Pseudohypoparathyroidism pathophysiology

Jump to: navigation, search

Pseudohypoparathyroidism Microchapters

Home

Patient Information

Overview

Historical Perspective

Classification

Pathophysiology

Causes

Differentiating Pseudohypoparathyroidism from other Diseases

Epidemiology and Demographics

Risk Factors

Screening

Natural History, Complications and Prognosis

Diagnosis

Diagnostic Criteria

History and Symptoms

Physical Examination

Laboratory Findings

Electrocardiogram

X Ray

CT

MRI

Echocardiography or Ultrasound

Other Imaging Findings

Other Diagnostic Studies

Treatment

Medical Therapy

Surgery

Primary Prevention

Secondary Prevention

Cost-Effectiveness of Therapy

Future or Investigational Therapies

Case Studies

Case #1

Pseudohypoparathyroidism pathophysiology On the Web

Most recent articles

Most cited articles

Review articles

CME Programs

Powerpoint slides

Images

American Roentgen Ray Society Images of Pseudohypoparathyroidism pathophysiology

All Images
X-rays
Echo & Ultrasound
CT Images
MRI

Ongoing Trials at Clinical Trials.gov

US National Guidelines Clearinghouse

NICE Guidance

FDA on Pseudohypoparathyroidism pathophysiology

CDC on Pseudohypoparathyroidism pathophysiology

Pseudohypoparathyroidism pathophysiology in the news

Blogs on Pseudohypoparathyroidism pathophysiology</small>

Directions to Hospitals Treating Pseudohypoparathyroidism

Risk calculators and risk factors for Pseudohypoparathyroidism pathophysiology

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Mazia Fatima, MBBS [2]

Overview

Pseudohypoparathyroidism is characterized by end-organ resistance to parathyroid hormone. Gene mutation results in failure of signal transduction. Blomstrand's chondrodystrophy results in intrauterine death and is characterized by abnormal endochondral bone formation with prematurely occurring mineralization of the cartilaginous bone templates. Acrodysostosis patients have resistance to parathormone with normal calcium and phosphorus, in addition to resistance thyroid-stimulating hormone and growth hormone releasing hormone.

Pathogenesis

Genetics

Genetic mutations associated with parathyroid hormone resistance are discussed below [3][4][5][6][7][8]

Type of Pseudohyoparathyroidism Molecular Defect Origin Of Mutation Inheritance
Pseudohypoparathyroidism type I Pseudohypoparathyroidism Type 1a Heterozygous GNAS inactivating mutations that reduce expression or function of Gαs Maternal Autosomal dominant
Pseudohypoparathyroidism Type 1b Familial- heterozygous deletions in STX16, NESP55, and/or AS exons or loss of methylation at GNAS Maternal Autosomal dominant
Sporadic- paternal Uniparental disomy of chromosome 20q in some or methylation defect affecting all four GNAS DMRs Maternal Genomic imprinting
Pseudohypoparathyroidism Type 1c Heterozygous GNAS inactivating mutations Maternal Autosomal dominant
Pseudopseudohypoparathyroidism Combination of inactivating mutations of GNAS1 and Albright's osteodystrophy Paternal Genomic imprinting
Pseudohypoparathyroidism type II Insufficient data to suggest genetic or familial source N/A N/A
Blomstrand chondrodysplasia Homozygous or heterozygous mutations in both alleles encoding the type 1 parathyroid hormone receptor N/A Autosomal recessive
Acrodysostosis Acrodysostosis type 1 PRKAR1A germ-line mutation in the encoding gene N/A Autosomal dominant
Acrodysostosis type 2  Phosphodiesterase 4D (PDE4D) gene  N/A Autosomal dominant

Gross Pathology

On gross pathology, enlarged parathyroid glands occur as a result of associated hypocalcemia.

Microscopic Pathology

On microscopic histopathological analysis, secondary hyperplasia of the parathyroid glands occurs as a result of associated hypocalcemia.


References

  1. Spiegel AM (2007). "Inherited endocrine diseases involving G proteins and G protein-coupled receptors". Endocr Dev. 11: 133–44. PMID 17986833. doi:10.1159/0000111069. 
  2. Chase LR, Melson GL, Aurbach GD (1969). "Pseudohypoparathyroidism: defective excretion of 3',5'-AMP in response to parathyroid hormone". J. Clin. Invest. 48 (10): 1832–44. PMC 322419Freely accessible. PMID 4309802. doi:10.1172/JCI106149. 
  3. Levine MA (2012). "An update on the clinical and molecular characteristics of pseudohypoparathyroidism". Curr Opin Endocrinol Diabetes Obes. 19 (6): 443–51. PMC 3679535Freely accessible. PMID 23076042. doi:10.1097/MED.0b013e32835a255c. 
  4. Mantovani G (2011). "Clinical review: Pseudohypoparathyroidism: diagnosis and treatment". J. Clin. Endocrinol. Metab. 96 (10): 3020–30. PMID 21816789. doi:10.1210/jc.2011-1048. 
  5. Lee S, Mannstadt M, Guo J, Kim SM, Yi HS, Khatri A, Dean T, Okazaki M, Gardella TJ, Jüppner H (2015). "A Homozygous [Cys25]PTH(1-84) Mutation That Impairs PTH/PTHrP Receptor Activation Defines a Novel Form of Hypoparathyroidism". J. Bone Miner. Res. 30 (10): 1803–13. PMC 4580526Freely accessible. PMID 25891861. doi:10.1002/jbmr.2532. 
  6. Jobert AS, Zhang P, Couvineau A, Bonaventure J, Roume J, Le Merrer M, Silve C (1998). "Absence of functional receptors for parathyroid hormone and parathyroid hormone-related peptide in Blomstrand chondrodysplasia". J. Clin. Invest. 102 (1): 34–40. PMC 509062Freely accessible. PMID 9649554. doi:10.1172/JCI2918. 
  7. Michot C, Le Goff C, Goldenberg A, Abhyankar A, Klein C, Kinning E, Guerrot AM, Flahaut P, Duncombe A, Baujat G, Lyonnet S, Thalassinos C, Nitschke P, Casanova JL, Le Merrer M, Munnich A, Cormier-Daire V (2012). "Exome sequencing identifies PDE4D mutations as another cause of acrodysostosis". Am. J. Hum. Genet. 90 (4): 740–5. PMC 3322219Freely accessible. PMID 22464250. doi:10.1016/j.ajhg.2012.03.003. 
  8. Linglart A, Menguy C, Couvineau A, Auzan C, Gunes Y, Cancel M, Motte E, Pinto G, Chanson P, Bougnères P, Clauser E, Silve C (2011). "Recurrent PRKAR1A mutation in acrodysostosis with hormone resistance". N. Engl. J. Med. 364 (23): 2218–26. PMID 21651393. doi:10.1056/NEJMoa1012717. 

Linked-in.jpg