Case Highlights:
01
In this case, the child's growth and development progressed rapidly at the time of diagnosis, the hormone level increased significantly, the growth rate accelerated in the past 1 year, and the height was higher than the average height of the age group, and the predicted adult height was 152 cm at the time of consultation, which was 10 cm lower than the median genetic target height (162.5 cm).
曲普瑞林三月剂型治疗3个月后，下丘脑-垂体-性腺轴功能处于抑制状态，迅速抑制LH及FSH. （LH：1.02 IU/L→0.24 IU/L；FSH：5.63 IU/L→1.05 IU/L）。
03
After 6 months of treatment with triptorelin in the three-month dosage form, the efficacy was certain. THE GROWTH RATE DECREASED TO THE PREPUBERTAL LEVEL, THE HEIGHT OF THE CHILD INCREASED BY 2.4 CM FROM BASELINE, THE BREAST TISSUE DID NOT CONTINUE TO ENLARGE AND THE LONG AXIS OF THE UTERUS RETRACTED FROM BASELINE, THE PROGRESSION OF BONE AGE WAS DELAYED, AND THE RATIO TO THE ACTUAL AGE DECREASED SLIGHTLY, AND THE FINAL ADULT HEIGHT WAS PREDICTED TO INCREASE BY 3 CM (152 CM → 155 CM) FROM BASELINE ACCORDING TO BLINE. In line with treatment expectations.
04
Long-acting gonadotropin-releasing hormone analogue (GnHRa) formulations are one of the drugs of choice for the treatment of central precocious puberty (CPP)1,2. The three-month dosage form of triptorelin has a rapid onset of action, is stable and efficient, and has a long interval between administrations, which has more economic value of the drug. In terms of disease burden, families are saved about 25% of the annual per capita treatment cost and about 70% of the caregiver labor loss3,4.
Case sharing
Expert|Family|Brief|Introduction
Liang Cuili is the attending physician
Attending physician of the Department of Genetics and Endocrinology, Guangzhou Women and Children's Medical Center, Master of Pediatrics
He is a member of the Youth Club of the South China Collaborative Group of the Endocrinology, Genetics and Metabolism Group of the Pediatric Branch of the Chinese Medical Association
Secretary of the Spinal Muscular Atrophy Diagnosis and Treatment Collaboration Group of Guangdong Rare Disease Diagnosis and Treatment Collaboration Network
Secretary of the Progressive Muscular Dystrophy Diagnosis and Treatment Collaboration Group of Guangdong Rare Disease Diagnosis and Treatment Collaboration Network
Member of the Child Health Development Branch of Guangdong Health Economics Society
Basic information
The child is a female who is 8 years old and 3 months old.
Chief complaint: found that both breasts were enlarged for more than 1 year.
History of present illness: The child was found to have enlarged breasts more than 1 year ago (starting at about 7 years and 3 months), with tenderness, no increased vaginal discharge, and no vaginal bleeding. No dizziness and headache, no blurred vision, no polydipsia, polyphagia, no convulsions, the height growth rate has been faster than that of children of the same age, 9cm in height in the past 1 year, and he denied taking sex hormone drugs. Spirit, reflexes, stomach acceptable, bowel and bowel movements are normal. Dad is 178cm tall, Mom is 160cm tall, and the genetic target is 162.5±5cm tall. Mother had menarche at the age of 13.
入院查体：身高136.7cm（+1.25 SD），体重26.8kg（+0.18 SD）。 体质指数（BMI）：14.34 kg/m2(-0.65 SD)，双乳B2+期，核（+）。 乳晕无色素沉着，无阴毛，无腋毛，皮肤未见牛奶咖啡斑及色素沉着，未见特殊体征及特殊外貌。
Predicted height: The predicted adult height before treatment was 152 cm, which was 10 cm lower than the median genetic target height.
