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Corticotropin test reliable for excluding secondary adrenal insufficiency
Test is simpler than the insulin tolerance test and gave accurate long-term results.
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A study testing the long-term predictive accuracy of the corticotropin stimulation test found it safe with regard to excluding secondary adrenal insufficiency in pituitary patients.
“The choice of the most appropriate test for the assessment of the hypothalamic-pituitary-adrenal [HPA] axis has been the subject of much controversy over the last 20 years,” wrote Amar Agha, MD, of Queen Elizabeth Hospital in Birmingham, United Kingdom, and colleagues in the Journal of Clinical Endocrinology and Metabolism. Agha and colleagues tested the long-term accuracy of the high-dose short Synacthen (corticotropin) test, or SST.
Traditionally, the insulin tolerance test is considered the gold standard for assessment of the HPA axis, but it has a number of limitations. “The insulin tolerance test requires the inducement of significant hypoglycemia by giving intravenous insulin, so it is unpleasant for the patient and can be dangerous in situations where the patient has heart disease, seizure disorder or is very elderly,” Agha told Endocrine Today. “It requires admission to [the] hospital for several hours and medical supervision.”
Simple test
In contrast, the SST is “simple and cheap.” Patients receive only one intramuscular injection of synthetic ACTH, and two cortisol samples taken at baseline and after 30 minutes are required. “It is very safe with almost no side effects, can be carried out in the outpatient setting and does not require supervision,” Agha said.
Despite this, several previous studies raised concern about the accuracy of the SST, which were based on the observation that some patients who pass the SST showed a subnormal response to the insulin tolerance test — therefore, suggesting that the SST may give rise to falsely reassuring results.
Agha and colleagues performed their long-term study to determine the safety of the SST by directly assessing the clinical outcome of the patients who passed the SST and did not receive steroid replacement to see whether they came to any harm.
From a total of 748 patients who received an SST between 1998 and 2004, 178 achieved a response between the 2.5th and 15th percentiles of the normal response (510 nmol/L and 635 nmol/L); these patients were eligible for inclusion in the study. One hundred forty-eight (94 women) were used for the final analysis.
Follow-up and results
“All patients were followed up in our pituitary clinic at regular intervals, and clinical assessment of symptoms or signs of adrenal insufficiency and ability to cope with intercurrent illness were made and recorded in the notes,” the investigators wrote.
Patients averaged 41 years old (15 to 85 years) and had a median follow-up duration of 4.2 years. The SST was performed after a median of six weeks after a hypophysectomy and 41 months after radiotherapy. Three patients of the original 178 died during the follow-up period, all from causes unrelated to adrenal disease.
Among patients who achieved a “clear pass” of the SST, only one patient later was found to have adrenal insufficiency, which was most likely dure to evolving hypopituitarism rather than inaccuracy of the initial test. Among patients who achieved borderline results, again only one patient later demonstrated clinically significant glucocorticoid deficiency under stressed conditions. The researchers wrote that “taking clinical outcome as the gold standard, the SST gives a false reassurance rate of less than 1%.”
“For the purpose of clinical decision-making, the SST is reliable [and] a much simpler alternative to the ITT in the assessment of adrenal function in pituitary patients,” Agha said. “Therefore, it should be used as the first-line investigation for that purpose in the majority of cases.” – by Dave Levitan
For more information:
- Agha A, Tomlinson JW, Clark PM, et al. The long-term predictive accuracy of the short Synacthen (corticotropin) stimulation test for the assessment of the hypothalamic-pituitary-adrenal axis. J Clin Endocrinol Metab. 2005;91:43-47.