A 2-Year-Old With Pubic Hair
What's Your Diagnosis?
Sharpen Your Diagnostic Skills
A 2-year-old girl presented with pubic hair, the development of which her mother had noted 6 months ago. The mother’s health had been unremarkable during the pregnancy. The parents are nonconsanguineous. There is no family history of congenital adrenal hyperplasia or precocious development of pubic hair. The child’s past health is unremarkable, and she was taking no medications.
The patient was a healthy girl with isolated development of pubic hair. In particular, there was no breast enlargement, clitoromegaly, or hirsutism.
What’s Your Diagnosis?
(Answer and discussion on next page)
Answer: PREMATURE ADENARCHE
Adrenarche refers to the puberty of the adrenal gland and is characterized by activation of adrenal androgen production and impressive increases in dehydroepiandrosterone (DHEA), dehydroepiandrosterone sulfate (DHEAS), androstenedione, and testosterone.1-3 Premature or precocious adrenarche refers to an earlier than normal secretion of adrenal androgens, which results in isolated development of pubic hair (pubarche) before 8 years of age in girls and 9 years in boys, without the appearance of other signs of sexual maturation.4
In a study conducted in Italy, the prevalence of premature adrenarche was 6% among 7-year-old girls and 9% among 8-year-old girls.5 In another study, premature adrenarche was found in 4.6% of Turkish girls younger than 8 years.6 In the United States, premature adrenarche occurs in 2.8% of white girls and 17.7% of black girls.6 The female to male ratio is approximately 10:1.4,7 Prematurity and intrauterine growth retardation might predispose a susceptible individual to premature adrenarche.8 Excess weight gain might be a trigger for adrenarche, and obesity is reported to be associated with a higher incidence of premature adrenarche.8 The occurrence of premature adrenarche usually is sporadic.
Premature adrenarche is secondary to an early isolated maturation of the zona reticularis, with an increase in adrenal androgen secretion for chronologic age, but with normal glucocorticoid levels.9 Adrenarche is independent of gonadarche and proceeds even in individuals with gonadal dysgenesis. Oversecretion of adrenocorticotropic hormone (ACTH) or corticotropin-releasing hormone might have a permissive role in the modulation of adrenal androgen secretion.4 An increase of a central androgen-stimulating proopiomelanocortin-derived hormone might be the primum movens of premature adrenarche.10
Increased sensitivity of the sexual hair follicles to androgens also has been suggested as a mechanism, because in some patients, premature pubarche occurs despite normal androgen levels.3 This might account for the increased prevalence of premature adrenarche among black children.1,2 The association of premature adrenarche with prematurity and intrauterine growth retardation suggests that premature adrenarche might be a component of a fetal or neonatal programming event.7,11
The frequency of premature adrenarche increases with age between 3 and 8 years of age in girls and between 3 and 9 years of age in boys, although cases have been reported as early as 5 weeks of age.2 Dark, coarse, and often curly hair is the first clinical sign. The hair initially is limited to the labia majora in girls or the root of the penis in boys and then extends gradually into the pubic region. The amount and thickness of the hair might progress very slowly or not at all. Axillary hair, increased body odor, oily skin, and acne also might be noted. Acanthosis nigricans is more common in patients with premature adrenarche.2 Hirsutism, deepening of the voice, clitoral enlargement, breast development, phallic or testicular enlargement, and other evidence of virilization or precocious puberty are characteristically absent.1
A transient acceleration of growth is common, but final height is usually not affected.10 The onset of puberty usually occurs at the normal age.10
Premature adrenarche must be differentiated from the following conditions. In pubic hair of infancy, pubic hair usually occurs in an atypical location, such as the scrotum in boys and the mons pubis in girls.12 The growth of the pubic hair is slowly progressive in the first few months of life, remains stationary for a few more months, and then might regress. Pubic hair of infancy is due to transiently elevated androgen levels in the first few months of life and increased sensitivity of sexual hair follicles to androgens.12
Precocious puberty can be differentiated by the concomitant appearance of pubic hair with breast development in girls or testicular enlargement in boys. Premature adrenarche is extremely difficult if not impossible to differentiate from the early stage of constitutional precocious puberty.2
Pubic hair might be the first sign of virilization related to an adrenocortical or gonadal tumor. In these conditions, other evidence of excessive androgen secretion such as acne, clitoral or phallic enlargement, hirsutism, increased muscle mass, markedly accelerated linear growth, and deepening of the voice usually appears at the same time or shortly after the onset of pubic hair development. In boys with an adrenocortical tumor, testicular size usually is small, whereas the reverse is true for boys with a testicular tumor.1,2 Exogenous androgen can cause development of pubic hair and other signs of virilization.
