3. Classification of PHP
Response
Gsα
Hypocalcemia, of Urinary Serum
Type Subunit AHO
Hyperphosphatemia cAMP to PTH
Deficiency
PTH
PHP-Ia Yes ↓ ↑ Yes Yes
PHP-Ib Yes ↓ ↑ No No
PHP-II Yes Normal ↑ No No
PPHP No Normal Normal Yes Yes
4. PHP-Ia
• Hypocalcemia, hyperphosphatemia, ↓urinary
cAMP, ↑ serum PTH, Gsa subunit deficiency
• Features of AHO:
– Short stature
– Round face
– Brachydactyly
– Heterotopic calcification
5. Inheritance and Genetic Patterns
GNAS-1 gene on
chromosome 20q
PHP-1a becomes manifest only in patients who inherit the defective gene
from an obligate female carrier (left). If the genetic defect is inherited from an
obligate male gene carrier, there is no biochemical abnormality;
administration of PTH causes an appropriate increase in the urinary cyclic
AMP and phosphate concentration. Both patterns of inheritance lead to
Albright's hereditary osteodystrophy (AHO)
6. PHP-1b
• Upstream deletions on maternal allele
• There is no Gsa in renal cortex but normal
expression in other tissues
• Hypocalcemia, hyperphosphatemia, ↓ urinary
cAMP, ↑ serum PTH
• May have excessive bone responsiveness
8. Treatment of PHP
• Lower doses of Vitamin D & calcium are
required than those required in true
hypoparathyroidism
• Establish optimal regimen for each patient
• Maintain appropriate blood calcium level (8.5
– 10.5mg/dl) & urinary calcium excretion
(100-250mg/24h)
10. Severe, Acute Hyperphosphatemia
• release of phosphate from muscle & impaired
phosphate excretion due to renal failure
• Hypocalcemia is reversed with tissue repair &
renal function restoration may lead to mild
hypercalcemia
• Other Causes: hypothermia, hepatic failure, &
hematologic malignancies
11. Treatment
• Lower blood phosphate through phosphate-
binding antacids or dialysis
• Calcium replacement is necessary in severe
hypocalcemia
12. Osteitis Fibrosis after
Parathyroidectomy
• Osteitis fibrosa cystica: rare manifestation of
hyperparathyroidism
• Characterized by bone pain & bone fragility &
brown tumor
• If severe, bone mineral deficits are large
• Hypocalcemia can persist for days after
parathyroidectomy if calcium replacement is
inadequate
14. • PTH level is central to the evaluation of
hypocalcemia
– A low PTH level → hypoparathyroidism
– Further history will often elicit the underlying
cause
– An elevated PTH level → secondary
hyperparathyroidism → vitamin D deficiency
– serum 25-hydroxyvitamin D levels (>20ng/ml)
15.
16. Treatment
• Acute, symptomatic hypocalcemia:
– calcium gluconate, 90 mg or 2.2 mmol IV, diluted in
50 mL of 5% dextrose or 0.9% sodium chloride,
given IV over 5 min
• Continuing hypocalcemia : constant IV infusion
(10 ampuls of ca or 900 mg of ca in 1 L of 5%
dextrose or 0.9% sodium chloride administered
over 24 h)
17. Treatment
• Hypomagnesemia: magnesium supplementation
• Chronic hypocalcemia due to
hypoparathyroidism:
– calcium supplements (1000–1500 mg/d elemental
calcium in divided doses) AND
– either vitamin D2 or D3 (25,000–100,000 U daily) OR
calcitriol [1,25(OH)2D, 0.25–2 g/d]
18. Treatment
• Vitamin D deficiency - vitamin D supplementation
• Nutritional vitamin D deficiency:
– low doses of vitamin D (50,000 U, 2–3 times per week
for several months)
• Vitamin D deficiency due to malabsorption:
– higher doses (100,000 U/d or more)
• Goal is to bring serum calcium into the low
normal range and to avoid hypercalciuria, which
may lead to nephrolithiasis
