endocrine and metabolic disorders
Hypocalcemia
Etiology of Hypocalcemia
Hypocalcemia has a number of causes, including Hypoparathyroidism Pseudohypoparathyroidism Renal disease Vitamin Ddeficiency and dependency Hypoparathyroidism is characterized by hypocalcemia and Risk factors for severe hypocalcemia after subtotal parathyroidectomy include Severe preoperative hypercalcemia Removal of a large adenoma Elevated alkaline phosphatase Evidence of osteitis fibrosa cystica on bone x-rays Chronic kidney disease is an uncommon sporadic or inherited condition in which the parathyroid glands are absent or atrophied. It manifests in childhood. The parathyroid glands are occasionally absent and thymic aplasia and abnormalities of the arteries arising from the brachial arches ( DiGeorge Syndrome ) are present. Other inherited forms include Pseudohypoparathyroidism is an uncommon group of disorders characterized not by hormone deficiency but by target organ resistance to PTH. Complex genetic transmission of these disorders occurs. Type Ia pseudohypoparathyroidism(Albright hereditary osteodystrophy) is caused by a mutation in the stimulatory Gs-alpha1 protein of the adenylyl cyclase complex (GNAS1). The result is failure of normal renal phosphaturic response or increase in urinary cAMP (cyclicadenosinemonophosphate) to PTH. Patients are usually hypocalcemic and hyperphosphatemic. Secondary hyperparathyroidism and hyperparathyroid bone disease can occur. Associated abnormalities include short stature, round facies, intellectual disability with calcification of the basal ganglia, shortened metacarpal and metatarsal bones, mild hypothyroidism, and other subtle endocrine abnormalities. Because only the maternal allele forGNAS1is expressed in the kidneys, patients whose abnormal gene is paternal, although they have many of the somatic features of the disease, do not have hypocalcemia, hyperphosphatemia, or secondary hyperparathyroidism; this condition is sometimes described as pseudopseudohypoparathyroidism. is less well known. Affected patients have hypocalcemia, Hyperphosphatemia , and secondary hyperparathyroidism but do not have the other associated abnormalities. Type II pseudohypoparathyroidismis even less common than type I. In affected patients, exogenous PTH raises the urinary cAMP normally but does not raise serum calcium or urinary phosphate. An intracellular resistance to cAMP has been proposed. Vitamin D Deficiency and Dependency are discussed in full elsewhere. Vitamin Dis ingested in foods naturally high invitamin Dor fortified with it. It is also formed in the skin in response to sunlight (ultraviolet light).Vitamin Ddeficiency may result from inadequate dietary intake or decreased absorption due to hepatobiliary disease or intestinal malabsorption. It can also result from alterations invitamin Dmetabolism as occur with certain drugs (eg,phenytoin,phenobarbital,rifampin) or from decreased formation in the skin due to lack of exposure to sunlight. Aging also decreases skin synthetic capacity. Decreased skin synthesis is an important cause of acquiredvitamin Ddeficiency among people who spend a great deal of time indoors, who live in high northern or southern latitudes, and who wear clothing that covers them completely or frequently use sun-blocking agents. Accordingly, subclinicalvitamin Ddeficiency is fairly common, especially during winter months in temperate climates among older adults. Older adults in residential elder care settings are at particular risk because of decreased skin synthetic capacity, undernutrition, and lack of sun exposure. In fact, most people with deficiency have both decreased skin synthesis and dietary deficiency. However, most clinicians feel that the significant dangers of skin cancer outweigh the as yet unproven risk of moderately lowvitamin Dlevels so increasing sun exposure or doing without sunblocks is not recommended;vitamin Dsupplements are readily available for patients with concerns. Vitamin Ddependency results from the inability to convertvitamin Dto its active form or decreased responsiveness of end-organs to adequate levels of active vitamin. Type Ivitamin D–dependent rickets (pseudovitamin D–deficiency rickets) is an autosomal recessive disorder involving a mutation in the gene encoding the 1-alpha-hydroxylase enzyme. Normally expressed in the kidney, 1-alpha-hydroxylase is needed to convert inactivevitamin Dto the active formcalcitriol. In type IIvitamin D–dependent rickets, target organs cannot respond tocalcitriol.Vitamin Ddeficiency, hypocalcemia, and severe hypophosphatemia occur. Muscle weakness, pain, and typical bone deformities can occur. Renal tubular disease, including proximal and distal renal tubular acidosis, can cause severe hypocalcemia due to abnormal renal loss of calcium and decreased renal conversion ofvitamin Dto active 1,25(OH)2D. Renal failure can result in diminished formation of 1,25(OH)2D due to Direct renal cell damage Suppression of 1-alpha-hydroxylase (needed for thevitamin Dconversion) by hyperphosphatemia Other causes of hypocalcemia include Acute Pancreatitis (when lipolytic products released from the inflamed pancreas chelate calcium) metabolism, and medications generally used to Treatment None Hungry bone syndrome (persistent hypocalcemia and hypophosphatemia occurring after surgical or medical correction of moderate to severe hyperparathyroidism in patients in whom serum calcium concentrations had been supported by high bone turnover induced by greatly elevated PTH—hungry bone syndrome has been described after parathyroidectomy, after renal transplantation, and rarely in patients with end-stage renal disease treated with calcimimetics) Hyperphosphatemia (causes hypocalcemia by poorly understood mechanisms; patients with renal failure and subsequent phosphate retention are particularly prone) Hypoproteinemia (reduces the protein-bound fraction of serum calcium; hypocalcemia due to diminished protein binding is asymptomatic—because ionized calcium is unchanged, this entity has been termed factitious hypocalcemia) Infusion ofgadolinium(may spuriously lower calcium concentration) Etiology (can cause relative Sepsis and Septic Shock due to suppression of PTH release and decreased conversion of 25(OH)D to 1,25(OH)2D Transfusion of>10 units of citrate-anticoagulated blood Use of radiocontrast agents containing the divalent ion-chelating agent ethylenediaminetetraacetate (EDTA—can decrease the concentration of bioavailable ionized calcium while total serum calcium concentrations remain unchanged) due to Medullary Thyroid Carcinoma . 