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Disorders of puberty
Consultant Paediatric Endocrinologist, Birmingham Children's Hospital
Paediatric Registrar, Birmingham Children's Hospital
Executive Editor, InnovAiT
E-mail: jeremy.kirk{at}bch.nhs.uk
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Abstract |
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 TOP Abstract The GP curriculum and...Normal pubertyPrecocious pubertyAbnormal patterns of pubertySpecific conditionsAssessment of abnormal puberty...References |
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Puberty is defined as the time when the onset of sexual maturity occurs and the reproductive organs become functional, and it is therefore the time when a child becomes an adult capable of reproduction. Although the terms puberty and adolescence are commonly used interchangeably, the term puberty tends to be used for the physical, and adolescence for the psychological and social changes.
Puberty is manifested:
- In both sexes by the development of pubic and axillary hair
- In girls, between the ages of 8 and 14 years, by growth of the breasts and menstruation.
- In boys, between the ages of 9 and 15 years, by growth of the penis, testes and scrotum, deepening of the voice, initiation of spermatogenesis, and by growth of facial hair requiring shaving
Puberty is a time of great physical and emotional change and can be a difficult time in any family. It can cause a great deal of anxiety both to the child and the parents if puberty does not progress as expected and is either too advanced or delayed for the age of the child. This makes assessment and management of disorders of puberty particularly challenging.
Curriculum statement 8: Care of children and young people, requires GPs in training to be able to:
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Normal puberty |
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TOPAbstractThe GP curriculum and...Normal pubertyPrecocious pubertyAbnormal patterns of pubertySpecific conditionsAssessment of abnormal puberty...References |
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There is a wide range of ‘normality’ of puberty. Normal puberty commences from approximately 10 years onwards, although girls tend to start puberty somewhat earlier than boys. Puberty usually lasts 3–4 years, with passage from one stage to another approximately every year. Pubertal assessment is usually performed with reference to the Tanner stages (Tables 1 and 2).
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Bone age
Assessment of the biological age of the child, as opposed to chronological age, is performed using the ‘bone age’. This uses assessment of epiphyses on an X-ray of the left hand (Fig. 1). It enables assessment of remaining growth and correlates better with pubertal staging than chronological age alone.
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Assymetric breast growth in girls
Asymmetrical breast growth in girls during puberty is the rule rather than the exception. Reassure that the asymmetry usually evens out by the time of full maturation.
Gynaecomastia in boys
Gynaecomastia refers to male breast enlargement, and occurs in about 50% of boys as they go through puberty. A small, firm, and sometimes tender lump is noticed under one or both nipples. Reassure that gynaecomastia is common, normal, and usually goes away in time without any treatment.
Mechanism of puberty
The bodily changes that occur with puberty are due to the action of the sex hormones on the body. These sex hormones include testosterone and other androgens for both sexes, together with oestrogen and progesterone in girls. The secretion of these hormones is from the testes in boys and ovaries in girls and to a lesser extent from the adrenal glands in both sexes. Some oestrogen is also produced in both sexes from peripheral conversion of sex hormones.
Secretion of sex hormones is under the control of hormones, or gonadotrophins, released from the anterior pituitary gland at the base of the brain (Fig. 2). There are two gonadotrophin hormones, follicle stimulating hormone (FSH) and luteinizing hormone (LH). The release of gonadotrophin hormones from the anterior pituitary gland is in turn controlled by gonadotrophin-releasing hormone (GnRH) from the hypothalamus.
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A negative feedback loop (Fig. 2) prevents excess hormone production. If there is sufficient sex hormone circulating, then this feeds back to both the pituitary gland and hypothalamus to reduce the amount of FSH and LH being produced.
At birth, the circulating levels of FSH and LH are similar to those of an adult. Soon after birth, however, both GnRH secretion and levels of circulating FSH and LH reduce to very low levels. As a child progresses towards puberty, the hypothalamus starts to secrete pulses of GnRH. The frequency and size of these pulses increase with time until there is constant secretion of GnRH, as in adulthood.
