Abstract
Allgrove’s syndrome is an inherited condition caused by mutations in the AAAS gene (encoding the protein ALADIN) and is inherited in an autosomal recessive pattern (1). It classically is characterized by three specific features: achalasia, Addison’s disease, and alacrima (reduced or absent ability to secrete tears). This has led to the name “Triple A syndrome”, and some have suggested a 4th ‘A’ of autonomic disturbance (2). It is important to note that the phenotype of this condition is variable, and some patients may have all three (or four) of the manifestations at initial presentation, and that other patients may develop or have worsening of the ‘As’ over time. In this clinical vignette, we present a patient with Allgrove’s syndrome who developed clinical manifestations of the third ‘A’ of Addison’s disease later in life. A 46-year-old female patient presented to our tertiary referral center for follow-up of Allgrove’s disease after having been diagnosed with genetic testing as an adolescent. Prior to presentation, she underwent esophagectomy in 1995 and additionally had confirmed alacrima with ophthalmology. She was undergoing annual surveillance testing with 8 am cortisol and ACTH stimulation testing to monitor for the development of adrenal insufficiency. Prior to consultation, her baseline cortisol was 8.7 ug/dL. At presentation and the age of 46, her ACTH stimulation test (0.25 mg cosyntropin, 3 timepoints) was positive for adrenal insufficiency with a baseline cortisol of < 0.5 ug/dL (8 am), with 30-minute value of 4.4 ug/dL and 60-minute value of 6.3 ug/dL (peak). She was started on replacement dosing of hydrocortisone 20 mg at 8 am and 10 mg at 2 pm, in addition to calcium and vitamin D supplementation. Of note, her adrenal antibody (21-hydroxylase antibodies) were negative on two separate occasions. Allgrove’s syndrome is a rare condition described by the development of three, or at times four, characteristics with support of genetic testing. This case demonstrates that patients with Allgrove’s syndrome can present with two clinical manifestations of the condition (alicrima and achalasia) and develop the third (adrenal insufficiency) later in life. Therefore, regular screening for the missing clinical manifestation of this disease should be considered. References: 1. National Institute of Health: Genetic and Rare Disease Information Center. Triple A Syndrome. Genetics Home Reference. February 2010; http://ghr.nlm.nih.gov/condition/triple-a-syndrome. Accessed 2/1/2020. 2. Kimber J, McLean BN, Prevett M, Hammans SR. Allgrove or 4 “A” syndrome: an autosomal recessive syndrome causing multisystem neurological disease. J Neurol Neurosurg Psychiatry. 2003;74:654-657.
X-linked congenital adrenal hypoplasia: a case presentation
