Hypoparathyroidism
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For patient information click here Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Omar Elshafei, MD[2] Anmol Pitliya, M.B.B.S. M.D.[3] Synonyms and keywords: Hypoparathyroid, parathyroid hormone levels decreased, parathyroid related hypocalcemia, underactive parathyroid glands, PTH deficiency, chronic HypoPT
| Hypoparathyroidism | |
| ICD-10 | E20, E89.2, P71.4 |
|---|---|
| ICD-9 | 252.1 |
| DiseasesDB | 6490 |
| MeSH | D007011 |
Hypoparathyroidism is a rare endocrine disorder defined biochemically by hypocalcemia in the presence of a low or inappropriately normal serum parathyroid hormone (PTH) concentration. Loss of PTH action reduces distal tubular calcium reabsorption, reduces renal 1-alpha-hydroxylation of vitamin D and reduces bone remodeling, producing the characteristic combination of low serum calcium, high serum phosphate, relative hypercalciuria and a low bone turnover state. Approximately three quarters of cases follow anterior neck surgery, most often total thyroidectomy, and the remaining quarter arise from genetic, autoimmune, infiltrative, radiation-related or functional causes.
Clinical expression ranges from asymptomatic biochemical abnormality to paresthesia, muscle cramps, carpopedal spasm, tetany, seizures and laryngospasm. Chronic disease carries a substantial burden of long-term complications including nephrocalcinosis, nephrolithiasis, renal impairment, cataract, basal ganglia calcification, neuropsychiatric symptoms, infection and vascular calcification, together with impaired quality of life.
Diagnosis rests on paired measurement of albumin-adjusted or ionized serum calcium with intact PTH, after correction of hypomagnesemia. Postsurgical disease is regarded as permanent when it persists beyond twelve months, although late recovery remains possible. Early postoperative PTH measurement is the single most useful predictor of whether hypoparathyroidism will become chronic.
Conventional treatment consists of oral calcium salts and an active vitamin D analogue, which controls symptomatic hypocalcemia but does not restore normal mineral physiology and is associated with hypercalciuria, fluctuating calcium levels, high pill burden and renal complications. Hypoparathyroidism was for many years the only classic hormone deficiency state not managed by replacement of the missing hormone. That has changed: long-acting PTH replacement is now approved, and additional PTH receptor agonists and calcium-sensing receptor antagonists are in late-stage development. Recombinant human PTH(1-84) is no longer manufactured and is of historical interest only.
For most of the twentieth century, hypoparathyroidism was managed exclusively with calcium salts and vitamin D metabolites, making it the only classic endocrine deficiency for which hormone replacement was not the standard of care.[1]
The modern therapeutic era began with the REPLACE trial of recombinant human PTH(1-84), the first randomized phase 3 study of hormone replacement in this disease.[2] The first European Society of Endocrinology guideline followed in 2015 and was explicit that the evidence base was too thin to support recommendations based on strict evidence.[3]
Recombinant human PTH(1-84) was withdrawn from the United States market in 2019 because of a particulate contamination problem, and the manufacturer announced in October 2022 that global manufacturing would be discontinued at the end of 2024.[4]
The Second International Workshop published formal GRADE-based guidance in 2022, and palopegteriparatide, a prodrug of PTH(1-34) designed to provide continuous exposure over the dosing interval, was approved by the European Medicines Agency in November 2023 and by the United States Food and Drug Administration on 9 August 2024.[5][6] The European Society of Endocrinology guideline was revised in 2025 to reflect this changed landscape.[7]
Hypoparathyroidism may be classified by etiology, by duration and, in the postsurgical setting, by whether the diagnosis is biochemical or clinical.
| Axis | Category | Defining features |
|---|---|---|
| Etiology | Postsurgical | Follows anterior neck surgery. Accounts for approximately 75% of cases.[8] |
| Nonsurgical | Genetic, autoimmune, infiltrative, radiation-related or functional. Accounts for approximately 25% of cases.[8][9] | |
| Duration after surgery | Transient | Hypocalcemia and low PTH that resolve within the early postoperative period.[10] |
| Protracted | Continued requirement for treatment beyond the immediate postoperative period but before the twelve month threshold.[11] | |
| Permanent (chronic) | Persisting for more than 12 months after surgery. Late recovery may still occur beyond this point.[5][7] | |
| Postoperative biochemical versus clinical | Biochemical | Low PTH with hypocalcemia in the absence of symptoms.[12] |
| Clinical | Low PTH with hypocalcemia accompanied by symptoms of neuromuscular irritability.[12] | |
| Relative | Symptomatic patients with a marked postoperative fall in PTH despite calcium values that do not meet the hypocalcemia threshold.[12] |
Parathyroid hormone is the principal minute-to-minute regulator of extracellular calcium. It increases distal tubular calcium reabsorption, promotes renal phosphate excretion, stimulates renal 1-alpha-hydroxylase to generate 1,25-dihydroxyvitamin D and therefore indirectly increases intestinal calcium absorption, and drives bone remodeling by acting on the PTH1 receptor.[9]
In hypoparathyroidism, deficient PTH signaling produces a predictable set of derangements. Renal calcium reabsorption falls, so any given serum calcium concentration is accompanied by a disproportionately high filtered calcium load and hypercalciuria. Renal phosphate excretion falls, producing hyperphosphatemia and a raised calcium phosphate product that predisposes to ectopic calcification. Reduced 1-alpha-hydroxylation lowers 1,25-dihydroxyvitamin D and impairs intestinal calcium absorption, which is why native vitamin D alone is usually insufficient and an active analogue is required. Bone remodeling is suppressed, generating a low turnover skeleton with increased bone mineral density and abnormal microarchitecture rather than the osteopenia seen in most endocrine bone disease.[9][13]
Conventional therapy compounds several of these problems. Calcium and active vitamin D raise serum calcium by increasing intestinal absorption without restoring distal tubular reabsorption, so urinary calcium excretion rises further, which explains why nephrocalcinosis, nephrolithiasis and progressive renal impairment are the dominant long-term complications rather than incidental findings.[9][8]
