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Hypercalcemia

Related to Parathyroid gland

Unrelated to parathyroid gland

Primary hyperparathyroidism

Secondary hyperparathyroidism

Tertiary hyperparathyroidism

Typical primary hyperparathyroidism

Familial hypocalciuric hypercalcemia

Malignancy

Medication induced

Nutritional

Granulomatous disease

Surgical

Para-neoplastic syndrome: Parathyroid hormone related peptide

Metaplasia: Hypercalcemia due to bone destruction

Thiazide diuretics

Lithium

Milk alkali syndrome

Vitamin D toxicity

Sarcoidosis

Immobilization

Differential diagnosis

Hypoparathyroidism				Inheritance	Gene mutation	Clinical features
Autoimmune
Isolated		Familial Isolated hypoparathyroidism		Autosomal dominant	PTH gene
					GCM2 gene	Dominant negative mutation
				Autosomal recessive	PTH gene
					GCM2 gene
				X-linked	FHL1 gene (exon 4, c.C283T, p.R95W) on chromosome locus Xq26-q27.
		Autosomal dominant hypercalcemia	Autosomal dominant hypocalcemia type 1	Autosomal dominant	G protein G11 (GNA11) mutation	Calcium-sensing receptor gene activating mutation. Most common genetic form of hypoparathyroidism. Also known as familial hypercalciuric hypocalcemia. The activating mutation results in gain in function. Calcium-sensing receptor gene activating mutation can also cause Bartter syndrome type 5.This mutation cause the inhibition of apical potassium channel in the thick ascending limb of the loop of Henle in the kidney.
			Autosomal dominant hypocalcemia type 2	Autosomal dominant	G protein G11 (GNA11) mutation
Congenital multisystem syndromes		DiGeorge syndrome		Autosomal dominant	22q11.2 deletion.	Presents with thymus dysfunction, cardiac defects, immunodeficiency, hypocalcemia, and other clinical problems. Also known as 22q11.2DS, CATCH 22 syndrome, Cayler cardiofacial syndrome, conotruncal anomaly face syndrome (CTAF), deletion 22q11.2 syndrome, Sedlackova syndrome, Shprintzen syndrome, VCFS, velocardiofacial syndrome, and velo-cardio-facial syndrome. CATCH 22 stands for cardiac defects, abnormal facies, thymic aplasia, cleft palate, and hypocalcemia with 22q11.2 deletion.
		CHARGE syndrome		Autosomal dominant	CHD7 G744S missense mutation	Presents with coloboma, heart defects, atresia choanae, retarded growth and development, genitourinary abnormalities, and ear anomalies and/or deafness.
		Kenny-Caffey syndrome type 1		Autosomal recessive	Deletion of the TBCE gene	Presents with hypoparathyroidism due to absent parathyroid tissue, growth retardation, medullary stenosis of tubular bones.
		Kenny-Caffey syndrome type 2		Autosomal dominant	Mutation of “family with sequence similarity 111, member A″ (FAM111A) gene located on chromosome locus 11q12.1	Patients with Kenny-Caffey sundrome type 2 have same clinical features as Kenny-Caffey syndrome type 1 except for mental retardation.
		Sanjad-Sakati syndrome		Autosomal recessive	Mutation in TBCE gene.	Sanjad-Sakati syndrome in exclusively found in arabian descent population. Presents with hypoparathyroidism, intellectual disability, dysmorphism.
		Barakat syndrome		Autosomal recessive	Mutations in the GATA3 gene	Also known as hypoparathyroidism, deafness, and renal dysplasia (HDR) syndrome Presents with primary hypoparathyroidism, nerve deafness, steroid-resistant nephrosis.
Metabolic diseases	Mitochondiral polyneuropathies	Kearns–Sayre syndrome
		Maternally inherited diabetes and deafness (MIDD)
	Mitochondrial enzyme deficiencies	Mitochondrial trifunctional protein deficiency (MTP deficiency)
		Long-chain 3-hydroxyacyl-coenzyme A dehydrogenase deficiency (LCHAD deficiency)
	Heavy metal storage disorders	Hemochromatosis
		Wilson's disease