Hypoparathyroidism

Background

• Hypoparathyroidism is a rare condition characterized by absent or inappropriately low parathyroid hormone resulting in hypocalcemia and serum phosphate levels in the upper normal or elevated range.
• The most common cause of hypoparathyroidism is surgery-associated removal of, damage to, or devascularization of parathyroid tissue.
• Clinical presentation of hypoparathyroidism can vary from an asymptomatic laboratory finding (even in the setting of severe hypocalcemia) to a severe, life-threatening condition, with symptoms of hypocalcemia due to both serum level and rate of change of serum calcium levels.
• Complications of hypoparathyroidism include (but are not limited to) nephrolithiasis, nephrocalcinosis, ischemic heart disease, cataracts, and extrapyramidal signs due to calcification of basal ganglia.

Evaluation

• Perform blood testing for diagnosis:
  • calcium with either total calcium (corrected for albumin) or ionized calcium
  • concurrent parathyroid hormone (PTH)
  • magnesium (hypomagnesemia can cause functional hypoparathyroidism)
• Perform electrocardiography (ECG) to assess for potential changes associated with hypoparathyroidism.
• If hypoparathyroidism is confirmed:
  • Blood tests include:
    • phosphate
    • creatinine (to calculate estimated glomerular filtration rate)
    • 25-hydroxyvitamin D
    • 1,25-dihydroxyvitamin D (in patients where absorption or compliance of active vitamin D metabolites are a concern and parenteral administration is being considered)
  • Consider urine studies, such as 24-hour urine calcium and supersaturation or stone profile (such as citrate, oxalate, urate) as a baseline.
  • Consider target organ imaging:
    • Kidney imaging (kidney ultrasound or computed tomography scanning) is recommended for patients with symptoms of nephrolithiasis (kidney stones) or if serum creatinine levels begin to rise.
    • Brain computed tomography should only be performed in patients with unexplained neurological manifestations to assess for basal ganglia and other intracerebral calcifications.
    • Bone mineral density measurement by dual-energy x-ray absorptiometry is suggested in patients taking parathyroid hormone therapy or who have fragility fractures.
• Consider genetic testing to confirm suspected genetic causes of hypoparathyroidism or if the patient presents with hypoparathyroidism of unknown etiology.

Management

• Acute management of hypoparathyroidism may be required.
  • Indications for IV calcium include:
    • symptomatic/severe hypocalcemia or persistent hypocalcemia due to an ongoing process
    • requirement for rapid correction, such as a patient with cardiac arrhythmias due to prolonged QT intervals or laryngospasm
  • For patients with transient postsurgical hypoparathyroidism, treat with calcium and calcitriol (if needed) (Weak recommendation).
• Management of permanent (chronic) hypoparathyroidism:
  • Indications:
    • Treat all patients with chronic hypoparathyroidism who have hypocalcemia symptoms and/or total calcium (corrected for albumin) or ionized calcium below the lower limit of normal (Strong recommendation).
    • Consider offering treatment for patients with chronic hypoparathyroidism who are asymptomatic and with total calcium (corrected for albumin) between 8 mg/dL (2 mmol/L) and lower limit of normal in order to determine if this might improve well-being (Weak recommendation).
  • Conventional therapy:
    • Administer oral calcium supplementation (in divided doses) and vitamin D analogs ("active" or "activated" vitamin D such as calcitriol or alfacalcidol) as primary therapy (Strong recommendation).
    • Oral calcium supplements of choice are calcium carbonate (taken with meals) and calcium citrate (taken with or without meals).
    • For patients managed with vitamin D analog, add vitamin D3 (cholecalciferol) or vitamin D2 (ergocalciferol) 400-800 units/day (Strong recommendation) to ensure adequate 25-hydroxyvitamin D levels.
    • Vitamin D3 and vitamin D2 used alone without vitamin D analog is typically not preferred; if vitamin D analogs are unavailable, treat with high dose calciferol (preferentially with vitamin D3 [cholecalciferol]).
    • Titrate vitamin D analog, vitamin D3, or vitamin D2 so the patient is without hypocalcemia symptoms and serum calcium levels are maintained within the target range (Strong recommendation).
  • Consider parathyroid hormone replacement with recombinant PTH 1-84 for management of hypoparathyroidism in patients who are not well-controlled with calcium supplementation and vitamin D analog.
  • Consider additional medications based on clinical presentation, including hypomagnesemia, hypercalciuria, or hyperphosphatemia.
• Follow-up:
  • Assess for symptoms of hypocalcemia or hypercalcemia at regular intervals (every 3-6 months).
  • Evaluate quality of life, well-being, and symptoms every 3-6 months.
  • Monitor:
    • serum electrolyte levels (using tests such as phosphate and magnesium, in addition to calcium)
    • kidney function (using blood tests such as serum creatinine and calculation of estimated glomerular filtration rate)
    • risk for or presence of hypercalciuria, nephrocalcinosis, and nephrolithiasis (using urine studies and kidney imaging)
    • bone mineral density, especially in pati