In autosomal dominant hypocalcemia type 1, activating variants of the calcium-sensing receptor gene reset the extracellular calcium set point downward, so PTH secretion is suppressed at calcium concentrations that would normally stimulate it, and renal calcium excretion is inappropriately high for the level of calcemia. This is the mechanistic reason that conventional therapy worsens the renal phenotype in this subgroup.[14]
Surgical hypoparathyroidism results from devascularization, inadvertent removal or thermal injury of parathyroid tissue. Gland viability rather than gland count is the determinant of outcome, which is the rationale for intraoperative assessment of perfusion and for autotransplantation of glands judged to be ischemic.[9][10]
| Category | Specific causes |
|---|---|
| Postsurgical | Total thyroidectomy; parathyroidectomy for multiglandular disease; central neck dissection; radical neck surgery for head and neck malignancy; repeat neck exploration[9][10] |
| Autoimmune | Isolated autoimmune hypoparathyroidism; autoimmune polyendocrine syndrome type 1 (APECED) due to AIRE variants, typically with chronic mucocutaneous candidiasis and primary adrenal insufficiency[15][16] |
| Genetic, isolated | Activating variants of CASR (autosomal dominant hypocalcemia type 1); activating variants of GNA11 (autosomal dominant hypocalcemia type 2); GCM2 variants; PTH gene variants[16][14] |
| Genetic, syndromic | 22q11.2 deletion (DiGeorge syndrome) and other defects of thymic development; GATA3-related hypoparathyroidism, deafness and renal dysplasia; TBCE-related Sanjad-Sakati and Kenny-Caffey syndromes; mitochondrial disorders including Kearns-Sayre syndrome[16][17] |
| Infiltrative and destructive | Hemochromatosis and transfusional iron overload; Wilson disease with copper deposition; granulomatous infiltration; metastatic infiltration of the parathyroid glands; external beam radiation therapy to the neck[9][16] |
| Functional and reversible | Hypomagnesemia, which impairs both PTH secretion and PTH action; severe hypermagnesemia; suppression of the neonatal parathyroid axis by maternal hypercalcemia[16][8] |
The differential diagnosis of hypocalcemia is resolved chiefly by the intact PTH concentration measured on the same sample as the calcium, after correction of hypomagnesemia and after confirmation that the calcium is genuinely low rather than an artifact of hypoalbuminemia.[16]
| Condition | Serum calcium | Intact PTH | Serum phosphate | Distinguishing features |
|---|---|---|---|---|
| Hypoparathyroidism | Low | Low or inappropriately normal | High | History of neck surgery, syndromic features or positive family history; relative hypercalciuria for the level of calcemia[16][5] |
| Pseudohypoparathyroidism | Low | Elevated | High | PTH resistance rather than deficiency; brachydactyly, short stature, early-onset obesity, ectopic ossification, frequent TSH resistance; molecular confirmation required[18] |
| Vitamin D deficiency | Low | Elevated | Low or low normal | Low 25-hydroxyvitamin D, raised alkaline phosphatase, low urinary calcium; corrects with repletion[16] |
| Chronic kidney disease mineral and bone disorder | Low | Elevated | High | Reduced eGFR, raised FGF23, secondary hyperparathyroidism[16] |
| Hypomagnesemia | Low | Low or inappropriately normal | Variable | Mimics hypoparathyroidism exactly; PTH and calcium both normalize after magnesium repletion, so magnesium must be corrected before the diagnosis is made[16][8] |
| Hungry bone syndrome | Low | Normal or elevated | Low | Follows parathyroidectomy for severe primary hyperparathyroidism; accompanied by hypophosphatemia and hypomagnesemia; reported in 25 to 90% of patients with radiological hyperparathyroid bone disease versus 0 to 6% without skeletal involvement[19] |
| Autosomal dominant hypocalcemia type 1 | Low | Low or inappropriately normal | High | Activating CASR variant; hypercalciuria at diagnosis in 34% and marked worsening of hypercalciuria after conventional therapy is started[14] |
| Acute pancreatitis, massive transfusion, rhabdomyolysis | Low | Elevated | Variable | Acute precipitant identifiable; calcium sequestration or chelation rather than PTH failure[16] |
| Pseudohypocalcemia | Total low, ionized normal | Normal | Normal | Hypoalbuminemia; resolved by albumin adjustment or direct ionized calcium measurement[16] |
Prevalence and Incidence
Reported prevalence of chronic hypoparathyroidism ranges from 6.4 to 37 per 100,000 population, and incidence from 0.8 to 2.3 per 100,000 per year.[13]
In the Danish nationwide cohort, the prevalence of postsurgical hypoparathyroidism was 22 per 100,000 inhabitants, based on 688 validated cases.[20] The prevalence of nonsurgical hypoparathyroidism in the same registry was 2.3 per 100,000 inhabitants, based on 180 identified patients.[21]
A large United States claims analysis estimated 58,793 insured patients with chronic hypoparathyroidism, and found that 7.6% of relevant neck surgeries resulted in hypoparathyroidism, of which 75% were transient and 25% chronic.[22]
Age and Gender
In the Danish postsurgical cohort the average age at diagnosis was 49 years, with a range of 17 to 87 years, and 88% of patients were women, reflecting the female predominance of thyroid surgery.[20]
Mortality
Mortality was not increased in studies from Denmark or South Korea but was increased in studies from Scotland and Sweden.[13]
Risk factors for post-thyroidectomy hypoparathyroidism include bilateral thyroid operations, autoimmune thyroid disease, central neck dissection, substernal goiter, surgeon inexperience and malabsorptive conditions.[10]
In a five year retrospective series of 1749 patients undergoing primary total thyroidectomy for papillary thyroid carcinoma, transient hypoparathyroidism occurred in 458 patients (26.2%) and permanent hypoparathyroidism in 63 patients (3.6%). Female sex, age 55 years or older, unintentional parathyroid gland resection and autotransplantation of two or more parathyroid glands were independent risk factors for transient biochemical hypoparathyroidism. A postoperative day one reduction in PTH of more than 51.1% was an independent risk factor for relative hypoparathyroidism, with an odds ratio of 4.892 and a 95% confidence interval of 1.653 to 14.480.[12]
Risk factors for nonsurgical disease include a positive family history, syndromic features and presentation before the age of 40 years, all of which should prompt consideration of genetic testing.[5]
There is no role for population screening. Screening in hypoparathyroidism means early postoperative risk prediction after bilateral neck surgery, together with targeted genetic evaluation of patients with nonsurgical disease.
