*The Warren Alpert Medical School of Brown University, Providence, RI†Division of Pediatric Gastroenterology‡Division of Pediatric Endocrinology, University of Massachusetts Medical School, Worcester, MA.
Checking for direct PDF access through Ovid
Individuals with Down syndrome (DS) have an increased prevalence of autoimmune disorders, with reported rates of 3% to 54% for thyroid disorders and 5% to 20% for celiac disease (CD) (1–3). CD can present with extraintestinal manifestations such as poor growth, osteoporosis, neuropsychiatric manifestations, delayed puberty, infertility, and menstrual irregularities (4,5). We describe an adolescent girl with DS and Graves disease presenting with polymenorrhea as the initial symptom of CD.CASE PRESENTATIONA 7-year-old girl with DS presented with a 2-month history of weight loss, restlessness, and difficulty sleeping. She weighed 19.2 kg (10th percentile) and had a height of 114.6 cm (5th percentile), using the National Center for Health Statistics growth charts for girls without DS, heart rate 136, and blood pressure 108/50. She had mild exophthalmos, a hyperdynamic precordium, and a nongoitrous thyroid gland. Thyroid function tests (TFTs) confirmed hyperthyroidism with an elevated T4 13.2 μg/dL (normal 6.4–10.9 μg/dL) and T3 320 ng/dL (normal 94–241 ng/dL), suppressed thyroid-stimulating hormone (TSH) <0.03 μIU/mL (normal 0.35–5.5 μIU/mL), and positive antithyroid peroxidase, antithyroglobulin, and thyroid-stimulating immunoglobulins (Table 1). She was started on methimazole 7.5 mg twice daily. She was lost to follow-up and returned at age 8 with weight gain, fatigue, and TFT consistent with profound hypothyroidism (elevated TSH 192 μIU/mL and low T3 81 ng/dL and T4 4.0 μg/dL). TFT normalized with levothyroxine 100 μg/day (3.2 μg · kg−1 · day−1). At age 10, routine CD screening revealed a normal serum immunoglobulin A (IgA) 78 mg/dL, elevated endomysial antibody (EMA) 1:80 (normal <1:5), and tissue transglutaminase (TG2) IgA antibody 141 units (normal <20 units). A pediatric gastroenterologist recommended deferring small intestinal biopsy until symptoms developed. Menarche occurred at age 12 with regular monthly menstrual periods. At age 13, she was euthyroid on levothyroxine 125 μg/day (2.7 μg · kg−1 · day−1) and started to menstruate bimonthly for 5 to 6 days. She had a mildly elevated serum prolactin 47 ng/dL (normal 3–29 ng/dL), normal TSH, gonadotropins, testosterone, Von Willebrand Disease screen, hemoglobin, and red blood cell indices. A hypothalamic-pituitary magnetic resonance imaging was normal. A repeat fasting morning prolactin was normal at 15 ng/dL.An oral contraceptive pill (OCP) was started, but breakthrough bleeding occurred whenever OCP doses were taken >24 hours apart. Within 4 months, she developed abdominal pain, intermittent diarrhea, and aggressive behavior. Subsequent endoscopy revealed villous blunting, crypt hyperplasia, increased intraepithelial lymphocytes, and inflammatory changes consistent with CD. Six months after instituting a gluten-free diet, she no longer had breakthrough bleeding when >24 hours lapsed between OCP doses. By age 15, she fully transitioned to a gluten-free diet and had a negative TG2. The OCP was discontinued and menses remained normal for >3 years. Her levothyroxine requirement decreased to 100 μg/day (1.8 μg · kg−1 · day−1).DISCUSSIONMenstrual disorders and infertility have been reported in individuals with CD. Zajadacz et al (6) described a 17-year-old girl whose polymenorrhea resolved on a gluten-free diet. Malabsorption from CD can cause nutritional deficiency of essential elements, such as zinc, selenium, iron, and folate, leading to reproductive dysfunction (4). Serum prolactin levels correlate with the degree of mucosal atrophy (7); therefore, hyperprolactinemia is cited as a possible cause of impotence and decreased libido in individuals with CD (4). Because our patient's prolactin was normal, her polymenorrhea may have been as a result of the effects of a chronic illness on menstruation.Even in populations with a known increased risk for CD, routine serological screening is controversial. The 2.