Hypoparathyroidism
Hasan 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
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:
– Decreased
Serum iPTH
• Increased values in a range appropriate to the degree of
hypocalcemia
– pseudohypoparathyroidism,
vit D deficiency,
dependency (end-organ resistance to PTH)
vit
D
– 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
Hypoparathyroidism
PO4
PTH
25-vit D
1,25 -Vit D
Normal
/N
Pseudohypoparathyroidism
Normal
/N
Liver disease
Renal disease
Normal
/N
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
dihydrotachysterol,
its
in
more
potent
combination
analog
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
Thank you!