A Collage of Genital Lesions, Part 5

Premature Adrenarche
A 7-year-old girl had growth of pubic hair for the past 6 months. The hair was initially limited to the labia majora and then extended gradually into the pubic area. She grew 8 cm (3.1 in) in the past year. Her health history was unremarkable; she was not taking any medications. On examination, her weight was 35 kg (77.2 lb); height, 125 cm (49.2 in). She did not have breast development, axillary hair, acne, or clitoral enlargement.

Premature or precocious adrenarche refers to an earlier than normal secretion of adrenal androgens that results in isolated development of pubic hair (pubarche) before age 8 years in girls and 9 years in boys, without the appearance of other signs of sexual maturation. It affects about 0.8% of white girls aged 7 to 7.9 years. The condition is more common in African American children. The female to male ratio is approximately 10:1.

Premature adrenarche is secondary to an early isolated maturation of the zona reticularis, with increased adrenal androgen secretion for chronological age but with normal glucocorticoid levels. Another suggested mechanism is increased sensitivity of the sexual hair follicles to androgens, because in some patients, premature pubarche is associated with normal androgen levels.

Precocious puberty can be differentiated from premature adrenarche by the concomitant appearance of pubic hair with breast development in girls and with testicular enlargement in boys. Other differential diagnoses include virilization caused by congenital adrenal hyperplasia and an adrenocortical or gonadal tumor. In premature adrenarche, serum concentrations of dehydroepiandrosterone, dehydroepiandrosterone sulfate (DHEAS), androstenedione, and testosterone and urinary 17-ketosteroids are usually increased for chronological age and in the range of those found in early puberty. The bone age is usually within 2 standard deviations of the chronological age. Moderately elevated levels of serum androgen other than DHEAS, bone age advancement, or signs of atypical premature pubarche (such as cystic acne or symptoms of systemic virilization) indicate the need for a corticotropin test to rule out late-onset congenital adrenal hyperplasia. Marked elevation of serum androgen levels and advanced bone age suggest the possibility of an adrenocortical or gonadal tumor.

Education and reassurance of the patient and family along with psychological/emotional support are essential to clinical management of premature adrenarche. Continued observation and periodic reevaluation are necessary because premature adrenarche might be the first sign of precocious puberty. Premature adrenarche in girls is associated with a higher incidence of polycystic ovary syndrome later in life. In some girls, premature adrenarche may be a forerunner of polycystic ovary syndrome or syndrome X (obesity, hypertension, insulin resistance, type 2 diabetes mellitus, and dyslipidemia). Affected patients are at increased risk for early atherosclerotic cardiovascular disease. In contrast, premature adrenarche in boys is not associated with an increased incidence of endocrine or metabolic abnormalities.

Girls with higher body mass index warrant particularly close follow-up. Early identification of these patients can allow for earlier treatment of the associated conditions with a reduction in risk of early cardiovascular disease.

FOR MORE INFORMATION:
• Andiran N, Yordam N, Kirazli S. Global fibrinolytic capacity is decreased in girls with premature adrenarche: a new pathological finding? J Pediatr Endocrinol Metab. 2005;18:1373-1381.
• Leung AK, Robson WL. Premature adrenarche. J Pediatr Health Care. 2008; 22:230-233.
• Saenger P, DiMartino-Nardi J. Premature adrenarche. J Endocrinol Invest. 2001;24:724-733.

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Isolated Scrotal Hair of Infancy
This infant was born at term to a 32-year-old gravida 2 para 3 after a normal vaginal delivery. It was a twin pregnancy that was otherwise uncomplicated. The mother had not taken any medications during the pregnancy and had no virilization or hirsutism. The parents were nonconsanguineous. There was no family history of congenital adrenal hyperplasia. The baby’s birth weight and length were 2784 g (6.1 lb) and 55 cm (21.7 in), respectively. Scrotal hair developed at age 1 month. The hair growth gradually progressed over the next 2 to 3 months. Physical examination at 4 months revealed curly, black terminal hair on the scrotum. The testes and penis were normal size. Levels of serum electrolytes and 17-hydroxyprogesterone were normal. The serum testosterone level was 1.8 nmol/L. Findings from an abdominal ultrasonographic examination were normal. The other identical twin also had scrotal hair first noted at 1 month of age and had a similar unremarkable clinical course.

Isolated genital hair of infancy presumably results from transiently elevated androgen levels in the first few months of life and an increased sensitivity of sexual hair follicles to androgens. Shortly after birth, a transient surge of gonadotropins occurs and leads to a sharp increase in testosterone levels, which peaks at 1 to 3 months of age (2.8 to 13.9 nmol/L). Thereafter, the gonadotropin levels fall; by age 6 months, serum testosterone levels decrease to the low prepubertal levels (0.3 to 0.7 nmol/L) that persist until the beginning of puberty. In isolated genital hair of infancy, sexual hair usually occurs in an atypical location, such as the scrotum in boys and the mons pubis in girls. The growth of hair is slowly progressive in the first few months of life, remains stationary for a few more months, and then might regress.

The development of sexual hair in infancy can be the first sign of virilization, which may result from congenital adrenal hyperplasia, an adrenal tumor, or a gonadal tumor. In such cases, evidence of excessive androgen production (eg, acne, phallic enlargement, hirsutism, and markedly accelerated growth) usually appears at the same time as or shortly after the onset of sexual hair development. In boys with congenital adrenal hyperplasia, the testes remain infantile but other secondary sexual characteristics are advanced. In boys with an adrenal tumor, the testes are usually small, whereas the reverse is true for boys with a testicular tumor.

FOR MORE INFORMATION:
• Leung AK, Hegde HR, Stephure DK. Scrotal hair in identical twin infants. Int J Dermatol. 2005;44:1042-1044.
• Papadimitriou A, Beri D, Nicolaidou P. Isolated scrotal hair in infancy. J Pediatr. 2006;148:690-691.