ﺑﺎﺯﮔﺸﺖ ﺑﻪ ﺻﻔﺤﻪ ﻗﺒﻠﯽ
خرید پکیج
تعداد آیتم قابل مشاهده باقیمانده : 3 مورد
نسخه الکترونیک
medimedia.ir

Hypoparathyroidism

Hypoparathyroidism
Literature review current through: Jan 2024.
This topic last updated: Aug 24, 2023.

INTRODUCTION — Parathyroid hormone (PTH) is one of the major hormones (along with vitamin D) that regulates serum calcium via direct effects on bone and kidney and indirect effects on the gastrointestinal tract. Hypoparathyroidism occurs when there is destruction of the parathyroid glands (autoimmune, surgical), abnormal parathyroid gland development, altered regulation of PTH production, or impaired PTH action (table 1). When PTH secretion is insufficient, hypocalcemia develops. Hypocalcemia due to hypoparathyroidism may be associated with a spectrum of clinical manifestations, ranging from few, if any, symptoms if the hypocalcemia is mild, to life-threatening seizures, refractory heart failure, or laryngospasm if it is severe. In addition to severity of hypocalcemia, the rate of development and chronicity determine the clinical manifestations.

The clinical features, diagnosis, and management of hypoparathyroidism will be reviewed here. The etiology, clinical manifestations, diagnostic approach to, and treatment of hypocalcemia in general are reviewed separately.

(See "Etiology of hypocalcemia in adults".)

(See "Etiology of hypocalcemia in infants and children".)

(See "Neonatal hypocalcemia".)

(See "DiGeorge (22q11.2 deletion) syndrome: Clinical features and diagnosis".)

(See "Clinical manifestations of hypocalcemia".)

(See "Diagnostic approach to hypocalcemia".)

(See "Treatment of hypocalcemia".)

ETIOLOGY — Acquired hypoparathyroidism is most often the result of postsurgical or autoimmune damage to the parathyroid glands (table 1) [1]. In adults, the most common cause is surgical. In a retrospective analysis of adults evaluated in a metabolic bone unit of an endocrinology service in Brazil, over 80 percent of cases of acquired hypoparathyroidism were postsurgical, whereas less than 20 percent were autoimmune [2].

Postsurgical – Postsurgical hypoparathyroidism can occur after thyroid, parathyroid, or radical neck surgery for head and neck cancer, and it may be transient, with recovery in days, weeks, or months; permanent; or even intermittent. In observational studies, transient hypoparathyroidism occurred in up to 20 percent of patients after surgery for thyroid cancer, and permanent hypoparathyroidism occurred in 0.8 to 3.0 percent of patients after total thyroidectomy [3,4]. Permanent hypoparathyroidism occurs particularly when the goiter is very large and anatomic landmarks are displaced and obscured during surgery. Transient hypoparathyroidism may be due to manipulation of the blood supply to or removal of one or more parathyroid glands during surgery, whereas intermittent hypoparathyroidism is due to decreased parathyroid reserve (parathyroid insufficiency). (See "Differentiated thyroid cancer: Surgical treatment", section on 'Hypoparathyroidism' and "Surgical management of hyperthyroidism", section on 'Hypocalcemia' and 'Postsurgical parathyroid insufficiency' below.)

Autoimmune – Immune-mediated destruction of the parathyroid glands typically results in permanent hypoparathyroidism. Permanent hypoparathyroidism is part of the autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy syndrome, also known as polyglandular autoimmune syndrome type 1 (PAS 1). It is a result of mutations in the autoimmune regulator (AIRE) gene. Hypoparathyroidism typically appears during childhood or adolescence. (See "Etiology of hypocalcemia in infants and children", section on 'Autoimmune mechanisms'.)

Activating antibodies to the calcium-sensing receptor (CaSR) have been reported in patients with isolated acquired hypoparathyroidism and in patients with hypoparathyroidism associated with polyglandular autoimmune syndrome. These antibodies decrease parathyroid hormone (PTH) secretion but do not appear to be destructive. Hypoparathyroidism resulting from activating antibodies to the CaSR may remit spontaneously. (See "Disorders of the calcium-sensing receptor: Familial hypocalciuric hypercalcemia and autosomal dominant hypocalcemia", section on 'Hypoparathyroidism'.)

Genetic disorders – Genetic defects may be identified in infants and children due to defects associated with abnormal parathyroid development, including isolated hypoparathyroidism, hypoparathyroidism with congenital multisystem abnormalities, hypoparathyroidism with congenital metabolic abnormalities, and parathyroid resistance syndromes (table 2). These disorders are reviewed separately. (See "Etiology of hypocalcemia in infants and children", section on 'Genetic mechanisms' and "DiGeorge (22q11.2 deletion) syndrome: Clinical features and diagnosis".)

Other – Other rare causes of hypoparathyroidism due to parathyroid gland destruction include radiation therapy and storage or infiltrative diseases of the parathyroid glands (hemochromatosis, Wilson disease, granulomas, or metastatic cancer) (table 1). (See "Etiology of hypocalcemia in adults", section on 'Hypocalcemia with low PTH (hypoparathyroidism)'.)

CLINICAL FEATURES — Hypoparathyroidism may be associated with a spectrum of clinical manifestations, ranging from few, if any, symptoms when hypocalcemia is mild, to life-threatening seizures, refractory heart failure, or laryngospasm if it is severe. In addition to severity, the rate of development of hypocalcemia and chronicity determine the clinical manifestations (table 3).

Acute manifestations — The manifestations of acute hypoparathyroidism (eg, postsurgical hypoparathyroidism) are due to acute hypocalcemia. The hallmark of acute hypocalcemia is tetany, which is a disorder characterized by neuromuscular irritability. The symptoms of tetany may be mild (perioral numbness, paresthesias of the hands and feet, muscle cramps) or severe (carpopedal spasm, laryngospasm, and focal or generalized seizures, which must be distinguished from the generalized tonic muscle contractions that occur in severe tetany) [1]. The classic physical findings in patients with neuromuscular irritability due to latent tetany are Trousseau's and Chvostek's signs. (See "Clinical manifestations of hypocalcemia", section on 'Acute manifestations'.)

Other patients have less specific symptoms, such as fatigue, hyperirritability, anxiety, and depression, and some patients, even with severe hypocalcemia, have no neuromuscular symptoms. Cardiac findings may include a prolonged QT interval, hypotension, heart failure, and arrhythmia. (See "Clinical manifestations of hypocalcemia", section on 'Cardiovascular'.)

Chronic manifestations — Although the signs and symptoms of acute hypocalcemia are similar regardless of the etiology, there are several features that are unique to chronic hypoparathyroidism. These include the presence of basal ganglia calcifications, cataracts, dental abnormalities, and ectodermal manifestations. Some patients also report poor quality of life [5].

Ocular disease — Chronic hypocalcemia, particularly when due to hypoparathyroidism, may cause cataracts, and treatment of hypocalcemia arrests their progression [5-8]. Keratoconjunctivitis has also been described [9].

Skeletal manifestations — While patients with several hypocalcemic disorders have skeletal abnormalities, such findings do not appear to be direct consequences of hypocalcemia but rather are related to the underlying disease. Patients with hypoparathyroidism have variable skeletal abnormalities.

As a result of reduced bone turnover, patients with idiopathic or postsurgical hypoparathyroidism may have increased bone mineral density (BMD) as compared with healthy individuals [10,11].

Patients with congenital hypoparathyroid syndromes may have osteosclerosis, cortical thickening, and craniofacial abnormalities. (See "Etiology of hypocalcemia in infants and children", section on 'Genetic mechanisms'.)

Extrapyramidal disorders — Basal ganglia calcifications are a manifestation of longstanding hypoparathyroidism [12,13]. They can be detected by computed tomography (CT) when routine skull radiographs are normal [14]. Some patients with basal ganglia calcifications develop parkinsonism, other movement disorders (dystonia, hemiballismus, choreoathetosis, and oculogyric crises), or dementia, while others remain asymptomatic [13,15]. In some cases, extrapyramidal symptoms improve after treatment with vitamin D and calcium [12,16].

Dental abnormalities — Dental abnormalities occur when hypocalcemia is present during early development. They include dental hypoplasia, failure of tooth eruption, defective enamel and root formation, and abraded carious teeth [8,17]. Early treatment of hypocalcemia can reverse these changes.

