Pediatric Hypoparathyroidism

Hypoparathyroidism results from defective synthesis or secretion of parathyroid hormone (PTH), end-organ resistance, or inappropriate regulations that result from the activated or antibody-stimulated calcium-sensing receptor (CaSR).[1] These defects can be inherited or acquired. PTH secretion by the parathyroid glands (prime regulators of serum calcium concentration) maintains serum calcium within a strict range. Biochemical hallmarks of hypoparathyroidism include hypocalcemia and hyperphosphatemia. Severe hypocalcemia presents with seizures, stridor, prolonged QTc, and tetany.

Electrocardiogram (ECG) findings in severe hypocalcemia.

Mature PTH is an 84–amino acid protein. Production and secretion of PTH are regulated by a G protein–coupled calcium-sensing receptor. Unlike other protein hormones, its production and secretion are stimulated by decreased intracellular calcium concentrations, which reflect serum calcium concentrations. PTH exerts its action through the PTH receptor, which is another member of the G protein–linked receptor family.

The net effects of PTH activity are an increase in serum calcium and a decrease in serum phosphate. PTH acts directly on bone to stimulate bone resorption and cause calcium and phosphate release. PTH acts directly on the kidney to decrease calcium clearance and to inhibit phosphate reabsorption. By stimulating renal 1-alpha-hydroxylase activity, PTH increases serum concentrations of 1,25-dihydroxyvitamin D, the active form of vitamin D and, thus, indirectly stimulates calcium and phosphate absorption by the gut through the actions of vitamin D. The phosphaturic effect of PTH offsets the increases of serum phosphate driven by increased bone resorption and GI absorption.

Hypoparathyroidism results in loss of both the direct and indirect effects of PTH on bone, the kidney, and the gut. Calcium and phosphate release from bone is impaired, calcium absorption from the gut is limited, calciuria develops despite hypocalcemia, and retention of phosphate from the urine causes increased plasma phosphate levels.

Frequency

United States

The incidences of idiopathic hypoparathyroidism and pseudohypoparathyroidism (PHP) have not been determined in the United States. Rates following surgical procedures such as thyroidectomy vary depending on the extent of the surgery and experience of the surgeon.

International

In Japan, a recent survey found the prevalence of idiopathic hypoparathyroidism to be 7.2 cases per million people and the prevalence of PHP to be 3.4 cases per million people.

Mortality/Morbidity

Complications of hypoparathyroidism result from hypocalcemia.

• Neurologic: Neuromuscular irritability, paresthesias, muscle cramping, tetany, or seizures. However, patients can be asymptomatic. Neck muscle cramping can cause dystoniclike neck movements.

• Cardiac: Prolongation of the QTc interval. Affected individuals may be asymptomatic or experience syncope, seizure, or death due to arrhythmias, such as polymorphic ventricular tachycardia.

• Respiratory: Laryngospasm, a form of tetany, can lead to stridor and significant airway obstruction.

Sex

Hypoparathyroidism is equally prevalent in males and females.

Age

Age of onset depends on the etiology of hypoparathyroidism. Transient hypoparathyroidism is common during the first few days of life in preterm infants, infants of mothers with diabetes mellitus, infants of mothers with hypercalcemia, and infants with a prolonged delay in parathyroid gland responsiveness.

Transient hypoparathyroidism in newborns usually presents with hypocalcemia; however, it can recur during the adolescent period as seen in some patients with DiGeorge Syndrome.

In general, patients with DiGeorge syndrome present during the first few weeks of life. In patients with velocardiofacial syndrome (DiGeorge variant) and autoimmune and PTH resistance syndromes (pseudohypoparathyroidism), hypocalcemia tends to present as late as adolescence.

Symptoms of hypoparathyroidism can be attributed to hypocalcemia. Symptoms of hypocalcemia include muscle aches, facial twitching, carpopedal spasm, stridor, seizures, and syncope.

Review of the past medical history or symptoms is very helpful in determining the etiology of the hypoparathyroidism.

• DiGeorge syndrome, which is one manifestation of the 22q11 deletion syndrome, is associated with recurrent infections related to T-cell abnormalities and conotruncal abnormalities, such as tetralogy of Fallot and truncus arteriosus. Affected individuals may also have a history of speech delay from velopharyngeal insufficiency.

