Updated: 6/18/2021

Pseudohypoparathyroidism

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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
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  • summary
    • Pseudohypoparathyroidism is a rare genetic metabolic bone disease caused by a defect in the GNAS1 protein that leads to a decreased response to PTH. Patients present with characteristic findings of short 4th and 5th metacarpals, round facies, short stature, and symptoms of hypocalcemia. 
    • Diagnosis is made based on physical examination findings, serum labs, and results of the Ellsworth-Howard test.
    • Treatment is medical management with oral calcium and 1alpha-hydroxylated vitamin D metabolites.
  • Etiology
    • 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
          • 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
          • 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
    • Labs
      Type
      Appearance
      PTH
      Calcium
      Phos
      Vitamin 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
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