Delayed puberty and hypogonadism in adolescents — formative SAQs

SAQ 1 (10 marks)

A 14-year-old boy is referred because he is the shortest in his class and has no signs of puberty. His father recalls being "always the smallest until age sixteen," and his mother reached menarche at 16. On examination his testicular volumes are 3 mL bilaterally, his height is on the 3rd centile (mid-parental target on the 40th), his growth velocity is normal, and his bone age lags his chronological age by two and a half years. [1] [2]

a) Define delayed puberty for this boy and explain why the triad of short stature, delayed bone age and family history points to constitutional delay of growth and puberty. (3 marks) [1] [2]

b) Outline the first-line investigations you would request, and explain how the gonadotrophin result would split the differential into a central versus a gonadal cause. (2 marks) [1]

c) Discuss how you would separate constitutional delay from permanent congenital hypogonadotropic hypogonadism at this presentation, including the role of anosmia testing, the neonatal history, and the standing-height trajectory. (3 marks) [1] [6]

d) Describe the management of constitutional delay, including the indications for and the protocol of a short course of testosterone. (2 marks) [12]

SAQ 2 (10 marks)

A 15-year-old boy presents with absent puberty, a tall thin habitus, small firm testes (4 mL bilaterally) and gynaecomastia. His morning testosterone is low at 4 nmol/L, his FSH and LH are both markedly elevated, and his bone age is appropriate for his chronological age. [7] [1]

a) Classify this presentation using the gonadotrophin framework and name the most likely diagnosis. Explain the pathophysiology. (3 marks) [1] [7]

b) State the confirmatory investigation and outline the additional systemic features and long-term risks of this syndrome. (2 marks) [7]

c) Describe the pubertal induction protocol you would use, including the principle of gradual sex-steroid escalation over 18 to 24 months and why rapid escalation is harmful. (3 marks) [9] [12]

d) Discuss the fertility implications and the role of early semen analysis and cryopreservation in this condition. (2 marks) [7] [9]

Marking guide

SAQ 1. Delayed puberty in a boy is no testicular enlargement (under 4 mL) by 14 years, or a stall of more than 2 years after onset. Constitutional delay of growth and puberty is the commonest cause in boys (~60% of referrals per the Sedlmeyer series) and presents with the triad of short stature tracking along a lower centile through childhood, a delayed bone age that matches the height age, and a family history of late puberty (both parents here). The first-line investigations are a morning testosterone with FSH, LH, TSH and prolactin, and a bone age — low or inappropriately normal gonadotrophins with a low testosterone confirm a central (hypogonadotropic) cause, while high gonadotrophins would point to primary gonadal failure and trigger a karyotype. Separating CDGP from permanent CHH relies on the anosmia test (absent here, anosmia would point to Kallmann), the neonatal history (micropenis or cryptorchidism at birth would point to CHH), and the standing-height trajectory (short-for-age throughout childhood favours CDGP, whereas a normal-to-tall prepubertal stature favours CHH). The management of CDGP is reassurance and monitoring, with a short course of intramuscular testosterone (50 to 100 mg monthly for three to six months) reserved for the boy with significant psychological burden — it both relieves distress and serves as a diagnostic trial, because a pubertal response that continues after the course stops confirms CDGP. [1] [2] [12]

SAQ 2. The markedly elevated FSH and LH with a low testosterone classify this as hypergonadotropic (primary gonadal) failure, and the tall thin habitus with small firm testes and gynaecomastia make Klinefelter syndrome (47,XXY) the most likely diagnosis, with an incidence of roughly one in 600 male births. The pathophysiology is a supernumerary X chromosome causing dysgenesis of the seminiferous tubules, low testosterone from Leydig-cell dysfunction, loss of feedback, and rising gonadotrophins. The confirmatory investigation is a karyotype (or chromosomal microarray). The systemic features and long-term risks include learning and behavioural vulnerabilities, increased metabolic and cardiovascular risk, osteoporosis from chronic hypogonadism, infertility from impaired spermatogenesis, and an increased risk of certain malignancies and autoimmune disease. Pubertal induction uses escalating sex steroids over 18 to 24 months — low-dose intramuscular or transdermal testosterone started at a fraction of the adult dose and increased gradually to a full replacement dose, per the Endo-ERN guideline — because rapid escalation advances bone age prematurely and compromises final height, and because gradual escalation allows psychosocial maturation to keep step with physical change. Fertility is impaired but micro-dissection testicular sperm extraction can recover sperm in many men, so early semen analysis and cryopreservation counselling are part of the plan. [7] [9] [1]