Evaluation of delayed puberty: what diagnostic tests should be performed in the seemingly otherwise well adolescent?

Abstract

Delayed puberty (DP) is defined as the lack of pubertal development by an age that is 2-2.5 SDs beyond the population mean. Although it generally represents a normal variant in pubertal timing, concern that DP could be the initial presentation of a serious underlying disorder has led to a diagnostic approach that is variable and may include tests that are unnecessary and costly. In this review, we examine available literature regarding the recommended diagnostic tests and aetiologies identified during the evaluation of youth with DP. We view this literature through the prism of the seemingly otherwise well adolescent. To provide further clinical context, we also evaluate the clinical and laboratory data from patients seen with DP in our centre over a 2-year period. The literature and our data reveal wide variability in the number of tests performed and raise the question of whether tests, other than gonadotropins, obtained in the absence of signs or symptoms of an underlying disorder are routinely warranted. Together this information provides a pragmatic rationale for revisiting recommendations calling for broad testing during the initial diagnostic evaluation of an otherwise healthy adolescent with DP. We highlight the need for further research comparing the utility of broader screening with a more streamlined approach, such as limiting initial testing to gonadotropins and a bone age, which, while not diagnostic, is often useful for height prediction, followed by close clinical monitoring. If future research supports a more streamlined approach to DP, then much unnecessary testing could be eliminated.

Single-Centre Experience of Testosterone Therapy for Boys with Hypogonadism

“…Given that the indications and goals for testosterone therapy in adolescence are more variable than in adults, guidance for monitoring of therapy in adults cannot be simply replicated in adolescents and may be influenced by the underlying condition and/or the duration of therapy. Whilst clear guidance on starting doses for testosterone as well as the advantages and disadvantages of the different preparations in boys exist already [5, 13], guidance on the extent of investigations that are performed in a boy who presents with delayed puberty is more debatable [2, 14] and guidance on how to monitor the safety and efficacy of testosterone therapy is very rare [5, 13] and may require some personalisation for the underlying condition as well as the duration and form of therapy. Although there is no substitute to the assessment of physical virilisation as the primary outcome measure, we would recommend that, as a minimum, all boys who start testosterone therapy have a thorough biochemical and haematological evaluation in addition to anthropometric assessment prior to starting therapy and at 6-month intervals as well as at stopping therapy.…”

“…It is a common indication for referral to paediatric endocrine services, affecting approximately 2% of adolescents [2]. Boys with delayed puberty may present with significant psychosocial distress secondary to this, as well as long-term health consequences such as osteopaenia [3, 4].…”

Management of hypogonadism from birth to adolescence

“…represents the commonest cause of DP in both sexes. Up to 83% of boys, and 30-55% of girls, with pubertal delay have self-limited DP (20)(21)(22)(23). Individuals with selflimited DP lie at the extreme end of normal pubertal timing, with the absence of testicular enlargement in boys or breast development in girls at an age that is 2 to 2.5 standard deviations (SD) later than the population mean (4).…”

Serum relaxin-3 hormone relationship to male delayed puberty

“…Puberty may be delayed for several years and still occur normally, in which case it is considered constitutional delay, a variation of the healthy physical development (Dunkel & Quinton, ). Delayed puberty may also occur due to malnutrition, some systemic disease or to defects of the reproductive system or the body's response to sex hormones (Abitbol, Zborovski, & Palmert, ; Fenichel, ; Traggiai & Stanhope, ).…”