Ectodermal manifestations — In patients with chronic hypocalcemia, the skin is dry, puffy, and coarse. Other dermatologic manifestations include coarse, brittle, and sparse hair with patchy alopecia, and brittle nails with characteristic transverse grooves [8]. These abnormalities correlate with the severity and chronicity of hypocalcemia, are not specific to hypoparathyroidism, and are reversible with restoration of normocalcemia.

Moniliasis occurs only in patients with idiopathic hypoparathyroidism, usually as a component of polyglandular autoimmune syndrome type 1 (PAS 1), which is characterized by mutations in the autoimmune regulator (AIRE) gene and may be sporadic or inherited as an autosomal recessive disorder. Moniliasis precedes the other immune disorders and first appears during childhood or adolescence. This disorder is associated with defective cellular immunity that persists despite correction of hypocalcemia. The nails, skin, and gastrointestinal tract are typically involved. The moniliasis is often refractory to antifungal therapy. Other associated clinical manifestations of PAS 1 include those of adrenal insufficiency and, less frequently, those of other autoimmune disorders. (See "Causes of primary adrenal insufficiency (Addison disease)", section on 'Type 1 (monogenic)'.)

Quality of life — Some adult patients report a general perception of poor health with reduced vitality and limitations due to poor physical health [18-21]. In a study of 19 hypoparathyroid patients, 13 had an impairment in cognition scores, particularly processing scores, which correlated with lower serum calcium and higher serum phosphate levels [18].

Laboratory findings — The main biochemical findings in patients with hypoparathyroidism are:

Hypocalcemia with a low or inappropriately normal (for the degree of hypocalcemia) serum intact parathyroid hormone (PTH) level

Most patients with hypoparathyroidism also have the following findings:

Elevated serum phosphorus level

Normal or low serum 25-hydroxyvitamin D (25[OH]D)

Normal or low 1,25-dihydroxyvitamin D (1,25D; because of the reduced capacity of PTH to stimulate renal production of 1,25D)

Normal magnesium

Normal creatinine

Elevated fractional urinary excretion of calcium

Although hypocalciuria is a feature of all hypocalcemic states due to a decreased filtered load, urinary calcium excretion is relatively high in patients with hypoparathyroidism because of loss of the stimulatory effect of PTH on renal tubular calcium reabsorption. Therefore, frank hypercalciuria can occur as the serum calcium concentration is raised toward normal, and concern about hypercalciuria and possible nephrolithiasis may prevent full correction of hypocalcemia. (See 'Managing hypercalciuria' below.)

In contrast to relatively high urinary calcium excretion noted in patients with hypoparathyroidism, loss of the inhibitory effect of PTH on renal tubular phosphorus reabsorption can result in reduced renal phosphorus excretion.

DIAGNOSIS AND EVALUATION — Persistent hypocalcemia with a low or inappropriately normal parathyroid hormone (PTH) level and hyperphosphatemia, in the absence of hypomagnesemia, is diagnostic of hypoparathyroidism (PTH deficiency) (algorithm 1) [22]. Hypomagnesemia can lead to functional hypoparathyroidism and must be excluded. (See 'Differential diagnosis' below and "Hypomagnesemia: Clinical manifestations of magnesium depletion", section on 'Calcium metabolism'.)

In patients with hypoalbuminemia or hyperalbuminemia, measurement of serum ionized calcium is preferable. If a laboratory known to measure ionized calcium reliably is not available, the measured serum calcium concentration should be corrected for the abnormality in albumin [(calculator 1) for conventional units, (calculator 2) for the international system of units].

When to suspect hypoparathyroidism – The diagnosis of postsurgical hypoparathyroidism is usually obvious in a patient who has acute onset of symptoms of hypocalcemia (eg, neuromuscular irritability) immediately following neck surgery. Hypoparathyroidism should also be suspected in any patient with mild (perioral numbness, paresthesias of the hands and feet, muscle cramps) or severe (carpopedal spasm, laryngospasm, focal or generalized seizures) symptoms of neuromuscular irritability (algorithm 1).

In addition, hypoparathyroidism should be suspected in patients who are incidentally noted to have a low serum total calcium or low ionized calcium, particularly when there is a personal or family history of autoimmune diseases, past history of head and neck surgery, or the presence of a neck scar. Such patients may have mild symptoms of hypocalcemia (eg, muscle cramps) or no symptoms.

Initial biochemical testing

Severe symptoms of hypocalcemia or symptoms occurring in the postoperative setting – In patients with severe symptoms of hypocalcemia or symptoms occurring in the postoperative setting, the diagnosis of hypoparathyroidism is confirmed by simultaneously measuring calcium (ionized or total calcium corrected for albumin), magnesium, phosphorus, creatinine, and intact PTH levels (algorithm 1).

Asymptomatic hypocalcemia – In patients with incidentally noted hypocalcemia, the presence of hypocalcemia should be confirmed by repeat sampling and corrected for albumin, if needed. For patients with persistent hypocalcemia, serum intact PTH, creatinine, phosphorus, and magnesium should be measured to determine the cause of the hypocalcemia. Serum PTH can be interpreted correctly only when serum calcium is measured simultaneously. For patients with newly diagnosed nonsurgical hypoparathyroidism, calcium and PTH are often repeated two weeks after initial testing to confirm the diagnosis [22].

Additional evaluation – Once hypoparathyroidism is diagnosed, we measure 24-hour urine calcium and creatinine to establish a baseline urine calcium excretion prior to initiating therapy. In addition, we typically measure serum 25-hydroxyvitamin D (25[OH]D) to identify and correct underlying vitamin D deficiency, which is prevalent in the population. (See "Vitamin D deficiency in adults: Definition, clinical manifestations, and treatment".)

Testing to determine the etiology – Additional evaluation to determine the etiology of hypoparathyroidism is warranted in patients who have nonsurgical hypoparathyroidism (algorithm 1). (See 'Etiology' above.)

Suspected autoimmune etiology – For patients with suspected autoimmune hypoparathyroidism (a personal or family history of autoimmune diseases, no history of head and neck surgery), some experts measure autoantibodies against the parathyroid glands [23]. Although polyglandular autoimmune syndrome type 1 (PAS 1) usually presents in childhood, components of the syndrome, including hypoparathyroidism, may occur in early adult life [24]. Consequently, on the rare occasion that an adult presents with hypoparathyroidism and a history of one component of PAS 1 such as candidiasis, it is important to assess adrenal function to exclude adrenal insufficiency and to consider assessment for an autoimmune regulator (AIRE) gene mutation. (See "Determining the etiology of adrenal insufficiency in adults" and "Causes of primary adrenal insufficiency (Addison disease)", section on 'Type 1 (monogenic)'.)

Suspected autosomal dominant hypocalcemia – For patients with suspected autosomal dominant hypocalcemia (asymptomatic hypocalcemia in a child or young adult; family history of hypocalcemia; ectopic calcifications affecting the kidneys, especially during treatment with calcium and vitamin D supplementation), genetic testing for activating mutations in the calcium-sensing receptor (CaSR) gene or its downstream pathway can confirm the diagnosis. Most individuals are diagnosed with a hypocalcemia-related disorder when <18 years of age (median 4 years of age, range 0 to 66 years) [25]. (See "Disorders of the calcium-sensing receptor: Familial hypocalciuric hypercalcemia and autosomal dominant hypocalcemia", section on 'Autosomal dominant hypocalcemia'.)

Uncertain etiology – In patients with nonsurgical hypoparathyroidism of uncertain etiology, genetic testing may identify other genetic forms of hypoparathyroidism (table 2) [22]. (See "Etiology of hypocalcemia in infants and children", section on 'Genetic mechanisms' and "DiGeorge (22q11.2 deletion) syndrome: Clinical features and diagnosis".)

DIFFERENTIAL DIAGNOSIS — The combination of low or inappropriately normal intact parathyroid hormone (PTH) with a low corrected serum calcium may also occur in patients with hypomagnesemia or due to assay interference (eg, high doses of biotin). Although kidney disease, vitamin D deficiency (as diagnosed by low 25-hydroxyvitamin D [25(OH)D]), and pancreatitis may all cause hypocalcemia, PTH levels are generally increased rather than decreased in association with the low serum calcium in these other clinical conditions. (See "Etiology of hypocalcemia in adults".)

