Initial Dose Of Levothyroxine Research Articles

Higher initial levothyroxine doses and very early treatment start may lead to better cognitive outcomes in children with congenital hypothyroidism.

This study aimed to assess the cognitive development of individuals with congenital hypothyroidism. Using hospital records, we identified 180 patients with congenital hypothyroidism born between 1980 and 2018 in Turku and Kuopio University Hospital catchment areas. Cognitive development was evaluated in 22 adults (7 males and 15 females) and 20 children (8 males and 12 females) using age-specific Wechsler Intelligence Scales. Full-scale IQ (FSIQ) and the four indices were compared to standardisation samples. Simple linear regression was used to test whether treatment-related variables predicted FSIQ. FSIQ and its four indices differed significantly from the standardisation sample in adults with congenital hypothyroidism (FSIQ 87.64, SD 13.70, p < 0.001) but not in children (FSIQ 97.90, SD 15.12). Adults had received a lower initial levothyroxine dose than children (8.1 mg/kg, 95% CI 7.2-9.0 vs. 10.2 mg/kg 9.7-10.7, p < 0.001), and their treatment was initiated later (4.8 days, 95% CI 4.0-5.6 vs. 3.6 days, 2.9-4.2, p = 0.018). Adults with congenital hypothyroidism had a significantly lower FSIQ compared to the population standard, while children's FSIQ did not differ. Our findings suggest that a higher initial levothyroxine dose together with very early treatment start may lead to better cognitive outcomes.

Association between immunotherapy and hypothyroidism in a Latin American population: An analytical study of cases and controls from 2019 to 2023.

e24135 Background: In different clinical studies worldwide, the use of immunotherapy has been related to the development of hypothyroidism; However, there is no data on this association in Latin American population. Methods: An analytical observational case-control study conducted in a 3-year follow-up cohort at an oncology institute of cancer patients treated with immunotherapy who developed hypothyroidism in Colombia. The aim of the study was to evaluate the development of new hypothyroidism cases after immunotherapy. Cases and controls were randomized in a ratio of 1:3. A multivariate analysis was performed to identify risk factors for developing hypothyroidism and an inferential analysis was performed over time between levothyroxine dose vs TSH levels. Results: 112 patients were included, 57% men and 42% women with a mean age of 63 years. 21% developed hypothyroidism after immunotherapy, while 12% presented with thyrotoxicosis as first alteration and 9% with central hypothyroidism. During the first semester 54% of patients developed hypothyroidism, 84% in the first year and 100% at 2 years . Pembrolizumab and nivolumab were used most frequently with 58% and 29% respectively developing hypothyroidism. The most common underlying pathology was lung cancer with 33% and kidney at 38%. In the multivariate analysis, female were found as a protective factor compared to men (OR:0.10 CI: 0.05-0.63 95% p = 0.02), and the use of pembrolizumab was associated with a higher risk trend, but this result was not statistically significant (OR:2.49 CI: 0.5-2.7 p = 0.2). The average initial dose of levothyroxine was 1.4 mcg/kg, at 3 months of 1.2 mcg/kg and 6 months of 0.82 mcg/kg. Average TSH levels at diagnosis were 23.3, uUI/ml, achieving target values for 100% of patients after 9 months of substitution. After two years of follow-up, patients continued with an average dose of levothyroxine of 0.8 mcg/kg. Conclusions: The incidence of hypothyroidism in our population is similar to that reported worldwide. Male patients who start immunotherapy should have their thyroid profile monitored strictly given that they present a higher risk. Additionally, monthly monitoring of the thyroid profile should be done within the first year. In Latin American population, more conservative initial doses of levothyroxine (1.0 - 1.1 mcg/kg) could be used and titrated.

Efficacy of a levothyroxine dosage regimen based on serum thyrotropin level, for primary hypothyroidism. An open label dose finding study.

