Hypoparathyroidism

Hypoparathyroidism 

Updated: 07/02/2023

© Jun Wang, MD, PhD

General features

• Primary: Inadequate PTH activity
• Secondary: Low PTH levels in response to a primary process that causes hypercalcemia

Etiology

• Post-surgical: Most common cause, especially for acute presentation
• Genetic disorders

Abnormal parathyroid gland development

Abnormal PTH synthesis

Activating mutations of calcium-sensing receptor (autosomal dominant hypocalcemia or sporatic isolated hypoparathyroidism)

• Autoimmune

Polyglandular autoimmune syndromes (associated with chronic mucocutaneous candidiasis and primary adrenal insufficiency)

Isolated hypoparathyroidism due to activating antibodies to calcium-sensing receptor

• Infiltration of the parathyroid gland (granulomatous, iron overload, metastases)
• Radiation-induced destruction parathyroid glands
• Hungry bone syndrome (post parathyroidectomy)
• HIV infection

Clinical presentations

• Associated with hypocalcemia
• Acute 
•  Neuromuscular irritability ranging from mild (peri-oral numbness, paresthesias of the hands and feet, muscle cramps) to severe (carpopedal spasm, laryngospasm, and focal or generalized seizures)

• Chronic 
• Basal ganglia calcifications: due to hyperphosphatemia and subsequently increased calcium phosphorus product deposited in tissue
• Cataracts
• Mood swings and/or personality disturbances, dental abnormalities, cardiovascular and skin manifestations (dry, puffy, and coarse)

• Chvostek sign: Twitching of ipsilateral facial muscle after tapping the muscles
• Trousseau sign: Muscle contraction of forearm after brachial artery compressed by a sphygmomanometer above systolic pressure
• Psychiatric disturbance and cardiac conduction defects (prolonged QT intervals)

Polyglandular autoimmune syndrome type 1

• AKA autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) or as Whitaker syndrome
• Very rare in the States, but shows clusters in Finns, Sardinians, and Iranian Jews
• Autoimmune multiple endocrine gland insufficiencies
• Associated with candidiasis, hypoparathyroidism, and adrenal failure
• 3 main types of autoantibodies: Against the surface receptor molecules, intracellular enzymes, and secreted proteins
• Monogeneic mutation of AIRE (autoimmune regulator)

Autosomal-dominant hypoparathyroidism

• Gain of function mutation of calcium-sensing receptor
• Overactive CaSR resulting in inhibition of PTH release even at low calcium level
• Majority asymptomatic
• Hypocalcemia and hypercalciuria, with normal or low PTH
• May have low serum magnesium
• Recurrent nephrolithiasis and nephrocalcinosis, particularly during treatment with vitamin D and calcium supplementation

Familial isolated hypoparathyroidism

• A group of extremely rare genetic disorders of hypoparathyroidism
• Classified based on genetic alterations: GCM2, pre-proPTH
• Hypocalcemia associated symptoms and signs: Fatigue, muscle weakness, twitching and cramping of the extremities, or spasms of the hands, feet, arms, or face
• Diagnosis based on clinical presentations, lab tests and molecular genetics
• Goal of treatment: Normalize calcium, with Vitamin D analogs etc

Diagnosis

• Persistent hypocalcemia
• Low or inappropriately normal parathyroid hormone (PTH) level
• Hyperphosphatemia
• Absence of hypomagnesemia

Treatment

• Symptom relieve
• Raise calcium
• Prevent iatrogenic kidney stone

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