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Delayed puberty

delayed puberty in males, delayed puberty
Delayed puberty is described as delayed puberty with exceptions when an organism has passed the usual age of onset of puberty with no physical or hormonal signs that it is beginning Puberty may be delayed for several years and still occur normally, in which case it is considered constitutional delay of growth and puberty, a variation of healthy physical development Delay of puberty may also occur due to malnutrition, many forms of systemic disease, or to defects of the reproductive system hypogonadism or the body's responsiveness to sex hormones

Contents

  • 1 Causes
    • 11 Constitutional delay of growth and puberty
  • 2 Normal timing
  • 3 Diagnosis
    • 31 Evaluation
      • 311 Lateness
      • 312 Discordance
      • 313 Indications of specific disorders
  • 4 Management
  • 5 See also
  • 6 References
  • 7 External links

Causes

  • Variation of normal constitutional delay of growth and puberty
  • In females, prolonged high level of physical exertion, eg from being an athlete
  • Systemic disease, eg undiagnosed and untreated coeliac disease which often occurs without gastrointestinal symptoms, inflammatory bowel disease principally Crohn's disease, chronic renal failure
  • Undernutrition eg anorexia nervosa, zinc deficiency
  • Hypothalamic defects and diseases eg Prader-Willi syndrome, Kallmann syndrome
  • Pituitary defects and diseases eg hypopituitarism
  • Gonadal defects and diseases eg Turner syndrome, Klinefelter syndrome, Testicular failure due to mumps orchitis, Coxsackievirus B, irradiation, chemotherapy, or trauma Testicular failure is treated with testosterone replacement, Ovarian failure
  • Absence or unresponsiveness of target organs eg androgen insensitivity syndrome, Müllerian agenesis
  • Other hormone deficiencies and imbalances, Endocrine disorders eg hypothyroidism, Cushing's syndrome, endocrine disruptors
  • Cystic fibrosis
  • Mutations in FSHB
  • Frasier syndrome
  • Various forms of congenital adrenal hyperplasia
  • Gonadotropin deficiency, resulting from a number of congenital and acquired abnormalities of the central nervous system
  • Biedl-Bardet syndrome
  • Brain tumors eg craniopharyngioma, prolactinoma, germinoma, glioma; diseases of hypothalamus, irradiation and trauma
  • Anorexia Nervosa
  • Hyperprolactinaemia
  • Excessive physical exercise and physical stress
  • Noonan Syndrome

Constitutional delay of growth and puberty

Children who are healthy but have a slower rate of physical development than average have constitutional delay of growth and puberty These children have a history of stature shorter than their age-matched peers throughout childhood, but their height is appropriate for bone age, and skeletal development is delayed more than 25 SD They usually are thin and often have a family history of delayed puberty Children with a combination of a family tendency toward short stature and constitutional delay of growth and puberty are the most likely to seek evaluation They quite often seek evaluation when classmates or friends undergo pubertal development and growth, thereby accentuating their delay

It is often difficult to establish if it is a true constitutional delay of growth and puberty or if there is an underlying pathology, because biochemical tests are not always discriminatory Short stature, delayed growth in height and weight, and/or delayed puberty may be the only clinical manifestations of coeliac disease, in absence of any other symptoms

Normal timing

Approximate mean ages for the onset of various pubertal changes are as follows Ages in parentheses are the approximate 3rd and 97th percentiles for attainment For example, less than 3% of girls have not yet achieved thelarche by 13 years of age Developmental changes during puberty in girls occur over a period of 3 – 5 years, usually between 10 and 15 years of age They include the occurrence of secondary characteristics beginning with breast development, the adolescent growth spurt, the onset of menarche – which does not correspond to the end of puberty – and the acquisition of fertility, as well as profound psychological modifications

The normal variation in the age at which adolescent changes occur is so wide that puberty cannot be considered to be pathologically delayed until the menarche has failed to occur by the age of 18 or testicular development by the age of 20

For North American, Indo-Iranian India, Iran and European girls For North American, Indo-Iranian India, Iran and European boys
  • Thelarche breast development 100y5m 8y–13y
  • Pubarche pubic hair 11y 85y–135y
  • Growth spurt 1125y 10y–125y
  • Menarche first menstrual bleeding 125y 105y–145y
  • Adult height reached 15y -
  • Gonadarche testicular enlargement 12y 10y–14y
  • Pubarche pubic hair 12y 10y–14y
  • Growth spurt 14y 11y-17y
  • Completion of growth 17y 15y-21y

The sources of the data, and a fuller description of normal timing and sequence of pubertal events, as well as the hormonal changes that drive them, are provided in the principal article on puberty It is worthwhile to consider the world geographical and ethnographic/demographic limits and deficits of this study

Diagnosis

Pediatric endocrinologists are the physicians with the most training and experience evaluating delayed puberty A complete medical history, review of systems, growth pattern, and physical examination will reveal most of the systemic diseases and conditions capable of arresting development or delaying puberty, as well as providing clues to some of the recognizable syndromes affecting the reproductive system

