Hypoparathyroidism

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.

• Postoperative: (most common cause of hypoparathyroidism in adults): secondary to thyroidectomy, parathyroidectomy, or radical neck dissection
• Autoimmune: second most common cause
• Congenital:
  • Parathyroid aplasia or hypoplasia (DiGeorge syndrome)
  • PTH gene mutation
  • Autosomal dominant hypocalcemia
• Nonautoimmune destruction:
  • Infiltration of parathyroid gland (Wilson's disease, hemochromatosis, granulomas, metastases)
  • Radiation-induced destruction
  • Gram-negative sepsis
  • Toxic shock syndrome
  • HIV infection
• Pseudohypoparathyroidism (type 1A):
  • Etiology: defective G_s protein alpha subunit
  • Pathophysiology: end-organ resistance to parathyroid hormone (PTH) despite sufficient PTH synthesis.
  • Clinical features: persistent hypocalcemia dispite increased levels of PTH, developmental delay, short stature, obesity, shortened 4^th and 5^th finger (Albright hereditary osteodystrophy)
  • Inheritance
    • If associated with Albright hereditary osteodystrophy → autosomal dominant
    • Can be inherited due to imprinting in the mother
• Pseudohypoparathyroidism:
  • Etiology: defective G_s protein alpha subunit
  • Pathophysiology: no end-organ resistance to PTH → normal PTH levels
  • Clinical features: no hypocalcemia, normal PTH, features of Albright hereditary osteodystrophy
  • Inheritance: paternal

References:^[1][2]

• Acute manifestations: symptoms of hypocalcemia (see disorders of calcium balance)
  • Chvostek sign: hypocalcemia → hyperexcitable nerves → tapping the facial nerve on the cheek → contraction of facial muscles
  • Trousseau sign: inflate BP cuff → allow for occlusion of brachial artery for a few minutes → carpal spasm
• Chronic manifestations
  • Extrapyramidal disorders : symptoms include parkinsonism, dystonia, hemiballismus, choreoathetosis, oculogyric crises, or dementia
  • Ocular disease: cataracts, keratoconjunctivitis
  • Skeletal: increased bone mineral density, osteosclerosis
  • Dental abnormalities: dental hypoplasia, failure of tooth eruption, defective root formation
  • Cutaneous manifestations: dry, puffy, coarse skin

References:^[2][3]

• Hypocalcemia with low or inappropriately normal PTH
• Hyperphosphatemia
• Normal 25-hydroxyvitamin D (25[OH]D)
• Normal or low 1,25-dihydroxyvitamin D (1,25D): low concentration of PTH cannot stimulate renal production of 1,25D
• Normal magnesium
• Normal creatinine

References:^[2][3]

See differential diagnosis of hypocalcemia.

The differential diagnoses listed here are not exhaustive.