J Pediatr Endocr Met 2015; aop
Havva Nur Peltek Kendirci*, Sebahat Yılmaz Ağladıoğlu, Aşan Önder, Veysel Nijat Baş, Semra Çetinkayaa and Zehra Aycan
Effects of GnRH analogue treatment on anterior pituitary hormones in children with central precocious puberty Abstract
DOI 10.1515/jpem-2014-0222 Received May 27, 2015; accepted April 9, 2015
Introduction and purpose: This study aims to investigate the effect of Gonadotropin-releasing hormone analogues (GnRHa) treatment on anterior pituitary hormones in female children with central precocious puberty (CPP). Subjects and method: There were 62 female children who had been diagnosed with CPP and received GnRHa (Leuprolide acetate, 3.75 mg intramuscular/subcutaneous/28 days) included in the study. All subjects were clinically evaluated prior to treatment and every 3 months during treatment with serum LH, FSH, ACTH, TSH, PRL as pituitary hormones, and the end hormones such as plasma E2, cortisol, fT3, fT4 levels were measured. IGF-1 and IGFBP-3 levels were measured, and SDS was evaluated according to age and gender. Results: Prolactin levels were higher during GnRHa treatment compared to pre-treatment values although the increase was statistically significant only at month 3. In addition, while 2 (3.2%) of the patients had hyperprolactinemia before treatment, 11 (17.7%) patients developed hyperprolactinemia at different time points during treatment. Conclusion: This study concluded that GnRHa treatment resulted in hyperprolactinemia and had no significant effect other pituitary hormones. Keywords: females; gonadotropin releasing hormone agonist; pituitary function; pituitary gland; precocious puberty.
a ESPE member *Corresponding author: Havva Nur Peltek Kendirci, MD Pediatric Endocrinologist, Dr. Sami Ulus Women Health, Children’s Training and Research Hospital, Clinics of Pediatric Endocrinology, Ankara,Turkey, Phone: +90-312-305-65-12, Fax: +90-312-317-03-53, E-mail: [email protected] Sebahat Yılmaz Ağladıoğlu, Aşan Önder, Veysel Nijat Baş, Semra Çetinkaya and Zehra Aycan: Dr. Sami Ulus Women Health, Children’s Training and Research Hospital, Clinics of Pediatric Endocrinology, Ankara, Turkey
Introduction and objective Gonadotropin-releasing hormone (GnRH) analogues are widely used for the treatment of endocrinal disorders due to their suppressive effects on LH, FSH, and gonadal sex steroids such as androgens/estrogens. It is predicted that GnRHa reduces LH and FSH release from gonadotrophs and may affect the hormones relaesed from other pituitary cells due to close vicinity (growth hormone, thyroidstimulating hormone, prolactin, adrenocorticotropic hormone) (1). Although they have been in use for more than 30 years, limited data is available on the effects of long-term treatment with GnRH analogues on pituitary hormones as well as on their mechanisms of action, and the majority of the studies were conducted with adult populations. Because there are a few studies on this topic on pediatric patients and their results are contradictory, there is a need for studies to determine the effects of GnRH analogues, particularly their pituitary effects, in the pediatric population. The present study aims to identify the effects of GnRH analogues on anterior pituitary hormones (LH, FSH, TSH, prolactin, ACTH, GH-IGF-1 axis) and on the hormones which they stimulate periferally in patients being treated with GnRH analogues for central precocious puberty (CPP).
Subjects and methods The study was performed with girls who had been diagnosed with CPP at the Pediatric Endocrinology Clinic of the Dr. Sami Ulus Gynecology, Pediatric Health and Diseases Training and Research Hospital of the T.R. Ministry of Health and who were receiving treatment with a GnRH analogue (Leuprolide acetate). Approval of the ethical board of Ankara University Medical Faculty was obtained for the study. The patients and their families were given oral explanation on the subject and purpose of the study after which informed consent
Brought to you by | New York University Bobst Library Technical Services Authenticated Download Date | 6/4/15 8:37 PM
2 Kendirci et al.: Effects of GnRH analogue treatment on anterior pituitary hormones forms were received from the parents of the participants agreeing to participate in the study. The following criteria were used for the diagnosis of CPP in all girls referred for premature sexual maturation in our pediatric endocrine clinic (2, 3): –– Girls with idiopatic CPP entered puberty with breast development at Tanner stage 2 or 3 before the age of 8 years –– Accelerated somatic development according to age and gender –– Bone age was accelarated by 2 years compared to the chronological age –– Increased gonadothropin levels in a range accepting as pubertal (basal LH level ≥ 0.3 mIU/mL or peak response LH ≥ 5 mIU/mL in standard IV GnRH test) –– Pelvic ultrasounds also demonstrated positive pubertal findings (incrased ovarian volume and number and volume of follicles, and increased size of uterus) Patients with peripheral precocious puberty, pituitary hormone deficiency, primary thyroid pathology, primary adrenal or gonadal pathology, dysmorphic syndromes, systemic disorders, chronically treated patients and patients with organic pituitary or hypothalamus lesion shown on MRI were excluded from the study. There were 75 females who were diagnosed with CPP and were started on treatment with GnRHa included in the study. Of these patients, 13 patients were excluded due to GnRHa treatment time of
