Primary Hyperparathyroidism: Part One: Evaluation.

Primary hyperparathyroidism (PHPT) is a disorder characterized by the autonomous overproduction of parathyroid hormone (PTH) that leads to hypercalcemia, multiple clinical sequelae, and heterogenous presentation. Whether PHPT is caused by a single benign adenoma (85%), multiglandular disease (15%), or parathyroid carcinoma (1%), surgery is the definitive treatment.

Results of a novel intervention to increase rates of diagnosis and treatment of primary hyperparathyroidism.

BACKGROUND: Veterans with primary hyperparathyroidism are under diagnosed and undertreated. We report the results of a pilot study to address this problem. METHODS: We implemented a stakeholder-driven, multi-component intervention to increase rates of diagnosis and treatment for primary hyperparathyroidism at a single VA hospital. Intervention effects were evaluated using an interrupted time series analysis. RESULTS: The mean age of Veterans affected by the intervention was 67 years (SD 12.1) and 84 â€‹% were men. Compared to the pre-intervention period, the intervention doubled the proportion of Veterans who were appropriately evaluated for hyperparathyroidism (absolute difference 25 â€‹%, 95 â€‹% CI 11 â€‹%-38 â€‹%, p â€‹< â€‹0.001) and increased referrals for treatment by 27 â€‹% (95 â€‹% CI 7 â€‹%-47 â€‹%, p â€‹< â€‹0.012). CONCLUSION: Our pilot study suggests it is feasible to address the underdiagnosis and undertreatment of primary hyperparathyroidism among Veterans.

Disparities in the treatment of primary hyperparathyroidism: A scoping review and conceptual model.

BACKGROUND: Primary hyperparathyroidism is underdiagnosed and surgical treatment is underutilized and inequitably distributed. We present a review of the current literature on disparities in the treatment of hyperparathyroidism, with a focus on gaps in knowledge and paths forward. METHODS: We searched PubMed and Scopus for abstracts related to disparities in hyperparathyroidism. RESULTS: 16 articles (of 1541) met inclusion criteria. The most commonly examined disparity was race. Notably, Black, Hispanic, and Asian patients were less likely to undergo surgery after diagnosis, face delays in obtaining treatment, and less likely to see a high-volume surgeon. Similar disparities in care were noted among those without insurance, older patients, and patients with limited English proficiency. CONCLUSION: There are clear inequities in the treatment of hyperparathyroidism. Current research is in an early "identification" phase of disparities research; a new conceptual model based on established socioecological frameworks is provided to help move the field forward to "understanding" and "intervening" in surgical disparities.

Italian Guidelines for the Management of Sporadic Primary Hyperparathyroidism.

AIM: This guideline (GL) is aimed at providing a clinical practice reference for the management of sporadic primary hyperparathyroidism (PHPT) in adults. PHPT management in pregnancy was not considered. METHODS: This GL has been developed following the methods described in the Manual of the Italian National Guideline System. For each question, the panel appointed by Associazione Medici Endocrinology (AME) and Società Italiana dell'Osteoporosi, del Metabolismo Minerale e delle Malattie dello Scheletro (SIOMMMS) identified potentially relevant outcomes, which were then rated for their impact on therapeutic choices. Only outcomes classified as "critical" and "important" were considered in the systematic review of evidence. Those classified as "critical" were considered for the clinical practice recommendations. RESULTS: The present GL provides recommendations about the roles of pharmacological and surgical treatment for the clinical management of sporadic PHPT. Parathyroidectomy is recommended in comparison to surveillance or pharmacologic treatment in any adult (outside of pregnancy) or elderly subject diagnosed with sporadic PHPT who is symptomatic or meets any of the following criteria: • Serum calcium levels >1 mg/dL above the upper limit of normal range. • Urinary calcium levels >4 mg/kg/day. • Osteoporosis disclosed by DXA examination and/or any fragility fracture. • Renal function impairment (eGFR <60 mL/min). • Clinic or silent nephrolithiasis. • Age ≤50 years. Monitoring and treatment of any comorbidity or complication of PHPT at bone, kidney, or cardiovascular level are suggested for patients who do not meet the criteria for surgery or are not operated on for any reason. Sixteen indications for good clinical practice are provided in addition to the recommendations. CONCLUSION: The present GL is directed to endocrinologists and surgeons - working in hospitals, territorial services or private practice - and to general practitioners and patients. The recommendations should also consider the patient's preferences and the available resources and expertise.

