Review

Authors: John P Bilezikian

BACKGROUND

Hypoparathyroidism is a rare endocrine disorder characterized by hypocalcemia and low or undetectable levels of parathyroid hormone.

METHODS

This review is an evidence-based summary of hypoparathyroidism in terms of relevant pathophysiological, clinical, and therapeutic concepts.

RESULTS

Many clinical manifestations of hypoparathyroidism are due to the lack of the physiological actions of parathyroid hormone on its 2 major target organs: the skeleton and the kidney. The skeleton is inactive, accruing bone without remodeling it. The kidneys lose the calcium-conserving actions of parathyroid hormone and, thus, excrete a greater fraction of calcium. Biochemical manifestations, besides hypocalcemia and low or undetectable levels of parathyroid hormone, include hyperphosphatemia and low levels of 1,25-dihydroxyvitamin D. Calcifications in the kidney, brain, and other soft tissues are common. Removal of, or damage to, the parathyroid glands at the time of anterior neck surgery is, by far, the most likely etiology. Autoimmune destruction of the parathyroid glands and other genetic causes represent most of the other etiologies. Conventional treatment with calcium and active vitamin D can maintain the serum calcium level but high doses may be required, adding to the risk of long-term soft tissue calcifications. The advent of replacement therapy with recombinant human PTH(1-84) represents a major step in the therapeutics of this disease.

CONCLUSIONS

Advances in our knowledge of hypoparathyroidism have led to greater understanding of the disease itself and our approach to it.

Topics: Humans; Hypocalcemia; Hypoparathyroidism; Parathyroid Hormone; Prognosis

PubMed: 32322899
DOI: 10.1210/clinem/dgaa113

Review

Authors: Grzegorz J Kowalski, Grzegorz Buła, Dominika Żądło...

Primary hyperparathyroidism is an endocrine disorder that results in overproduction of parathyroid hormone by overactivated parathyroid gland leading to a significant rise in blood serum calcium. It results in hypercalcaemia, which has a significant impact mainly on the kidneys and bones and results in a variety of signs and symptoms. Primary hyperparathyroidism should be treated because, if left without any therapy, it can lead even to death. Surgery is considered as the best and only successful therapy, with very low risk of recurrence and relatively low complication rate. The aim of this review is to present clinical basis, aetiology, diagnostic possibilities, and treatment opportunities.

Topics: Female; Humans; Hyperparathyroidism, Primary; Male; Parathyroid Hormone; Parathyroidectomy

PubMed: 32797471
DOI: 10.5603/EP.a2020.0028

Review

Authors: Syed Jalal Khundmiri, Rebecca D Murray, Eleanor Lederer...

PTH and Vitamin D are two major regulators of mineral metabolism. They play critical roles in the maintenance of calcium and phosphate homeostasis as well as the development and maintenance of bone health. PTH and Vitamin D form a tightly controlled feedback cycle, PTH being a major stimulator of vitamin D synthesis in the kidney while vitamin D exerts negative feedback on PTH secretion. The major function of PTH and major physiologic regulator is circulating ionized calcium. The effects of PTH on gut, kidney, and bone serve to maintain serum calcium within a tight range. PTH has a reciprocal effect on phosphate metabolism. In contrast, vitamin D has a stimulatory effect on both calcium and phosphate homeostasis, playing a key role in providing adequate mineral for normal bone formation. Both hormones act in concert with the more recently discovered FGF23 and klotho, hormones involved predominantly in phosphate metabolism, which also participate in this closely knit feedback circuit. Of great interest are recent studies demonstrating effects of both PTH and vitamin D on the cardiovascular system. Hyperparathyroidism and vitamin D deficiency have been implicated in a variety of cardiovascular disorders including hypertension, atherosclerosis, vascular calcification, and kidney failure. Both hormones have direct effects on the endothelium, heart, and other vascular structures. How these effects of PTH and vitamin D interface with the regulation of bone formation are the subject of intense investigation.

