Journal of Perinatology (2006) 26, 256–258 r 2006 Nature Publishing Group All rights reserved. 0743-8346/06 $30 www.nature.com/jp PERINATAL/NEONATAL CASE PRESENTATION Neonatal hypertrichosis in an infant of a diabetic mother with congenital hypothyroidism

M Akcakus1, E Koklu2, S Kurtoglu1, S Koklu1, M Keskin1 and D Buyukkayhan2 1Department of Pediatrics, School of Medicine, Erciyes University, Kayseri, Turkey and 2Department of Neonatology, School of Medicine, Erciyes University, Kayseri, Turkey

delivery at 38 weeks of gestation. She was the seventh child of a 35- Hypertrichosis in a newborn girl infant of a diabetic mother with congenital year-old mother and a healthy 40-year-old father. The parents were hypothyroidism is reported. Both neonatal hyperinsulism and increased first-degree relatives. The family’s first five children were healthy. testosterone levels were documented. The hypertrichosis resolved after 3 The sixth child died on the third day after birth of unknown cause. months’ of thyroxine replacement treatment. The possible causal The seventh and eighth pregnancies ended with premature association between hypothyroidism, and hypertrichosis has not been deliveries at 28 and 30th gestational weeks, respectively. During the previously reported in neonatal period. Thyroid function should be current pregnancy, a 100-g 3-h oral glucose tolerance test was evaluated in all newborn babies with hypertrichosis or abnormal performed at 28th gestational week and gestational diabetes was distribution of body hair. diagnosed. Only dietary regulation was initiated and prenatal Journal of Perinatology (2006) 26, 256–258. doi:10.1038/sj.jp.7211461 follow-up and management of the mother was not good. Keywords: congenital hypothyroidism; hypertrichosis; newborn infant; At birth the infant weighed 3600 g (90th percentile), her height testosterone was 53 cm (>90th percentile) and head circumference was 35 cm (75–90th percentile). The baby was icteric and plump with puffy plethoric facies. Fine long hair was detected all over the body (Figure 1). The child was noticed to be excessively hairy Introduction (Figure 2). Congenital hypothyroidism (CH) is a relatively common congenital On admission to our pediatric emergency service, she was disorder occurring in about one of 3000 to one of 4000 live births.1 irritable with focal clonic seizures. Blood glucose, total calcium, As few signs or symptoms are present in the neonatal period, routine magnesium and phosphorus concentrations were 27, 5.8, 0.7 and screening is the only means of detection.2 Hypertrichosis, a rare 4.2 mg/dl, respectively. After 5 ml/kg of 10% glucose as a bolus condition, can be defined as an excessive growth of hair (terminal, injection, a continued glucose infusion of 8 mg/kg/min was vellus or lanugo) in areas of the body that are not predominantly administered. Additional treatment included intravenous injection androgen-dependent, and is independent of age, race or sex.3 of 8 ml of a 10% solution of calcium gluconate at the rate of 1 ml/ Hypothyroidism is usually associated with loss of hair,4,5 however, min and intramuscular injection with 0.2 ml/kg of a 50% solution in older children has been associated with an increased amount of MgSO4 With these therapies, the serum glucose, calcium and of hair.6–8 In addition, neonatal hairy pinna has been reported magnesium concentrations became normal. as pathognomonic sign in infants of diabetic mothers.9 Laboratory findings include hemoglobin 21.2 g/dl, hematocrit We wish to report a newborn girl infant of a diabetic mother 65%, and white blood cell count 22 000/mm3 (60% neutrophil, 40% with CH with significant hypertrichosis that resolved after 3 lymphocytes, 35% normoblast). The reticulocyte count was 1% and months’ replacement treatment with thyroxine. This association the platelet count was 162 000/mm3. The peripheral smear revealed has not been previously reported. normochromic-macrocytic erythrocyte morphology. Blood grouping of mother and baby were both A Rh ( þ ). Total bilirubin Case report was 23.4 mg/dl with a direct component of 1.5 mg/dl. The result of A 3-day-old female infant with seizures was referred to our direct Coombs test was negative. Serum electrolytes, blood urea University Hospital. The baby was born by spontaneous vaginal nitrogen, creatinine, SGOT, SGPT, total protein, albumin and urinalysis were normal. Radiographic examination of the chest Correspondence: Dr E Koklu, Department of Pediatrics, School of Medicine, Erciyes University, 38039 Kayseri, Turkey. E-mail: [email protected] revealed mildly enlarged heart. Echocardiography showed a Received 19 November 2005; revised 10 December 2005; accepted 19 January 2006 hypercontractile, thickened myocardium with septal hypertrophy. Hypertrichosis and CH M Akcakus et al 257