There are no guidelines on individualized initial levothyroxine dosage in primary hypothyroidism. This prospective observational study was done to assess whether a predetermined dose of levothyroxine based on Thyroid Stimulating Hormone (TSH) levels would be able to make the patient euthyroid during a period of six weeks and to find other factors which influence the levothyroxine requirement. Newly diagnosed patients with primary hypothyroidism or those patients who were not on levothyroxine therapy were divided into TSH-based groups-Group 1, 5-9.99, Group 2, 10-29.99, Group 3, 30-99.99 and Group 4, >100 μIU/ml and treated with an initial levothyroxine dose of 25,50,75 and100 μg/day for next six weeks. Factors correlating with levothyroxine requirement were determined. Of the 171 patients who were included 142 completed the study, 34,46,28 and 34 patients were included in groups 1 to 4, respectively. Normalization of TSH with the above criteria was achieved in 111 (78.7%) out of 141 patients, and 91%, 67%, 75%, and 82% respectively in the 4 groups. Among adequately replaced patients pre-treatment TSH level (r = 0.81), T4 level (r = 0.61), and body weight (r = 0.19) correlated with the levothyroxine requirement. Based on these factors predicted initial dose (μg/day) was found to be 0.54 (Body Weight [Kg]) +0.47 (TSH [μIU/m]) - 1.4 (Total T4 [μg/dl]) +17.79 or 0.27 (Body Weight) +0.553 (TSH) +21. Serum thyrotropin-based categorization for initial levothyroxine dose leads to euthyroidism in nearly four of five patients with primary hypothyroidism. The dose required for adequate replacement of levothyroxine has correlation with pre-treatment serum TSH levels serum thyroxine levels and body weight.

Effect of initial levothyroxine dose on neurodevelopmental and growth outcomes in children with congenital hypothyroidism

Effect of initial levothyroxine dose on neurodevelopmental and growth outcomes in children with congenital hypothyroidism

Cognitive performance of preschoolers with Congenital Hypothyroidism enrolled in a follow-up program

To evaluate the cognitive performance of preschool children with CH incorporated into a follow- up program. Prospective study of 93 patients with a confirmed diagnosis of CH. Intelligence quotient (IQ) was assessed using the Wechsler Preschool and Primary Intelligence Scale (WPPSI) at 4 and 5 years, and the WISC-R at 6 years of age. Full-Scale IQ (FSIQ), Verbal IQ (VIQ), and Performance IQ (PIQ) scores were analyzed. The study sample was 80 children. The average age at starting hormonal treatment was 42 ± 18 days; treatment started early in 25 patients (24 ± 6 days) and late in 55 patients (50 ± 16 days). The mean initial dose of Levothyroxine was 13.5 ± 1.5µg/kg/day. Children with athyrosis and late initiation of treatment had lower scores on the VIQ (85 ± 14), the PIQ (89 ± 12), and the FSIQ (86 ± 13) scales at 4 years of age, in comparison with patients with early initiation of treatment. These patients scored within the cut-off point for the normal IQ classification (90-109 points). IQ comparison at 6 years of age revealed differences up to 14 points in the PIQ and 11 points in the FSIQ between children with athyrosis and early initiation of treatment, with and without regular attendance to the follow-up program. These results support the importance of early initiation of treatment and the incorporation of children in follow-up programs and early stimulation. The etiology of hypothyroidism and the age at initiation of treatment were the most significant factors that affected cognitive performance.

Effect of initial levothyroxine dose on neurodevelopmental and growth outcomes in children with congenital hypothyroidism

ObjectivesWe designed a multicentre open prospective randomized trial to evaluate the risk-benefit profile of two different initial treatment schemes with levothyroxine (L-T4), 10-12.5 μg/kg/day vs 12.6-15 μg/kg/day, on growth and neurodevelopmental outcomes in children with congenital hypothyroidism (CH) detected by neonatal screening to identify the best range dose to achieve optimal neurocognitive development.Design, patients and methodsChildren detected by neonatal screening were randomly assigned to receive an initial L-T4 dose of 10-12.5 μg/kg/day (Low) or 12.6-15 μg/kg/day (High). All patients underwent periodical clinical examination with measurement of growth parameters and measurement of TSH and FT4. Neurocognitive development was evaluated at the age of 24 months using Griffiths Mental Development Scales (GMDS) and cognitive and behavioral assessment was performed at 48 months of age using Wechsler Preschool and Primary scale of Intelligence (WIPPSI-III). The study was registered with clinicaltrials.gov (NCT05371262).ResultsTreatment schemes below or above 12.5 μg/kg/day were both associated with rapid normalization of TSH and thyroid hormone levels in most patients with no differences in the risk of over- and under-treatment episodes in the first months of life. Growth parameters were normal and comparable between the two groups. Developmental quotients at 24 months of age were normal in both groups (Low 100.6 ± 15.5 vs High 96.9 ± 16.6). Likewise, at 4 years of age IQ and subtest scores were comparable between patients from Low and High (Total IQ 104.2 ± 11.4 vs 101.0 ± 20.3, Verbal IQ 103.9 ± 11.5 vs 98.7 ± 15.1, Performance IQ 105.3 ± 10.4 vs 100.3 ± 19.8). 6/45 CH patients (13.3%) showed a total IQ below 85 (73.7 ± 5.9) regardless of age at diagnosis, L-T4 starting dose, time of FT4 and TSH normalization and episodes of over and undertreatment. Worse socioeconomic status and delayed bone age at diagnosis were the only predictors of an increased risk of having suboptimal IQ at 24 and IQ at 48 months.ConclusionsOur results indicate that initial treatment with L-T4, 10-12.5 μg/kg/day vs 12.6-15 μg/kg/day, are both associated with normal growth and neurodevelopmental outcomes in children with CH detected by neonatal screening. Further studies with a long-term follow-up on a larger number of patients are needed to confirm these results.Clinical trial registration https://clinicaltrials.gov/ct2/show/NCT05371262?term=NCT05371262&draw=2&rank=1 identifer NCT05371262.

