AUTHOR AND EDITOR INFORMATION

Section 1 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Acknowledgments
• References

INTRODUCTION

Section 2 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Acknowledgments
• References

Background

Hypoparathyroidism describes a condition in which there are low circulating levels of parathyroid hormone (PTH) or insensitivity to its action. The causes of hypoparathyroidism vary; however, they all share a common feature of hypocalcemia. The presentation of hypoparathyroidism also varies depending on the chronicity of the resultant hypocalcemia. Muscle spasms/tetany, paresthesias, and seizures may occur in an acute onset, whereas chronic hypoparathyroidism may only be evidenced by visual impairment due to cataract formation.

See Hypocalcemia for more information.

Pathophysiology

Many underlying pathologic etiologies of hypoparathyroidism exist.

• The most common causes are neck surgery and autoimmune processes. Hypoparathyroidism resulting from thyroid or parathyroid surgery can become clinically apparent 1-2 days after the procedure or follow the operation by many years. The incidence of permanent hypoparathyroidism varies with the extent of the procedure, the surgeon’s experience, and the underlying disease process being treated. Rarely, hypoparathyroidism can be a complication of radioactive iodine treatment of external localized radiotherapy.¹
• Autoimmune insult to the parathyroid gland can be isolated or associated with a variety of polyglandular syndromes. Antibodies to the parathyroids have been detected in up to 30% of patients with isolated hypoparathyroidism and 40% of patients with polyglandular disease.² The calcium sensor-receptor is another target of autoantibodies in hypoparathyroidism. In patients with polyglandular autoimmune syndrome type 1, more than 50% will have this antibody. See Polyglandular Autoimmune Syndrome, Type I.
• Maternal hyperparathyroidism can result in transient neonatal hypoparathyroidism.^{3, 4, 5} Maternal PTH suppresses neonatal parathyroid activity; however, this resolves rapidly after birth and removal from excessive maternal PTH.
• Both hypermagnesemia and hypomagnesemia can result in decreased PTH secretion. In the case of hypermagnesemia, elevated magnesium levels result in stimulation of a calcium-sensing receptor on the pituitary. This, in turn, attenuates PTH secretion. In the case of chronic alcoholics with hypomagnesemia, there is diminution of PTH secretion levels and a resistance to hormone activity.⁶ See Hypermagnesemia and Hypomagnesemia.
• This condition is characterized by thymus and parathyroid dysgenesis, cardiac malformation, and facial dysmorphogenesis.⁷ Other complex syndromes associated with hypoparathyroidism have been described and include Sanjat-Sakati syndrome, HDR syndrome, Kenny-Caffey syndrome, Kearns-Sayre syndrome, and Pearson marrow-pancreas syndrome.⁸ See DiGeorge Syndrome and Kearns-Sayre Syndrome.
• Infiltration of the parathyroid gland can lead to clinically significant hypoparathyroidism. Causes include metastatic carcinoma, hemochromatosis, transfusion-related iron overload, Wilson disease⁹, and sarcoidosis¹⁰. See Hemochromatosis, Wilson Disease, and Sarcoidosis.

PTH functions to maintain plasma calcium levels by withdrawing calcium from bone tissue, glomerular filtrate reabsorption, and indirectly through increased intestinal absorption of calcium by activation of vitamin D-1,25. Insufficient production of PTH is known as true hypoparathyroidism, while decreased action on target tissues is called pseudohypoparathyroidism.² See Pseudohypoparathyroidism.

Frequency

United States

Primary hypoparathyroidism is rare. Familial cases occur with autosomal dominant, autosomal recessive, and X-linked transmission.

Mortality/Morbidity

Acute hypocalcemia can be treated with good outcome. The mortality rate of hypoparathyroidism depends on the underlying cause.

Sex

With the exception of X-linked transmitted syndromes, no sex predilection exists.

