medwireNews: The Endocrine Society has published a clinical practice guideline on the diagnosis and treatment of children with central precocious puberty (CPP) in The Journal of Clinical Endocrinology & Metabolism.
Ana Claudia Latronico (Hospital das Clínicas Avenida Doutor Enéas de Carvalho Aguiar, São Paulo, Brazil) and fellow guideline development panel (GDP) members answered 10 of the “most controversial clinical questions” on the management of CPP using the “best available scientific evidence regarding clinical outcomes judged to be most important to patients and families.”
Following the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach, the team conducted systematic reviews of literature and collated evidence-to-decision framework elements, including stakeholder values and preferences, costs and feasibility, for each clinical question.
These were then used to create a diagnostic algorithm and a treatment algorithm, with five recommendations in each, the authors report.
The five diagnostic recommendations were:
- Girls who begin thelarche (Tanner B2) at age 7–8 years should be managed with watchful waiting and physical examinations at 4–6-month intervals, whereas girls younger than 8 years at Tanner B3 and higher should undergo immediate investigation;
- Girls younger than 7 years at Tanner B2 should be monitored for 4–6 months to determine whether they are in unsustained or slowly progressing puberty or rapidly progressing puberty;
- Girls and boys with evidence of PP should be assessed initially with an ultrasensitive basal luteinizing hormone assay, followed by gonadotropin-releasing hormone (GnRH)/GnRH agonist stimulation test if high suspicion of CPP;
- Girls aged 6–8 years and boys aged 8–9 years with CPP and no central nervous system findings do not require routine magnetic resonance imaging assessment;
- Children with CPP do not require routine genetic testing – in cases of familial CPP genetic testing should be based on shared decision-making with the family.
The researchers also put together five recommendations on the management of CPP. These were:
- The use of GnRH agonist therapy for children with CPP, although the benefit may be limited for those unlikely to gain height from treatment, such as girls aged 7–8 years with slowly progressing CPP and children past peak pubertal growth spurt;
- Starting children expected to undergo long-term GnRH agonist therapy on a long-acting agent rather than monthly treatment;
- No routine biochemical testing of luteinising hormone and sex steroids during GnRH agonist therapy for children undergoing regular assessments of Tanner staging, growth velocity, and bone age who have no evidence of treatment failure;
- Not routinely adding growth hormone therapy to GnRH agonist therapy unless there is another specific indication for treatment;
- Not routinely continuing GnRH agonist therapy in girls and boys after chronological age 10–11 and 11–12 years, respectively, and/or after bone age 11–12 and 12–13 years, respectively, but may be considered based on growth trajectory, psychosocial factors, developmental delay and other individual factors.
However, Latronico and fellow GDP members say that the systematic reviews identified “few randomized controlled trials”, which meant the GDP had to “rely predominantly on observational studies and indirect evidence.” And there was a similar lack of “high-quality evidence” for the GRADE evidence-to-decision framework elements.
They therefore conclude: “The guideline-development process highlighted important knowledge gaps and the substantial need for additional research.”
By Lynda Williams
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