Growth and puberty

After reading this chapter you should:

  • know the causes of problems relating to growth and puberty

  • be able to assess, diagnose and manage problems relating to growth and puberty

Disorders of growth

Growth is an excellent clinical tool to help distinguish between health and disease in any child in any setting and can be affected by genetics, nutrition and pathology in any system. It is a dynamic process so the position of a child on a growth chart matters less than how they arrived there, and sourcing and plotting previous growth data is invaluable.

Children who are short for expected family height and relatively overweight are likely to have an endocrine or syndromic cause for their short stature, especially if there is evidence of slow growth. Constitutional early puberty is the commonest cause of unusually tall stature in children and is often related to overnutrition. Such children enter puberty relatively early and therefore reach their expected height early compared with their healthy weight peers. Pathological causes of tall stature are rare and are often syndromic.

Short stature

In the UK, it is possible to obtain previous growth measurements from the Personal Child Health Record and the National Childhood Measurement Programme which measures height and weight of all children entering a reception class (aged 4–5 years) and all leaving primary school (Year 6—aged 10–11 years). These measurements can be used to establish the pattern of growth.

Clinical presentation

The key point when assessing any child with concerns about short stature is to seek any of the ‘red flags’ that help distinguish the minority with an identifiable or treatable cause from the majority with familial short stature. To do so necessitates a broad and detailed history and examination since growth can be affected by pathology in any system.

Important features in the history include:

  • general health—whether the child is otherwise healthy and active

  • whether the child has always been small or growth is a new concern

  • whether siblings are overtaking them in height

  • past medical history including pregnancy, birthweight, early feeding and growth in infancy. Some syndromic causes are linked to feeding difficulties in infancy, e.g., Turner, William, Noonan, 22q.11 deletion, Silver Russell and Prader-Willi

  • history of prolonged conjugated neonatal jaundice or neonatal hypoglycaemia that may point to hypothalamo-pituitary problems

  • history of any chronic illness such as asthma or inflammatory bowel disease that can slow growth

  • family history including the health and heights of parents, grandparents and wider family along with a family history suggestive of constitutional growth delay with later than average puberty

  • full systems review—particularly any history suggestive of malabsorption or gut inflammation, headaches or visual problems that might suggest a pituitary tumour and any symptoms of hypothyroidism such a cold intolerance or constipation

  • any symptoms suggestive of an undiagnosed chronic illness such as coeliac disease

  • history of developmental, education or behaviour problems

  • current and previous drug history especially of steroid use to include dose, mode of delivery and adherence to treatment

  • psychosocial history as short stature may be the result of emotional abuse

  • Important features in the examination include:

  • height, weight and, if indicated, BMI plotted on an age and sex appropriate chart. Previous data will help to establish the growth pattern

  • height centiles of both parents and target centile range should be calculated. The target range is the mid-parental centile (the midpoint between the parents’ centiles) ± 8.5cm and further assessment is required if the child falls outside this range

  • sitting height or crown rump length is compared with leg length. Disproportionate short stature suggests a skeletal dysplasia, possibly inherited from a parent especially if they too are exceptionally small

  • head circumference is measured and plotted as patients with some skeletal dysplasias have relatively large heads

  • BMI is calculated and plotted on a UK Standard chart

  • full examination to include general health and appearance as disease of any system can present with poor growth

Practice Point – short stature: ‘red flags’ suggesting pathological cause

  • extreme short stature—the further below the 0.4 th centile the greater the chance of identifiable pathology

  • short and greater than one major centile below target range for normal parents although many will be constitutional

  • dysmorphic features

  • skeletal disproportion

  • evidence of slow growth with downwards crossing of the centiles

  • short and overweight—suggests an endocrine cause

  • evidence of chronic illness


These will be dictated by the differential diagnosis that emerges after the history and examination. If a child is healthy, falls within an acceptable range for their parents and there is no evidence of growth slowing, further tests may not be necessary. A system-related condition such as inflammatory bowel disease should be investigated if there is clear evidence found in the history.