Characteristics, management and outcomes of primary hyperparathyroidism from 2009 to 2021: a single centre report from South Africa.

BACKGROUND: There has been a notable shift towards the diagnosis of less severe and asymptomatic primary hyperparathyroidism (PHPT) in developed countries. However, there is a paucity of recent data from sub-Saharan Africa (SSA), and also, no reported data from SSA on the utility of intra-operative parathyroid hormone (IO-PTH) monitoring. In an earlier study from Inkosi Albert Luthuli Central Hospital (IALCH), Durban, South Africa (2003-2009), majority of patients (92.9%) had symptomatic disease. The aim of this study was to evaluate the clinical profile and management outcomes of patients presenting with PHPT at IALCH. METHODS: A retrospective chart review of patients with PHPT attending the Endocrinology clinic at IALCH between July 2009 and December 2021. Clinical presentation, laboratory results, radiologic findings, surgical notes and histology were recorded. RESULTS: Analysis included 110 patients (87% female) with PHPT. Median age at presentation was 57 (44; 67.5) years. Symptomatic disease was present in 62.7% (n:69); 20.9% (n:23) had a history of nephrolithiasis and 7.3% (n:8) presented with previous fragility fractures. Mean serum calcium was 2.87 ± 0.34 mmol/l; median serum-PTH was 23.3 (15.59; 45.38) pmol/l, alkaline phosphatase 117.5 (89; 145.5) U/l and 25-hydroxyvitamin-D 42.9 (33.26; 62.92) nmol/l. Sestamibi scan (n:106 patients) identified an adenoma in 83.02%. Parathyroidectomy was performed on 84 patients with a cure rate of 95.2%. Reasons for conservative management (n:26) included: no current surgical indication (n:7), refusal (n:5) or deferral of surgery (n:5), loss to follow-up (n:5) and assessed as high anaesthetic risk (n:4). IO-PTH measurements performed on 28 patients indicated surgical success in 100%, based on Miami criteria. Histology confirmed adenoma in 88.1%, hyperplasia in 7.1% and carcinoma in 4.8%. Post-operative hypocalcaemia developed in 30 patients (35.7%), of whom, 14 developed hungry bone syndrome (HBS). In multivariate analysis, significant risk factors associated with HBS included male sex (OR 7.01; 95% CI 1.28, 38.39; p 0.025) and elevated pre-operative PTH (OR 1.01; 95% CI 1.00, 1.02; p 0.008). CONCLUSIONS: The proportion of asymptomatic PHPT has increased at this centre over the past decade but symptomatic disease remains the dominant presentation. Parathyroidectomy is curative in the majority of patients. IO-PTH monitoring is valuable in ensuring successful surgery.

Hypercalcemic Crisis Due to Parathyroid Adenoma Improved by Continuous Hemodialysis with a Common Calcium Concentration Dialysate: Discussion of Therapeutic Management.

A hypercalcemic crisis due to primary hyperparathyroidism is a life-threatening condition. We herein report a 71-years-old man with hypercalcemic crisis due to primary hyperparathyroidism with parathyroid adenoma. Generally, hemodialysis or continuous hemodiafiltration using calcium-free or low-calcium dialysate is performed early for hypercalcemic crisis. In this case, continuous hemodialysis with a common calcium concentration dialysate improved the hypercalcemic crisis, and parathyroidectomy was performed. The patient recovered sufficiently. Prediction of hypercalcemia crisis, appropriate introduction and methods of blood purification therapy, and timing decisions for parathyroidectomy are required for therapeutic management of hypercalcemic crisis with parathyroid adenoma.

[Diagnosis and management of primary hyperparathyroidism during pregnancy: A systematic review and a longitudinal case study]. / Diagnostic et prise en charge d'hyperparathyroïdie primaire pendant la grossesse : revue de la littérature autour d'un cas.

