Endocrine Abstracts (2016) 45 OC5.5 | DOI: 10.1530/endoabs.45.OC5.5

The performance of early childhood Human Chorionic Gonadotrophin (HCG) testing to investigate male undervirilisation

Joshua van Geffen1, Amish Chinoy1, Fiona Ivison2, Lesley Tetlow2 & Indi Banerjee1


1Department of Paediatric Endocrinology, Royal Manchester Children’s Hospital, Manchester, UK; 2Department of Paediatric Biochemistry, Royal Manchester Children’s Hospital, Manchester, UK.


Background: The 3 day human chorionic gonadotrophin (HCG) test is commonly performed to investigate male undervirilisation. However, the utility of routine HCG testing for male undervirilisation in early childhood and correlation with pubertal progress is unclear.

Aims: To review performance of the 3 day HCG test for diagnosis and outcomes.

Methods: Standard 3 day HCG test data were analysed in 130 boys of age <3 years with undervirilised male genitalia over a 15 year period in a single regional centre. Androgen response measured by mass spectrometry was correlated with diagnostic outcomes in all and with pubertal progress in 14 (11%) boys >11 years of age. Undervirilisation was characterised by findings of micropenis (stretched penile length <2.5 cm), hypospadias, undescended testes and External Masculinisation Score (EMS). Puberty was delayed if there was no sign of onset or progress by age 12 years.

Results: Nineteen (15%) boys had primary hypogonadism/adrenal dysfunction and 11 (8%) boys had hypogonadtrophic hypogonadism with the cause for undervirilisation being unknown in 100 (77%) boys. Stimulated tesosterone concentration (T-stim) and ratio of stimulated to basal testosterone (T-ratio) declined after 1.5 years, suggesting gonadal unresponsiveness to HCG beyond age 2 years. Lower T-stim (P=0.002) and T-ratio (P=0.01), but not EMS (P=0.38), were associated with a primary adrenal/testicular diagnoses (P-dx). The combination of short penile length and hypospadias was correlated with lower T-ratios (R2=0.5, P<0.001). A cut-off T-stim >12.5 nmol/l excluded P-dx [Odds ratio (OR) 3.3 95% CI (1.1–10.5), P=0.04], while the composite variable [T-stim <12.5 nmol/l or T-ratio <20] had the greatest probability of predicting P-dx [OR 95%CI 7.3(3.2–16.7), P<0.001]. In older boys with information on puberty, higher T-stim [median (range) 12.1(7.3–32.3) v 9.3(0.3–13.1), P=0.24] and T-ratio [18.9(1.6–69.7) v 10.2(1.0–43.7), P=0.46] trended towards spontaneous puberty than delayed puberty.

Conclusions: The 3 day HCG stimulation test yields a primary adrenal/testicular diagnosis in 15% of undervirilised boys. Testosterone response to HCG correlates with the severity of undervirilisation; a generous response may exclude underlying pathology and predict spontaneous pubertal progress.

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