Hypomagnesemia – Hypomagnesemia (serum magnesium concentration below 0.8 mEq/L [1 mg/dL or 0.4 mmol/L]) causes hypocalcemia by inducing PTH resistance or deficiency. It is therefore a reversible cause of hypocalcemia associated with low or inappropriately normal PTH. Hypoparathyroidism should resolve within minutes or hours after restoration of normal serum magnesium concentrations if hypomagnesemia was the cause. (See "Hypomagnesemia: Clinical manifestations of magnesium depletion", section on 'Hypoparathyroidism and parathyroid hormone resistance' and "Hypomagnesemia: Evaluation and treatment" and "Treatment of hypocalcemia", section on 'Concurrent hypomagnesemia'.)

Assay interference – In some assays, PTH may be falsely low in patients taking large amounts (eg, 5 to 10 mg daily) of biotin [26-28]. Discontinue biotin and repeat the serum PTH after at least three days, and longer (eg, after one week) if they are taking >10 mg daily [29].

MANAGEMENT — The management of hypoparathyroidism depends upon whether the presentation is severe and acute (with potential life-threatening manifestations such as seizures, refractory heart failure, laryngospasm) or mild and chronic. (See 'Acute hypoparathyroidism: Postsurgical' below and 'Chronic hypoparathyroidism' below.)

The treatment approach outlined below assumes normal magnesium levels. To effectively treat hypocalcemia in patients with magnesium deficiency, hypomagnesemia should be corrected first. (See "Hypomagnesemia: Evaluation and treatment" and "Treatment of hypocalcemia", section on 'Concurrent hypomagnesemia'.)

Goals of therapy — The goals of therapy for all patients with hypoparathyroidism are to [30]:

Relieve symptoms.

Raise and maintain the serum calcium concentration in the low-normal range, eg, 8.0 to 8.5 mg/dL (2.0 to 2.1 mmol/L). Attainment of higher serum calcium values is not necessary and is usually limited by the development of hypercalciuria due to the loss of renal calcium-retaining effects of parathyroid hormone (PTH).

Avoid hypercalciuria and iatrogenic development of nephrocalcinosis and kidney stones. (See 'Monitoring' below and 'Managing hypercalciuria' below.)

Avoid hyperphosphatemia.

Acute hypoparathyroidism: Postsurgical — In adults, acute hypoparathyroidism may occur after thyroid, parathyroid, or radical neck surgery for head and neck cancer. (See "Differentiated thyroid cancer: Surgical treatment", section on 'Hypoparathyroidism' and "Surgical management of hyperthyroidism", section on 'Hypocalcemia' and "Parathyroid exploration for primary hyperparathyroidism", section on 'Postoperative hypocalcemia'.)

Preoperative assessment and treatment of vitamin D deficiency — Prior to thyroid, parathyroid, or radical neck surgery, assessment of serum calcium and 25-hydroxyvitamin D (25[OH]D) is warranted. Prior to parathyroid surgery, laboratory evaluation also includes serum PTH and 24-hour urinary calcium. Vitamin D deficiency should be treated prior to surgery since vitamin D deficiency increases the risk of postsurgical hypocalcemia. Vitamin D dosing in patients with primary hyperparathyroidism requires special consideration since worsening hypercalcemia and hypercalciuria have been reported in this setting. Vitamin D replacement is reviewed in detail separately. (See "Vitamin D deficiency in adults: Definition, clinical manifestations, and treatment", section on 'Dosing' and "Vitamin D deficiency in adults: Definition, clinical manifestations, and treatment", section on 'Coexisting primary hyperparathyroidism' and "Primary hyperparathyroidism: Management", section on 'Concomitant vitamin D deficiency'.)

Monitoring for and prevention of postsurgical hypocalcemia

Thyroid surgery – For patients undergoing near-total or total thyroidectomy, serum calcium and albumin should be measured in the evening of the day of surgery and the morning after the day of surgery. Oral and/or intravenous (IV) calcium and oral calcitriol supplementation should be administered based upon the results of the serum calcium corrected for albumin (table 4). Supplementation protocols are often hospital-specific; there are few data evaluating outcomes [31]. (See 'Management of acute hypocalcemia' below.)

In patients whose risk of postoperative hypocalcemia is high due to the surgical procedure or vitamin D deficiency, some centers routinely administer calcium and calcitriol in the immediate postoperative period (regardless of serum calcium levels) to decrease the development of hypocalcemia symptoms and allow for an earlier discharge. Assessment of postoperative serum PTH level 12 to 24 hours after surgery is used in some centers to predict risk of hypocalcemia. The prevention of post-thyroidectomy hypocalcemia is reviewed in more detail elsewhere. (See "Differentiated thyroid cancer: Surgical treatment", section on 'Hypoparathyroidism' and "Surgical management of hyperthyroidism", section on 'Hypocalcemia'.)

Parathyroid surgery – After parathyroid exploration for hyperparathyroidism, parathyroid hormone and calcium are typically measured on the first postoperative day or before discharge. Transient postoperative hypocalcemia is more common in patients with severe preoperative hypercalcemia and in those with chronic vitamin D deficiency (<15 ng/mL) [32]. (See "Parathyroid exploration for primary hyperparathyroidism", section on 'Postoperative hypocalcemia'.)

Hungry bone syndrome may occur in hyperparathyroid patients who developed bone disease and high bone turnover preoperatively due to a chronic increase in bone resorption induced by high levels of PTH (osteitis fibrosa). In these patients, calcium is avidly taken up by the demineralized bone after surgery, and calcium supplementation is required to maintain a normal serum calcium concentration. Vitamin D-deficient post-parathyroidectomy patients may require prolonged, massive calcium and vitamin D therapy due to hungry bone syndrome. The prevention and treatment are reviewed in detail separately. (See "Hungry bone syndrome following parathyroidectomy in patients with end-stage kidney disease", section on 'Hypocalcemia' and "Primary hyperparathyroidism: Clinical manifestations", section on 'Skeletal'.)

Management of acute hypocalcemia

Severe symptoms or rapid decrease in calcium to ≤7.5 mg/dL – Patients who develop severely symptomatic acute hypocalcemia (eg, laryngospasm, carpopedal spasm, seizures, or markedly prolonged QT intervals on electrocardiogram) are initially treated with IV calcium plus oral calcitriol supplementation. We also suggest IV calcium in asymptomatic or mildly symptomatic patients who have a rapid decline in serum corrected calcium to ≤7.5 mg/dL (1.9 mmol/L) (algorithm 2). These patients may develop severe symptoms if hypocalcemia is not treated quickly.

Adults – Treatment in adults is initiated with the IV administration of one or two 10 mL ampules of 10 percent calcium gluconate (90 mg of elemental calcium per 10 mL vial) in 50 mL of 5 percent dextrose infused over 10 to 20 minutes, followed by an IV infusion of calcium gluconate. (See "Treatment of hypocalcemia", section on 'Intravenous calcium dosing'.)

Oral calcitriol (0.5 mcg two times daily) and calcium (1 to 4 g of elemental calcium carbonate daily in divided doses) should be initiated as soon as the patient is able to take oral supplements, to facilitate weaning of IV calcium. When the serum calcium is in a safe range (>7.5 mg/dL [1.9 mmol/L]) and the patient is asymptomatic, IV calcium is gradually weaned (table 4).

Children – Acute management in children is with IV administration of calcium gluconate (90 mg elemental calcium per 10 mL vial) at a slow rate (not greater than 2 mL [1.86 mg of elemental calcium]/kg over 10 minutes) while closely monitoring pulse rate and the QT interval.

Asymptomatic or mild to moderate symptoms and calcium >7.5 mg/dL – For asymptomatic adults or those with milder symptoms (eg, paresthesias) and hypocalcemia (corrected serum calcium >7.5 mg/dL [1.9 mmol/L]), initial treatment with oral calcium and active vitamin D (eg, calcitriol) is sufficient (algorithm 2 and table 4).

Adults – The initial dose in adults is 1 to 4 g of elemental calcium carbonate in divided doses along with calcitriol 0.5 mcg twice daily. If symptoms do not improve with oral calcium, IV calcium infusion is required.

Children – For children with milder symptoms of hypocalcemia in the postoperative period, oral calcium citrate, calcium carbonate, or calcium glubionate (30 to 75 mg/kg elemental calcium daily in four divided doses) and calcitriol 0.02 to 0.06 mcg/kg per day in two equally divided doses (usual dose 1 mcg per day, maximum reported dose 2 mcg per day) are initiated [33].

