Endocrine Abstracts

ACTH insensitivity syndromes comprise a rare, and underrecognised, group of disorders, which include familial glucocorticoid deficiency (FGD) and triple A or Allgrove syndrome (ACTH insensitivity, alacrima, achalasia and neurological involvement). They are characterised by undetectable cortisol and very high circulating ACTH with resultant hyperpigmentation and are inherited in an autosomal recessive manner. Distinction between FGD and triple A syndrome may be difficult and is facilitated by the presence of additional features in the later.

We describe three cases from three unrelated families, all born to consanguineous parents, with ACTH insensitivity syndromes. These patients presented in early life with varying clinical features. The first patient now aged 22, presented at the age of 1 year with an acute illness while the second patient, now aged 27, presented at 10 with hyperpigmentation. A third patient, now aged 18, presented at the age of 2 years with peripheral neuropathy and subsequently developed ACTH insensitivity at age 5 and alacrmia and achalasia at age 8.

All these patients had negative adrenal autoimmune screen, normal levels of very-long-chain fatty acids with normal adrenal imaging. None of these patients had features of salt loss. No gene mutation for ACTH receptor (MC2-R) was identified in any of these patients. However it is well known that approximately half of the patients with FGD will have no identifiable mutation within the coding region of ACTH receptor.

Untreated, ACTH insensitivity syndromes are potentially lethal while glucorticoid replacement alone is highly effective. These patients usually have very high circulating ACTH and administering hydrocortisone to suppress ACTH will invariably result in supraphysiological doses. In the management of Allgrove syndrome neurological and gastrointestinal aspects of the disease can only be treated symptomatically.