Since bone maturation is a good indicator of overall physical maturation, an x-ray of the hand to assess bone age usually reveals whether the child has reached a stage of physical maturation at which puberty should be occurring Visible secondary sexual development usually begins when girls achieve a bone age of 11 years, and boys achieve a bone age of 12 years

The most valuable blood tests are the gonadotropins, because elevation confirms immediately a defect of the gonads or deficiency of the sex steroids In many instances, screening tests such as a complete blood count, general chemistry screens, thyroid tests, and urinalysis may be worthwhile

More expensive and complicated tests, such as a karyotype or magnetic resonance imaging of the head, are usually obtained only when specific evidence suggests they may be useful

Use of gonadotropin releasing hormone can be of value in the differential diagnosis

If delayed puberty is accompanied with a lack of sense of smell anosmia or a history of un-descended testicles cryptorchidism when born then a diagnosis of Kallmann syndrome could be considered

Evaluation

There are three indications that pubertal delay may be due to an abnormal cause

Lateness

The first is simply degree of lateness: although no recommended age of evaluation cleanly separates pathologic from physiologic delay, a delay of 2–3 years or more warrants evaluation

  • In girls, no breast development by 13 years, or no menarche by 3 years after breast development or by 16
  • In boys, no testicular enlargement by 14 years, or delay in development for 5 years or more after onset of genitalia enlargement

A delay of two standard deviations has been proposed as a standard

Discordance

The second indicator is discordance of development In most children, puberty proceeds as a predictable series of changes in specific order In children with ordinary constitutional delay of growth and puberty, all aspects of physical maturation typically remain concordant but a few years later than average If some aspects of physical development are delayed, and others are not, it is likely that something is wrong

  • For instance, in most girls, the beginning stages of breast development precede pubic hair If a 12-year-old girl were to reach Tanner stage 3 pubic hair for a year or more without breast development, it would be unusual enough to suggest an abnormality such as defective ovaries
  • Similarly, if a 13-year-old boy had reached stage 3 or 4 pubic hair with testes that still remained prepubertal in size, it would be unusual and suggestive of a testicular abnormality

Indications of specific disorders

The third indicator is the presence of clues to specific disorders of the reproductive system

  • Malnutrition or anorexia nervosa severe enough to delay puberty will give other clues as well
  • Poor growth would suggest the possibility of coeliac disease, hypopituitarism or Turner syndrome
  • Reduced sense of smell hyposmia or no sense of smell anosmia suggests Kallmann syndrome

Management

If a child is healthy but simply late, reassurance and prediction based on the bone age can be provided No other intervention is usually necessary In more extreme cases of delay, or cases where the delay is more extremely distressing to the child, a low dose of testosterone or estrogen for a few months may bring the first reassuring changes of normal puberty

If the delay is due to systemic disease or undernutrition, the therapeutic intervention is likely to focus mainly on those conditions In patients with coeliac disease, an early diagnosis and the establishment of a gluten-free diet prevents long-term complications and allows restore normal maturation

If it becomes clear that there is a permanent defect of the reproductive system, treatment usually involves replacement of the appropriate hormones testosterone/dihydrotestosterone for boys, estradiol and progesterone for girls

Pubertal delay due to gonadotropin deficiency is treated with testosterone replacement or with HCG

Growth hormone is another option that has been described

Subnormal vitamin A intake is one of the aetiological factors in delayed pubertal maturation Supplementation of both vitamin A and iron to normal constitutionally delayed children with subnormal vitamin A intake is as efficacious as hormonal therapy in the induction of growth and puberty

See also

  • Developmental milestones
  • Endocrinology
  • Hypogonadism
  • Kallmann syndrome
  • Precocious puberty

