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Galactorrhea with Metoclopramide Use in the Neonatal Unit

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Galactorrhea with Metoclopramide Use in the Neonatal Unit Journal of Perinatology (2009) 29, 391–392 r 2009 Nature Publishing Group All rights reserved. 0743-8346/09 $32 www.nature.com/jp PERINATAL/NEONATAL CASE PRESENTATION Galactorrhea with metoclopramide use in the neonatal unit B Paturi, RM Ryan, KA Michienzi and S Lakshminrusimha Women and Children’s Hospital of Buffalo, Buffalo, NY, USA persistent stridor and respiratory distress, he was started on We report a 3½-month-old infant with trisomy 21 presenting with lansoprazole at 1.5 mg kgÀ1 per dose every 24 h and his galactorrhea in the neonatal intensive care unit (NICU). Endocrine work-up metoclopramide dose was increased to 0.2 mg kgÀ1 per dose every 6 h À1 À1 showed a high prolactin level (64.4 ng ml Fnormal: 0.5 to 30 ng ml ). (maximum dose in the standard pediatric reference handbook4). There À1 Cessation of therapy with metoclopramide (0.2 mg kg per dose q 6 h) was no improvement in the symptoms despite the escalation of resulted in the resolution of galactorrhea with a decrease in serum prolactin metoclopramide dosage. He underwent an emergent tracheostomy at 3 À1 level (20.1 ng ml ). We present this case to highlight this uncommon side months of age due to his deteriorating respiratory status because of effect of a commonly used medication in the NICU. subglottic narrowing. He was continued on metoclopramide to Journal of Perinatology (2009) 29, 391–392; doi:10.1038/jp.2008.246 enhance gastric emptying. Two weeks after treatment with À1 Keywords: prolactin; gastroesophageal reflux; gynecomastia metoclopramide at 0.8 mg kg per day, he was noted to have prominent breasts (asymmetric gynecomastia, right greater than left) with milk discharge. Endocrine work-up showed a normal thyroid profile (T4 1.67 ng per 100 ml, TSH 5.24 IU mlÀ1). Serum HCG Introduction (negative), estradiol (<20 pg mlÀ1), FSH (4.6 mIU mlÀ1), and LH À1 Galactorrhea in the newborn (sometimes referred to as ‘witch’s (7 mIU ml ) were within normal limits. Scrotal ultrasound was milk’) was first described in the medical literature in the normal with both testes present. Serum prolactin level was elevated at À1 F À1 seventeenth century.1 It is a common condition and is seen in B5 56.8 ng ml (normal range 0.5to30ngml ). When this report 2 was received, a repeat prolactin level was checked immediately and was to 6% of term infants with no gender preponderance. This À1 condition is considered physiologic, secondary to withdrawal from again high at 64.4 ng ml . Metoclopramide was discontinued. Gynecomastia and galactorrhea resolved within 1 week. Repeat maternal hormones after birth. Most of these infants present during À1 the first week of life (between the fifth and seventh days of life) prolactin level was within normal limits (20.6 ng ml ) 2 weeks after followed by a spontaneous resolution in a few weeks.3 Galactorrhea discontinuing metoclopramide. is uncommon in infants beyond 3 months of age. We describe a 3½-month-old infant who developed galactorrhea in the neonatal intensive care unit (NICU) after metoclopramide therapy. Discussion Lactation, as opposed to breast gland proliferation, is inhibited during pregnancy by high levels of the circulating progesterone. Case Progesterone withdrawal occurs around the time of delivery in A term male neonate, with trisomy 21, with patent ductus arteriosus, association with a continuing increase in prolactin levels, which 5 stridor, and feeding intolerance was evaluated by a pediatric initiates milk secretion in the mother. These changes in maternal otorhinolaryngologist at 40 days of age. Laryngomalacia, glottic hormones may result in bilateral breast hypertrophy and edema, and erythema were observed on flexible laryngoscopy. He was galactorrhea in infants. Prolactin levels are elevated markedly in À1 À1 suspected to have gastroesophageal reflux-induced irritation of the cord blood at 170 ng ml compared with adults (<20 ng ml ) 6,7 airway, and was treated with metoclopramide at 0.15 mg kgÀ1 per dose and are declined by >60% in the first week after birth. every 8 h for 45 days. He underwent surgical closure of a patent ductus The regulation of prolactin is unique because it is secreted arteriosus at 1 month of life. His stay in the NICU was prolonged consistently unless it is inhibited actively by dopamine (also called because of his poor ability to tolerate oral feeds and stridor. Owing to the prolactin inhibitory factor), which is produced by neurons in the hypothalamus.8 Dopamine antagonists may result in increased Correspondence: Dr S Lakshminrusimha, Department of Pediatrics/Neonatology, Women and serum levels of prolactin. Metoclopramide is a dopamine Children’s Hospital of Buffalo, 219 Bryant St, Buffalo, NY 14222, USA. E-mail: [email protected] antagonist and is used commonly as a prokinetic drug to treat 9–11 Received 17 September 2008; revised 18 December 2008; accepted 19 December 2008 gastroesophageal reflux disease in infants. Its gastrointestinal Galactorrhea with metoclopramide B Paturi et al 392 smooth muscle stimulatory effects are related to its ability to 3 McKiernan JF, Hull D. Breast development in the newborn. Arch Dis Child 1981; 56: antagonize the inhibitory neurotransmitter dopamine and to 525–529. augment acetylcholine release. In adults, metoclopramide has been 4 Lee C, Robertson J, Shilkofski N. Drug dosesFThe Harriet Lane Handbook, 17th reported to cause gynecomastia and galactorrhea from edn. Elsevier Mosby: Philadelphia, 2005. 