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

 

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?

What is the connection between cirrhosis and adrenal insufficiency (AI)?

The reported prevalence of AI in patients with liver disease varies widely (30-60%)1. However, there is no consensus on how to define AI in such patients, nor is the methodology for its evaluation standardized. 

A common criticism is the frequent reliance on total, not free, serum cortisol in cirrhosis which may overestimate the prevalence of AI because cortisol is bound to corticosteroid binding globulin and albumin, commonly found at lower concentrations in cirrhosis. However, even when based on measuring free cortisol, AI is found in 12%-29% of clinically stable cirrhotic patients1.

 Secondary AI due to hypothalamic-pituitary dysfunction has been reported in Child-Pugh class A, B, and C patients (42%, 69%, and 80%, respectively)2. The mechanism of AI in cirrhosis is unclear, but low serum cholesterol in cirrhosis leading to lack of substrate for steroidogenesis, and increased levels of circulating endotoxin and pro-inflammatory cytokines impairing the hypothalamic-pituitary-adrenal axis have been postulated1.

 

References

  1. Fede G, Spadaro L, Purrello F. Review: adrenal insufficiency in liver disease. J Liver 2014;3:1. https://www.ncbi.nlm.nih.gov/pubmed/22234976
  2. Zietz, B, Lock, G, Plach, B, et al. Dysfunction of the hypothalamic-pituitary-glandular axes and relation to Child-Pugh classification in male patients with alcoholic and virus-related cirrhosis. Eur J Gastroenterol Hepatology 2003;15:495-501. https://www.ncbi.nlm.nih.gov/pubmed/12702906
What is the connection between cirrhosis and adrenal insufficiency (AI)?