16.3 Growth Disorders & Puberty

Evaluating Short Stature

Short stature is generally defined as height more than 2 standard deviations below the mean for age and sex (below the 3rd percentile), or a growth velocity that crosses percentile lines downward over time — the pattern of growth over time is usually more diagnostically useful than a single height measurement.

Three conditions dominate exam questions, and the discriminating features are growth velocity and bone age:

Mid-parental height gives a quick screening estimate:

• Boys: (father's height + mother's height + 13 cm) / 2
• Girls: (father's height + mother's height - 13 cm) / 2

GHD clues beyond growth velocity: congenital GHD can present in the neonatal period with hypoglycemia and, in boys, microphallus (GH supports genital growth); midline craniofacial defects (cleft lip/palate, a single central maxillary incisor, septo-optic dysplasia) raise suspicion for an associated pituitary abnormality. Screening labs show low IGF-1 and IGFBP-3; diagnosis requires a GH stimulation test (e.g., arginine, clonidine, glucagon, or insulin tolerance testing) showing a peak GH response below the assay's diagnostic cutoff (commonly <10 ng/mL, though cutoffs are assay-dependent), plus brain MRI of the hypothalamic-pituitary region to look for a structural cause.

Exam trap: a child who is short with delayed bone age but a normal growth velocity is far more likely to have constitutional delay (reassurance and watchful waiting) than growth hormone deficiency — GHD requires a subnormal growth velocity, not just short stature with delayed bone age.

Precocious Puberty

Precocious puberty is the onset of secondary sexual characteristics before age 8 in girls or before age 9 in boys. It is subclassified by whether the hypothalamic-pituitary-gonadal (HPG) axis has been prematurely activated.

• Central precocious puberty (CPP) — "true," GnRH-dependent puberty: the HPG axis reactivates prematurely, so puberty proceeds through the normal sequence, just early. Basal or GnRH-stimulated LH is in the pubertal range. Most cases in girls are idiopathic; boys with CPP are far more likely than girls to have an identifiable central nervous system (CNS) cause (hypothalamic hamartoma or another CNS lesion), so brain MRI is more strongly indicated in boys, and in any girl younger than about 6 years.
• Peripheral precocious puberty — GnRH-independent: sex steroids are produced independent of the HPG axis, so LH/FSH are suppressed (prepubertal), and pubertal features may appear out of the normal sequence (for example, isolated vaginal bleeding without breast development). Causes include McCune-Albright syndrome, ovarian or testicular tumors, adrenal tumors, non-classic CAH, and exogenous hormone exposure.

Tanner staging basics: breast development (thelarche) is normally the first physical sign of puberty in girls (Tanner breast stage B2), while in boys the first sign is testicular enlargement to a volume ≥4 mL (Tanner genital stage G2) — not pubic hair or penile growth in either sex, a frequently tested distinction. The full staging systems (B1-B5 for breasts, G1-G5 for male genitalia, PH1-PH5 for pubic hair in both sexes) track progression, but the exam mainly wants you to know what marks the onset.

Workup: bone age (advanced relative to chronological age in true precocious puberty of either type), basal or GnRH-stimulated LH and FSH, estradiol or testosterone, pelvic or testicular ultrasound, and brain MRI when CPP is suspected. Treatment of CPP is a GnRH agonist (e.g., leuprolide), which paradoxically suppresses the axis through continuous rather than pulsatile stimulation, halting pubertal progression and protecting adult height potential.

Delayed Puberty: Red Flags

Delayed puberty is the absence of breast development by age 13 in girls, testicular volume <4 mL by age 14 in boys, or absence of menarche by age 15-16 (primary amenorrhea) despite otherwise normal development.

Most delayed puberty, like most short stature, is constitutional delay of growth and puberty — self-limited, often familial, and associated with delayed bone age on an otherwise normal trajectory. Certain features, however, are red flags pointing to pathology rather than a normal variant:

• Anosmia (absent sense of smell) with absent puberty suggests Kallmann syndrome, a form of hypogonadotropic hypogonadism from defective GnRH neuron migration.
• Short stature combined with delayed or absent puberty in a girl should prompt karyotyping to evaluate for Turner syndrome (45,X) — other clues include a webbed neck, wide-spaced nipples, and coarctation of the aorta; gonadotropins (FSH/LH) are elevated (hypergonadotropic hypogonadism) because the ovaries are streak gonads that cannot respond.
• Tall stature with small, firm testes and delayed puberty in a boy suggests Klinefelter syndrome (47,XXY), the most common cause of male hypogonadism; FSH/LH are also elevated (hypergonadotropic).
• Signs of chronic disease, malnutrition, excessive athletic training, or an eating disorder point toward functional hypogonadotropic hypogonadism, in which gonadotropins are low or inappropriately normal (not elevated) because the hypothalamic-pituitary axis itself is suppressed.

The gonadotropin level is the fastest way to split the differential: elevated FSH/LH (hypergonadotropic) means the problem is at the gonad (Turner syndrome, Klinefelter syndrome, other gonadal failure); low/normal FSH/LH (hypogonadotropic) means the problem is at the hypothalamus or pituitary (Kallmann syndrome, functional suppression, constitutional delay).