Causes and Differential Diagnosis of Hypocalcemia -Recommendation Proposed by Expert Panel Supported by Ministry of Health, Labour and Welfare, Japan-

Abstract

Abstract. Serum calcium (Ca) level is maintained within a narrow range mainly by actions of parathyroid hormone (PTH) and 1,25-dihydroxyvitmain D [1,25(OH) 2 D]. While it is not rare to encounter hypocalcemia in clinical practice, there is currently no practical guideline for the differential diagnosis of hypocalcemia. We therefore propose flowcharts for the differential diagnosis of hypocalcemia and hypoparathyroidism, especially PTH-deficient hypoparathyroidism in which many genetic or other causes have been identified recently. Hypocalcemia can be divided into two categories, hypocalcemia with low serum phosphate level, and one with normal to elevated serum phosphate level. Deficient actions of 1,25(OH) 2 D, loss of Ca into urine, and deposition of Ca in bone or soft tissues are main causes of hypocalcemia with low to low normal serum phosphate level. Hypocalcemia with high normal to high serum phosphate level includes chronic renal failure and hypoparathyroidism. Hypoparathyroidism is subdivided into PTH-deficient hypoparathyroidism and pseudohypoparathyroidism. Recent investigations identified several causes of PTH-deficient hypoparathyroidism, including genetic abnormalities and parathyroid autoantibodies, which should be differentiated from idiopathic hypoparathyroidism. Physical and laboratory findings, the time of the onset of diseases and accompanying illness can be clues for identifying causes of PTH-deficient hypoparathyroidism.

A case of Adult onset Pseudohypoparathyroidism yet to be resolved: “No money no genetics”

“…JRPMS level are usually due to chronic renal disease, whereas the abiding cases are caused either by impaired PTH secretion such as in hypoparathyroidism or by resistance to its actions [16][17][18] . PHP is a genetic disorder related to increased secretion of PTH and target-tissue unresponsiveness to its biological actions, mainly in the proximal nephron.…”

“…PHP type 1a is characterized by hormone resistance accompanied with a cluster of developmental and somatic defects that are overall defined as AHO. Both PHP type 1b and PHP type 2 patients present with PTH resistance in the absence of AHO's phenotype but they differ since PHP type 1b patients fail to show adequate increases in the urinary excretion of either cAMP or phosphate while those with PHP type 2 exhibit normal urinary excretion of cAMP but an impaired phosphaturic response during Ellsworth-Howard test [17][18][19] . PHP type 2 is a very rare disorder that was first reported by Drezner et al in 1973 and until to date very few cases have been documented 20,21 .…”

Pseudohypoparathyroidism Type II in a Woman with a History of Thyroid Surgery

“…Parathyroid hormone (PTH) is a peptide hormone that controls the level of ionized calcium in the blood within a narrow range. An impairment of the PTH function induces changes in calcium homeostasis that lead to clinical problems associated with symptoms resulting from hypocalcemia (2). Hypocalcemic disorders can be divided into two categories: hypocalcemia with a low serum phosphate level and hypocalcemia with a normal to elevated serum phosphate level.…”

“…Hypocalcemic disorders can be divided into two categories: hypocalcemia with a low serum phosphate level and hypocalcemia with a normal to elevated serum phosphate level. The latter can be subdivided into PTH-deficient hypoparathyroidism and pseudohypoparathyroidism (PHP) without chronic renal failure (1,2).…”

“…PTH-deficient hypoparathyroidism primarily develops in patients undergoing total thyroidectomy (1,2). The risk of permanent hypocalcemia following thyroidectomy is related to the number of preserved parathyroid glands and the PTH level, and patients with PTH deficiency usually develop profound hypocalcemia if appropriate therapy with oral supplementation of calcium and activated vitamin D is not administered.…”