Managing delayed or altered puberty in boysBMJ 2012; 345 doi: http://dx.doi.org/10.1136/bmj.e7913 (Published 03 December 2012) Cite this as: BMJ 2012;345:e7913
- Nelly Pitteloud, professor
- 1Endocrinology, Diabetes, Metabolism, Centre Hospitalier Universitaire Vaudois, Lausanne 1011, Switzerland
Two linked patient journeys describe the experience of male puberty gone awry (doi:10.1136/bmj.e6938, doi:10.1136/bmj.e6971). Puberty is a period of substantial physical development that culminates in reproductive capacity, and it is marked by major psychological changes. The normal timing of puberty is influenced by several factors, including those that are familial, ethnic, and environmental. It is estimated that genetic factors account for 50-80% of the variance in the onset of puberty.1 Accumulating evidence suggests a secular trend towards decreasing age of onset of puberty, which could be related, in part, to obesity.1 2 Failure to initiate spontaneous puberty, which represents the extreme end of the pubertal spectrum, could trigger presentation to medical services for a number of adolescents. For the clinician faced with an adolescent male patient who is not developing signs of starting puberty, differentiating normal variation from pathology is not always straightforward. However, as the linked patient stories clearly show, failure to deal with clinical concerns in a timely fashion for such patients can have longlasting psychological and emotional effects.
Delayed puberty is defined as the absence of testicular enlargement in boys 2 to 2.5 standard deviations later than the population mean (which is traditionally age 14 years for boys).3 Assessment of delayed puberty in boys includes clinical and biochemical evaluation to rule out potential underlying disorders, such as those that cause hypergonadotrophic hypogonadism (Klinefelter’s syndrome), hypogonadotrophic hypogonadism (Kallmann syndrome), or functional hypogonadotrophic hypogonadism (which may be secondary to systemic illness).3
The first important step is to take a thorough family history to identify parents’ patterns of growth and puberty. Next, establish the boy’s medical history. This would include reviewing his growth chart, current drug treatments, and nutritional status; ruling out any chronic illness; and assessing congenital findings (that is, midline defects, cryptorchidism, microphallus), dental anomalies, sense of smell, and cognitive development. Physical examination should include weight, and careful measurements of height, arm span, and upper and lower segments. Estimate the Tanner stage (which for boys is based on development of pubic hair and genitals) and monitor the development of other signs of puberty, including acne, change in voice, and musculature. Evaluation of gynaecomastia and galactorrhoea and measurement of testicular volume is essential (>3 mL by Prader orchidometer or >2.5 cm in length indicate the onset of puberty3).
Serum hormone measurements of luteinising hormone, follicle stimulating hormone, testosterone, prolactin, and insulin like growth factor 1, and thyroid function tests can rule out pathological causes of delayed puberty and differentiate hypergonadotrophic from hypogonadotrophic hypogonadism. Molecular testing, such as karyotyping or copy number variation, can help identify cases of Klinefelter’s syndrome. A wrist film to assess bone age can provide additional information, and magnetic resonance imaging is useful if a patient shows signs and symptoms of a possible lesion in the central nervous system.
Delayed puberty in about 5-10% of boys can be attributed to hypergonadotrophic hypogonadism, which includes Klinefelter’s syndrome, caused by an additional X chromosome.3 Although this is the most common sex chromosome disorder (occurring in about one in 500 male births), it is estimated that only 25% of patients with Klinefelter’s syndrome are ever diagnosed.4 This low rate of diagnosis highlights the importance of paying careful attention to physical signs such as eunuchoidal proportions (span is 7 cm greater than height, upper:lower segment ratio less than 1), gynaecomastia, and small testicular volume. Pay particular attention to delayed speech, learning difficulties, and difficult peer interactions.5 Fine or gross motor, cognitive, and behavioural problems are additional factors that can aid in detection.
Delayed puberty in a further 10% of boys can be attributed to hypogonadotrophic hypogonadism.3 A variety of features are associated with congenital hypogonadotrophic hypogonadism, ranging from syndromic features, synkinesia (mirror movements), cryptorchidism, micropenis, cleft lip and palate, absent sense of smell, dental agenesis, skeletal anomalies, and hearing loss.6 Even those patients who report a normal sense of smell may well not have intact olfaction.7
Early detection is paramount to helping minimise the effect of these disorders. Early implementation of androgen treatment in adolescent patients, to promote growth, develop secondary sexual characteristics, and muscle mass, can help ameliorate some of the psychosocial effect of altered puberty.8 For patients with severe congenital hypogonadotrophic hypogonadism, neonatal gonadotrophin treatment could have a role in managing impaired fertility and unsatisfactory sexuality in adulthood. Early initiation of gonadotrophin treatment might have beneficial effects on psychosexual development; it may ease some of the psychosocial effect of atrophic testes and severely reduced penis size that can have serious effects on self confidence in engaging in sexual activity.9
Both Klinefelter’s syndrome and Kallmann syndrome disrupt puberty, albeit by different mechanisms, yet both of the linked patient journeys poignantly express the emotional and psychological effect of these disorders in puberty and beyond. Furthermore, the stories clearly demonstrate the important role that sexuality has in self concept. Correction of the hormonal disruption is only one facet of care for patients with these disorders. Management should also include anticipatory guidance about treatment outcomes and fertility, as well as psychological support and appropriate referral to counselling services when needed. Another important problem is that patients with disorders of puberty are all too often lost in transition from paediatric to adult care. Because hypogonadism has negative effects beyond the endocrine system, in terms of bone loss and metabolic disturbances, a smooth planned transition to adult care should be a key concern for those caring for adolescents diagnosed with pubertal disorders.
Cite this as: BMJ 2012;345:e7913
Competing interests: The author has completed the ICMJE uniform disclosure form at www.icmje.org/coi_disclosure.pdf (available on request from the corresponding author) and declares: no support from any organisation for the submitted work; no financial relationships with any organisations that might have an interest in the submitted work in the previous three years; no other relationships or activities that could appear to have influenced the submitted work.
Provenance and peer review: Commissioned; not externally peer reviewed.