Constitutional delay of puberty

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Overview

Puberty is described as delayed when a boy or girl 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, a variation of healthy physical development. Delay of puberty may also occur due to undernutrition, many forms of systemic disease, or to defects of the reproductive system (hypogonadism) or the body's responsiveness to sex hormones.

Normal timing

Approximate mean ages for 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 9 and 14 years of age. They include the occurrence of secondary sex 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 17 or testicular development by the age of 20.

For North American, Indo-Iranian (India, Iran) and European girls

• Thelarche 10y5m (8y–13y)
• Pubarche 11y (8.5–13.5y)
• Growth spurt 10–12.5y
• Menarche 12.5y (10.5–14.5)
• Adult height reached 14.5y

For North American, Indo-Iranian (India, Iran) and European boys

• Testicular enlargement 11.5y (9.5–13.5y)
• Pubic hair 12y (10–14y)
• Growth spurt 12.5–15y
• Completion of growth 17.5

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.

Evaluation

Obviously anyone who is later than average is late in the ordinary sense. There are three indications that pubertal delay may be due to an abnormal cause. 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.

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, 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, there is likely something 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.

The third indicator is the presence of clues to specific disorders of the reproductive system. For example, malnutrition or anorexia nervosa severe enough to delay puberty will give other clues as well. Poor growth would suggest the possibility of hypopituitarism or Turner syndrome. Reduced sense of smell (hyposmia) suggests Kallmann syndrome.

Possible causes

• Variation of normal (constitutional delay)
• Prolonged high level of physical exertion / being an athlete
• Systemic disease, e.g. Inflammatory bowel disease, chronic renal failure
• Undernutrition e.g. anorexia nervosa, zinc deficiency
• Hypothalamic defects and diseases e.g. Prader-Willi syndrome
• Pituitary defects and diseases e.g. hypopituitarism, Kallmann syndrome
• Gonadal defects and diseases e.g. Turner syndrome, Klinefelter syndrome
• Absence or unresponsiveness of target organs e.g. androgen insensitivity syndrome, mullerian agenesis
• Other hormone deficiencies and imbalances e.g. hypothyroidism, Cushing's syndrome

Constitutional delay

Children who are healthy but have a slower rate of physical development than average have constitutional delay in growth and adolescence. 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 2.5 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 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.

Medical evaluation

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 10.5 to 11 years, and boys achieve a bone age of 11.5 to 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.

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.

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

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Epidemiology and Demographics

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Risk Factors

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Screening

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Pathophysiology & Etiology

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Molecular Biology

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Genetics

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Natural History

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Diagnosis

Differential Diagnosis

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History and Symptoms

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Physical Examination

Appearance of the Patient

Vital Signs

Skin

Eyes

Ear Nose and Throat

Heart

Lungs

Abdomen

Extremities

Neurologic

Other

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Laboratory Findings

Electrolyte and Biomarker Studies

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Electrocardiogram

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Chest X Ray

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MRI and CT

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Echocardiography or Ultrasound

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Other Imaging Findings

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Other Diagnostic Studies

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Risk Stratification and Prognosis

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Treatment

Pharmacotherapy

Acute Pharmacotherapies

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Chronic Pharmacotherapies

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Surgery and Device Based Therapy

Indications for Surgery

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Pre-Operative Assessment

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Post-Operative Management

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Transplantation

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Primary Prevention

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Secondary Prevention

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Cost-Effectiveness of Therapy

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Future or Investigational Therapies

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"The Way I Like To Do It ..." Tips and Tricks From Clinicians Around The World

Suggested Revisions to the Current Guidelines

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Acknowledgements

The content on this page was first contributed by: C. Michael Gibson, M.S., M.D.