Topics: Animals; Calcium; Fibroblast Growth Factor-23; Humans; Parathyroid Diseases; Parathyroid Hormone; Receptors, Calcitriol; Receptors, Parathyroid Hormone; Vitamin D; Vitamin D Deficiency

PubMed: 27065162
DOI: 10.1002/cphy.c140071

Review

Authors: Natalie E Cusano, Filomena Cetani

Normocalcemic primary hyperparathyroidism (PHPT) is a newer phenotype of PHPT defined by elevated PTH concentrations in the setting of normal serum calcium levels. It is increasingly being diagnosed in the setting of evaluation for nephrolithiasis or metabolic bone diseases. It is important to demonstrate that PTH values remain consistently elevated and to measure ionized calcium levels to make the diagnosis. A diagnosis of normocalcemic disease is one of exclusion of secondary forms of hyperparathyroidism, including vitamin D deficiency, renal failure, medications, malabsorption, and hypercalciuria. Lack of rigorous diagnostic criteria and selection bias of the studied populations may explain the different rates of bone and renal complications. The natural history still remains unknown. Caution should be used in recommending surgery, unless clearly indicated. Here we will review the diagnostic features, epidemiology, clinical presentation, natural history, medical and surgical management of normocalcemic PHPT.

Topics: Humans; Hyperparathyroidism, Primary; Parathyroid Hormone; Calcium; Bone Diseases, Metabolic; Vitamin D Deficiency

PubMed: 36382756
DOI: 10.20945/2359-3997000000556

European Expert Consensus on Practical Management of Specific Aspects of Parathyroid Disorders in Adults and in Pregnancy: Recommendations of the ESE Educational Program of Parathyroid Disorders.

Authors: Jens Bollerslev, Lars Rejnmark, Alexandra Zahn...

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

Topics: Adult; Calcium; Female; Humans; Hypercalcemia; Hyperparathyroidism, Primary; Hypoparathyroidism; Infant, Newborn; Lactation; Parathyroid Diseases; Parathyroid Hormone; Pregnancy

PubMed: 34863037
DOI: 10.1530/EJE-21-1044

Review

Authors: Li-Xi Zhang, Ben Zhang, Xu-Yao Liu...

Secondary hyperparathyroidism (SHPT) and tertiary hyperparathyroidism (THPT) are common and complicated clinical endocrine diseases. The parathyroid glands maintain endocrine homeostasis by secreting parathyroid hormone to regulate blood calcium levels. However, structural alterations to multiple organs and systems occur throughout the body due to hyperactivity disorder in SHPT and THPT. This not only decreases the patients' quality of life, but also affects mortality. Since current treatments for these diseases remains unclear, we aimed to develop a comprehensive review of advances in the treatment of SHPT and THPT according to the latest relevant researches.

Topics: Humans; Hyperparathyroidism, Secondary; Parathyroid Glands; Parathyroid Hormone; Parathyroidectomy; Quality of Life

PubMed: 36561571
DOI: 10.3389/fendo.2022.1059828

Review

Authors: Francisco Bandeira, Janiere de Moura Nóbrega, Lucian Batista de Oliveira...

Primary hyperparathyroidism (PHPT) is an endocrine disorder resulting from the hyperfunction of one or more parathyroid glands, with hypersecretion of parathyroid hormone (PTH). It can be managed by parathyroidectomy (PTX) or non-surgically. Medical therapy with pharmacological agents is an alternative for those patients with asymptomatic PHPT who meet guidelines for surgery but are unable or unwilling to undergo PTX. In this review, we focus upon these non-surgical aspects of PHPT management. We emphasize the most studied and widely used pharmacological alternatives: bisphosphonates, denosumab, cinacalcet and hormone therapy, in addition to combined therapy. We also address the relevant aspects of perioperative management.

Topics: Humans; Hyperparathyroidism, Primary; Parathyroidectomy; Cinacalcet; Parathyroid Hormone; Parathyroid Glands

PubMed: 36382758
DOI: 10.20945/2359-3997000000558

Authors: Michael Mannstadt, Luisella Cianferotti, Rachel I Gafni...

