madman
Super Moderator
Klinefelter syndrome: going beyond the diagnosis (2022)
Gary Butler, Umasuthan Srirangalingam, Jennie Faithfull, Philippa Sangster, Senthil Senniappan, Rod Mitchell
ABSTRACT
Although Klinefelter syndrome (KS) is common, it is rarely recognized in childhood, sometimes being identified with speech or developmental delay or incidental antenatal diagnosis. The only regular feature is testicular dysfunction. Postnatal gonadotropin surge (mini puberty) may be lower, but treatment with testosterone needs prospective studies. The onset of puberty is at the normal age and biochemical hypogonadism does not typically occur until late puberty. Testosterone supplementation can be considered then or earlier for clinical hypogonadism. The size at birth is normal, but growth acceleration is more rapid in early and mid-childhood, with an adult height greater than mid-parental height. Extreme tall stature is unusual. The incidence of adolescent gynecomastia (35.6%) is not increased compared with typically developing boys and can be reduced or resolved by testosterone supplementation, potentially preventing the need for surgery. Around two-thirds require speech and language therapy or developmental support and early institution of therapy is important. The provision of psychological support may be helpful in ameliorating these experiences and provide opportunities to develop strategies to recognize, process, and express feelings and thoughts. Boys with KS are at increased risk of impairment in social cognition and less accurate perceptions of social-emotional cues. The concept of likely fertility problems needs introduction alongside regular reviews of puberty and sexual function in adolescents. Although there is now greater success in harvesting sperm through techniques such as testicular sperm extraction, it is more successful later than in early adolescence. In vitro maturation of germ cells is still experimental.
INTRODUCTION
This review presents the contemporary approach to the provision of support for boys and adolescents with Klinefelter syndrome (KS) and their parents by practitioners who have a special interest in their clinical care and research.
*GETTING THE DIAGNOSIS
*COMMUNICATING THE DIAGNOSIS
*INFANCY AND EARLY CHILDHOOD
-Growth
-Testicular function
-Speech and developmental delay
*MID-CHILDHOOD
-Hypogonadism
-Education and behavior
ADOLESCENCE
-Hypogonadism
-Gynaecomastia
-Growth spurt
-Psychological support
-Gender incongruence
-Education
-Fertility
-Future experimental consideration
*INTO ADULT LIFE
We know from population mortality and morbidity studies that there is no significant lowering of life expectancy in males with KS; however, higher risk areas include osteoporosis, cardiovascular disease, and breast cancer.32 33 Lifelong follow-up is important not only from the endocrine and metabolic perspective but also for emotional, psychological, and fertility support. Only recently have specialist services for adults with KS been established, such as our University College London Hospital KF-Xtra Clinic, a multidisciplinary team, co-authors of this paper, transitioning boys with KS seamlessly from childhood and adolescence to adult services to provide lifelong care. This approach can provide benefits both to quality of life and physical well-being and also research.
*Testosterone treatment and metabolic care
Testosterone therapy is the mainstay of treatment for men with KS, with benefits including reduced fat mass and improved muscle strength, bone density, libido, and mood.34 35 Current formulations of testosterone include testosterone gels (topical daily application), weekly to monthly mixed testosterone esters given either by subcutaneous or intramuscular injections and 3monthly testosterone undecanoate (box 3). No data exist to guide optimal formulation and dosing in adults with KS. Testosterone gels, in metered pumps, allow self-administration and easy dose titration, minimize fluctuation in testosterone levels, and can be helpful when introducing therapy. Intramuscular treatment requires administration by the healthcare staff, so patients often find the long-acting formulation convenient and can be useful where compliance is an issue. Three to four-weekly injections lead to greater fluctuations in testosterone levels, which can be problematic, particularly in mood variations and energy. More frequent, lower-dose self-administered subcutaneous injections can be considered as well.36 Monitoring of therapy includes an assessment of the testosterone concentration, full blood count, hematocrit, and prostate-specific antigen in relevant subjects. Polycythaemia is the most frequent side effect encountered, particularly with long-acting testosterone.35
KS is associated with an increased risk of metabolic syndrome, insulin resistance and type 2 diabetes mellitus, obesity, dyslipidemia, and an approximate doubling of the risk of cardiovascular disease.37 While the exact mechanisms responsible for this remain to be elucidated, data on the modifying influence of testosterone therapy are conflicting in men with hypogonadism.35 38 Education on healthy lifestyle choices, and provision of careful surveillance and appropriate interventions to actively manage cardiovascular risk, therefore, remain essential.
CONCLUSIONS
The approach to supporting boys and adolescents with KS is age-dependent and needs multiagency input. Provision of an accurate picture of the condition in contrast to internet search findings is important for reassurance. A report in this journal regarding the outcome of boys with KS identified in the Edinburgh newborn population screening study presents a balanced perspective on the range of functioning and lifestyle of adults with KS and this can help guide parents when KS is diagnosed.39 Although the information in this review may benefit those in whom KS is already recognized, how do we address the issue of the 75% of males with KS who remain unidentified? Discussion around population genetic screening and prospective identification continues, but this has many ethical and financial considerations.