Measurement of serum PTH within 12 to 24 hours after total thyroidectomy is a strong recommendation supported by moderate quality evidence. A PTH value above 10 pg/mL (1.05 pmol/L) virtually excludes long-term hypoparathyroidism.[5] In the supporting diagnostic meta-analysis of 18 studies and 4325 patients, a PTH above 10 pg/mL at 12 to 24 hours gave a post-test probability of not developing chronic hypoparathyroidism of 100% irrespective of pretest probability, whereas values below 10 pg/mL were associated with post-test probabilities ranging from 3% to 64%, so these patients require careful monitoring rather than a presumptive diagnosis.[23]
The American Thyroid Association statement notes that a postoperative PTH below 15 pg/mL indicates increased risk for acute hypoparathyroidism and can be used to select patients for supplementation.[10]
In individuals with nonsurgical hypoparathyroidism, genetic testing may be helpful in the presence of a positive family history, in the presence of syndromic features, or in individuals younger than 40 years.[5]
Natural History
Postsurgical hypoparathyroidism most often resolves within weeks. When hypocalcemia and low PTH persist beyond 12 months the condition is regarded as permanent, although recovery of parathyroid function may still occur after that point.[7][5] Nonsurgical disease is generally lifelong, and the genetic forms may present at any age from the neonatal period to adulthood.[16]
Complications
A systematic review of 93 studies enrolling 18,973 patients identified nine complications and symptoms probably associated with chronic hypoparathyroidism, with the following median prevalences.[23]
| Complication | Median prevalence |
|---|---|
| Nephrocalcinosis or nephrolithiasis | 15% |
| Renal insufficiency | 12% |
| Cataract | 17% |
| Seizures | 11% |
| Cardiac arrhythmia | 7% |
| Ischemic heart disease | 7% |
| Depression | 9% |
| Infection | 11% |
| All-cause mortality | 6% |
Registry data support the renal and neurological burden. In the Danish postsurgical cohort, compared with matched controls, patients had an increased risk of renal complications with a hazard ratio of 3.67 and a 95% confidence interval of 2.41 to 5.59, and of hospitalization due to seizures with a hazard ratio of 3.82 and a 95% confidence interval of 2.15 to 6.79. There was no increased risk of cardiac arrhythmias, with a hazard ratio of 1.11 and a 95% confidence interval of 0.79 to 1.57, or of cardiovascular disease or death, with a hazard ratio of 0.89 and a 95% confidence interval of 0.73 to 1.09.[20]
The same cohort showed an increased risk of hospitalization due to infections, with a hazard ratio of 1.42 and a 95% confidence interval of 1.20 to 1.67, and of depression or bipolar affective disorder, with a hazard ratio of 1.99 and a 95% confidence interval of 1.14 to 3.46. The risk of fractures at the upper extremities was decreased, with a hazard ratio of 0.69 and a 95% confidence interval of 0.49 to 0.97, consistent with the low turnover skeletal phenotype.[24]
Nonsurgical disease carries a heavier complication burden. Compared with controls, patients had significantly increased risks of renal insufficiency (hazard ratio 6.01), cardiovascular disease (hazard ratio 1.91), neuropsychiatric complications (hazard ratio 2.45), infections (hazard ratio 1.94), seizures (hazard ratio 10.05), cataract (hazard ratio 4.21) and fractures at the upper extremities (hazard ratio 1.93), with a reduced risk of malignant disease (hazard ratio 0.44).[21]
Vascular calcification has been demonstrated directly. In a study of 50 patients with chronic postsurgical hypoparathyroidism and 50 matched controls assessed by coronary computed tomography angiography, coronary atherosclerotic plaques were present in 68% of patients compared with 42% of controls, severe coronary artery disease with a calcium score of 400 or above was present in 18% of patients versus 2% of controls, and hypoparathyroidism was associated with increased odds of coronary calcification with an odds ratio of 3.19 and a 95% confidence interval of 1.40 to 7.24, independent of renal function.[25]
Additional recognized complications include hypercalciuria, low bone turnover, cardiac and vascular calcification, basal ganglia calcification and difficulties in pregnancy, and the disorder imposes a substantial financial and health care resource burden.[13]
Diagnosis
History and Symptoms | Physical Examination | Laboratory Findings | Electrocardiogram | X Ray | CT | MRI | Echocardiography or Ultrasound | Other Imaging Findings | Other Diagnostic Studies
Diagnostic Approach
| Low albumin-adjusted or ionized serum calcium confirmed on repeat testing | |||||||||||||||||||||||||||
| Measure intact PTH, phosphate, magnesium, creatinine and 25-hydroxyvitamin D on the same sample | |||||||||||||||||||||||||||
| Correct hypomagnesemia and repeat testing before interpreting PTH | |||||||||||||||||||||||||||
| Postsurgical hypoparathyroidism PTH low or inappropriately normal Prior anterior neck surgery Permanent if persisting beyond 12 months | Nonsurgical hypoparathyroidism PTH low or inappropriately normal No neck surgery Consider genetic testing if family history, syndromic features or age under 40 years | Not hypoparathyroidism PTH elevated Vitamin D deficiency, CKD, pseudohypoparathyroidism, acute calcium sequestration | |||||||||||||||||||||||||
History and Symptoms
Symptoms reflect neuromuscular irritability and range from perioral and acral paresthesia, muscle cramps and carpopedal spasm to overt tetany, laryngospasm and seizures. Many patients also report fatigue, reduced physical stamina, difficulty concentrating, impaired memory and low mood, and these non-specific symptoms contribute substantially to reduced quality of life.[26][23] A history of anterior neck surgery, autoimmune disease, family history of hypocalcemia, recurrent candidiasis or developmental and cardiac anomalies should be sought specifically.[16]
Physical Examination
Latent tetany may be elicited as the Chvostek sign, which is neither sensitive nor specific and may be present in normocalcemic individuals, and as the Trousseau sign, which is generally regarded as the more informative of the two. Neither sign should be used alone to establish or exclude the diagnosis.[26] Chronic disease may be accompanied by cataract, dry skin, brittle nails and coarse hair.[26] Enamel opacities, enamel hypoplasia, hypodontia and eruption disturbances have been reported in nonsurgical hypoparathyroidism and pseudohypoparathyroidism, reflecting disease onset during tooth development.[27] Syndromic features such as brachydactyly, short stature, sensorineural deafness or the facial phenotype of 22q11.2 deletion should be documented.[16]
Laboratory Findings
The diagnosis is biochemical. Low albumin-adjusted or ionized calcium with a concurrent inappropriately low serum PTH concentration are the hallmarks of the disease, and attention to the pitfalls of both calcium and PTH assays is essential.[16]
The recommended initial panel comprises serum calcium (albumin-adjusted or ionized), magnesium, creatinine, phosphate and 25-hydroxyvitamin D, together with a 24 hour urine collection for creatinine and calcium.[28] The typical pattern is hypocalcemia, hyperphosphatemia, low or inappropriately normal intact PTH and low 1,25-dihydroxyvitamin D.[9]
Electrocardiogram
Hypocalcemia prolongs the QT interval on the electrocardiogram, and severe hypocalcemia may be associated with cardiac arrhythmia and, rarely, reversible cardiomyopathy.[26] Arrhythmia was one of the nine complications probably associated with chronic hypoparathyroidism, with a median reported prevalence of 7%.[23]
