Clinical Spectrum and Causes of Delayed Puberty Among Patients Presenting to the Endocrine Clinic at Jinnah Postgraduate Medical Centre

Abstract

Introduction: It has been observed that 5% of adolescents are affected by pubertal timing disorders. However, there is limited data about this in Pakistan. This cross-sectional study aimed to observe the patterns and causes of delayed puberty (DP) among patients presenting at the endocrine clinic of a tertiary care hospital in Karachi.Methods: This observational study was conducted at the endocrine clinic of Jinnah Postgraduate Medical Centre (JPMC) Unit II from 2007 to 2015. A detailed history was obtained from patients presenting with DP. We noted the available demographic data, main complaints, and family history of DP. Physical examinations were performed and the data recorded. Tanner staging was used to assess pubertal development. Relevant laboratory and imaging investigations were performed; data analysis was performed using SPSS 17 (IBM Corp., Armonk, NY).Results: A total of 2670 patients were registered in the endocrine clinic during the study period, of which 171 presented with DP; 119 were males and 52 were females. There was a wide variation in age at presentation ranging from 10 to 32 years. The majority of patients presented with short stature -69 (57.98%) males and 19 (36.53%) females. Small testes were present in 28 patients (23.52%); 19 (15.96%) males presented with absent secondary sexual characteristics and infertility was present in three (2.54%) males, primary amenorrhea was observed in 25 (48.07%), both primary amenorrhea and short stature were the presenting symptoms of five (9.61%), and failure of breast development was seen in three (5.76%) females. Constitutional delayed growth and puberty (CDGP) was diagnosed in 42 patients (24.6%). The definitive diagnosis of idiopathic hypogonadotropic hypogonadism (IHH) was made in 18 (10.5%) patients. In another 18 (10.5%) patients, we could not differentiate between CDGP and IHH. Functional hypogonadotropic hypogonadism (FHH) due to non-endocrine illness was present in 16 patients (9.4%). The cause of DP was hypogonadotropic hypogonadism in 33 (19.3%) patients whereas 44 patients presenting with DP could not be classified due to incomplete data.Conclusion: This study showed that CDGP was the most common cause of DP in our patients with the most common presentation being short stature in males and amenorrhea in females. It is essential to differentiate CDGP in children from a small fraction of the pathological and treatable causes of DP.

Key features of puberty onset and progression can help distinguish self-limited delayed puberty from congenital hypogonadotrophic hypogonadism

“…Indeed, the proportion of patients with HH in our cohort was higher than in some previous studies ( 7 ), likely reflecting the fact that our study recruitment sites are mainly tertiary or quaternary paediatric endocrine centres, with more referrals of extreme and complex cases. Our population was also predominantly male in both diagnostic groups, as is well documented to be the norm for adolescent DP cohorts ( 4 ), and thus provided more insights into male puberty in these conditions. SLDP is well-recognised to be a commonly inherited condition with strong genetic drivers ( 27 ), and whilst a family history of delayed puberty was seen more frequently in patients with SLDP, a family history of delay was also seen in patients with HH, particularly with pHH.…”

“…The diagnostic complexity is particularly true for patients with incomplete or partial GnRH deficiency, who may have entered puberty and then stalled in their pubertal progression, and whose clinical and biochemical parameters may be intermediate between those of SLDP and complete HH ( 3 , 4 , 7 ). Indeed, it is exactly this group of patients with severe delayed puberty but without clear ‘red flag’ signs for the diagnosis of congenital HH that present that greatest clinical challenge.…”

“…It affects 2% of adolescents and is more commonly a presentation in adolescence in boys ( 2 ). This predominance is thought to be due to a combination of referral bias in boys with short stature due to DP ( 3 , 4 ), with a later onset of the pubertal growth spurt in boys ( 5 ), as well as earlier detection of the first signs of puberty in girls.…”