Follow-up care — Postsurgical hypoparathyroidism may be transient, resolving within three to six weeks but occasionally only after a year [34]. Because it may be transient, calcium and vitamin D supplements should be tapered slowly three to six weeks after surgery.

We typically see patients approximately one week postoperatively for assessment of serum calcium, albumin, magnesium, PTH, and 25(OH)D (if previously low).

If the PTH and/or calcium are low-normal or frankly low, we do not begin a taper. We adjust the doses of calcium and calcitriol if needed and repeat testing in one to two weeks.

If results are normal, we begin to taper the calcium and calcitriol, reducing the dose of each by 25 percent each week. We repeat calcium and PTH testing once weekly or sooner if symptoms return or are persistent.

Most patients are able to discontinue supplements entirely. Patients with a recurrence of hypocalcemia during the taper are more likely to have permanent hypoparathyroidism and should continue oral supplementation. (See 'Chronic hypoparathyroidism' below.)

Postsurgical parathyroid insufficiency — Parathyroid insufficiency is a term used to describe decreased parathyroid reserve. It is described most often in patients undergoing routine postoperative monitoring of serum calcium and PTH after thyroid or other neck surgery and is believed to be due to intraoperative injury to the parathyroid glands or their vascular supply [35]. Patients with parathyroid insufficiency have intermittent mild hypocalcemia (7.0 to 8 mg/dL [1.75 to 2.0 mmol/L]) with inappropriately low-normal serum PTH levels (11.6 to 24.5 pg/mL [normal range 6 to 40 pg/mL]). They are typically asymptomatic and are able to maintain stable serum calcium concentrations without calcium and vitamin D supplements.

However, patients with parathyroid insufficiency are at risk for developing more severe hypocalcemia with the initiation of certain medications (eg, bisphosphonates, denosumab) or in the setting of severe vitamin D deficiency. Hypocalcemia is more likely to occur when high doses of especially potent bisphosphonates, such as zoledronic acid, are used [36] or when denosumab is used, particularly in the setting of impaired kidney function [37]. Patients should be alerted to this risk and should receive adequate calcium and vitamin D supplementation during bisphosphonate or denosumab therapy. (See "Denosumab for osteoporosis", section on 'Hypocalcemia' and "Risks of bisphosphonate therapy in patients with osteoporosis", section on 'Hypocalcemia'.)

Chronic hypoparathyroidism

Initial treatment — For the initial management of patients with chronic hypoparathyroidism, we suggest oral calcium and active vitamin D (table 5), rather than PTH. Patients with chronic hypoparathyroidism require lifelong treatment.

Chronic hypoparathyroidism due to autoimmune parathyroid gland destruction, irradiation, or infiltrative diseases is more insidious in onset, and these patients typically do not require IV calcium supplementation. However, IV calcium is indicated to prevent or treat acute hypocalcemia in patients with chronic hypoparathyroidism who become unable to take or absorb oral supplements, as may occur after complex surgical procedures requiring prolonged recuperation. IV calcium also may be indicated in patients with chronic hypoparathyroidism who develop severely symptomatic hypocalcemia due to nonadherence with calcium and active vitamin D therapy. (See "Treatment of hypocalcemia", section on 'Intravenous calcium dosing' and 'Management of acute hypocalcemia' above.)

Active vitamin D preparations — Calcitriol is the most active vitamin D metabolite and the treatment of choice for hypocalcemia due to hypoparathyroidism because it has a rapid onset of action (hours) and a shorter half-life. Other acceptable vitamin D analogs include alfacalcidol or dihydrotachysterol (table 5).

The various active vitamin D preparations differ in onset of action, duration of action, and cost. Because PTH is required for the renal conversion of calcidiol (25[OH]D) to the active metabolite calcitriol (1,25-dihydroxyvitamin D [1,25D]), calcitriol is preferable [8,38]. Other advantages of calcitriol include rapid onset of action (hours) and a biologic half-life of approximately four to six hours. While hypercalcemia is more common during treatment with calcitriol than with vitamin D, cessation of treatment is followed by resolution of hypercalcemia in a few days rather than a few weeks [39,40].

Alfacalcidol (1-alpha-hydroxyvitamin D3) is a synthetic analog of vitamin D that is converted in the liver to the active metabolite 1,25D. Similar to calcitriol, it has a rapid onset of action and relatively short half-life. Although it is not available in the United States, it is used in other countries for the treatment of hypocalcemia associated with hypoparathyroidism (table 5) [41] and as a treatment adjunct in chronic kidney disease.

Dihydrotachysterol is the functional equivalent of 1-alpha-hydroxyvitamin D, in that only 25-hydroxylation in the liver is required to form the active drug. As a result, dihydrotachysterol is effective in patients in whom renal 1-hydroxylation is impaired, such as those with chronic kidney disease. It has a rapid onset of action and a relatively short duration of action, so that toxicity resolves in a few days.

Calcium and active vitamin D dosing

Adults – For adults with stable chronic hypoparathyroidism, the dose of oral calcium is typically 1 to 2 g of elemental calcium daily, in divided doses (table 5) [38]. Although calcium carbonate is often used (it is the least expensive), it may be less well absorbed in older patients and those who have achlorhydria. These patients might be treated with another preparation, such as calcium citrate. (See "Treatment of hypocalcemia", section on 'Mildly symptomatic or chronic hypocalcemia'.)

A typical starting dose of calcitriol is 0.25 mcg twice daily, with weekly dose increments of 0.25 mcg/day to achieve a low-normal serum calcium. Many adults require up to 2 mcg daily. Vitamin D requirements vary considerably from patient to patient, and the correct dose in any given patient is primarily determined by trial and error.

Children – For children, oral calcium glubionate, calcium carbonate, or calcium citrate is administered (30 to 75 mg/kg elemental calcium daily) in four divided doses, along with calcitriol 0.02 to 0.06 mcg/kg/day in two equally divided doses (maximum reported dose 2 mcg per day). The dose of calcitriol may be adjusted at two- to four-week intervals aiming to maintain the serum calcium concentrations within the low-normal range and to avoid hypercalciuria (>4 mg/kg/24 hours) (table 5).

Monitoring — Monitoring is important to confirm adequacy of treatment and to identify any adverse effects of treatment.

Laboratory tests – We measure urinary and serum calcium and serum phosphate weekly initially, until a stable serum calcium concentration (at the low end of the normal range) is reached (see 'Goals of therapy' above). Thereafter, monitoring urinary and serum calcium, and serum creatinine, phosphorus, and 25(OH)D at less frequent intervals (eg, every three months and then every 6 to 12 months) may be sufficient [42-44]. The dose of calcium and active vitamin D should be reduced if urinary calcium is elevated (≥300 mg [7.5 mmol] for men, ≥250 mg [6.25 mmol] for women in 24 hours). Hypercalciuria is the earliest sign of toxicity and can develop in the absence of hypercalcemia.

Imaging – For patients receiving long-term calcium and vitamin D treatment, we obtain kidney imaging (typically ultrasound) at least once during therapy to assess for renal calcification or stones. For patients with persistently elevated urinary calcium levels, we obtain kidney imaging within two years of diagnosis and treatment. If urinary calcium levels are generally within goal range, we obtain imaging three to five years after diagnosis and treatment.

The major side effects of calcium and active vitamin D therapy in patients with hypoparathyroidism are hypercalcemia and hypercalciuria, which, if chronic, can cause nephrolithiasis, nephrocalcinosis, and chronic kidney disease [5,45,46]. Nephrocalcinosis/nephrolithiasis and kidney impairment have been reported in 15 and 13 percent of patients, respectively. An increase in urinary calcium excretion is a predictable consequence of raising the serum calcium in patients with hypoparathyroidism [47]. These patients lack the normal stimulatory effect of PTH on renal tubular calcium reabsorption [48] and, therefore, excrete more calcium than normal subjects at the same serum calcium concentration.

Managing hypercalciuria — The initial treatment of hypercalciuria in patients with hypoparathyroidism is to reduce the dose of calcium and active vitamin D while maintaining the serum calcium in the target range. If hypercalciuria persists and the serum calcium is at the lower limit of the target range, the addition of thiazide diuretics (eg, hydrochlorothiazide, 12.5 to 50 mg daily or twice daily), with or without dietary sodium restriction, can decrease urinary calcium excretion [49,50]. A thiazide is typically added when the 24-hour urinary calcium approaches 250 mg (6.25 mmol) [38].

