Retrospective evaluation of the patients who were referred to our clinic for congenital hypothyroidism anddiagnosed as congenital hypothyroidism in our clinic

Introduction-Aim: Congenital hypothyroidism (CH) is one of the most common endocrinological problems encountered in the neonatal period and may cause permanent mental retardation if not diagnosed and treated early. In this study it was aimed to document the first regional data by determining the etiological distribution, anthropometric characteristics, age at diagnosis and start of treatment, symptoms at admission, the course of thyroid functions during diagnosis and follow-up, optimal oral sodium-levothyroxine (LT4) dose level and duration that provides euthyroidism according to age groups, evaluating the effects of initial and follow-up LT4 doses on clinical and anthropometric parameters, comparing permanent and transient CH and primary CH subgroups, evaluating the effects of TRH (thyrotropin releasing hormone) test in diagnosis of patients who term and preterm cases followed with the diagnosis of CH. Material-Method: This study was done by retrospectively examining the files of 956 patients who referred to the Karadeniz Technical University Medical Faculty Pediatric Endocrinology Department with a preliminary diagnosis of CH and treated with the diagnosis of CH in our clinic and who were born between 2006-2018. A total of 669 term and preterm cases diagnosed with primary CH were included in the study. Anthropometric, demographic, clinical, laboratory findings and imaging methods of these cases were evaluated. Results: Of our 575 cases with term-CH, 72% had permanent CH and 28% had transient CH. We had 94 cases of preterm-CH and 64% of them were permanent and 36% were transient CH. Thyroid dysgenesis was present in 21% of our 412 cases with term-permanent CH. Of those with dysgenesis, 63% had thyroid hypoplasia, 4% had hemiagenesis, 17% had thyroid ectopia (14 patients had sublingual and one patient had lingual ectopic thyroid tissue), and 16% had thyroid agenesis. The remaining cases of permanent CH (n=326, 79%) were considered as dyshormonogenesis. In gender-related comparisons, the rate of girls (63%) was significantly higher than boys (37%) only in the term thyroid dysgenesis group (p <0.005). Thyroid dysgenesis was found in 11 (12%) of our cases with preterm permanent CH and 9 of them had thyroid hypoplasia, 1 of them had agenesis and 1 of them had hemiagenesis. The most common reason for admission in our term cases was TSH elevation in the heel blood, TSH elevation detected later in routine control, prolonged jaundice, and constipation. The rate of consanguinity in the parents of our cases with term-CH was 35% (65% in the group with permanent and 35% in the group with transient CH), and the rate of consanguinity was significantly higher in the permanent group (p <0.05). Of the cases with term-permanent CH, whose parents were consanguineous, 76% had dyshormonogenesis and 24% had thyroid dysgenesis (p <0.05). The median age of our cases with term CH was 26 days and 27 days in permanent CH; 22 days in thyroid dysgenesis, 30 days in dyshormonogenesis and 25 days in transient CH (p >0.05). When the diagnosis ages of our cases with permanent-transient CH and dysgenesis-dyshormonogenesis were compared, there was no significant difference; age at diagnosis of our cases in the thyroid agenesis group; was significantly younger than our cases with dyshormonogenesis, hypoplasia, and transient CH (p <0.05). The median age of diagnosis in our cases with term-CH was 26 days, and 27 days in permanent CH; thyroid dysgenesis was 22 days, dyshormonogenesis was 30 days, and transient CH was 25 days (p >0.05). Age at diagnosis of our cases with permanent-transient CH and dysgenesis-dyshormonogenesis was not different (p >0.05). Our patients in the thyroid agenesis group were younger at diagnosis than those with dyshormonogenesis, hypoplasia, and transient CH (p <0.05). While the median age at diagnosis of our cases with preterm-permanent CH was 35 days, it was 41 days in our cases with preterm-transient CH (p >0.05). When the term-permanent with preterm-permanent and term-transient with preterm-transient groups are compared the age at diagnosis of our preterm cases was higher than that of our term cases (p <0.05). Weight, height and head circumference SDS of our cases with term and preterm CH were within normal limits and no difference was found between the permanent and transient groups (p >0.05). At the time of diagnosis; in our cases with term and preterm-permanent CH, while the fT4 level was significantly lower than the group with transient CH, the TSH level was significantly higher (p <0.05). Thyroglobulin (Tg) values of our patients with term-CH with thyroid dysgenesis were lower than those with dyshormonogenesis (p <0.05). TRH stimulation test was performed in 21% of our cases with term-CH. When the TRH test results of the permanent-transient and thyroid dysgenesis-dyshormonogenesis groups with term-CH were compared, no significant difference was found (p >0.05). Thyroid ultrasonography (US) volumes of our cases with term-transient CH were within the normal range according to the age group and thyroid volumes were significantly higher than the permanent group (p = 0.005). In patients with term-permanent and preterm-permanent CH, excluding initial doses (4.49±3.64 mcg/kg/day, 3.61±3.43 mcg/kg/day, respectively), the LT4 doses determined in all controls were higher than in the transient group (p <0.05). In our cases with term-dysgenesis, there was a negative correlation between the initial LT4 dose and the age at diagnosis, serum fT4 level at diagnosis, and thyroid volumes (p <0.05) and was found positive correlation with serum TSH levels at diagnosis, birth weight, birth weight-SDS, weight and weight-SDS in all controls (p <0.05). In the term-dyshormonogenesis and transient group at diagnosis and in all controls; there was no significant correlation between LT4 doses and weight-SDS and height-SDS (p >0.05). Despite appropriate dose treatment, proportion of those who were found to have biochemical hyperthyroidism in term CH cases at the 15th day follow-up after the initiation of treatment was 29%. Conclusion: This study is the first to document the data of our region in patients with CH. Accurate classification of CH is important to prevent unnecessary long-term drug use. At the time of diagnosis serum fT4, TSH levels, thyroid ultrasound and scintigraphy results, LT4 doses needed during follow-up are important in distinguishing permanent-transient CH. In the differential diagnosis of thyroid dysgenesis and dyshormonogenesis, in addition to fT4, TSH, Tg, LT4 dose at the time of diagnosis, serum TSH level and LT4 dose levels can be guiding during the follow-up period. In order to prevent iatrogenic hyperthyroidism, at the time of diagnosis and in the follow-up, the feasibility of euthyroidism with moderate LT4 doses has been demonstrated by clinical and laboratory evaluation of each patient with CH. Key words: Primary congenital hypothyroidism, permanent congenital hypothyroidism, transient congenital hypothyroidism, etiology, sodium-levothyroxine.