Saudi Journal of Gastroenterology
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Year : 2006  |  Volume : 12  |  Issue : 1  |  Page : 34-35
Allgrove syndrome: reports of cases and literature review


1 Department of Surgery, Guilan University of Medicine, Rasht, Iran
2 Department of Medicine, Guilan University of Medicine, Rasht, Iran

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   Abstract 

We report a series of three mentally-retarded patients who presented with dysphagia, cough and recurrent pulmonary infection, adrenal insufficiency and alacrimia. Investigations included ultrasonography and CT scan of the abdomen, in addition to barium swallow, esophageal manometry and esophagoscopy confirming the diagnosis of achalasia. Glucocorticoid therapy was prescribed whereas alacrimia was managed by lubricants. In two of our patients dysphagia responded to dilatation while the third required cardiomyotomy.

How to cite this article:
Aghajanzadeh M, Safarpoor F, Hydayati MH, Kohssari MR, Mashhour MY, Soleymani AS. Allgrove syndrome: reports of cases and literature review. Saudi J Gastroenterol 2006;12:34-5

How to cite this URL:
Aghajanzadeh M, Safarpoor F, Hydayati MH, Kohssari MR, Mashhour MY, Soleymani AS. Allgrove syndrome: reports of cases and literature review. Saudi J Gastroenterol [serial online] 2006 [cited 2017 Jun 23];12:34-5. Available from: http://www.saudijgastro.com/text.asp?2006/12/1/34/27743


In 1978, Allgrove and colleagues described two unrelated pairs of siblings with isolated glucocorticoid failure and achalasia.

Three of these individuals also had defective tear production, leading the authors to speculate that the combination of achalasia, adrenal insufficiency and alacrima represented an inherited familial disorder. [1] In the following years a number of authors published similar reports that have helped to define the primary and associated features of this syndrome. [2],[3] In addition several authors published description of a more global autonomic disturbance associated with the original Allgrove triad suggesting the name (4A) syndrome (adrenal insufficiency, achalasia, alacrima and autonomic abnormalities. [4]

Case No.1:

The patient is a 16-year-old mentally retarded male from the North of Iran (Rasht) admitted with grade IV dysphagia.

His complaints started six years before admission and got more severe in the following two years. Other complaints were nocturnal cough, recurrent pulmonary infection and bad-smelling belching. There was a history of admission to hospital at the age of six years for seizure and shock with truncal and facial hyper-pigmentation. He was treated with phenobarbital, glucose 50% and hydrocortison, and normal saline solution. The seizure and shock were controlled. Laboratory tests during seizure and shock were as follow: FBS=32mg/dl, Na=120 meq/dl, K=4.5 meq/dl, WBC=9000/cm3, HgP=13, BUN=15mg/dl, creatinine=0.9 mg/dl, Ca=8.5mg/dl, phos=4mg/dl, ACTH=18mcg/dl, cortisol serum=2.2 mcg/dl, and 17 ketostroid of 24 hours urine (700 cc) =2.6mcg/dl. The cause of seizure and shock was adrenal insufficiency and the patient was treated with 10 mg prednisolone daily.

All of his symptoms and signs disappeared and laboratory data returned to the normal range. In the last admission, the patient presented with mental retardation, failure to thrive, microcephaly, a long thin face with a long philtrum, narrow upper lip, down-turned mouth and conjunctivitis. Other signs and symptoms included hyper-reflexia, dysarthria, hyper-nasal speech with palatopharyngeal incompetence. Diagnostic studies included barium swallow, esophageal manometry and endoscopy all of which demonstrated achalasia. Alacrimia was confirmed with schimer test. Dysphagia was managed by dilatation of the lower esophageal sphincter with poor results. Because of this failure; the patient was treated with cardioesophageal myotomy and discharged in good condition. During the one year follow up the patient recovered from dysphagia.

Case No. 2:

A 20-year-old female referred from the North of Iran (Rasht) because of achalasia and dysphagia grade IV for the last three years. She was admitted to the hospital at the age of eight years because of seizure and shock. The diagnosis of adrenal insufficiency was confirmed by hyponatremia Na (125 meq/dl) and hypoglycemia, (glucose=36mg/dl). K (4.5 meq/dl), serum calcium, phosphorus and magnesium were normal. Serum cortisone level (1.9 mcg/dl) and ACTH (15mcg/dl). All symptoms improved by injection of hydrocortisone and glucose (50%). The family history is positive for seventeen-year-old brother with adrenal insufficiency, achalasia and alacrimia (case no3). The physical examination on admission showed failure to thrive, weight loss, alacrimia, hyper-reflexia.

The dysphagia improved with pneumatic dilatation and, during the one-year follow-up of the patient, weight increased by 8kg and she was in good condition on 10 mg prednisolone daily.

Case no 3:

A seventeen-year-old male referred to our department from the North of Iran (Rasht) with achalasia and grade IV dysphagia. The past medical history is relevant. When he was six years old he was admitted to hospital for convulsion and shock. Laboratory findings showed the following: (Na=126 meq/dl), (glucose=42mg/dl), (K =4.3 meq/dl), calcium, phosphor and magnesium were normal. Serum cortisol level was low (2 mcg/dl) and (ACTH=16mcg/dl). Adrenal insufficiency was diagnosed and treatment with hydrocortisone and glucose 50% was started while the patient continued to take 7.5 mg of prednisolone daily. The family history is positive for one sister with this syndrome (case no. 2).

The physical examination at the time of referral showed weight loss, failure to thrive, alacrimia, nasal speech and hyper-reflexia. After swallowing a measured dose of barium, an esophagoscopy and dilatation of the esophagus was successfully performed. Dysphagia markedly improved and the weight increased during the one-year follow up.