Delayed puberty
Delayed puberty is defined as no pubertal changes in a girl aged 13 years or boy aged 14 years, or failure of progression of puberty over 2 years. It affects about 2% of the population. The most common cause of delayed puberty in boys is constitutional delay (more than 50%). However, 80% of girls have a pathological cause for delayed puberty. Pathological causes can be divided into those caused by failure of the ovaries or testes (also termed primary or hypergonadotrophic hypogonadism) and those caused by failure of stimulation of normal gonads to produce sex hormones (termed secondary or hypogonadotrophic hypogonadism). In all cases, refer to a paediatrician or paediatric endocrinologist for further assessment.
Hypergonadotrophic delayed puberty
There are many possible causes of testicular or ovarian failure. Lack of sex hormone production results in low levels of circulating sex hormones, reduced negative feedback on the hypothalamus and pituitary, and high levels of circulating FSH and LH. Causes of testicular and ovarian failure are listed in Table 3.
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Hypogonadotrophic delayed puberty
If the hypothalamus does not secrete enough GnRH or the pituitary gland does not secrete enough LH or FSH, then the normal gonads will not be stimulated to secrete sufficient sex hormones for pubertal changes to occur. Biochemically, circulating levels of sex hormones, FSH and LH are all reduced. Depending on whether the underlying cause of the problem is in the hypothalamus or pituitary, GnRH levels may be reduced or increased. Causes of hypogonadotrophic delayed puberty are listed in Box 1.
Box 1. Causes of hypogonadotrophic delayed puberty
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Social effects of delayed puberty
Many children, particularly boys, have great difficulty in coping with delayed puberty. They may be considerably shorter, and appear much younger, than their friends. Later on their lack of sexual development may cause them embarrassment and make them feel left out. In some, this may result in immature behaviour (playing the child), while in others, it may manifest as aggressive and/or antisocial behaviour.
The reactions of others to the child may also be affected by delayed puberty. Children who are small are often treated according to their size and not their age. Parents may continue to do things for a child that he or she should be doing alone, or children may be barred from doing social activities that their friends are allowed to do—for example children who look small may not be granted access to certain films at the cinema. Appearing immature and unable to join in with group activities may then lead to further exclusion by the child's peer group. The small teenager can be a natural target for bullying and sometimes, inappropriate skills are developed to compensate in order to survive with some self-esteem.
Provide information and talk through any worries with both the child and the parents. The Child Growth Foundation is a useful source of information and support (website: www.childgrowthfoundation.org). Consider involving other involved professionals such as schoolteachers. Referral for specialist counseling may be appropriate in some circumstances.
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Precocious puberty |
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TOPAbstractThe GP curriculum and...Normal pubertyPrecocious pubertyAbnormal patterns of pubertySpecific conditionsAssessment of abnormal puberty...References |
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Precocious puberty is defined as puberty before the normal age for the population. In the UK, this is under the age of 8 years for girls and 9 years for boys. Precocious puberty affects about 4–5% of girls and is about five times more commonly seen in girls than boys.
Central or true precocious puberty
Premature activation of the hypothalamic–pituitary–gonadal axis results in a gonadotrophin-driven early puberty. In all cases, refer for further investigation to exclude hypothalamic tumours and other central nervous system pathology. No pathological cause for this pattern of precocious puberty is absent in 50–60% of males and 90% of females. In these individuals, there may be a family history of precocious puberty. Obesity may also be involved in development of precocious puberty in girls but not boys.
Pseudoprecocious puberty
Pseudoprecocious puberty, or gonadotrophin-independent precocious puberty, accounts for 20% of all cases of precocious puberty. There is an increased level of sex hormones in the absence of excess FSH or LH. The causes of pseudoprecocious puberty are listed in Table 4. Many are rare. All require specialist investigation and management. Refer to a paediatrician or paediatric endocrinologist.
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Social effects of precocious puberty
Children who are taller than other children of the same age will often be treated as older than they actually are. This can result in children being punished or teased for behaviour appropriate to their age or considered stupid or behind when in fact they are attaining expected developmental milestones.
