New diagnostic approaches to subclinical adrenal insufficiency
Authors:
K. Šimůnková 1,2; K. Vondra 1
Authors‘ workplace:
Endokrinologický ústav, Praha
Ředitel: doc. MUDr. Vojtěch Hainer, CSc.
1; III. interní klinika 1. LF UK a VFN, Praha
Přednosta: prof. MUDr. Štěpán Svačina, DrSc. MBA
2
Published in:
Prakt. Lék. 2009; 89(12): 698-702
Category:
Diagnostis
Overview
The diagnosis of subclinical forms of hypocorticalism is an ongoing problem. New diagnostic approaches to adrenal insufficiency are still being sought, aimed at increasing and improving the specificity and sensitivity of results. Correct interpretation of the results is a pre-condition to early and correct treatment. Dynamic tests play a major role in the diagnosis of various degrees of hypocorticalism. The low dose ACTH test is described in detail, and its benefits and disadvantages are reviewed in comparison to standard high dose ACTH test. Evaluation of free fraction of cortisol would be beneficial, but is technically challenging. Therefore the total serum cortisol is assessed, but its concentration is affected by binding proteins of cortisol, especially by the concentration of transcortin. Estrogens in combined oral contraception are a big problem in daily practice since estrogens increase the concentration of transcortin and consequently the levels of cortisol are artificially increased. At the end of the article, the authors discuss new diagnostic approaches - mainly the evaluation of salivary cortisol.
Key words:
adrenal insufficiency, Short Synacthen test, low-dose ACTH test, transcortin, salivary cortisol.
Sources
1. Aardal, E., Holm, A.C. Cortisol in saliva - reference ranges and relation to cortisol in serum. Eur. J. Clin. Chem. Clin. Biochem. 1995, 33, p. 927-932.
2. Alia, P., Villabona, C., Gimenez, O. et al. Profile, mean residence time of ACTH and cortisol responses after low and standard ACTH tests in healthy volunteers. Clin. Endocrinol. 2006, 65, p. 346-351.
3. Angeli, A., Ramenghi, U., Del Bello, S. et al. Increased plasma corticosteroid-binding globulin in insulin-dependent pubertal diabetics: relationships with other glycoproteins, growth hormone and prolactin. Acta Diabetol. Lat. 1979, 16, p. 295–304.
4. Arlt, W. The approach to the adult with newly diagnosed adrenal insufficiency. J. Clin. Endocrinol. Metab. 2009, 94, p. 1059-1067.
5. Contreras. L.N., Arregger, A.L., Persi, G.G. et al. A new less-invasive and more informative low-dose ACTH test: salivary steroids in response to intramuscular corticotrophin. Clin. Endocrinol. 2004, 61, p. 675-682.
6. Coolens, J.L., Heyns, W. Marked elevation and cyclic variation of corticosteroid-binding globulin: an inherited abnormality? J. Clin. Endocrinol. Metab. 1989, 68, p. 492-494.
7. Courtney, C.H., McAllister, A.S. Bell, P.M. et al. Low- and standard-dose corticotropin and insulin hypoglycemia testing in the assessment of hypothalamic-pituitary-adrenal function after pituitary surgery. J. Clin. Endocrinol. Metab. 2004, 89, p. 1712-1717.
8. Dhillo, W.S., Kong, W.M., Le Roux, C.W. et al. Cortisol-binding globulin is important in the interpretation of dynamic tests of the hypothalamic-pituitary-adrenal axis. Eur. J. Endocrinol. 2002, 146, p. 231-235.
9. Dickstein, G., Shechner, C., Nicholson, W.E. et al. Adrenocorticotropin stimulation test: effects of basal cortisol level, time of day, and suggested new sensitive low dose test. J. Clin. Endocrinol. Metab. 1991, 72, p. 773-778.
10. Dickstein, G., Spigel, D. Arad, E. Shechner, C. One microgram is the lowest ACTH dose to cause a maximal cortisol response. There is no diurnal variation of cortisol response to submaximal ACTH stimulation. Eur. J. Endocrinol. 1997, 137, p. 172-175.
11. Dickstein, G. The assessment of the hypothalamo-pituitary-adrenal axis in pituitary disease: are there short cuts? J. Endocrinol. Invest. 2003, 26, p. 25-30.
12. Dickstein, G. The low dose (1 microgram) ACTH test-when and how to use it. Clin. Endocrinol. 1998, 49, p. 135.
13. Doi, S.A.R., Lasheen, I., Al-Humood, K., Al-Shoumer, K.A.S. Relationship between cortisol increment and basal cortisol: Implications for the low-dose short adrenocorticotropic hormone stimulation test. Clin. Chem. 2006, 52, p. 746-749.
14. Emptoz-Bonneton, A., Cousin, P., Seguchi, K., Avvakumov, G.V. Novel human corticosteroid-binding globulin variant with low cortisol-binding afinity. J. Clin. Endocrinol. Metab. 2000, 85, p. 361-367.
