FP37-4 Decreased Adrenomedullary Function in Newborns with Classical Congenital Adrenal Hyperplasia (CAH)

Program: Abstracts - Orals, Featured Poster Presentations, and Posters
Session: FP37-Clinical Pediatric Endocrinology
Monday, June 17, 2013: 10:45 AM-11:15 AM
Presentation Start Time: 11:00 AM
Room 102 (Moscone Center)

Poster Board MON-599
Anna Ryabets-Lienhard*1, Bhavna Bali1, Sandra Hall2, Christianne Lane3, Ashley H. Park1, Mitchell E. Geffner4 and Mimi S Kim1
1Children's Hospital Los Angeles, Los Angeles, CA, 2Children's Hospital Los Angeles, 3University of Southern California, Keck School of Medicine, 4Children's Hospital of Los Angeles, The Saban Research Institute, Los Angeles, CA
Background:Classical CAH is a potentially life-threatening disorder with risk for serious adrenal crises as early as the first week of life. Affected babies and toddlers are also at risk for hypoglycemia, attributable mostly to cortisol deficiency. Although it is known that older children and adolescents with classical CAH have impaired adrenomedullary function, this has yet to be evaluated in infants and toddlers. We hypothesize that decreased levels of catecholamines are already present in newborns with classical CAH at birth, suggesting impaired fetal adrenal development.

Methods:Plasma catecholamines were measured by high performance liquid chromatography in 6 newborns with classical CAH and in 9 newborn controls with congenital hypothyroidism. Baseline measurements were collected at the time of diagnosis (visit 1) for both groups, and 3-5 weeks later in the control group (visit 2) after infants were rendered euthyroid with thyroxine replacement.

Results: Both study groups consisted of full-term, female infants, with no significant difference in age (CAH 4.2 ± 1.5 days for 5 CAH babies, one additional subject was 61 days old; controls 7.7 ± 3.4 days), birth weight, birth length, weight, length, or vital signs at study entry. CAH subjects had ambiguous genitalia (67% Prader 4, 33% Prader 3). Controls were not stressed at visits 1 or 2 (cortisol 6.15 ± 4.19 and 3.28 ± 2.75 μg/dL, p = 0.4). Basal plasma epinephrine (epi) levels were significantly lower in the CAH group compared to controls (83.8 ± 12.3 vs. 119.8 ± 38.5 pg/mL, p = 0.04). Basal plasma norepinephrine (norepi) levels did not differ between the CAH and control groups (1243 ± 667.8 vs. 952.8 ± 221.8 pg/mL, p = 0.27). In addition, compared to older children (mean age 12.4 ± 4 years) previously studied in our institution, basal plasma epi and norepi levels were significantly higher in the newborns (older children: epi 32 ± 25.47 pg/mL, norepi 327 ± 111.45 pg/mL; p < 0.001 for both). There was a negative, although not significant, correlation between epi and newborn screen 17-hydroxyprogesterone (17-OHP) (r = -0.6, p = 0.2). There was no significant change in plasma epi from visit 1 to 2 in the control group (p = 0.65), thus, accounting for a possible confounding effect of hypothyroidism on catecholamine production.

Discussion: Newborns with classical CAH have decreased levels of plasma epi compared to controls, indicating that adrenomedullary hypofunction may be present at birth. Conversion of norepi to epi is mediated by intra-adrenal glucocorticoids; thus, decreased levels of plasma epi in newborns with CAH may be due to adrenocortical dysfunction during fetal development. In addition, the lower catecholamine levels in older children may imply a further decrease in adrenomedullary function over time. Larger prospective longitudinal studies of adrenomedullary dysfunction in patients with CAH are warranted.

Nothing to Disclose: AR, BB, SH, CL, AHP, MEG, MSK

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