Imaging Findings
Renal ultrasound is performed at baseline to evaluate for nephrocalcinosis and nephrolithiasis.[28] Computed tomography of the head may demonstrate basal ganglia calcification, and magnetic resonance imaging may show corresponding signal abnormality.[13] Coronary computed tomography angiography demonstrates an increased burden of coronary, aortic valve and aortic calcification in chronic postsurgical disease.[25] Dual energy x-ray absorptiometry typically shows normal or increased bone mineral density reflecting low bone turnover rather than a protective skeletal state.[9]
Other Diagnostic Studies
Genetic testing is directed by phenotype in nonsurgical disease and should be considered with a positive family history, syndromic features, or presentation under 40 years of age.[5][16] Autoantibody testing and evaluation for associated endocrinopathies are appropriate when autoimmune polyendocrine syndrome type 1 is suspected.[15] Slit lamp examination is used to detect cataract, and audiometry and renal imaging are indicated when GATA3-related disease is suspected.[16]
Treatment
Medical Therapy | Surgery | Primary Prevention | Secondary Prevention | Cost-Effectiveness of Therapy | Future or Investigational Therapies
Postoperative Management Algorithm
| Total thyroidectomy or bilateral neck exploration | |||||||||||||||||||||||||||
| Measure serum PTH 12 to 24 hours after surgery | |||||||||||||||||||||||||||
| PTH above 10 pg/mL (1.05 pmol/L) Long-term hypoparathyroidism virtually excluded | PTH at or below 10 pg/mL (1.05 pmol/L) At risk: start oral calcium with or without an active vitamin D analogue and monitor serum calcium | ||||||||||||||||||||||||||
| Reassess at intervals with attempted tapering of therapy; monitor for rebound hypercalcemia | |||||||||||||||||||||||||||
| Recovery of parathyroid function: discontinue therapy and monitor Persistent hypocalcemia with low PTH beyond 12 months: permanent (chronic) hypoparathyroidism | |||||||||||||||||||||||||||
Initial Management
Severe or symptomatic hypocalcemia requires intravenous calcium gluconate with cardiac monitoring, followed by oral calcium and an active vitamin D analogue, and inpatient management may be necessary.[10] Coexisting hypomagnesemia must be corrected, because magnesium deficiency both impairs PTH secretion and blunts PTH action and will otherwise render calcium replacement ineffective.[8][19]
After thyroidectomy, effective management of mild to moderate potential or actual hypoparathyroidism can be achieved by administering empiric or prophylactic oral calcium and vitamin D, by selective oral calcium and vitamin D based on rapid postoperative PTH levels, or by using serial serum calcium levels as a guide. Monitoring for rebound hypercalcemia is necessary to avoid metabolic and renal complications.[10]
Medical Therapy
Treatment Escalation Algorithm
| Confirmed chronic hypoparathyroidism | |||||||||||||||||||||||||||
| Conventional therapy Oral calcium salt plus active vitamin D analogue Target albumin-adjusted calcium in the low normal range or just below normal, with normal phosphate and magnesium and controlled urinary calcium | |||||||||||||||||||||||||||
| Reassess symptoms, serum and urine biochemistry, and renal imaging | |||||||||||||||||||||||||||
| Targets met and patient well Continue conventional therapy with periodic monitoring | Conventional therapy unsatisfactory Unstable calcium, hypercalciuria, renal impairment, high pill burden or poor quality of life | ||||||||||||||||||||||||||
| Consider PTH replacement therapy with palopegteriparatide, with protocol-guided reduction of conventional therapy | |||||||||||||||||||||||||||
Conventional Therapy
Conventional therapy consists of 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 to normalize serum phosphorus, magnesium concentrations and urine calcium levels. Its limitations include wide fluctuations in serum calcium, high pill burden, poor quality of life and renal complications.[8] On the basis of a systematic review and meta-analysis, the panel made a graded recommendation suggesting conventional therapy as first line therapy rather than administration of PTH, a weak recommendation supported by low quality evidence.[8][5]
The choice of calcium salt is not trivial. In a randomized, double-blind, crossover trial of 24 adults with postsurgical chronic hypoparathyroidism, calcium citrate did not change the ion activity product of calcium oxalate compared with calcium carbonate, but was associated with a significant reduction in the oxalate to creatinine ratio, at -2.46 mmol/mol (SD 11.93) versus 7.42 mmol/mol (SD 17.63), p = 0.029, and with less constipation, p = 0.047. Serum calcium and phosphorus concentrations did not differ between the two preparations.[29]
PTH Replacement Therapy
PTH replacement therapy may improve the biochemical profile in those in whom conventional therapy proves unsatisfactory.[8] A meta-analysis of seven randomized trials enrolling 386 patients found that, compared with conventional therapy, PTH therapy probably achieves a small improvement in physical health-related quality of life, with a mean difference of 3.4 and a 95% confidence interval of 1.5 to 5.3 against a minimally important difference of 3.0 (moderate certainty), results in more patients reaching a 50% or greater reduction in the dose of active vitamin D and calcium, with a relative risk of 6.5 and a 95% confidence interval of 2.5 to 16.4 (high certainty), and may increase hypercalcemia, with a relative risk of 2.4 and a 95% confidence interval of 1.2 to 5.04 (low certainty).[30]
A meta-analysis of 25 prospective studies including 588 patients treated with PTH(1-34) or PTH(1-84) found a neutral effect on serum calcium with a reduction in serum phosphate of -0.21 mmol/L, 95% confidence interval -0.31 to -0.11 mmol/L, p < 0.001, and a reduction in urinary calcium excretion of -1.21 mmol per 24 hours, 95% confidence interval -2.03 to -0.41 mmol per 24 hours, p = 0.003.[1]
Recombinant human PTH(1-84) was the first hormone replacement studied in a phase 3 trial. In REPLACE, 134 patients were randomized to rhPTH(1-84) (n = 90) or placebo (n = 44); 48 patients (53%) in the rhPTH(1-84) group achieved the primary endpoint compared with one patient (2%) in the placebo group, a percentage difference of 51.1 with a 95% confidence interval of 39.9 to 62.3, p < 0.0001.[2] This molecule is of historical interest only, since global manufacturing was discontinued at the end of 2024 because of unresolved product-specific supply issues.[4][31]
Palopegteriparatide (developed as TransCon PTH) is a prodrug of PTH(1-34) administered once daily and designed to provide continuous exposure to released PTH across the 24 hour dosing period. It is approved for the treatment of hypoparathyroidism in adults and was not studied in adults with acute post-surgical hypoparathyroidism.[6] In the double-blind, placebo-controlled, 26 week phase 3 PaTHway trial, 84 participants were randomized 3:1. At week 26, 79% (48 of 61) of participants treated with palopegteriparatide versus 5% (1 of 21) with placebo met the composite primary efficacy endpoint, p < 0.0001, and 93% (57 of 61) achieved independence from conventional therapy. Mean 24 hour urine calcium was normalized.[32]
At week 52, 81% (63 of 78) met the multicomponent efficacy endpoint, 95% (74 of 78) achieved independence from conventional therapy, and none required active vitamin D. Mean 24 hour urine calcium excretion decreased from 376 (168) mg per day at baseline to 195 (114) mg per day at week 52, and mean bone mineral density Z-scores decreased toward age- and sex-matched norms.[33]
