BACKGROUND AND AIM OF THE STUDY: The frequency of new visits for precocious puberty increased during the Covid-19 pandemic in the pediatric endocrinology clinic at Rady Childrens Hospital in San Diego, CA, US. A few recent studies have shown an increase in the frequency of Central Precocious Puberty (CPP) in other centers during this pandemic. This study evaluated the change in incidence of new CPP cases requiring treatment with GnRH agonist (GnRHa) at Rady Childrens Hospital during the Covid-19 pandemic and compared it to pre-pandemic years. METHODS: Data were reviewed retrospectively to compare the number of visits of children newly diagnosed with CPP treated with GnRHa during the Covid-19 pandemic (5/2020-4/2021) and before the pandemic (5/2018-4/2019). Clinical and bone maturation data were evaluated as well as differences in timing from diagnosis to onset of treatment. The incidence of CPP requiring treatment for 5 years prior to the pandemic was also reviewed to evaluate for trends over time. RESULTS: A total of 92 subjects were included. During pre-Covid year, 28 children (1 boy, 27 girls) were treated with GnRHa for CPP out of 2,340 new endocrinology visits (1.2% of patients seen). During Covid-19 year, 64 children (7 boys, 57 girls) were treated out of 2,261 new visits (2.8%). The incidence of new CPP cases requiring GnRHa during the pandemic more than doubled compared to pre-pandemic. Age at onset of treatment, degree of bone age (BA) advancement, time from diagnosis to onset of treatment, and changes in BMI during the pandemic were not different from pre-pandemic. CONCLUSION: CPP cases requiring GnRHa treatment significantly increased during the first year of the Covid-19 pandemic. This was not related to increased BMI or delay in onset of treatment. Age at diagnosis, degree of bone age advancement, and time from diagnosis to onset of treatment were all similar during the first year of the pandemic compared to the prior year.

Objectives

Gonadotropin-releasing hormone agonist treatment is important for optimal growth in girls with central precocious puberty (CPP). Data are lacking regarding benefit to height outcome when treatment is started after chronological age (CA) of 7 years, and if continued beyond CA of 10 years or bone age (BA) of 12 years.

Methods

Forty-eight girls with CPP were treated with monthly leuprolide depot. Change in predicted adult height (PAH) during treatment was assessed. Changes in PAH and growth velocity were compared between girls initiating treatment at CA <7 vs. ≥7 years, and BA ≥12 vs. BA <12 years.

Results

Mean baseline CA was 6.8 years, BA, 10.2 years; and PAH, 156.4 cm. BA/CA ratio decreased from pretreatment values, averaging 1.5 to 1.2 at the end of treatment. Proportion of girls with >5 cm PAH change during treatment was similar, and PAH increased throughout treatment in most girls, regardless of age at treatment initiation. PAH continued to increase in 16/19 girls who continued treatment after BA of 12 years, and also in 16/22 girls who continued treatment after CA of 10 years.

Conclusions

PAH improved in most girls who initiated treatment after CA of 7 years. It continued to improve in most girls with longer treatment, even past BA of 12 years or CA of 10 years, which suggests that no absolute CA or BA limit should define initiation or end of treatment. Treatment plans need to be individualized, and neither treatment initiation nor cessation should be based on BA or CA alone.

Background and aim of the study: We previously published the increased frequency of new CPP cases during the Covid-19 pandemic in our pediatric endocrinology clinic at Rady Children's Hospital in San Diego, CA, US. We conducted this follow-up study to examine the incidence of new CPP cases requiring treatment with GnRH agonist (GnRHa) in our clinic during 2 years post-pandemic. Methods: We performed a retrospective comparison of the number of visits of children newly diagnosed with CPP treated with GnRHa during the 2 years following the first year of Covid-19 pandemic (5/2021–7/2023). We evaluated clinical and bone maturation data as well as differences in timing from diagnosis to onset of treatment. Results: We previously reported in the pre-Covid year, 28 children (1 boy, 27 girls) treated with GnRHa for CPP out of 2,340 new endocrinology visits (1.2% of patients seen). During Covid-19 year, 64 children (7 boys, 57 girls) were treated out of 2,261 new visits (2.8%). The incidence of new CPP cases requiring GnRHa during the pandemic more than doubled compared to pre-pandemic. In the first year post-year 1 of the pandemic (5/2021–4/2022), 46 children (3 boys, 40 girls) started treatment with GnRHa for CPP out of 2,595 new endocrinology visits (1.6% of patients seen). During the second follow-up year (5/2022–4/2023), 22 children (4 boys, 18 girls) started treatment with GnRHa for CPP out of 2,676 new endocrinology visits (0.8% of patients seen). Age at onset of treatment, degree of bone age (BA) advancement, time from diagnosis to onset of treatment, and changes in BMI during the pandemic were not different from pre-pandemic or post-pandemic. Conclusions: CPP cases requiring GnRHa treatment significantly increased during the first year of the Covid-19 pandemic and then decreased each year post-pandemic. This was not related to BMI, age at diagnosis, degree of bone age advancement, or time from diagnosis to onset of treatment as all these factors have been similar during pre-pandemic, pandemic, and post-pandemic years. It is reasonable that the postulated hypotheses published regarding the increase during the pandemic would resolve post-pandemic.

Objectives

It is important to understand what variables influence change in predicted adult height (PAH) throughout GnRHa treatment for central precocious puberty (CPP) to individualize treatment decisions and optimize care.

Methods

Changes in PAH, chronological age (CA), bone age (BA), BA/CA, and height velocity (HV) were evaluated in girls with CPP throughout treatment with leuprolide acetate (n=77). A second analysis focused on changes in the 3 years preceding the first observed BA of ≥12 years. Relationships were characterized using plot inspection and linear mixed-effects analyses. Association between treatment duration and last assessed PAH was examined using multiple linear regression models.

Results

BA/CA and HV showed a nonlinear change during treatment, with the largest changes and improvement in PAH observed in the first 6-18 months. Rate of BA advancement tended to decrease more slowly in girls initiating treatment at a younger BA. On-treatment change in PAH was predicted by concurrent BA/CA change, HV, and BA, as well as CA at treatment initiation. Last assessed PAH was positively associated with longer treatment durations (primary/exploratory models cut-offs of ≥33/≥55 months).

Conclusions

These findings support individualized monitoring during GnRHa treatment. Initial response should be interpreted with caution until 6-18 months after treatment initiation and failure should not be assumed based on continued bone maturation in girls starting therapy at a younger age. Treatment cessation should not be automatically based on a diminishing change in PAH or HV, as ongoing treatment may result in continued increase or maintenance of PAH.