• Familial autoimmune polyglandular syndrome type I (APS I) is associated with chronic mucocutaneous candidiasis and adrenal insufficiency. Other nonendocrine clues to the presence of this autoimmune etiology include vitiligo and dental enamel hypoplasia. Candidal infections of the skin or GI tract that last more than 3 months are considered chronic and are the presenting symptom in 60% of individuals with hypoparathyroidism due to APS I.

• Individuals with pseudohypoparathyroidism (PHP) type Ia are obese, have short stature and short fourth and fifth metacarpal/metatarsal, and may have subcutaneous calcifications and disturbances of taste, smell, hearing, and vision. Patients also have mental retardation and developmental delay. Other endocrine abnormalities, such as TSH resistance, could be associated findings.

• A history of radioactive iodine ablation of the thyroid for Grave disease may predate the development of acquired hypoparathyroidism by several months. However, it could be sooner in those patients who underwent thyroid surgery.

• Sensorineural deafness, renal dysplasia, and mental retardation are also associated with syndromes that include hypoparathyroidism.

See the list below:

• Hyperreflexia due to hypocalcemia is common.

  • Trousseau sign is a carpopedal spasm that occurs after a blood pressure cuff around the arm is inflated above the systolic blood pressure for several minutes.

  • Chvostek sign (ie, twitching of ipsilateral facial muscles with tapping on the facial nerve in front of the ear and just below the zygomatic bone) is a manifestation of neuromuscular excitability. Chvostek sign is present in 25% of healthy adults and in even higher rates in children. Thus, its presence or absence should be documented prior to thyroidectomy.

• Chromosome band 22q11 deletion/velocardiofacial syndrome/DiGeorge syndrome has characteristic physical features, but hypoparathyroidism may be the only immediately recognizable manifestation.

  • Nasal speech can occur from a cleft palate or velopharyngeal insufficiency.

  • Bulbous nasal tip, micrognathia, ear anomalies, and short philtrum are typical facial features but may not be evident in nonwhite children.

  • A heart murmur may signify a conotruncal heart defect.

  • Short stature may be a feature of the genetic syndrome, but in some cases, it is due to growth hormone deficiency.

• PHP is an uncommon metabolic disorders characterized by biochemical hypoparathyroidism (ie, hypocalcemia and hypophosphatemia), and PTH resistance.

• Albright hereditary osteodystrophy (AHO) is the characteristic phenotype of PHP type Ia and Ic.

  • Short stature, obesity, round face, short distal phalanges of the thumbs, brachymetacarpals and brachymetatarsals, subcutaneous calcifications, dental hypoplasia, and developmental delay characterize this phenotype.

  • Pseudopseudohypoparathyroidism (PPHP) is characterized by normal calcium homeostasis in the setting of the AHO phenotype.

Hypoparathyroidism may be transient, genetically inherited, or acquired. Genetically inherited forms arise from defects of parathyroid gland development, defects in the parathyroid hormone (PTH) gene, defects in the calcium-sensing receptor gene, defects in PTH action, defects in the autoimmune regulator gene, and genetic syndromes. Acquired hypoparathyroidism may be due to an autoimmune process or may occur after neck irradiation or surgery.

• Transient hypoparathyroidism occurs during the neonatal period. Preterm infants are at increased risk, and as many as 50% of very low birth weight infants may have a deficient surge in PTH that results in hypocalcemia.

  • Hypocalcemia is noted in 10-20% of infants of diabetic mothers. These infants may be born prematurely, which is a risk factor for insufficient PTH response. They may have hypomagnesemia from maternal magnesuria complicating glucosuria. Low serum magnesium can impair PTH release and action.

  • PTH secretion is suppressed in the fetus because of high placental transfer of calcium, particularly in the third trimester. With cord clamping, calcium transfer abruptly stops; serum calcium concentrations decrease rapidly, and PTH secretion is triggered. Prolonged delay in PTH responsiveness in some otherwise healthy infants causes transient hypoparathyroidism.