Congenital adrenal hyperplasia, usually due to 21-hydroxylase deficiency, classically produces prenatal virilization in females but can, in a late-onset attenuated form, present with premature development of sexual hair, hirsutism, and menstrual irregularities. In the male, the testes usually remain infantile, but other secondary sexual characteristics are advanced.1,2
Precocious development of pubic hair can cause embarrassment for the child and anxiety for the parents.2 Mood and behavioral problems are more common in girls with premature adrenarche than in those with on-time adrenarche.13 These problems may interfere with parent-child interaction, peer relationships, and school performance.13
Girls with premature adrenarche have a higher incidence of polycystic ovary syndrome (PCOS) later in life.7 PCOS is characterized by menstrual irregularities, obesity, acne, hirsutism, and polycystic ovaries.7 In some girls, premature adrenarche may be a forerunner of metabolic syndrome (obesity, hypertension, insulin resistance, type 2 diabetes, and dyslipidemia).4,13 Affected patients are at increased risk for early atherosclerotic cardiovascular disease.4 In contrast, premature adrenarche in boys is not associated with an increased incidence of endocrine or metabolic abnormalities.1,2
Serum concentrations of DHEA, DHEAS, androstenedione, and testosterone, along with urinary 17-ketosteroids, should be measured. In premature adrenarche, these levels usually are increased for chronologic age and are in the range of those found in early puberty.10 DHEAS levels, however, might exceed those of pubertal controls.2 A radiographic assessment of bone age should be performed. In premature adrenarche, the bone age usually is within 2 standard deviations of chronologic age.
Moderately elevated levels of serum androgens other than DHEAS, bone age advancement, or signs of atypical premature adrenarche such as cystic acne or signs of systemic virilization indicate the need to assess ACTH levels to rule out congenital adrenal hyperplasia.2 An excessive increase in the serum 17-hydroxyprogesterone level to greater than 45 nmol/L after an ACTH stimulation test suggests late-onset congenital adrenal hyperplasia.10
Marked elevation of serum androgen levels and advanced bone age suggest the possibility of an adrenocortical or gonadal tumor.2 A patient with an androgen-producing adrenocortical tumor does not respond to ACTH stimulation or dexamethasone suppression, whereas a patient with congenital adrenal hyperplasia does respond.2 Adrenal computed tomography or ultrasonography should be performed if significant virilization has occurred and ACTH stimulation does not reveal congenital adrenal hyperplasia.2
Pelvic ultrasonography should be performed if PCOS is suspected. The presence of an enlarged ovary and multiple small follicles scattered around an echogenic stroma establishes the diagnosis.10 Color Doppler flow measurements might reveal significant vascular changes within the intraovarian vessels in patients with PCOS.10 Serum glucose, insulin, cholesterol, and triglyceride levels should be measured if metabolic syndrome is suspected.
Education and reassurance of the patient and family, as well as psychological and emotional support for the child and family, are essential to the clinical management of such patients.1 The parents and child should be reassured that in most cases premature adrenarche is a benign condition and that the child will develop normally. Continued observation and periodic reevaluation are necessary, because premature adrenarche might be the first sign of precocious puberty. In some girls, premature adrenarche might be a forerunner of PCOS or metabolic syndrome. Girls with a higher body mass index warrant particularly close follow-up.2
1. Leung AK. Premature adrenarche. In: Leung AK, ed. Common Problems in Ambulatory Pediatrics: Symptoms and Signs. New York, NY: Nova Science Publishers; 2011:277-282.
2. Leung AK, Robson WL. Premature adrenarche. J Pediatr Health Care. 2008;22(4):230-233.
3. Güven A, Cinaz P, Ayvali E. Are growth factors and leptin involved in the pathogenesis of premature adrenarche in girls? J Pediatr Endocrinol Metab. 2005;18(8):785-791.
4. Saenger P, DiMartino-Nardi J. Premature adrenarche. J Endocrinol Invest. 2001;24(9):724-733.
5. Danubio ME, De Simone M, Vecchi F, Amicone E, Altobelli E, Gruppioni G. Age at menarche and age of onset of pubertal characteristics in 6-14-year-old girls from province of L’Aquila (Abruzzo, Italy). Am J Hum Biol. 2004;16(4):470-478.
6. Atay Z, Turan S, Guran T, Furman A, Bereket A. The prevalence and risk factors of premature thelarche and pubarche in 4- to 8-year-old girls. Acta Paediatr. 2012;101(2):e71-e75.
7. Oberfield SE, Sopher AB, Gerken AT. Approach to the girl with early onset of pubic hair. J Clin Endocrinol Metab. 2011;96(6):1610-1622.
8. Neville KA, Walker JL. Precocious pubarche is associated with SGA, prematurity, weight gain, and obesity. Arch Dis Child. 2005;90(3):258-261.
9. Azziz R, Farah LA, Moran C, Knochenhauer ES, Potter HD, Boots LR. Early adrenarche in normal prepubertal girls: a prospective longitudinal study. J Pediatr Endocrinol Metab. 2004;17(9):1231-1237.
10. Battaglia C, Regnani G, Mancini F, et al. Isolated premature pubarche: ultrasonographic and color Doppler analysis—a longitudinal study. J Clin Endocrinol Metab. 2002;87(7):3148-3154.
11. van Weissenbruch MM. Premature adrenarche, polycystic ovary syndrome and intrauterine growth retardation: does a relationship exist? Curr Opin Endocrinol Diabetes Obes. 2007;14(1):35-40.
12. Leung AK, Hegde HR, Stephure DK. Scrotal hair in identical twin infants. Int J Dermatol. 2005;44(12):1042-1044.
13. Dorn LD, Rose SR, Rotenstein D, et al. Differences in endocrine parameters and psychopathology in girls with premature adrenarche versus on-time adrenarche. J Pediatr Endocrinol Metab. 2008;21(5):439-448.