Age

• Maternal hyperparathyroidism resulting in newborn hypoparathyroidism usually manifests by the third week of life;^{3, 4} however, cases have been reported as late as 2 months of age.⁵
• Patients with DiGeorge syndrome present for clinical evaluation between birth and 3 months of age with a variety of symptoms.
• Patients with polyglandular autoimmune syndrome type I present early in life. These patients typically have candidiasis by age 5 years and hypoparathyroidism by age 10 years.
• For other forms of hypoparathyroidism, no age predilection is noted.

CLINICAL

Section 3 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Acknowledgments
• References

History

• Neuromuscular irritability, arising from hypocalcemia, is the hallmark of the condition. These features can range from mild-to-moderate paresthesias of the extremities or lips to painful muscle cramps. In severe cases, tetany can result in carpopedal spasm, laryngospasm,¹¹ or generalized seizures. Recurrent laryngospasm should prompt an investigation of underlying hypoparathyroidism.¹²
• Additionally, severe hypocalcemia can result in neuropsychiatric and cardiovascular abnormalities. Neuropsychiatric manifestations include irritability, anxiety, psychosis, dementia, hallucinations, depression, and confusion. The cardiovascular effects of hypocalcemia are usually bradydysrhythmias or prolongation of the QT interval. Severe hypocalcemia can rarely mimic myocardial infarction.¹³
• Gastrointestinal complaints may result from hypocalcemia as well. Smooth muscle spasms can result in intestinal and biliary cramping. Several cases of dysphagia have been described in the setting of hypocalcemia.¹⁴
• Symptoms are rare unless the ionized calcium level drops below 2.8 mg/dL.²

Physical

The clinical manifestation of hypoparathyroidism is due to hypocalcemia.

• Head, ears, eyes, nose, and throat signs
• • Surgical/traumatic scars
  • Mucocutaneous candidiasis (in the setting of polyglandular failure type 1¹⁵)
• Neurologic signs
• • Hyperreflexia
  • Tetany
  • Chvostek sign - Chvostek sign has low sensitivity and specificity. Twenty-five percent of healthy persons will have a positive result; 29% of hypocalcemic patients will have a negative result.²
  • Trousseau sign (carpal spasm caused by occluding the brachial artery) - Trousseau sign is more reliable. Only 1-4% of healthy persons will have a positive sign; 94% of hypocalcemic persons will have a positive sign.²
  • Seizures
  • Altered mental status
• Cardiovascular signs
• • Heart failure^{16, 17}
  • Bradycardia¹⁸
  • Hypotension not responsive to fluids or pressors¹⁹
• Ophthalmologic signs - Cataracts²⁰
• Signs in infants
• • Vomiting
  • Abdominal distention
  • Apneic spells
  • Intermittent cyanosis
  • Twitching, tremors, and seizures

Causes

Hypoparathyroidism has multiple etiologies:

• Postsurgical
• Autoimmune
• Sporadic²¹
• Polyglandular syndromes
• Activating antibodies to the calcium-sensing receptor^{22, 23}
• Infiltration
• Parathyroid destruction
• Copper⁹
• Malignancy
• Granulomatous disease¹⁰
• Mitochondrial neuropathies
• Inactivating mutations of the PTH gene²¹
• DiGeorge syndrome⁷
• Impaired secretion and/or action of PTH
• Hypomagnesemia²⁴
• Pseudohypoparathyroidism
• Hemochromatosis²⁵
• Infarction²⁶
• Hypermagnesemia²⁷
• Medication induced (aluminum.²⁸ doxorubicin,²⁴ aminoglycoside,²⁹ cimetidine,³⁰ alendronate³¹)

DIFFERENTIALS

Section 4 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Acknowledgments
• References

Other Problems to be Considered

Increased protein binding of calcium
Pseudohypoparathyroidism
Vitamin D deficiency
Rickets and osteomalacia
Addison disease
Pernicious anemia

WORKUP

Section 5 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Acknowledgments
• References

Lab Studies

• The diagnosis of hypoparathyroidism is supported by hypocalcemia, hyperphosphatemia, and low parathyroid hormone levels in the absence of renal failure or intestinal malabsorption. 
• Both total and ionized calcium are decreased. Normal total serum calcium levels range from 9-10.5 mg/dL (2.2-2.6 mmol/L). Normal ionized calcium levels are 4.5-5.6 mg/dL (1.1-1.4 mmol/L). 
• Radioimmunoassay (RIA) will show decreased PTH level. 
• Serum magnesium level can be low, high, or normal.
• Serum phosphorous level is increased. 
• An alkaline environment results in increased binding of free calcium to albumin.