The following tests should be requested when there are concerns about the growth pattern with no obvious cause:

  • full blood count, indices and film—to exclude anaemia

  • CRP—to exclude undiagnosed inflammation

  • urea, electrolytes and creatinine—assessing renal function

  • liver function tests—low albumin can be seen in many chronic conditions

  • bone profile—calcium, phosphate and ALP

  • IgA and anti-TTG antibodies—screening tests for coeliac disease

  • thyroid function tests—FT4 and TSH—TSH without the FT4 may miss secondary hypothyroidism

  • IgF-1 and IgF-BP3—limited value in screening for growth hormone deficiency but reassuring if normal. Varies with age, so age-related values should be used

  • karyotype in girls—to exclude Turner Syndrome and possibly DNA for SHOX (Short stature Homeobox-containing gene) mutations in both sexes

  • bone age estimation for skeletal maturity

Further investigations will depend on the results and the clinical scenario but could include:

  • skeletal survey (modified)—to exclude a skeletal dysplasia

  • formal pituitary functions tests—to assess growth hormone production

Important sequelae

There are many publications supporting the view that short stature is a source of psychological and behaviour problems in affected children but many of these studies risk bias as they only include patients seen in a growth service. Population studies show very little impact on adult functioning and this may be important when counselling families.

Specific conditions

Familial short stature

Familial short stature is the most common diagnosis in children referred to a growth clinic. A healthy child whose height is within expectation for parents, who are themselves of normal height, and without evidence of slow growth should be discharged after explanations and reassurance.

Small for gestational age (SGA)

Definitions of SGA vary but the UK cut-off is a birthweight below minus 2.0 SDS on the centile charts. Length is not routinely measured at birth. About 80% of babies who are born SGA show catch-up growth and in those who remain small, other pathology might be identified such as:

  • Silver Russell syndrome

  • Turner syndrome

  • Prader-Willi syndrome

  • Fetal alcohol spectrum disorder

Growth hormone is licensed in the UK for those who have not shown catch up and remain short for expected family size by the age of 4 years. Early studies show a modest increase in final height.

Chronic conditions

Any disorder associated with poor health—physical or emotional—can impair growth, and management should be directed at correcting the underlying pathology. Examples include:

  • coeliac disease—introducing a gluten-free diet

  • juvenile idiopathic arthritis—using disease-modifying agents

  • asthma control—addressing inadequate treatment or reducing doses of inhaled steroids

  • psychosocial short stature—by a successful change of environment

Chronic renal impairment is the only such condition where growth hormone is part of the management although higher than replacement doses are needed due to growth hormone resistance.

Endocrine causes

The impact on growth is presented here, but further details of these conditions can be found in Chapter 25 Endocrinology.

Growth hormone deficiency

Clinical presentation

The age at which growth hormone deficiency (GHD) presents depends on the extent of the deficiency. Unless there are obvious midline anomalies, undescended testes or micropenis, GHD in neonates is usually identified during investigations for hypoglycaemia and GH should be part of a ‘hypoglycaemia screen’ at any age.

Growth during the first 2 years is predominantly nutritionally driven, so in older children GHD tends to manifest with slowing of growth with increased body fat—the child who is overnourished yet short. There might also be symptoms or signs of skeletal immaturity, e.g., slow tooth eruption or delayed puberty. This might be isolated GHD, part of evolving hypopituitarism or as the result of a midline brain tumour such as a craniopharyngioma or optic nerve glioma. GHD is also one of the consequences of high-dose cranial irradiation needed for some brain tumours.


Children with possible GHD should undergo standard formal pituitary function ‘stress’ tests ( Table 4.1 ) ensuring that thyroid function is normal in advance to avoid a false-positive diagnosis (the GH response can be blunted if metabolism is slow due to hypothyroidism). A TRH test is rarely indicated because thyroid involvement can usually be detected from standard tests of Free T4 and TSH. Similarly, an LHRH test as puberty is best assessed clinically.


Results of pituitary function stress testing with glucagon in a 6 year old with slow growth. The ‘stress’ response is as a result of an initial increase in blood glucose that stimulates insulin release and thus a rapid drop in glucose. These results show severe GHD but no evidence of cortisol deficiency.

Time (minutes) Glucose mmol/l (3.5–6.5 mmol/l) Growth Hormone (>8.3 ng/dl) Cortisol (>550 nmol/l)
0 4.5 2.8 450
30 6.4 3.4 320
60 2.9 2.1 685
90 3.7 3.7 420
120 4.9 3.3 330
150 4.7 3.2 295

All neonates and children diagnosed with clinical and biochemical evidence of GHD should undergo an MRI scan and most will have an abnormality of varying severity. They should also be screened and then monitored for the development of other pituitary hormone deficiencies.

Treatment and management

Treatment is with daily injections of recombinant GH until final height is achieved when all patients should be retested. In adults, lower doses are needed to maintain normal body composition, bone health and to avoid cardiovascular risk factors.

Pharmacological agents used

Growth hormone is manufactured using recombinant technology and is administered by daily subcutaneous injection using a choice of device although adherence to treatment can be a problem. Headache is the commonest side effect but rarely severe enough to stop treatment, and idiopathic intracranial hypertension has been reported. Starting GH can also unmask latent deficiencies of ACTH and thyroid hormone.


