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Short ACTH stimulation test: A single 60-minute cortisol sample is sufficient
Clinica Chimica Acta 395 (2008) 183
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Clinica Chimica Acta j o u r n a l h o m e p a g e : w w w. e l s e v i e r. c o m / l o c a t e / c l i n c h i m
Letter to the editor Short ACTH stimulation test: A single 60-minute cortisol sample is sufficient Dear Editor, The short ACTH stimulation test is routinely used for dynamic testing of adrenal function in cases of suspected adrenal insufficiency [1]. This study was designed to assess which short ACTH stimulation test sampling strategy gave the best performance compared to the full 0, 30 and 60 min sampling regime. Details of serum cortisol measurements (using a Beckman Coulter DxI 800 immunoassay analyser) on short ACTH stimulation test samples over 2 years were extracted from the laboratory information system for study. A normal response was defined as a 0, 30 or 60 min cortisol concentration ≥550 nmol/l [2]. Other responses were considered subnormal. Five thousand nine hundred seventy one serum cortisol measurements were performed on 2174 patients (Table 1). There was no significant difference between the 4 sampling regimes in age, gender or requesting discipline. Of the normal responses, the 60-minute cortisol concentration exceeded the 30-minute cortisol concentration Table 1 Details of short ACTH stimulation tests over 2 years Sampling regime
n
Mean age in years (SD)
% Male
% Subnormal response
0, 30 and 60 min 0 and 30 min 0 and 60 min 30 and 60 min
1623 490 52 9
62.1 (16.6) 61.1 (16.2) 64.4 (14.7) 61.2 (17.2)
52 56 52 56
28 39 31 11
Table 2 Performance measures (and 95% confidence intervals) for different short ACTH stimulation test sampling regimes compared to 0, 30 and 60-minute sampling Sampling regime
Specificity, %
Positive predictive value, %
Accuracy, %
0 min 30 min 60 min 0 and 30 min 0 and 60 min 30 and 60 min
28.3 (25.7–30.9) 84.7 (82.6–86.8) 98.9 (98.3–99.5) 85.1 (83.1–87.2) 99.7 (99.5–100) 99.7 (99.3–100)
35.5 (32.9–38.1) 72.1 (68.6–75.5) 97.2 (95.8–98.7) 72.6 (69.2–76.1) 99.4 (98.6–100) 99.1 (98.3–100)
48.6 (46.1–51.0) 89.0 (87.5–90.6) 99.2 (98.8–99.6) 89.3 (87.8–90.8) 99.8 (99.6–100) 99.8 (99.5–100)
0009-8981/$ – see front matter © 2008 Elsevier B.V. All rights reserved. doi:10.1016/j.cca.2008.04.024
in 87% of cases. Using the individual data and the final classification (normal or subnormal) for the 0/30/60-minute regime group, the anticipated ability of different sampling regimes to identify a subnormal response is shown in Table 2 (for calculation purposes, disease positive = subnormal response; test positive = all cortisol concentrations of given regime b550 nmol/l). Using this approach, there are no false negatives and thus sensitivity and negative predictive value of all regimes were 100%. This study shows that different sampling regimes are used even within the same institution for no obvious clinical reason. The 60minute sample was the single most useful sample, demonstrated by the superior performance of the 60, 0/60, 30/60 min regimes. The 0/60minute regime provides a 0-minute sample for ACTH determination, which can be used to evaluate a subnormal response for primary or secondary adrenal insufficiency, but requires collection and analysis of 2 samples. The single 60-minute regime offers reduced phlebotomy discomfort and analytical cost with similar accuracy and a 2.8% false positive rate compared to the 0/30/60-minute regime. This supports a similar smaller study suggesting that a single 60-minute sample can replace the 30/60-minute regime [3]. The high percentage of subnormal responses in the 0/30-minute regime (Table 1) indicates a significant false positive rate (27%) and this strategy should be discouraged. Laboratories should help standardize such dynamic endocrine tests to ensure that the best diagnostic data is available to clinicians at the minimum cost and discomfort to patients. References [1] Grinspoon SK, Biller BM. Clinical review 62: laboratory assessment of adrenal insufficiency. J Clin Endocrinol Metab 1994;79:923–31. [2] May ME, Carey RM. Rapid adrenocorticotropic hormone test in practice. Retrospective review. Am J Med 1985;79:679–84. [3] Mansoor S, Islam N, Siddiqui I, Jabbar A. Sixty-minute post-Synacthen serum cortisol level: a reliable and cost-effective screening test for excluding adrenal insufficiency compared to the conventional short Synacthen test. Singap Med J 2007;48:519–23.