Renal function improved rather than deteriorated. Over 52 weeks, treatment resulted in a mean increase in estimated glomerular filtration rate of 9.3 (11.7) mL/min/1.73 m2 from baseline, p < 0.0001, with 43% of participants showing an increase of at least 10 mL/min/1.73 m2, and a mean increase of 11.5 (11.3) mL/min/1.73 m2 in those with baseline eGFR below 60 mL/min/1.73 m2.[34]
At week 104, 93% (76 of 82) of participants remained in the open-label extension; of those, 82% had albumin-adjusted serum calcium in the normal range of 8.3 to 10.6 mg/dL and 97% were independent from conventional therapy. The mean increase in eGFR from baseline was 9.0 (10.3) mL/min/1.73 m2, p < 0.0001, and 24 hour urine calcium was maintained below 250 mg per day at 158.8 (90.5) mg per 24 hours. No cases of treatment-related nephrolithiasis were reported.[35]
Procedural / Surgical Therapy
The most effective intervention is prevention at the time of the index operation. Medical and surgical strategies to minimize perioperative hypoparathyroidism include optimizing vitamin D levels, preserving parathyroid blood supply and autotransplanting ischemic parathyroid glands.[10] Attention to parathyroid gland viability and the use of intraoperative PTH monitoring during and after neck surgery are central to reducing the incidence of permanent disease.[9]
Standardized definitions and reporting of postoperative hypoparathyroidism have been agreed by the European Society of Endocrine Surgeons, the American Association of Endocrine Surgeons and the International Association of Endocrine Surgeons, and should be used when auditing surgical outcomes.[11]
Parathyroid allotransplantation has been investigated as a definitive therapy. The revised European guideline concluded that a substantial role for parathyroid allotransplantation in the treatment of chronic hypoparathyroidism cannot be recommended.[7]
Long-Term Management
For new patients, assessment usually includes a serum laboratory profile comprising calcium (either albumin-adjusted or ionized), magnesium, creatinine, phosphate and 25-hydroxyvitamin D, a 24 hour urine collection for creatinine and calcium, and a renal ultrasound to evaluate for the presence of nephrocalcinosis or nephrolithiasis. For follow-up patients, most clinicians perform blood and urine testing every six months or less frequently. Practice patterns for monitoring complications vary considerably.[28]
Minimizing complications requires careful evaluation and close monitoring of laboratory indices.[5] Surveillance should be directed at the complications with the highest documented burden: renal imaging and function, ophthalmological assessment for cataract, screening for depressive symptoms, and awareness of an increased burden of coronary and vascular calcification.[23][25] Cardiovascular risk stratification and preventive strategies deserve particular attention in chronic postsurgical disease.[25]
Special Populations
Pregnancy and Lactation
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.[8][36]
In the largest population-based analysis to date, comprising 204 pregnancies in mothers with chronic hypoparathyroidism and 9,096,584 pregnancies without, and after adjustment for age, insurance plan type, obesity, chronic hypertension, thyroid disease, pregestational diabetes mellitus and previous caesarean section, hypoparathyroidism was associated with an increased rate of preterm birth before 37 weeks at 19.1% versus 7.2% with an adjusted odds ratio of 2.49 and a 95% confidence interval of 1.74 to 3.54, blood transfusion at 4.9% versus 1.0% with an adjusted odds ratio of 4.07 and a 95% confidence interval of 2.15 to 7.73, and congenital anomalies in the neonate at 4.4% versus 0.4% with an adjusted odds ratio of 6.50 and a 95% confidence interval of 3.31 to 12.75. Rates of small-for-gestational-age neonates and intrauterine fetal death were comparable.[37]
Autosomal Dominant Hypocalcemia Type 1
This subgroup requires a distinct approach because conventional therapy aggravates the renal phenotype. Among 191 patients with clinical data, 27% lacked symptoms, 32% had mild or moderate symptoms and 41% had severe symptoms, with seizures the most frequent presenting feature in 39%. At diagnosis, hypocalcemia was present in 99%, hyperphosphatemia in 59%, low PTH in 57% and hypercalciuria in 34%. Among 57 patients on conventional therapy, 75% had at least one complication, and hypercalciuria was associated with nephrocalcinosis, nephrolithiasis, renal impairment or brain calcifications with an odds ratio of 9.3 and a 95% confidence interval of 2.4 to 37.2, p < 0.01. In 27 patients with urine calcium measured before and after starting conventional therapy, the incidence of hypercalciuria increased by 91%, p < 0.05.[14] Treatment should therefore aim only to relieve symptoms rather than to normalize serum calcium, and calcium-sensing receptor antagonists are under investigation for this indication.[14][31]
Children and Syndromic Disease
Patients with 22q11.2 deletion and other defects of thymic development require coordinated immunological as well as endocrine follow-up, including structured assessment of immune function and specific criteria before administration of live vaccines.[17]
Renal Impairment
Renal insufficiency is both a complication of the disease and a constraint on therapy, and monitoring of urinary calcium excretion and renal imaging is central to management in this group.[23][28]
Emerging and Investigational Therapies
Eneboparatide (AZP-3601) is an investigational PTH1 receptor agonist. In a phase 1 randomized, double-blind, placebo-controlled study of 104 healthy volunteers, single ascending doses produced a dose-dependent increase in serum calcium and decrease in serum phosphorus, urinary calcium excretion did not increase as a function of dose, and bone turnover markers did not change over the treatment period.[38] In the phase 3 CALYPSO trial, 31.1% of patients treated with eneboparatide met the composite primary endpoint of albumin-adjusted serum calcium within the normal range of 8.3 to 10.6 mg/dL together with independence from active vitamin D and oral calcium supplements at week 24, compared with 5.9% in the placebo arm, and urinary calcium excretion normalized in 56.6% of those with hypercalciuria at baseline.[39]
Encaleret is an orally administered calcium-sensing receptor antagonist that has shown efficacy and safety in autosomal dominant hypocalcemia type 1 and is in phase 3 development for that indication.[40][31]
An oral PTH1 receptor agonist is in phase 1 clinical trials and a weekly PTH molecule is being evaluated in phase 2 clinical trials.[31]
Case Studies
Related Chapters
References
- ↑ 1.0 1.1 Puliani G, Hasenmajer V, Simonelli I, Sada V, Pofi R, Minnetti M, Cozzolino A, Napoli N, Pasqualetti P, Gianfrilli D, Isidori AM (July 2022). "Safety and Efficacy of PTH 1-34 and 1-84 Therapy in Chronic Hypoparathyroidism: A Meta-Analysis of Prospective Trials". J Bone Miner Res. 37 (7): 1233–1250. doi:10.1002/jbmr.4566. PMID 35485213 Check
|pmid=value (help). - ↑ 2.0 2.1 Mannstadt M, Clarke BL, Vokes T, Brandi ML, Ranganath L, Fraser WD, Lakatos P, Bajnok L, Garceau R, Mosekilde L, Lagast H, Shoback D, Bilezikian JP (December 2013). "Efficacy and safety of recombinant human parathyroid hormone (1-84) in hypoparathyroidism (REPLACE): a double-blind, placebo-controlled, randomised, phase 3 study". Lancet Diabetes Endocrinol. 1 (4): 275–83. doi:10.1016/S2213-8587(13)70106-2. PMID 24622413.
