Allgrove syndrome: an autosomal recessive syndrome of ACTH insensitivity, achalasia and alacrima.
Allgrove syndrome (isolated glucocorticoid deficiency, achalasia and alacrima) was found in eight members of an inbred French Canadian/North American Indian pedigree. The high degree of consanguinity supports an autosomal recessive mode of inheritance for this disorder. Six patients presented with hypoglycaemia and other evidence of cortisol deficiency between 2.5 and 8 years of age; however, two others became cortisol deficient after initial testing showed normal cortisol responses to ACTH, evidence that the glucocorticoid insufficiency of this syndrome may not be congenital, but may develop as late as the third decade. No evidence of mineralocorticoid deficiency has been found during 65 patient-years of follow-up. Alacrima was the earliest and most consistent clinical sign of Allgrove syndrome. Other manifestations of peripheral or autonomic neuropathy were found in four patients. The patients showed similar facial features, and three had significant velo-pharyngeal incompetence. All showed oesophageal dysmotility even in the absence of symptomatic dysphagia. In-vitro studies of lymphocyte ACTH binding showed no differences from normal controls. If such lymphocyte binding, as has been suggested, reflects adrenal ACTH receptor activity, these data would suggest that the glucocorticoid deficiency of Allgrove syndrome is not the result of a defect in that receptor. However, the observation that ACTH does not elicit increased adenylate cyclase activity even in normal lymphocytes casts considerable doubt on the physiological significance of ACTH binding to lymphocytes. It seems likely, therefore, that true ACTH receptors are not expressed on peripheral lymphocytes, and any conclusions regarding a possible receptor defect in Allgrove syndrome must await studies of receptor expression on adrenal cell membranes.
Moore
P S
PS
Department of Pediatrics, Winnipeg, Manitoba, Canada.
Couch
R M
RM
Perry
Y S
YS
Shuckett
E P
EP
Winter
J S
JS
D000324:Adrenocorticotropic Hormone / Q000378:metabolism*; D000328:Adult; D002648:Child; D002675:Child, Preschool; D003241:Consanguinity; D004931:Esophageal Achalasia / Q000235:genetics* / Q000378:metabolism; D005260:Female; D005808:Genes, Recessive; D006801:Humans; D006854:Hydrocortisone / Q000172:deficiency*; D007766:Lacrimal Apparatus Diseases / Q000235:genetics* / Q000378:metabolism; D008214:Lymphocytes / Q000378:metabolism; D008297:Male; D010375:Pedigree; D013577:Syndrome
D000324:Adrenocorticotropic Hormone; D006854:Hydrocortisone