Hypoparathyroidism Hasan AYDIN, MD Endocrinology and Metabolism Yeditepe University Medical Faculty

Hypoparathyroidism Clinically Biochemically Symptoms of neuromuscular hyperactivity Biochemically hypocalcemia, hyperphosphatemia, diminished to absent circulating iPTH.

Etiology Surgical (most common) Familial Idiopathic Functional

Etiology Surgical hypoparathyroidism Idiopathic hypoparathyroidism Most common cause is neck surgery eg.total thyroidectomy Idiopathic hypoparathyroidism Age of onset is 2-10 years Female preponderance Circulating parathyroid antibodies common

Autoimmune hypoparathyroidism Component of autoimmune polyglandular syndrome Associated with primary adrenal insufficiency, mucocutaneous candidiasis Age of onset 5-9 years Familial hypoparathyroidism Autosomal dominant Mutation in PTH gene leads to defective PTH

Others Di George’s syndrome MEDAC syndrome (multiple endocrine deficiency, autoimmune candidiasis) HAM syndrome (hypoparathyroidism, Addison's disease, and mucocutaneous candidiasis) Congenital aplasia of the parathyroids Iron deposition in the glands Copper deposition Aluminum deposition Infiltration with metastatic carcinoma

Functional Hypoparathyroidism Long periods of hypomagnesemia selective gastrointestinal magnesium absorption defects generalized gastrointestinal malabsorption alcoholism. Serum PTH low Hypocalcemia (Mg is required for PTH release and peripheral action of PTH)

Clinical Features PTH deficiency leads to hypocalcemia Effects depend on severity and rate of drop Neuromuscular features: Paresthesias (perioral, fingertips) Muscle weakness and cramps, fasciculations Tetany (Chvostek’s and Trousseau’s signs)

Signs of Hypocalcemia Neuromuscular CNS CVS Ophtalmalogical Skin Dental GIS

Neuromuscular Manifestations Paresthesias Tetany Chvostek's sign. Trousseau's sign Hyperventilation Adrenergic symptoms anxiety, tachycardia, sweating, and peripheral and circumoral pallor Convulsions more common in young people: generalized form of tetany followed by prolonged tonic spasms; typical epileptiform seizure Extrapyramidal signs- Classic parkinsonism

Chvostek’s sign Elicited by tapping over facial nerve causing twitching of ipsilateral facial muscles

Trousseau’s sign Carpal spasm in response to inflation of BP cuff to 20 mm Hg above SBP for 3 min

Clinical Features CNS manifestations Depression Irritability Confusion Focal or generalized seizures

Clinical Features CVS manifestations Decreased myocardial contractility Hypotension Congestive heart failure CVS features seen particularly in patients with underlying cardiac disease, or those on digoxin or diuretics ECG: prolonged QT Laryngeal or bronchospasm (rare)

Other Clinical Manifestations Posterior lenticular cataract Dental manifestations Abnormalities in enamel formation Delayed or absent dental eruption Defective dental root formation with short or blunted roots Malabsorption syndrome

Diagnosis Serum Calcium: Decreased Serum Phosphorus: Increased Serum iPTH:

Serum iPTH Increased values in a range appropriate to the degree of hypocalcemia pseudohypoparathyroidism, vit D deficiency, vit D dependency (end-organ resistance to PTH) secondary hyperparathyroidism (dietary deficiency of calcium, intestinal malabsorption of calcium, or excessive intake of absorbable phosphate- containing drugs) Undetectable serum iPTH hypoparathyroidism functional hypoparathyroidism due to hypomagnesemia 

Laboratory Evaluation Hypocalcemia Corrected total calcium (mg/dL) = (measured total calcium mg/dL) + 0.8 (4.0 - measured albumin g/dL) PO4, Mg, iPTH, BUN/Cr, 25 (OH) Vit D, 1,25 (OH) vit D3, Alk Phos ECG: prolonged QT interval Skeletal X-rays Bone biopsy