  • Maternal hypercalcemia from hyperparathyroidism can also cause prolonged suppression of PTH secretion in the neonate.

• DiGeorge syndrome (ie, hypoparathyroidism, absence of thymus gland [T-cell abnormalities], cardiac anomalies) is associated with abnormal development of the third and fourth pharyngeal pouches from which the parathyroids derive embryologically and represents an example of a defect in parathyroid gland development. DiGeorge syndrome and velocardiofacial syndrome are variants of the chromosome arm 22q11 microdeletion syndrome. Several cases of chromosome 10p deletion have also been reported in which affected individuals have some features of DiGeorge syndrome.

  • Hypocalcemia associated with a 22q11 microdeletion may be transiently present in infancy but recur later in life, particularly during periods of stress.

  • Hypocalcemia may be the first apparent and, at times, only manifestation of a chromosome arm 22q11.2 microdeletion.

  • Patients with chromosome arm 22q11.2 microdeletion who present with late-onset hypoparathyroidism in adolescence have been described.

• X-linked recessive hypoparathyroidism has been associated with parathyroid agenesis and has been mapped to chromosome arm Xq26-q27, the location of a putative developmental gene.

• Familial cases of hypoparathyroidism due to mutations of the PTH gene located on chromosome arm 11p15 have been identified. These mutations have been both dominantly and recessively inherited.

• Autosomal recessive forms of hypoparathyroidism have been shown to be caused by rare homozygous mutations in the genes encoding pre-pro-PTH or glial cell missing B (GCMB).[2]

• Autosomal dominant forms of hypoparathyroidism could be due to a dominant negative GCMB muation.[3]

• Defects in PTH action occur in PHP. The hallmark of PHP is PTH resistance. Four forms of PTH resistance are recognized. These include PHP Ia, Ib, Ic and II. Theoretically, defects in the PTH receptor (also shared by PTH-related peptide or PTHrP) should also be responsible for PTH resistance. Yet, PTH receptor defects are now known to possibly lead to Jansen metaphysial dysplasia and Blomstrand lethal chondrodysplasia. Researchers also hypothesize that bioinactive PTH could cause a hypoparathyroid state.

  • PHP Ia is due to loss-of-function mutations of the subunit of the G protein–coupled calcium-sensing receptor (Gsa). Mutations cause decreased nephrogenous adenosine 3',5'-cyclic adenosine monophosphate (cAMP) response to PTH. These mutations also cause a generalized resistance to other hormones, which act through Gsa and are associated with primary hypogonadism (eg, resistance to luteinizing hormone [LH] and follicle-stimulating hormone [FSH]) and primary hypothyroidism resistance to thyroid-stimulating hormone (TSH). Affected individuals have the Albright osteodystrophy phenotype.

  • PPHP describes family members of individuals with PHP Ia who have the AHO phenotype but normal serum calcium homeostasis and normal renal cAMP responsiveness to PTH.

  • PHP and PPHP are manifestations of imprinting of the stimulatory G protein defect located on chromosome arm 20q. PPHP results when the defect is inherited from the father. PHP Ia results when the defect is inherited from the mother.

  • PHP Ib arises from epigenetic defects in the imprinted gene GNAS, which encodes the alpha subunit of the stimulatory G protein and the NESP55 protein. In the autosomal dominant form, maternally inherited mutations in STX16 have been identified and are thought to disrupt a cis-acting element required for methylation at exon 1A of GNAS. Mutations in the maternally derived NESP55 cause loss of methylation of multiple normally methylated regions on the maternal allele and cause autosomal dominant PHP Ib. Because most of the G protein in the thyroid is thought to be maternally derived, these epigenetic defects may lead to decreased G protein expression, but G protein activity is normal in vitro. Borderline TSH resistance has also been described in some patients, but affected individuals otherwise lack the AHO phenotype.

  • PHP Ic: Patient will have similar features to PHP Ia except they do not have a demonstrable defect in Gs alpha subunit mutation. The nature of the lesion in such patients is unclear, but it could be related to some other general component of the receptor-adenylyl cyclase system, such as catalytic unit. Alternatively, these patients could have functional defects of Gs (or Gi) that do not become apparent in the assays presently available.

