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Updated: 6/18/2021

Pseudohypoparathyroidism

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https://devupload.orthobullets.com/topic/9029/images/pseudohypopth knuckles._moved.jpg
https://devupload.orthobullets.com/topic/9029/images/pseudohypopth hand_moved.jpg
https://devupload.orthobullets.com/topic/9029/images/knuckle-dimple_moved.jpg
https://devupload.orthobullets.com/topic/9029/images/round_face_moved.jpg
https://devupload.orthobullets.com/topic/9029/images/pphtph knuckles_moved.jpg
  • 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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