154 Available online at www.medicinescience.org CASE REPORT Medicine Science 2017;6(1):154‐6 Two siblings with familial subclinical hyperthyroidism with unknown etiology Elif Ozsu 1 , Gul Yesiltepe Mutlu 2 , Filiz Mine Cizmecioglu 3 , Rifat Bircan 4 , Sukru Hatun 2 ¹Department of Pediatrics, Samsun Obstetrics and Children Hospital Samsun, Turkey ²Koç University, School of Medicine, department of Pediatric Endocrinology İstanbul,Turkey, ³ Kocaeli University School of Medicine, Department of Pediatric Endocrinology, Kocaeli, Turkey 4 Namık Kemal University College of Science, Department of Molecular Biology and Genetic Tekirdağ, Turkey Received 18 August 2016; Accepted 18 October 2016 Available online 26.10.2016 with doi: 10.5455/medscience.2016.05.8537 Abstract Subclinical hyperthyroidism is defined as low or undetectable concentration of serum thyrotrophin (TSH) with normal free triiodothyronine (FT3) and free thyroxine (FT4) levels. 1) . Familial subclinical hyperthyroidism is a rare entity. Activating mutations of the TSH receptor (TSH-R) gene cause genetic hyperthyroidism. Here we present a family with more than one affected individual. All family members were investigated for TSH-R mutation. No mutation was detected, while a A459 polymorphism was found in one of the cases and three other siblings. Despite the clinical and biochemical findings suggesting a TSH-R mutation, a reasonable cause could not be detected. Epigenetic and environmental modifiers, including iodine intake, should be considered in families with mutation negative, familial non auto-immune hyperthyroidism (FNAH). Keywords: Familial, subclinical hyperthyroidism, genetics Introduction Subclinical hyperthyroidism is a condition describing the low TSH levels with normal thyroid hormone levels [1-3]. The prevalence of subclinical hyperthyroidism is 0.5% in children and 15% in elderly [4]. The definition is based on laboratory findings. It can be transient or permanent. Although serum thyroid hormones are in the normal reference ranges, they might be high for the individual. Low or undetectable serum TSH levels suggest a mild tissue hyperthyroidism. Heart and bone are the most common affected organs. Although it is rare, TSH-R mutations must be considered when cases are familial and non-autoimmune. TSH-R activating mutation is a rare entity leading to familial hyperthyroidism. Activating mutations in this receptor can cause not only familial non- autoimmune hyperthyroidism and toxic adenoma, but also severe hyperthyroidism requiring surgery in neonatal period [3]. Beside these severe clinical presentations, TSH- R mutations can also be the cause of subclinical hyperthyroidism. In this study it was aimed to present two siblings with subclinical hyperthyroidism. Despite the presence of clinical findings of hyperthyroidism and goiter, no mutation was detected in TSH-R. Case-1: An 11-year-old male patient admitted to our clinic with the complaints of a swelling on the anterior neck, palpitation and nervousness. The swelling occurred nearly 5 years ago. He had previously been evaluated by a pediatric cardiologist because of his tachycardia and no pathologic finding had been determined. The patient was born from consanguineous parents, without any complications following the pregnancy and had no health problems. His mother, sister (Case-2), aunt and grandmother were suffering from goiter. The physical examination revealed normal anthropometric measurements and pubertal stage was Tanner Stage-3. The heart rate was 100/min, goiter was a grade-2 and exophthalmos was not observed. Thyroid function tests were indicating subclinical hyperthyroidism. Serum FT3 level was 4.92 pg/ml (N: 2-4), FT4 was 1.23 ng/ml (N:0.8- 2.3) and TSH was 0.199 uIU/ml (N: 0.5-4.8). Thyroid auto-antibodies and thyroid receptor anti-body (TRAB) were negative. Thyroid ultrasound imaging revealed a total thyroid volume of 34.73 ml, which is increased for his age. Graves ophthalmopathy was not detected in ophthalmologic assessment. No treatment was given to the patient. In the follow-up period an increase was observed in TSH level of the patient. At the end of one year hormone levels were as follows; TSH: 0.476 uIU/ml, FT4:1.22 ng/ml, FT3:4.75 pg/ml. Case 2: A 12-year-old female (sister of case 1) was admitted to our clinic with the complaint of nervousness *Corresponding Author: Elif Ozsu, Department of Pediatrics, Samsun Children’s and Obstetrics Hospital, 55000/İlkadım, Samsun, Turkey E-mail: elozdr@gmail.com Tel: +905054547589 Medicine Science International Medical Journal