- ↑ Bollerslev J, Rejnmark L, Marcocci C, Shoback DM, Sitges-Serra A, van Biesen W, Dekkers OM (August 2015). "European Society of Endocrinology Clinical Guideline: Treatment of chronic hypoparathyroidism in adults". Eur J Endocrinol. 173 (2): G1–20. doi:10.1530/EJE-15-0628. PMID 26160136.
- ↑ 4.0 4.1 "Takeda to Discontinue Manufacturing of NATPAR/NATPARA for Patients with Hypoparathyroidism at the End of 2024". Takeda Pharmaceutical Company. October 4, 2022. Retrieved August 27, 2026.
- ↑ 5.00 5.01 5.02 5.03 5.04 5.05 5.06 5.07 5.08 5.09 Khan AA, Bilezikian JP, Brandi ML, Clarke BL, Gittoes NJ, Pasieka JL, Rejnmark L, Shoback DM, Potts JT, Guyatt GH, Mannstadt M (December 2022). "Evaluation and Management of Hypoparathyroidism Summary Statement and Guidelines from the Second International Workshop". J Bone Miner Res. 37 (12): 2568–2585. doi:10.1002/jbmr.4691. PMID 36054621 Check
|pmid=value (help). - ↑ 6.0 6.1 "FDA approves new drug for hypoparathyroidism, a rare disorder". U.S. Food and Drug Administration. August 9, 2024. Retrieved August 27, 2026.
- ↑ 7.0 7.1 7.2 7.3 Bollerslev J, Buch O, Cardoso LM, Gittoes N, Houillier P, van Hulsteijn L, Makay O, Marcocci C, Pallais JC, Pilz S, Rejnmark L, Yavropoulou M, Dekkers OM (October 2025). "Revised European Society of Endocrinology Clinical Practice Guideline: Treatment of Chronic Hypoparathyroidism in Adults". Eur J Endocrinol. 193 (5): G49–G78. doi:10.1093/ejendo/lvaf222. PMID 41231236 Check
|pmid=value (help). - ↑ 8.00 8.01 8.02 8.03 8.04 8.05 8.06 8.07 8.08 8.09 Khan AA, Guyatt G, Ali DS, Bilezikian JP, Collins MT, Dandurand K, Mannstadt M, Murphy D, M'Hiri I, Rubin MR, Sanders R, Shrayyef M, Siggelkow H, Tabacco G, Tay YD, Van Uum S, Vokes T, Winer KK, Yao L, Rejnmark L (December 2022). "Management of Hypoparathyroidism". J Bone Miner Res. 37 (12): 2663–2677. doi:10.1002/jbmr.4716. PMID 36161671 Check
|pmid=value (help). - ↑ 9.00 9.01 9.02 9.03 9.04 9.05 9.06 9.07 9.08 9.09 Pasieka JL, Wentworth K, Yeo CT, Cremers S, Dempster D, Fukumoto S, Goswami R, Houillier P, Levine MA, Pasternak JD, Perrier ND, Sitges-Serra A, Shoback DM (December 2022). "Etiology and Pathophysiology of Hypoparathyroidism: A Narrative Review". J Bone Miner Res. 37 (12): 2586–2601. doi:10.1002/jbmr.4714. PMID 36153665 Check
|pmid=value (help). - ↑ 10.0 10.1 10.2 10.3 10.4 10.5 10.6 10.7 Orloff LA, Wiseman SM, Bernet VJ, Fahey TJ, Shaha AR, Shindo ML, Snyder SK, Stack BC, Sunwoo JB, Wang MB (July 2018). "American Thyroid Association Statement on Postoperative Hypoparathyroidism: Diagnosis, Prevention, and Management in Adults". Thyroid. 28 (7): 830–841. doi:10.1089/thy.2017.0309. PMID 29848235.
