Correlation of Gonadotropins and Estradiol Level 1 Hour after Depot Triptorelin with Clinical Criteria of Adequate Pubertal Suppression in Girls with Central Precocious Puberty

Research Article

J Pediatri Endocrinol. 2017; 2(1): 1016.

Correlation of Gonadotropins and Estradiol Level 1 Hour after Depot Triptorelin with Clinical Criteria of Adequate Pubertal Suppression in Girls with Central Precocious Puberty

Kobra SA*

Research Center for Biochemistry and Nutrition in Metabolic Diseases, Kashan University of Medical Sciences, Iran

*Corresponding author: Kobra SA, Research Center for Biochemistry and Nutrition in Metabolic Diseases, Kashan University of Medical Sciences, IR Iran

Received: January 27, 2017; Accepted: April 21, 2017; Published: May 01, 2017

Abstract

Background: GnRH analogues such as Triptorelin are main stay for treatment of Central Precocious Puberty (CPP). We evaluated correlation of gonadotropins and Estradiol level one hour after administration of depot Triptorelin with other evidences of pubertal suppression.

Materials and Methods: Twenty seven girls were considered for this study after written informed consent. All patients had rapidly progressive CPP according to clinical and laboratory criteria and were under treatment with depot Triptorelin. After 3-24 dose of depot Triptorelin, blood sample was collected 1 hour after drug injection for LH, FSH and Estradiol levels. The growth velocity determined and the left hand graph obtained to determine bone age and skeletal maturation rate. Correlation of gonadotropins and Estradiol level with other evidences of pubertal suppression determined.

Results: In a period of 2 years (from 2014 to 2015), 28 patients enrolled. The mean age was 9.27 ± 1.49 years. Four patients (12.1%) recognized as inadequate pubertal suppression. Mean growth velocity was 6.21 ± 1.81 cm/ year. The mean LH ± SD was 1.34 ± 1.16 IU/l (range 0.1-5.7 IU/l). Bone maturity index was at or above one in 6 (23.1%) of 26 patients. Mean LH/FSH ratio was 0.77 ± 0.7 and 23 subjects (71.9%) has LH/FSH ratio less than one. LH, FSH and Estradiol level did not correlate with growth velocity, bone maturation rate, or with interval of Triptorelin administration. Serum LH level had significant correlation only with FSH (R= 0.383, P= 0.030) and bone age (R = -0.421, P = 0.032). Estradiol level had significant correlation with bone age (R = -0.798, P < 0.0001).

Conclusion: Diagnosis of inadequate pubertal suppression in girls with CPP is dependent on clinical, laboratory and radiological findings. LH levels one hour after injection of depot Triptorelin alone is not sufficient for finding of inadequate suppression. Serum Estradiol levels can also help to find the inadequacy of treatment.

Keywords: Gonadotropin-releasing hormone; Triptorelin; Central precocious puberty

Introduction

Precocious puberty is defined with onset of early signs of puberty at an age less than two standard deviations below the mean age of onset of puberty in normal individuals. Precocious puberty is defined in girls with the appearance of secondary sexual characteristics before the age of 8 years [1-3]. Treatment of precocious puberty noticed hypothalamic-pituitary-gonadal-axis. Gonadotropin-releasing hormone agonists (GnRHa) are standard treatment of true precocious puberty [4]. GnRH agonists can prevent many complications of precocious puberty [5]. Early diagnosis and treatment of premature sexual development during can delay puberty, reverse secondary sexual characters, reduce emotional disorders and their families concerns, reduce the risk of sexual abuse the risk of breast cancer, delay menarche in girls and eventually improve final height [6]. Biochemical methods (the level of LH, FSH, Estradiol) or the clinical score (pubertal tanner stage, skeletal maturity rate, growth rate) can be used to assess the appropriate response to treatment with GnRH analogue and adequate suppression of puberty. Intravenous gonadotropin stimulation test is the gold standard test in the evaluation of sufficient suppression of central precocious puberty but it is not pleasant for time and economy [7,8]. Therefore, the measurement of LH levels before or after injection of gonadotropin analog is used as a standard test in patients, to ensure the accuracy of the test in the evaluation of sufficient suppression of puberty; it can be compared with the clinical scores. Clues to enough suppression of puberty include the following: 1) regression or lack of progress in maturity tanner stage [2] skeletal maturity index of 1 or less (bone age changes / chronological age changes) 3) growth rate less than 2SDS for chronological age [9]. The most previous studies regarding the evaluation of sufficient suppression of puberty after GnRH agonist injection had focus on the LH level and less focused on clinical evidence of maturation inhibition. Also most of these studies have been paid to the assessment of LH after injection of leuprolide and there is only two studies have been done on Triptorelin Depot [3,10]. Therefore, this study aimed to investigate the correlation between hormone levels of LH, FSH and Estradiol an hour after administration of depot Triptorelin with clinical criteria of pubertal regression in girls with central precocious puberty.

