Chronic endocrine problems run the gamut from mild to severe in the pediatric setting. The long-term implications of an undiagnosed or inadequately managed endocrine disorder can affect a child’s quality of life and may even be life threatening. In many instances of endocrine pathology, the primary care provider will need to consult with a pediatric endocrine specialist before embarking on a course of therapy. Often comanagement provides a more optimal management framework for the child with a chronic endocrine problem, whether in pubertal development, growth, or thyroid regulation. This chapter focuses on disorders of pubertal development, growth disorders, and congenital hypothyroidism. Specific indications for specialist consultation and referral and for comanagement are presented.

Normally, the hypothalamic-pituitary-gonadal axis is suppressed in prepubertal children. As a result, the physiology of gonadotropin secretion is one of infrequent, low-amplitude pulses, with a predominance of follicle-stimulating hormone (FSH) relative to luteinizing hormone (LH). Circulating gonadotropins are at a nadir at 6 or 7 years of age but are not completely suppressed. As children approach puberty, there is a change in sensitivity, or disinhibition of the axis, and overriding central nervous system (CNS) control causes episodic pulses of gonadotropin-releasing hormone (GnRH) to be released. As a result, there is an increase in LH and FSH levels, with a relatively greater increase in LH.

The first evidence of the hormonal changes of puberty is episodic LH pulses of high amplitude and short duration. These bursts first occur only during sleep, but with maturity, they also occur regularly throughout the day. The first sign of puberty in girls is generally thelarche, or breast enlargement. Generally gonadarche, or enlargement of the testes, is the first sign in boys.

Data analyzed in a recent cross-sectional study involving 17,077 girls between ages 3 and 12 and followed in various pediatric practices across the United States, suggest that girls are entering puberty at younger ages than previously established norms. Caucasian girls were found to be entering puberty at an average age of 10 years (6 months to 1 year earlier than girls in previous studies), and African American girls were found to be entering puberty at an average age of 8 to 9 years. The African American girls were more physically mature than the Caucasian girls at all ages and for all secondary sexual characteristics (Herman-Giddens et al., 1997).

In response to the data collected by Herman-Giddens et al., (1997), the Lawson Wilkins Pediatric Endocrine Society launched a comprehensive review on this topic (Kaplowitz, Oberfield, & the Drug and Therapeutics and Executive Committees of the Lawson Wilkins Pediatric Endocrine Society, 1999). New guidelines were formulated, proposing criteria deserving pediatric endocrine referral:

The new Lawson Wilkins guidelines support the currently accepted normal lower limit of 9 years for puberty in boys (Kaplowitz et al., 1999).

Menarche in Caucasian girls in the United States has remained stable over the last 45 years at 12.88 years. In African American girls, on the other hand, the mean age of menarche has apparently decreased from 12.52 years to 12.16 years. This apparent decrease may be related to the move of African Americans toward achievement of optimal health and nutritional status (Kaplowitz et al., 1999).

Why is there a trend toward earlier onset of puberty? The HANES data and the National Growth and Health Study showed similar increases in the heights and weights of Caucasian and African American girls, particularly with increases in age. It is hypothesized that earlier onset of puberty in African American girls may be related in some way to the use of hair products containing estrogen or placenta. A viable etiology for all girls is the more widespread use of certain plastics, insecticides, and pesticides, such as DDT (xenoestrogens), which contain or degrade into substances having estrogen-related physiologic effects (Herman-Giddens et al., 1997; Murkies, Wilcox, & Davis, 1998; Tham et al., 1998).

Recent evidence points to the possible role of serum leptin levels in the initiation of puberty. Leptin, the product of the ob gene, is involved in body composition, specifically fat composition. Studies to date have revealed that a minimum weight for height is necessary for the onset and maintenance of normal menstrual periods. Furthermore, an association has been found between mild obesity and earlier menarche. Palmert, Radovick, and Boepple (1998) found that girls with central precocious puberty had modestly elevated serum leptin levels, compared with the healthy controls, which may be critical in the initiation of puberty in girls.

The history should begin with noting the age of symptom onset. More importantly, the provider needs to identify the tempo of symptom progression. Review of systems should include questions about the appearance of acne, axillary odor, and axillary and pubic hair. Vaginal discharge in girls should be noted. Headaches and visual disturbances and symptoms of thyroid disease, such as constipation, fatigue, and cold intolerance are also important to note. The possibility of exposure to exogenous hormones, such as oral contraceptives, or androgens, such as DHEA-S or androstenedione, should be raised.

Even before examining a child with early development, review of the growth chart is very informative. Evidence of a rapid height acceleration suggests the possibility of true precocious puberty or CAH. The physical examination should include a look at the fundi and visual fields and a neurologic examination, given the possibility of a brain tumor, such as an astrocytoma or craniopharyngioma. The thyroid should be palpated to rule out a goiter. The examination should focus on the presence of acne and axillary hair, with Tanner staging for breasts and pubic hair. Examination of the skin is important, because café au lait spots may be evidence of neurofibromatosis or McCune-Albright syndrome.

True precocious puberty is defined as the development of secondary sexual characteristics before 8 years in girls (with a new cut-off of 6 to 7 years proposed by the Lawson Wilkins Pediatric Endocrine Society [Kaplowitz et al., 1999]) or 9 years in boys.

True, or central, precocious puberty can be diagnosed by the demonstration of pubertal levels of gonadotropins and a pubertal response to GnRH stimulation. Both premature thelarche and premature adrenarche are benign, isolated, self-limited conditions that show a prepubertal response to GnRH (Lincoln & Zuber, 1998).

Laboratory tests for precocious puberty should include the following:

If CAH is suspected (ie, with evidence of height acceleration, acne, adrenarche, and hirsutism), adrenal hormones studies should be ordered, including the following:

In all cases of premature thelarche, with or without other signs of puberty, a βHCG should be sent to rule out the possibility of an hCG-producing tumor. If androgen levels are increased and there is a suspicion of CAH, the test of choice is an ACTH-stimulation test. This test shows an elevation of androgens at baseline, with a marked rise in the precursor hormones after stimulation. A pelvic ultrasound can be useful in looking for ovarian tumors, ovarian cysts, and endometrial thickness.

The gold standard of treatment for central precocious puberty is GnRH analogues. Not only do these agents decelerate the pace of puberty and even cause regression of secondary sexual characteristics, but they can also improve final height outcome. GnRH analogues offer the advantage of a powerful, sustained suppression of gonadotropins in a convenient monthly depot preparation, without significant side effects (Kauli et al., 1997).

GnRH analogues cause a tonic inhibition of the hypothalamic-pituitary-gonadal axis, causing significant suppression of gonadotropin secretion and consequently a decline in the levels of circulating sex steroids. This slows down growth cartilage activity and ultimately reduces growth velocity and skeletal maturation (Galluzzi, Salti, Bindi, Pasquini, & LaCauza, 1998).

In girls, there is a reduction of breast size and amount of pubic hair within the first 6 months of therapy. If menses were present prior to treatment, they stop. Pelvic ultrasound shows a decreased size of the uterus and ovaries. Potential side effects include recurrent hot flashes and moodiness.

In boys, there is similarly a reduction in testicular size and amount of pubic hair, along with a regression of acne, seborrhea, and frequency of penile erections. With treatment, aggressive behavior gradually diminishes, and self-esteem improves (Styne, 1997).