Thiazide diuretics are not recommended in congenital hypoparathyroidism due to PAS 1, or in patients who concurrently have Addison disease. In patients who develop thiazide-induced hypokalemia, potassium supplementation is necessary, or a potassium- and magnesium-sparing diuretic (eg, amiloride 2.5 to 5 mg once or twice a day) may be used with the thiazide to prevent hypokalemia and hypomagnesemia. The mechanism by which both PTH and thiazides enhance distal calcium reabsorption is reviewed elsewhere. (See "Diuretics and calcium balance".)

Managing nonadherence to therapy — Some patients find it difficult to adhere to large doses of calcium twice daily. Patients with chronic hypoparathyroidism who stop taking calcium and vitamin D may develop severe symptoms of hypocalcemia that warrant treatment with IV calcium. In patients with milder symptoms, resuming oral calcium and active vitamin D therapy may be sufficient.

Patient education is key to addressing nonadherence. For some patients, the addition of PTH may reduce the calcium and active vitamin D requirements. (See 'PTH-based therapies' below.)

Persistent hypocalcemia or hypercalciuria, or intolerance to conventional therapy

PTH-based therapies — PTH-based therapies are not considered initial therapy for hypoparathyroidism, because of high cost, the necessity for subcutaneous administration, and uncertainty about long-term safety of dosing for primary hypoparathyroidism (related to its skeletal effects, particularly in growing children who may be at greater risk of osteosarcoma).

PTH – For patients with chronic hypoparathyroidism who cannot maintain stable serum and urinary calcium levels with calcium and active vitamin D, the addition of PTH is an option [51]. Patients with malabsorption or intolerance to large doses of calcium and active vitamin D are also candidates for PTH. Although PTH preparations are available, there are no preparations with regulatory approval for the treatment of hypoparathyroidism alone.

In a meta-analysis of seven trials comparing recombinant human parathyroid hormone (rhPTH) (1-84) and synthetic PTH (1-34) with conventional therapy, more patients in the PTH group were able to maintain serum calcium levels while reducing the need for large doses of calcium and vitamin D [52]. Patients in the PTH group also had a small improvement in physical health-related quality of life (mean difference 3.4 points, 95% CI 1.5-5.3). Examples of trials in the meta-analysis include the following [53-63]:

In a double-blind, randomized trial of rhPTH (1-84) (initial dose 50 mcg daily, titrated up to 75 and then 100 mcg daily) or placebo in 134 hypoparathyroid patients, rhPTH (1-84) significantly reduced supplemental calcium and calcitriol requirements without altering serum and urinary calcium concentrations [60]. This product is no longer commercially available.

In two randomized trials from the same group, subcutaneous administration of synthetic PTH (1-34) controlled hypocalcemia with a lower risk of hypercalciuria when compared with calcitriol (all subjects received oral calcium supplementation) [53,54]. Twice-daily administration of PTH (1-34) provided better metabolic control and allowed a reduction in total daily PTH dose (46 versus 97 mcg daily) [55]. Similar findings were noted in a trial comparing once- versus twice-daily PTH (1-34) administration in 14 children with chronic hypoparathyroidism (total daily dose 25 versus 58 mcg) [56].

PTH may also improve abnormal skeletal properties (eg, reduced bone turnover) in hypoparathyroidism [64]. In a study of rhPTH (1-84) in 30 patients with hypoparathyroidism, bone mineral density (BMD) significantly increased in the lumbar spine (2.9 percent) and decreased in the distal one-third radius (2.4 percent) [57]. In a histomorphometric analysis of paired iliac crest biopsy samples from 30 patients with primary hypoparathyroidism, rhPTH (1-84) treatment was associated with an increase in the remodeling rate in both trabecular and cortical compartments with tunneling resorption in the trabecular compartments [58]. These findings suggest that PTH restores bone metabolism to levels more typical of euparathyroid individuals; however, the clinical significance of this finding is not yet clear.

Administration – Prior to administering PTH, serum 25(OH)D should be measured to identify and correct underlying vitamin D deficiency. Patients should be receiving adequate supplemental calcium and active vitamin D (eg, calcitriol), as evidenced by serum calcium concentrations >7.5 mg/dL (1.9 mmol/L) [65].

The goal is to find the lowest dose of PTH to maintain the serum calcium concentration in the lower half of the normal range, with the need for minimal active vitamin D (eg, calcitriol) and with calcium supplementation as close as possible to daily requirements. Once a maintenance dose is achieved, monitoring at three- to six-month intervals is likely sufficient. Monitoring of serum calcium should be performed more frequently in patients taking digoxin because hypercalcemia increases the risk of digoxin toxicity. (See "Cardiac arrhythmias due to digoxin toxicity", section on 'Plasma digoxin levels associated with toxicity'.)

Discontinuation instructions – For patients who need to discontinue PTH (eg, due to product unavailability or patient preference), increase the dose of calcium supplementation approximately 12 hours after the last dose of PTH to doses used before initiation of PTH and resume the pre-PTH dose of active vitamin D (eg, calcitriol). Because some patients transiently may require significantly higher doses of calcium/calcitriol therapy than before starting PTH, careful monitoring of serum calcium post-discontinuation is necessary. In a report of nine patients with hypoparathyroidism treated with PTH (1-34) and then transitioned back to calcium/calcitriol, two patients required higher pretreatment doses of calcium/calcitriol to maintain calcium levels, presumably secondary to sequestration of calcium in bone, as occurs in hungry bone syndrome [66]. Experts differ on the magnitude of the dosing change for calcium and calcitriol, but this should be guided by close follow-up (eg, approximately every three days) of serum calcium during the transition [67].

Adverse effects

-Short-term – The most commonly reported adverse events of PTH are tingling, prickling or burning of skin, hypocalcemia, hypercalcemia, headache, nausea, vomiting, arthralgia, and hypercalciuria.

PTH can cause hypercalcemia, particularly during initial therapy when the doses of supplemental calcium and vitamin D are being reduced. Hypercalcemia may be mitigated by careful patient monitoring, with titration of calcium, calcitriol, and PTH. Hypercalcemia may cause nausea, vomiting, constipation, low energy, or muscle weakness. If a dose of PTH is missed, hypocalcemia may develop. Symptoms of hypocalcemia include paresthesias, cramping of the hands and feet, or twitching of the facial muscles.

-Long-term – There are few data evaluating long-term safety in patients with hypoparathyroidism. In a report of 24 patients with hypoparathyroidism treated with rhPTH (1-84) for eight years, urinary calcium excretion was lower and estimated glomerular filtration rate (eGFR) unchanged compared with baseline values [68]. Hypercalcemia and hypocalcemia were uncommon. There was one episode of nephrolithiasis.

In a report of 31 patients treated with PTH (1-34) for up to five years, 16 patients developed new-onset or progressive nephrocalcinosis or nephrolithiasis, possibly due to hypocitraturia and an elevated urinary calcium to urinary citrate ratio [69]. In a separate case report, diffuse joint pain with bone scan evidence of intense bone uptake in the peripheral joints and in the axial skeleton developed after three years of PTH (1-34) (administered once or twice daily) [70]. Although symptoms resolved within 48 hours of discontinuing therapy, the patient developed transient hypocalcemia requiring high doses of IV calcium with alfacalcidol, presumably due to hungry bone syndrome.

In a rat model, PTH (1-84) caused an increase in the incidence of osteosarcoma [71]. The risk was dependent on dose and duration of treatment. However, extensive clinical experience in adults treated for osteoporosis with rhPTH (1-84) or PTH (1-34) has not shown an increased risk for the development of osteosarcoma. Nevertheless, PTH is contraindicated in patients who are at increased risk for developing osteosarcoma, such as patients with a prior history of external beam radiation therapy involving the skeleton, Paget disease of bone, unexplained elevations in alkaline phosphatase, or in children with open epiphyses. (See "Parathyroid hormone/parathyroid hormone-related protein analog therapy for osteoporosis", section on 'Adverse events'.)

