Summary
Hypoparathyroidism may be due to a variety of mechanisms, including destruction of parathyroid glands (autoimmune or surgical), abnormal parathyroid gland development, altered regulation of parathyroid hormone (PTH), or impaired PTH action on end organs. The resulting hypocalcemia can trigger a variety of symptoms, ranging from muscle cramps to seizures or heart failure. Manifestations of chronic hypoparathyroidism, however, are quite specific, and include basal ganglia calcifications (resulting in movement disorders), cataracts, and skeletal and dental abnormalities. Laboratory findings in hypoparathyroidism include hypocalcemia with low or inappropriately normal PTH, hyperphosphatemia, and normal renal function. Treatment usually includes correcting the hypocalcemia through calcium and vitamin D supplementation and treatment of the underlying cause.
Etiology
- Postoperative: most commonly occurs as the result of accidental injury to parathyroids (or their blood supply) during thyroidectomy, parathyroidectomy, or radical neck dissection
- Autoimmune: : second most common cause
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Nonautoimmune destruction
- Infiltration of parathyroid gland
- Radiation-induced destruction
- Gram-negative sepsis
- Toxic shock syndrome
- HIV infection
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Congenital
- Parathyroid gland aplasia or hypoplasia (DiGeorge syndrome)
- PTH gene mutation
- Autosomal dominant hypocalcemia
Clinical features
Acute manifestations [1]
- Symptoms of hypocalcemia, such as tetany (see “Clinical features of hypocalcemia.”)
Chronic manifestations
- Extrapyramidal disorders
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Ocular disease
- Cataracts
- Keratoconjunctivitis
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Skeletal manifestations
- Increased bone mineral density
- Osteosclerosis
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Dental abnormalities
- Dental hypoplasia
- Failure of tooth eruption
- Defective root formation
- Cutaneous manifestations: dry, puffy, coarse skin
Diagnostics
Physical examination
Laboratory tests
- Hypocalcemia with low or inappropriately normal PTH
- Hyperphosphatemia
- Normal 25-hydroxyvitamin D (25[OH]D)
- Normal or low 1,25-dihydroxyvitamin D (1,25[OH]2D): low concentration of PTH cannot stimulate renal production of 1,25[OH]2D
- Normal magnesium
- Normal creatinine
Differential diagnoses
See “Interpretation of laboratory findings in hypocalcemia.”
Pseudohypoparathyroidism type 1A (PHP1A)
- Definition: end-organ (i.e., bones and kidneys) resistance to parathyroid hormone (PTH) despite sufficient PTH synthesis due to a defective Gs protein α subunit
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Inheritance
- Autosomal dominant
- Inherited from the mother (GNAS gene imprinting)
- Pathophysiology: mutations in GNAS1 → impaired encoding of α subunit → missing activation of adenylate cyclase when PTH binds to Gs → resistance to PTH in kidney and bone tissue
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Clinical features
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Albright hereditary osteodystrophy (AHO)
- Round face
- Short stature
- Obesity
- Brachydactyly of the 4th and 5th fingers
- Intellectual disability
- Subcutaneous ossifications
- Symptoms related to low calcium and high phosphate levels
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Albright hereditary osteodystrophy (AHO)
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Diagnostics
- Persistent hypocalcemia despite ↑ PTH levels
- ↑ Phosphate levels
Pseudopseudohypoparathyroidism
- Definition: extremely rare condition that mimics PHP1A but without end-organ resistance to PTH
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Inheritance
- Autosomal dominant
- Defective Gs protein α subunit is inherited from the father (GNAS gene imprinting).
- The normal allele from the mother allows for maintaining the responsiveness of the kidneys to PTH.
- Clinical features: Albright hereditary osteodystrophy
- Diagnostics: normal calcium, PTH, and phosphate
The differential diagnoses listed here are not exhaustive.