BMI Helps to Calculate the Initial Levothyroxine Dose After Total Thyroidectomy

Abstract After total thyroidectomy, an initial dose of levothyroxine is often prescribed based on the patient’s body weight (1.6 mcg / kg / day), regardless of body mass index (BMI). The current literature required that hormone maintenance therapy (THR) in obese patients differs from non-obese patients. Review of the clinical processes of patients with papillary carcinoma followed in the multidisciplinary consultation of Endocrine Pathology at CHVNG / E followed a total thyroidectomy from 2015 to 2017. Patients who achieved euthyroidism with THR were included in the analysis and divided according with BMI. Statistical analysis was performed using SPSS version 25.0. A value of p &amp;lt;0.05 was considered statistically significant. The sample included 82 patients, 90.2% (n = 74) female and 9.8% (n = 8) male, with an average age of 53.02 ± 14.27 years. Of the female gender, 52.4% (n = 43) were in menopause. In the postoperative period, 14 patients (17.1%) had a normal BMI, 46 (50%) were overweight and 22 (32.9%) were obese. The average follow-up time was 75.3 months (32-128). A dose of LT4 required to achieve euthyroidism based on the BMI categories mentioned above was 1.70; 1.54 and 1.49 mcg / kg. Patients with a higher BMI needed a higher dose of LT4 to achieve euthyroidism (p &amp;lt;0.05), but the dose was lower in relation to weight (mcg / kg) (p &amp;lt;0.05). There were no differences related to age and need for L-T4 suplementation (p&amp;gt; 0.05). Our study shows that de calculation of the initial levothyroxine dose should also take into account BMI. Overweight and obese individuals should receive a lower dose than that used in normal weight patients, which goes against what has been described in the literature. The weight-based formula, unlike BMI, does not account for the volume of distribution of L-T4 well. Other methods, which include, for example, ideal body weight instead of actual weight, are being developed to help choose the starting levothyroxine dose.

Socioeconomic aspects are crucial to better intellectual outcome in early-treated adolescents with congenital hypothyroidism

ABSTRACT Congenital hypothyroidism (CH) is an important cause of preventable intellectual disability. Implementation of CH neonatal screening programs leading to early treatment has improved cognitive outcome. However, more subtle cognitive impairments are still reported, and there is lack of clarity regarding factors that impact long-term cognitive outcome. Research to better understand these factors can lead to further improvements in the cognitive prognosis for these patients. The current study aimed to evaluate the cognitive performance of adolescents who were early-treated for primary permanent CH and possible associated variables. Neurocognitive evaluation was carried out in 66 adolescents, 11 to 16 years old: 34 with CH and 29 paired controls. Intellectual quotient (IQ), verbal fluency, processing speed, executive functions, and memory were investigated. CH patients and control subjects were comparable regarding sex, age, schooling, family’s socioeconomic status and caregiver’s educational level. Both groups presented not only similar IQ scores but also equivalent performances regarding Perceptual Reasoning, Working Memory and Processing Speed index scores. Patients presenting different CH etiologies (dysgenesis and dyshormonogenesis) showed similar cognitive performance. Socioeconomic aspects along with the initial levothyroxine dose were the main variables to positively influence the cognitive performance, the family’s socioeconomic status having the strongest association with patients’ cognitive skills.

