Hypoparathyroidism is defined as reduced parathyroid hormone (PTH) levels due to poor function of the parathyroid glands. The cause of hypoparathyroidism is most commonly iatrogenic following neck surgery, but it can also be associated with genetic or autoimmune disorders as well as infiltrative diseases causing destruction of the normal parathyroid tissue. Deficiency of PTH results in hypocalcemia, which leads to increased neuromuscular excitability and osteosclerosis, as well as cardiac and neuropsychiatric manifestations. Treatment is based on calcium and vitamin D supplementation.

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Hypoparathyroidism is a condition associated with insufficient secretion of parathyroid hormone (PTH). Hypocalcemia and hyperphosphatemia are the pathognomonic biochemical features of hypoparathyroidism, and result directly from a lack of PTH action on the kidney.


  • Prevalence in the US is 37 per 100,000 person years
  • 74% of patients are 45 years or older.
  • More common in women (75%)


  • Iatrogenic (most common):
    • Thyro/parathyroidectomy
    • Neck dissection
    • Radiation
  • Idiopathic/familial hypoparathyroidism
  • Autoimmune parathyroid destruction: autoimmune polyendocrine syndrome type 1
  • Genetic: DiGeorge syndrome (triad of: conotruncal cardiac anomalies, hypoplastic thymus (→ T cell immunodeficiency), and hypocalcemia (from parathyroid hypoplasia))
  • Infiltrative disease of the parathyroid glands: 
    • Hemochromatosis
    • Wilson’s disease

Pathophysiology and Clinical Presentation


Normal physiology of PTH: 

  • Hormone produced by the parathyroid glands
  • Essential for the regulation of serum calcium (Ca) and phosphate levels
  • Regulates Ca and phosphate levels by:
    • Activation of osteoclasts: ↑ release of Ca and phosphate from bone
    • ↓ Excretion of renal Ca
    • ↑ Excretion of renal phosphate
    • ↑ Synthesis of 1,25-dihydroxyvitamin D, which increases intestinal Ca absorption

Effects of hypoparathyroidism: 

  • ↓ PTH → ↓ serum Ca levels (and ↑ phosphate levels)
  • Physiological effects are related to hypocalcemia:
    • Uninhibited activity of voltage-gated sodium (Na) channels
    • Increased neuromuscular irritability → tetany 
Parathyroid hormone (PTH) schematic diagram role and function

Parathyroid hormone has only one function: to correct hypocalcemia and maintain the serum level of calcium within narrow limits.
If the serum calcium is low, the four parathyroid glands secrete PTH, which is made and stored in the glands. When released, PTH works with and through vitamin D to restore the calcium level to normal.

Image by Lecturio.

Clinical presentation


  • Tetany (increased neuromuscular excitability):
    • Mild:
      • Perioral numbness
      • Paresthesias
      • Muscle cramps/spasms
    • Severe:
      • Carpopedal spasm
      • Laryngospasm
      • Seizures
  • Cardiac findings:
    • Prolongation of the QT interval
    • Arrhythmias
    • Hypotension
    • Heart failure
  • Neuropsychiatric symptoms:
    • Depression
    • Fatigue
    • Irritability/anxiety


  • Basal-ganglia calcifications:
    • Parkinsonism
    • Dementia
  • Coarse, brittle hair and dry skin
  • Tetanic cataracts (paradox intraocular lens calcification)
  • Decreased insulin secretion
  • Osteosclerosis, cortical thickening, craniofacial abnormalities
  • Dental abnormalities when hypocalcemia is present in early childhood
  • Idiopathic familial hypoparathyroidism may be associated with immune disorder and moniliasis.