Gary Butler, Umasuthan Srirangalingam, Jennie Faithfull, Philippa Sangster, Senthil Senniappan, Rod Mitchell
ABSTRACT
Although Klinefelter syndrome (KS) is common, it is rarely recognized in childhood, sometimes being identified with speech or developmental delay or incidental antenatal diagnosis. The only regular feature is testicular dysfunction. Postnatal gonadotropin surge (mini puberty) may be lower, but treatment with testosterone needs prospective studies. The onset of puberty is at the normal age and biochemical hypogonadism does not typically occur until late puberty. Testosterone supplementation can be considered then or earlier for clinical hypogonadism. The size at birth is normal, but growth acceleration is more rapid in early and mid-childhood, with an adult height greater than mid-parental height. Extreme tall stature is unusual. The incidence of adolescent gynecomastia (35.6%) is not increased compared with typically developing boys and can be reduced or resolved by testosterone supplementation, potentially preventing the need for surgery. Around two-thirds require speech and language therapy or developmental support and early institution of therapy is important. The provision of psychological support may be helpful in ameliorating these experiences and provide opportunities to develop strategies to recognize, process, and express feelings and thoughts. Boys with KS are at increased risk of impairment in social cognition and less accurate perceptions of social-emotional cues. The concept of likely fertility problems needs introduction alongside regular reviews of puberty and sexual function in adolescents. Although there is now greater success in harvesting sperm through techniques such as testicular sperm extraction, it is more successful later than in early adolescence. In vitro maturation of germ cells is still experimental.
INTRODUCTION
This review presents the contemporary approach to the provision of support for boys and adolescents with Klinefelter syndrome (KS) and their parents by practitioners who have a special interest in their clinical care and research.
*GETTING THE DIAGNOSIS
*COMMUNICATING THE DIAGNOSIS
*INFANCY AND EARLY CHILDHOOD
-Growth
-Testicular function
-Speech and developmental delay
*MID-CHILDHOOD
-Hypogonadism
-Education and behavior
ADOLESCENCE
-Hypogonadism
-Gynaecomastia
-Growth spurt
-Psychological support
-Gender incongruence
-Education
-Fertility
-Future experimental consideration
*INTO ADULT LIFE
We know from population mortality and morbidity studies that there is no significant lowering of life expectancy in males with KS; however, higher risk areas include osteoporosis, cardiovascular disease, and breast cancer.32 33 Lifelong follow-up is important not only from the endocrine and metabolic perspective but also for emotional, psychological, and fertility support. Only recently have specialist services for adults with KS been established, such as our University College London Hospital KF-Xtra Clinic, a multidisciplinary team, co-authors of this paper, transitioning boys with KS seamlessly from childhood and adolescence to adult services to provide lifelong care. This approach can provide benefits both to quality of life and physical well-being and also research.
*Testosterone treatment and metabolic care
Testosterone therapy is the mainstay of treatment for men with KS, with benefits including reduced fat mass and improved muscle strength, bone density, libido, and mood.34 35 Current formulations of testosterone include testosterone gels (topical daily application), weekly to monthly mixed testosterone esters given either by subcutaneous or intramuscular injections and 3monthly testosterone undecanoate (box 3). No data exist to guide optimal formulation and dosing in adults with KS. Testosterone gels, in metered pumps, allow self-administration and easy dose titration, minimize fluctuation in testosterone levels, and can be helpful when introducing therapy. Intramuscular treatment requires administration by the healthcare staff, so patients often find the long-acting formulation convenient and can be useful where compliance is an issue. Three to four-weekly injections lead to greater fluctuations in testosterone levels, which can be problematic, particularly in mood variations and energy. More frequent, lower-dose self-administered subcutaneous injections can be considered as well.36 Monitoring of therapy includes an assessment of the testosterone concentration, full blood count, hematocrit, and prostate-specific antigen in relevant subjects. Polycythaemia is the most frequent side effect encountered, particularly with long-acting testosterone.35
KS is associated with an increased risk of metabolic syndrome, insulin resistance and type 2 diabetes mellitus, obesity, dyslipidemia, and an approximate doubling of the risk of cardiovascular disease.37 While the exact mechanisms responsible for this remain to be elucidated, data on the modifying influence of testosterone therapy are conflicting in men with hypogonadism.35 38 Education on healthy lifestyle choices, and provision of careful surveillance and appropriate interventions to actively manage cardiovascular risk, therefore, remain essential.
CONCLUSIONS
The approach to supporting boys and adolescents with KS is age-dependent and needs multiagency input. Provision of an accurate picture of the condition in contrast to internet search findings is important for reassurance. A report in this journal regarding the outcome of boys with KS identified in the Edinburgh newborn population screening study presents a balanced perspective on the range of functioning and lifestyle of adults with KS and this can help guide parents when KS is diagnosed.39 Although the information in this review may benefit those in whom KS is already recognized, how do we address the issue of the 75% of males with KS who remain unidentified? Discussion around population genetic screening and prospective identification continues, but this has many ethical and financial considerations.
