Delayed Puberty

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Delayed Puberty

• Pediatrics in Review
• Vol.22 No.9 Sept. 2001

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Delayed Puberty

• Introduction
• Differential Diagnosis
• Evaluation of Pubertal Delay
• Management
• Psychosocial Consequences of Delayed Puberty

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Puberty

• Development maturation of the reproductive
  system begins in fetal life is an active
  process.
• Puberty begins with increased pulsatile secretion
  of Gonadotropin releasing hormone ( GnRH ) from
  the hypothalamus ,increased pituitary hormones ,
  gonadal maturation, increasing production of sex
  steroids.
• Secondary sexual characteristics, acceleration of
  growth ,ultimate fertility.
• Timing of puberty ??

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Delayed Puberty

• Delay of more than 2-3 standard deviations from
  the mean age of pubertal onset.
• Delayed no sexual maturity by 14 years in boys
  13 years in girls.
• Absence of menarche by 16 years of age ,or
  within 5 years of pubertal onset.
• Pubertal development begins ,but progression
  stalls,the duration of a given characteristic is
  longer than expected.

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Delayed Puberty

• 2.5 of adolescents .
• Most are boys.
• Most will be found to have no pathology , and
  will have normal progression of puberty as soon
  as it starts.
• A variety of causes that can be diagnosed with
  proper evaluation.

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Constitutional Delay

• Constitutional delay explains 90-95 of pubertal
  delay.
• It is a normal variant that results from
  persistence of the prepubertal hypogonadotropic
  state.
• Typically, 14-15 year old boy presents after most
  of his peers have begun puberty.
• Boys present more often than girls.
• It may be superimposed on constitutional short
  stature.

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Constitutional Delay

• More than 60 of patients have positive family
  history.
• Findings on physical examination are
  unremarkable.
• Delayed bone age that is consistent with the
  pubertal maturation.
• Outcome in isolated constitutional delay is
  excellent.
• Sexual maturity final height are not affected.

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Chronic Illness

• Pathophysiology is multifactorial.
• Steroids , chemotherapy , medications , radiation
  may have short or long term effects.
• Close monitoring of pubertal course is required.
• Often only reassurance is required.

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Chronic Illness

• When pathologic pubertal derangements are
  detected , early treatment should be initiated.
• Nutrition should be maximized, with
  supplementation .
• Investigations for other explanations of delay if
  not adequately explained by the chronic illness.
• Hormone replacement or augmentation is
  appropriate in some settings , but should not be
  a substitute for management of the underlying
  condition.

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Hypopituitarism

• Panhypopituitarism (congenital or acquired)
• Typically present with short stature in early
  childhood.
• In adolescence it is usually due to idiopathic
  hypothalamic failure.
• Other CNS etiologies should be ruled out.
• Tumors , histiocytosis, severe trauma.

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Hypopituitarism

• Isolated Gonadotropin Deficiencies (Kallman
  Syndrome)
• Heterogeneous in presentation, difficult to
  distinguish from constitutional delay.
• More in boys .
• Associated with anosmia.
• KAL-1 gene.
• Examination may be normal apart from a small
  phallus testes.
• Delayed bone age is the only consistent finding.

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Endocrinopathies

• Hypothyroidism
• Thyroid hormone is required for normal puberty
• Thyroid replacement therapy usually normalizes
  gonadotropin secretion allows puberty to
  proceed normally.

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Endocrinopathies

• Hyperprolactinemia
• Pituitary adenoma , drug associated.
• May cause primary or secondary amenorrhea.
• Serum prolactin measurement is a part of patients
  evaluation.
• Imaging studies of the brain may be normal.

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Bilateral Gonadal Failure

• Uncommon.
• Markedly elevated serum gonadotropins.
• Congenital
• Turner Syndrome
• Klinefelter Syndrome
• Other congenital acquired causes are rare.

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Turner Syndrome

• Short stature.
• Variable but incomplete puberty.
• Primary amenorrhea.
• Characteristic congenital anomalies.
• Growth retardation begins in utero.
• High levels of gonadotropin by adolescence due to
  primary ovarian failure.
• Girls may show mild sexual maturity.
• Long term estrogen replacement therapy is
  required.