Imaging Studies

• Radiography: Bone density is increased³²; tooth enamel and root abnormalities have been described.³³ Ossification of the paravertebral ligaments is frequently observed.³⁴ 
• CT scan: Calcification of subcortical nuclei, dentate nucleus,³⁵ and basal ganglia³⁶ can occur.

Other Tests

• ECG may show prolonged QT interval, bradycardia, or rarely ST-segment elevations.¹³
• For D-xylose absorption test, the results are usually normal.³⁷

Procedures

• Slit lamp examination for cataracts²⁰

TREATMENT

Section 6 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Acknowledgments
• References

Prehospital Care

• Address and stabilize ABCs.
• Obtain intravenous access.
• Control seizures with benzodiazepines.

Emergency Department Care

Acute, symptomatic hypocalcemia is a medical emergency. The main goal of treatment is to restore serum calcium levels to alleviate symptoms of acute hypocalcemia. Care to prevent long-term complications from hypocalcemia or hypercalcemia³⁸ should be coordinated with an endocrinologist.

• Intravenous calcium - 100-300 mg elemental calcium diluted in 150 mL D5W over 10 minutes (10-30 mL of 10% calcium gluconate [9.3 mg/mL elemental calcium])
• • This solution raises ionized calcium level by 0.5-1.5 mmol. Calcium chloride may be used if infused through a central line, as it can be harmful when given in a peripheral vein.
• • Initial rate of infusion is 0.3-2 mg elemental calcium/kg/h. This scale is not exact; base subsequent adjustments on serial calcium measurements every 2-4 hours.
  • Infuse children with 2 mg/kg elemental calcium, or about 0.2 mL of 10% calcium gluconate/kg, IV.

Consultations

Consult an endocrinologist.

MEDICATION

Section 7 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Acknowledgments
• References

Hypoparathyroidism is treated primarily with vitamin D. Dietary supplementation with Ca²⁺ may be necessary.

Drug Category: Electrolyte supplements

Hypoparathyroidism manifests as hypocalcemia. As a result, calcium supplementation may be indicated.

Drug Category: Vitamin D Analog

Vitamin D enhances absorption of calcium and maintains calcium homeostasis.

FOLLOW-UP

Section 8 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Acknowledgments
• References

Further Inpatient Care

• Effects of 1 bolus of intravenous calcium will wane after 2 hours; therefore, subsequent continuous infusion is required to control hypocalcemia.
• Cardiac monitoring is indicated.

Further Outpatient Care

• High-calcium diet
• Calcium supplementation
• Calcitriol

Complications

• Neuromuscular symptoms
• Cataracts²⁰
• Intracranial calcifications^{35, 36}
• Growth stunting (with HDR syndrome)³⁹
• Tooth malformation³³
• Mental retardation (with HDR syndrome)³⁹
• Hypothyroidism
• Cardiomyopathy³⁸
• Parkinsonian symptoms⁴⁰
• Ossification of paravertebral ligaments³⁴  
• Adhesive capsulitis⁴¹

Prognosis

• Prognosis is determined by the underlying cause of hypoparathyroidism.

Patient Education

• Educate patients concerning regulation and effects of calcium on the body.
• Educate patients about the importance of periodic blood chemistry evaluation.

ACKNOWLEDGMENTS

Section 9 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Acknowledgments
• References

The authors and editors of eMedicine gratefully acknowledge the contributions of previous authors, John Halpern, DO, and N Ewen Wang, MD, to the development and writing of this article.

REFERENCES

Section 10 of 10

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Acknowledgments
• References

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Article Last Updated: Mar 13, 2008