pg/ml (normal range: 0.5 to 2.5), respectively. Sex hormone binding globulin concentration was 1.3 mg/dl (normal range: 1.5 to 6.3 mg/dl). The serum insulin level was 22.6 mU/ml (normal range: 2.0 to 13.0 mU/ml). And 17 a-hydroxyprogesterone, androstenedion, and dehydroepiandrosterone sulfate concentrations were all normal. Ultrasonographic examination of adrenal and ovaries was normal. On follow-up the infant was noted to be lethargic with feeding difficulty, and knee X-ray noted absence of distal femoral epiphysis. Thyroid function tests were performed on the 10th day of life: free T3 0.76 pg/ml (normal range: 2.4 to 5.6 pg/ml), free T4 0.60 (normal range: 0.9 to 2.6 ng/dl) and TSH 55.7 (normal range: 3to18mU/ml). Thyroid volume was measured 1.3 ml in a normal range. Sodium-L-thyroxine (15 mg/kg) was given and the thyroid function tests became normal (free T3 2.37 pg/ml, free T4 1.79 ng/dl, TSH 0.58 mU/ml) within 30 days. Total testosterone, free testosterone, insulin, sex hormone binding globulin levels of infant were normalized around the end of the third month of life (38.00 ng/dl (normal range: 20 to 64 ng/dl), 1.71 pg/ml (normal range: 0.5 to 2.5 pg/ml), 3.1 mU/ml (normal range: 2.0 to 13.0 mU/ml), 4.8 mg/dl (normal range: 1.5 to 6.3 mg/dl), respectively). During 3 months her hypertrichosis resolved progressively.

Discussion Hypertrichosis, defined as an increase in the nonandrogen- modulated hair on the body, may be congenital or acquired, Figure 1 Fine long hair was detected all over the body. localized or generalized.10 Congenital hypertrichosis is a generic term for any excessive hair growth visible on a child at birth. The hair growth can be excessive for a wide variety of reasons and may involve the entire body with a mass of fine long hair, diffuse excess hair, or may be restricted to specific areas. Causes of congenital hypertrichosis vary. It is sometimes a secondary symptom of various syndromes with a genetic inheritance component.11 A characteristic facial appearance in a child with hypertrichosis may lead to the recognition of one of a number of dysmorphic syndromes for example Brachmann-de Lange syndrome, Coffin- Siris syndrome, Rubinstein-Taybi syndrome, Seckel’s syndrome, cerebro-oculofacioskeletal syndrome, Gorlin’s syndrome, Schinzel Giedion midface retraction syndrome or Barber Say syndrome.12 It is unusual to find a cause of hypertrichosis or hirsutism and treatment is often unsatisfactory.13 The causal association between hypothyroidism and hypertrichosis has not been reported in Figure 2 The child was noticed to be excessively hairy. neonatal period, although congenitally hypothyroid infants often have a low hairline. Perloff reported four cases of what he called Double volume exchange transfusion was performed to reduce hirsutism in children, who responded to thyroxine replacement bilirubin to acceptable levels. Cranial ultrasonography was normal. therapy.6 Stern et al.7 reported a 10-year-old girl with Her karyotype was 46, XX. On the seventh day of life, total and free hypertrichosis associated with primary hypothyroidism that resolved testosterone, 168.00 ng/dl (normal range: 20 to 64), and 3.81 by thyroxine therapy. Three children with untreated primary