- ↑ 11.0 11.1 Barczyński M, Van Den Heede K, Lee JC, Lorenz K, Mihai R, Norlen O, Patel KN, Raffaelli M, Sippel RS, Wang TS, Solorzano CC (November 2025). "Standardizing the reporting of postoperative hypoparathyroidism following thyroidectomy: consensus statement from the European Society of Endocrine Surgeons, the American Association of Endocrine Surgeons, and the International Association of Endocrine Surgeons". Br J Surg. 112 (11). doi:10.1093/bjs/znaf247. PMID 41229353 Check
|pmid=value (help). - ↑ 12.0 12.1 12.2 12.3 Qiu Y, Xing Z, Fei Y, Qian Y, Luo Y, Su A (September 2021). "Role of the 2018 American Thyroid Association statement on postoperative hypoparathyroidism: a 5-year retrospective study". BMC Surg. 21 (1): 334. doi:10.1186/s12893-021-01333-w. PMID 34474672 Check
|pmid=value (help). - ↑ 13.0 13.1 13.2 13.3 13.4 Bjornsdottir S, Ing S, Mitchell DM, Sikjaer T, Underbjerg L, Hassan-Smith Z, Sfeir J, Gittoes NJ, Clarke BL (December 2022). "Epidemiology and Financial Burden of Adult Chronic Hypoparathyroidism". J Bone Miner Res. 37 (12): 2602–2614. doi:10.1002/jbmr.4675. PMID 36054571 Check
|pmid=value (help). - ↑ 14.0 14.1 14.2 14.3 14.4 Roszko KL, Stapleton Smith LM, Sridhar AV, Roberts MS, Hartley IR, Gafni RI, Collins MT, Fox JC, Nemeth EF (October 2022). "Autosomal Dominant Hypocalcemia Type 1: A Systematic Review". J Bone Miner Res. 37 (10): 1926–1935. doi:10.1002/jbmr.4659. PMID 35879818 Check
|pmid=value (help). - ↑ 15.0 15.1 Husebye ES, Anderson MS, Kämpe O (March 2018). "Autoimmune Polyendocrine Syndromes". N Engl J Med. 378 (12): 1132–1141. doi:10.1056/NEJMra1713301. PMID 29562162.
- ↑ 16.00 16.01 16.02 16.03 16.04 16.05 16.06 16.07 16.08 16.09 16.10 16.11 16.12 16.13 16.14 16.15 16.16 16.17 Mannstadt M, Cianferotti L, Gafni RI, Giusti F, Kemp EH, Koch CA, Roszko KL, Yao L, Guyatt GH, Thakker RV, Xia W, Brandi ML (December 2022). "Hypoparathyroidism: Genetics and Diagnosis". J Bone Miner Res. 37 (12): 2615–2629. doi:10.1002/jbmr.4667. PMID 36375809 Check
|pmid=value (help). - ↑ 17.0 17.1 Mustillo PJ, Sullivan KE, Chinn IK, Notarangelo LD, Haddad E, Davies EG, de la Morena MT, Hartog N, Yu JE, Hernandez-Trujillo VP, Ip W, Franco J, Gambineri E, Hickey SE, Varga E, Markert ML (February 2023). "Clinical Practice Guidelines for the Immunological Management of Chromosome 22q11.2 Deletion Syndrome and Other Defects in Thymic Development". J Clin Immunol. 43 (2): 247–270. doi:10.1007/s10875-022-01418-y. PMID 36648576 Check
|pmid=value (help). - ↑ Mantovani G, Bastepe M, Monk D, de Sanctis L, Thiele S, Ahmed SF, Bufo R, Choplin T, De Filippo G, Devernois G, Eggermann T, Elli FM, Perez de Nanclares G, Linglart A (2020). "Recommendations for Diagnosis and Treatment of Pseudohypoparathyroidism and Related Disorders: An Updated Practical Tool for Physicians and Patients". Horm Res Paediatr. 93 (3): 182–196. doi:10.1159/000508985. PMID 32756064 Check
|pmid=value (help). - ↑ 19.0 19.1 Witteveen JE, van Thiel S, Romijn JA, Hamdy NA (March 2013). "Hungry bone syndrome: still a challenge in the post-operative management of primary hyperparathyroidism: a systematic review of the literature". Eur J Endocrinol. 168 (3): R45–53. doi:10.1530/EJE-12-0528. PMID 23152439.
- ↑ 20.0 20.1 20.2 Underbjerg L, Sikjaer T, Mosekilde L, Rejnmark L (November 2013). "Cardiovascular and renal complications to postsurgical hypoparathyroidism: a Danish nationwide controlled historic follow-up study". J Bone Miner Res. 28 (11): 2277–85. doi:10.1002/jbmr.1979. PMID 23661265.
- ↑ 21.0 21.1 Underbjerg L, Sikjaer T, Mosekilde L, Rejnmark L (September 2015). "The Epidemiology of Nonsurgical Hypoparathyroidism in Denmark: A Nationwide Case Finding Study". J Bone Miner Res. 30 (9): 1738–44. doi:10.1002/jbmr.2501. PMID 25753591.
- ↑ Powers J, Joy K, Ruscio A, Lagast H (December 2013). "Prevalence and incidence of hypoparathyroidism in the United States using a large claims database". J Bone Miner Res. 28 (12): 2570–6. doi:10.1002/jbmr.2004. PMID 23737456.
- ↑ 23.0 23.1 23.2 23.3 23.4 23.5 Yao L, Hui X, Li M, Li J, Ahmed MM, Lin C, Kandi M, Sreekanta A, Makhdami N, Tamilselvan D, Ali DS, Dandurand K, Yang K, Bilezikian JP, Brandi ML, Clarke BL, Mannstadt M, Rejnmark L, Khan AA, Guyatt G (December 2022). "Complications, Symptoms, Presurgical Predictors in Patients With Chronic Hypoparathyroidism: A Systematic Review". J Bone Miner Res. 37 (12): 2642–2653. doi:10.1002/jbmr.4673. PMID 36375810 Check
|pmid=value (help). - ↑ Underbjerg L, Sikjaer T, Mosekilde L, Rejnmark L (November 2014). "Postsurgical hypoparathyroidism--risk of fractures, psychiatric diseases, cancer, cataract, and infections". J Bone Miner Res. 29 (11): 2504–10. doi:10.1002/jbmr.2273. PMID 24806578.
- ↑ 25.0 25.1 25.2 25.3 Thornhøj S, Underbjerg L, Madsen LR, Wither S, Böttcher M, Rejnmark L (2026). "Increased Prevalence of Coronary Artery Calcification in Patients with Post-Surgical Hypoparathyroidism". J Bone Miner Res. doi:10.1093/jbmr/zjag102. PMID 42335032 Check
|pmid=value (help). - ↑ 26.0 26.1 26.2 26.3 Cetani F, Bertoldo F, Bononi M, Tarallo M, Camozzi V, Cipriani C, Palermo A, Pasquali D, Zavatta G (2025). "Unveiling the complexities of hypoparathyroidism: a comprehensive review of clinical manifestations, diagnosis, and novel therapies". J Endocrinol Invest. 49 (4): 725–746. doi:10.1007/s40618-025-02760-9. PMID 41335198 Check
|pmid=value (help). - ↑ Hejlesen J, Underbjerg L, Gjørup H, Bloch-Zupan A, Sikjaer T, Rejnmark L, Haubek D (2018). "Dental Findings in Patients With Non-surgical Hypoparathyroidism and Pseudohypoparathyroidism: A Systematic Review". Front Physiol. 9: 701. doi:10.3389/fphys.2018.00701. PMID 29971010.