This narrative report summarizes diagnostic criteria for hypoparathyroidism and describes the clinical presentation and underlying genetic causes of the nonsurgical forms. We conducted a comprehensive literature search from January 2000 to January 2021 and included landmark articles before 2000, presenting a comprehensive update of these topics and suggesting a research agenda to improve diagnosis and, eventually, the prognosis of the disease. Hypoparathyroidism, which is characterized by insufficient secretion of parathyroid hormone (PTH) leading to hypocalcemia, is diagnosed on biochemical grounds. Low albumin-adjusted calcium or ionized calcium with concurrent inappropriately low serum PTH concentration are the hallmarks of the disease. In this review, we discuss the characteristics and pitfalls in measuring calcium and PTH. We also undertook a systematic review addressing the utility of measuring calcium and PTH within 24 hours after total thyroidectomy to predict long-term hypoparathyroidism. A summary of the findings is presented here; results of the detailed systematic review are published separately in this issue of JBMR. Several genetic disorders can present with hypoparathyroidism, either as an isolated disease or as part of a syndrome. A positive family history and, in the case of complex diseases, characteristic comorbidities raise the clinical suspicion of a genetic disorder. In addition to these disorders' phenotypic characteristics, which include autoimmune diseases, we discuss approaches for the genetic diagnosis. © 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).

Topics: Humans; Calcium; Hypocalcemia; Hypoparathyroidism; Parathyroid Hormone

PubMed: 36375809
DOI: 10.1002/jbmr.4667

Review

Authors: María E Rodríguez-Ortiz, Mariano Rodríguez

Secondary hyperparathyroidism is a complex pathology that develops as chronic kidney disease progresses. The retention of phosphorus and the reductions in calcium and vitamin D levels stimulate the synthesis and secretion of parathyroid hormone as well as the proliferation rate of parathyroid cells. Parathyroid growth is initially diffuse but it becomes nodular as the disease progresses, making the gland less susceptible to be inhibited. Although the mechanisms underlying the pathophysiology of secondary hyperparathyroidism are well known, new evidence has shed light on unknown aspects of the deregulation of parathyroid function. Secondary hyperparathyroidism is an important feature of chronic kidney disease-mineral and bone disorder and plays an important role in the development of bone disease and vascular calcification. Thus, part of the management of chronic kidney disease relies on maintaining acceptable levels of mineral metabolism parameters in an attempt to slow down or prevent the development of secondary hyperparathyroidism. Here, we will also review the latest evidence regarding several aspects of the clinical and surgical management of secondary hyperparathyroidism.

Topics: Calcium; Chronic Kidney Disease-Mineral and Bone Disorder; Humans; Hyperparathyroidism, Secondary; Parathyroid Hormone; Phosphorus; Renal Insufficiency, Chronic; Vitamin D

PubMed: 32913635
DOI: 10.12688/f1000research.22636.1

Review

Authors: Bart L Clarke, Edward M Brown, Michael T Collins...

CONTEXT

Hypoparathyroidism is a disorder characterized by hypocalcemia due to insufficient secretion of PTH. Pseudohypoparathyroidism is a less common disorder due to target organ resistance to PTH. This report summarizes the results of the findings and recommendations of the Working Group on Epidemiology and Diagnosis of Hypoparathyroidism.

EVIDENCE ACQUISITION

Each contributing author reviewed the recent published literature regarding epidemiology and diagnosis of hypoparathyroidism using PubMed and other medical literature search engines.

EVIDENCE SYNTHESIS

The prevalence of hypoparathyroidism is an estimated 37 per 100 000 person-years in the United States and 22 per 100 000 person-years in Denmark. The incidence in Denmark is approximately 0.8 per 100 000 person-years. Estimates of prevalence and incidence of hypoparathyroidism are currently lacking in most other countries. Hypoparathyroidism increases the risk of renal insufficiency, kidney stones, posterior subcapsular cataracts, and intracerebral calcifications, but it does not appear to increase overall mortality, cardiovascular disease, fractures, or malignancy. The diagnosis depends upon accurate measurement of PTH by second- and third-generation assays. The most common etiology is postsurgical hypoparathyroidism, followed by autoimmune disorders and rarely genetic disorders. Even more rare are etiologies including parathyroid gland infiltration, external radiation treatment, and radioactive iodine therapy for thyroid disease. Differentiation between these different etiologies is aided by the clinical presentation, serum biochemistries, and in some cases, genetic testing.

CONCLUSIONS

Hypoparathyroidism is often associated with complications and comorbidities. It is important for endocrinologists and other physicians who care for these patients to be aware of recent advances in the epidemiology, diagnosis, and genetics of this disorder.

Topics: Cataract; Denmark; Humans; Hypoparathyroidism; Incidence; Kidney Calculi; Prevalence; Renal Insufficiency; Risk; United States

PubMed: 26943720
DOI: 10.1210/jc.2015-3908