An Update on Aetiopathology, Various Genetic Causes and Management of Delayed Puberty: A Minireview

Abstract

Kulvinder Kaur, Gautam Allahbadia and Mandeep Singh

Delayed Puberty (DP), especially in boys, is a common presentation in paediatrics. By definition DP is defined as the presentation of clinical signs of puberty 2-2.5SD later than in the normal population. With the recent advances in understanding of the neuroendocrine, genetic and environmental factors controlling pubertal development it has become easier to understand the pathophysiology of DP. The discovery of kisspeptin signaling through its receptor identified neuroendocrine mechanisms controlling the gonadotropin releasing hormone (GnRH) pulse generator at the onset of puberty. Genetic mechanisms from single gene mutations to single nucleotide polymorphisms associated with DP are being identified. Environmental factors, including nutritional factors, besides endocrine disruptors, have been associated with the secular trends and abnormal timing of puberty. Inspite of these advances, the main question remains how to differentiate DP associated with underlying pathology of hypogonadism from constitutional delay in growth and puberty (CDP) that remains challenging as biochemical tests do not always discriminate the 2.The diagnostic accuracies of newer investigations which include the 36-hour luteininzing hormone releasing hormone(LHRH) tests, GnRH agonist tests, antimullerian hormone and inhibin B, need further evaluation. Sex hormone replacement remains the main therapy that is available for DP, whose choice is based on clinical practice and the availability of the various sex steroid preparations. Spontaneous reversal of hypogonadism has been reported in boys having idiopathic hypogonadotropic hypogonadism following sex steroid treatment, which highlights the importance of reassessment at the end of pubertal induction .Novel therapies having a more physiological bases like gonadotropins or kisspeptin agonists are getting investigated for the management of hypogonadotropic hypogonadism. A careful assessment and knowledge of the normal physiology remains the mainstay of managing patients with DP.

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