[Familial glucocorticoid insufficiency (author's transl)]

Area of Science:

• Endocrinology
• Genetics
• Pediatrics

Background:

• Familial glucocorticoid insufficiency is a rare genetic disorder characterized by the adrenal glands' lack of response to ACTH.
• This condition has not been previously documented in Europe.

Observation:

• A family with 21 diagnosed patients across 9 families experienced 13 sibling deaths before diagnosis.
• The described family had three children who died young, one from suspected encephalitis and another from status epilepticus.
• The surviving sister exhibited pronounced pigmentation, growth retardation, and adrenal insufficiency despite normal aldosterone secretion.

Findings:

• Autopsy revealed extremely small adrenal glands with only the glomerulosa zone developed and pituitary hyperplasia of ACTH-producing cells.
• The patient presented with undetectable plasma cortisol levels after stimulation, extremely high ACTH levels, and altered renin-aldosterone dynamics.
• These findings confirm isolated glucocorticoid deficiency with preserved aldosterone production and elevated ACTH.

Implications:

• Early diagnosis and management are crucial to prevent mortality in familial glucocorticoid insufficiency.
• This case highlights the diagnostic challenges and the importance of recognizing this rare condition.
• Further research is needed to understand the genetic basis and develop targeted therapies for this disorder.