My Clinical Notes

• Far less common than hyperparathyroidism
• Causes include;
  • Surgical
  • Congenital absence of all glands
  • Familial hyperparathyroidism – often associated with chronic mucocutaneous candidiasis and primary adrenal insufficiency. This syndrome is known as autoimmune polyendocrine syndrome type1 (APS1) and is caused by mutation in the AIRE gene (autoimmune regulator gene)
  • Idiopathic hypoparathyroidism – most likely autoimmune. 60% of patients have autoantibodies which recognise the calcium-sensing receptor of the parathyroid gland

 

Clinical manifestations

• Tetany
• Mental status changes – emotional instability, anxiety and depression, confusion and psychosis
• Intracranial manifestations – calcifications of the basal ganglia, parkinsonian-like movement disorders and increased intracranial pressure with resultant papilloedema
• Ocular disease with calcification of the lens resulting in cataract formation
• Cardiovascular manifestations including a conduction defect producing a prolonged QT interval in the ECG
• Dental abnormalities when hypocalcaemia is present early in development

 

Pseudohypoparathyroidism

 

• Occurs because of end-organ resistance to the actions of PTH
• Underlying this is the parental imprinting of the gene GNAS1 which encodes Gsα
• In the kidneys there is silencing of the paternal copy of the gene so only maternal GNAS1 is expressed therefore a mutation in the maternal allele results in a complete loss in Gsα expression in the kidney
• Elsewhere in the body GNAS1 is expressed from both copies of the gene so a mutation in either copy results in a 50% decrease in Gsα in the tissues
• Two types of pseudohypoparathyroidism have been identified due to the parent origin of the mutant allele;
  • Pseudohypoparathyroidism Type 1A – associated with multihormone resistance and Albright hereditary osteodystrophy (AHO).
    • Patients have a short stature, obesity, short metacarpals and metatarsals and variable mental defects
    • The multi hormone resistance involves PTH, TSH and LH/FSH all of which activate the Gsα-mediated pathways in the tissues
    • The mutation in this disorder is inherited from the maternal side
  • Pseudopseudohypoparathyroidism – mutation is inherited from the paternal side and is characterised by AHO without accompanying multihormonal resistance.

This entry was posted on Sunday, December 30th, 2007 at 2:13 pm and is filed under Endocrine. You can follow any responses to this entry through the RSS 2.0 feed. You can leave a response, or trackback from your own site.