15. Giordano, R., Balbo, M., Picu, A. et al. Hypothalamus-pituitary adrenal axis evaluation in patients with hypothalamo-pituitary-disorders: comparison of different provocative tests. Clin. Endocrinol. 2008, 68, p. 935-941.
16. Gozansky, W.S., Lynn, J.S., Laudenslager, M.L., Kohrt, W.M. Salivary cortisol determined by enzyme immunoassay is preferable to serum total cortisol for assessment of dynamic hypothalamic-pituitary-adrenal axis activity. Clin. Endocrinol. 2005, 63, p. 336-341.
17. Christ-Crain, M., Jutla, S., Widmer, I. et al. Measurement of serum free cortisol shows discordant responsivity to stress and dynamic evaluation. J. Clin. Endocrinol. Metab. 2007, 92, p. 1729-1735.
18. Klose, M., Lange ,M., Rasmussen, A.K. et al. Factors influencing the adrenocorticotropin test: role of contemporary cortisol assays, body composition, and oral contraceptive agents. J. Clin. Endocrinol. Metab. 2007, 92, p. 1326-1333.
19. Landon, J., James, V.H., Cryer, R.J. et al. Adrenocorticotropic effects of syntetic polypeptide-b1-24-corticotropin-in man. J. Clin. Endocrinol. Metab. 1964, 24, p. 1206-1213.
20. Le Roux, C.W., Meeran, K., Alaghband-Zadeh, J. Is a 0900-h serum cortisol useful prior to a short synacthen test in outpatient assessment? Ann. Clin. Biochem. 2002, 39, p. 148-150.
21. Lewis, J.G., Bagley, C.J., Doder, P.A. et al. Plasma free cortisol fraction reflects levels of functioning corticosteroid-binding globulin. Clin. Chim. Acta. 2005, 359, p. 189-194.
22. Lewis, J.G., Mopert, B., Srand, B.I. et al. Plasma variation of corticosteroid-binding globulin and sex hormone-binding globulin. Horm. Metab. Res. 2006, 38, p. 241-245.
22. Mihrshahi, R., Lewis, J.G., Ali, S.O. Hormonal effects on the secretion and glycoform profile of corticosteroid-binding globulin. J. Steroid. Biochem. Mol. Biol. 2006, 101(4-5), p. 275-285.
23. Mishra, S.K., Gusta, N., Goswami, R. Plasma adrenocorticotropin (ACTH) values and cortisol response to 250 and 1 ∝g ACTH stimulation in patients with hyperthyroidism before and after carbimazole therapy: case-control comparative ctudy. J. Clin. Endocrinol. Metab. 2007, 92, p. 1693-1696.
24. Nieman, L.K. Dynamic evaluation of adrenal hypofunction. J. Endocrinol. Invest. 2003, 26, p. 74-82.
25. Paisley, N.A., Rowles, S.V., Brandon, D., Trainer, P.J. Subnormal peak cortisol response to stimulation testing does not predict a subnormal cortisol production rate. J. Clin. Endocrinol. Metab. 2009, 94, p. 1757-1760.
26. Park, Y.J., Park, K.S., Kim, J.H. et al. Reproducibility of the cortisol response to stimulation with the low dose (1 microg) of ACTH. Clin. Endocrinol. (Oxf) 1999, 51, p. 153-158.
27. Patel, L., Clayton, P.E. Clinical usefulness of the low dose ACTH test. J. Endocrinol. Invest. 1999, 22, p. 401-404.
28. Poršová, I., Stárka, L., Blahoš, J., Putz, Z. Stupňovaný nitrosvalový ACTH test se stanovením kortizolu ve slinách. Vnitř. Lék. 1987, 33, s. 356-360.
29. Putignano, P., Toja, P., Dubini, A. et al. Midnight salivary cortisol versus urinary free and midnight serum cortisol as screening tests for Cushing’s syndrome. J. Clin. Endocrinol. Metab. 2003, 88, p. 4153-4157.
30. Quereshi, A.C., Bahri, A., Breen, L.A. et al. The influence of the route of oestrogen administration on serum levels of cortisol-binding globulin and total cortisol. Clin. Endocrinol. 2007, 66, p. 632-635.
31. Rasmuson, S., Olsson, T., Hagg, E. A low dose ACTH test to assess the function of the hypothalamic-pituitary-adrenal axis. Clin. Endocrinol. 1996, 44, p. 151-180.
32. Suliman, A.M., Smith, T.P., Labib, M. et al. The low-dose ACTH test not provide a useful assessment of the hypothalamic-pituitary-adrenal axis in secondary adrenal insufficiency. Clin. Endocrinol. 2002, 56, p. 533-539.
33. Ten, S., New, M., Maclaren, N. Addison’s disease 2001. J. Clin. Endocrinol. Metab. 2001, 86, p. 2909-2922.
34. Tordjman, K., Jaffe, A., Grazas, N. et al. The role of the low dose (1 microgram) adrenocorticotropin test in the evaluation of patients with pituitary diseases. J. Clin. Endocrinol. Metab. 1995, 80, p. 1301-1305.
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