Untreated hypothyroidism whatever the cause will slow growth, and a history that the child’s peer group or sibs are overtaking is probably the commonest presentation as this is noticed more than the other insidious classic features. Treatment is with thyroxine replacement in a dose that increases with body size.

Cushing syndrome or disease

Excess steroids can impair growth and lead to excess weight gain, and children usually have very few of the other characteristic signs. The commonest cause is iatrogenic and, as an example, the guidelines in the UK are that all children on regular inhaled steroids should have their height and weight measured and plotted every 6 months.

Syndromic causes

The impact on growth is presented here but further details on each of these syndromes can be found in Chapter 5 Genetics.

Turner syndrome

Endocrine features invariably include short stature and almost invariably primary ovarian failure. GH use is licensed, but the recommended dose is about twice the standard replacement dose to help overcome the growth hormone resistance linked to the bone dysplasia. The features of TS are variable, partly dependent on karyotype, and may be very mild so chromosome analysis should be requested on all girls with significant short stature irrespective of parental heights. Primary ovarian failure is managed with induction of puberty at an appropriate age and monitoring through adulthood. Further details are provided below in the section on primary gonadal failure.

SHOX mutations

The short stature homeobox-containing gene (SHOX) has an important role in long bone growth. The frequency of SHOX-deficient short stature is thought to be relatively common (estimated at 6%–22%), and analysis of the gene should be considered in all children with significant short stature. Growth hormone is licensed in the UK for children with SHOX mutations.

Noonan syndrome

Noonan syndrome is inherited in an autosomal dominant fashion, and the phenotypic features can be mild and include short stature plus other features. The use of GH to improve final height in Noonan syndrome is controversial and it is not currently licensed in the UK.

Silver Russell syndrome (SRS)

This rare imprinting disorder is characterised by severe pre- and postnatal growth restriction, no catch up and typical dysmorphic features (see Chapter 5 Genetics). These children have marked feeding difficulties, low muscle mass, excessive sweating and are at risk of hypoglycaemia well beyond the neonatal period. Older children with SRS are at risk of exaggerated adrenarche and subsequently other complications of insulin resistance. It is primarily a clinical diagnosis but an underlying molecular cause can currently be identified in around 60% of patients. Again, the use of GH is controversial but it may help prevent hypoglycaemia, improve appetite and motor development.

Fetal alcohol spectrum disorder

There is a wide spectrum of teratogenic effects of alcohol on an unborn baby, but one cardinal feature in severe toxicity is impaired childhood growth.

Skeletal dysplasias

There are numerous skeletal dysplasias described that are associated with short stature and slow growth. Many children or affected adults will show disproportionate limb or spinal growth that might not be obvious on clinical examination. There is therefore a need to measure sitting height or crown rump length, calculate leg length and then plot both on the relevant chart in all significantly short children. The more obvious skeletal dysplasias include achondroplasia and hypochondroplasia. Growth hormone has been trialled but is ineffective.

Tall stature

Referrals of children with unusually tall stature are much less common than short stature and most do not have a pathological cause. The commonest causes are overnutrition or normal, but early, puberty in a child with tall parents. These children will complete their growth phase and reach their predicted height earlier than their peers and within expectations for their parents.

All children and young people with unusually tall stature should be weighed, measured and plotted on the appropriate growth chart along with sitting height and calculated leg length. This will help identify the rare child with disproportionate, long-limbed tall stature. The presence of other dysmorphic features may help identify any recognised syndromes.

Investigations are rarely indicated although an estimation of bone age can be reassuring for final height if it confirms advanced skeletal maturity. In a rapidly growing child, any signs of abnormally early puberty, growth hormone excess or symptoms and signs of thyrotoxicosis should be investigated.

Syndromic causes with disproportionate long-limbed tall stature

Marfan syndrome

The clinical diagnosis of this autosomal dominant connective tissue disorder condition relies on a set of defined criteria but ectopia lentis or a significant aortic root abnormality are cardinal. Skeletal disproportion, including arachnodactyly ( Figure 4.1 ), contributes to the ‘systemic score’ of other typical features used when one of the above signs is absent and there is no positive family history. The diagnosis and decision to analyse the FBN1 gene should almost always be made by a clinical geneticist as a diagnosis of Marfan syndrome has potentially serious repercussions for future health of the patient and their family.

Jul 31, 2022 | Posted by in PEDIATRICS | Comments Off on Growth and puberty

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