Paeds · endocrinology-diabetes-and-growth

Delayed puberty and hypogonadism in adolescents

Also known as Constitutional delay of growth and puberty · CDGP · Delayed puberty · Hypogonadotropic hypogonadism · Congenital hypogonadotropic hypogonadism · CHH · Kallmann syndrome · Hypergonadotropic hypogonadism · Primary gonadal failure

A fellowship approach to the adolescent whose puberty is late or has stalled: confirm the timing against sex-specific thresholds (no testicular enlargement by 14 in boys, no thelarche by 13 in girls, or a pause over 2 years), split the differential with gonadotrophins into central versus gonadal causes, separate the common and benign constitutional delay of growth and puberty from permanent congenital hypogonadotropic hypogonadism, and treat by reassuring the temporary, inducing puberty in the permanent, and replacing sex steroids for life in primary gonadal failure.

high12 referencesUpdated 13 July 202628 min readVerification in progress

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Target exams

RACP General PaediatricsRACP DWERACP DCE

Red flags

An adolescent with absent puberty plus anosmia — the hallmark of Kallmann syndrome, a permanent congenital hypogonadotropic hypogonadism that will not self-correct
Delayed puberty with headache, visual-field loss, growth arrest or new diabetes insipidus — a hypothalamic-pituitary tumour such as craniopharyngioma until imaging proves otherwise
Short stature, delayed puberty and high gonadotrophins in a girl — Turner syndrome with streak ovaries; the karyotype and cardiac evaluation are urgent
A boy with small firm testes, gynaecomastia and tall stature and high gonadotrophins — Klinefelter syndrome (47,XXY), the commonest genetic cause of primary gonadal failure
Low body mass, intense exercise and secondary amenorrhoea in an adolescent girl — functional hypothalamic suppression and the female athlete triad, reversible but bone-depleting
Micropenis or undescended testes noted in infancy now presenting with absent puberty — deficient GnRH drive from birth, pointing away from constitutional delay toward permanent CHH

Life stages

school-ageadolescentyoung-adult-transition

Care settings

outpatientwarded-acuterural-remotetelehealth

Clinical exam formats

written-only

Board mappings

Definition and timing thresholds for delayed puberty in boys and girls
Growth-chart and bone-age interpretation in the short late-maturing adolescent
When to refer to a paediatric endocrinologist
Gonadotrophin-based classification into hypogonadotropic versus hypergonadotropic causes
Separating constitutional delay of growth and puberty from permanent congenital hypogonadotropic hypogonadism
Genetics of Kallmann syndrome and congenital hypogonadotropic hypogonadism
Recognising delayed puberty and the red flags for a CNS tumour
Interpreting FSH, LH and sex-steroid results
Principles of pubertal induction and the role of short-course testosterone
Long case of a boy with delayed puberty and short stature distinguishing CDGP from CHH
Long case of a girl with Turner syndrome discussing induction and surveillance
Short case examining pubertal staging and growth trajectory
Endocrinology and growth: pubertal disorders
Investigation of the child with delayed puberty
Psychosocial impact of delayed puberty and chronic endocrine conditions
Physiology of the hypothalamic-pituitary-gonadal axis and the hormonal control of puberty
Classification and causes of delayed puberty
Pubertal induction protocols and fertility considerations
Communication: explaining a delayed puberty diagnosis to an adolescent and family
Clinical assessment of pubertal staging and growth
Delayed puberty and hypogonadism
Turner and Klinefelter syndromes
Functional hypothalamic amenorrhoea in the adolescent athlete
Disorders of puberty
Hypogonadotropic and hypergonadotropic hypogonadism
Adolescent endocrinology and transition of care
Endocrinology: delayed puberty
Approach to the short late-maturing adolescent
Kallmann syndrome and congenital hypogonadotropic hypogonadism

On this page

Study tools

Your progress

Saved on this device.

Practise this topic

Target exams

RACP General PaediatricsRACP DWERACP DCE

Red flags

An adolescent with absent puberty plus anosmia — the hallmark of Kallmann syndrome, a permanent congenital hypogonadotropic hypogonadism that will not self-correct
Delayed puberty with headache, visual-field loss, growth arrest or new diabetes insipidus — a hypothalamic-pituitary tumour such as craniopharyngioma until imaging proves otherwise
Short stature, delayed puberty and high gonadotrophins in a girl — Turner syndrome with streak ovaries; the karyotype and cardiac evaluation are urgent
A boy with small firm testes, gynaecomastia and tall stature and high gonadotrophins — Klinefelter syndrome (47,XXY), the commonest genetic cause of primary gonadal failure
Low body mass, intense exercise and secondary amenorrhoea in an adolescent girl — functional hypothalamic suppression and the female athlete triad, reversible but bone-depleting
Micropenis or undescended testes noted in infancy now presenting with absent puberty — deficient GnRH drive from birth, pointing away from constitutional delay toward permanent CHH