  • PHP II: Patients with PHP II have normal physical appearance. There is no association with the AHO phenotype. The genetic basis of PHP II is unknown. The defect appears to lie downstream of the signal for cAMP generation because PTH causes an increase in urinary cAMP without the phosphaturia that normally accompanies PTH stimulation. Hormone resistance is limited to PTH. PHP II is not associated with the AHO phenotype.

• Polyendocrinopathy-candidiasis-ectodermal dystrophy syndrome, also known as APS I, has been linked to mutations of an autoimmune regulator gene located on chromosome band 21q22.3.

  • Patients with hypoparathyroidism of APS I usually present within the first few years of life after the onset of chronic mucocutaneous candidiasis and before the onset of adrenal insufficiency.

  • More than 75% of individuals with APS I develop hypoparathyroidism, more than 85% of patients develop adrenal insufficiency, and 60% of women have ovarian failure.

  • The spectrum of clinical manifestations of APS I is wide. Lifelong monitoring for the development of new components of APS I is indicated.

• The hypoparathyroidism, deafness, and renal dysplasia (HDR) syndrome is associated with partial monosomy of chromosome arm 10p.

• Mitochondrial cytopathies, such as Kearns-Sayre syndrome (ie, external ophthalmoplegia, ataxia, sensorineural deafness, heart block, and elevated cerebral spinal fluid [CSF] protein), are associated with hypoparathyroidism.

• Hypoparathyroidism-retardation-dysmorphism (HRD) syndrome and Kenny-Caffey syndrome have also been associated with hypoparathyroidism. Mutations in the TBCE gene, which encodes a chaperone protein required for alpha tubulin subunit folding, have been identified in both HRD and autosomal recessive Kenny-Caffey syndrome

• Hypoparathyroidism incurred during neck surgery may be transient or permanent depending upon the extent of injury and preservation of the parathyroid glands. The risk varies depending on the series and experience of the surgeon. Parathyroid autotransplantation can be used to preserve parathyroid function.

• Hypoparathyroidism following months of radioactive iodine ablation of the thyroid has been described as more common in treatment of Grave disease than with treatment of thyroid cancer. Radiation to the chest or neck area for cancer is also associated with hypoparathyroidism.

• Parathyroid gland destruction due to deposition of iron (as with hemochromatosis or multiple blood transfusions) or deposition of copper (as with Wilson disease) has been described.

• Autoimmune destruction of the parathyroid glands can be due to the autosomal recessively inherited APS I, which is associated with ectodermal abnormalities and adrenal insufficiency.

• Calcium-sensing receptor (CaSR) mutations represent a resetting of the calciostat and are not considered an etiology of a true hypoparathyroid state. However, patients present with hypocalcemia, inappropriate normal PTH levels, and mild-to-moderate elevations of phosphate levels, and, hence, mimic hypoparathyroidism. Patients may present with hypocalcemia any time from birth to adulthood.

  • Autosomal dominant and sporadic gain-of-function mutations of the Ca2+ receptor, a G-protein coupled receptor, cause hypocalcemic hypercalciuria by lowering the serum calcium concentration that is required for PTH secretion and urinary calcium reabsorption.

  • Individuals with Ca2+ receptor mutations have PTH concentrations that are within the reference range in the setting of hypocalcemia; they can be asymptomatic or severely affected.

  • These individuals must be differentiated from individuals with true hypoparathyroidism because treatment with active vitamin D (calcitriol) can cause nephrocalcinosis and renal insufficiency by exacerbating the already high urinary calcium excretion. Therapy with calcitriol should be restricted to symptomatic individuals and should be sufficient enough to relieve symptoms without normalizing serum calcium concentrations. Treatment with hydrochlorothiazide has been shown to be beneficial. In addition, PTH therapy could be effective in correcting serum and urine calcium and the phosphate levels in this disorder.[4]

See the list below:

• Total and ionized serum calcium: In hypoparathyroidism and pseudohypoparathyroidism (PHP), total and ionized calcium levels are low. Ionized serum calcium level should be evaluated when patient has low protein or albumin in the blood.

