ESPE Abstracts

Background: The circulating steroid metabolome in boys undergoes significant changes during infancy reflecting functional and structural rearrangements of the adrenal glands as well as the transient activity of the hypothalamic–pituitary–gonadal axis, also called minipuberty. Studies investigating the serum steroid metabolome dynamics during infancy in a longitudinal manner are however sparse.

Objective: We aimed to explore the dynamics of the serum steroid metabolome in healthy, term male infants and establish male-specific reference curves for steroid hormones in infancy.

Participants & Methods: In a prospective, longitudinal cohort (The COPENHAGEN Minipuberty Study, 2016-2018) we followed healthy, term, newborns from birth onwards with repeated clinical examinations including blood sampling during a one-year follow-up. Serum levels of 16 steroid hormones were measured using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Age-specific reference values (Standard deviation scores, SDS) were modelled using GAMLSS. Correlations were analyzed using the Spearman rank correlation method.

Results: The steroid metabolome exhibited a distinct pattern with increasing Cortisol and Corticosterone levels as well as sharply decreasing 11-deoxycortisol, Androstenedione, 17-OHP and Progesterone levels. The majority of steroid hormones decreased to <50% of their maximum value within three months of age. Testosterone concentrations peaked around 1-2 months after birth. Mean steroid hormone SDS exhibited predominantly positive and partially strong correlations during the first year of life, e.g. 17-OHP vs. 11-deoxycortisol (rs = 0.7) and 17-OHP vs. Androstenedione (rs = 0.6). However, correlations exhibited marked alterations over time, e.g. Corticosterone vs. 17-OHP (0-60 days: rs = 0.0; 180-400 days: rs = 0.7) or DHEAS vs. Androstenedione (0-60 days: rs = 0.6; 180-400 days: rs = 0.2).

Conclusions: Our findings provide a detailed description of the serum steroid metabolome dynamics. In addition, changes in ratio between individual steroids may provide insights in changes in steroidogenic enzyme activity during the first year of life. The detailed age-specific reference ranges can be used in clinical settings like diagnosis and monitoring of treatment of rare steroidogenic disorders.