The diagnosis of adrenal insufficiency in a patient with Allgrove syndrome and a novel mutation in the ALADIN gene.
Allgrove syndrome is a genetic disorder inherited in an autosomal recessive pattern and characterized by a triad of adrenal insufficiency, achalasia, and alacrima. The gene affected by the mutation in patients with Allgrove syndrome is termed either AAAS or ALADIN (alacrima/achalasia/adrenal insufficiency/neurologic disorder). Adrenal insufficiency in patients with this disorder may develop as late as the third decade of life. We describe a 24-year-old female with Allgrove syndrome, in whom initial testing with 250 microg corticotropin (ACTH) stimulation test performed on 3 occasions produced normal serum cortisol values and results of the 1-microg ACTH stimulation tests performed on 6 occasions were conflicting. Insulin-induced hypoglycemia produced a nadir serum glucose value of 36 mg/dL without adequate serum cortisol stimulation, confirming presence of adrenal insufficiency. Gene sequencing identified 2 mutations in the triple A gene: an IVSC14 + 1 G to A mutation, which has been previously reported, and a novel R155P exon 6 mutation. We conclude that a novel R155P mutation in the ALADIN gene is associated with Allgrove syndrome and that insulin-induced hypoglycemia, rather than ACTH stimulation tests, should be used for accurate diagnosis of adrenal insufficiency in this disorder.
Salehi
Marzieh
M
Department of Medicine, Division of Endocrinology and Metabolism, Beth Israel Medical Center, Albert Einstein College of Medicine, New York, NY 10003, USA.
Houlden
Henry
H
Sheikh
Arsalan
A
Poretsky
Leonid
L
D000305:Adrenal Cortex Hormones / Q000097:blood; D000309:Adrenal Insufficiency / Q000150:complications / Q000175:diagnosis* / Q000235:genetics; D000324:Adrenocorticotropic Hormone / Q000008:administration & dosage / Q000097:blood; D000328:Adult; D000450:Aldosterone; D001786:Blood Glucose / Q000378:metabolism; D001794:Blood Pressure / Q000502:physiology; D004247:DNA / Q000235:genetics; D004305:Dose-Response Relationship, Drug; D004931:Esophageal Achalasia; D005260:Female; D006579:Heterozygote; D006801:Humans; D006854:Hydrocortisone / Q000097:blood / Q000627:therapeutic use; D007004:Hypoglycemic Agents; D007328:Insulin; D007766:Lacrimal Apparatus Diseases; D009154:Mutation / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013577:Syndrome
D000305:Adrenal Cortex Hormones; D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007328:Insulin; D000450:Aldosterone; D000324:Adrenocorticotropic Hormone; D004247:DNA; D006854:Hydrocortisone