Endocrine Abstracts

Genetic defects causing primary, central secondary or tertiary adrenal insufficiency (AI) belong to the group of rare diseases that involve multiple candidate genes. In primary AI adrenal defects lead to hormonal deficiencies. Underlying genetic mutations may be found either in genes involved in the development of the adrenal gland (e.g. DAX1/NR0B1) or in genes that are essential for the signaling, regulation (e.g. MC2R, MRAP) or the biosynthesis of steroid hormones (e.g. StAR, CYP11A1 etc.) and their cofactors (e.g. POR) and mitochondrial partners (e.g. NNT).

Genetic defects causing isolated, secondary (central) AI due to corticotropin deficiency are very rare and include TPIT, while genetic mutations of PCSK1 and POMC not only cause AI but also manifest with massive obesity, hypogonadotropic hypogonadism and abnormal glucose homeostasis. In addition, AI may also be part of the clinical spectrum of developmental defects of the pituitary gland leading to multiple pituitary hormone deficiency (e.g. HESX1, LIM4, PROP1).

This symposium lecture will cover the genetics of human mutations causing AI and elucidate what we learnt from those experiments of nature.