hypoparathyroidism hasan aydin, md endocrinology and metabolism yeditepe university medical faculty

HypoparathyroidismHasan AYDIN, MD

Endocrinology and Metabolism

Yeditepe University Medical Faculty

Hypoparathyroidism

• Clinically– Symptoms of neuromuscular hyperactivity

• Biochemically – hypocalcemia, – hyperphosphatemia, – diminished to absent circulating iPTH.

Etiology

• Surgical (most common)

• Familial

• Idiopathic

• Functional

Etiology

Surgical 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

• 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

Others

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:

– Decreased

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

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 !