Palopegteriparatide – Palopegteriparatide is an investigational long-acting prodrug of PTH (1-34) that shows promise. As an example, in double-blind randomized trials of palopegteriparatide, the addition of the prodrug reduced supplemental calcium and calcitriol requirements compared with placebo [72,73]. In addition, there was a decrease in 24-hour urinary calcium and an improvement in quality-of-life scores. This prodrug has not received regulatory approval, but it is available in some countries as part of a compassionate use program.

Pregnancy — Special care should be taken in the management of hypoparathyroidism during pregnancy and following delivery. Serum calcium concentrations should be measured frequently (eg, every three to four weeks) during pregnancy [30]. The doses of calcium and active vitamin D should be adjusted based on the albumin-adjusted or ionized calcium level. During late pregnancy and lactation, serum calcium should be measured even more frequently (eg, every one to two weeks) as there may be a rise in serum calcium requiring a decrease in calcitriol dose [74-78].

There are conflicting data as to whether calcitriol requirements fall [74-76] or do not fall [79-81] during pregnancy. On the other hand, there is uniform agreement that calcitriol requirements decrease during lactation [74-77,82,83]. Serum concentrations of 1,25D (calcitriol) double during a normal pregnancy. However, intact PTH concentrations remain low to normal, suggesting that PTH does not mediate the late partum rise in 1,25D production. The increase in serum 1,25D may be regulated by other pregnancy hormones, which are normal in hypoparathyroid women, such as PTH-related protein (PTHrP), prolactin, estrogen, and placental growth hormone [74,77,84]. If the calcitriol dose is not reduced, the combination of elevated serum 1,25D and PTHrP can cause increases in intestinal absorption and bone resorption and lead to hypercalcemia [82]. The requirement for calcitriol will return to antepartum levels with cessation of lactation.

Thiazide diuretics and PTH should not be used during pregnancy [30].

INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)

Basics topics (see "Patient education: Hypoparathyroidism (The Basics)")

SUMMARY AND RECOMMENDATIONS

Etiology – Hypoparathyroidism occurs when there is destruction of the parathyroid glands (surgical, autoimmune), abnormal parathyroid gland development, altered regulation of parathyroid hormone (PTH) production, or impaired PTH action (table 1). Acquired hypoparathyroidism is most often the result of postsurgical or autoimmune damage to the parathyroid glands. (See 'Etiology' above.)

Clinical features – The manifestations of acute hypoparathyroidism (eg, postsurgical hypoparathyroidism) are due to hypocalcemia and vary depending on the severity and the rate of development of hypocalcemia. Features that are unique to chronic hypoparathyroidism include the presence of basal ganglia calcifications, cataracts, dental abnormalities, and ectodermal manifestations (table 3). (See 'Clinical features' above.)

Diagnosis – Hypoparathyroidism should be suspected in patients with mild (perioral numbness, paresthesias of the hands and feet, muscle cramps) or severe (carpopedal spasm, laryngospasm, and focal or generalized seizures) symptoms of neuromuscular irritability or in asymptomatic patients who are incidentally noted to have a low serum total calcium, particularly when there is a personal or family history of autoimmune diseases, past history of head and neck surgery, or the presence of a neck scar (algorithm 1).

The diagnosis is confirmed by simultaneously measuring calcium, albumin, magnesium, phosphorus, creatinine and intact PTH levels. In patients with hypoalbuminemia or hyperalbuminemia, measurement of serum ionized calcium is preferable. If a laboratory known to measure ionized calcium reliably is not available, the measured serum calcium concentration should be corrected for the abnormality in albumin [(calculator 1) for conventional units, (calculator 2) for the international system of units]. Persistent hypocalcemia with a low or inappropriately normal PTH level and hyperphosphatemia, in the absence of hypomagnesemia, is diagnostic of hypoparathyroidism (PTH deficiency). (See 'Diagnosis and evaluation' above.)

Differential diagnosis – The combination of low or inappropriately normal intact PTH with a low corrected serum calcium may also be found in patients with hypomagnesemia or due to assay interference (eg, high doses of biotin). (See 'Differential diagnosis' above and "Hypomagnesemia: Clinical manifestations of magnesium depletion", section on 'Hypoparathyroidism and parathyroid hormone resistance' and "Hypomagnesemia: Evaluation and treatment".)

Goals of therapy – The goals of therapy in all patients with hypoparathyroidism are to relieve symptoms, to raise and maintain the serum calcium concentration in the low-normal range (eg, 8.0 to 8.5 mg/dL [2.0 to 2.1 mmol/L]), and to prevent iatrogenic development of kidney stones. Attainment of higher serum calcium values is not necessary and is usually limited by the development of hypercalciuria due to the loss of renal calcium-retaining effects of PTH. (See 'Goals of therapy' above.)

Management of acute hypoparathyroidism – Acute hypoparathyroidism may occur after thyroid, parathyroid, or radical neck surgery for head and neck cancer. Vitamin D deficiency should be identified and treated prior to surgery since vitamin D deficiency increases the risk of postsurgical hypocalcemia. Patients undergoing these surgeries should be monitored for postsurgical hypocalcemia (table 4). (See 'Acute hypoparathyroidism: Postsurgical' above.)

Severe symptoms or rapid decrease to ≤7.5 mg/dL – Patients who develop severely symptomatic acute hypocalcemia (eg, laryngospasm, carpopedal spasm, seizures, or markedly prolonged QT intervals on electrocardiogram) are initially treated with intravenous (IV) calcium (algorithm 2). For mildly symptomatic or asymptomatic patients with an acute decrease in serum corrected calcium to ≤7.5 mg/dL (1.9 mmol/L), we also administer IV calcium therapy. These patients may develop severe symptoms if hypocalcemia is not treated quickly. All patients should receive oral calcitriol when able to take oral medications. (See 'Management of acute hypocalcemia' above and "Treatment of hypocalcemia", section on 'Therapeutic approach'.)

Asymptomatic or mild to moderate symptoms and calcium >7.5 mg/dL – For asymptomatic adults or those with milder symptoms (eg, paresthesias) and hypocalcemia (corrected serum calcium >7.5 mg/dL [1.9 mmol/L]), initial treatment with oral calcium and active vitamin D is sufficient (table 4).

Postsurgical hypoparathyroidism may be transient; calcium and active vitamin D should be tapered slowly three to six weeks after surgery. Patients with a recurrence of hypocalcemia during the taper are more likely to have permanent hypoparathyroidism and should remain on oral supplementation. (See 'Follow-up care' above.)

Management of chronic hypoparathyroidism – For the initial management of patients with chronic hypoparathyroidism, we suggest calcium and active vitamin D rather than PTH (Grade 2C). Calcitriol is the vitamin D metabolite of choice, because it does not require renal activation, has a rapid onset of action (hours), and has a shorter half-life. Other acceptable vitamin D analogs include alfacalcidol or dihydrotachysterol (table 5). (See 'Initial treatment' above and 'Persistent hypocalcemia or hypercalciuria, or intolerance to conventional therapy' above.)

The addition of PTH is an option for patients with chronic hypoparathyroidism who cannot maintain stable serum and urinary calcium levels with calcium and vitamin D supplementation. Although PTH preparations are available, there are no preparations with regulatory approval for the treatment of hypoparathyroidism alone. (See 'PTH-based therapies' above.)

Monitoring chronic hypoparathyroidism – Monitoring of urinary and serum calcium and serum phosphate is required weekly initially, until a stable serum calcium concentration (at the low end of the normal range) is reached. Thereafter, monitoring urinary and serum calcium, and serum creatinine, phosphorus, and 25(OH)D at less frequent intervals (eg, every 3 months and then every 6 to 12 months) may be sufficient. For patients receiving long-term calcium and active vitamin D treatment, we obtain kidney imaging (typically ultrasound) after two to five years of therapy to assess for renal calcifications or stones. (See 'Monitoring' above.)

