune disease or prior neck surgery. A new diagnosis of a hereditary disease has familial implications and needs genetic counselling. It is also important to discard other syndrome’s comorbidities.

Hypoparathyroidism is a rare endocrine disorder characterized by low serum calcium and parathyroid hormone levels. The most common cause is parathyroid iatrogenic surgical removal. However, innumerous and rarer conditions can cause hypoparathyroidism. The authors describe a 27-year-old man that presented in emergency department with confusion, amnesia and decreased attention span. A cerebral computed tomography revealed bilateral extensive calcification in the basal ganglia. A complete work-up revealed low serum calcium, high serum phosphorus and low parathyroid hormone, leading to the diagnosis of idiopathic primary hypoparathyroidism. Initial intravenous therapy with calcium gluconate and calcitriol was administered, with clinical and analytical improvement. The authors describe a rare condition, with an exuberant cerebral presentation and extreme hypocalcemia, which did not directly correlate to the severity of symptoms. Not only this is a treatable disorder that may have catastrophic results if overlooked but also its symptoms may be completely reversed with prompt treatment.

There are very few reports on the epidemiology of chronic hypoparathyroidism. A population-based study was undertaken to describe the prevalence and incidence of hypoparathyroidism in Tayside, Scotland. Data on biochemistry, hospital admissions, prescribing, and death records in Tayside, Scotland, from 1988 to 2015 were linked electronically. Patients with at least three serum albumin-corrected calcium concentrations below the reference range that were taken in an outpatient setting were included in the study. Patients with severe chronic kidney disease before low calcium were excluded from the study. Patients with hypocalcemia were included if they had either previous neck surgery/irradiation, a low serum parathyroid hormone (PTH), or were treated with vitamin D. Patients were identified as having either a postsurgical or a nonsurgical cause or had secondary hypoparathyroidism, eg, hypomagnesemia. Overall, 18,955 patients were identified with hypocalcemia. Of these, 222 patients had primary hypoparathyroidism, 116 with postsurgical and 106 with nonsurgical chronic hypoparathyroidism. In 2015, the prevalence of primary hypoparathyroidism was 40 per 100,000, with a rate of 23 and 17 per 100,000, respectively, for postsurgical and nonsurgical. Eighty percent of the former and 64% of the latter were female. The mean serum calcium at diagnosis was 1.82 mmol/L (SD ± 0.24) and the annual incidence varied from 1-4 per 100,000. Overall, 71% of patients were prescribed vitamin D and/or calcium, whereas activated vitamin D was used in 48% of postsurgical cases and 43% of nonsurgical cases. Thyroxine and/or hydrocortisone were prescribed in more than 90% of postsurgical and 64% of nonsurgical cases. In conclusion, the prevalence of nonsurgical chronic hypoparathyroidism was greater than previously reported using this population-based approach. Many had mild hypocalcemia and did not receive any treatment. © 2017 American Society for Bone and Mineral Research.

In the last decade, there have been a number of significant advances made in the field of rare bone diseases. In this review, we discuss the expansion of the classification system for osteogenesis imperfecta (OI) and the resultant increase in therapeutic options available for management of OI. Bisphosphonates remain the most widely used intervention for OI, although the effect on fracture rate reduction is equivocal. We review the other therapies showing promising results, including denosumab, teriparatide, sclerostin, transforming growth factor β inhibition and gene targeted approaches. X-linked hypophosphataemia (XLH) is the most common heritable form of osteomalacia and rickets caused by a mutation in the phosphate regulating endopeptidase gene resulting in elevated serum fibroblast growth factor 23 (FGF23) and decreased renal phosphate reabsorption. The traditional treatment is phosphate replacement. We discuss the development of a human anti-FGF23 antibody (KRN23) as a promising development in the treatment of XLH. The current management of primary hypoparathyroidism is replacement with calcium and active vitamin D. This can be associated with under or over replacement and its inherent complications. We review the use of recombinant parathyroid hormone (1–84), which can significantly reduce the requirements for calcium and vitamin D resulting in greater safety and quality of life for individuals with hypoparathyroidism. The use of receptor activator of nuclear factor κB ligand infusions in the treatment of a particular form of osteopetrosis and enzyme replacement therapy for hypophosphatasia are also discussed.