Discussion

Allgrove syndrome is considered an autosomal recessive disorder with a variable presentation. [1],[2],[3] The pathology of this syndrome may be due to a progressive loss of cholinergic function throughout the body. [2] The age of onset of symptoms is variable. Glococorticosteroid deficiency is not apparent at birth, but develops after the second decade of life. [5] In our patients the glocorticosteroid deficiency symptoms presented at the ages of ten, eight and six years of age respectively. Alacrima generally presents from early infancy, while symptoms of achalasia may appear in individuals as young as 6 months or as late as early adulthood. [6] In our patients alacrimia presented at six to eight years of age.

Most patient present with classic symptoms of primary adrenal insufficiency, including hypoglycemic seizures and shock. Less frequently, a child initially evaluated for recurrent vomiting - dysphagia, and failure to thrive or ocular symptoms may be positive for crying without tears. In our patients dysphagia presented in 10 and 17 and 11 years of age. Other presentations may include hyper-pigmentation, developmental delay, nasal speech, orthostatic and hypotension. [7],[8],[9] Hyper-pigmentation was present in one of our patients.

Distinct facial appearance of Allgrove syndrome includes long thin face with a long philtrum, narrow upper lip, down-turned mouth and microcephaly. Conjunctiva congestion and irritation may be the only sign of alacrimia. [10] Neurological examination reveals hyper-reflexia, dysarthria, hyper-nasal speech and ataxia. None of our patients had the above neurological problems.

Baseline ACTH, cortisol level, and ACTH stimulation test are used to evaluate adrenal insufficiency and the schimer test is used to evaluate tear production [9]. Measurement of serum sodium, potassium aldesterone, renin, antiadrenal antibodies is also indicated. [10] MRI or CT of the brain is needed if neurologic problems are observed, and abdominal CT scan and ultrasonography are used for evaluation of the adrenal glands. [8] Barium swallow, manometry and esophagoscopy are needed for the diagnosis of achalasia. [8],[11] Lacrimal gland CT scan may be helpful, [8] and lacrimal gland biopsy may show neuronal degeneration associated with depletion of secretory granules in the acinar cell. [8] The diagnosis of achalasia was confirmed by the barium-swallow, manometry and esophgoscopy in all of our patients. Careful replacement of glucocorticoids in patients with adrenal insufficiency is critical to avoid adrenal crises and allow for normal growth in children. [6],[8] Achalasia is best managed with surgical correction or esophageal dilatation, while alacrimia is managed with the regular application of topical lubricants and surgical punctal occlusion with synthetic tears. [10] In two of our patients, dysphagia responded to dilatation and in one with cardiomyotomy.

Acknowledgement: Dr. Hadi Tuzandehjany for his cooperation in editing text and pictures

Allgrove syndrome: (Achalasia with familial adernocortical insufficiency) in childhood (Reports of three cases and review of literature

 
   References Top

1.Allgrove J, Clayden GS, grant DB: Familial glucocorticoid deficiency with achalasia of the cardia and deficient tear production. Lancet 1978; 1: 1284-1286.   Back to cited text no. 1    
2.Chu ML, Berlin D, Axelrod FB: Allgrove syndrome: documenting cholinergic dysfunction by autonomic tests. J Pediatric 1996; 129: 156-159.   Back to cited text no. 2    
3.Grant DB, Barnes ND, and Dumic M: Neurological and adrenal dysfunction in the adrenal insufficiency/ alacrima/achalasia (3A) syndrome. Arch Dis Child 1993; 68: 779-782.  Back to cited text no. 3    
4.Gazarian M, Cowell CT, Bonney M: The " 4A" syndrome: adrenocortical insufficiency associated with achalasia, alacrima, autonomic and other neurological abnormalities. Euro J Pediatric 1995; 154: 18-23.  Back to cited text no. 4    
5.Makari G, Hoffman WH, and Carroll JE: Autonomic dysfunction and adrenocortical unresponsiveness to ACTH. J Child Neural 1988; 3: 174-6.  Back to cited text no. 5    
6.Tuck JS, Bisset RA, and Doig CM: Achalasia of the cardia in childhood and the syndrome of achalasia alacrima and ACTH insensitivity. Clin Radiol 1991; 44: 260-264.  Back to cited text no. 6    
7.Fagan JE, McArthur RG, Machida H: Palatopharyngeal incompetence in association with esophageal dysmotility, acquired glucocorticoid deficiency, and deficient tear production. Clin Invest Med 1987 Jul; 10: 345-349.  Back to cited text no. 7    
8.Lanes R, Plotnick LP, Bynum TE: Glucocorticoid and partial mineral corticoid deficiency associated with achalasia. J Clin Endocrinol Metab 1980; 50: 268-270.  Back to cited text no. 8    
9.Dumic M, Radica A, Jusic A: Selective ACTH insensitivity associated with autonomic nervous system disorders and sensory polyneuropathy. Euro J Pediatric 1987 Nov; 146(6): 592-594.   Back to cited text no. 9    
10.Heinrichs C, Tsigos C, Deschepper J: Familial adrenocorticotropin unresponsiveness associated with alacrima and achalasia: biochemical and molecular studies in two siblings with clinical heterogeneity. Euro J Pediatric 1995; 154: 191-196.  Back to cited text no. 10    
11.Cameron D.Wright and Earle W .Wilkins, Jr. : Motor Disturbances of Deglutition. General thoracic surgery, Thomas W. Shields, fifth edit, Lippincott Williams&Wilkins. 2000: 1826.  Back to cited text no. 11    

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Correspondence Address:
Manochehr Aghajanzadeh
Department of General Surgery, Razi Hospital, P O Box 41448-95655, Rasht
Iran
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/1319-3767.27743

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