Life stages

school-ageadolescentyoung-adult-transition

Care settings

outpatientwarded-acuterural-remotetelehealth

Clinical exam formats

written-only

Board mappings

Definition and timing thresholds for delayed puberty in boys and girls
Growth-chart and bone-age interpretation in the short late-maturing adolescent
When to refer to a paediatric endocrinologist
Gonadotrophin-based classification into hypogonadotropic versus hypergonadotropic causes
Separating constitutional delay of growth and puberty from permanent congenital hypogonadotropic hypogonadism
Genetics of Kallmann syndrome and congenital hypogonadotropic hypogonadism
Recognising delayed puberty and the red flags for a CNS tumour
Interpreting FSH, LH and sex-steroid results
Principles of pubertal induction and the role of short-course testosterone
Long case of a boy with delayed puberty and short stature distinguishing CDGP from CHH
Long case of a girl with Turner syndrome discussing induction and surveillance
Short case examining pubertal staging and growth trajectory
Endocrinology and growth: pubertal disorders
Investigation of the child with delayed puberty
Psychosocial impact of delayed puberty and chronic endocrine conditions
Physiology of the hypothalamic-pituitary-gonadal axis and the hormonal control of puberty
Classification and causes of delayed puberty
Pubertal induction protocols and fertility considerations
Communication: explaining a delayed puberty diagnosis to an adolescent and family
Clinical assessment of pubertal staging and growth
Delayed puberty and hypogonadism
Turner and Klinefelter syndromes
Functional hypothalamic amenorrhoea in the adolescent athlete
Disorders of puberty
Hypogonadotropic and hypergonadotropic hypogonadism
Adolescent endocrinology and transition of care
Endocrinology: delayed puberty
Approach to the short late-maturing adolescent
Kallmann syndrome and congenital hypogonadotropic hypogonadism

The fellowship answer

Delayed puberty is the failure of the pubertal clock to start on time, and the fellowship task is to separate the common, benign, temporary delay from the permanent hypogonadism that needs lifelong treatment. The thresholds are sex-specific: no testicular enlargement (under 4 millilitres) by 14 years in boys, or no breast development by 13 years in girls, or a stall of more than two years once puberty has begun. The single most discriminating investigation is the gonadotrophin level, which splits the differential in half — low or inappropriately normal follicle-stimulating hormone and luteinising hormone point to a central problem in the hypothalamic-pituitary-gonadal axis, while high gonadotrophins point to primary gonadal failure. Within the central group, the dominant diagnosis is constitutional delay of growth and puberty, a temporary late-running clock that affects roughly 60 percent of boys referred for delayed puberty, carries a strong family history, runs alongside a delayed bone age, and resolves spontaneously. The permanent central group is congenital hypogonadotropic hypogonadism, the prototype of which is Kallmann syndrome with anosmia, and these adolescents need pubertal induction with escalating sex steroids. The gonadal-failure group — Klinefelter syndrome in boys, Turner syndrome in girls, and chemotherapy or radiation damage in either — needs lifelong sex-steroid replacement plus disease-specific surveillance. ^[1] ^[2]

The fellowship mark goes to the candidate who works through three layers in order. The first is the timing: has puberty genuinely failed to start, or has it started and then stalled, and where does this adolescent sit against the sex-specific thresholds. The second is the axis: a morning testosterone or oestradiol with gonadotrophins, read against bone age and growth velocity, tells you whether the problem is central or gonadal. The third is the clock versus the furnace: constitutional delay is a late but intact clock that will start on its own, whereas congenital hypogonadotropic hypogonadism is a permanently defective clock that needs exogenous sex steroids to drive puberty, and primary gonadal failure is a clock with no furnace to drive. The candidate who can name the anosmia of Kallmann, the streak ovaries of Turner, and the small firm testes of Klinefelter, and who knows when to order a pituitary MRI, passes the station. ^[1] ^[10]

Anosmia with absent puberty is Kallmann syndrome until proven otherwise

The combination of an absent or impaired sense of smell with failure of pubertal onset is the signature of Kallmann syndrome, the olfactory variant of congenital hypogonadotropic hypogonadism. The embryological defect is shared: the gonadotropin-releasing hormone neurons and the olfactory neurons both fail to migrate from the olfactory placode to the brain, so the hypothalamus lacks the GnRH pulse generator and the olfactory bulbs are aplastic or hypoplastic. This is a permanent condition that will never self-correct, and anosmia is the single clinical feature that most reliably separates it from constitutional delay. Test smell directly — ask the adolescent to identify common scents such as coffee or soap — because adolescents rarely volunteer the loss and many discover it only when formally tested. ^[6] ^[5]