Journal of Perinatology Hypertrichosis and CH M Akcakus et al 258 hypothyroidism were reported by Nishi et al.8 have pituitary disturbances of thyroid function we suggest that full assessment of hyperplasia, hypertrichosis and blunted growth hormone (GH) thyroid function be carried out in all newborn babies with secretion. These abnormalities disappeared and improved after hypertrichosis or abnormal distribution of body hair. thyroid hormone therapy. The pathophysiology of this relationship is unclear. Bilowus 14 et al. reported a newborn with female pseudohermaphroditism References (profound masculinization of the external genitalia and preservation of the internal female genitalia). During pregnancy 1 Fisher DA. Second International Conference on Neonatal Thyroid Screening: progressive hirsutism was noted in the mother, and polycystic progress report. J Pediatr 1983; 102: 653–654. 2 Stephen L. Disorders of the thyroid gland. In: Behrman RE, Kliegman MR, ovaries were found at cesarean section. The serum testosterone Jenson HB (eds). Nelson Text Book of Pediatrics. W.B. Saundres Co: level in the cord blood was elevated markedly (1232 ng/dl). After Philadelphia, 2004, pp 1870–1879. birth the serum testosterone levels of the mother and newborn 3 Beighton P. Congenital hypertrichosis lanuginosa. Arch Dermatol 1970; decreased dramatically. They speculated that the polycystic ovaries 101: 669–672. were the source of the excessive androgen secretion that caused 4 Puavilai S, Puavilai G, Charuwichitratana S, Sakuntabhai A, Sriprachya- maternal and fetal masculinization during the pregnancy. There Anunt S. Prevalence of thyroid diseases in patients with alopecia areata. was no polycystic ovaries and elevated serum testosterone level in Int J Dermatol. 1994; 33: 632–633. our infant’s mother. 5 Lutz G, Biersack HJ, Bauer R, Kreysel HW. Value of pathologic thyroid gland We followed up an infant of diabetic mother. On admission we findings in alopecia areata. Z Hautkr 1987; 62: 1253–1261. detected hypertrichosis. In our baby, CH and additionally elevated 6 Perloff WH. Hirsutism; a manifestation of juvenile hypothyroidism. JAm insulin, free and total testosterone levels were detected. Stimulation Med Assoc 1955; 157: 651. of the growth of hair via adrenal androgens by thyroid stimulating 7 Stern SR, Kelnar CJ. Hypertrichosis due to primary hypothyroidism. Arch Dis Child 1985; 60: 763–766. hormone may be the pathophysiological mechanism in our 15 8 Nishi Y, Hamamoto K, Kajiyama M, Fujita A, Kawamura I, Kagawa Y et al. patient. Shoupe et al. reported that serum testosterone showed a Pituitary enlargement, hypertrichosis and blunted growth hormone secretion positive correlation with insulin resistance, and sex hormone in primary hypothyroidism. Acta Paediatr Scand 1989; 78: 136–140. binding globulin showed a negative correlation. Our patient had 9 Rafaat M. Hypertrichosis pinnae in babies of diabetic mothers. Pediatrics three hormones, two of which increased (the serum levels of 1981; 68: 745–746. insulin and testosterone), and one of which decreased (the serum 10 Garcia-Cruz D, Figuera LE, Cantu JM. Inherited hypertrichoses. Clin Genet level sex hormone binding globulin). Hypertrichosis might also be 2002; 61: 321–329. related to free testosterone on account of hyperinsulinism in our 11 Baumeister FA, Schwarz HP, Stengel-Rutkowski S. Childhood hypertrichosis: patient. The fact that the hypertrichosis resolved after 3 months’ diagnosis and management. Arch Dis Child 1995; 72: 457–459. replacement treatment with thyroxine supports the suggestion that 12 Giannetti L, Consolo U, Bambini F. Tooth and oral mucosa hereditary the hair growth in this case was related to the interrelationship of anomalies in complex syndromes characterized by hyper- or hypotrichosis. thyroid function and androgen levels augmented by the Minerva Stomatol 2003; 52: 25–30. 13 Barth JH, Wilkinson JD, Dawber RP. Prepubertal hypertrichosis: normal or hyperinsulinism. abnormal? Arch Dis Child 1988; 63: 666–668. In conclusion, we detected hypertrichosis concomitant with CH 14 Bilowus M, Abbassi V, Gibbons MD. Female pseudohermaphroditism in a in an infant of diabetic mother. Given the fact that IDM neonates neonate born to a mother with polycystic ovarian disease. J Urol 1986; 136: have hairy pinna, the generalized hypertrichosis may be part of the 1098–1100. spectrum of the effect of the hyperinsulin state. However, as 15 Shoupe D, Lobo RA. The influence of androgens on insulin resistance. Fertil increased hair growth has been reported in older children with Steril 1984; 41: 385–388.

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