• Serum phosphate: Serum phosphate levels are elevated in hypoparathyroidism and PHP, although they can be within the reference range, especially in the infant without enteral feeding and low phosphate/protein intake.

• Serum magnesium: Serum magnesium levels are obtained to rule out hypomagnesemia as a cause of hypoparathyroidism. In this condition, hypocalcemia could be corrected very rapidly with magnesium therapy. In general, magnesium levels are within the reference range in hypoparathyroidism and PHP.

• Intact parathyroid hormone (iPTH): Obtain iPTH at the time of hypocalcemia. Nomograms have been developed for the interpretation of serum iPTH concentration with respect serum calcium. In hypoparathyroidism, iPTH is low. An iPTH that falls within the reference range must be interpreted with caution. The value might be considered low in the face of hypocalcemia. In PHP, iPTH is usually elevated.

• BUN and creatinine levels: BUN and creatinine concentrations are obtained to assess renal function. These test results are normal in hypoparathyroidism and PHP.

• 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D: 25-Hydroxyvitamin D and 1,25-dihydroxyvitamin D concentrations are obtained to rule out a vitamin D–deficient or vitamin D–resistant state as the etiology of hypocalcemia. 25-Hydroxyvitamin D levels are within the reference range in hypoparathyroidism and PHP. 1,25-Dihydroxyvitamin D levels are expected to be low in hypoparathyroid states because of lack of PTH-stimulated 1-alpha-hydroxylase activity. Elevated 1,25-dihydroxyvitamin D concentrations have been documented in PHP, but the mechanism remains unclear.

• Urine calcium and creatinine ratio: Urine calcium is elevated in PTH-resistant and PTH-deficient states and particularly elevated in calcium-sensing receptor mutations.

• Thyroid studies (thyroid-stimulating hormone [TSH], thyroxine, and thyroid antibodies [antiperoxidase and antithyroglobulin antibodies]. If an autoimmune process is suspected as the etiology of hypoparathyroidism, thyroid studies may uncover a concomitant hypothyroid state. TSH resistance could be associated with PHP Ia.

• Adrenocorticotropic hormone (ACTH) and adrenal antibodies: If an autoimmune process is suspected, concomitant primary adrenal insufficiency can be revealed by an elevated ACTH level, and adrenal antibodies may be present.

See the list below:

• Chest radiography: Thymic aplasia is associated with the 22q11 deletion syndrome and can be assessed with chest radiography.

• Echocardiography: An infant with a murmur and in whom hypoparathyroidism is suggested should have echocardiography performed to assess for conotruncal lesions that are associated with the 22q11 deletion syndrome.

• Renal ultrasonography: Treatment of hypoparathyroidism can lead to nephrocalcinosis as a result of hypercalciuria. Baseline renal ultrasonography with initial treatment should be performed.

• Left hand and wrist radiography (bone age): Brachymetacarpals (shortening of fourth and fifth metacarpals) are a feature of Albright hereditary osteodystrophy (AHO) phenotype and can aid in the diagnosis of PHP Ia. There may be some degrees of advanced bone age as well in those patients with PHP.

• Brain MRI: Basal ganglia calcifications are quite common in both hypoparathyroidism and PHP. These suggest a long-standing presence of calcium disorder and are more common with PHP. These calcifications occur even before the treatment of hypocalcemia was initiated.

See the list below:

• Electrocardiography: A prolonged QTc interval is found with hypocalcemia and resolves with correction of serum calcium.

• ACTH stimulation testing: Adrenal insufficiency can be life threatening. If APS I is suggested, an ACTH stimulation study should be performed to assess adrenal function (if basal ACTH levels are elevated).

• Thyrotropin-releasing hormone stimulation testing: PHP Ia is associated with generalized hormone resistance. Hypothyroidism may be subtle and may only be detected with a thyrotropin-releasing hormone (TRH) stimulation study. Unfortunately, TRH is not commercially available at this time.

• Genetic studies, when applicable

• In neonates, a fluorescence in situ hybridization (FISH) for the chromosome band 22q11 deletion

Symptomatic hypocalcemia (eg, seizure, tetany, laryngospasm) in patients with hypoparathyroidism requires intravenous calcium and continuous monitoring for cardiac arrhythmias.

