Challenges and controversies in diagnosis and management of gonadotropin dependent precocious puberty: An Indian perspective

Managing precocious puberty (PP) has been a challenge due to lack of standardized definition, gonadotrophins assay, gonadotrophin stimulation, timings for blood sampling, and parameters for assessing outcomes. This review evaluated available literature to simplify the algorithm for managing gonadotrophin dependent/central PP (CPP), with an Indian perspective. CPP is one of the commonest forms of PP and mimics the normal course of puberty, at an age <8 and 9 years for girls and boys respectively. Basal and post gonadotrophin hormone releasing hormone analog (GnRHa) luteinizing hormone (LH) ≥0.3–0.6 IU/L and ≥4–5 IU/L (30–60 min after GnRH/GnRHa administration) respectively, using modern ultrasensitive automated chemiluminescence assays, can be considered positive for central puberty initiation. Uterine length of >3.5 cm and uterine volume of >1.8 ml are two most specific indicators for true CPP. Therapy is indicated in children with CPP with accelerated bone age, height advancement, or psychosocial stress. Treatment goal is to halt puberty progression to a socially acceptable age, allowing the child to attain optimal height potential. GnRHa is the treatment of choice, with best height outcomes when initiated <6 years age. Treatment is recommended till 11 years age. LH suppression to <3 U/L may be a reasonable target in patients on GnRHa therapy. Medroxyprogesterone acetate holds an important place in managing PP in India, cause of high costs associated with GnRHa therapy. There is an urgent need for clinical trials from India, for establishing Indian cut-off for diagnosis, treatment and follow-up of children with PP.

[1]  D. Dunger,et al.  Pros and cons of GnRHa treatment for early puberty in girls , 2014, Nature Reviews Endocrinology.

[2]  M. Cappa,et al.  The response to gonadotropin releasing hormone (GnRH) stimulation test does not predict the progression to true precocious puberty in girls with onset of premature thelarche in the first three years of life. , 2014, The Journal of clinical endocrinology and metabolism.

[3]  J. Fuqua Treatment and outcomes of precocious puberty: an update. , 2013, The Journal of clinical endocrinology and metabolism.

[4]  F. Tao,et al.  Effects of growth environments and two environmental endocrine disruptors on children with idiopathic precocious puberty. , 2012, European journal of endocrinology.

[5]  P. A. Lee,et al.  Efficacy and safety of leuprolide acetate 3-month depot 11.25 milligrams or 30 milligrams for the treatment of central precocious puberty. , 2012, The Journal of clinical endocrinology and metabolism.

[6]  E. Neely,et al.  A randomized trial of 1- and 3-month depot leuprolide doses in the treatment of central precocious puberty. , 2011, The Journal of pediatrics.

[7]  S. Radovick,et al.  Timing and completion of puberty in female mice depend on estrogen receptor α-signaling in kisspeptin neurons , 2010, Proceedings of the National Academy of Sciences.

[8]  Peter A. Lee,et al.  Leuprolide Acetate 1-Month Depot for Central Precocious Puberty: Hormonal Suppression and Recovery , 2010, International journal of pediatric endocrinology.

[9]  K. Mogi,et al.  Neurokinin B and Dynorphin A in Kisspeptin Neurons of the Arcuate Nucleus Participate in Generation of Periodic Oscillation of Neural Activity Driving Pulsatile Gonadotropin-Releasing Hormone Secretion in the Goat , 2010, The Journal of Neuroscience.

[10]  J. Godbold,et al.  ORIGINAL ARTICLE: Leuprolide stimulation testing for the evaluation of early female sexual maturation , 2010, Clinical endocrinology.

[11]  V. Mericq,et al.  Comparison of three doses of leuprolide acetate in the treatment of central precocious puberty: preliminary results , 2009, Clinical endocrinology.

[12]  A. Kunselman,et al.  Adequacy of a Single Unstimulated Luteinizing Hormone Level to Diagnose Central Precocious Puberty in Girls , 2009, Pediatrics.

[13]  N. Shah,et al.  Utility of single luteinizing hormone determination 3 h after depot leuprolide in monitoring therapy of gonadotropin-dependent precocious puberty , 2009, Pituitary.

[14]  A. Rogol,et al.  Consensus Statement on the Use of Gonadotropin-Releasing Hormone Analogs in Children , 2009, Pediatrics.

[15]  D. Larizza,et al.  Utility of breast ultrasonography in the diagnostic work‐up of precocious puberty and proposal of a prognostic index for identifying girls with rapidly progressive central precocious puberty , 2009, Ultrasound in obstetrics & gynecology : the official journal of the International Society of Ultrasound in Obstetrics and Gynecology.

[16]  G. Saggese,et al.  Effect of central precocious puberty and gonadotropin-releasing hormone analogue treatment on peak bone mass and final height in females , 1998, European Journal of Pediatrics.

[17]  S. Radovick,et al.  Puberty and its disorders in the female , 2008 .

[18]  M. Segni,et al.  Long-term observation of 87 girls with idiopathic central precocious puberty treated with gonadotropin-releasing hormone analogs: impact on adult height, body mass index, bone mineral content, and reproductive function. , 2008, The Journal of clinical endocrinology and metabolism.

[19]  M. Phillip,et al.  Growth pattern and final height after cessation of gonadotropin-suppressive therapy in girls with central sexual precocity. , 2007, The Journal of clinical endocrinology and metabolism.