Chromosome 22q11.2 deletion syndrome (22q11.2 DS) has a very wide phenotypic spectrum that includes dysmorphic features, cardiac anomalies, and hypocalcemia arising from hypoparathyroidism. We herein describe an adult case of 22q11.2 DS with associated hypoparathyroidism and anomalies of the aortic arch. Because the patient had been diagnosed with primary hypoparathyroidism at another hospital, a diagnosis of 22q11.2 DS had been overlooked. A chest X-ray examination revealed widening of the mediastinum caused by a high-positioned right aortic arch, and we subsequently confirmed a diagnosis of 22q11.2 DS using fluorescence in situ hybridization. Because primary hypoparathyroidism is a rare disorder, physicians should be aware of the variable phenotypic features of 22q11.2 DS.

An 1-year-old, female, mixed-breed dog weighing 17 kg was referred for abrupt collapse. She had remarkable hypocalcemia and hyperphosphatemia, and survey radiographs revealed a severe gas-filled intestine. Treatment with serial injections of calcium gluconate was initiated promptly and most of the gastrointestinal distension disappeared after 4 h. However, the clinical signs were not resolved completely. The serum intact parathyroid hormone concentration was not elevated in the context of hypocalcemia, which suggested primary hypoparathyroidism. The clinical signs and laboratory abnormalities in the patient were resolved completely 3 days after administration of calcium gluconate and calcitriol. This case describes the unique presentation of severe gastrointestinal distension in a dog diagnosed with primary hypoparathyroidism.

Polyglandular autoimmune syndrome is defined as multiple endocrine gland insufficiencies accompanied by autoimmune diseases of the endocrine and nonendocrine system. After Schmidt introduced a case of nontuberculosis adrenal gland dysfunction with thyroiditis in 1926, Neufeld defined polyglandular autoimmune syndrome by I, II, and III subtypes in 1980 by their presentation of occurrence age, heredity methods, relationship with human leukocyte antigen, and accompanying diseases. We report a case of a 32-year-old female with polyglandular autoimmune syndrome III accompanied by type 1 diabetes mellitus that was treated with insulin (36 units per day) for 11 years. She had insulin deficiency and Hashimoto thyroiditis as an autoimmune disorder. In addition, she had several features similar to Albright's hereditary osteodystrophy including short stature, truncal obesity, round face, short neck, low intelligence (full IQ 84), and decreased memory. Although Albright's hereditary osteodystrophy is morphological evidence of pseudohypoparathyroidism or pseudopseudohypoparathyroidism, she had primary hypoparathyroidism on laboratory results. Here, we report a case of polyglandular autoimmune syndrome III with type 1 diabetes mellitus, autoimmune thyroiditis, and primary hypoparathyroidism, accompanied by clinical features similar to Albright's hereditary osteodystrophy.

Isolated familial hypoparathyroidism is an extremely rare disorder, which to date has been linked to several loci including mutations in CASR, GCM2, and PTH, as well as a rare condition defined as X-linked recessive hypoparathyroidism, previously associated with a 1.5 Mb region on Xq26-q27. Here, we report a patient with hypocalcemia-induced seizures leading to the diagnosis of primary hypoparathyroidism. Mutations in CASR, GCM2, and PTH were ruled out, while whole exome sequencing of the family suggested FHL1, located on chromosome Xq26, as the most likely causative gene variant (FHL1, exon 4, c.C283T, p.R95W). Since FHL1 has not been linked to calcium regulation before, we provide evidence for its functional role in hypoparathyroidism by: (i) bioinformatics analysis coupling its action to known modulators of PTH function; (ii) observing strong expression of fhl1b in Corpuscles of Stannius, gland-like aggregates in zebrafish that function in calcium regulation similar to mammalian PTH; and (iii) implicating fhl1b and FHL1 as regulators of calcium homeostasis in zebrafish and human cells, respectively. Altogether, our data suggest that FHL1 is a novel regulator of calcium homeostasis and implicate it as the causative gene for X-linked recessive hypoparathyroidism. Electronic supplementary material The online version of this article (doi:10.1007/s00439-017-1804-9) contains supplementary material, which is available to authorized users.