OBJECTIVE: There is no specific recommendation for management in pregnant women: the aim of this review, based on a clinical case study, is to clarify its development, complications, risk factor and treatment. METHODS: A review of the literature was performed by consulting the Pubmed, Cochrane Library, and Science Direct databases. RESULTS: Primary hyperparathyroidism is defined as excessive production of parathyroid hormone resulting in hypercalcemia. The prevalence of primary hyperparathyroidism during pregnancy is not known. Indeed, the symptomatology, related to hypercalcemia, is not very specific and easily confused with the clinical manifestations of pregnancy. The physiological changes specific to the pregnant state frequently lead to a slight hypocalcemia which may complicate the diagnosis of primary hyperparathyroidism. Primary hyperparathyroidism results from a parathyroid adenoma in the majority of cases and is detected by ultrasound during pregnancy. Primary hyperparathyroidism in pregnancy causes significant risks to both mother and fetus. The maternal complication rate is 14-67%, however, the most serious complication is hypercalcemic crisis, which requires increased surveillance in the postpartum period. Obstetrical complications are also induced by primary hyperparathyroidism, such as acute polyhydramnios, or intrauterine growth retardation. The fetal complication rate can reach 45-80% of cases with neonatal hypocalcemia as the main complication. If medical treatment is based on hyperhydration, only surgical treatment is curative. CONCLUSION: Surgery should be proposed to symptomatic patients or those with high blood calcium levels, discussed in interdisciplinary committee and should be organized ideally in the second trimester to avoid maternal and fetal complications.

Evaluation of risk factors for recurrent renal stone formation among Saudi Arabian patients: Comparison with first renal stone episode.

OBJECTIVES: We evaluated the baseline characteristics, and risk factors of renal stone recurrence among Saudi Arabian patients after successful primary stone treatment. MATERIALS AND METHODS: In this cross-sectional comparative study, we reviewed the medical records of patients who presented consecutively with a first renal stone episode from 2015 to 2021 and were followed-up by mail questionnaire, telephone interviews, and/or outpatient clinic visit. We included patients who achieved stone-free status after primary treatment. Patients were divided into two groups: group I (patients with first episode renal stone) and group Ⅱ (patients who developed renal stone recurrence). The study outcomes were to compare the demographics of both groups and to evaluate the risk factors of renal stone recurrence after successful primary treatment. We used Student's t-test, Mann Whitney test or chi-square (x2) to compare variables between groups. Cox regression analyses were used to examine the predictors. RESULTS: We investigated 1260 participants (820 males and 440 females). Of this number, 877 (69.6%) didn't develop renal stone recurrence and 383 (30.4%) had recurrence. Primary treatments were percutaneous nephrolithotomy (PCNL), retrograde intrarenal surgery (RIRS), extracorporeal shock wave lithotripsy (ESWL), surgery and medical treatment in 22.5%, 34.7%, 26.5%, 10.3%, and 6%, respectively. After primary treatment, 970 (77%) and 1011 (80.2%) of patients didn't have either stone chemical analysis or metabolic work-up, respectively. Multivariate logistic regression analysis revealed that male gender (OR: 1.686; 95% CI, 1.216-2.337), hypertension (OR: 2.342; 95% CI, 1.439-3.812), primary hyperparathyroidism (OR: 2.806; 95% CI, 1.510-5.215), low fluid intake (OR: 28.398; 95% CI, 18.158-44.403) and high daily protein intake (OR: 10.058; 95% CI, 6.400-15.807) were predictors of renal stone recurrence. CONCLUSIONS: Male gender, hypertension, primary hyperparathyroidism, low fluid intake and high daily protein intake increase the risk of renal stone recurrence among Saudi Arabian patients.

[Special features of the diagnostics and treatment of hereditary primary hyperparathyroidism]. / Besonderheiten in Diagnostik und Therapie des hereditären primären Hyperparathyreoidismus.

Between 2% and 10% of patients with primary hyperparathyroidism (pHPT) are diagnosed with hereditary forms of primary hyperparathyroidism (hpHPT). They are more prevalent in younger patients before the age of 40 years, in patients with persistence or recurrence of pHPT and pHPT patients with multi-glandular disease (MGD). The various forms of hpHPT diseases can be classified into four syndromes, i.e., hpHPT associated with diseases of other organ systems, and four diseases that are confined to the parathyroid glands. Approximately 40% of patients with hpHPT suffer from multiple endocrine neoplasia type 1 (MEN-1) or show germline mutations of the MEN­1 gene. Currently, germline mutations that lead to a specific diagnosis in patients with hpHPT have currently been described in 13 different genes, which enables a clear diagnosis of the disease; however, a clear genotype-phenotype correlation does not exist, even though the complete loss of a coded protein (e.g. due to frame-shift mutations in the calcium sensing receptor, CASR) often leads to more severe clinical consequences than merely a reduced function of the protein (e.g. due to point mutation). As the various hpHPT diseases require different treatment approaches, which do not correspond to that of sporadic pHPT, a clear definition of the specific form of hpHPT must always be strived for. Therefore, before surgery of a pHPT with clinical, imaging or biochemical suspicion of hpHPT, genetic proof or exclusion of hpHPT is necessary. The differentiated treatment approach for hpHTP can only be defined by taking the clinical and diagnostic results of all the abovenamed findings into account.

