Allgrove (AAA) Syndrome Treatment & Management
- Author: Robert J Ferry, Jr, MD; Chief Editor: Stephen Kemp, MD, PhD more...
Careful replacement of glucocorticoids in patients with known adrenal insufficiency is critical to avoid an adrenal crisis and to allow for normal growth in children. Growth must be closely monitored because overtreatment with glucocorticoids impairs linear growth. Providing stress doses of corticosteroids during illness or injury is also important.
Every patient should always wear a medical alert bracelet or necklace and carry the emergency medical information card supplied with it.
In adult patients, as well as those who have difficulty with compliance, replacing cortisone with an equipotent dose of prednisone or dexamethasone is appropriate.
Prednisone and dexamethasone are less preferred for maintenance than hydrocortisone which has balanced 1:1 effects of mineralocorticoid vs. glucocorticoid. Also, these corticosteroids are not preferred in children due to potential for growth-suppressive effects with greater potency and longer duration of action compared to hydrocortisone.
Achalasia is best managed with surgical correction. Monitoring patients for pulmonary complications (due to reflux and aspiration) and providing gastric acid reduction therapy in patients with symptomatic reflux after surgical intervention is important.
Alacrima is managed with regular application of topical lubricants and with punctal occlusion. Children may need to be frequently reminded to use artificial tears. Children must have an annual ophthalmologic evaluation.
The symptoms of alacrima improve with punctal occlusion. This procedure is only necessary when therapy with topical lubricants is unsuccessful because of poor compliance.
The symptoms of lower esophageal sphincter spasm in patients with achalasia can be ameliorated partially with pneumatic dilatation. In patients who remain symptomatic after pneumatic dilatation, an anterior cardiomyotomy (modified Heller operation) may be performed. This surgical procedure involves directly cutting the muscles of the spastic sphincter. Both procedures have a risk of esophageal perforation and a high rate of postsurgical reflux.
Patients with Allgrove syndrome who undergo surgery must be treated with stress doses of glucocorticoids in the perioperative period.
A Schirmer test provides a semiquantitative measure of tearing. Other ophthalmologic testing, including slit lamp examination and fluorescein staining, is helpful in identifying patients with corneal pathology secondary to poor lacrimation.
Neurologic tests highlight a myriad of neurologic and developmental issues. Palatopharyngeal incompetence, sensory impairment, ataxia, and muscle weakness are among the documented findings.
Other than the diet changes mandated by the mechanical issues related to achalasia, no specific diet is indicated.
In a subset of patients with autonomic disturbance, some activities may need to be limited because of problems with recurring orthostatic hypotension and diminished heart rate variability. Otherwise, no specific limitations on activity are necessary.
Allgrove J, Clayden GS, Grant DB. Familial glucocorticoid deficiency with achalasia of the cardia and deficient tear production. Lancet. 1978 Jun 17. 1(8077):1284-6. [Medline].
Kasar PA, Khadilkar VV, Tibrewala VN. Allgrove syndrome. Indian J Pediatr. 2007 Oct. 74(10):959-61. [Medline].
Kelch RP, Kaplan SL, Biglieri EG. Hereditary adrenocortical unresponsiveness to adrenocorticotropic hormone. J Pediatr. 1972 Oct. 81(4):726-36. [Medline].
Counahan R, West R. Ocular and fingertip abnormalities in isolated glucocorticoid deficiency. J Pediatr. 1974 Oct. 85(4):580-1. [Medline].
Gazarian M, Cowell CT, Bonney M. The "4A" syndrome: adrenocortical insufficiency associated with achalasia, alacrima, autonomic and other neurological abnormalities. Eur J Pediatr. 1995 Jan. 154(1):18-23. [Medline].
Li W, Gong C, Qi Z, Wu DI, Cao B. Identification of AAAS gene mutation in Allgrove syndrome: A report of three cases. Exp Ther Med. 2015 Oct. 10 (4):1277-1282. [Medline].
Sarathi V, Shah NS. Triple-A syndrome. Adv Exp Med Biol. 2010. 685:1-8. [Medline].
Alhussaini B, Gottrand F, Goutet JM, Scaillon M, Michaud L, Spyckerelle C, et al. Clinical and manometric characteristics of Allgrove syndrome. J Pediatr Gastroenterol Nutr. 2011 Sep. 53(3):271-4. [Medline].
Moschos MM, Margetis I, Koehler K, Gatzioufas Z, Huebner A. New ophthalmic features in a family with triple A syndrome. Int Ophthalmol. 2011 Jun. 31(3):239-43. [Medline].
Vallet AE, Verschueren A, Petiot P, Vandenberghe N, Nicolino M, Roman S, et al. Neurological features in adult Triple-A (Allgrove) syndrome. J Neurol. 2012 Jan. 259(1):39-46. [Medline].
Stratakis CA, Lin JP, Pras E. Segregation of Allgrove (triple-A) syndrome in Puerto Rican kindreds with chromosome 12 (12q13) polymorphic markers. Proc Assoc Am Physicians. 1997 Sep. 109(5):478-82. [Medline].
Weber A, Wienker TF, Jung M. Linkage of the gene for the triple A syndrome to chromosome 12q13 near the type II keratin gene cluster. Hum Mol Genet. 1996 Dec. 5(12):2061-6. [Medline].
Prpic I, Huebner A, Persic M, et al. Triple A syndrome: genotype-phenotype assessment. Clin Genet. 2003 May. 63(5):415-7. [Medline].
Chu ML, Berlin D, Axelrod FB. Allgrove syndrome: documenting cholinergic dysfunction by autonomic tests. J Pediatr. 1996 Jul. 129(1):156-9. [Medline].
Alakeel A, Raynaud C, Rossi M, Reix P, Jullien D, Souillet AL. [Allgrove syndrome]. Ann Dermatol Venereol. 2015 Feb. 142 (2):121-4. [Medline].