Premature Pubertal Development in a Five Year Old Female Sexual development occurring before 8 years of age in females is considered precocious puberty, the most recognized endocrinopathy in a female pediatric patient. In more than 90% of girls, sexual precocity is idiopathic and requires a diagnosis of exclusion (Midyett, 2003). Precocious pubertal development may be classified as: • (1) GnRH-dependent, called true or central precocious puberty; or • (2) GnRH-independent, called peripheral precocious puberty or precocious pseudopuberty Presenting condition A five year old Old Order Mennonite female presented to the pediatrician with her 27 year old mother who was concerned she was ‘maturing too early’. The patient’s mother described the child’s development of sparse pubic hair resembling that of an adolescent in color and texture. She noticed the hair approximately three months previously and has since noticed a slight proliferation. The child’s mother had not noticed any other physical, mental, or neurological symptoms she believed to be out of the ordinary. The patient is the first child of the family and has two younger male siblings. According to the mother, the child had a NEGATIVE history of the following contributory or predisposing factors of precocious puberty: • History of trauma, infection, or insults to central nervous system • Previous history of head injury, or cranial irradiation (e.g. treatment for leukemia) • Exposure to environmental sex hormones, products containing sex steroids, (birth control pills, anabolic steroids), estrogen-containing products, or herbal preparations • family history of premature pubertal development • rapid or delayed growth in first- and second-degree relatives Pertinent exam findings: • General: The patient appears, by stature, to be around age 8. At a true age of 5 years and 3 months and 62 lbs and 49 inches tall, the child charts at significantly greater than the 97th percentile for both height and weight in her age range. The child’s growth charts from age 3 to the present are not available for calculation of growth velocity. Growth from birth to age 2 is within normal range for age. There are no other characteristics anomalous of the child’s stated history. • Skin: No myxedema, café-au-lait spots, hyperpigmentation suggesting McCune Albright Syndrome. Age and sex appropriate texture and distribution of hair, pubic hair being the only exception. • Neck: No palpable thyroid or lumps • Skeleton: no deformities, symmetric throughout • Abdomen: Soft, NT, ND, no abdominal masses, no tenderness, rebound, or guarding. Liver, spleen, and kidneys not palpable. • Genitals: No evidence of virilization or ambiguity of genitals, no changes in skin vascularity related to increased hormonal activity. Pubic Hair: Tanner II, minimal coarse pigmented hair mainly on the labia majora (normal mean onset of pubic hair growth is 12 years of age). • Breasts: Tanner I – prepubertal, no glandular tissue; areola follows the skin contours of the chest (normal for the child’s age) • Neurologic system, funduscopic examination, cranial nerve tests, cerebellar tests, peripheral motor examination, sensory examination, and all parts of the physical exam unmentioned were unremarkable and age appropriate. Summary of tests: Initial investigations performed by the pediatrician included: • Bone Age: A complete radiologic view of both hands was performed to evaluate bone age. The bone age best corresponds to the female standard of 7 years and 10 months. This is roughly 3 standards beyond the chronologic age of 5 years and 3 months. (In most patients with precocious puberty, bone age is more than 2 years ahead of chronologic age) •LH: within normal range for chronological age •FSH: within normal range for chronological age •Pitocin: within normal range for chronological age •Testosterone and estradiol: pending • TSH : within normal range for chronological age • GnRH stimulating test: pending •Cranial MRI: pending •Abdominal US: No significant abnormality detected. •Pelvic US: Age-appropriate measurement of the uterus. Mild amount of free cul-de-sac fluid, nonvisualization of the ovaries. Differential Diagnosis • Idiopathic true or peripheral precocious puberty • Premature Adrenarche • Organic brain disease (tumors, cysts, injury) • Hypothyroidism • Congenital adrenal hyperplasia • McCune-Albright syndrome • Gonadal tumors • Adrenal tumors • Medication-related precocity • In this child, pending additional labs, there aren’t clear signs that activation of the normal hypothalamic-pituitary-gonadal axis has been ‘kicked on’, suggesting precocious pseudopuberty. The other possible option, most probable if all tests return negative, is premature adrenarche, (the appearance of pubic or axillary hair, usually occurring in girls between ages 4 and 8, without other evidence of maturation). Children affected by premature adrenarche are of slightly advanced height and osseous maturation. This condition is benign and self-limiting, “requiring no therapy, but long-term follow-up suggests that girls with premature adrenarche are at high risk (20%) of hyperandrogenism and polycystic ovarian syndrome as adults” (Midyett, 2003). • In this particular case, the plan is to try to confirm the diagnosis of premature adrenarche by testing gonadotrophin and gonadal steroid secretions (should be at pre-pubertal levels) and circulating dehydroepiandrosterone concentrations (should be matched with appropriate bone age and pubic hair development). These tests will also help to rule out CAH and possible adrenal tumors. If premature adrenarche is diagnosed, follow-up would require continuation of routine growth charting, monitoring for additional pubertal and hormonal changes, and reassurance that premature andrenarche is a benign pubertal variant. Goals • Identify the cause of sexual precocity • Delay sexual maturation to prevent short stature in adulthood caused by premature epiphyseal fusion brought on by precocious puberty (GnRH analog) • Provide full psychological support for child and parents. REFERENCES • Larsen, R.(2003.Precocious Puberty.[Electronic version]. Williams Textbook of Endocrinology. (10th ed.). • Midyett LK, Moore WV, Jacobson JD. (2003). Are pubertal changes in girls before age 8 benign? Pediatrics;111:47-51. Retrieved from http://www.firstconsult.com/fc_home/members/?urn=com.firstconsult/ • Pinto SM, Garden AS. (2006). Prepubertal adrenarche: a defined clinical entity. Am J Obstet Gynecol;195:327-9. Retrieved from http://www.firstconsult.com/fc_home/members/?urn=com.firstco nsult/