Expert consensus on multidisciplinary approach to the diagnosis and treatment of primary hyperparathyroidism in pregnancy in China.

Primary hyperparathyroidism in pregnancy is a rare disease that can have detrimental effects on both maternal and fetal/neonatal outcomes. The physiological changes that occur during pregnancy can complicate the diagnosis, imaging examinations, and treatment of this disorder. To enhance our understanding and management of primary hyperparathyroidism in pregnancy, experts from various fields, including endocrinology, obstetrics, surgery, ultrasonography, nuclear medicine, pediatrics, nephrology, and general practice in China, collaborated to develop a consensus addressing the critical aspects of the diagnosis and treatment of primary hyperparathyroidism in pregnancy with a multidisciplinary team approach. This consensus provides valuable guidance for healthcare professionals in managing this condition, ultimately improving outcomes for both mothers and their babies.

Approach to the Patient: Management of Parathyroid Diseases Across Pregnancy.

Taking care of patients with parathyroid disorders during pregnancy requires consideration of the physiological fundamental changes in bone and mineral metabolism occurring in these women. Diagnostic and therapeutic procedures regarding primary hyperparathyroidism (PHPT) and hypoparathyroidism significantly differ from the nonpregnant population. PHPT should preferably be cured by parathyroidectomy before pregnancy since in women with hypercalcemic PHPT, maternal and fetal pregnancy complications seem to increase according to the degree of hypercalcemia. Parathyroidectomy, if needed during pregnancy, is preferentially performed in the second trimester. Conservative treatment is recommended for milder cases and is mainly restricted to hydration, with only limited evidence regarding drug treatment. Women with hypoparathyroidism can be informed that there are no major concerns regarding disease-associated infertility and that the risk of pregnancy complications is low if the disease is properly managed. Regular active surveillance is recommended, as requirements for calcium and active vitamin D may change during the course of pregnancy in either direction, with an overall trend for rather reduced doses. Any woman suffering from parathyroid disorders during pregnancy requires further surveillance in the postpartum period and during lactation, as there is an increased risk of hypercalcemia after delivery. Newborns of mothers with parathyroid diseases should, depending on disease severity, be carefully monitored for calcium levels in the first days (to weeks) after delivery since intrauterine exposure to hyper- or hypocalcemia may impact their postnatal regulation of calcium metabolism.

Quality of Life in Primary Hyperparathyroidism.

Quality of life is impaired in primary hyperparathyroidism (PHPT), regardless of the severity of the disease. Clinical studies have employed different instruments, including standardized and disease-specific questionnaires, and including patients with different phenotypes of PHPT. Neuropsychiatric symptoms and decline in cognitive status are common in PHPT. Patients may complain of these issues or they can be ascertained by questionnaires; they include depression, anxiety, impaired vitality, social and emotional functions, sleep disturbances, and altered mental function. Randomized controlled trials on the effects of surgical versus non-surgical treatments have collectively shown improvement in quality of life after parathyroidectomy, but results have been heterogeneous.

Evaluation and Management of Primary Hyperparathyroidism: Summary Statement and Guidelines from the Fifth International Workshop.

The last international guidelines on the evaluation and management of primary hyperparathyroidism (PHPT) were published in 2014. Research since that time has led to new insights into epidemiology, pathophysiology, diagnosis, measurements, genetics, outcomes, presentations, new imaging modalities, target and other organ systems, pregnancy, evaluation, and management. Advances in all these areas are demonstrated by the reference list in which the majority of listings were published after the last set of guidelines. It was thus, timely to convene an international group of over 50 experts to review these advances in our knowledge. Four Task Forces considered: 1. Epidemiology, Pathophysiology, and Genetics; 2. Classical and Nonclassical Features; 3. Surgical Aspects; and 4. Management. For Task Force 4 on the Management of PHPT, Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) methodology addressed surgical management of asymptomatic PHPT and non-surgical medical management of PHPT. The findings of this systematic review that applied GRADE methods to randomized trials are published as part of this series. Task Force 4 also reviewed a much larger body of new knowledge from observations studies that did not specifically fit the criteria of GRADE methodology. The full reports of these 4 Task Forces immediately follow this summary statement. Distilling the essence of all deliberations of all Task Force reports and Methodological reviews, we offer, in this summary statement, evidence-based recommendations and guidelines for the evaluation and management of PHPT. Different from the conclusions of the last workshop, these deliberations have led to revisions of renal guidelines and more evidence for the other recommendations. The accompanying papers present an in-depth discussion of topics summarized in this report. © 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).