Differential Diagnosis Calcium PO4 PTH 25-vit D 1,25 -Vit D Hypoparathyroidism Normal Pseudohypoparathyroidism /N Liver disease Renal disease

Differential for Hypocalcemia Vitamin D Deficiency Congenital rickets Malnutrition Malabsorption Liver disease Renal disease Acute on chronic RF Nephrotic syndrome Hypomagnesemia Sepsis Anticonvulsants (phenytoin, primidone) Pseudohypoparathyroidism PTH resistance Ca Chelation Hyperphosphatemia Citrate Free fatty acids Alkalosis Fluoride Poisoning

Treatment Physiologic replacement of PTH Pharmacologic doses of vitamin D (ergocalciferol or its more potent analog dihydrotachysterol, in combination with oral calcium administration) Diets low in phosphate (restriction of dairy products and meat) and oral aluminum hydroxide gels

Emergency Measures for Tetany Intravenous calcium (10-20 ml of a 10% solution of calcium gluconate (40 mg elemental calcium per 10 mL) Vitamin D Oral calcium 200 mg of elemental calcium (as the carbonate salt) every 2 hours and gradually increasing to 500 mg every 2 hours if necessary. Continuous calcium infusion (500 ml of 5% glucose and water containing 10 ml of 10% calcium gluconate is given over 6 hours initially) Anticonvulsive agents (phenytoin, phenobarbital)

Severe Hypocalcemia Hypocalcemia may be profound and resistant to treatment (“bone hunger” syndrome). 10 g of elemental calcium IV infusion over 24 hours 1,25(OH)2D3 (calcitriol [Rocaltrol]) in doses ranging from 0.5 to 2 µg daily

Marked Hypoparathyroidism Long-term vitamin D treatment dihydrotachysterol ( 1 mg is equivalent to about 120,000 units or 3 mg of vitamin D2), 4 mg/d as a single dose for 2 days, then 2 mg/d for 2 days, then 1 mg/d Ergocalciferol (vitamin D2 40,000 units/mg). Cholecalciferol metabolites calcifediol and calcitriol Calcium- total (dietary and supplemental) intake of 1 g or more of the element daily in patients under age 40 and 2 g in patient over age 40.

Complications Hypercalcemia Hypercalciuria

PTH Resistance Syndromes

Pseudohypoparathyroidism Abnormal target tissue responses receptor binding of the hormone final expression of the cellular actions of PTH Resistance to several other hormones (vasopressin, glucagon). Secretion of a biologically inert form of PTH, Circulating inhibitors of PTH action, An intrinsic abnormality of PTH receptors, Autoantibodies to the PTH receptor, 

Pseudohypoparathyroidism Rare familial disorder Target tissue resistance to PTH Hypocalcemia, hyperphosphatemia Increased parathyroid gland function Short stature and short metacarpal and metatarsal bones.

Pseudopseudohypoparathyroidism Developmental defects without biochemical abnormalities of pseudohypoparathyroidism. Lack evidence of PTH resistance 50% reduction in Gs alpha function Autosomal dominant

PsHP Type Ia (Albright Syndrome) Hypoparathyroidism, short stature, round facies, obesity, brachydactily, neck webbing, sc calcifications Defect in the function of Gs protein TSH, Glucagon, Gonadotropin resistance Autosomal dominant Intermittant hypocalcemia, elevated PTH, low urine Ca

Diagnosis Developmental abnormalities Serum calcium and phosphorus normal  pseudopseudohypoparathyroidism Hypocalcemia and hyperphosphatemia  pseudohypoparathyroidism Increased serum iPTH and markedly diminished phosphaturic and nephrogenous cAMP responses to PTH distinguish Serum phosphorus normal, low in a hypocalcemic patient  secondary hyperparathyroidism due to vitamin D or dietary calcium deficiency and intestinal malabsorption of calcium

T h a n k y o u !