Children with precocious puberty may show more awareness of sexual parts and masturbate which can create embarrassment, especially in adults, and confusion in the child. Underarm deodorants and more frequent baths and hair washing, may be necessary as sweating and body odour can be a problem.
All children want to look and act like friends of their own age. Although early puberty can give a child distinct physical advantages when playing many sports, being different from other children of the same age can lead to embarrassment for the child, teasing or bullying, and social exclusion. This, in turn can lead to poor self-esteem. Parents, relations and others also have to cope with their own reactions to the changes in their child. These may include alarm, distress, distaste, guilt and confusion.
As for children with delayed puberty, provide information and talk through any worries with both the child and the parents. The Child Growth Foundation is a useful source of information and support (website: www.childgrowthfoundation.org). Consider involving other involved professionals such as schoolteachers. Referral for specialist counseling may be appropriate in some circumstances.
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Abnormal patterns of puberty |
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TOPAbstractThe GP curriculum and...Normal pubertyPrecocious pubertyAbnormal patterns of pubertySpecific conditionsAssessment of abnormal puberty...References |
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Primary amenorrhoea
Primary amenorrhoea occurs in any girl who has no secondary sexual characteristics or menstruation by age 14 years with growth failure or no menstruation by the age of 16 years when growth and sexual development is normal. The causes are the same as the causes of delayed puberty with the addition of conditions with absent uterus e.g. Mayer-Rokitansky-Kuster-Hauser Syndrome, androgen insensitivity syndrome (testicular feminization), and physical barriers to menstruation such as a transverse vaginal septum or imperforate hymen.
Physical barriers to menstruation may cause cryptomenorrhoea (literally meaning ‘hidden menstruation’), which presents as primary amenorrhoea. If suspected, then refer to a gynaecologist for surgical release.
Premature pubarche
Premature pubarche (or adrenarche) refers to the early appearance of pubic hair, and sometimes also axillary hair, together with development of the apocrine glands that result in adult body odour, without other signs of precocious puberty. It is due to excess of androgens. As long as there are no other signs of androgen excess, such as clitoral enlargement in girls, or a growth spurt in either sex, then this is usually a temporary condition. Other changes soon catch up and there is no cause for concern.
If there are other signs of androgen excess, then referral for further investigation is warranted. Possible causes include:
- Congenital adrenal hyperplasia
- Virilizing tumour—adrenal, ovarian or testicular
- Cushing syndrome
- Polycystic ovarian syndrome (girls only)
Premature thelarche
Premature thelarche refers to the development of breasts in girls without other signs of puberty. This usually occurs in very young girls, under the age of 3 years. Some breast tissue develops, but then often waxes and waned over time before burning itself out. The child has normal growth appropriate for her age and a age-appropriate bone age. Pelvic ultrasound shows that she has a normal uterus for her age. Refer to exclude other pathology.
The cause of premature thelarche is not clear but external oestrogens, for example phytooestrogens in foods such as soya products may be implicated. Another possible cause is the presence of small, transient, secretary ovarian cysts. True puberty occurs at the usual time and there are no long-term consequences.
Premature menarche
Premature menarche is periodic vaginal bleeding in a girl under the age of 8 years with no other signs of precocious puberty. Rarely, premature menarche can be the first manifestation of precocious puberty. Always refer for exclusion of serious underlying causes.
The cause of premature menarche is not clear, and as for premature thelarche, both exogenous oestrogens from food or drugs, and endogenous oestrogens from ovarian cysts have been proposed. Usually, the bleeding stops spontaneously and then restarts again after normal pubertal development when the child is older. The condition is not associated with menstrual or fertility problems later in life.