Havva Nur Peltek Kendirci*, Sebahat Yılmaz Ağladıoğlu, Aşan Önder, Veysel Nijat Baş, Semra Çetinkayaa and Zehra Aycan
Effects of GnRH analogue treatment on anterior pituitary hormones in children with central precocious puberty Abstract
DOI 10.1515/jpem-2014-0222 Received May 27, 2015; accepted April 9, 2015
Introduction and purpose: This study aims to investigate the effect of Gonadotropin-releasing hormone analogues (GnRHa) treatment on anterior pituitary hormones in female children with central precocious puberty (CPP). Subjects and method: There were 62 female children who had been diagnosed with CPP and received GnRHa (Leuprolide acetate, 3.75 mg intramuscular/subcutaneous/28 days) included in the study. All subjects were clinically evaluated prior to treatment and every 3 months during treatment with serum LH, FSH, ACTH, TSH, PRL as pituitary hormones, and the end hormones such as plasma E2, cortisol, fT3, fT4 levels were measured. IGF-1 and IGFBP-3 levels were measured, and SDS was evaluated according to age and gender. Results: Prolactin levels were higher during GnRHa treatment compared to pre-treatment values although the increase was statistically significant only at month 3. In addition, while 2 (3.2%) of the patients had hyperprolactinemia before treatment, 11 (17.7%) patients developed hyperprolactinemia at different time points during treatment. Conclusion: This study concluded that GnRHa treatment resulted in hyperprolactinemia and had no significant effect other pituitary hormones. Keywords: females; gonadotropin releasing hormone agonist; pituitary function; pituitary gland; precocious puberty.
a ESPE member *Corresponding author: Havva Nur Peltek Kendirci, MD Pediatric Endocrinologist, Dr. Sami Ulus Women Health, Children’s Training and Research Hospital, Clinics of Pediatric Endocrinology, Ankara,Turkey, Phone: +90-312-305-65-12, Fax: +90-312-317-03-53, E-mail: [email protected] Sebahat Yılmaz Ağladıoğlu, Aşan Önder, Veysel Nijat Baş, Semra Çetinkaya and Zehra Aycan: Dr. Sami Ulus Women Health, Children’s Training and Research Hospital, Clinics of Pediatric Endocrinology, Ankara, Turkey
Introduction and objective Gonadotropin-releasing hormone (GnRH) analogues are widely used for the treatment of endocrinal disorders due to their suppressive effects on LH, FSH, and gonadal sex steroids such as androgens/estrogens. It is predicted that GnRHa reduces LH and FSH release from gonadotrophs and may affect the hormones relaesed from other pituitary cells due to close vicinity (growth hormone, thyroidstimulating hormone, prolactin, adrenocorticotropic hormone) (1). Although they have been in use for more than 30 years, limited data is available on the effects of long-term treatment with GnRH analogues on pituitary hormones as well as on their mechanisms of action, and the majority of the studies were conducted with adult populations. Because there are a few studies on this topic on pediatric patients and their results are contradictory, there is a need for studies to determine the effects of GnRH analogues, particularly their pituitary effects, in the pediatric population. The present study aims to identify the effects of GnRH analogues on anterior pituitary hormones (LH, FSH, TSH, prolactin, ACTH, GH-IGF-1 axis) and on the hormones which they stimulate periferally in patients being treated with GnRH analogues for central precocious puberty (CPP).
Subjects and methods The study was performed with girls who had been diagnosed with CPP at the Pediatric Endocrinology Clinic of the Dr. Sami Ulus Gynecology, Pediatric Health and Diseases Training and Research Hospital of the T.R. Ministry of Health and who were receiving treatment with a GnRH analogue (Leuprolide acetate). Approval of the ethical board of Ankara University Medical Faculty was obtained for the study. The patients and their families were given oral explanation on the subject and purpose of the study after which informed consent
Brought to you by | New York University Bobst Library Technical Services Authenticated Download Date | 6/4/15 8:37 PM
2 Kendirci et al.: Effects of GnRH analogue treatment on anterior pituitary hormones forms were received from the parents of the participants agreeing to participate in the study. The following criteria were used for the diagnosis of CPP in all girls referred for premature sexual maturation in our pediatric endocrine clinic (2, 3): –– Girls with idiopatic CPP entered puberty with breast development at Tanner stage 2 or 3 before the age of 8 years –– Accelerated somatic development according to age and gender –– Bone age was accelarated by 2 years compared to the chronological age –– Increased gonadothropin levels in a range accepting as pubertal (basal LH level ≥ 0.3 mIU/mL or peak response LH ≥ 5 mIU/mL in standard IV GnRH test) –– Pelvic ultrasounds also demonstrated positive pubertal findings (incrased ovarian volume and number and volume of follicles, and increased size of uterus) Patients with peripheral precocious puberty, pituitary hormone deficiency, primary thyroid pathology, primary adrenal or gonadal pathology, dysmorphic syndromes, systemic disorders, chronically treated patients and patients with organic pituitary or hypothalamus lesion shown on MRI were excluded from the study. There were 75 females who were diagnosed with CPP and were started on treatment with GnRHa included in the study. Of these patients, 13 patients were excluded due to GnRHa treatment time of