References

  1. ^ Villanueva C, Argente J 2014 "Pathology or normal variant: what constitutes a delay in puberty" Horm Res Paediatr Review 82 4: 213–21 doi:101159/000362600 PMID 25011467 
  2. ^ Maïmoun L, Georgopoulos NA, Sultan C Nov 2014 "Endocrine disorders in adolescent and young female athletes: impact on growth, menstrual cycles, and bone mass acquisition" J Clin Endocrinol Metab Review 99 11: 4037–50 doi:101210/jc2013-3030 PMID 24601725 
  3. ^ a b Leffler DA, Green PH, Fasano A Oct 2015 "Extraintestinal manifestations of coeliac disease" Nat Rev Gastroenterol Hepatol Review 12 10: 561–71 doi:101038/nrgastro2015131 PMID 26260366 
  4. ^ Tersigni C, Castellani R, de Waure C, Fattorossi A, De Spirito M, Gasbarrini A, Scambia G, Di Simone N 2014 "Celiac disease and reproductive disorders: meta-analysis of epidemiologic associations and potential pathogenic mechanisms" Hum Reprod Update Review 20 4: 582–93 doi:101093/humupd/dmu007 PMID 24619876 
  5. ^ Sanderson IR Oct 2014 "Growth problems in children with IBD" Nat Rev Gastroenterol Hepatol Review 11 10: 601–10 doi:101038/nrgastro2014102 PMID 24957008 
  6. ^ Wong SC, Catto-Smith AG, Zacharin M Feb 2014 "Pathological fractures in paediatric patients with inflammatory bowel disease" Eur J Pediatr Review 173 2: 141–51 doi:101007/s00431-013-2174-5 PMID 24132387 
  7. ^ Thébaut A, Amouyal M, Besançon A, Collet M, Selbonne E, Valentin C, Vonthron M, Zakariya M, Linglart A Jun 2013 "Puberty, fertility and chronic diseases" Arch Pediatr Review 20 6: 673–84 doi:101016/jarcped201303015 PMID 23619213 
  8. ^ a b c Marianne J Legato, ed 2004 "Principles of Gender-Specific Medicine, Volume 1-2", ISBN 0-12-440905-9, p 22
  9. ^ a b Greenspan, FS; Gardner DG 2004 "Puberty" Basic & Clinical Endocrinology pp 617–627 ISBN 0-07-140297-7 
  10. ^ Johannesson M, Gottlieb C, Hjelte L 1997 "Delayed puberty in girls with cystic fibrosis despite good clinical status" Pediatrics 99 1: 29–34 doi:101542/peds99129 PMID 8989333 
  11. ^ Layman LC, Lee EJ, Peak DB, et al 1997 "Delayed puberty and hypogonadism caused by mutations in the follicle-stimulating hormone β-subunit gene" N Engl J Med 337 9: 607–11 doi:101056/NEJM199708283370905 PMID 9271483 
  12. ^ Chan WK, To KF, But WM, Lee KW June 2006 "Frasier syndrome: a rare cause of delayed puberty" Hong Kong Med J 12 3: 225–7 PMID 16760553 
  13. ^ Template:Https://rarediseasesorg/rare-diseases/noonan-syndrome/
  14. ^ Wei C, Crowne EC Sep 9, 2015 "Recent advances in the understanding and management of delayed puberty" Arch Dis Child Review 101: 481–8 doi:101136/archdischild-2014-307963 PMID 26353794 
  15. ^ a b c Mearin ML Jun 2015 "The prevention of coeliac disease" Best Pract Res Clin Gastroenterol Review 29 3: 493–501 doi:101016/jbpg201504003 PMID 26060113 
  16. ^ Guandalini S, Assiri A Mar 2014 "Celiac disease: a review" JAMA Pediatr 168 3: :272–8 doi:101001/jamapediatrics20133858 PMID 24395055 
  17. ^ a b Levy J, Bernstein L, Silber N Dec 2014 "Celiac disease: an immune dysregulation syndrome" Curr Probl Pediatr Adolesc Health Care Review 44 11: 324–7 doi:101016/jcppeds201410002 PMID 25499458 
  18. ^ Jungmann E, Trautermann C 1994 "" Med Klin Munich in German 89 10: 529–33 PMID 7808353 
  19. ^ Oxford Endocrinology Library Testosterone Deficiency in Men 2008 ISBN 978-0199545131 Editor: Hugh Jones Chapter 9 Puberty & Fertility
  20. ^ Male Hypogonadism Friedrich Jockenhovel Uni-Med Science 2004 ISBN 3-89599-748-X Chapter 3 Diagnostic work up of hypogonadism
  21. ^ Traggiai C, Stanhope R 2003 "Disorders of pubertal development" Best Pract Res Clin Obstet Gynaecol 17 1: 41–56 doi:101053/ybeog20030360 PMID 12758225 
  22. ^ Saad RJ, Keenan BS, Danadian K, Lewy VD, Arslanian SA October 2001 "Dihydrotestosterone treatment in adolescents with delayed puberty: does it explain insulin resistance of puberty" J Clin Endocrinol Metab 86 10: 4881–6 doi:101210/jc86104881 PMID 11600557 
  23. ^ Heinrichs C, Bourguignon JP 1991 "Treatment of delayed puberty and hypogonadism in girls" Horm Res 36 3–4: 147–52 doi:101159/000182149 PMID 1818011 
  24. ^ Massa G, Heinrichs C, Verlinde S, et al September 2003 "Late or delayed induced or spontaneous puberty in girls with Turner syndrome treated with growth hormone does not affect final height" J Clin Endocrinol Metab 88 9: 4168–74 doi:101210/jc2002-022040 PMID 12970282 
  25. ^ Zadik Z, Sinai T, Zung A, Reifen R 2004 "Vitamin A and iron supplementation is as efficient as hormonal therapy in constitutionally delayed children" Clin Endocrinol 60 6: 682–7 doi:101111/j1365-2265200402034x PMID 15163330 

External links

Classification V · T · D
  • ICD-10: E300
  • ICD-9-CM: 2590
  • MeSH: D011628
  • DiseasesDB: 17462


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Delayed puberty


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