[20]  E. M. Resende,et al.  Assessment of basal and gonadotropin-releasing hormone-stimulated gonadotropins by immunochemiluminometric and immunofluorometric assays in normal children. , 2007, The Journal of clinical endocrinology and metabolism.

[21]  R. Rosenfield Clinical review: Identifying children at risk for polycystic ovary syndrome. , 2007, The Journal of clinical endocrinology and metabolism.

[22]  A. Pasquino,et al.  Menstrual cycle pattern during the first gynaecological years in girls with precocious puberty following gonadotropin-releasing hormone analogue treatment , 2006, European Journal of Pediatrics.

[23]  T. K. Jensen,et al.  Prevalence and Incidence of Precocious Pubertal Development in Denmark: An Epidemiologic Study Based on National Registries , 2005, Pediatrics.

[24]  R. Brauner,et al.  Predictive factors for the effect of gonadotrophin releasing hormone analogue therapy on the height of girls with idiopathic central precocious puberty , 1992, European Journal of Pediatrics.

[25]  M. Kempers,et al.  Idiopathic precocious puberty versus puberty in adopted children; auxological response to gonadotrophin-releasing hormone agonist treatment and final height. , 2002, European journal of endocrinology.

[26]  C. Teinturier,et al.  Treatment of central precocious puberty by subcutaneous injections of leuprorelin 3-month depot (11.25 mg). , 2002, The Journal of clinical endocrinology and metabolism.

[27]  W. Chemaitilly,et al.  Factors predicting adult height in girls with idiopathic central precocious puberty: implications for treatment * , 2002, Clinical endocrinology.

[28]  M. Kabra,et al.  Precocious Puberty: Clinical and Endocrine Profile and Factors Indicating Neurogenic Precocity in Indian Children , 2002, Journal of pediatric endocrinology & metabolism : JPEM.

[29]  K. Klein,et al.  Increased final height in precocious puberty after long-term treatment with LHRH agonists: the National Institutes of Health experience. , 2001, The Journal of clinical endocrinology and metabolism.

[30]  D. Mul,et al.  Psychological assessments before and after treatment of early puberty in adopted children , 2001, Acta paediatrica.

[31]  Stef van Buuren,et al.  Pubertal Development in The Netherlands 1965–1997 , 2001, Pediatric Research.

[32]  P. Czernichow,et al.  Do all girls with apparent idiopathic precocious puberty require gonadotropin-releasing hormone agonist treatment? , 2000, The Journal of pediatrics.

[33]  S. Heger,et al.  Long-term outcome after depot gonadotropin-releasing hormone agonist treatment of central precocious puberty: final height, body proportions, body composition, bone mineral density, and reproductive function. , 1999, The Journal of clinical endocrinology and metabolism.

[34]  M. Lawson,et al.  A single sample subcutaneous luteinizing hormone (LH)-releasing hormone (LHRH) stimulation test for monitoring LH suppression in children with central precocious puberty receiving LHRH agonists. , 1999, The Journal of clinical endocrinology and metabolism.

[35]  J. Coste,et al.  Lack of effect of GnRH agonists on final height in girls with advanced puberty: a randomized long-term pilot study. , 1999, The Journal of clinical endocrinology and metabolism.

[36]  A. Balsamo,et al.  Randomised trial of LHRH analogue treatment on final height in girls with onset of puberty aged 7.5–8.5 years , 1999, Archives of disease in childhood.

[37]  P. Kaplowitz,et al.  Reexamination of the Age Limit for Defining When Puberty Is Precocious in Girls in the United States: Implications for Evaluation and Treatment , 1999, Pediatrics.

[38]  A. C. Thirone,et al.  Diagnostic value of fluorometric assays in the evaluation of precocious puberty. , 1999, The Journal of clinical endocrinology and metabolism.

[39]  A. Pasquino,et al.  Analysis of the factors affecting auxological response to GnRH agonist treatment and final height outcome in girls with idiopathic central precocious puberty. , 1999, European journal of endocrinology.

[40]  J. Carel,et al.  Final height after long-term treatment with triptorelin slow release for central precocious puberty: importance of statural growth after interruption of treatment. French study group of Decapeptyl in Precocious Puberty. , 1999, The Journal of clinical endocrinology and metabolism.

[41]  G. Cutler,et al.  Reproductive axis after discontinuation of gonadotropin-releasing hormone analog treatment of girls with precocious puberty: long term follow-up comparing girls with hypothalamic hamartoma to those with idiopathic precocious puberty. , 1999, The Journal of clinical endocrinology and metabolism.

[42]  E. Pasquini,et al.  Adult height comparison between boys and girls with precocious puberty after long‐term gonadotrophin‐releasing hormone analogue therapy , 1998, Acta paediatrica.

[43]  D. Styne,et al.  Puberty : ontogeny, neuroendocrinology, physiology, and disorders , 1998 .

[44]  M. Craen,et al.  Longitudinal study of behavioral and affective patterns in girls with central precocious puberty during long‐acting triptorelin therapy , 1997, Acta paediatrica.

[45]  R. Odink,et al.  Final height in central precocious puberty after long term treatment with a slow release GnRH agonist. , 1996, Archives of disease in childhood.

[46]  P. A. Lee,et al.  Spontaneous serum gonadotropin concentrations in the evaluation of precocious puberty. , 1995, The Journal of pediatrics.

[47]  N. Bayley,et al.  Tables for predicting adult height from skeletal age: revised for use with the Greulich-Pyle hand standards. , 1952, The Journal of pediatrics.