Can sarcoidosis lead to hypercalcemia?

Hypercalcemia in sarcoidosis occurs due to excess unregulated 1,25(OH)2D synthesized in macrophages in granulomas. There is a positive correlation between 25(OH)D levels (reflecting vitamin D intake) and the circulating concentration of 1,25(OH)2D. This is normally not the case as there is no increase in 1,25(OH)2D with increasing 25(OH)D levels due to multiple feedback controls on renal 1α-hydroxylase. These controls are lost in granulomatous diseases like sarcoidosis.

↑ 1,25(OH)2D , ↓ PTH → hypercalciuria

Treatment is to ↓ intake of vitamin D, avoid excessive sunlight exposure, and hydrocortisone. Hypercalcemia of sarcoidosis is usually associated with disseminated disease. Almost all have abnormal chest X-ray (CXR). Sarcoidosis is unlikely as a cause of hypercalcemia, if CXR is normal. Hypergammaglobu- linemia is a clue to the disease.

William’s Syndrome

It is an autosomal dominant disorder characterized by Elfin facies, mental retardation, supravalvular aortic stenosis. The hypercalcemia is due to abnormal sensitivity to vitamin D. Increased levels of 1,25(OH)2D are seen.

Vitamin A Intoxication

This is an uncommon cause for hypercalcemia and is usually due to dietary faddism. It is presumed to be due to increased bone resorption. Periosteal calcifications, especially in hands may be seen. Diagnosis is by elevated serum vitamin A levels. Treatment includes stopping vitamin A intake and hydrocortisone.

Thiazides

Thiazide diuretics like hydrochlorothiazide induce hypocalciuria due to increased proximal tubular resorption of Na and Ca in response to sodium depletion. They can cause hypercalcemia in patients with high rates of bone turnover which is usually mild.

Immobilization

Hypercalcemia is seen with prolonged immobilization, especially after spinal cord injury and paraplegia or quadriplegia. This is more common in children or adolescents.

Hyperthyroidism

Hypercalciuria is more common than hypercalcemia. Mild hypercalcemia occurs in around 20% of patients.

Aluminum Intoxication

This is nowadays no longer seen. It used to occur in patients on chronic hemodialysis with aluminum in the dialysis regimen. Patients may present with acute dementia, unresponsive and severe osteomalacia with bone pain, multiple fractures, especially of ribs and pelvis and proximal myopathy. When these patients on chronic hemodialysis are treated with vitamin D, hypercalcemia results. Aluminum is present at the site of osteoid mineralization but osteoblastic activity is minimal. The calcium incorporation into the skeleton is impaired in these individuals. Treatment is to avoid aluminum excess in the dialysis regimen and deferoxamine.

Milk Alkali Syndrome

This is a triad of hypercalcemia, metabolic alkalosis and renal insufficiency. The chronic form of the disease associated with irreversible renal damage is known as Burnett syndrome. It results due to excessive ingestion of Calcium via absorbable antacids (e.g. milk, CaCO3). Investigations reveal ↑HCO3, ↑Serum creatinine, and decreased chloride.