A 14-year-old Caucasian girl with a history of primary hypoparathyroidism and unstable calcium and phosphorus levels and on ongoing treatment was admitted to the Department of Pediatric Nephrology because of the onset of nephrocalcinosis and difficulties achieving normocalcemia. Coexistence of hypoparathyroidism, oral candidiasis, dental enamel hypoplasia, and subclinical Hashimoto's disease was strongly suggestive for autoimmune polyglandular syndrome (APS) type I. One of the clinical implications of this diagnosis is the high probability of future occurrence of adrenal insufficiency and hence the importance of maintaining a high level of suspicion in case of the onset of symptoms like weakness, fainting, hypotonia, or hyperkaliemia. Addison's disease would, in fact, be quite challenging for the future management of this patient.This clinical quiz highlighted the importance of careful evaluation of all multiorgan symptoms occurring in a patient to prevent further complications.

Pregnancy and lactation are associated with remarkable changes in calcium homeostasis, resulting from pregnancy-induced alterations in the production, metabolism and excretion of calcium and calcitropic hormones. Therefore, the clinical course of disorders affecting the parathyroid glands during pregnancy and lactation is often atypical. As the symptoms experienced by patients with parathyroid disorders are not specific, their diagnosis during gestation and breastfeeding may be sometimes very difficult. If left untreated, parathyroid disorders may pose a significant risk to the mother and fetus associated with increased perinatal and maternal morbidity and mortality. Hypoparathyroidism is a disorder rarely observed during pregnancy, resulting in most cases from surgical thyroidectomy. In our article, we present the case of a 32-year-old female with primary hypoparathyroidism diagnosed for the first time during pregnancy. We describe in details the treatment strategies undertaken in this patient and their impact on the outcome of pregnancy and lactation.

Cardiomyopathy is a rare but life-threatening condition in children. Myocarditis is the leading cause of dilated cardiomyopathy (DCM) and prognosis is generally poor without heart transplantation. We report a rare case of hypocalcemic DCM due to primary hypoparathyroidism in a male infant. In our patient, aggressive management of hypoparathyroidism significantly improved the manifestations of DCM. He is currently 10 years old and has no symptoms of exercise intolerance. Latest echocardiogram revealed near-normal cardiac function. Our case emphasizes that early diagnosis of this treatable cause of cardiomyopathy prevents serious sequelae.

A 24-year-old female presented with sudden heart failure and ventricular fibrillation. A complete work-up suggested the existence of primary hypoparathyroidism in an otherwise previously healthy young woman. Left ventricle enlargement was detected by echocardiography with an ejection fraction of 30%. Electrolyte disorders dominated the laboratory results, with severe hypocalcemia, hypokalemia, hypomagnesemia and other changes, which were corrected with infusion therapy. An improvement of her overall condition prompted a switch from electrolyte infusion therapy to the oral route after the first week of treatment. The patient was discharged under calcium, calcitriol, diuretics and angiotensin-converting-enzyme-inhibitors oral maintenance therapy. Two months after discharge, her ejection fraction remained low (33%), although the end-systolic volume had returned to normal values, and her general status had substantially improved. Within a period of 4 months her cardiac function improved significantly and the follow-up surveillance echocardiography showed an ejection fraction of 53%, with normal left ventricle dimensions.