List of contributors:

Suggested Reading and Key General References

Suggested Links and Web Resources

For Patients

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Articles on Constitutional delay of puberty	Most recent articles on Constitutional delay of puberty • Most cited articles on Constitutional delay of puberty • Review articles on Constitutional delay of puberty • Articles on Constitutional delay of puberty in N Eng J Med, Lancet, BMJ
Media (Slides, Video, Images, MP3) on Constitutional delay of puberty	Powerpoint slides on Constitutional delay of puberty • Images of Constitutional delay of puberty • Photos of Constitutional delay of puberty • Podcasts & MP3s on Constitutional delay of puberty • Videos on Constitutional delay of puberty
Evidence Based Medicine Regarding Constitutional delay of puberty	Cochrane Collaboration on Constitutional delay of puberty • Bandolier on Constitutional delay of puberty • TRIP on Constitutional delay of puberty
Cost Effectiveness of Constitutional delay of puberty	Cost Effectiveness of Constitutional delay of puberty
Clinical Trials Involving Constitutional delay of puberty	Ongoing Trials on Constitutional delay of puberty at Clinical Trials.gov • Trial results on Constitutional delay of puberty • Clinical Trials on Constitutional delay of puberty at Google
Guidelines / Policies / Government Resources (FDA/CDC) Regarding Constitutional delay of puberty	US National Guidelines Clearinghouse on Constitutional delay of puberty • NICE Guidance on Constitutional delay of puberty • NHS PRODIGY Guidance • FDA on Constitutional delay of puberty • CDC on Constitutional delay of puberty
Textbook Information on Constitutional delay of puberty	Books and Textbook Information on Constitutional delay of puberty
Pharmacology Resources on Constitutional delay of puberty	Dosing of Constitutional delay of puberty • Drug interactions with Constitutional delay of puberty • Side effects of Constitutional delay of puberty • Allergic reactions to Constitutional delay of puberty • Overdose information on Constitutional delay of puberty • Carcinogenicity information on Constitutional delay of puberty • Constitutional delay of puberty in pregnancy • Pharmacokinetics of Constitutional delay of puberty •
Genetics, Pharmacogenomics, and Proteinomics of Constitutional delay of puberty	Genetics of Constitutional delay of puberty • Pharmacogenomics of Constitutional delay of puberty • Proteomics of Constitutional delay of puberty
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Patient Resources on Constitutional delay of puberty	Patient resources on Constitutional delay of puberty • Discussion groups on Constitutional delay of puberty • Patient Handouts on Constitutional delay of puberty • Directions to Hospitals Treating Constitutional delay of puberty • Risk calculators and risk factors for Constitutional delay of puberty
Healthcare Provider Resources on Constitutional delay of puberty	Symptoms of Constitutional delay of puberty • Causes & Risk Factors for Constitutional delay of puberty • Diagnostic studies for Constitutional delay of puberty • Treatment of Constitutional delay of puberty
Continuing Medical Education (CME) Programs on Constitutional delay of puberty	CME Programs on Constitutional delay of puberty
International Resources on Constitutional delay of puberty	Constitutional delay of puberty en Espanol • Constitutional delay of puberty en Francais
Business Resources on Constitutional delay of puberty	Constitutional delay of puberty in the Marketplace • Patents on Constitutional delay of puberty
Informatics Resources on Constitutional delay of puberty	List of terms related to Constitutional delay of puberty

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Acknowledgement and Attribution Regarding Sources of Content

Some of the initial content on this page may be incorporated in part from copyleft sources in the public domain including wikis such as Wikipedia and AskDrWiki. Drug information for patients came from the The National Library of Medicine. Infectious disease information may have come from the Centers for Disease Control (CDC). Differential Diagnoses are drawn from clinicians as well as an amalgamation of 3 sources: 1.The Disease Database; 2. Kahan, Scott, Smith, Ellen G. In A Page: Signs and Symptoms. Malden, Massachusetts: Blackwell Publishing, 2004:3; 3. Sailer, Christian, Wasner, Susanne. Differential Diagnosis Pocket. Hermosa Beach, CA: Borm Bruckmeir Publishing LLC, 2002:7 .