Chapter 173 Puberty: Abnormal
THE CHALLENGE
Scope of the Problem: For all patients with precocious puberty (pubertal changes before age 7 or cyclic menstruation before age 10), the possibility of a serious process, either central or peripheral, must be evaluated. (Because of evolving changes in maturation rates, these traditional ages should be adjusted downward by 1 year for African American girls.) Precocious puberty is customarily divided into two classifications: true or gonadotropin-releasing hormone (GnRH)-dependent (70%), and precocious pseudopuberty that is independent of GnRH control. For most girls older than 4 years, no specific cause is discovered for the early development. By contrast, the most common cause of precocious change in girls younger than 4 is a central nervous system lesion, most often hamartomas of the hypothalamus. Even when the sequence of events appears normal, a serious process (such as a slowly progressing brain tumor) must be aggressively sought initially and watched for with long-term continuing follow-up. Delayed puberty is a relatively uncommon problem in girls. When it occurs, the possibility of a genetic or hypothalamic–pituitary abnormality must be considered, along with a moderately large number of other possibilities. Based on the average age and normal variation of puberty, any girl who has not exhibited breast budding by age 13 requires preliminary investigation. Similarly, girls who do not menstruate by age 15 or 16, regardless of other sexual development, should be evaluated. Patients should also be evaluated any time there is a disruption in the normal sequence of puberty or when there is patient or parental concern. Patients with significant abnormalities of either height or weight should be evaluated for chromosomal abnormalities or endocrinopathies.
TACTICS
Relevant Pathophysiology: True precocious puberty, also known as complete, isosexual, or central precocity, is related to early activation of the hypothalamic–pituitary–gonadal axis. In three fourths of patients, there is no indication of how or why the normal processes of puberty are accelerated. In the remaining one fourth, a central nervous system abnormality is the cause. A number of central nervous system pathologic conditions may result in activation of GnRH secretion and the early onset of pubertal changes. Precocious pseudopuberty is also referred to as incomplete or peripheral and may be isosexual or heterosexual. In these patients, there may be secretion of sex steroids or human chorionic gonadotropin from sources other than the pituitary. More than 10% of girls with precocious puberty have an ovarian tumor. These tumors are palpable in 80% of patients or may be readily detected by ultrasonography or tomographic studies. Bleeding is heavy and irregular in character, befitting escape from the normal control mechanisms. One of the most common chromosomal causes of absent (delayed) menstruation is the premature ovarian failure found in patients with Turner’s syndrome (45,X). The absence of one X chromosome results in accelerated ovarian follicular atresia, to the extent that by the age of puberty, no functionally competent follicles remain. The appearance of these patients is noteworthy for short stature, webbed neck (pterygium colli), a shieldlike chest with widely spaced nipples, and an increased carrying angle of the arms (cubitus valgus). Buccal smears do not demonstrate Barr bodies, and chromosomal analysis confirms the diagnosis. Because these women will not undergo any secondary sexual maturation, referral to a specialist for counseling and management of replacement hormonal manipulations is advisable. Deletions of only a part of the long arm of the X chromosome have been shown to be associated with premature ovarian failure, with the earliest failures associated with the greatest deletions.
Strategies: The evaluation of patients with precocious puberty is focused on detecting possible life-threatening disease and defining the velocity of the process. When the diagnosis of true precocious puberty is established, generally by exclusion, treatment with GnRH agonists usually halts the progression of change. This therapy is expensive and is effective only if the observed changes are under central control. Suppression of GnRH may also be carried out using medroxyprogesterone acetate (Depo-Provera), in doses of 100 to 200 mg given intramuscularly every 2 to 4 weeks. This therapy is less likely to control bone growth abnormalities than is GnRH agonist treatment. (Without any therapy, approximately 50% of girls will not reach 5 feet in height.) The evaluation of patients with delayed pubertal development must begin with a general history, including general health, weight and height records, and family history, including the pubertal experience of others in the family. Physical examination should identify the type and degree of sexual development present. The presence of breast changes generally indicates the production of estrogen, and the development of pubic or axillary hair indicates the production of androgens. Laboratory evaluation should include serum follicle-stimulating hormone (FSH), luteinizing hormone (LH), and prolactin measurements; skull radiographs; and thyroid function studies. Bone age, chromosomal or cytologic studies, and pelvic ultrasonography or other imaging studies may also be indicated. Because of the significance of the potential causes of disordered puberty, most of these patients should be evaluated by or in consultation with a specialist.
Patient Education: Reassurance; American College of Obstetricians and Gynecologists Patient Education Pamphlet AP041 (Growing Up [Especially for Teens]), AP049 (Menstruation [Especially for Teens]).
IMPLEMENTATION
Special Considerations: Although precocious puberty is most often heralded by the sequence of increased growth, thelarche, and adrenarche, these events may occur simultaneously, or menarche itself may be the first indication. Idiopathic or constitutional precocious puberty is associated with a normal reproductive life and normal age of menopause. The greatest risk for abnormality comes from the early closure of the bony growth plates that often leaves these patients with short stature. Therapy is worth considering for young children to achieve adult height and to avoid the social and emotional stresses that early maturation can entail. If the cause of delayed puberty is found to be hypogonadism, hormonal therapy initiates and sustains the development of normal secondary sex characteristics. Hormonal therapy also allows for normal height and bone mass deposition to be achieved. Adolescents require much less hormone therapy than do adults or postmenopausal women. Therapy usually begins with unopposed estrogen at a dose of 0.3 mg of conjugated estrogen, 0.5 mg of estradiol, or their equivalent daily. In 6 to 12 months, this dose is roughly doubled and medroxyprogesterone acetate is added (10 mg for the first 12 days of the month). This combination results in regular menstruation but is insufficient for contraception. Normal pubertal development generally proceeds when the patient reaches a bone age of 13.
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