Hypercalcemia: A Review.

Importance: Hypercalcemia affects approximately 1% of the worldwide population. Mild hypercalcemia, defined as total calcium of less than 12 mg/dL (<3 mmol/L) or ionized calcium of 5.6 to 8.0 mg/dL (1.4-2 mmol/L), is usually asymptomatic but may be associated with constitutional symptoms such as fatigue and constipation in approximately 20% of people. Hypercalcemia that is severe, defined as total calcium of 14 mg/dL or greater (>3.5 mmol/L) or ionized calcium of 10 mg/dL or greater (≥2.5 mmol/L) or that develops rapidly over days to weeks, can cause nausea, vomiting, dehydration, confusion, somnolence, and coma. Observations: Approximately 90% of people with hypercalcemia have primary hyperparathyroidism (PHPT) or malignancy. Additional causes of hypercalcemia include granulomatous disease such as sarcoidosis, endocrinopathies such as thyroid disease, immobilization, genetic disorders, and medications such as thiazide diuretics and supplements such as calcium, vitamin D, or vitamin A. Hypercalcemia has been associated with sodium-glucose cotransporter 2 protein inhibitors, immune checkpoint inhibitors, denosumab discontinuation, SARS-CoV-2, ketogenic diets, and extreme exercise, but these account for less than 1% of causes. Serum intact parathyroid hormone (PTH), the most important initial test to evaluate hypercalcemia, distinguishes PTH-dependent from PTH-independent causes. In a patient with hypercalcemia, an elevated or normal PTH concentration is consistent with PHPT, while a suppressed PTH level (<20 pg/mL depending on assay) indicates another cause. Mild hypercalcemia usually does not need acute intervention. If due to PHPT, parathyroidectomy may be considered depending on age, serum calcium level, and kidney or skeletal involvement. In patients older than 50 years with serum calcium levels less than 1 mg above the upper normal limit and no evidence of skeletal or kidney disease, observation may be appropriate. Initial therapy of symptomatic or severe hypercalcemia consists of hydration and intravenous bisphosphonates, such as zoledronic acid or pamidronate. In patients with kidney failure, denosumab and dialysis may be indicated. Glucocorticoids may be used as primary treatment when hypercalcemia is due to excessive intestinal calcium absorption (vitamin D intoxication, granulomatous disorders, some lymphomas). Treatment reduces serum calcium and improves symptoms, at least transiently. The underlying cause of hypercalcemia should be identified and treated. The prognosis for asymptomatic PHPT is excellent with either medical or surgical management. Hypercalcemia of malignancy is associated with poor survival. Conclusions and Relevance: Mild hypercalcemia is typically asymptomatic, while severe hypercalcemia is associated with nausea, vomiting, dehydration, confusion, somnolence, and coma. Asymptomatic hypercalcemia due to primary hyperparathyroidism is managed with parathyroidectomy or observation with monitoring, while severe hypercalcemia is typically treated with hydration and intravenous bisphosphonates.

Methodology for the Guidelines on Evaluation and Management of Hypoparathyroidism and Primary Hyperparathyroidism.

To develop guidelines for hypoparathyroidism and primary hyperparathyroidism, the panel assembled a panel of experts in parathyroid disorders, general endocrinologists, representatives of the Hypoparathyroidism Association, and systematic review and guideline methodologists. The guideline panel referred to a formal process following the Recommendations, Assessment, Development, and Evaluation Working Group (GRADE) methodology to issue GRADEd recommendations. In this approach, panelists and methodologists formatted the questions, conducted systematic reviews, evaluated risk of bias, assessed certainty of evidence, and presented a summary of findings in a transparent fashion. For most recommendations, the task forces used a less structured approach largely based on narrative reviews to issue non-GRADEd recommendations. The panel issued Eight GRADEd recommendations (seven for hypoparathyroidism and one for hyperparathyroidism). Each GRADEd recommendation is linked to the underlying body of evidence and judgments regarding the certainty of evidence and strength of recommendations, values and preferences, and costs, feasibility, acceptability and equity. This article summarizes the methodology for issuing GRADEd and non-GRADEd recommendations for patients with hypoparathyroidism or hyperparathyroidism. © 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).

