Diagnosis

CONFIRMATORY TESTS MAY BE NEEDED TO DIAGNOSE HYPERCORTISOLISM1

A secondary abnormal cortisol test result may be needed for a hypercortisolism diagnosis. When selecting a secondary test, it is important to consider1:

  • Patient presentation
  • Suspected source of hypercortisolism

Available data suggest that patients who have type 2 diabetes (T2D) as the primary complication are more likely to have an adrenal source of excess cortisol.2-5 It may be helpful to take this into consideration when interpreting the following biochemical test results.

CONSIDERATIONS FOR SECONDARY TESTS

1-MG DEXAMETHASONE SUPPRESSION TEST (DST)

Measures suppression of adrenocorticotropic hormone (ACTH) and autonomous cortisol secretion1

Repeat test to confirm initial abnormal test result. Consider checking serum dexamethasone levels for adequate suppression of the hypothalamic-pituitary-adrenal axis1

URINARY-FREE CORTISOL (UFC)

Measures excretion of circulating unbound cortisol in the urine over a 24-hour period1

Patients with confirmed autonomous adrenal cortisol secretion often have 24-hour UFC levels within the normal range despite the presence of hypercortisolism-related comorbidities6,7

LATE-NIGHT SALIVARY CORTISOL (LNSC)

Measures free cortisol in the saliva when cortisol should be at its lowest level1

Studies have shown that patients with confirmed autonomous adrenal cortisol secretion often have discordant LNSC results6

Additional tests can be performed to confirm ACTH-independent hypercortisolism

The following tests can provide additional evidence of autonomous, ACTH-independent cortisol secretion. Please refer to the protocols and procedures established by your lab provider.

  • Plasma ACTH: Low or suppressed* levels (<10 pg/mL) suggest ACTH-independent hypercortisolism, >20 pg/mL suggests ACTH-dependent hypercortisolism8,9
  • DHEA-S: Low levels (<40 μg/dL) suggest ACTH-independent hypercortisolism7
  • Adrenal computed tomography scan10

*Suppressed is defined as <5 pg/mL; however, recent studies have shown ACTH levels as high 26.9 pg/mL in patients with confirmed adrenal hypercortisolism.11

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References

1. Nieman LK, Biller BM, Findling JW, et al. J Clin Endocrinol Metab. 2008;93(5):1526-1540. doi:10.1210/jc.2008-0125 2. Catargi B, Rigalleau V, Poussin A, et al. J Clin Endocrinol Metab. 2003;88(12):5808-5813. doi:10.1210/jc.2003-030254 3. Chiodini I, Torlontano M, Scillitani A, et al. Eur J Endocrinol. 2005;153(6):837-844. doi:10.1530/eje.1.02045 4. Steffensen C, Pereira AM, Dekkers OM, Jørgensen JO. Eur J Endocrinol. 2016;175(6):R247-R253. doi:10.1530/EJE-16-0434 5. Giovanelli L, Aresta C, Favero V, et al. J Endocrinol Invest. 2021;44(8):1581-1596. doi:10.1007/s40618-020-01484-2 6. Kuzu I, Zuhur SS, Demir N, Aktas G, Yener Ozturk F, Altuntas Y. Endokrynol Pol. 2016;67(5):487-492. doi:10.5603/EP.a2016.0028 7. Chiodini I, Ramos-Rivera A, Marcus AO, Yau H. J Endocr Soc. 2019;3(5):1097-1109. doi:10.1210/js.2018-00382 8. Vaidya A, Hamrahian A, Bancos I, Fleseriu M, Ghayee HK. Endo Pract. 2019;25(2):178-192. doi:10.4158/DSCR-2018-0565 9. Lacroix A, Feelders RA, Stratakis CA, Nieman LK. Lancet. 2015;386(9996):913-927. doi:10.1016/S0140-6736(14)61375-1 10. Fleseriu M, Auchus R, Bancos I, et al. Lancet Diabetes Endocrinol. 2021;9(12):847-875. doi:10.1016/S2213-8587(21)00235-7 11. Eller-Vainicher C, Morelli V, Aresta C, et al. J Endocr Soc. 2020;4(8):bvaa079. doi:10.1210/jendso/bvaa079