PMCCPMCCPMCC

Search tips
Search criteria 

Advanced

 
Logo of postmedjPostgraduate Medical JournalVisit this articleSubmit a manuscriptReceive email alertsContact usBMJ
 
Postgrad Med J. 2007 June; 83(980): 420–421.
PMCID: PMC2600050

Screening for Addison's disease in patients with type 1 diabetes mellitus and recurrent hypoglycaemia

Abstract

Background

Addison's disease may present with recurrent hypoglycaemia in subjects with type 1 diabetes mellitus. There are no data, however, on the prevalence of Addison's disease presenting with recurrent hypoglycaemia in patients with diabetes mellitus.

Methods

Three year retrospective study of diabetic patients with “unexplained” recurrent hypoglycaemia investigated with a short Synacthen test to exclude adrenocortical insufficiency.

Results

95 patients with type 1 diabetes mellitus were studied. Addison's disease was identified as the cause of recurrent hypoglycaemia in one patient with type 1 diabetes mellitus.

Conclusion

Addison's disease is a relatively rare but remedial cause of recurrent hypoglycaemia in patients with type 1 diabetes mellitus. A low threshold for investigating patients with type 1 diabetes mellitus and recurrent hypoglycaemia to detect Addison's disease is therefore suggested.

Addison's disease may present as recurrent hypoglycaemia in patients with type 1 diabetes mellitus1,2,3,4,5,6,7 and it is recommended that diabetic patients with unexplained recurrent hypoglycaemia be screened for Addison's disease.8 There are, however, no data on the prevalence of Addison's disease presenting with recurrent hypoglycaemia in patients with diabetes. We report on the prevalence of Addison's disease presenting with recurrent hypoglycaemia in patients with type 1 diabetes mellitus.

METHODS

In a 3 year retrospective study we studied the frequency of Addison's disease as a cause of recurrent hypoglycaemia in patients with types 1 diabetes mellitus. All patients had recurrent hypoglycaemic episodes which appeared unrelated to insulin treatment, meal plans, exercise patterns, alcohol consumption, co‐morbidity and concurrent medication. Exclusion criteria included those receiving or who had recently received steroid treatment and those with known pituitary, liver, renal, asthma and malignant disease.

Short Synacthen tests, which can be carried out at any time of the day,9 were performed in the afternoon. An intravenous cannula was inserted into an antecubital fossa vein and a baseline blood sample was collected between 14.00 and 14.30. A dose of 250 μg tetracosactide (Synacthen, Alliance Pharmaceuticals Ltd, Chippenham, UK) was then administered intravenously and further blood samples collected 30 and 60 min later. Blood was separated and serum cortisol measured by electrochemiluminescence immunoassay (Elecsys Cortisol, Roche Diagnostics GmbH, Mannheim, Germany) on the Roche Modular Analytics E170 immunoassay analyser. The assay has a detection limit of 2 nmol/l (Package insert, Elecsys Cortisol, Roche Diagnostics GmbH, Mannheim Germany). The inter‐assay coefficient of variation for the cortisol assay is 1.7% at 410 nmol/l. Internal quality control and external quality assessment for cortisol were satisfactory throughout the study period. A normal cortisol response to Synacthen was defined as a post‐stimulation peak cortisol value of [gt-or-equal, slanted]500 nmol/l at either 30 or 60 min with an incremental cortisol response [gt-or-equal, slanted]200 nmol/l.9

Since data had a normal distribution (Kolmogorov‐Smirnov test), results are expressed as means with standard deviations (SD) in parentheses.

RESULTS

Synacthen tests were performed on 95 patients with type 1 diabetes mellitus and recurrent hypoglycaemia (table 11).

Table thumbnail
Table 1 Demographics and Synacthen test results in patients with diabetes mellitus and recurrent hypoglycaemia

One subject, a 39‐year‐old man with type 1 diabetes mellitus, was diagnosed with autoimmune Addison's disease (peak cortisol 111 nmol/l; incremental cortisol 32 nmol/l; adrenocorticotropic hormone (ACTH) 449 ng/l; adrenal antibodies positive; normal thyroid function tests; negative thyroid microsomal antibodies). Hydrocortisone replacement therapy led to a resolution of hypoglycaemia, improved glycaemic control, re‐instatement of his driving licence, and resumption of his job as a gas fitter.

DISCUSSION

Addison's disease occurs more frequently in patients with type 1 diabetes mellitus as part of the autoimmune polyendocrine syndromes.10,11,12,13,14 The diagnosis of Addison's disease is, however, often delayed because the onset of diabetes mellitus usually precedes the diagnosis of Addison's disease.10,14 Cortisol deficiency increases insulin sensitivity resulting in increased peripheral glucose utilisation, impaired gluconeogenesis and decreased hepatic glucose output.15 Hypoglycaemia would, therefore, be expected to be a prominent and early feature of Addison's disease in diabetic patients on hypoglycaemic treatment. This audit, however, indicates that recurrent hypoglycaemia in patients with type 1 diabetes is only rarely due to Addison's disease.

