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      Clinical and Laboratory Characteristics of Hyperprolactinemia in Children and Adolescents: National Survey

      1 , * , 2 , 3 , 4 , 5 , 5 , 6 , 7 , 8 , 1 , 8 , 8 , 1 , 8 , 9 , 8 , 10 , 11 , 12 , 13 , 12 , 14 , 12 , 15 , 16 , 15 , 17 , 18 , 19 , 1

      Journal of Clinical Research in Pediatric Endocrinology

      Galenos Publishing

      Pituitary, prolactin, children, microadenomas, macroadenomas, cabergoline, surgery

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          Abstract

          Objective:

          We aimed to report the characteristics at admission, diagnosis, treatment, and follow-up of cases of pediatric hyperprolactinemia in a large multicenter study.

          Methods:

          We reviewed the records of 233 hyperprolactinemic patients, under 18 years of age, who were followed by different centers. The patients were divided as having microadenomas, macroadenomas, drug-induced hyperprolactinemia and idiopathic hyperprolactinemia. Complaints of the patients, their mode of treatment (medication and/or surgery) and outcomes were evaluated in detail.

          Results:

          The mean age of the patients with hyperprolactinemia was 14.5 years, and 88.4% were females. In terms of etiology, microadenomas were observed in 32.6%, macroadenomas in 27%, idiopathic hyperprolactinemia in 22.7% and drug-induced hyperprolactinemia in 6.4%. Other causes of hyperprolactinemia were defined in 11.3%. Common complaints in females (n=206) were sorted into menstrual irregularities, headaches, galactorrhea, primary or secondary amenorrhea and weight gain, whereas headache, gynecomastia, short stature and blurred vision were common in males (n=27). Median prolactin levels were 93.15 ng/mL, 241.8 ng/mL, 74.5 ng/mL, 93.2 ng/mL, and 69 ng/mL for microadenomas, macroadenomas, idiopathic hyperprolactinemia, drug-induced hyperprolactinemia, and other causes of hyperprolactinemia, respectively. Of 172 patients with hyperprolactinemia, 77.3% were treated with cabergoline and 13.4% with bromocriptine. 20.1% of the patients with pituitary adenomas underwent pituitary surgery.

          Conclusion:

          We present the largest cohort of children and adolescents with hyperprolactinemia in the literature to date. Hyperprolactinemia is more common in females and cabergoline is highly effective and practical to use in adolescents, due to its biweekly dosing. Indications for surgery in pediatric cases need to be revised.

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          Most cited references 34

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          Reference Values for Weight, Height, Head Circumference, and Body Mass Index in Turkish Children

          Objective: This study aimed to integrate the existing updated reference standards for the growth of Turkish infants and children and to compare these values with World Health Organization (WHO) reference data, data from some European countries, and also with previous local data. Weight, height, and head circumference measurements were obtained on 2,391 boys and 2,102 girls who were regular attenders of a well child clinic and on 1,100 boys and 1,020 girls attending schools in relatively well-off districts in İstanbul. Mean number of measurements per child was 8.2±3.6 in the age group 0-5 years and 5.5±3.3 in the age group 6-18 years. All children were from well-to-do families and all were healthy. All measurements with the exception of measurements at birth, which were based on reported values, were done by trained personnel. Methods: The LMS method was used in the analyses and in the construction of the percentile charts. There is an increase in weight for age and body mass index values for age starting in prepubertal ages, indicating an increasing trend for obesity. Results: Compared to WHO reference data, weight and height values in Turkish children were slightly higher in infants and in children younger than 5 years, while they showed similarity to those reported for children from Norway and Belgium. Head circumference values, which were slightly higher than the WHO references in the first 5 years, were comparable to the data on Belgian and Norwegian children in the first 9 years of life. At older ages, Turkish children showed higher values for head circumference. Conclusion: The relatively larger head circumference values were interpreted to reflect a genetic characteristic.
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            New insights in prolactin: pathological implications.

            Prolactin is a hormone that is mainly secreted by lactotroph cells of the anterior pituitary gland, and is involved in many biological processes including lactation and reproduction. Animal models have provided insights into the biology of prolactin proteins and offer compelling evidence that the different prolactin isoforms each have independent biological functions. The major isoform, 23 kDa prolactin, acts via its membrane receptor, the prolactin receptor (PRL-R), which is a member of the haematopoietic cytokine superfamily and for which the mechanism of activation has been deciphered. The 16 kDa prolactin isoform is a cleavage product derived from native prolactin, which has received particular attention as a result of its newly described inhibitory effects on angiogenesis and tumorigenesis. The discovery of multiple extrapituitary sites of prolactin secretion also increases the range of known functions of this hormone. This Review summarizes current knowledge of the biology of prolactin and its receptor, as well as its physiological and pathological roles. We focus on the role of prolactin in human pathophysiology, particularly the discovery of the mechanism underlying infertility associated with hyperprolactinaemia and the identification of the first mutation in human PRLR.
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              Mutant prolactin receptor and familial hyperprolactinemia.

