Delayed puberty

Specialty: Endocrine and metabolic.

• persistent sexual infantilism
• constitutional delay in pubertal growth and development (RCCP)
• pubertal hypogonadism

Why it occurs

• Constitutional delay of puberty and growth (physiological variant of development characterized by a global maturation delay of polygenic and familial origin, with a prognosis of normal but late height and puberty)
• Turner syndrome or 45,X gonadal dysgenesis (primary ovarian insufficiency with elevated levels of gonadotropins)
• Klinefelter syndrome or 47,XXY karyotype (primary testicular dysgenesis with hypergonadotropic hypogonadism)
• Kallmann syndrome (congenital hypogonadotropic hypogonadism characterized by a failure in the migration of GnRH-producing neurons and cells of the olfactory bulb, presenting with anosmia or hyposmia)
• Craniopharyngioma or pituitary adenoma (sellar or suprasellar tumors that destroy or compress the gonadotroph cells of the anterior pituitary)
• Systemic chronic inflammatory or metabolic diseases such as celiac disease or ulcerative colitis (chronic malnutrition with suppression of the pubertal axis)

Initial workup

Determination of basal gonadotropins LH and FSH in serum to differentiate hypogonadotropic hypogonadism (low or inappropriately normal LH/FSH) from hypergonadotropic hypogonadism (elevated LH/FSH); total testosterone levels in boys and estradiol in girls; serum prolactin and thyroid hormones (TSH and free T4); high resolution karyotype in peripheral blood; anti-tissue transglutaminase IgA antibodies; left hand x-ray for bone age; and nuclear magnetic resonance of the sellar region and olfactory bulbs.

Standard management

• Testosterone enanthate — androgen administered intramuscularly at low initial doses of 50 mg once a month in males over 14 years of age to induce progressive virilization and accelerate longitudinal growth without prematurely closing the cartilage epiphyses
• Transdermal estradiol in patches — initial estrogen therapy at low doses of 3.12 to 6.25 mcg/24 hours in girls over 13 years of age to promote breast and uterine development, adding oral progesterone 2 years after initiation to prevent endometrial hyperplasia and regularize cycles
• Human chorionic gonadotropin — hCG, used in central hypogonadotropic hypogonadism to stimulate spermatogenesis and endogenous testosterone production in mature men
• Levothyroxine — if the pubertal delay is secondary to severe primary hypothyroidism