Updated: 10/10/2016

Pseudohypoparathyroidism

Topic
Review Topic
0
0
Cases
1
https://upload.orthobullets.com/topic/9029/images/mas.jpg
https://upload.orthobullets.com/topic/9029/images/pseudohypopth knuckles._moved.jpg
https://upload.orthobullets.com/topic/9029/images/pseudohypopth hand_moved.jpg
https://upload.orthobullets.com/topic/9029/images/knuckle-dimple_moved.jpg
https://upload.orthobullets.com/topic/9029/images/round_face_moved.jpg
https://upload.orthobullets.com/topic/9029/images/pphtph knuckles_moved.jpg
Introduction
  • Rare genetic disorder
  • Mechanism
    • PTH resistance
      • decreased target cell response to PTH 
Classification
  • Type 1a - Albright hereditary osteodystrophy 
    • defect in GNAS1 (Gsα protein)
      • defective gene from mother
      • upstream defect 
        • proximal to formation of cAMP
    • skeletal defects
      • short 4th, and 5th metacarpals and metatarsals or short 4th metacarpal only   
        • "knuckle, knuckle, dimple, dimple" sign on closed fist
        • differentials
          • Turner syndrome
            • short 4th metacarpal only  
            • "knuckle, knuckle, dimple, knuckle"
          • Down syndrome
            • short middle phalanx
      • brachydactyly
      • exostoses
    • round facies  
    • obesity 
    • short stature
    • diminished intelligence
  • Type 1b
    • defect in GNAS1 (Gsα protein)
    • normal appearance
  • Type 2
    • unknown gene defect
    • downstream defect
      • distal to formation of cAMP
    • normal appearance
Presentation
  • Symptom
    • symptoms of hypocalcemia
      • paresthesia 
        • fingertip, toes, perioral
      • abdominal pain, biliary colic
      • muscle cramps, tetany
      • dyspnea (laryngospasm, bronchospasm)
      • convulsions
      • mental status changes 
        • anxiety, fatigue, mood swings
  • Physical exam
    • findings of tetany
      • Trousseau's Sign post
        • carpopedal spasm after blood pressure readings
          • inflate BP cuff 20mmHg above systolic BP x 3-5min
        • hand adopts a MCP flexed, DIP and PIP extended position
        • more sensitive than Chvostek's sign 
      • Chvostek's Sign post
        • facial muscle contractions after tapping on the facial nerve
    • dermatologic 
      • fungal nail infections
      • hair loss
      • blotchy skin
        • pigment loss, vitiligo
Evaluation
  • Laboratory
    • high PTH
    • low calcium
    • high phosphate
    • low vit D
  • Ellsworth-Howard test
    • method to differentiate type 1 and type 2 by administering exogenous PTH 
      • Type 1
        • will show no increase in urinary cAMP and phosphate
      • Type 2
        • will show increased excretion of urinary cAMP and phosphate
Differential
  • Causes of hypocalcemia
    • renal osteodystrophy (low Ca, high PTH, high phosphate, high ALP)
    • hypoparathyrodism (low Ca, low PTH, high phosphate)
    • pseudopseuodohypoparathyroidism
      • mechanism
        • no PTH resistance
        • normal target cell response to PTH 
      • genetics
        • defect in GNAS1 (Gsα protein)
        • defective gene from father
      • skeletal defects
        • also has short 4th metacarpal and metatarsal 
        • metastatic calcification  
      • laboratory
        • normal PTH
        • normal calcium
        • normal phosphate
        • normal vit D
    • decreased vitamin D3
Type
Appearance
PTH
Calcium Phos Vit D Response to PTH administration Genetics
Hypoparathyroidism Normal
- -
Pseudohypoparathyroidism Type 1a
Skeletal defects
no increase in urinary cAMP or phosphate

GNAS1 (maternal defect, upstream)

Pseudohypoparathyroidism Type 1b Normal
  GNAS1 and STX16
Pseudohypoparathyroidism Type 2 Normal
increased urinary cAMP and phosphate GNAS1 (downstream)
Pseudopseudohypoparathyroidism Skeletal defects
N
N
N
N
  GNAS1 (paternal defect)
 
Treatment
  •  Nonoperative
    • oral calcium and 1alpha-hydroxylated vitamin D metabolites
      • indications
        • all patient with pseudohypoparathyroidism
    • IV calcium replacement
      • indications
        • patients with severe symptoms of hypocalcemia
 

Please rate topic.

Average 3.4 of 10 Ratings

Thank you for rating! Please vote below and help us build the most advanced adaptive learning platform in medicine

The complexity of this topic is appropriate for?
How important is this topic for board examinations?
How important is this topic for clinical practice?
CASES (1)
Topic COMMENTS (3)
Private Note