References12Show

[1]Palmert MR, Dunkel L. Clinical practice. Delayed puberty. N Engl J Med, 2012.PMID 22296078
[2]Sedlmeyer IL, Palmert MR. Delayed puberty: analysis of a large case series from an academic center. J Clin Endocrinol Metab, 2002.PMID 11932291
[3]Sedlmeyer IL, Hirschhorn JN, Palmert MR. Pedigree analysis of constitutional delay of growth and maturation: determination of familial aggregation and inheritance patterns. J Clin Endocrinol Metab, 2002.PMID 12466356
[4]Wehkalampi K, Widén E, Laine T, Palotie A, Dunkel L. Patterns of inheritance of constitutional delay of growth and puberty in families of adolescent girls and boys referred to specialist pediatric care. J Clin Endocrinol Metab, 2008.PMID 18160460
[5]Howard SR. The Genetic Basis of Delayed Puberty. Front Endocrinol (Lausanne), 2019.PMID 31293522
[6]Stamou MI, Georgopoulos NA. Kallmann syndrome: phenotype and genotype of hypogonadotropic hypogonadism. Metabolism, 2018.PMID 29108899
[7]Groth KA, Skakkebæk A, Høst C, Gravholt CH, Bojesen A. Clinical review: Klinefelter syndrome--a clinical update. J Clin Endocrinol Metab, 2013.PMID 23118429
[8]Gravholt CH, Andersen NH, Conway GS, et al. Clinical practice guidelines for the care of girls and women with Turner syndrome: proceedings from the 2016 Cincinnati International Turner Syndrome Meeting. Eur J Endocrinol, 2017.PMID 28705803
[9]Nordenström A, Ahmed SF, van den Akker E, et al. Pubertal induction and transition to adult sex hormone replacement in patients with congenital pituitary or gonadal reproductive hormone deficiency: an Endo-ERN clinical practice guideline. Eur J Endocrinol, 2022.PMID 35353710
[10]Klein DA, Emerick JE, Sylvester JE, Vogt KS. Disorders of Puberty: An Approach to Diagnosis and Management. Am Fam Physician, 2017.PMID 29094880
[11]Butler G, Purushothaman P. Delayed puberty. Minerva Pediatr, 2020.PMID 32748610
[12]Stancampiano MR, Lucas-Herald AK, Russo G, Ahmed SF. Testosterone Therapy in Adolescent Boys: The Need for a Structured Approach. Horm Res Paediatr, 2019.PMID 31851967

Delayed puberty and hypogonadism in adolescents

high12 referencesUpdated 13 July 202628 min readVerification in progress

Practise this topic

The fellowship answer

Anosmia with absent puberty is Kallmann syndrome until proven otherwise

References12Show

[1]Palmert MR, Dunkel L. Clinical practice. Delayed puberty. N Engl J Med, 2012.PMID 22296078
[2]Sedlmeyer IL, Palmert MR. Delayed puberty: analysis of a large case series from an academic center. J Clin Endocrinol Metab, 2002.PMID 11932291
[3]Sedlmeyer IL, Hirschhorn JN, Palmert MR. Pedigree analysis of constitutional delay of growth and maturation: determination of familial aggregation and inheritance patterns. J Clin Endocrinol Metab, 2002.PMID 12466356
[4]Wehkalampi K, Widén E, Laine T, Palotie A, Dunkel L. Patterns of inheritance of constitutional delay of growth and puberty in families of adolescent girls and boys referred to specialist pediatric care. J Clin Endocrinol Metab, 2008.PMID 18160460
[5]Howard SR. The Genetic Basis of Delayed Puberty. Front Endocrinol (Lausanne), 2019.PMID 31293522
[6]Stamou MI, Georgopoulos NA. Kallmann syndrome: phenotype and genotype of hypogonadotropic hypogonadism. Metabolism, 2018.PMID 29108899
[7]Groth KA, Skakkebæk A, Høst C, Gravholt CH, Bojesen A. Clinical review: Klinefelter syndrome--a clinical update. J Clin Endocrinol Metab, 2013.PMID 23118429
[8]Gravholt CH, Andersen NH, Conway GS, et al. Clinical practice guidelines for the care of girls and women with Turner syndrome: proceedings from the 2016 Cincinnati International Turner Syndrome Meeting. Eur J Endocrinol, 2017.PMID 28705803
[9]Nordenström A, Ahmed SF, van den Akker E, et al. Pubertal induction and transition to adult sex hormone replacement in patients with congenital pituitary or gonadal reproductive hormone deficiency: an Endo-ERN clinical practice guideline. Eur J Endocrinol, 2022.PMID 35353710
[10]Klein DA, Emerick JE, Sylvester JE, Vogt KS. Disorders of Puberty: An Approach to Diagnosis and Management. Am Fam Physician, 2017.PMID 29094880
[11]Butler G, Purushothaman P. Delayed puberty. Minerva Pediatr, 2020.PMID 32748610
[12]Stancampiano MR, Lucas-Herald AK, Russo G, Ahmed SF. Testosterone Therapy in Adolescent Boys: The Need for a Structured Approach. Horm Res Paediatr, 2019.PMID 31851967