Delayed puberty

(Threshold ages 13, 14, 16; initial workup CBC, LH/FSH, chromosomes, prolactin, thyroid studies, bone age, pelvic ultrasound)

• when pubertal develoment is 2 SD behind normal
• no pubertal development by:
  • 13 years in girls, or has some development (ie breasts) but no menses by age 16
  • 14 years in boys (testicular volume not increased)
• or an arrest in pubertal maturation (allow 4 years for completion)
• *special note: if a girl has a chronic illness or is in extremely competitive athletics, give her an extra year to begin pubertal development (i.e. wait until age 14 for workup, same as boys). If she begins development by age 14, give her until age 17 to begin menses)

Differential

• 2 major categories
  1. hypergonadotropic hypogonadism (high LH and FSH)
     • think of it like end-organ damage
     • common causes: chemo, radiation therapy, autoimmune glandular failure
     • androgen insensitivity, Turner syndrome, Klinefelter, Laurence-Moon-Biedl
  2. Hypogonatropic hypogonadism
     • constitutional delay, or central gonadotropin deficiency
     • Kallman's syndrome is the most common cause of isolated gonadotropin deficiency
     • CNS tumors, hypopituitary, Prader Willi, chronic disease

Ask these questions in the history, or look for on PE.

• Current symptoms
  • diet, eating habits, weight changes, intensity of exercise
  • headaches, abdominal pain
  • galactorrhea
  • ability to smell
  • hirsutism
  • substance abuse
• Past medical history
  • surgeries, irradiation, chemotherapy
  • age of pubertal development and progression
• Neonatal history
  • hypoglycemia as a neonate
  • neonatal stigmata of turner syndrome
• Family history
  • heights of parents
  • parental ages of pubertal development
  • tumors
  • endocrine problems

Physical Exam

• Height, mid-parental height
• Weight, BP
• Tanner staging
• acne, hirsutism, visual fields, thyroid size, galactorrhea
• sense of smell
• syndrome stigmata
  • Prader-Willi: obesity, short stature, almond shaped eyes, MR, facies
  • Noonan Syndrome: webbed neck, ptosis, short stature, wide carrying angle, undescended testes
  • Laurence-Moon-Biedl: obesity, polydactyly, short stature, MR, retinitis pigmentosa

DDx

• Simply put: gonads are not responding to CNS hormones OR CNS not producing adequate stimulation

Hypergonadotrophic hypogonadism. Think about syndromes and end-organ failure.

• Turner Syndrome (XO or mosaic): short stature, primary/secondary amenhorrhea, little/no breast development, usually normal pubic/axillary hair (due to absent ovarian fn but normal adrenal gland)
• Noonan Syndrome Syndrome
• 17-alpha hydroxylase deficiency: (enzyme is found in gonads and adrenals), reduced production of androgens/estrogens, boys are incompletely virilized or pseudohermaphrodite, girls look normal but failure of puberty. (see Congenital Adrenal Hypoplasia)
• Klinefelter: often begin puberty at normal age, but do not progress normally. Firm testicles, prepubertal in size, even though penis may be normal in size. Tend to be tall and lack facial/body hair.
• CHARGE
• Ovarian failure: inability to respond to FSH/LH may be secondary to radiation, chemotherapy, autoimmune disease, resistant ovary syndrome, or other underlying condition i.e. galactosemia, trisomy 21, sarcoidosis, torsion, hemorrhage, etc.
• Testicular failure: may be due to trauma, torsion, chemo, radiation, mumps, coxsackievirus B, vanishing testes syndrome.

Hypogonadotrophic hypogonadism (think syndromes, nutrition, psych, other disease states)

• Syndromes
  • Kallman syndrome: lack of pulsatile GnRH and midline craniofacial defects or anosmia
  • Prader-Willi
  • Laurence-Moon-Biedl
• Nutrition/Activity
  • chronic disease with malnutrition and/or increased caloric requirements
  • anorexia nervosa
  • athletic competition - may have disturbance in GnRH secretion
• Psych: depression
• CNS tumors
• Infiltrative diseases (sarcoid, TB, histiocytosis, CNS leukemia)
• head trauma
• Pituitary:
  • Hyperprolactinemia
    • elevated PRL interferes w/ gonadotropin production
    • due to prolactinoma, pregnancy, hypothyroid, chronic renal failure (decreased clearanc), meds
  • post-partum necrosis (Sheehan's syndrome)
  • empty-sella syndrome
• Endocrinopathies (e.g. DM, Cushings, steroid use, GH deficiency)
• drugs causing hyperPRL (phenothiazines, cocain)
• constitutional delay (with or without constitutional short stature)
• thyroid (hypo/hyper, may interfere w/ gonadotropin secretion)
• adrenal (e.g. cushing, addision, late onset CAH)

Start with:

• CBC for chronic disease
• LH, FSH to delineate between hypergonadotrophic (high LH & FSH) vs hypogonadotropic (low/nl LH and FSH) hypogonadism
• prolactin
• thyroid studies
• karyotype
• bone age
• pelvic ultrasound (if female has pubertal development but delayed menarche; to evaluate internal genital structures and exclude any anatomic abnormalities)

Management

• treat underlying
• review health and nutrition
• endo referral for hormone replacement
• psychosocial eval

Harriet Lane 16th ed
CHLA board review 2005.