Calcium homeostasis phosphate Calcium PTH Bone Resorption Kidney

Calcium homeostasis phosphate Calcium PTH Bone Resorption Kidney Ca reabsorption Negative feedback Kidney 1, 25(OH)D Intestine Ca absorption Calcium 3

Pathogenesis of hypocalcemia 1. Failure to secrete PTH. 2. Failure to respond to PTH. 3. Deficiency of vitamin D. 4. Failure to respond to vitamin D. 4

Etiology of hypocalcemia PTH deficiency (hypoparathyroidism) – – Surgical Radiation Idiopathic Functional (low Mg) PTH resistance – – – Pseudohypoparathyroidism Renal failure Drugs Vitamin D deficiency – Renal failure – Heredetary type 1 vitamin D dependant rickets Vitamin D resistance – Heredetary type 2 vitamin D dependant rickets Others 5

Etiology of hypocalcemia Low PTH levels (hypoparathyroidism) High PTH levels (secondary hyperparathyroidism) 1. PT destruction: 1. post-surgery 2. Radiation 3. autoimmune 1. 2. 3. 4. Vitamin D deficiency Renal failure Vitamin D resistance PTH resistance 1. 2. 5. Pseudohypoparathyroidism hypomagnesemia Drugs 6

Hypocalcemia – clinical features Mild (Ca 8 -8. 8 mg/dl) – usually asymptomatic. Moderate (Ca 7 -8 mg/dl) – Chvostek’s sign, Trousseau’s sign Severe (Ca < 7 mg/dl) – – – acute signs of neuromuscular irritability calcifications of basal ganglia. subcapsular cataract Papilledema abnormal dentition. 7

Hypocalcemic symptoms of increased neuromuscular irritability Chvostek’s sign, Trousseau’s sign. Parasthesia, muscle cramps. Tetany Seizures Prolonged QT on ECG. Laryngospasm, bronchospasm. 8

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Chvostek’s and Trousseau’s signs 10

Prolonged QT 11

Hypocalcemia - treatment Acute – depends on symptoms I. v. calcium gluconate correct hypomagnesemia if diagnosed. Persistent – oral treatment calcium vitamin D – vitamin D 2 1 -α- D 3. (1α hydroxycholecalciferol) calcitriol. 12

Etiology of hypocalcemia Low PTH levels (hypoparathyroidism) High PTH levels (secondary hyperparathyroidism) 1. PT destruction: 1. post-surgery 2. Radiation 3. autoimmune 1. 2. 3. 4. Vitamin D deficiency Renal failure Vitamin D resistance PTH resistance 1. 2. 5. Pseudohypoparathyroidism hypomagnesemia Drugs 13

PTH deficiency Hypoparathyroidism 1. Post surgical 2. Autoimmune Laboratory: Calcium Phosphate PTH 14

Post surgical hypoparathyroidism The most common cause of hypoparathyroidism in adults. Presumptive diagnosis for hypocalcemia for any patients with a surgical scar on the neck. Total thyroidectomy for cancer. Causes: Edema, hemorrhage to PT glands. Destruction of blood supply. Presenting symptoms: tetany 1 -2 post op. Usually transient (more than 50%), reversible. 15

PTH deficiency – Idiopathic hypoparathyroidism Isolated or part of polyglandular endocrinopathy type I. – – – Addison disease Hypogonadism Autoimmune thyroid D. M. type 1 Mucocutaneus candidiasis Aqcuired – age 2 -10. Circulating parathyroid antibodies common. Women > men 16

1 מיקרה PTH 5 pg/ml (12 -72) Diagnosis: hypoparathyroidism – post surgical. Treatment: acute - intravenous calcium persistent - 1 -α- D 3 calcium 18

Etiology of hypocalcemia Low PTH levels (hypoparathyroidism) High PTH levels (secondary hyperparathyroidism) 1. PT destruction: 1. post-surgery 2. Radiation 3. autoimmune 1. 2. 3. 4. Vitamin D deficiency Renal failure Vitamin D resistance PTH resistance 1. 2. 5. Pseudohypoparathyroidism hypomagnesemia Drugs 19

Secondary causes of hyperparathyridism Vitamin D Calcium Phsophate PTH 20

Etiology of hypocalcemia Low PTH levels (hypoparathyroidism) High PTH levels (secondary hyperparathyroidism) 1. PT destruction: 1. post-surgery 2. Radiation 3. autoimmune 1. 2. 3. 4. Vitamin D deficiency Renal failure Vitamin D resistance PTH resistance 1. 2. 5. Pseudohypoparathyroidism hypomagnesemia Drugs 21

Vitamin D metabolism 22

Vitamin D Metabolism • Normal vitamin D >20 ng/dl • Vitamin D deficiency <8 ng/dl 23

Vitamin D deficiency - etiology: 25 (OH)D deficiency 1. Cutaneus 1. 2. 3. 4. 5. 2. 3. Clothes Sunscreens Melanin Latitude season Dietary absence Malabsorption Impaired 25 hydroxylation liver diseases-severe Impaired 1 alpha hydroxylation 1. renal failure 2. enzyme mutations I) 3. oncogenic osteomalacia Target organ resistance receptor mutation (II) 24

: מצב שכיח - D חסר ויטמין . 20 -80% בעבודות שונות שכיחות נעה בין NEJM 3/98, Thomas Boston, 290 medical inpatients 57% high risk: diet, winter, housebound also in low risk: age<65 42% multivitamins - 46% 60 -83% שכיחות גבוהה בארצות מזרח תיכוניות . 24 -35% – ישראל 26

25(OH)D deficiency - laboratory 25(OH)Vitamin D Calcium P PTH bone kidneys intestine ALP 28

2 מיקרה PTH – 238 pg/ml (12 -72) 25(OH)D 3 – 5 ng/dl (20 -46) Diagnosis: secondary hyperparathyroidism vitamin D deficiency Treatment ? 30

Etiology of hypocalcemia Low PTH levels (hypoparathyroidism) High PTH levels (secondary hyperparathyroidism) 1. PT destruction: 1. post-surgery 2. Radiation 3. autoimmune 1. 2. 3. 4. Vitamin D deficiency Renal failure Vitamin D resistance PTH resistance 1. 2. 5. Pseudohypoparathyroidism hypomagnesemia Drugs 32

Hypocalcemia in chronic renal failure Phosphate PTH 1. 1, 25(OH)2 D 2. 3. Calcium bone resistance to PTH actions reduced VDR and Ca. SR on PT gland 33

Evaluation of hypocalcemia 34