              Hyperprolactinemia that is not associated with gestation or the puerperium is usually due to tumors in the anterior pituitary gland and occurs occasionally in hereditary multiple endocrine neoplasia syndromes. Here, we report data from three sisters with hyperprolactinemia, two of whom presented with oligomenorrhea and one with infertility. These symptoms were not associated with pituitary tumors or multiple endocrine neoplasia but were due to a heterozygous mutation in the prolactin receptor gene, PRLR, resulting in an amino acid change from histidine to arginine at codon 188 (His188Arg). This substitution disrupted the high-affinity ligand-binding interface of the prolactin receptor, resulting in a loss of downstream signaling by Janus kinase 2 (JAK2) and signal transducer and activator of transcription 5 (STAT5). Thus, the familial hyperprolactinemia appears to be due to a germline, loss-of-function mutation in PRLR, resulting in prolactin insensitivity.
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                Author and article information

                Journal
                J Clin Res Pediatr Endocrinol
                J Clin Res Pediatr Endocrinol
                JCRPE
                Journal of Clinical Research in Pediatric Endocrinology
                Galenos Publishing
                1308-5727
                1308-5735
                June 2019
                28 May 2019
                : 11
                : 2
                : 149-156
                Affiliations
                [1 ]Uludağ University Faculty of Medicine, Department of Pediatric Endocrinology, Bursa, Turkey
                [2 ]Kırıkkale University Faculty of Medicine, Department of Pediatric Endocrinology, Kırıkkale, Turkey
                [3 ]Sakarya University Faculty of Medicine, Department of Pediatric Endocrinology, Sakarya, Turkey
                [4 ]Ondokuz Mayıs University Faculty of Medicine, Department of Pediatric Endocrinology, Samsun, Turkey
                [5 ]Ankara University Faculty of Medicine, Department of Pediatric Endocrinology, Ankara, Turkey
                [6 ]İstanbul University Faculty of Medicine, Department of Pediatric Endocrinology and Diabetes, İstanbul, Turkey
                [7 ]Yüzüncü Yıl University Faculty of Medicine, Department of Pediatric Endocrinology, Van, Turkey
                [8 ]Marmara University Faculty of Medicine, Department of Pediatric Endocrinology, İstanbul, Turkey
                [9 ]İstanbul University Cerrahpaşa Faculty of Medicine, Department of Pediatric Endocrinology, İstanbul, Turkey
                [10 ]Necmettin Erbakan University Faculty of Medicine, Department of Pediatric Endocrinology, Konya, Turkey
                [11 ]Balıkesir Atatürk State Hospital, Clinic of Pediatric Endocrinology, Balıkesir, Turkey
                [12 ]Gazi University Faculty of Medicine, Department of Pediatric Endocrinology, Ankara, Turkey
                [13 ]İnönü University Faculty of Medicine, Department of Pediatric Endocrinology, Malatya, Turkey
                [14 ]Osmangazi University Faculty of Medicine, Department of Pediatric Endocrinology and Diabetes, Eskişehir, Turkey
                [15 ]Dokuz Eylül University Faculty of Medicine, Department of Pediatric Endocrinology, İzmir, Turkey
                [16 ]Erciyes University Faculty of Medicine, Department of Pediatric Endocrinology, Kayseri, Turkey
                [17 ]Çukurova University Faculty of Medicine, Department of Pediatric Endocrinology, Adana, Turkey
                [18 ]Kanuni Sultan Süleyman Training and Research Hospital, Clinic of Pediatric Endocrinology, İstanbul, Turkey
                [19 ]Dicle University Faculty of Medicine, Department of Pediatric Endocrinology, Diyarbakır, Turkey
                Author notes
                * Address for Correspondence: Uludağ University Faculty of Medicine, Department of Pediatric Endocrinology, Bursa, Turkey Phone: +90 505 768 69 47 E-mail: erderen@ 123456yahoo.com
                Article
                19906
                10.4274/jcrpe.galenos.2018.2018.0206
                6571533
                30396878
                ©Copyright 2019 by Turkish Pediatric Endocrinology and Diabetes Society | The Journal of Clinical Research in Pediatric Endocrinology published by Galenos Publishing House.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                Categories
                Original Article

                Pediatrics

                prolactin, children, microadenomas, macroadenomas, cabergoline, surgery, pituitary

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