Oral calcium and active vitamin D (calcitriol) should be initiated as soon as possible (eg, when the patient is tolerating oral feeds).

Once serum calcium concentrations are in a safe range (>7.5 mg/dL), intravenous calcium can be stopped. Prolonged intravenous calcium therapy with existing high serum phosphate will increase further precipitation of calcium-phosphate compound. However, rebound hypocalcemia can occur and requires that a patient be monitored for therapeutic success on oral agents for at least 24 hours after intravenous calcium is withdrawn. In patients with hungry bone syndrome, prolonged intravenous calcium therapy may be needed.

The active form of vitamin D, 1,25-dihydroxyvitamin D (calcitriol), is preferred in the treatment of hypoparathyroidism because both the parathyroid hormone (PTH) deficiency/resistance and the hyperphosphatemia impair the activation of 25-hydroxyvitamin D by 1-alpha-hydroxylase.

General recent guidelines on chronic hypoparathyroidism by the European Society of Endocrinology are below:[5]

• Consider a diagnosis of chronic hypoparathyroidism (HypoPT) in a patient with hypocalcemia and inappropriately low parathyroid hormone (PTH) levels.
• Consider genetic testing and/or family screening in a patient with HypoPT of unknown etiology.
• Treatment targeted to maintain serum calcium level (albumin adjusted total calcium or ionized calcium) in the lower part or slightly below the lower limit of the reference range (target range) is suggested, with patients being free of symptoms or signs of hypocalcemia.
• Treat patients with chronic HypoPT with symptoms of hypocalcemia and/or an albumin adjusted serum calcium level < 2.0 mmol/L (< 8.0 mg/dL/ionized serum calcium levels [S-Ca ²] < 1.00 mmol/L).
• Offer treatment to asymptomatic patients with chronic HypoPT and an albumin adjusted calcium level between 2.0 mmol/L (8.0 mg/dL/S-Ca ²⁺ 1.00 mmol/L) and the lower limit of the reference range in order to assess whether this may improve their well-being.
• Use activated vitamin D analogues plus calcium supplements in divided doses as the primary therapy.
• If activated vitamin D analogues are not available, treat with calciferol (preferentially cholecalciferol).
• Titrate activated vitamin D analogues or cholecalciferol in such a manner that patients are without symptoms of hypocalcaemia and serum calcium levels are maintained within the target range.
• Provide vitamin D supplementations in a daily dose of 400–800 IU to patients treated with activated vitamin D analogues.
• In a patient with hypercalciuria, consider a reduction in calcium intake, a sodium-restricted diet, and/or treatment with a thiazide diuretic.
• In a patient with renal stones, evaluate renal stone risk factors and management according to relevant international guidelines.
• In a patient with hyperphosphatemia and/or an elevated calcium-phosphate product, consider dietary interventions and/or adjustment of treatment with calcium and vitamin D analogues.
• In a patient with hypomagnesemia, consider measures that may increase serum magnesium levels.
• The routine use of replacement therapy with PTH or PTH analogues is not recommended.

No special diet is required, but adequate calcium and vitamin D intake is recommended.

Calcium and calcitriol (active vitamin D) are the mainstays of treatment for hypoparathyroidism and pseudohypoparathyroidism (PHP). To relieve immediate severe symptoms of hypocalcemia, an intravenous bolus of 9-15 mg elemental calcium/kg (1 g calcium gluconate = 90 mg elemental calcium = 4.5 mEq elemental calcium) is administered over 10-30 min. Then, either intermittent boluses or a continuous IV infusion is initiated (60 mg elemental calcium/kg/d). Oral calcium is initiated for a total of 100 mg elemental calcium/kg/d divided 4 times daily. Once serum calcium concentrations range from 8-9 mg/dL, the calcium dose is weaned to the minimum dose necessary to maintain a low-normal serum calcium concentration.

