Hypoparathyroidism differential diagnosis

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Anmol Pitliya, M.B.B.S. M.D.[2]

Overview

Hypoparathyroidism should be differentiated from other causes of hypocalcemia. Causes of hypocalcemia other than hypoparathyroidism include pseudohypoparathyroidism, hypomagnesemia, hypovitaminosis D, chronic kidney disease, and relative hypocalcemia due to hypoalbuminemia.

Differentiating Hypoparathyroidism from other Diseases

Hypoparathyroidism should be differentiated from other causes of hypocalcemia. Causes of hypocalcemia other than hypoparathyroidism include:

• Pseudohypoparathyroidism
  • Pseudohypoparathyroidism type 1
    • Pseudohypoparathyroidism type 1a
    • Pseudohypoparathyroidism type 1b
    • Pseudohypoparathyroidism type 1c
    • Pseudopseudohypoparathyroidism
  • Pseudohypoparathyroidism type 2
• Hypomagnesemia
• Hypovitaminosis D
• Chronic kidney disease
• Hypoalbuminemia (relative hypocalcemia).

Differential diagnosis of hyperparathyroidism on the basis of hypocalcemia
Disorders		Mechanism of hypocalcemia	Laboratory findings
			Serum PTH	Serum Calcium	Serum Phosphate	Other findings
Hypoparathyroidism		There is deficiency of parathyroid hormone in hypoparathyroidism. Deficiency of parathyroid hormone causes body to decrease: Reabsorption of calcium from bone. Excretion of phosphate. Reabsorption of calcium from distal tubules. Vitamin D mediated absorption of calcium from intestine.	↓	↓	↑	↓ 1,25 Dihydroxy vitamin D Normal urinary cAMP Normal urinary phosphate
Pseudohypoparathyroidism	Type 1a	Genetic defect causing end organ resistance to the action of parathyroid hormone (PTH). Heterozygous GNAS inactivating mutations that reduce expression or function of Gαs	↑	↓	↑	↓ 1,25 Dihydroxy vitamin D ↓ Urinary cAMP ↓ Urinary phosphate
	Type 1b	Genetic defect causing end organ resistance to the action of parathyroid hormone (PTH). Familial- heterozygous deletions in STX16, NESP55, and/or AS exons or loss of methylation at GNAS	↑	↓	↑	↓ 1,25 Dihydroxy vitamin D ↓ Urinary cAMP ↓ Urinary phosphate
	Type 1c	Genetic defect causing end organ resistance to the action of parathyroid hormone (PTH). Heterozygous GNAS inactivating mutations that reduce expression or function of Gαs	↑	↓	↑	↓ 1,25 Dihydroxy vitamin D ↓ Urinary cAMP ↓ Urinary phosphate
	Type 2	Genetic defect causing end organ resistance to the action of parathyroid hormone (PTH).	↑	↓	↑	↓ ↓ 1,25 Dihydroxy vitamin D Normal urinary cAMP ↓ Urinary phosphate
	Pseudopseudohypoparathyroidism	Genetic defect causing end organ resistance to the action of parathyroid hormone (PTH). Combination of inactivating mutations of GNAS1 and Albright's osteodystrophy	Normal	Normal	Normal	--
Hypomagnesemia		Decreased parathyroid hormone (PTH) secretion. Skeletal resistance to parathyroid hormone.	Inappropriately ↓	Normal/↓	--	↓ Serum magnesium ↓/Normal serum potassium
Hypoalbuminemia		Majority of calcium in blood is bound to albumin. So, when there is a decrease in concentration of albumin due to any condition, there is a relative hypocalcemia as well.	--	↓	--	↓ Serum albumin Normal albumin-corrected serum total calcium Normal ionized calcium
Hypovitaminosis D		Decrease in vitamin D mediated calcium absorption from intestine.	↑	↓	↓/Low-normal	↓ 25 Hydroxy vitamin D
Chronic kidney disease		Chronic renal failure leads to high serum inorganic phosphate and low serum calcium and deficiency of active form of vitamin D (1,25-dihydroxy vitamin D/calcitriol)	↑	↓/Normal	↑	↓ Glomerular filtration rate