Pubertal development and adult height in patients with congenital hypothyroidism detected by neonatal screening in southern Brazil.

Objectives Adequate treatment of congenital hypothyroidism (CH) is required for normal growth and sexual development. To evaluate pubertal development in patients with permanent CH detected by a statewide Neonatal Screening Program of Paraná and, secondly, to evaluate adult height (AH) in a subgroup of patients. Methods Clinical, laboratory, and auxological data obtained from medical records of 174 patients (123 girls). Results Median chronological age (CA) at treatment initiation was 24days, and mean initial levothyroxine dose was 11.7±1.9μg/kg/day; mean CA at puberty onset was 11.5±1.3 years (boys) and 9.7±1.2 years (girls); mean CA in girls who underwent menarche (n=81) was 12.1±1.1 years. Thyroid-stimulating hormone (TSH) values above the normal range were observed in 36.4% of the boys and 32.7% of the girls on puberty onset, and in 44.6% around menarche. Among 15 boys and 66 girls who had reached the AH, the median height z-score value was significantly greater than the target height (TH) z-score value in boys (p=0.01) and in girls (p<0.001). Boys with normal TSH values at puberty onset had greater mean AH z-score compared with boys with TSH values above the normal range (p=0.04). Conclusions In this group, pubertal development in girls with CH was not different from that reported in healthy girls in the general Brazilian population. Boys with higher TSH at puberty onset may have an increased risk of not reaching their potential height compared with those with normal TSH during this period. In a subgroup who attained AH, the median AH z-score was greater than the median TH z-score.

Comparison of the Efficacy of Levothyroxine Suppression Dose Computed Based on Actual Body Weight vs. Lean Body Mass among Differentiated Thyroid Cancer Patients: A Randomized Controlled Trial

BackgroundThe dose of levothyroxine (LT4) after total thyroidectomy is usually computed based on actual body weight. However, metabolism through deiodination of thyroid hormones usually occur in the lean body compartment. An optimal dose to reduce delay in achieving target levels is essential to improve quality of life, reduce risk factors and cost.ObjectiveComparison of the efficacy of two methods of computation for the initial levothyroxine dose in patients with differentiated thyroid cancer based on actual body weight vs. lean body mass in achieving thyroid-stimulating hormone (TSH) goals.MethodologyRandomized, single-center, 12-week open label controlled trial among adult patients with differentiated thyroid cancer post total thyroidectomy who underwent radioactive therapy at St. Luke’s Medical Center Quezon City from July-December 2018. Participants were divided into 2 groups - Actual Body Weight (ABW) and Lean Body Mass (LBM). Levothyroxine dose was computed based on ABW vs. LBM and TSH determined at 6th and 12th weeks after.Results52 participants (ABW n=26; LBM n=26) were included. ABW group had significantly higher mean LT4 dosage (2.2 mcg/kg) compared to the LBM group (1.4 mcg/kg) (p-value<0.001). ABW group had lower TSH levels at 6th week (5.7 uIU/mL) than LBM group (18.4 uIU/mL) but the difference was not significant. (p-value=0.064). A significantly lower TSH level was observed at week 12 in the ABW group (1.6 uIU/mL) compared to the LBM group (3.8 uIU/mL) (p-value=0.010). However, both methods were not associated with achievement of TSH goal at 6th and 12th week (p-value=0.512 and 0.780, respectively).ConclusionAmong patients with differentiated thyroid cancer who underwent 1st time RAI therapy, ABW method of computation for LT4 dosage is better compared to the LBM method due to the lower TSH trend seen at 6th week and statistically significantly lower mean TSH at week 12, although, both method of computations did not achieve target TSH levels at the 6th nor 12th week.

Mifepristone Increases Thyroid Hormone Requirements in Patients With Central Hypothyroidism: A Multicenter Study

