Does the time of day matter when performing cosyntropin stimulation test on my patient with suspected adrenal insufficiency?

 

No, it doesn’t! Although there is a diurnal variation in serum cortisol level, time of the day does not have an appreciable impact on the synthetic ACTH, also known as cosyntropin (Cortrosyn), stimulation test results.

A 2018 retrospective cohort study found that outcomes from cosyntropin stimulation (CS) testing was not affected by time of the day (0800-1000 h vs 1001-1200 h vs after 1200 h).1

An experimental study involving healthy volunteers with normal adrenal function also found that the time of day of CS testing (250  mcg IV) did not influence the peak or the delta of cortisol levels when measured by immunoassay.2 Similarly, an experiment involving normal volunteers concluded that while compared to testing at 0800 h the afternoon (1600) cortisol response to CS was more pronounced at 5 and 15 min, there was no significant difference in cortisol levels at 30 min.3  Parenthetically, peak cortisol level is usually obtained at 1 h after IV cosynstropin administration.

So if you think your patient should undergo CS testing, there is no reason to wait until the next morning!

Bonus Pearl: Did you know that while the half-life of cortisol is between 70-120 min, the half-life of cosyntropin is only 15 min? 4

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References

  1. Munro V, Elnenaei M, Doucette S, et al. The effect of time of day testing and utility of 30 and 60 min cortisol values in the 250 mcg ACTH stimulation test. Clin Biochem 2018;54:37-41. https://www.ncbi.nlm.nih.gov/pubmed/29458002
  2. Jonklaas J, Holst JP, Verbalis JG, et al. Changes in steroid concentration with the timing of corticotropin stimulation testing in participants with adrenal insufficiency. Endocr Pract 2012;18:66-75. https://www.ncbi.nlm.nih.gov/pubmed/21856601
  3. Dickstein G, Shechner C, Nicholson WE, et al. Adrenocorticotropin stimulation test: effect of basal cortisol level, time of day, and suggested new sensitive low dose test. J Clin Endocrinol Metab 72:773-78. https://www.ncbi.nlm.nih.gov/pubmed/2005201
  4. Hamilton DD, Cotton BA. Cosyntropin as a diagnostic agent in the screening of patients for adrenocortical insufficiency. Clinical Pharmacology Advances and Applications 2010;2:77-82. https://www.ncbi.nlm.nih.gov/pubmed/22291489

Disclosures: The listed questions and answers are solely the responsibility of the author and do not necessarily represent the official views of Massachusetts General Hospital, Harvard Catalyst, Harvard University, its affiliate academic healthcare centers, or its contributors. Although every effort has been made to provide accurate information, the author is far from being perfect. The reader is urged to verify the content of the material with other sources as deemed appropriate and exercise clinical judgment in the interpretation and application of the information provided herein. No responsibility for an adverse outcome or guarantees for a favorable clinical result is assumed by the author. Thank you!

Does the time of day matter when performing cosyntropin stimulation test on my patient with suspected adrenal insufficiency?

Can I rule out primary adrenal insufficiency by obtaining a single morning serum cortisol level in my hospitalized patient with unexplained hyponatremia?

Primary adrenal insufficiency (PAI) can be confidently ruled out when the morning (eg, 6 AM) serum cortisol level is greater than 17 ug/dl. Lower cut-off values are associated with lower probability of excluding PAI: > 10 ug/dl, 62%-67% and ≥5 ug/dl, 36%. 1,2 Conversely, PAI is highly likely when the morning serum cortisol level is less than 3 ug/dl. 3

Since many patients may have serum cortisol levels between 3 ug/dl and 17 ug/dl (ie, in the “indeterminate” range), confirmatory testing commonly performed through cosyntropin stimulation test (CST) is often necessary.

Although the standard CST involves measuring serum cortisol levels at baseline, 30 min, and 60 min with peak cortisol level <18 ug/dl indicative of PAI, several studies have reported that a single post-CST cortisol level obtained at 60 min may also be diagnostic. 3

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References

  1. Erturk E, Jaffe CA, Barkan AL. Evaluation of the integrity of the hypothalamic-pituitary-adrenal axis by insulin hypoglycemia test. J Clin Endocrinol Metab 83;2350-54. https://www.ncbi.nlm.nih.gov/pubmed/9661607
  2. Bornstein SR, Allolio B, Arlt W, et al. Diagnosis and treatment of primary adrenal insufficiency: An Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab 2016;101:364-89. https://academic.oup.com/jcem/article/101/2/364/2810222
  3. Odom DC, Gronowski AM, Odom E, et al. A single, post-ACTH cortisol measurement to screen for adrenal insufficiency in the hospitalized patient. J Hosp Med 2018;13: E1-E5. https://www.ncbi.nlm.nih.gov/pubmed/29444197
Can I rule out primary adrenal insufficiency by obtaining a single morning serum cortisol level in my hospitalized patient with unexplained hyponatremia?