ACTH stimulation tests for the diagnosis of adrenal insufficiency: Systematic review and meta-analysis

Naykky Singh Ospina, Alaa Al Nofal, Irina Bancos, Asma Javed, Khalid Benkhadra, Ekta Kapoor, Aida N. Lteif, Neena Natt, M. Hassan Murad

Research output: Contribution to journalArticlepeer-review

103 Scopus citations


Context: The diagnosis of adrenal insufficiency is clinically challenging and often requires ACTH stimulation tests. Objective: To determine the diagnostic accuracy of the high-(250 mcg) and low-(1 mcg) doseACTH stimulation tests in the diagnosis of adrenal insufficiency. Methods: We searched six databases through February 2014. Pairs of independent reviewers selected studies and appraised the risk of bias. Diagnostic association measures were pooled across studies using a bivariate model. Data Synthesis: For secondary adrenal insufficiency, we included 30 studies enrolling 1209 adults and 228 children. High-and low-dose ACTH stimulation tests had similar diagnostic accuracy in adults and children using different peak serum cortisol cutoffs. In general, both tests had low sensitivity and high specificity resulting in reasonable likelihood ratios for a positive test (adults: high dose, 9.1; low dose, 5.9; children: high dose, 43.5; low dose, 7.7), but a fairly suboptimal likelihood ratio for a negative test (adults: high dose, 0.39; low dose, 0.19; children: high dose, 0.65; low dose, 0.34). For primary adrenal insufficiency, we included five studies enrolling 100 patients. Data were only available to estimate the sensitivity of high dose ACTH stimulation test (92%; 95% confidence interval, 81-97%). Conclusion: Both high-and low-dose ACTH stimulation tests had similar diagnostic accuracy. Both tests are adequate to rule in, but not rule out, secondary adrenal insufficiency. Our confidence in these estimates islowtomoderatebecause of the likely risk of bias, heterogeneity,andimprecision.

Original languageEnglish (US)
Pages (from-to)427-434
Number of pages8
JournalJournal of Clinical Endocrinology and Metabolism
Issue number2
StatePublished - Feb 2016

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Endocrinology
  • Clinical Biochemistry
  • Biochemistry, medical


Dive into the research topics of 'ACTH stimulation tests for the diagnosis of adrenal insufficiency: Systematic review and meta-analysis'. Together they form a unique fingerprint.

Cite this