1. Hypoparathyroidism Objectives of this lecture Causes Clinical features Diagnosis and lab. findings Differential diagnosis Treatment

2. Hypoparathyroidism AETIOLOGY In the neonate it may be due to functional immaturity of the parathyroid glands early neonatal hypocalcemia: Hypocalcemia is common between 12 and 72 hr of life, (premature infants, in infants with asphyxia, and in infants of diabetic mothers) late neonatal hypocalcemia: After the 2nd to 3rd day and during the 1st wk of life, depending on the type of feeding( artificial)

3. PARATHYROID HORMONE (PTH) DEFICIENCY Aplasia or hypoplasia of parathyroids DiGeorge syndrome maternal diabetes mellitus X-linked isolated hypoparathyroidism Suppression of neonatal PTH secretion due to maternal hyperparathyroidism Autosomal dominant Autoimmune parathyroiditis type 1 autoimmune polyendocrinopathy Infiltrative lesions: Hemosiderosis (treatment of thalassemia), Copper deposition ( wilson disease) SURGICAL HYPOPARATHYROIDISM PTH RECEPTOR DEFECTS (PSEUDOHYPOPARATHYROIDISM) Type 1a With gonadotropin-independent precocious puberty,Type 1b Type 2

4. Clinical Manifestations: *There is a spectrum of parathyroid deficiencies with clinical manifestations varying from no symptoms to those of complete and long-standing deficiency. Mild deficiency may be revealed only by appropriate laboratory studies. Muscular pain and cramps are early manifestations; they progress to numbness, stiffness, and tingling of the hands and feet. There may be only a positive Chvostek or Trousseau sign or the patient may have carpopedal and laryngeal spasms. Convulsions with or without loss of consciousness may occur at intervals of days, weeks, or months.These episodes may begin with abdominal pain, followed by tonic rigidity, retraction of the head, and cyanosis. Hypoparathyroidism is frequently mistaken for epilepsy. Headache, vomiting, increased intracranial pressure, and papilledema may be associated with convulsions and may suggest a brain tumor.

5. Mucocutaneous candidiasis, when present, antedates the development of hypoparathyroidism; the candidal infection most often involves the nails, the oral mucosa, the angles of the mouth, and less often, the skin; it is difficult to treat. *Cataracts in patients with long-standing untreated disease are a direct consequence of hypoparathyroidism. * Manifestations of Addison disease, lymphocytic thyroiditis, pernicious anemia, alopecia areata or totalis, hepatitis, and primary gonadal insufficiency may also be associated with those of hypoparathyroidism. *Permanent physical and mental deterioration occur if initiation of treatment is delayed.

6. Laboratory Findings: S.Ca ++ : low (5–7 mg/dL), Blood levels of ionized calcium (usually approximately 45% of the total) are low. S.Ph: elevated (7–12 mg/dL). S.alkaline phosphatase: normal or low 1,25[OH] 2 D 3 is usually low, but high levels have been found in some children with severe hypocalcemia. S.Mg is normal but should always be checked in hypocalcemic patients. Levels of PTH are low when measured by immunometric assay. Radiographs of the bones occasionally reveal an increased density limited to the metaphyses, suggestive of heavy metal poisoning.

7. Radiographs or CT scans of the skull may reveal calcifications in the basal ganglia. ECG :There is a prolongation of the QT interval, which disappears when the hypocalcemia is corrected. EEG: reveals widespread slow activity; the tracing returns to normal after the serum calcium concentration has been within the normal range for a few weeks, unless irreversible brain damage has occurred or unless the parathyroid insufficiency is associated with epilepsy.

8. Treatment: *Emergency treatment of neonatal tetany consists of intravenous injections of 5–10 mL of a 10% solution of calcium gluconate at the rate of 0.5–1 mL/min while the heart rate is monitored. *Older children IV calcium gluconate 1 ml/Kg/dose untill spasm relieved and then the dose reduced to 0.5 ml/Kg/dose every 6-8 hours. *Additionally, 1,25-dihydroxycholecalciferol (calcitriol) should be given. The initial dosage is 0.25 μg/24 hr; the maintenance dosage ranges from 0.01–0.10 μg/kg/24 hr Calcitriol has a short half-life and should be given in 2 equal divided doses; it has the advantages of rapid onset of effect (1–4 days) and rapid reversal of hypercalcemia after discontinuation in the event of over dosage (calcium levels begin to fall in 3–4 days).

9. *An adequate intake of calcium should be ensured. Supplemental calcium can be given in the form of calcium gluconate or calcium glubionate to provide 800 mg of elemental calcium daily, but it is rarely essential. Sometimes calcium carbonate used as phosphate binding agent *Foods with high phosphorus content such as milk, eggs, and cheese should be reduced in the diet. *Clinical evaluation of the patient and frequent determinations of the serum calcium levels are indicated in the early stages of treatment to determine the requirement for calcitriol or vitamin D 2. If hypercalcemia occurs, therapy should be discontinued and resumed at a lower dose after the serum calcium level has returned to normal. *Pigmentation, lowering of the blood pressure or weight loss may indicate adrenal insufficiency, which requires specific treatment.

10. Differential Diagnosis: Magnesium deficiency must be considered in patients with unexplained hypocalcemia. Concentrations of serum magnesium less than 1.5 mg/dL (1.2 mEq/L) are usually abnormal. CAUSES: *Familial hypomagnesaemia with secondary hypocalcemia *Hypomagnesemia also occurs in malabsorption syndromes such as Crohn disease and cystic fibrosis. *Patients with autoimmune polyglandular disease type I and hypoparathyroidism may also have concurrent steatorrhea and low magnesium levels. *Therapy with aminoglycosides causes hypomagnesemia by increasing urinary losses. It is not clear how low levels of magnesium lead to hypocalcemia. Evidence suggests that hypomagnesemia impairs release of PTH and induces resistance to the effects of the hormone.

11. Pseudohypoparathyroidism (Albright Hereditary Osteodystrophy) (PHP) *the parathyroid glands are normal or hyperplastic and they can synthesize and secrete parathyroid hormone (PTH). *Serum levels of immunoreactive PTH are elevated even when the patient is hypocalcemic and may be elevated when the patient is normocalcemic. *Neither endogenous nor administered PTH raises the serum levels of calcium or lowers the levels of phosphorus. *The genetic defects in the hormone receptor adenylate cyclase system are classified into various types depending on the phenotypic and biochemical findings. pseudopseudohypoparathyroidism : Some affected members may have the usual anatomic stigmata of PHP, but serum levels of calcium and phosphorus are normal, however PTH levels may be slightly elevated.