Background This manuscript provides a summary of the current evidence to support the criteria for diagnosing a child or adult with hypophosphatasia (HPP). The diagnosis of HPP is made on the basis of integrating clinical features, laboratory profile, radiographic features of the condition, and DNA analysis identifying the presence of a pathogenic variant of the tissue nonspecific alkaline phosphatase gene (ALPL). Often, the diagnosis of HPP is significantly delayed in both adults and children, and updated diagnostic criteria are required to keep pace with our evolving understanding regarding the relationship between ALPL genotype and associated HPP clinical features. Methods An International Working Group (IWG) on HPP was formed, comprised of a multidisciplinary team of experts from Europe and North America with expertise in the diagnosis and management of patients with HPP. Methodologists (Romina Brignardello-Petersen and Gordon Guyatt) and their team supported the IWG and conducted systematic reviews following the GRADE methodology, and this provided the basis for the recommendations. Results The IWG completed systematic reviews of the literature, including case reports and expert opinion papers describing the phenotype of patients with HPP. The published data are largely retrospective and include a relatively small number of patients with this rare condition. It is anticipated that further knowledge will lead to improvement in the quality of genotype-phenotype reporting in this condition. Conclusion Following consensus meetings, agreement was reached regarding the major and minor criteria that can assist in establishing a clinical diagnosis of HPP in adults and children.

Hypoparathyroidism (HypoPT) is a rare disorder characterized by hypocalcemia in the presence of a low or inappropriately normal parathyroid hormone level. HypoPT is most commonly seen after neck surgery, which accounts for approximately 75% of cases, whereas approximately 25% have HypoPT due to nonsurgical causes. In both groups of patients, conventional therapy includes calcium and active vitamin D analogue therapy aiming to maintain serum calcium concentration in the low normal or just below the normal reference range and normalize serum phosphorus, magnesium concentrations, and urine calcium levels. The limitations of conventional therapy include wide fluctuations in serum calcium, high pill burden, poor quality of life, and renal complications. Parathyroid hormone (PTH) replacement therapy may improve the biochemical profile in those in whom conventional therapy proves unsatisfactory. Based on a systematic review and meta-analysis of the literature, the panel made a graded recommendation suggesting conventional therapy as first line therapy rather than administration of PTH (weak recommendation, low quality evidence). When conventional therapy is deemed unsatisfactory, the panel considers use of PTH. Because pregnancy and lactation are associated with changes in calcium homeostasis, close monitoring is required during these periods with appropriate adjustment of calcium and active vitamin D analogue therapy to ensure that serum calcium remains in the mid to low normal reference range in order to avoid maternal and fetal complications. Emerging therapies include molecules with prolonged PTH action as well as different mechanisms of action that may significantly enhance drug efficacy and safety. © 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).

The complications and symptoms of hypoparathyroidism remain incompletely defined. Measuring serum parathyroid hormone (PTH) and calcium levels early after total thyroidectomy may predict the development of chronic hypoparathyroidism. The study aimed (i) to identify symptoms and complications associated with chronic hypoparathyroidism and determine the prevalence of those symptoms and complications (Part I), and (ii) to examine the utility of early postoperative measurements of PTH and calcium in predicting chronic hypoparathyroidism (Part II). We searched Medline, Medline In-Process, EMBASE, and Cochrane CENTRAL to identify complications and symptoms associated with chronic hypoparathyroidism. We used two predefined criteria (at least three studies reported the complication and symptom and had statistically significantly greater pooled relative estimates). To estimate prevalence, we used the median and interquartile range (IQR) of the studies reporting complications and symptoms. For testing the predictive values of early postoperative measurements of PTH and calcium, we used a bivariate model to perform diagnostic test meta-analysis. In Part I, the 93 eligible studies enrolled a total of 18,973 patients and reported on 170 complications and symptoms. We identified nine most common complications or symptoms probably associated with chronic hypoparathyroidism. The complications or symptoms and the prevalence are as follows: nephrocalcinosis/nephrolithiasis (median prevalence among all studies 15%), renal insufficiency (12%), cataract (17%), seizures (11%), arrhythmia (7%), ischemic heart disease (7%), depression (9%), infection (11%), and all-cause mortality (6%). In Part II, 18 studies with 4325 patients proved eligible. For PTH measurement, regarding the posttest probability, PTH values above 10 pg/mL 12–24 hours postsurgery virtually exclude chronic hypoparathyroidism irrespective of pretest probability (100%). When PTH values are below 10 pg/mL, posttest probabilities range from 3% to 64%. Nine complications and symptoms are probably associated with chronic hypoparathyroidism. A PTH value above a threshold of 10 pg/mL 12–24 hours after total thyroidectomy is a strong predictor that the patients will not develop chronic hypoparathyroidism. Patients with PTH values below the threshold need careful monitoring as some will develop chronic hypoparathyroidism. © 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).

Primary hyperparathyroidism (PHPT) is the most common cause of hypercalcemia in the outpatient setting. Symptomatic presentation includes non-specific signs and symptoms of hypercalcemia, skeletal fragility, nephrolithiasis and nephrocalcinosis. The majority of individuals present at an asymptomatic stage following routine biochemical screening, without any signs or symptoms of calcium or parathyroid hormone (PTH) excess or target organ damage. Indications for surgery have recently been revised as published in recent guidelines and consensus statements. Parathyroidectomy is advised in patients younger than 50 years old and in the presence of either significant hypercalcemia, impaired renal function, renal stones or osteoporosis. Surgery is always appropriate in suitable surgical candidates, however, medical management may be considered in those with mild asymptomatic disease, contraindications to surgery or failed previous surgical intervention. We summarized the optimal medical interventions available in the care of PHPT patients not undergoing parathyroidectomy. Calcium and vitamin D intake should be optimized. Antiresorptive therapy may be used for skeletal protection in patients with an increased fracture risk. Cinacalcet, a calcimimetic agent, has been shown to effectively lower serum calcium and PTH levels. The effect of medical treatment on the reduction in fracture risk is unknown and should be the focus of future research.

Background: Parathyroid disease is uncommon in pregnancy. During pregnancy, multiple changes occur in the calcium regulating hormones which may make the diagnosis of primary hyperparathyroidism more challenging. Close monitoring of serum calcium during pregnancy is necessary in order to optimize maternal and fetal outcomes. In this review, we will describe the diagnosis and management of primary hyperparathyroidism during pregnancy. Methods: We searched MEDLINE, CINAHL, EMBASE and Google scholar bases from 1 January 1990 to 31 December 2020. Case reports, case series, book chapters and clinical guidelines were included in this review. Conclusions: Medical management options for primary hyperparathyroidism during pregnancy are severely limited due to inadequate safety data with the various potential therapies available, and surgery is advised during the 2nd trimester of pregnancy in the presence of severe hypercalcemia (calcium adjusted for albumin greater than 3.0 mmol/L (12.0 mg/dL)). Hypercalcemia should be avoided during pregnancy in order to minimize maternal and fetal complications.