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Specific conditions |
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TOPAbstractThe GP curriculum and...Normal pubertyPrecocious pubertyAbnormal patterns of pubertySpecific conditionsAssessment of abnormal puberty...References |
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Turner syndrome
Turner syndrome is a common cause of hypergonadotrophic delayed puberty in girls. It occurs in 1 in 2500 live female births and is a chromosomal disorder in which all (45XO) or part of one of the X chromosomes is absent. The features of Turner syndrome are variable but include:
- Abnormalities of appearance—short stature (girls with Turner syndrome have a reduction in final height of about 20 cm); lymphoedema of the hands and feet; webbed neck; broad chest with wide-set nipples; low hairline and low set ears; hyperconvex, small or spoon-shaped nails; and multiple pigmented naevi
- Other health concerns—congenital heart disease, hypertension, renal anomalies hypothyroidism, eye and ear problems
- Ovarian failure causing delayed puberty, amenorrhoea and infertility.
- Cognitive deficit—in particular, difficulties in visuospatial awareness, difficulties with mathematics and poor memory
Klinefelter syndrome
Klinefelter syndrome may cause hypergonadotrophic delayed puberty in boys. It is thought to occur in 1 in 500 live male births. Affected individuals have at least two X chromosomes and at least one Y chromosome (47XXY). Although there may be a degree of cognitive deficit associated with Klinefelter syndrome, and there are physical features associated with it (tall stature, increased arm span : height ratio, small testes and gynaecomastia), these features are inconsistent.
Polycystic ovarian syndrome
About one in five women in the UK have polycystic ovaries on ultrasound, but only one in three of those women have polycystic ovarian syndrome. This is a cause of delayed puberty. Diagnosis requires the presence of two or more of the following:
- Oligomenorrhoea and/or anovulation
- Hyperandrogenism—clinical and/or biochemical
- Polycystic ovaries—defined as the presence of 12 or more follicles in each ovary measuring 2–9 mm in diameter and/or ovarian volume of more than 10 cm3
Other common symptoms and signs include central obesity, acne, hirsutism and male pattern baldness. It is currently thought that excess LH secretion from the anterior pituitary leads to overstimulation of the ovarian theca cells, causing excessive androgen production (predominantly testosterone and androstenedione). Low FSH levels prevent the ovarian granulosa cells converting these androgens into oestrogens. This in turn leads to delayed puberty.
Androgen insensitivity syndrome
Androgen insensitivity syndrome (AIS) is an X-linked genetic disorder affecting 1 in 62 000 male births. Complete or partial abnormalities within androgen receptors in target tissues results in the individual being genotypically male (46XY) but phenotypically female.
External genitalia are female in complete AIS (CAIS), but are often ambiguous in partial AIS (PAIS), along with a blind-ending vagina, with no uterus and no ovaries. The testes fail to descend and are usually found in the groin—rarely within the abdomen. At puberty, breast development occurs and female contours form, but there is little or no pubic or axillary hair. Patients often present with primary amenorrhoea.
Young people with CAIS have usually been treated as female since birth. As diagnosis is often not made until the teenage years, it is devastating to be told your chromosomes are male instead of female and that you will be unable to become pregnant or have children. Specialist support is always required. Testes are usually removed as they have malignant potential, and oestrogens given to complete secondary sexual development.
Congenital adrenal hyperplasia
Congenital adrenal hyperplasia (CAH) is also known as ‘adrenogenital syndrome’. It is an autosomal recessive genetic trait due to absence or deficiency of any one of the enzymes needed for synthesis of cortisol, and often aldosterone. Each enzyme block causes a characteristic deficiency and more than eight different syndromes have been described. The most common enzyme deficiencies are:
- 21-hydroxylase deficiency (95%)—1 : 15,000 live births. This results in increased 17-alpha-hydroxyprogesterone and its metabolites, androstenedione and testosterone. Cortisol is also reduced, and aldosterone deficiency occurs in roughly 80%.
- 11-beta-hydroxylase deficiency (5%)—1 : 100 000 live births. Increased aldosterone precursors result in hypertension.
Severe forms present with ambiguity of the external genitalia in affected females, and with salt-losing crises in both sexes in the first 1-2 weeks of life. Less severe forms may present with disorders of puberty - usually precocious pseudopuberty.