Materials and Methods

In a longitudinal study during a period of 2 years (from 2014 to 2015) 28 girls with CPP who were under treatment with depot triptorelin considered for this research. The study conducted in the pediatric endocrinology clinic of Kashan University of Medical Sciences. The diagnosis of precocious puberty made if onset of secondary sexual characteristics was before 8 years or menarche before 9 years of age. The hormonal criteria for the diagnosis of CPP have been used on the basis of international recommendations [11- 13]. Patients were included in the study if 1) CPP has been proved with clinical and laboratory criteria and 2) good compliance for treatment and hormonal and radiologic studies. Exclusion criteria: irregular follow up visits, irregular use of depot triptorelin, no cooperation for hormonal and radiologic investigations, growth hormone deficiency, thyroid dysfunction, chronic diseases and developmental disorders. The weight, height, BMI and pubertal stage were determined at first and at 3 month intervals. Sexual maturation staging determined by Marshall-Tanner method [14]. Growth rate expressed as centimeters per year. Bone age determination performed by Bayley-Pinneau method and adult height prediction by Greulich- Pyle method [15,16]. Our treatment protocol is to treat all patients at first by depot Triptorelin 3.75 mg IM every once 28 days and in the absence of sufficient suppression of puberty, injection intervals will be reduced to 25 and then to 21 days. Within 3-24 months after starting treatment, blood sample was drawn for LH and FSH and Estradiol level one hour after depot Triptorelin injection. Serum levels of LH and FSH and estradiol were measured by immunoassay. Patients according to the clinical, laboratory and radiological findings divided into two groups:

Group A: adequate suppression of puberty,

Group B: inadequate suppression of puberty. The study design approved by ethical committees of Kashan University of Medical Sciences and written consent obtained from the parents of patients.

Statistical analysis was performed with SPSS, version 16.0 (SPSS software Inc, Chicago, IL, USA). Values were presented as mean ± standard deviation. P values lesser than 0.05(two-sided) considered as statistically significant.

Results

We have 32 girls with central precocious puberty under treatment with Triptorelin, 4 cases were excluded because of the simultaneous growth hormone therapy. In a period of 24 months, 28 patients enrolled. The mean age at the diagnosis of precocious puberty was 7.41 ± 1.51 years. The mean age at study time was 9.28 ± 1.54 years. Age had positive correlation with bone age (R: 0.821, P< 0.001). At the time of study Triptorelin 3.75 mg has been used for 14 children (50%) every 28 days, 8 children (28.6%) every 25 days and 6 (21.4%) children every 21 days. Drug interval did negative correlation with age (R: -0.456, P: 0.008) and bone age (R: -0.533, P: 0.005). A total of 4(14.3%) patients recognized as the inadequate pubertal inhibition based on the clinical, laboratory and radiologic criteria (group B), others diagnosed as adequate inhibition of puberty (group A). General characteristics and comparison of two groups showed in (Table 1). Two groups were not different in respect of age, weight, height, BMI, Bone Maturity Rate (BMR) and growth velocity. Clinical and laboratory characteristics of children with insufficient pubertal suppression showed in (Table 2). Adequate suppression of physical signs of puberty was seen in 26 (92.9%) subjects, but no in 2 (7.1%), these two patients were obese and both had Estradiol level of over 100 pg/ml. Ten subjects (35.7%) were obese. Obesity did negative correlation with age (R: -0.361, P: 0.039) and negative correlation with adequate suppression of breast tanner staging (R: -0.359, P: 0.042). Pubertal stage suppression had negative correlation with bone age (R: -0.492, P: 0.012).

Citation: Kobra SA. Correlation of Gonadotropins and Estradiol Level 1 Hour after Depot Triptorelin with Clinical Criteria of Adequate Pubertal Suppression in Girls with Central Precocious Puberty. J Pediatri Endocrinol. 2017; 2(1): 1016.