  1. Pasieka JL, Wentworth K, Yeo CT, et al. Etiology and Pathophysiology of Hypoparathyroidism: A Narrative Review. J Bone Miner Res 2022; 37:2586.
  2. Lopes MP, Kliemann BS, Bini IB, et al. Hypoparathyroidism and pseudohypoparathyroidism: etiology, laboratory features and complications. Arch Endocrinol Metab 2016; 60:532.
  3. Hundahl SA, Cady B, Cunningham MP, et al. Initial results from a prospective cohort study of 5583 cases of thyroid carcinoma treated in the united states during 1996. U.S. and German Thyroid Cancer Study Group. An American College of Surgeons Commission on Cancer Patient Care Evaluation study. Cancer 2000; 89:202.
  4. Rafferty MA, Goldstein DP, Rotstein L, et al. Completion thyroidectomy versus total thyroidectomy: is there a difference in complication rates? An analysis of 350 patients. J Am Coll Surg 2007; 205:602.
  5. Yao L, Hui X, Li M, et al. Complications, Symptoms, Presurgical Predictors in Patients With Chronic Hypoparathyroidism: A Systematic Review. J Bone Miner Res 2022; 37:2642.
  6. Rajendram R, Deane JA, Barnes M, et al. Rapid onset childhood cataracts leading to the diagnosis of autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy. Am J Ophthalmol 2003; 136:951.
  7. Stein R, Godel V. Hypocalcemic cataract. J Pediatr Ophthalmol Strabismus 1980; 17:159.
  8. Goltzman D, Cole DEC. Hypoparathyroidism. In: Primer on the metabolic bone diseases and disorders of mineral metabolism, 6th ed, Favus MJ (Ed), American Society of Bone and Mineral Research, Washington, DC 2006. p.216.
  9. Merenmies L, Tarkkanen A. Chronic bilateral keratitis in autoimmune polyendocrinopathy-candidiadis-ectodermal dystrophy (APECED). A long-term follow-up and visual prognosis. Acta Ophthalmol Scand 2000; 78:532.
  10. Laway BA, Goswami R, Singh N, et al. Pattern of bone mineral density in patients with sporadic idiopathic hypoparathyroidism. Clin Endocrinol (Oxf) 2006; 64:405.
  11. Chan FK, Tiu SC, Choi KL, et al. Increased bone mineral density in patients with chronic hypoparathyroidism. J Clin Endocrinol Metab 2003; 88:3155.
  12. Tambyah PA, Ong BK, Lee KO. Reversible parkinsonism and asymptomatic hypocalcemia with basal ganglia calcification from hypoparathyroidism 26 years after thyroid surgery. Am J Med 1993; 94:444.
  13. Rastogi R, Beauchamp NJ, Ladenson PW. Calcification of the basal ganglia in chronic hypoparathyroidism. J Clin Endocrinol Metab 2003; 88:1476.
  14. Illum F, Dupont E. Prevalences of CT-detected calcification in the basal ganglia in idiopathic hypoparathyroidism and pseudohypoparathyroidism. Neuroradiology 1985; 27:32.
  15. Preusser M, Kitzwoegerer M, Budka H, Brugger S. Bilateral striopallidodentate calcification (Fahr's syndrome) and multiple system atrophy in a patient with longstanding hypoparathyroidism. Neuropathology 2007; 27:453.
  16. Abe S, Tojo K, Ichida K, et al. A rare case of idiopathic hypoparathyroidism with varied neurological manifestations. Intern Med 1996; 35:129.
  17. Kinirons MJ, Glasgow JF. The chronology of dentinal defects related to medical findings in hypoparathyroidism. J Dent 1985; 13:346.
  18. Rubin MR, Tabacco G, Omeragic B, et al. A Pilot Study of Cognition Among Hypoparathyroid Adults. J Endocr Soc 2022; 6:bvac002.
  19. Sikjaer T, Moser E, Rolighed L, et al. Concurrent Hypoparathyroidism Is Associated With Impaired Physical Function and Quality of Life in Hypothyroidism. J Bone Miner Res 2016; 31:1440.
  20. Stamm B, Blaschke M, Wilken L, et al. The Influence of Conventional Treatment on Symptoms and Complaints in Patients With Chronic Postsurgical Hypoparathyroidism. JBMR Plus 2022; 6:e10586.
  21. Büttner M, Musholt TJ, Singer S. Quality of life in patients with hypoparathyroidism receiving standard treatment: a systematic review. Endocrine 2017; 58:14.
  22. Mannstadt M, Cianferotti L, Gafni RI, et al. Hypoparathyroidism: Genetics and Diagnosis. J Bone Miner Res 2022; 37:2615.
  23. Betterle C, Garelli S, Presotto F. Diagnosis and classification of autoimmune parathyroid disease. Autoimmun Rev 2014; 13:417.
  24. Wolff AS, Erichsen MM, Meager A, et al. Autoimmune polyendocrine syndrome type 1 in Norway: phenotypic variation, autoantibodies, and novel mutations in the autoimmune regulator gene. J Clin Endocrinol Metab 2007; 92:595.
  25. Roszko KL, Stapleton Smith LM, Sridhar AV, et al. Autosomal Dominant Hypocalcemia Type 1: A Systematic Review. J Bone Miner Res 2022; 37:1926.
  26. Samarasinghe S, Meah F, Singh V, et al. BIOTIN INTERFERENCE WITH ROUTINE CLINICAL IMMUNOASSAYS: UNDERSTAND THE CAUSES AND MITIGATE THE RISKS. Endocr Pract 2017; 23:989.
  27. Waghray A, Milas M, Nyalakonda K, Siperstein AE. Falsely low parathyroid hormone secondary to biotin interference: a case series. Endocr Pract 2013; 19:451.
  28. Li D, Radulescu A, Shrestha RT, et al. Association of Biotin Ingestion With Performance of Hormone and Nonhormone Assays in Healthy Adults. JAMA 2017; 318:1150.
  29. Holmes EW, Samarasinghe S, Emanuele MA, Meah F. Biotin Interference in Clinical Immunoassays: A Cause for Concern. Arch Pathol Lab Med 2017; 141:1459.
  30. Khan AA, Guyatt G, Ali DS, et al. Management of Hypoparathyroidism. J Bone Miner Res 2022; 37:2663.
  31. Edafe O, Mech CE, Balasubramanian SP. Calcium, vitamin D or recombinant parathyroid hormone for managing post-thyroidectomy hypoparathyroidism. Cochrane Database Syst Rev 2019; 5:CD012845.
  32. Silverberg SJ. Vitamin D deficiency and primary hyperparathyroidism. J Bone Miner Res 2007; 22 Suppl 2:V100.
  33. Root AW, Levine MA. Disorders of mineral metabolism II. Abnormalities of mineral homeostasis in the newborn, infant, child, and adolescent. In: Sperling Pediatric Endocrinology, 5th, Sperling MA, Majzoub JA, Menon RK, Stratakis CA (Eds), Elsevier, 2021. p.705.
  34. Sitges-Serra A, Ruiz S, Girvent M, et al. Outcome of protracted hypoparathyroidism after total thyroidectomy. Br J Surg 2010; 97:1687.
  35. Promberger R, Ott J, Kober F, et al. Normal parathyroid hormone levels do not exclude permanent hypoparathyroidism after thyroidectomy. Thyroid 2011; 21:145.
  36. Schussheim DH, Jacobs TP, Silverberg SJ. Hypocalcemia associated with alendronate. Ann Intern Med 1999; 130:329.
  37. Cowan A, Jeyakumar N, McArthur E, et al. Hypocalcemia Risk of Denosumab Across the Spectrum of Kidney Disease: A Population-Based Cohort Study. J Bone Miner Res 2023; 38:650.
  38. Shoback D. Clinical practice. Hypoparathyroidism. N Engl J Med 2008; 359:391.
  39. Kanis JA, Russell RG. Rate of reversal of hypercalcaemia and hypercalciuria induced by vitamin D and its 1alpha-hydroxylated derivatives. Br Med J 1977; 1:78.
  40. Bell NH, Stern PH. Hypercalcemia and increases in serum hormone value during prolonged administration of 1alpha,25-dihydroxyvitamin D. N Engl J Med 1978; 298:1241.
  41. Halabe A, Arie R, Mimran D, et al. Hypoparathyroidism--a long-term follow-up experience with 1 alpha-vitamin D3 therapy. Clin Endocrinol (Oxf) 1994; 40:303.
  42. Mortensen L, Hyldstrup L, Charles P. Effect of vitamin D treatment in hypoparathyroid patients: a study on calcium, phosphate and magnesium homeostasis. Eur J Endocrinol 1997; 136:52.