A short Synacthen test is usually the initial endocrine investigation for adrenocortical insufficiency,9 but it is time consuming, involves administration of parenteral ACTH, and may require admission to a day unit. The difficulty is predicting which diabetic patients with recurrent hypoglycaemia are unlikely to have Addison's disease in order to reduce the number of unnecessary short Synacthen tests. Addison's disease should be considered if typical clinical and biochemical features are present (table 22)) and in the presence of other organ specific autoimmune disease, especially autoimmune thyroid disease.11 Other than recurrent hypoglycaemia, our patient had none of characteristic features of Addison's disease or associated endocrinopathy (table 22)) indicating that recurrent hypoglycaemia was the sole and perhaps early presenting feature of adrenal failure. This, therefore, suggests that Addison's disease should be considered as a cause of unexplained recurrent hypoglycaemia in all patients with type 1 diabetes. It has also been suggested that screening with 09.00 serum cortisol could reduce the number of unnecessary short Synacthen tests by 21%,16 but this would involve the patient attending for venepuncture on at least two occasions if a short Synacthen test is necessary. An alternative approach would be to use adrenal antibodies to screen for Addison's disease, but doubts remain about their specificity since only 15% of diabetic subjects positive for adrenal antibodies have biochemical evidence of Addison's disease12 and negative adrenal antibody status does not exclude Addison's disease.17

Table thumbnail
Table 2 Common clinical and laboratory features of Addison's disease15

Our audit indicates that, although rare, recurrent hypoglycaemia in patients with type 1 diabetes mellitus may be the sole presenting feature of Addison's disease. We therefore suggest a low threshold for performing appropriate tests in patients with type 1 diabetes and recurrent hypoglycaemia is essential to detect Addison's disease.

Footnotes

Conflict of interest: none stated

References

1. Hardy K J, Burge M R, Boyle P J. et al A treatable cause of recurrent severe hypoglycaemia. Diabetes Care 1994. 17722–724.724 [PubMed]
2. Phornphutkul C, Boney C M, Gruppuso P A. A novel presentation of Addison disease: hypoglycemia unawareness in an adolescent with insulin‐dependent diabetes mellitus. J Pediatr 1998. 132882–884.884 [PubMed]
3. Armstrong L, Bell P M. Lesson of the week: Addison's disease presenting as reduced insulin requirement in insulin dependent diabetes. BMJ 1996. 3121601–1602.1602 [PMC free article] [PubMed]
4. McAulay V, Frier B M. Addison's disease in type 1 diabetes presenting with recurrent hypoglycaemia. Postgrad Med J 2000. 76230–232.232 [PMC free article] [PubMed]
5. Thomas J B, Petrovsky N, Ambler G R. Addison's disease presenting in four adolescents with type 1 diabetes. Pediatr Diabetes 2004. 5207–211.211 [PubMed]
6. Sakane N, Yoshida T, Yoshioka K. et al Severe hypoglycaemia and type1 diabetes with isolated ACTH deficiency. Diabetes Care 1995. 181621–1622.1622 [PubMed]
7. Schroter W, Arends J, Runte L. et al Hypoglycemia with loss of consciousness during insulin therapy as an initial symptom of Addison's disease. Report of 2 cases. Dtsch Med Wochenschr 1985. 110840–842.842 [PubMed]
8. Gill G V, Williams G. Causes and management of poor metabolic control. In: Pickup JC, Williams G, eds. Textbook of diabetes, 3rd ed. Oxford: Blackwell Science Ltd, 2006. 43.21–43.38.43.38
9. Dorin R I, Qualls C R, Crapo L M. Diagnosis of adrenal insufficiency. Ann Intern Med 2003. 139194–204.204 [PubMed]
10. Zelissen P M, Bast E J, Croughs R J. Associated autoimmunity in Addison's disease. J Autoimmun 1995. 8121–130.130 [PubMed]
11. Barker J M, Yu J, Yu L. et al Autoantibody “subspecificity” in type 1 diabetes: risk for organ‐specific autoimmunity clusters in distinct groups. Diabetes Care 2005. 28850–855.855 [PubMed]
12. Barker J M, Ide A, Hostetler C. et al Endocrine and immunogenetic testing in individuals with type 1 diabetes and 21‐hydroxylase autoantibodies: Addison's disease in a high‐risk population. J Clin Endocrinol Metab 2005. 90128–134.134 [PubMed]
13. Papadopoulos K I, Hallengren B. Polyglandular autoimmune syndrome type II in patients with idiopathic Addison's disease. Acta Endocrinol (Copenhagen) 1990. 122472–478.478 [PubMed]
14. Eisenbarth G S, Gottlieb P A. Autoimmune polyendocrine syndromes.N Engl J Med 2004. 3502068–2079.2079 [PubMed]
15. Orth D N, Kovacs W J. The adrenal cortex. In: Wilson JW, Foster DW, Kronenberg HM, Larsen PR, eds. Williams textbook of endocrinology, 9th ed. Philadelphia: WB Saunders, 1998. 517–664.664
16. Le Roux C W, Meeran K, Alaghband‐Zadeh J. Is a 09. 00‐h serum cortisol useful prior to a short synacthen in outpatient assessment Ann Clin Biochem 2002. 39148–150.150 [PubMed]
17. Leong K S, Wallymahmed M, Wilding J. et al Clinical presentation of thyroid dysfunction and Addison's disease in young adults with type 1 diabetes. Postgrad Med J 1999. 75467–470.470 [PMC free article] [PubMed]

Articles from Postgraduate Medical Journal are provided here courtesy of BMJ Publishing Group