Management of Primary Hyperparathyroidism.

Since the last international guidelines were published in 2014 on the evaluation and management of primary hyperparathyroidism (PHPT), new information has become available with regard to evaluation, diagnosis, epidemiology, genetics, classical and nonclassical manifestations, surgical and nonsurgical approaches, and natural history. To provide the most current summary of these developments, an international group, consisting of over 50 experts in these various aspects of PHPT, was convened. This paper provides the results of the task force that was assigned to review the information on the management of PHPT. For this task force on the management of PHPT, two questions were the subject of systematic reviews using the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) methodology. The full report addressing surgical and nonsurgical management of PHPT, utilizing the GRADE methodology, is published separately in this series. In this report, we summarize the results of that methodological review and expand them to encompass a much larger body of new knowledge that did not specifically fit the criteria of the GRADE methodology. Together, both the systematic and narrative reviews of the literature, summarized in this paper, give the most complete information available to date. A panel of experts then considered the last set of international guidelines in light of the newer data and assessed the need for their revision. This report provides the evidentiary background to the guidelines report. In that report, evidence from all task forces is synthesized into a summary statement and revised guidelines for the evaluation and management of PHPT. © 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).

Different treatment strategies in primary hyperparathyroidism during pregnancy.

PURPOSE: Primary hyperparathyroidism (PHPT) in pregnancy is rare enough and can be unrecognized because of nonspecific symptoms in most cases, but life-threatening complications for mother, fetus and neonate also occurs. PHPT requires frequent monitoring of the mother and fetus by a multidisciplinary team. Diagnostics and treatment approaches are limited and require individual risk-benefit assessment. METHODS: In this paper we describe 3 cases of PHPT in pregnant women with different managing approaches (surveillance, drug therapy and surgical treatment) and successful outcomes. Additionally, the most actual literature data on this problem is reviewed. RESULTS: The management of PHPT in pregnancy should be based on the clinical features, severity of hypercalcemia, gestational age and patient's preference. In the first case a conservative approach with low-calcium diet and oral hydration resulted in mother's reduced serum calcium level before delivery. The second patient had severe hypercalcemia and absolute indications for surgery that was successfully performed at 25 week of gestation. The third woman received cinacalcet because of severe hypercalcemia and potential perioperative risks in the third trimester with an improvement in well-being. CONCLUSION: Nowadays parathyroidectomy is the best choice for patients with symptomatic PHPT and severe hypercalcemia. This intervention should be carried out preferably in the second trimester to avoid maternal and fetal complications. Mild forms of the disease can require just a conservative management. The drug treatment of PHPT during pregnancy is still controversial.

Parathyroid Disorders.

Parathyroid disorders are most often identified incidentally by abnormalities in serum calcium levels when screening for renal or bone disease or other conditions. Parathyroid hormone, which is released by the parathyroid glands primarily in response to low calcium levels, stimulates osteoclastic bone resorption and serum calcium elevation, reduces renal calcium clearance, and stimulates intestinal calcium absorption through synthesis of 1,25-dihydroxyvitamin D. Primary hyperparathyroidism, in which calcium levels are elevated without appropriate suppression of parathyroid hormone levels, is the most common cause of hypercalcemia and is often managed surgically. Indications for parathyroidectomy in primary hyperparathyroidism include presence of symptoms, age 50 years or younger, serum calcium level more than 1 mg per dL above the upper limit of normal, osteoporosis, creatinine clearance less than 60 mL per minute per 1.73 m2, nephrolithiasis, nephrocalcinosis, and hypercalciuria. Secondary hyperparathyroidism is caused by alterations in calcium, phosphate, and vitamin D regulation that result in elevated parathyroid hormone levels. It most commonly occurs with chronic kidney disease and vitamin D deficiency, and less commonly with gastrointestinal conditions that impair calcium absorption. Secondary hyperparathyroidism can be managed with calcium and vitamin D replacement and reduction of high phosphate levels. There is limited evidence for the use of calcimimetics and vitamin D analogues for persistently elevated parathyroid hormone levels. Hypoparathyroidism, which is most commonly caused by iatrogenic surgical destruction of the parathyroid glands, is less common and results in hypocalcemia. Multiple endocrine neoplasia types 1 and 2A are rare familial syndromes that can result in primary hyperparathyroidism and warrant genetic testing of family members, whereas parathyroid cancer is a rare finding in patients with hyperparathyroidism.