Abstract
Purpose
The aims of the present study are to evaluate the effect of l-dopa on the secretion of cortisol and adrenocorticotropic hormone (ACTH) in short children and compare the performance of this test with the insulin tolerance test (ITT) in a large number of patients.
Methods
A total of 29 short but otherwise healthy children [mean age 9.5 ± 3.1 years (range 3.7–14.9 years)] who had inadequate growth hormone (GH) responses to ITT, which was performed as the first test, were consecutively enrolled in this study. GH, cortisol, and ACTH levels were measured just before administration of l-dopa and then at 30-min intervals afterward over a total time of 120 min. Peak concentrations of cortisol and ACTH exceeding 18 µg/dL (496 mmol/L) and 46 pg/mL (10.2 pmol/L), respectively, were defined as an adequate response.
Results
While the l-dopa test revealed that 26 of the 29 children (89.7%) had peak serum cortisol levels of > 18 µg/dL, the ITT revealed that only 23 children (79.3%) had adequate cortisol responses. The l-dopa test revealed normal ACTH responses (> 46 pg/mL) in 24 (82.8%) patients. Peak cortisol levels were higher in children with normal ACTH responses than in those with subnormal ACTH responses (25.6 ± 6.2 vs. 19.5 ± 6.4 µg/dL, p = 0.054), but the difference observed was statistically insignificant.
Conclusion
The results of the current study confirm that the l-dopa test is a reliable test of cortisol secretion. As such, this test may be applicable to assessments of the hypothalamic–pituitary–adrenal axis.
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Simunkova K, Duskova M, Kosak M, Krsek M, Hana V, Hill M, Jandikova H, Pospisilova H, Sramkova M, Bifulco E, Starka L (2015) Response of cortisol metabolites in the insulin tolerance test and Synacthen tests. Physiol Res 64(2):237–246
di Iorgi N, Napoli F, Allegri A, Secco A, Calandra E, Calcagno A, Frassinetti C, Ghezzi M, Ambrosini L, Parodi S, Gastaldi R, Loche S, Maghnie M (2010) The accuracy of the glucagon test compared to the insulin tolerance test in the diagnosis of adrenal insufficiency in young children with growth hormone deficiency. J Clin Endocrinol Metab 95(5):2132–2139
Galloway PJ, McNeill E, Paterson WF, Donaldson MD (2002) Safety of the insulin tolerance test. Arch Dis Child 87(4):354–356
Bancos I, Hahner S, Tomlinson J, Arlt W (2015) Diagnosis and management of adrenal insufficiency. Lancet Diabetes Endocrinol 3(3):216–226
Poyrazoglu S, Akcay T, Arslanoglu I, Atabek ME, Atay Z, Berberoglu M, Bereket A, Bideci A, Bircan I, Bober E, Can S, Cesur Y, Darcan S, Demir K, Dundar B, Ersoy B, Esen I, Guven A, Kara C, Keskin M, Kurtoglu S, Memioglu N, Ozbek MN, Ozgen T, Sari E, Siklar Z, Simsek E, Turan S, Yesilkaya E, Yuksel B, Darendeliler F (2015) Current practice in diagnosis and treatment of growth hormone deficiency in childhood: a survey from Turkey. J Clin Res Pediatr Endocrinol 7(1):37–44
Abdu TA, Elhadd TA, Neary R, Clayton RN (1999) Comparison of the low dose short synacthen test (1 microg), the conventional dose short synacthen test (250 microg), and the insulin tolerance test for assessment of the hypothalamo-pituitary-adrenal axis in patients with pituitary disease. J Clin Endocrinol Metab 84(3):838–843
Ospina NS, Al Nofal A, Bancos I, Javed A, Benkhadra K, Kapoor E, Lteif AN, Natt N, Murad MH (2016) ACTH stimulation tests for the diagnosis of adrenal insufficiency: systematic review and meta-analysis. J Clin Endocrinol Metab 101(2):427–434
Vizner B, Reiner Z, Sekso M (1983) Effect of l-dopa on growth hormone, glucose, insulin, and cortisol response in obese subjects. Exp Clin Endocrinol 81(1):41–48
Chambers JW, Brown GM (1976) Neurotransmitter regulation of growth hormone and ACTH in the rhesus monkey: effects of biogenic amines. Endocrinology 98(2):420–428
Hayek A, Crawford JD (1972) l-dopa and pituitary hormone secretion. J Clin Endocrinol Metab 34(5):764–766
King AB (1969) The effect of exogenous dopamine on ACTH secretion. Proc Soc Exp Biol Med 130(2):445–447
Nilsson KO, Thorell JI (1974) The effect of l-dopa on the blood concentrations of growth hormone, thyrotrophin, gonadotrophins, cortisol and glucose in children with short stature. Acta Paediatr Scand 63(6):812–816
Philippi H, Pohlenz J, Grimm W, Koffler T, Schonberger W (2000) Simultaneous stimulation of growth hormone, adrenocorticotropin and cortisol with l-dopa/l-carbidopa and propranolol in children of short stature. Acta Paediatr 89(4):442–446