Diagnosis and Management



  • Recent neck surgery/thyroidectomy/parathyroidectomy
  • Family history
  • Genetic syndromes

Physical exam:

  • Chvostek’s sign: Tapping on the facial nerve in the area of the cheek results in the twitching of the mouth musculature.
  • Trousseau’s sign: muscle spasms of the hand (“claw”) after BP-cuff inflation of the arm
  • Dry, puffy skin
  • Alopecia, thin/brittle hair

Laboratory studies:

  • ↓ Serum PTH levels
  • ↓ Ca and ↑ phosphate levels in serum
  • ↓ Phosphate levels in urine
  • Urine Ca level can be low or high depending on the degree of serum Ca correction.
  • Document normal levels of serum magnesium, creatinine, and 25-hydroxyvitamin D
Table: Laboratory findings associated with different causes of hypocalcemia
DiagnosisPTHPhosphateVitamin DMagnesiumClinical clues
HypoparathyroidismLowHighHigh/lowNormalHistory of neck surgery, irradiation, or autoimmune disease
Vitamin D deficiencyHigh or normalLowLow (25-hydroxyvitamin D)NormalBone tenderness, weakness, and osteomalacia
Hungry bone syndromeLowLowLowAcute bone uptake of Ca/P and Mg after parathyroidectomy
Magnesium deficiency (impaired PTH secretion and PTH resistance)Normal or lowNormalNormalLow
  • Diarrhea, loop and thiazide diuretics, alcohol use
  • Often associated with hypokalemia
  • Elevated creatine, BUN
  • Features of renal insufficiency
P: phosphate; Mg: magnesium; PTH: parathyroid hormone


Acute hypoparathyroidism:

  • Usually occurs post surgery
  • Severe symptoms or Ca ≤ 7.5 mg/dL:
    • Emergent treatment with IV Ca gluconate
    • Oral calcitriol (vitamin D)
    • Transition to oral Ca supplements when Ca > 7.5 mg/dL
  • Mild-to-moderate symptoms and Ca > 7.5 mg/dL:
    • Oral Ca supplements
    • Oral calcitriol (vitamin D)

Chronic hypoparathyroidism:

  • Usually occurs due to autoimmune or infiltrative disease, or post radiation
  • Insidious onset
  • Long-term vitamin D and Ca supplementation:
    • Need to measure urinary Ca excretion periodically to prevent hypercalciuria, nephrolithiasis, and nephrocalcinosis
    • Phosphate binders may be required.
  • Recombinant human PTH

Differential Diagnosis

  • Pseudohypoparathyroidism: an autosomal dominant disorder with end-organ resistance to PTH secondary to a mutation in G protein (GNAS). Parathyroid hormone is secreted normally, but kidneys and bones are resistant to its effects, which leads to hypocalcemia, hyperphosphatemia, and increased serum PTH levels. Treatment is with Ca and vitamin D supplementation.
  • Secondary hyperparathyroidism: secondary elevation of serum PTH due to hypocalcemia usually associated with CKD. Diagnosis is established based on elevated PTH levels in the setting of hypocalcemia and hyperphosphatemia. Management is focused on treating the underlying disease.
  • Hypomagnesemia: low serum magnesium levels. Hypomagnesemia causes hypocalcemia by impairing PTH release in response to low serum Ca levels as well as by inducing bone PTH resistance. Hypocalcemia responds promptly to the restoration of normal magnesium levels.


  1. Abate, E.G., Clarke, B.L. (2017). Review of Hypoparathyroidism. Front Endocrinol (Lausanne). 16(7),172. https://pubmed.ncbi.nlm.nih.gov/28138323/
  2. Goltzman, D. (2020). Hypoparathyroidism. Retrieved February 9, 2021, from https://www.uptodate.com/contents/hypoparathyroidism
  3. Gonzalez-Campoy, J.M. (2020). Hypoparathyroidism. Retrieved February 9, 2021, from https://emedicine.medscape.com/article/122207-overview
  4. Hans, S.K., Levine, S.N. Hypoparathyroidism. (2020). StatPearls. Retrieved February 9, 2021, from https://www.ncbi.nlm.nih.gov/books/NBK441899/

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