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Klinefelter Syndrome

• Genetically variable.
• Identified at puberty early adulthood.
• Sometimes spontaneous puberty occurs but testes
  become fibrotic as boys become older.
• Present with small testes,external genitalia
  gynecomastia.
• Borderline intellectual abilities behavioral
  difficulties may lead to the diagnosis.
• Tall as children , which often delays the
  diagnosis.
• Low testosterone , high FSH , oligospermia or
  azospermia are detected.

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Acquired causes of Gonadal Failure

• Causes
• Chemotherapy, radiation, Surgery.
• Trauma, infections, autoimmune, metabolic.
• Mumps orchitis is the most common infectious
  cause.
• Addison disease autoimmune oophoritis.
• Galagtosemia The effects of galactose its
  metabolites on the prenatal or neonatal ovary may
  delay puberty or cause menstrual dysfunction.

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Other Congenital Syndromes

• Androgen Resistance.
• Prader- Willi Syndrome.
• Laurence- Moon Bardet-Biedl Syndrome.
• Noonan Syndrome.
• Vanishing Testes Syndrome
• Resistant Ovaries Syndrome.
• Others.

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Hypogonadotropic Hypogonadism

• Eating disorders, malnutrition, excessive
  exercise.
• Girls more affected than boys present with
  Amenorrhea.
• Competitive Athletes have delays proportionate to
  the intensity of training.
• Weight gain usually corrects these abnormalities
  .
• Women with eating disorders are at risk of
  menstrual irregularities independent of weight.

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Congenital Anatomic Abnormalities.

• They present with delayed onset of menses despite
  normal development of secondary sexual
  characteristics.
• Imperforate hymen, vaginal atresia, vaginal
  aplasia .
• Canceled Menarche Cyclic abdominal pain.

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Evaluation of Pubertal Delay

• Careful History
• Anosmia, galactorrhea ,hypothyroidism
• Excessive exercise
• Chronic illness or psychiatric disease.
• Family history.
• Physical examination
• Growth parameters.
• Sexual maturity.
• Stigmata of congenital syndromes.

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Investigations

• Serum gonadotropin levels.
• High
• Turner , Klinefelter.
• Bilateral gonadal failure.
• Chromosomal analysis.
• Low or normal
• Screen for occult chronic illness or
  endocrinopathy
• CBC, ESR.
• Prolactin, TSH
• IGD vs. constitutional delay.
• First morning urinary testosterone, stimulation
  tests.

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Management

• Treat the underlying cause.
• Constitutional delay may be managed by
  reassurance alone, expectant management.
• jump start hormonal therapy may be used if
  delay has led to psychosocial dysfunction.
• Testosterone injections , monthly for six months
  ,if pubertal development has begun.
• Oral oxandrolone can be used if puberty has not
  yet begun.

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Management

• Treatment should be monitored By specialists
  familiar with side effects premature epiphyseal
  closure, hepatic peliosis.
• Asses response skeletal maturity at 3 to 6
  month intervals.
• Discontinue treatment when endogenous hormone
  production is established.

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Management

• Gonadotropin deficiency hypogonadism require
  life long replacement therapy should be managed
  in consultation with a pediatric endocrinologist.
• Supplementation is begun in boys at 12 years of
  age ( injectable, transdermal , gel )
• Starting doses are small increased gradually
  based on careful follow- up .
• Once puberty is complete , life long replacement
  is continued.

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Management

• Girls replacement hormonal therapy is started
  coinciding with puberty in peers.
• Transdermal patches of estrogen or small daily
  doses of conjugated estrogen or ethinyl
  estradiol.
• Careful monitoring is required.
• Cyclic hormonal replacement with low dose OCPs
  is started after 1-2 years of replacement or once
  break-through bleeding has occurred.

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Psychosocial Consequences

• Adolescents with markedly delayed puberty are at
  risk of psychosocial difficulties.
• It is more troublesome for boys.
• Delay may lead to low self esteem,teasing,
  bullying, parental overprotection,social
  withdrawal isolation.
• Boys who look younger than their chronological
  age have fewer opportunities for age appropriate
  activities.

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Psychosocial Consequences

• Girls present with fewer psychosocial concerns.
• Some value their immature body with eating
  disorders ,early puberty may cause
  dissatisfaction.
• The extent of intervention is determined by the
  psychosocial burden imposed on the adolescent .

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