INVESTIGATIONS
Hormone level test: Table 1.The results of the hormone level test of the child
*Triptorelin 0.1 mg provocation test LH, luteinizing hormone, FSH, follicle-stimulating hormone
Table 2.Other hormones in children
E2，雌二醇；PRL，泌乳素; T,睾酮；ACTH,促肾上腺皮质激素；COR，皮质醇；DHEAS,硫酸脱氢表雄酮; AND,雄烯二酮
imaging tests:
- Uterine ovarian ultrasound: the size of the uterine section was 26×19×14mm, the muscular echo was uniform, and no obvious abnormal echo was found. The left ovary is 21×10×13 m in size, and the right ovary is 25×11×13 mm in size, with small follicles visible in it (see Table 4).
- Bone age: Bone age is equivalent to about 11 years old in women.
- Pituitary MRI: noncontrast pituitary MRI showed no significant abnormalities.
Clinical diagnosis
Central Precocious Puberty (CPP)
Goals of treatment:
- Effectively inhibits the HPO axis
- Improve adult height
- Families want to reduce the number of hospital visits and follow-ups
Diagnosis and treatment process and efficacy evaluation
Combined with the child's own condition, triptorelin dihydroxynaphthalate 15mg (effective therapeutic dose of 11.25mg triptorelin) was given for treatment after comprehensive evaluation, and the changes in BMI, bone age and hormone level were paid close attention, and the specific medication time, dosage and trend of various indicators are shown in Table 3~5.
Table 3.Changes in medication regimens and indexes in children
BA, bone age, ovarian volume calculation formula: ovarian volume = major axis diameter× minor axis diameter × wide axis diameter × 0.523
Table 4.Changes in hormone levels during medication
LH, luteinizing hormone, FSH, follicle-stimulating hormone, E2, estradiol, PRL, prolactin, after provocation: after the use of sex hormone provocation test, those who did not note the time were all basic hormone levels
*Easy excitation of FSH, LH
Table 5.Imaging changes in children during medication
Summary of the case
The child, a female of 8 years and 3 months, was admitted to the hospital for "bilateral breast enlargement for more than 1 year", and the admission examination and imaging examination showed that the secondary sexual characteristics developed early, the B2 stage of both breasts, the stage I of pubic hair, the enlargement of both ovaries, and the difference between bone age and actual age was > 1 year. The serum gonadotropins and sex hormones were elevated, and the peak LH and FSH were 10.16 IU/L, 10.77 IU/L, and 1.06 respectively. Based on the comprehensive judgment of the child's sexual development status, gonadal development, height, bone age and other indications, the clinical diagnosis was CPP.
Referring to the Expert Consensus on the Diagnosis and Treatment of Central Precocious Puberty (2022) (hereinafter referred to as the "Consensus") and the instructions of triptorelin dihydroxynaphthalate for injection, the child was given triptorelin in a three-month dosage form (15mg specification, injected once every three months), and after 6 months of treatment, the levels of FSH, LH and various estrogens decreased significantly, and the levels of LH and FSH decreased significantly to prepubertal levels compared with the baseline, and continued to inhibit (LH: 1.02 IU/L→0.39 IU/ FSH: 5.63 IU/L →1.48 IU/L) (Fig. 1), the E2 level was controlled below the level of puberty, the development of secondary sexual characteristics was stable, the uterine development was retracted compared with the previous (26 mm → 22 mm on the long axis of the uterus), the difference between bone age and chronological age decreased from the initial 2.75 years to 2.25 years (Fig. 2), and the predicted adult height was 155 cm, an increase of about 3 cm from the baseline prediction.
The three-month dosage form of triptorelin was safe and no adverse drug events occurred. In addition, the injection interval of triptorelin in three months is once every 3 months, which is synchronized with the treatment monitoring interval, which can improve the convenience of treatment and further improve the compliance and satisfaction of children. Treatment adherence was good, and the benefits were significant.
