Eur J Pediatr (1991) !50:15~t-!57 034061999100004J
Massive breast enlargement in an infant girl with central nervous system dysfunction G. J. Mick 1, K. L. McCormick 1, and H. Wakimoto 2 1Pediatric Endocrine Division, Department of Pediatrics, SUNY Health Science Center, 750 East Adams Street, Syracuse, NY 13210, USA ZDepartment of Obstetrics and Gynecology, Osaka University Medical School, Osaka, Japan Received November 14, 1989 / Accepted May 23, 1990
Abstract. A 6-month-old female is described who presented with severe idiopathic macromastia. The breast enlargement began at 2 months of age and progressed such that subtotal mastectomies were necessary at 23 months. Extensive hormonal evaluation prior to surgery revealed no evidence of estrogenization or precocious puberty. T h e r e was no galactorrhea. A breast biopsy showed immature mammary tissue. In vitro analysis of the patient's serum using a mouse mammary thymidine incorporation assay revealed similar mitogenic activity in the patient's serum compared to adult controls. Post surgical follow up of this patient, 3.5 years later, has revealed no breast enlargement, precocious sexual development, or growth acceleration. Of interest, however, she has manifested an idiopathic degenerative neurologic condition characterized by psychomotor delay, ataxia, and seizures. Remarkably, h o r m o n e studies at age 5.5 years showed an exaggerated gonadotrophin response to intravenous gonadotrophin releasing h o r m o n e and prepubertal estrogen levels. While this case may represent an extraordinary example of idiopathic premature thelarche, the severe nature of this infant's macromastia in association with neurologic dysfunction and increased gonadotrophins suggests that central nervous system factors were etiologic.
girls without attendant signs of puberty. This form of breast tissue enlargement regresses in most cases and rarely requires therapeutic intervention [7, 13]. Possible etiologies for premature theiarche include increased circulating estrogens secondary to gonadotrophin stimulation [7, 14, 16], aromatization of adrenal androgens , ovarian cysts , and exposure to exogenous estrogens [2, 15] or estrogen like compounds . In most cases estrogen levels are low, hence, m a m m a r y hypersensitivity, episodic estrogen secretion, or increased circulating free estradiol  is presumed etiologic. Unlike this benign pediatric condition, adult m a m m a r y gigantism has been associated with D-penicitlamine therapy  and, furthermore, found unilaterally in two Nigerian families . We report a case of extraordinary bilateral breast enlargement in an infant girl with progressive idiopathic central nervous system dysfunction. Despite massive macromastia requiring surgery, there has been no progressive puberty or growth acceleration during 3.5 years of follow up and despite recent evidence of pituitary gonadotrophin activation. In vitro serum studies did not demonstrate the presence of a circulating m a m m a r y mitogenic factor.
Key words: Breast enlargement - Macromastia - Mammary gland - Premature thelarche
Introduction Premature thelarche is a generally benign condition characterized by isolated breast tissue development in Offprint requests to: G. J. Mick Abbreviations: FSH = follicle stimulating hormone; GnRH =
gonadotrophin releasing hormone; TRH = thyroid hormone re/easing hormone
A 6.5-month-old white female was referred for evaluation of severe, progressive macromastia. The patient was the 2950 g product of a term, uncomplicated pregnancy in her healthy 22-year-old gravida 2, para 2 mother. There was no history of maternal or patient exposure to any estrogen containing compounds, creams, or food products. Slight bilateral breast enlargement was noted at birth. This finding was unremarkable until between 1 and 2 months of age when rapidly progressive and mildly asymmetric (right greater than left) breast enlargement ensued. General health during this period was excellent as was growth and development. There was no other precocious sexual development. The diet consisted of a standard, commercially available formula and was never supplemented with breast milk. Family history was negative for endocrinopathies. Of note, the mother was slender with small breasts.
Table 1. Various blood and urine hormone studies on patient at age 21 months prior to mastectomies Parameter measured
Normal range for age
Total plasma estrogens (ng/dl) Prolactin (ng/ml)
< 2.5 0-20
< 2.0 11.4
FSH (random) (mIU/ml) LH (random) (mIU/ml) T4 (~tg/dl) TSH (mIU/ml) Somatomedin C (U/ml) Progesterone (ng/dl) 17-OH progesterone (ng/dl) DHEA-sulfate (gg/dl) DHEA (ng/dl) Androstenedione (ng/dl) ll-Deoxycortisol (ng/dl) Beta-HCG (mIU/ml) Urine 17-ketosteroids (rag/24 h) Urine 17-hydroxysteroids (rag/24 h) Urine total estrogen (gg/24 h) Urine pregnanetriol (rag/24 h)