Background Chronic hypocalcemia may cause electrocardiographic (ECG) changes and mimic acute myocardial infarction. It has also been associated with reversible cardiac dysfunction. On the other hand cardiomyopathy and heart failure have been reported in patients with idiopathic hypoparathyroidism or celiac disease. Clinical Case A 39-year-old male was admitted to the emergency room with acute retrosternal pain and dyspnea. He exhibited severe hypocalcemia and acute renal failure. High creatine kinase (CK) levels did not correlate with biomarkers of myocardial necrosis (negative troponin test, heart type creatine kinase isoenzyme (CK-MB) < 1% of CK value). The ECG showed an extremely long QT interval (0.6 sec) and T-wave inversions on V4 through V6. The left ventricular ejection fraction (LVEF) was as low as 25%, while coronary angiography was normal. Investigation of the hypocalcemia revealed primary hypoparathyroidism (Parathyroid hormone (PTH) < 3 pg/ml) and concomitant celiac disease with positive antigliadin and endomysial antibodies. The cardiovascular episodes and the dilated heart failure were attributed to the chronic hypocalcemia since no other cause was found. The correction of hypocalcemia has not been sufficient to reverse the end-stage heart failure after more than 6 months of treatment, even though ECG abnormalities have receded, implying permanent cardiac impairment. Conclusion This case demonstrates an unusual clinical condition where 2 calcium homeostasis disorders led to severe hypocalcemia with clinical manifestations of end-stage heart failure. The severe cardiac failure appeared to be nonreversible after calcium repletion suggesting permanent cardiac muscle dysfunction due to associated cardiomyopathy. Copyright © 2010 Wiley Periodicals, Inc.

A 59-year-old woman with idiopathic hypoparathyroidism who had tetany and zonular cataract is described. Twelve years ago she had had a period with cramps and convulsions, followed by an absence of symptoms for several years. Judging from the distance between the opacity of cataract and the surface of the lens, the onset of the cataract was estimated to have occurred 11 years ago and the apparent cessation of cataract development 10 years ago. It is suggested that the absence of hypocalcaemic symptoms during the last 10 years was associated with an increase in serum calcium levels, possibly connected with the onset of menopause. The occurrence of hypocalcaemia was analyzed in a health-screened population of 15903 persons. Nine of the subjects were found to have a serum calcium level of less than 2.10 mmol/l, giving a prevalence of 0.6%o. None had primary hypoparathyroidism, which illustrates the rarity of this condition.

Glial cells missing-2 (GCM2) is a transcription factor expressed in the parathyroid hormone (PTH)-secreting cells of the parathyroid gland and is essential for their development. Thus far, downstream targets of GCM2 have not been identified. Here, we show that both promoters (P1 and P2) of the calcium-sensing receptor (CASR) gene, a differentiation marker for the parathyroid gland, are transactivated by wild-type GCM2. GCM response elements within CASR P1 (-451 to -441; relative to the transcription start site at +1) and CASR P2 (-166 to -156) were identified by mutated promoter-reporter studies as well as oligonucleotide precipitation assays. Primary hypoparathyroidism is a heterogeneous group of conditions characterized by hypocalcemia and hyperphosphatemia due to deficient PTH secretion. A few cases of familial isolated hypoparathyroidism with autosomal recessive inheritance have been identified that are caused by homozygous inactivating mutations in the GCM2 gene. We describe the GCM2 mutations in two families with hypoparathyroidism, one inherited in an autosomal recessive fashion and the other in an autosomal dominant manner. In transfection studies using a promoter-reporter construct having synthetic multimerized GCM elements in the promoter, the dominantly inherited mutant GCM2 exerted a dominant-negative effect on wild-type GCM2 activity, whereas recessively inherited mutants did not. In addition, we show that the transactivation of the CASR promoter-reporter constructs by wild-type GCM2 is completely abolished in the presence of the dominant-negative mutant GCM2.

Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED), also known as autoimmune polyglandular syndrome type I, is a rare autosomal recessively inherited disorder characterized by variable combinations of endocrine and nonendocrine symptoms. In this report, we describe two 20- and 17-year-old Turkish siblings presenting with typical symptoms of APECED, including Addison disease, alopecia, vitiligo, and hypopituitarism, in whom electrocardiographic examinations demonstrated an abnormal prolongation of the QT interval. In both cases, excessive hypocalcemia due to primary hypoparathyroidism was identified as the underlying cause of the long QT syndrome. Sequencing the gene coding for the autoimmune regulator revealed a homozygous missense mutation in exon 14 with a C-to-T transition that resulted in the substitution of proline 539 for leucine in the carboxy-terminal protein molecule. Our data show that a single point mutation in the transcriptional active autoimmune regulator protein is associated with inherited alterations in calcium metabolism resulting from autoimmune reactions against the parathyroid glands. This finding defines a congenital autoimmune disease as a hereditary long QT syndrome.

A 28 year old man with primary hypoparathyroidism failed to respond to treatment with calcium and vitamin D analogues. Despite extensive investigation no reason for this was found and he is now successfully treated with teriparatide (synthetic human PTH)

Autoimmune hypoparathyroidism is thought to result from immune-mediated destruction of the parathyroid glands. We encountered two patients with hypoparathyroidism and other autoimmune conditions (Graves' disease and Addison's disease, respectively) in whom autoimmune destruction of the parathyroid glands had not taken place. In the first, a histologically normal parathyroid gland was observed at the time of subtotal thyroidectomy; and in the second, the hypoparathyroidism remitted spontaneously. Both patients had antibodies that reacted with the cell surface of bovine parathyroid cells and human embryonic kidney (HEK293) cells transfected with the extracellular calcium-sensing receptor (CaR) but not with nontransfected HEK293 cells. The antibodies also reacted with the same bands on Western analysis of extracts of bovine parathyroid tissue and CaR-transfected HEK293 cells that were identified by an authentic, polyclonal, anti-CaR antiserum and reacted with several peptides with sequences from the CaR's extracellular domain. These anti-CaR antibodies activated the receptor based on their ability to increase inositol phosphate accumulation, activate MAPK, and inhibit PTH secretion. These results, therefore, demonstrate that patients with the biochemical findings of primary hypoparathyroidism can harbor activating antibodies to the CaR, which, in the two cases studied here, did not produce irreversible destruction of the parathyroid glands.

A 42-yr-old woman presented with hyperthyroidism and a large, firm, irregular goiter. Within a few weeks she became hypothyroid. Five months later she developed increasingly severe neck pain and compressive symptoms. The goiter had become rock hard. A fine needle aspiration biopsy showed features of chronic thyroiditis and fibrosis. She partially responded to a course of glucocorticoids. Tamoxifen was added, with marked improvement in goiter size and pain. Both medications were tapered off. Two months later the patient experienced paresthesias of the fingertips, perioral numbness, and a seizure. She was found to have spontaneous primary hypoparathyroidism. Three months later the patient became hoarse and experienced difficulty in breathing. She was found to have a massively enlarged thyroid with compression of the right internal jugular vein and encasement of the right carotid artery as well as tracheal narrowing. She also had right vocal cord paralysis due to recurrent laryngeal nerve involvement. Because of airway compromise, an emergency isthmusectomy was performed, and the patient was given a postoperative course of glucocorticoids with gradual improvement. Postoperative diagnosis was Riedel's thyroiditis. Two months later she presented with near-syncope and was found to have bradycardia, hypotension, and right Horner's syndrome, presumably due to compression of the right carotid sheath. She was given i.v. glucocorticoids and tamoxifen. Six months later and 18 months after her initial presentation, the patient is doing remarkably well. Her goiter has regressed by more than 50%, and she no longer has any pain or difficulty breathing. She remains a little hoarse and has persistent hypothyroidism and hypoparathyroidism. She is taking prednisone (5 mg, this is being tapered very slowly) and tamoxifen (20 mg) daily. This case illustrates the protean manifestations of Riedel's thyroiditis, a rare but fascinating disease. The epidemiology of this disease, its pathophysiology and complications, and the roles of surgery and medical therapy are reviewed.