Stratakis CA, Rusovici DE, Kulin HE, Finkelstein JW (2000) Dysregulation of the hypothalamic-pituitary-adrenal axis in short children with and without growth hormone deficiency. J Pediatr Endocrinol Metab 13(8):1095–1100
Marakaki C, Papadimitriou DT, Kleanthous K, Papadopoulou A, Papadimitriou A (2015) l-dopa stimulates cortisol secretion through adrenocorticotropic hormone release in short children. Horm Res Paediatr 84(5):319–322
Marakaki C, Papadimitriou DT, Papadopoulou A, Fretzayas A, Papadimitriou A (2014) l-dopa is a potent stimulator of cortisol in short children. Horm Res Paediatr 81(6):386–390
Neyzi O, Bundak R, Gokcay G, Gunoz H, Furman A, Darendeliler F, Bas F (2015) Reference values for weight, height, head circumference, and body mass index in turkish children. J Clin Res Pediatr Endocrinol 7(4):280–293
Growth Hormone Research S (2000) Consensus guidelines for the diagnosis and treatment of growth hormone (GH) deficiency in childhood and adolescence: summary statement of the GH Research Society. GH Research Society. J Clin Endocrinol Metab 85(11):3990–3993
Shah A, Stanhope R, Matthew D (1992) Hazards of pharmacological tests of growth hormone secretion in childhood. BMJ 304(6820):173–174
Lopez FJ, Negro-Vilar A (1988) Estimation of endogenous adrenocorticotropin half-life using pulsatility patterns: a physiological approach to the evaluation of secretory episodes. Endocrinology 123(2):740–746
Renner U, Arzberger T, Pagotto U, Leimgruber S, Uhl E, Muller A, Lange M, Weindl A, Stalla GK (1998) Heterogeneous dopamine D2 receptor subtype messenger ribonucleic acid expression in clinically nonfunctioning pituitary adenomas. J Clin Endocrinol Metab 83(4):1368–1375
Pivonello R, Ferone D, Lombardi G, Colao A, Lamberts SW, Hofland LJ (2007) Novel insights in dopamine receptor physiology. Eur J Endocrinol 156(1):13–21
Itoi K, Suda T, Tozawa F, Dobashi I, Ohmori N, Sakai Y, Abe K, Demura H (1994) Microinjection of norepinephrine into the paraventricular nucleus of the hypothalamus stimulates corticotropin-releasing factor gene expression in conscious rats. Endocrinology 135(5):2177–2182
van Vught AJ, Nieuwenhuizen AG, Gerver WJ, Veldhorst MA, Brummer RJ, Westerterp-Plantenga MS (2009) Pharmacological and physiological growth hormone stimulation tests to predict successful GH therapy in children. J Pediatr Endocrinol Metab 22(8):679–694
Albertsson-Wikland K, Rosberg S, Karlberg J, Groth T (1994) Analysis of 24-h growth hormone profiles in healthy boys and girls of normal stature: relation to puberty. J Clin Endocrinol Metab 78(5):1195–1201
Mazzola A, Meazza C, Travaglino P, Pagani S, Frattini D, Bozzola E, Corneli G, Aimaretti G, Bozzola M (2008) Unreliability of classic provocative tests for the diagnosis of growth hormone deficiency. J Endocrinol Invest 31(2):159–162
Stanley TL, Levitsky LL, Grinspoon SK, Misra M (2009) Effect of body mass index on peak growth hormone response to provocative testing in children with short stature. J Clin Endocrinol Metab 94(12):4875–4881
Carel JC, Tresca JP, Letrait M, Chaussain JL, Lebouc Y, Job JC, Coste J (1997) Growth hormone testing for the diagnosis of growth hormone deficiency in childhood: a population register-based study. J Clin Endocrinol Metab 82(7):2117–2121
Kopelman PG, Grossman A, Lavender P, Besser GM, Rees LH, Coy D (1988) The cortisol response to corticotrophin-releasing factor is blunted in obesity. Clin Endocrinol (Oxf) 28(1):15–18
Borm K, Slawik M, Seiler L, Flohr F, Petrick M, Honegger J, Reincke M (2003) Is the plasma ACTH concentration a reliable parameter in the insulin tolerance test? Eur J Endocrinol 149(6):535–541
Acknowledgements
This research did not receive any specific grant from any funding agency in the public, commercial or not-for-profit sector. We would like to thank the children and their parents who participated in this study. The authors would like to thank Enago (www.enago.com) for the English language review.
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The study was approved by the local ethics committee of the Dokuz Eylul University, Faculty of Medicine in İzmir, in light of the Helsinki Declaration.
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Written informed consent was obtained from the children and their parents before the study.
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Acar, S., Paketçi, A., Tuhan, H. et al. Comparison of the effects of the l-dopa and insulin tolerance tests on cortisol secretion. J Endocrinol Invest 41, 901–907 (2018). https://doi.org/10.1007/s40618-017-0815-7
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DOI: https://doi.org/10.1007/s40618-017-0815-7