In some studies, synthetic human PTH 1-34, both once and twice daily, has been shown to effectively treat children with hypoparathyroidism. However, this therapy is not yet approved for the treatment of hypoparathyroidism.[6]

A study that included data from 42 children with hypoparathyroidism who presented with epileptic seizures reported that antiepileptic drug treatment does not improve seizure outcomes in children with parathyroid disorders.[7]

Class Summary

Numerous calcium preparations are available. An intravenous dose quickly but transiently corrects the serum calcium concentration and relieves hypocalcemic symptoms. Severe hypocalcemia can be treated with a continuous calcium infusion; a transition to the oral form can be made when the serum calcium concentration is within a safe range. Tailoring of calcium dosing to each patient's needs is essential. In fact, once adequate amounts of active vitamin D are present, some patients can absorb all the calcium they need through the diet and oral calcium preparations can be discontinued. Intravenous calcium gluconate is preferred in children. For enteral preparation in young children, liquid calcium glubionate (Neo-Calglucon, Calcionate) or calcium gluconate is preferred. For older children and adolescents, the authors prefer calcium citrate over calcium carbonate because the latter is not well absorbed through the gut and it needs to be taken with a meal because it requires acid for absorption.

Calcium citrate (Cal-Citrate, Citracal)

Oral formulation usually used as supplementation to IV calcium therapy. Moderates nerve and muscle-performance by regulating action potential excitation threshold and facilitates normal cardiac function. Give amount needed to supplement diet to reach recommended daily amounts.

Calcium gluconate

Used to correct serum calcium concentration and relieve hypocalcemic symptoms. Moderates nerve and muscle performance and facilitates normal cardiac function (1 g = 90 mg elemental = 4.5 mEq elemental calcium).

Calcium glubionate (Neo-Calglucon)

PO calcium can be used to correct mild hypocalcemia and for maintenance therapy. Moderates nerve and muscle performance and facilitates normal cardiac function (1 g = 64 mg elemental = 3.3 mEq elemental calcium).

Calcium carbonate (Tums, Oscal)

An alternative PO form of calcium that can be used to correct mild hypocalcemia and for maintenance therapy (1 g = 400 mg elemental = 20 mEq elemental calcium).

Class Summary

1,25-Dihyroxyvitamin D, calcitriol, is critical for maintaining serum calcium concentrations. Parathyroid hormone (PTH) deficiency impairs conversion of inactive vitamin D to the active form by renal 1-alpha-hydroxylase. To bypass this PTH-dependent step, the active form of vitamin D is administered and may eliminate the need for PO calcium once the patient has stabilized.

Calcitriol (Rocaltrol, Calcijex)

This drug has a short half-life, and its effects are quickly reversed with withdrawal of the medication in case of hypercalcemia. Calcitriol is available in 0.25- and 0.50-mcg gel cap or an oral solution of 1 mcg/mL. Also available in an injectable form of 1 mcg/mL and 2 mcg/mL.

See the list below:

• Close follow-up of serum calcium concentrations is required in the first months of hypoparathyroidism treatment; after the serum calcium and phosphate levels stabilize, monitor these serum data every 3-6 months. Urine calcium/creatinine ratio should be monitored as well for hypercalciuria. Therapeutic goal is to maintain serum calcium in the low-normal range to decrease risk for nephrocalcinosis.

• Renal ultrasonographic studies are needed annually to assess for nephrocalcinosis development.

See the list below:

• 1,25-Dihydroxyvitamin D: This medication bypasses the parathyroid hormone (PTH)-dependent step of 1-alpha hydroxylation of 25 hydroxyvitamin D. It should be used in combination with a calcium supplement to maintain the calcium in the low normal range and serum phosphate concentrations in the mid range.

• Calcium: Any of the oral calcium supplements may be used.

See the list below:

• Nephrocalcinosis

• Hypocalcemia-related events, including tetany, seizure, laryngospasm, arrhythmia, and syncope

See the list below:

• Hypoparathyroidism is a chronic disease requiring strict compliance with medications. As with any chronic illness, compliance can be difficult to achieve with adolescents.

• Nephrocalcinosis can lead to kidney damage requiring intervention.

See the list below:

• Family members should recognize the signs of hypocalcemia.

• During times of stress, such as surgery or significant intercurrent illness, inherited disorders of hypoparathyroidism that have seemingly resolved can be unmasked and require intervention.