Published on

  • Be the first to comment

  • Be the first to like this

No Downloads
Total views
On SlideShare
From Embeds
Number of Embeds
Embeds 0
No embeds

No notes for slide


  1. 1. Pseudohypoparathyroidism &Hypocalcemia due to PTH Overwhelmed Teena Luke 080201023
  2. 2. Pseudohypoparathyroidism (PHP)Hereditary disorder characterized by symptoms & signs of hypoparathyroidism, typically in association with distinctive skeletal and developmental defects
  3. 3. Classification of PHP Response Gsα Hypocalcemia, of Urinary Serum Type Subunit AHO Hyperphosphatemia cAMP to PTH Deficiency PTHPHP-Ia Yes ↓ ↑ Yes YesPHP-Ib Yes ↓ ↑ No NoPHP-II Yes Normal ↑ No NoPPHP No Normal Normal Yes Yes
  4. 4. PHP-Ia• Hypocalcemia, hyperphosphatemia, ↓urinary cAMP, ↑ serum PTH, Gsa subunit deficiency• Features of AHO: – Short stature – Round face – Brachydactyly – Heterotopic calcification
  5. 5. Inheritance and Genetic PatternsGNAS-1 gene onchromosome 20q PHP-1a becomes manifest only in patients who inherit the defective genefrom 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 Albrights hereditary osteodystrophy (AHO)
  6. 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
  7. 7. PHP-II• Hypocalcemia, hyperphosphatemia, normal urinary cAMP, ↑ serum PTH• Defect (in response to PTH) is at a locus distal to cyclic AMP production
  8. 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)
  9. 9. PTH Overwhelmed• Severe, Acute Hyperphosphatemia – Tumor lysis – Acute renal failure – Rhabdomyolysis• Osteitis Fibrosa after Parathyroidectomy
  10. 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. 11. Treatment• Lower blood phosphate through phosphate- binding antacids or dialysis• Calcium replacement is necessary in severe hypocalcemia
  12. 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
  13. 13. Diagnosis• Serum calcium level• Serum Albumin (3.5-5.3g/dL)• Serum Phosphorus (2.7-4.5mg/dL)• Serum Magnesium (0.7-1.0mmol/L)• Serum PTH: 10-65pg/ml
  14. 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. 15. 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)
  16. 16. 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]
  17. 17. 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