Delayed or absent puberty

If a girl shows no signs of puberty by age 13, or has not completed puberty by age 16, or if a boy shows no signs of puberty by age 14, or has not completed puberty by age 17, puberty is said to be delayed and merits investigation. Constitutional delay of growth and puberty is the commonest cause of this condition.

Who is concerned that there is a problem with the child's pubertal development?

Ensure that the family understands the normal timing of puberty. It may be helpful to outline normal development at first consultation as this may allay fears. 

Assess whether the parents are the only people with concerns. If so, monitoring may clarify whether there is a growth problem. If the child is the only person concerned about their size and development, then it is worth exploring whether they're being bullied. 

If other professionals, e.g. teacher, health visitor or GP, have expressed concerns about the child then this merits further investigation.

Is there a family history of growth problems or delayed puberty? What are the heights of the child's parents and siblings?

A family history and short stature in the parents is generally suggestive of familial short stature. Extreme short stature in a sibling suggests genetic causes such as Laron syndrome or a skeletal dysplasia.

A family history of constitutional delay of puberty is common, though a history of relatives with absent or arrested puberty raises the possibility of inherited disorders of development e.g. Kallman's syndrome.

Are the parents related? 

Consanguinity is very common in some populations and raises the possibility of inherited recessive conditions affecting growth. If a growth disorder is recessively inherited both parents will have normal heights.

What size was the child at birth?

It is important to document the child's birth weight and gestational age. Low birth weight for gestational age, i.e. small for gestational age (SGA), can cause short stature in 10 to 15% of SGA infants.

At what gestational age was the child born?

Premature babies are frequently small, and very premature infants may have incomplete catch-up growth and become small children. 

Were there any problems in the perinatal period? 

Ask about the mode of delivery - vaginal, instrumental or operative.

Determine whether the child required time in special care which may affect maternal bonding, or reflect underlying physical problems.

Did the child have any major physical problems as an infant that might affect long term growth and development? Pyloric stenosis and other congenital bowel problems may have led to undernourishment early in life.

Did the child breast or bottle feed and did they have early difficulties with feeding?

Difficulty swallowing, or intolerance to milk may have led to undernourishment early in life. 

Are they taking a normal diet? Do they have symptoms suggestive of an eating disorder? Do they take any special supplements or soya products, such as milk? 

Anorexia nervosa and very low BMI of any cause will cause delay of growth, and may also cause hypothalamic dysfunction and pubertal delay.

Soya contains large amounts of phytoestrogens which may interfere with the hypothalamic-pituitary-gonadal axis and may be associated with reversible gynaecomastia.

Steroids also interact with the hypothalamic-pituitary-gonadal axis and may occasionally be found in preparations thought by the patient to be 'natural' or 'herbal'.

Has the child achieved the normal developmental milestones? 

Failure to reach normal developmental milestones suggests an underlying more complex problem.

Does the child attend school?

If the child does not attend a normal school, this suggests possible underlying developmental problems which require thorough assessment before the issue of short stature can be addressed.

If the child has stopped attending their regular school, this may reflect underlying social issues or unhappiness. Neglect and malnutrition remain the commonest causes of short stature worldwide. Alternatively, if the child has had repeated absence from school due to illness, e.g. asthma, Crohn's disease, diabetes or cystic fibrosis, these chronic conditions are likely to explain their growth problems. 

Is this an isolated problem or do they have symptoms suggestive of other physical or developmental problems? 

The list of differential diagnoses will be different in a patient with multiple medical problems or an obvious congenital condition.

Serious systemic illness of any cause is also associated with pubertal and growth delay. The commonest would be chronic respiratory, renal or gastrointestinal conditions. Specific conditions associated with abnormal pubertal develoment include the intersex disorders, pseudopseudohypoparathyroidism, Cushing's syndrome and congenital hypothyroidism.

Does the child have problems with their breathing?

Chronic respiratory conditions such as asthma, cystic fibrosis or following premature delivery are commonly associated with growth failure.

Has the child had any other problems with their bowel? 

Constipation in children usually has social causes - they might be embarrassed to use a public or dirty toilet, or hold on too long as they do not want to stop what they are doing. It may also reflect a poor diet, insufficient fibre or fluid intake.

However, it may also reflect underlying problems such as hypothyroidism, spina bifida or in the neonate Hirschprung's disease or anorectal malformations. Any of these causes may be associated with growth failure and treatment should be directed at the underlying issue including social issues.

Diarrhoea may be a clue to underlying Coeliac disease or thyrotoxicosis. Abdominal pain and poor appetite may be symptoms of Crohn's disease, which affects growth.

