Is L-dopa test effective in detecting adrenal insufficiency with preliminary diagnosis of growth hormone deficiency in children with short stature?

Objectives: Growth hormone (GH) deficiency in children is characterized by impaired linear growth and reduced growth velocity, necessitating confirmation through two GH stimulation tests. At the time of diagnosis, approximately 4 % of children with GH deficiency exhibit concomitant adrenocorticotropic hormone (ACTH) deficiency, a prevalence that increases to 12 % over the course of follow-up. The insulin tolerance test is regarded as the gold standard for assessing both cortisol and GH secretion; however, its clinical application is constrained by potential risks and the requirement for close medical supervision. This study aims to evaluate the effect of the L-dopa stimulation test on cortisol secretion in pediatric patients with short stature.

Methods: This retrospective study included 138 children (65 females, 73 males) who underwent the L-dopa stimulation test for the assessment of GH deficiency at the Pediatric Endocrinology Clinic between January 2010 and December 2023. Serum cortisol concentrations were measured at the 90th and 120th min of the test. Patients with a peak cortisol response <18 μg/dL subsequently underwent a low-dose (1 μg) ACTH stimulation test to further evaluate adrenal function. Clinical, anthropometric, and biochemical data were extracted from medical records and subjected to statistical analysis.

Results: The mean age of the study cohort was 9.34 ± 3.79 years, with 65 (47.1 %) female and 73 (52.9 %) male patients. The mean height standard deviation score (SDS) was -2.62 ± 0.83, while the mean weight SDS was -1.81 ± 1.09. The mean peak GH response was 5.64 ± 4.0 ng/mL following the clonidine stimulation test and 7.29 ± 5.23 ng/mL following the L-dopa test. A total of 35 children exhibited a peak cortisol response <18 μg/dL during the L-dopa test. Among these, 35 underwent a low-dose (1 μg) ACTH stimulation test, and 7 patients (20 % of those tested; 5.1 % of the total cohort) were diagnosed with adrenal insufficiency, defined as a peak cortisol response <18 μg/dL. These patients were initiated on oral hydrocortisone therapy. Comparative analyses between patients with normal vs. impaired ACTH test responses (<18 μg/dL vs. ≥18 μg/dL) revealed no statistically significant differences in peak cortisol response to the L-dopa test, peak GH response to clonidine or L-dopa, age at presentation, gender, weight SDS, or height SDS.

Conclusions: The L-dopa stimulation test may represent a valuable adjunctive tool for the evaluation of cortisol sufficiency in children undergoing assessment for suspected GH deficiency. However, further prospective studies with larger sample sizes and standardized protocols are warranted to validate its diagnostic accuracy and clinical utility in detecting adrenal insufficiency.