Calcium Homeostasis Calcium Homeostasis n n n 99

Calcium Homeostasis

Calcium Homeostasis n n n 99% body calcium in skeleton 0. 9 % intracellular 0. 1% extracellular n 50% bound n Mostly albumin (alkalosis) n Smaller amount phosphorous and citrate

Calcium Regulation n PTH n n 4 parathyroid glands Release PTH in response to drop in serum calcium Magnesium needed to activate PTH release Effects on bone, kidney and indirectly on intestines n Activates osteoclasts/osteoblasts leading to bone resorption and release of calcium and phosphorous n Promotes reabsorption of calcium and excretion of phosphorous in the kidney n Activates vitamin D

Calcium Regulation n Vitamin D n 2 sources n n 25 (OH) Vitamin D n n n Skin and Diet Storage form Vitamin D Liver 1, 25 (OH) Vitamin D n n Active form Vitamin D Activated by PTH and hypophosphatemia through 1 alpha hydroxylase in the kidney

Calcium Regulation n 1, 25 (OH) Vitamin D n Small intestine n n Bone n n Activates osteoblasts/osteoclasts leading to bone resorption and release of calcium and phosphorous Parathyroid Gland n n Promotes absorption of calcium and phosphorous Decrease PTH m. RNA Kidney n Calcium and phosphate excretion

Calcium Homeostasis n Calcitonin n n Little role in calcium homeostasis Secreted by C cells Neural cell origin Medullary Hyperplasia/Cancer Most sporadic case n MEN IIA or IIB n n 15 % cases

Etiology of Hypercalcemia n Hyperparathyroidism n Primary n n Adenoma Hyperplasia Carcinoma Other Forms n n n Familial Hypocalciuric Hypercalcemia Lithium therapy Tertiary hyperparathyroidism

Hypercalcemia n n n Malignancy Granulomatous Disease Endocrinopathy n n Drug induced n n Thyrotoxicosis, adrenal insufficieny, pheochromocytoma (ectopic PTH secretion) Vitamin A and D, Milk-Alkali syndrome, Thiazide diuretics Immobilization n Paget’s

Primary Hyperparathyroidism n n n Most common cause hypercalcemia in ambulatory setting Incidence 1/500 Results from inappropriate secretion PTH by one or more glands 85% cases due to single parathyroid adenoma 15% cases due to hyperplasia

Primary Hyperparathyroidism Clinical Presentation n Asymptomatic n n Elevated calcium on routine labs History kidney stones, unexpected fracture/ osteopenia/osteoporosis

Primary Hyperparathyroidism n Evaluation/Diagnosis n n n Elevated calcium and i-PTH, low or normal phosphorous Alkaline phosphatase Creatinine 24 hour urine calcium/creatinine Renal US Bone Density

Primary Hyperparathyroidism n Treatment n Surgical n Indication for parathyroidectomy n n n 1 mg/dl above labs upper limit of normal Signs/symptoms hypercalcemia Kidney stones Hypercalciuria Minimally Invasive n PTH monitored intraoperatively

Primary Hyperparathyroidism n Medical Treatment n n n Monitor Hydration In general calcium intake should not be restricted Vitamin D supplementation Newer agents n cinacalcet, bisphonates

Hypocalcemia PTH deficiency n acquired n Thyroidectomy n Parathyroidectomy n Hypomagnesemia n Irradiation n Infiltrative n Developmental defect of parathyroid glands (Di. George) n Autosomal dominant hypocalcemia (activating mutation of calcium receptor gene)

Hypocalcemia n PTH Resistance n Pseudohypoparathyroidism n Congenital defect n Absent metacarpal, short stature, round face, mental disability n Target organ unresponsiveness to PTH n Serum PTH levels high

Hypocalcemia Vitamin D n Deficiency n Nutritional deficiency and lack of skin exposure n Osteomalacia n n Adult Proximal muscle weakness n Rickets Type 1 n Hereditary vitamin D deficiency due to lack of 1 -alpha hydroxylase n Renal insufficiency

Hypocalcemia Vitamin D n Resistance n Rickets Type II n Target organ unresponsiveness to vitamin D due to defect in receptor

Hypocalcemia Calcium Deposition n Extravascular Deposition n n Hyperphosphatemia due to tumor lysis, rhabdo, renal failure Pancreatitis “Hungry bone syndrome” Intravascular deposition n n Citrate in blood transfusion lactate

Hypocalcemia n Treatment n Calcium n n Vitamin D n n PO vs IV 25 and/or 1, 25 (OH) Vitamin D Magnesium