There may be a family history of CAH, ambiguous genitalia or neonatal death. Specialist management is always required. Treatment is usually with glucocorticoid replacement, often in conjunction with mineralocorticoid replacement.
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Assessment of abnormal puberty prior to referral |
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TOPAbstractThe GP curriculum and...Normal pubertyPrecocious pubertyAbnormal patterns of pubertySpecific conditionsAssessment of abnormal puberty...References |
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If a young person comes to the GP with worries about puberty, it is important to take a detailed history. Ask about:
- Previous growth and development
- The timing and sequence of any changes of puberty that have already occurred—both physical and psychological
- Past medical history—particularly serious illness, failure to thrive, genetic conditions, drugs
- Family history—early or delayed puberty and genetic diseases
- If underweight and delayed puberty—diet and eating habits
Plot height and weight on a growth chart and monitor growth velocity. Remember to calculate expected height before deciding that a child has short or tall stature (Box 2).
Check genitalia and secondary sexual characteristics. Document the stage of puberty (Tables 1 and 2). Check a neurological examination paying particular attention to the optic fundi, visual fields and sense of smell, looking for abnormalities associated with pituitary tumours. Look for evidence of thyroid dysfunction.
Except for checking thyroid function, if there are symptoms or signs suggesting thyroid disease, further investigations are not usually carried out in primary care. Any treatment needed is always consultant led
| Box 2. Calculating expected height Small parents have small children and tall parents have tall children—always calculate expected height of the child before deciding that the child has short stature or excessive height. Expected height = (mother's height + father's height) ÷ 2 Then: add 6 cm for a boy or subtract 6 cm for a girl Note: 3% of ‘normal’ children fall under the third and 3% above the 97th centile.
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Key points
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References |
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TOPAbstractThe GP curriculum and...Normal pubertyPrecocious pubertyAbnormal patterns of pubertySpecific conditionsAssessment of abnormal puberty...References |
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Carel JC, Léger J. Clinical practice: Precocious puberty. In: New England Journal of Medicine (2008) 358(22):2366–77.
Child Growth Foundation Congenital adrenal hyperplasia: a guide for patients and parents (1996) Accessed via www.childgrowthfoundation.org/pdf_files/Booklets/06_CongenitalAdrenalHyperplasia.pdf [date last accessed 4.10.2008] Constitutional delay of growth and puberty: a guide for patients and parents (2000) Accessed via www.childgrowthfoundation.org/pdf_files/Booklets/10_Constitutional%20Delay%20of%20Growth%20and%20Puberty.pdf [date last accessed 4.10.2008] Premature sexual maturation (including precocious puberty) 2003 Accessed via www.childgrowthfoundation.org/pdf_files/Booklets/04_Premature_Sexual_Maturation.pdf [date last accessed 4.10.2008] Turner's syndrome: a guide for patients and parents 2003 Accessed via www.childgrowthfoundation.org/pdf_files/Booklets/08_Turner_Syndrome_.pdf [date last accessed 4.10.2008].
Davies R, Bolland W, Simon C. Oxford GP Library: Men's health. In Press.
Draper R. Puberty—normal and abnormal (2007) PatientPlus. Accessed via www.patient.co.uk/showdoc/40024607 [date last accessed 4.10.2008].
Draper R. Precocious puberty (2007) PatientPlus. Accessed via www.patient.co.uk/showdoc/40000365 [date last accessed 4.10.2008].
RCGP Curriculum statement 8: Care of children and young people. Accessed via www.rcgp-curriculum.org.uk/PDF/curr_8_Care_of_Children_and_Young_People.pdf [date last accessed 4.10.2008].
Sadler C, White J, Everitt H, Simon C. Oxford GP Library: Women's health (2007) Oxford: Oxford University Press. ISBN: 9780199235438.
Simon C. Oxford GP Library: Endocrinology. In press.
Van Dorp F, Simon C. Oxford GP Library: Child health (2007) Oxford: Oxford University Press. ISBN: 0199215685.
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