12 5 McKiernan JF, Hull D. Prolactin, maternal oestrogens, and breast development in the hyperprolactinemia. In fact, it is prescribed to improve faltering newborn. Arch Dis Child 1981; 56: 770–774. 13 milk production in mothers of premature infants. 6 Gluckman PD, Ballard PL, Kaplan SL, Liggins GC, Grumbach MM. Prolactin The efficacy of metoclopramide with a dose range of in umbilical cord blood and the respiratory distress syndrome. J Pediatr 1978; 93: 0.1–0.3 mg kgÀ1 per dose in gastroesophageal reflux has been 1011–1014. studied in infants.14,15 Two recent reviews have concluded that 7 Sultan C, Bonardet A, Bonnal B, Descomps B, De Kerleau JC, Bonnet H et al. [Plasma prolactin levels in normal children from birth to adolescence]. C R Seances Soc Biol evidence for the safety and the efficacy of metoclopramide in Fil 1977; 171: 131–135. 9,16 infants for gastroesophageal reflux is inconclusive. The only 8 Parks JS, Felner EI. Hormones of the hypothalamus and pituitary. In: Kliegman RM, other case report of metoclopramide-induced galactorrhea in Behrman RE, Jenson HB, Stanton BF (eds). Nelson Textbook of Pediatrics. Elsievier: infants involved an infant with chondrodysplasia punctata.17 Philadelphia, 2007. Similar to our patient, this infant was on a dose of 0.2 mg kgÀ1 9 Hibbs AM, Lorch SA. Metoclopramide for the treatment of gastroesophageal four times a day and had a high prolactin level (37 ng mlÀ1). This reflux disease in infants: a systematic review. Pediatrics 2006; 118: À1 746–752. dose is higher than that recommended (0.033 to 0.1 mg kg per 10 Clark RH, Bloom BT, Spitzer AR, Gerstmann DR. Reported medication use in the 18 dose every 8 h) in a standard neonatal reference. It is interesting neonatal intensive care unit: data from a large national data set. Pediatrics 2006; 117: that the daily dose in the earlier case report and our patient 1979–1987. (0.8 mg kgÀ1 per day) exceeded the dose recommended in this 11 Malcolm WF, Gantz M, Martin RJ, Goldstein RF, Goldberg RN, Cotten CM. Use of reference, suggesting a dose-related effect without any evidence of medications for gastroesophageal reflux at discharge among extremely low birth weight infants. Pediatrics 2008; 121: 22–27. added benefit. Similar reports of galactorrhea in infants after the 12 Arroyo H, Aubert L. [Galactorrhoea following metoclopramide treatment]. Presse Med use of domperidone (a prokinetic agent not available in the United 1971; 79: 1859. 19 States) are present in the literature. 13 Ehrenkranz RA, Ackerman BA. Metoclopramide effect on faltering milk production by We conclude that careful physical examination of breast tissue mothers of premature infants. Pediatrics 1986; 78: 614–620. must be performed in infants on prolonged or high-dose therapy 14 Hyams JS, Leichtner AM, Zamett LO, Walters JK. Effect of metoclopramide on prolonged with metoclopramide. If evidence of gynecomastia or galactorrhea intraesophageal pH testing in infants with gastroesophageal reflux. J Pediatr Gastroenterol Nutr 1986; 5: 716–720. is found, prolactin levels should be obtained. If these levels are 15 Tolia V, Calhoun J, Kuhns L, Kauffman RE. Randomized, prospective double-blind trial high, attempts to discontinue or reduce the dose of metoclopramide of metoclopramide and placebo for gastroesophageal reflux in infants. J Pediatr 1989; should be considered. An awareness of this reversible side effect of 115: 141–145. metoclopramide will result in prompt diagnosis preventing an 16 Craig WR, Hanlon-Dearman A, Sinclair C, Taback S, Moffatt M. Metoclopramide, extensive endocrine work-up and reducing parental anxiety. thickened feedings, and positioning for gastro-oesophageal reflux in children under two years. Cochrane Database Syst Rev 2004 CD003502. 17 Madani S, Tolia V. Gynecomastia with metoclopramide use in pediatric patients. J Clin Gastroenterol 1997; 24: 79–81. References 18 Young T, Mangum B. Neofax 2008. Thomson Reuters Healthcare: Montvale, NJ, 2008; 1 Forbes TR. Witch’s milk and witches’ marks. Yale J Biol Med 1950; 22: 219–225. 8: 222. 2 Madlon-Kay DJ. ‘Witch’s milk’. Galactorrhea in the newborn. Am J Dis Child 1986; 19 van der Steen M, Du Caju MV, Van Acker KJ. Gynecomastia in a male infant given 140: 252–253. domperidone. Lancet 1982; 2: 884–885. Journal of Perinatology.
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