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Childhood-Specific Symptoms

Excess adrenal androgens may lead to early puberty

Excess androgens can drive signs of early puberty, including1:

  • Rapid increase in height
  • Appearance of pubic or axillary hair
  • Body odor
  • Enlargement of the penis
  • Breast growth
  • Menstruation

Early puberty can negatively impact mental health2*:

31%Girls with early puberty
9%Boys with early puberty

More likely to develop depressive symptoms in adolescence

Early menarche increases the risk of major depression and substance abuse by almost 2-fold3†

*Based on a study not specific to CAH with a sample size of ~5000 adolescents (aged 9-13 years) from the Adolescent Brain Cognitive Development (ABCD) Study. Earlier pubertal timing at ages 10-11 years. Depressive symptoms assessed 2 years later at ages 12-13 years.2

†This study was not specific to CAH and included 496 women. Early menarche was defined as prior to 11.6 years. Incidence of major depression was 21% and 11% with and without early menarche, respectively. Incidence of substance abuse was 33% and 18% with and without early menarche, respectively.3

Excess adrenal androgens may accelerate growth

Children with CAH may be initially taller than their peers.4

2.3 years

advanced bone age in children (age: 6-10 years) with CAH who had excess adrenal androgens vs their peers without CAH (n=32)4‡

Final height might be less than genetic potential.5

10 cm and

14 cm

shorter on average than their peers in adulthood in a study of 103 female patients and 61 male patients with CAH5§

Optimizing growth in children with CAH using GCs alone may be a balancing act:

  • Excess adrenal androgens can lead to initial accelerated growth, but result in shorter final adult stature due to premature closure of growth plates
  • The use of high GC doses to reduce excess adrenal androgens can suppress growth during critical development periods and lead to longer comorbidities
More on GC comorbidities

‡Androstenedione levels were compared with reference values for age and sex and expressed as treatment scores that represented normal, overtreatment (androgen oversuppression), and undertreatment (androgen excess). Absolute values for androstenedione were not reported in this study.4

§Patients with CAH were age- and sex-matched to the general population for comparison.5

GC=glucocorticoid.

Learn how glucocorticoids are used to treat CAH6

Role of GCs in CAH

REFERENCES

  1. Hindmarsh PC, Geertsma K. Congenital Adrenal Hyperplasia: A Comprehensive Guide. Elsevier/Academic Press; 2017.
  2. MacSweeney N, Allardyce J, Edmondson-Stait A, et al. The role of brain structure in the association between pubertal timing and depression risk in an early adolescent sample (the ABCD Study®): a registered report. Dev Cogn Neurosci. 2023;60:101223. doi:10.1016/j.dcn.2023.101223
  3. Stice E, Presnell K, Bearman SK. Relation of early menarche to depression, eating disorders, substance abuse, and comorbid psychopathology among adolescent girls. Dev Psychol. 2001;37(5):608-619. doi:10.1037/0012-1649.37.5.608
  4. Van der Kamp HJ, Otten BJ, Buitenweg N, et al. Longitudinal analysis of growth and puberty in 21-hydroxylase deficiency patients. Arch Dis Child. 2002;87(2):139-144. doi:10.1136/adc.87.2.139
  5. Arlt W, Willis DS, Wild SH, et al. Health status of adults with congenital adrenal hyperplasia: a cohort study of 203 patients. J Clin Endocrinol Metab. 2010;95(11):5110-5121. doi:10.1210/jc.2010-0917
  6. Mallappa A, Merke DP. Management challenges and therapeutic advances in congenital adrenal hyperplasia. Nat Rev Endocrinol. 2022;18(6):337-352. doi:10.1038/s41574-022-00655-w