  43. Khan AA, Bilezikian JP, Brandi ML, et al. Evaluation and Management of Hypoparathyroidism Summary Statement and Guidelines from the Second International Workshop. J Bone Miner Res 2022; 37:2568.
  44. Van Uum S, Shrayyef M, M'Hiri I, et al. Initial Assessment and Monitoring of Patients with Chronic Hypoparathyroidism: A Systematic Current Practice Survey. J Bone Miner Res 2022; 37:2630.
  45. Saha S, Kandasamy D, Sharma R, et al. Nephrocalcinosis, Renal Dysfunction, and Calculi in Patients With Primary Hypoparathyroidism on Long-Term Conventional Therapy. J Clin Endocrinol Metab 2020; 105.
  46. Ketteler M, Chen K, Gosmanova EO, et al. Risk of Nephrolithiasis and Nephrocalcinosis in Patients with Chronic Hypoparathyroidism: A Retrospective Cohort Study. Adv Ther 2021; 38:1946.
  47. Kurokawa K. Calcium-regulating hormones and the kidney. Kidney Int 1987; 32:760.
  48. Gesek FA, Friedman PA. On the mechanism of parathyroid hormone stimulation of calcium uptake by mouse distal convoluted tubule cells. J Clin Invest 1992; 90:749.
  49. Porter RH, Cox BG, Heaney D, et al. Treatment of hypoparathyroid patients with chlorthalidone. N Engl J Med 1978; 298:577.
  50. Santos F, Smith MJ, Chan JC. Hypercalciuria associated with long-term administration of calcitriol (1,25-dihydroxyvitamin D3). Action of hydrochlorothiazide. Am J Dis Child 1986; 140:139.
  51. Tabacco G, Bilezikian JP. New Directions in Treatment of Hypoparathyroidism. Endocrinol Metab Clin North Am 2018; 47:901.
  52. Yao L, Li J, Li M, et al. Parathyroid Hormone Therapy for Managing Chronic Hypoparathyroidism: A Systematic Review and Meta-Analysis. J Bone Miner Res 2022; 37:2654.
  53. Winer KK, Yanovski JA, Cutler GB Jr. Synthetic human parathyroid hormone 1-34 vs calcitriol and calcium in the treatment of hypoparathyroidism. JAMA 1996; 276:631.
  54. Winer KK, Ko CW, Reynolds JC, et al. Long-term treatment of hypoparathyroidism: a randomized controlled study comparing parathyroid hormone-(1-34) versus calcitriol and calcium. J Clin Endocrinol Metab 2003; 88:4214.
  55. Winer KK, Yanovski JA, Sarani B, Cutler GB Jr. A randomized, cross-over trial of once-daily versus twice-daily parathyroid hormone 1-34 in treatment of hypoparathyroidism. J Clin Endocrinol Metab 1998; 83:3480.
  56. Winer KK, Sinaii N, Peterson D, et al. Effects of once versus twice-daily parathyroid hormone 1-34 therapy in children with hypoparathyroidism. J Clin Endocrinol Metab 2008; 93:3389.
  57. Rubin MR, Sliney J Jr, McMahon DJ, et al. Therapy of hypoparathyroidism with intact parathyroid hormone. Osteoporos Int 2010; 21:1927.
  58. Rubin MR, Dempster DW, Sliney J Jr, et al. PTH(1-84) administration reverses abnormal bone-remodeling dynamics and structure in hypoparathyroidism. J Bone Miner Res 2011; 26:2727.
  59. Sikjaer T, Rejnmark L, Rolighed L, et al. The effect of adding PTH(1-84) to conventional treatment of hypoparathyroidism: a randomized, placebo-controlled study. J Bone Miner Res 2011; 26:2358.
  60. Mannstadt M, Clarke BL, Vokes T, et al. 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 2013; 1:275.
  61. Ramakrishnan Y, Cocks HC. Impact of recombinant PTH on management of hypoparathyroidism: a systematic review. Eur Arch Otorhinolaryngol 2016; 273:827.
  62. Cusano NE, Rubin MR, McMahon DJ, et al. Therapy of hypoparathyroidism with PTH(1-84): a prospective four-year investigation of efficacy and safety. J Clin Endocrinol Metab 2013; 98:137.
  63. Winer KK. Advances in the treatment of hypoparathyroidism with PTH 1-34. Bone 2019; 120:535.
  64. Bilezikian JP, Khan A, Potts JT Jr, et al. Hypoparathyroidism in the adult: epidemiology, diagnosis, pathophysiology, target-organ involvement, treatment, and challenges for future research. J Bone Miner Res 2011; 26:2317.
  65. https://natpara.com/prescribing-information/PDF#page=1 (Accessed on March 18, 2015).
  66. Gafni RI, Guthrie LC, Kelly MH, et al. Transient Increased Calcium and Calcitriol Requirements After Discontinuation of Human Synthetic Parathyroid Hormone 1-34 (hPTH 1-34) Replacement Therapy in Hypoparathyroidism. J Bone Miner Res 2015; 30:2112.
  67. https://endocrinenews.endocrine.org/endocrine-society-asbmr-issue-joint-statement-on-natpara-recall/ (Accessed on June 17, 2020).
  68. Tay YD, Tabacco G, Cusano NE, et al. Therapy of Hypoparathyroidism With rhPTH(1-84): A Prospective, 8-Year Investigation of Efficacy and Safety. J Clin Endocrinol Metab 2019; 104:5601.
  69. Gafni RI, Langman CB, Guthrie LC, et al. Hypocitraturia Is an Untoward Side Effect of Synthetic Human Parathyroid Hormone (hPTH) 1-34 Therapy in Hypoparathyroidism That May Increase Renal Morbidity. J Bone Miner Res 2018; 33:1741.
  70. Goujard C, Salenave S, Briot K, et al. Treating hypoparathyroidism with recombinant human parathyroid hormone (1-34): long-term safety concerns. Lancet 2020; 395:1304.
  71. Jolette J, Wilker CE, Smith SY, et al. Defining a noncarcinogenic dose of recombinant human parathyroid hormone 1-84 in a 2-year study in Fischer 344 rats. Toxicol Pathol 2006; 34:929.
  72. Khan AA, Rejnmark L, Rubin M, et al. PaTH Forward: A Randomized, Double-Blind, Placebo-Controlled Phase 2 Trial of TransCon PTH in Adult Hypoparathyroidism. J Clin Endocrinol Metab 2022; 107:e372.
  73. Khan AA, Rubin MR, Schwarz P, et al. 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 2023; 38:14.
  74. Cundy T, Haining SA, Guilland-Cumming DF, et al. Remission of hypoparathyroidism during lactation: evidence for a physiological role for prolactin in the regulation of vitamin D metabolism. Clin Endocrinol (Oxf) 1987; 26:667.
  75. Rude RK, Haussler MR, Singer FR. Postpartum resolution of hypocalcemia in a lactating hypoparathyroid patient. Endocrinol Jpn 1984; 31:227.
  76. Blickstein I, Kessler I, Lancet M. Idiopathic hypoparathyroidism with gestational diabetes. Am J Obstet Gynecol 1985; 153:649.
  77. Kovacs CS, Kronenberg HM. Maternal-fetal calcium and bone metabolism during pregnancy, puerperium, and lactation. Endocr Rev 1997; 18:832.
  78. Hartogsohn EAR, Khan AA, Kjaersulf LU, et al. Changes in treatment needs of hypoparathyroidism during pregnancy and lactation: A case series. Clin Endocrinol (Oxf) 2020; 93:261.
  79. Callies F, Arlt W, Scholz HJ, et al. Management of hypoparathyroidism during pregnancy--report of twelve cases. Eur J Endocrinol 1998; 139:284.
  80. Salle BL, Berthezene F, Glorieux FH, et al. Hypoparathyroidism during pregnancy: treatment with calcitriol. J Clin Endocrinol Metab 1981; 52:810.
  81. Sadeghi-Nejad A, Wolfsdorf JI, Senior B. Hypoparathyroidism and pregnancy. Treatment with calcitriol. JAMA 1980; 243:254.
  82. Caplan RH, Beguin EA. Hypercalcemia in a calcitriol-treated hypoparathyroid woman during lactation. Obstet Gynecol 1990; 76:485.
  83. Caplan RH, Wickus GG. Reduced calcitriol requirements for treating hypoparathyroidism during lactation. A case report. J Reprod Med 1993; 38:914.
  84. Sowers MF, Hollis BW, Shapiro B, et al. Elevated parathyroid hormone-related peptide associated with lactation and bone density loss. JAMA 1996; 276:549.
Topic 99737 Version 20.0

References

آیا می خواهید مدیلیب را به صفحه اصلی خود اضافه کنید؟