Robert C. Hawkins Department of Laboratory Medicine, Tan Tock Seng Hospital, 11 Jalan Tan Tock Seng, 308433, Singapore E-mail address: [email protected]. 10 April 2008
Contents lists available at ScienceDirect
Clinica Chimica Acta j o u r n a l h o m e p a g e : w w w. e l s e v i e r. c o m / l o c a t e / c l i n c h i m
Letter to the editor Short ACTH stimulation test: A single 60-minute cortisol sample is sufficient Dear Editor, The short ACTH stimulation test is routinely used for dynamic testing of adrenal function in cases of suspected adrenal insufficiency [1]. This study was designed to assess which short ACTH stimulation test sampling strategy gave the best performance compared to the full 0, 30 and 60 min sampling regime. Details of serum cortisol measurements (using a Beckman Coulter DxI 800 immunoassay analyser) on short ACTH stimulation test samples over 2 years were extracted from the laboratory information system for study. A normal response was defined as a 0, 30 or 60 min cortisol concentration ≥550 nmol/l [2]. Other responses were considered subnormal. Five thousand nine hundred seventy one serum cortisol measurements were performed on 2174 patients (Table 1). There was no significant difference between the 4 sampling regimes in age, gender or requesting discipline. Of the normal responses, the 60-minute cortisol concentration exceeded the 30-minute cortisol concentration Table 1 Details of short ACTH stimulation tests over 2 years Sampling regime
n
Mean age in years (SD)
% Male
% Subnormal response
0, 30 and 60 min 0 and 30 min 0 and 60 min 30 and 60 min
1623 490 52 9
62.1 (16.6) 61.1 (16.2) 64.4 (14.7) 61.2 (17.2)
52 56 52 56
28 39 31 11
Table 2 Performance measures (and 95% confidence intervals) for different short ACTH stimulation test sampling regimes compared to 0, 30 and 60-minute sampling Sampling regime
Specificity, %
Positive predictive value, %
Accuracy, %
0 min 30 min 60 min 0 and 30 min 0 and 60 min 30 and 60 min
28.3 (25.7–30.9) 84.7 (82.6–86.8) 98.9 (98.3–99.5) 85.1 (83.1–87.2) 99.7 (99.5–100) 99.7 (99.3–100)
35.5 (32.9–38.1) 72.1 (68.6–75.5) 97.2 (95.8–98.7) 72.6 (69.2–76.1) 99.4 (98.6–100) 99.1 (98.3–100)
48.6 (46.1–51.0) 89.0 (87.5–90.6) 99.2 (98.8–99.6) 89.3 (87.8–90.8) 99.8 (99.6–100) 99.8 (99.5–100)
0009-8981/$ – see front matter © 2008 Elsevier B.V. All rights reserved. doi:10.1016/j.cca.2008.04.024
in 87% of cases. Using the individual data and the final classification (normal or subnormal) for the 0/30/60-minute regime group, the anticipated ability of different sampling regimes to identify a subnormal response is shown in Table 2 (for calculation purposes, disease positive = subnormal response; test positive = all cortisol concentrations of given regime b550 nmol/l). Using this approach, there are no false negatives and thus sensitivity and negative predictive value of all regimes were 100%. This study shows that different sampling regimes are used even within the same institution for no obvious clinical reason. The 60minute sample was the single most useful sample, demonstrated by the superior performance of the 60, 0/60, 30/60 min regimes. The 0/60minute regime provides a 0-minute sample for ACTH determination, which can be used to evaluate a subnormal response for primary or secondary adrenal insufficiency, but requires collection and analysis of 2 samples. The single 60-minute regime offers reduced phlebotomy discomfort and analytical cost with similar accuracy and a 2.8% false positive rate compared to the 0/30/60-minute regime. This supports a similar smaller study suggesting that a single 60-minute sample can replace the 30/60-minute regime [3]. The high percentage of subnormal responses in the 0/30-minute regime (Table 1) indicates a significant false positive rate (27%) and this strategy should be discouraged. Laboratories should help standardize such dynamic endocrine tests to ensure that the best diagnostic data is available to clinicians at the minimum cost and discomfort to patients. References [1] Grinspoon SK, Biller BM. Clinical review 62: laboratory assessment of adrenal insufficiency. J Clin Endocrinol Metab 1994;79:923–31. [2] May ME, Carey RM. Rapid adrenocorticotropic hormone test in practice. Retrospective review. Am J Med 1985;79:679–84. [3] Mansoor S, Islam N, Siddiqui I, Jabbar A. Sixty-minute post-Synacthen serum cortisol level: a reliable and cost-effective screening test for excluding adrenal insufficiency compared to the conventional short Synacthen test. Singap Med J 2007;48:519–23.
Robert C. Hawkins Department of Laboratory Medicine, Tan Tock Seng Hospital, 11 Jalan Tan Tock Seng, 308433, Singapore E-mail address: [email protected]. 10 April 2008