What has the child's pattern of growth been?

If the child has previously followed the same centile line on a growth chart, and has recently deviated this suggests a specific problem. If the child has always been small, and continues to follow a centile line, significant new pathology is unlikely.

Constitutional delay of growth and puberty often follows a specific pattern, with retarded linear growth within the first 3 years of life. Linear growth velocity and weight gain slows as early as age 3-6 months, resulting in downward crossing of growth percentiles, which often continues until age 2-3 years. At that time, growth tends to resume at a normal rate, and these children grow either along the lower growth percentiles or beneath the curve but parallel to it for the remainder of the prepubertal years. At the expected time of puberty, the height of children with constitutional growth delay begins to drift further from the growth curve because of delay in the onset of the pubertal growth spurt.

Catch-up growth, onset of puberty, and pubertal growth spurt occur later than average, frequently resulting in normal adult stature and sexual development. Although constitutional growth delay is a variant of normal growth rather than a disorder, delays in growth and sexual development may contribute to psychological difficulties, warranting treatment for some individuals.

Bone age is usually delayed (typically 2-4 years by late childhood) and is most consistent with the child's height age (the age for which a child's height is at the 50th percentile) rather than the child’s chronologic age.

Has the child shown signs of the start of puberty?

Full assessment of pubertal staging is required and is outlined on the examination page. Formal Tanner staging should also be performed.

Puberty before 8 years in girls is likely to be precocious and further assessment is necessary. Between 8-13 years most girls will be either ‘Prepuberty’ or ‘In puberty’. If there are no signs of puberty by 13 years, then puberty is delayed and further assessment is indicated. From 13-16 years most girls will be either ‘In puberty’ or ‘Completing puberty’. After 16 years girls will usually be ‘Completing puberty’. If this is not the case, maturation is delayed and further assessment is required.

Puberty before 9 years in boys is likely to be precocious and further assessment is necessary. Between 9-14 years most boys will be either ‘Pre- puberty’ or ‘In puberty’. If there are no signs of puberty by 14 years, then puberty is delayed and further assessment is indicated. From 14-17 years most boys will be either ‘In puberty’ or ‘Completing puberty’. After 17 years boys will usually be ‘Completing puberty’. If this is not the case, maturation is delayed and further assessment may be needed. 

Fully assess pubertal development

 Has the girl noticed any change in her breasts or developed any new hair?

 If there has been no change to the nipples or breasts and no new hair, puberty has not started.

There has been some breast development or some hair

Any pubic or axillary hair, or any enlargement of the breasts and nipples confirms that the child is in puberty. This stage is usually reached between age 8 and 13 years.

 Has the girl started having periods?

 Once a girl has started menstruating, and has breast development and pubic and axillary hair, puberty is complete. This has usually occurred by age 16.

Has the boy noticed any change to his voice, any new hair, or any change in the size of his penis or testes?

If none of these things has happened, the boy is still pre pubertal. These changes usually start between age 9-14 years.

Any change in the voice, reddening of the scrotum or enlargement of the penis, or body hair indicates that puberty has started.

 Any of these signs indicate that the boy is now in puberty which should happen by age 14.

Has the boy developed facial hair or a fully broken voice?

These symptoms as well as the signs of adult sized testes and penis, as well as adult body hair indicate that puberty is complete. This has usually occurred by age 17.

Delayed or absent puberty confirmed

Does the patient have a normal sense of smell? 

Patients may not report anosmia unless specifically questioned. Kallmann’s syndrome is typified by anosmia and hypogonadotropic hypogonadism.

Has the patient had any dental problems? 

Dental aplasia, cleft palate and dental malalignment requiring orthodontic treatment may not be obvious and are associated with Kallmann’s syndrome.

Has the patient had any renal problems? 

Congenital abnormalities of the urogenital system may occur with Kallmann’s and Turner’s syndromes.

Is there a relevant family history? 

Specifically ask if any family members, for example cousins, have had late or absent puberty, infertility or simply never had children.

Ask also if any family members have had dental or palatal problems, kidney abnormalities or anosmia which might suggest a family history of Kallmann’s syndrome.

Does the patient have any symptoms suggestive of thyroid dysfunction? 

Congenital hypothyroidism is associated with delayed puberty.

Hypothyroidism is also associated with Turner's syndrome.

Is the patient known to have coarcation of the aorta, or other vascular abnormalities? 

These may be associated with Turner syndrome.

Has the patient had any hearing problems? 

Deafness may be associated with Turner syndrome.