- ↑ 28.0 28.1 28.2 28.3 Van Uum S, Shrayyef M, M'Hiri I, Dandurand K, Ali DS, Bilezikian JP, Collins MT, Mannstadt M, Rubin MR, Siggelkow H, Tabacco G, Tay YD, Vokes T, Winer KK, Yao L, Guyatt G, Rejnmark L, Khan AA (December 2022). "Initial Assessment and Monitoring of Patients with Chronic Hypoparathyroidism: A Systematic Current Practice Survey". J Bone Miner Res. 37 (12): 2630–2641. doi:10.1002/jbmr.4698. PMID 36066096 Check
|pmid=value (help). - ↑ Naciu AM, Tabacco G, Bilezikian JP, Santonati A, Bosco D, Incognito GG, Gaspa G, Manfrini S, Falchetti A, Trimboli P, Mazziotti G, Napoli N, Sanson G, Cesareo R, Vescini F, Palermo A (July 2022). "Calcium Citrate Versus Calcium Carbonate in the Management of Chronic Hypoparathyroidism: A Randomized, Double-Blind, Crossover Clinical Trial". J Bone Miner Res. 37 (7): 1251–1259. doi:10.1002/jbmr.4564. PMID 35466449 Check
|pmid=value (help). - ↑ Yao L, Li J, Li M, Lin C, Hui X, Tamilselvan D, Kandi M, Sreekanta A, Makhdami N, Ali DS, Dandurand K, Yang K, Bilezikian JP, Brandi ML, Clarke BL, Mannstadt M, Rejnmark L, Khan AA, Guyatt G (December 2022). "Parathyroid Hormone Therapy for Managing Chronic Hypoparathyroidism: A Systematic Review and Meta-Analysis". J Bone Miner Res. 37 (12): 2654–2662. doi:10.1002/jbmr.4676. PMID 36385517 Check
|pmid=value (help). - ↑ 31.0 31.1 31.2 31.3 Khan S, Khan AA (November 2025). "Chronic Hypoparathyroidism-Current and Emerging Therapies". Endocr Pract. 31 (11): 1478–1487. doi:10.1016/j.eprac.2025.07.011. PMID 40680836 Check
|pmid=value (help). - ↑ Khan AA, Rubin MR, Schwarz P, Vokes T, Shoback DM, Gagnon C, Palermo A, Marcocci C, Clarke BL, Abbott LG, Hofbauer LC, Kohlmeier L, Rejnmark L (January 2023). "Efficacy and Safety of Parathyroid Hormone Replacement With TransCon PTH in Hypoparathyroidism: 26-Week Results From the Phase 3 PaTHway Trial". J Bone Miner Res. 38 (1): 14–25. doi:10.1002/jbmr.4726. PMID 36271471 Check
|pmid=value (help). - ↑ Clarke BL, Khan AA, Rubin MR, Schwarz P, Vokes T, Shoback DM, Gagnon C, Palermo A, Abbott LG, Hofbauer LC, Kohlmeier L, Cetani F, Rejnmark L (March 2025). "Efficacy and Safety of TransCon PTH in Adults With Hypoparathyroidism: 52-Week Results From the Phase 3 PaTHway Trial". J Clin Endocrinol Metab. 110 (4): 951–960. doi:10.1210/clinem/dgae693. PMID 39376010 Check
|pmid=value (help). - ↑ Rejnmark L, Gosmanova EO, Khan AA, Makita N, Imanishi Y, Takeuchi Y, Sprague S, Shoback DM, Kohlmeier L, Rubin MR, Palermo A, Schwarz P, Gagnon C, Tsourdi E, Shu AD (June 2024). "Palopegteriparatide Treatment Improves Renal Function in Adults with Chronic Hypoparathyroidism: 1-Year Results from the Phase 3 PaTHway Trial". Adv Ther. 41 (6): 2500–2518. doi:10.1007/s12325-024-02843-8. PMID 38691316 Check
|pmid=value (help). - ↑ Rejnmark L, Gosmanova EO, Khan AA, Sprague S, Shoback DM, Kohlmeier L, Rubin MR, Palermo A, Schwarz P, Gagnon C, Tsourdi E, Takeuchi Y, Makita N, Imanishi Y, Gittoes N, Díez JJ, Prot-Bertoye C, Shu AD (2026). "Sustained Improvement in Renal Function with Palopegteriparatide in Adults with Chronic Hypoparathyroidism: 2-Year Results from the Phase 3 PaTHway Trial". J Bone Miner Res. doi:10.1093/jbmr/zjag085. PMID 42166177 Check
|pmid=value (help). - ↑ Cardoso LM, Rolighed L, Amrein K, Pilz S, Underbjerg L, Pretorius M, Cetani F, Zahn A, Almquist M, Makay O, Marcocci C, Rejnmark L, Siggelkow H, Tsourdi E, Kamenický P, Bollerslev J (November 2025). "Advances in the clinical management of parathyroid disorders: report from the 2024 workshop by the ESE educational program on parathyroid disorders". Eur J Endocrinol. 193 (6): R65–R88. doi:10.1093/ejendo/lvaf204. PMID 41032657 Check
|pmid=value (help). - ↑ Hochberg A, Pare A, Badeghiesh AM, Baghlaf HA, Dahan MH (December 2023). "Pregnancy, delivery and neonatal outcomes among women with hypoparathyroidism-A population-based study". Clin Endocrinol (Oxf). 99 (6): 525–532. doi:10.1111/cen.14969. PMID 37694589 Check
|pmid=value (help). - ↑ Ovize M, Allas S, Culler MD, Milano S, Ouldrouis T, Sumeray M, van de Wetering de Rooij J, Mannstadt M (June 2025). "Phase 1 clinical trial of eneboparatide, a novel PTH receptor 1 agonist". Endocr Connect. 14 (6). doi:10.1530/EC-24-0464. PMID 40423237 Check
|pmid=value (help). - ↑ "Eneboparatide normalised serum calcium and achieved independence from active vitamin D and oral calcium supplements in 31.1% of adults with hypoparathyroidism at week 24 in CALYPSO Phase III trial". AstraZeneca. May 12, 2026. Retrieved August 27, 2026.
- ↑ Gafni RI, Hartley IR, Roszko KL, Nemeth EF, Pozo KA, Lombardi E, Sridhar AV, Roberts MS, Fox JC, Collins MT (September 2023). "Efficacy and Safety of Encaleret in Autosomal Dominant Hypocalcemia Type 1". N Engl J Med. 389 (13): 1245–1247. doi:10.1056/NEJMc2302708. PMID 37754292 Check
|pmid=value (help).