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

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

3. Etiology
Surgical (most common)
Familial
Idiopathic
Functional

4. 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

5. 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

6. 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

7. 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)

8. 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)

9. Signs of Hypocalcemia Neuromuscular CNS CVS Ophtalmalogical Skin
Dental
GIS

10. 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

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

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

13. Clinical Features CNS manifestations Depression Irritability Confusion
Focal or generalized seizures

14. 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)

15. 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

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

17. 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 

18. Laboratory Evaluation
Hypocalcemia
Corrected total calcium (mg/dL) = (measured total calcium mg/dL) (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

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

20. 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

21. 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

22. 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)

23. 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

24. 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.

25. Complications
Hypercalcemia
Hypercalciuria

26. PTH Resistance Syndromes

27. 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, 

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

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

30. 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

33. 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

34. T h a n k y o u !