Figure 1. Changes in hormone levels in the child during treatment
Figure 2. Change in difference between bone age and chronological age
Expert commentary
Expert|Family|Brief|Introduction
Prof. Wen Zhang
Director of the Department of Genetics and Endocrinology, Guangzhou Women and Children's Medical Center
Chief Physician, Doctor of Medicine, Master's Supervisor
He is a standing member of the South China Collaboration Group of the Endocrinology, Genetics and Metabolism Group of the Pediatric Branch of the Chinese Medical Association
He is a member of the Pediatric Committee of the Chinese Association of Research Hospitals
He is a member of the Rare Disease Committee of the Chinese Hospital Association
He is a standing member of the Child Growth and Special Food Professional Committee of the China Eugenics Association
Member of the Endocrinology, Genetics and Metabolism Group of the Pediatric Branch of Guangdong Medical Association
Chairman of the Rare Disease Branch of Guangdong Medical Association
Vice Chairman of the Rare Disease Expert Committee of Guangdong Pharmaceutical Association
Professor Zhang Wen's comments:
In recent years, the incidence of CPP has been increasing year by year5. CPP can not only lead to the impairment of children's growth potential, but also may affect children's mental health, so timely diagnosis and treatment of CPP is particularly important to improve the adult height and promote physical and mental health development.
In this case, the child was diagnosed with CPP as early onset of secondary sexual characteristics, accelerated linear growth, enlarged gonads, serum gonadotropins and sex hormones reaching pubertal levels, and bone age exceeding the chronological age of ≥1 year.
Authoritative guidelines at home and abroad point out that the goal of CPP treatment is to inhibit the developmental process, delay the rapid maturation of bones, avoid psychological problems, and ultimately improve adult height. Currently, GnHRa is the drug of choice for the treatment of CPP1,2. According to the International Consensus on the Application of GnHRa (2019)6, the child in this case had significant acceleration of skeletal maturation and sexual development, exceeding the linear growth rate, and the growth potential was significantly impaired.
In this case, after 6 months of treatment with triptorelin in three months, the growth rate of the child returned to the prepubertal level, the progression of bone age was delayed, the ratio to the actual age decreased slightly, and the final adult height was predicted to increase by 3 cm compared with the baseline according to the bone age. The hormone level test showed that the levels of LH and FSH were inhibited and returned to prepubertal levels, and the long axis of the uterus was retracted from baseline, and the breast tissue did not continue to enlarge, and the safety was good and there were no side effects.
The phase III clinical study of triptorelin in China4 showed that the three-month dosage form of triptorelin can effectively control hormone levels, delay the development of secondary sexual characteristics, reduce growth rate, and improve the prediction of final adult height. The three-month dosage form of triptorelin only needs to be injected four times per year, which greatly reduces the number of injections and improves the treatment compliance of children, and the three-month dosage form of triptorelin has more pharmacoeconomic value than the one-month dosage form7.
The three-month dosage form of triptorelin provides a better treatment option for CPP, which enriches the treatment options for CPP in mainland China, and also brings benefits to children and their families.
Bibliography:
[1] Endocrinology, Genetics and Metabolism Group, Chinese Society of Pediatrics, Editorial Board of Chinese Journal of Pediatrics. Expert consensus on the diagnosis and treatment of central precocious puberty (2022)[J]. Chinese Journal of Pediatrics, 2023; 61(01):16-22.
[2] Eugster EA. J Endocr Soc. 2019; 3(5):965-972.
[3] Chung LY, Kang E, Nam HK, et al. J Korean Med Sci. 2021; 36(34):e219.
[4]11th International Meeting of Paediatric Endocrinology (IMPE) - Abstracts. Horm Res Paediatr. 2023;Vol. Suppl 2:1-197.
[5] Yang, K, et al. Hong Kong Journal of Paediatrics, 2022. 27(1): p. 19-24.
[6] Bangalore Krishna K, et al. Horm Res Paediatr. 2019; 91(6):357-372.
[7] Zhou Keruo, Tan Baoying, Jian Yifei, et al. An economic evaluation of gonadotropin-releasing hormone analogues in the treatment of central precocious puberty in Chinese children. 2023 Annual Meeting of the Pharmacoeconomics Committee of the Chinese Pharmaceutical Association. Poster No.: PE072.
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Document Number DIP-CN-012112
Expiration Date 3/15/2026
For medical and pharmacy professionals only