Is the patient known to have psychiatric problems or learning difficulties? 

Patients with Klinefelter's syndrome have an increased incidence of psychiatric problems.

Has the patient had other physical or learning difficulties in the past? 

Multiple congenital conditions include abnormalities of sexual development. Examples include pseudopseudohypoparathyroidism, Russell Silver syndrome, congenital hypothyroidism.

Specific disorders of sexual development may also be encountered: congenital adrenal hyperplasia, androgen insensitivity syndrome, 5-alpha reductase deficiency, aromatase deficiency, gonadal dysgenesis, Kallmann's syndrome, Turner syndrome, Klinefelter's syndrome, and other rarer conditions.

Has the patient lost or gained weight, or changed in body shape? 

Weight loss may indicate the development of hypopituitarism or hyperthyroidism. Hypogonadotropic hypogonadism may also occur with Cushing's syndrome and in obesity.

Tall stature and a feminine or 'eunuchoid' body shape may be associated with absent puberty in males.

Gynaecomastia may indicate gonadotropin deficiency but in the absence of other symptoms other causes should be considered. Gynaecomastia occurring in conjunction with weight loss should alert to the possibility of malignancy and other systemic diseases.

Has the patient had mumps, testicular torsion or other testicular trauma? 

These are all causes of gonadal failure, though orchitis is frequently asymptomatic.

Has the patient had any testicular surgery or maldescent of the testes? 

Maldescent may be associated with gonadal dysfunction as well as an increased risk of malignancy.

Are there any features of thyroid dysfunction? 

Hypothyroidism is a common cause of growth failure and delayed puberty. 

Also ask whether the patient has developed increased sweating, palpitations, tremor, weight loss or diarrhoea, as thyrotoxicosis may also cause gynaecomastia and oligomenorrhoea.

Are there any other symptoms of pituitary hormone deficiency? 

Growth failure is a common presenting feature of childhood hypopituitarism of any cause, and delayed puberty will also occur with paediatric hypopitutiarism. However, hypopituitarism is conversely a very unusual cause of short stature or pubertal delay - which is usually constitutional.

What level of exercise does the patient take? 

Excessive exercise may lead to hypothalamic dysfunction and growth failure.

Are they taking any prescribed or non prescribed medications? 

Various drugs in particular steroids are associated with growth failure and pubertal delay, and are commonly used for example in childhood asthma, inflammatory bowel disease or cystic fibrosis.

Various agents associated with hypogonadism are listed below (although it is not exhaustive): 

Opiates and recreational drugs, for example diamorphine, morphine sulphate, heroin, marijuana and alcohol are uncommonly encountered in paediatric patients.

Steroids, for example hydrocortisone, beclamethasone, fluticasone interfere with the hypothalamo-pituitary axis and cause growth and pubertal delay.

Exogenous testosterone, estrogens and drugs with estrogen-like activity, such as diethylstilbestrol and digoxin may cause gynaecomastia but are rarely encountered in children. 

Phenytoin and older antiepileptic agents enhance estrogen synthesis, and may cause abnormalities of pubertal development. The underlying condition may also cause growth failure.

Does the child - if male - complain of breast swelling?

How long has the gynaecomastia been present? 

A detailed history of gynaecomastia will help elucidate likely causes.

Define at what age the gynaecomastia developed. Breast swelling is common in infants and peripuberty and usually requires no treatment. Childhood obesity may also be associated with bilateral non-glandular breast swelling.

Sudden onset and unilateral gynaecomastia should alert to the possibility of breast cancer, though this is exceptionally rare in children.

Is the gynaecomastia bilateral or unilateral? 

Sudden onset and unilateral gynaecomastia should alert to the possibility of breast cancer.

Is there any galactorrhoea or mastalgia? 

Bilateral galactorrhoea and mastalgia are suggestive of elevated prolactin - either from medication use, a prolactinoma or non functioning pituitary tumour. This requires urgent evaluation in a child.

Changes in the skin, nipple or unilateral discharge is highly suspicious for breast cancer, though this is exceptionally rare in children.

Are there any features of thyroid dysfunction? 

Hyperthyroidism may be associated with gynaecomastia: ask about sweating, palpitations, tremor, weight loss or diarrhoea.

Hypothyroidism may be associated with delayed puberty.

Does the patient have any symptoms of cardiac or hepatic disease? 

Breathlessness, abdominal or ankle swelling should alert to the possibility of other problems. Congenital heart disease, or metabolic errors leading to congestive cardiac or liver failure will usually be obvious but may cause growth delay and frequently gynaecomastia.