PurposeMifepristone is a glucocorticoid and progesterone receptor blocker that can be used for patients with hyperglycemia and Cushing syndrome in whom surgery failed to achieve remission or who were ineligible for surgery. We report a case series of patients with Cushing disease (CD) and central hypothyroidism that presented with increased levothyroxine requirements during mifepristone therapy.MethodsRetrospective longitudinal case series of patients with CD and central hypothyroidism treated with mifepristone in a retrospective database at four pituitary centers in the United States.ResultsFive patients with CD were found, all women, median age 50 (interquartile range 47 to 64.5). They received mifepristone because no adequate response or intolerance to other drugs was observed. Mifepristone initiation was associated with a decrease in free thyroxine levels, mandating a dose increase of a median 1.83 (1.71 to 3.5) times the initial dose of levothyroxine to achieve normal levels. Weight loss was seen in four of five patients, ranging from 3.2 to 42.6 kg in up to 54 months of follow-up.ConclusionsAlthough the mechanism behind the decrease in thyroid hormone level is unknown, intestinal malabsorption, decreased residual thyroid function and increased inactivation of T4 via deiodinases are all potential causes. Whereas therapies for hypercortisolism aim to decrease features of hypercortisolemia such as weight gain and depression, hypothyroidism can hamper these goals. This case series raises awareness on the importance of assessment of thyroid status in patients receiving mifepristone to optimize clinical outcomes.

Developmental Screening of Children with Congenital Hypothyroidism Using Ages and Stages Questionnaires Test.

Congenital hypothyroidism (CH) is one of the most common causes of mental retardation in children. We investigated the developmental status of children with CH screened by Ages & Stages Questionnaires (ASQ) measurement scores. In this retrospective study, neurodevelopmental status of 78 children diagnosed with CH followed up at the Outpatient Pediatric Endocrinology Clinic of Besat Hospital, Hamadan, Iran from May 2006 to Mar 2013, was evaluated by ASQ method. Data on age, sex, birth weight, birth length, head circumference, residency location, parental education level, primary venous TSH and T4 levels, age at diagnosis, treatment start age and initial levothyroxine dosage were extracted from medical records. Data were analyzed using statistical software SPSS. P-value less than 0.05 was considered statistically significant. Of the 78 patients, 34 (43.6%) were female, 32 (41%) had developmental disorder, and 56 (71.8%) were living in urban areas. Types of developmental impairments included: global motor delay in 13 (40.6%) patients, problem-solving in 11 (34.3%), impaired communication skills in 5 (15.6%), impaired fine motor skills in 2 (6.2%), and impairment of personal social skills in 1 (3.1%). The average ages for diagnosis and treatment were 25.65 days in patients with developmental impairment and 17.99 days in those without developmental delay. ASQ results showed significant statistical correlation with initial dose of levothyroxine (P=0.017), age of hypothyroidism diagnosis (P=0.002) and age of treatment initiation (P=0.018). Early diagnosis and treatment along with initial levothyroxine dose were most important factors of ASQ scores of children with CH. Higher dose of the levothyroxine is required at onset.

Targeted Levothyroxine Therapy for Treatment of Congenital Hypothyroidism

The purpose of this study was to determine if infants with congenital hypothyroidism (CH) whose initial dose of levothyroxine (LT4) is based on thyroid gland anatomy require fewer dose adjustments in the first 6 months of life than those who were started empirically on LT4. Newborns with CH who had a thyroid ultrasound performed at diagnosis were eligible for this prospective, historical case-controlled study. The daily LT4 dose prescribed was based on results on the thyroid ultrasound as follows: 15 mcg/kg for athyreosis, 12 mcg/kg for a dysgenetic thyroid, and 10 mcg/kg for an anatomically normal gland. Routine labs according to standard guidelines were obtained, and the number of dose adjustments over the first 6 months of therapy was recorded. Each study participant was matched with 2 historical controls with CH based on sex and thyroid anatomy. Twenty-two subjects (10 with athyreosis, 4 with dysgenetic glands, and 8 with anatomically normal glands) were matched to 44 controls. There was no significant difference in the overall number of adjustments in the study group compared to controls (P = .74). However, there were significantly fewer adjustments made for undertreatment (P = .03) and significantly more adjustments made for overtreatment (P = .006) in subjects with athyreosis compared to controls. Targeted LT4 therapy does not appear to decrease the overall frequency of dose adjustments for infants with CH. However, 15 mcg/kg/day appears to exceed thyroid hormone requirements in infants with CH due to athyreosis. CH = congenital hypothyroidism LT4 = levothyroxine OT = overtreatment T4 = thyroxine TSH = thyroid-stimulating hormone UT = undertreatment.

Intellectual development in preschool children with early treated congenital hypothyroidism

PurposeDelayed treatment of congenital hypothyroidism (CH) is a common cause of mental retardation. The aim of the present study was to evaluate intellectual outcomes in preschool children with treated CH.MethodsWe retrospectively reviewed the clinical records of 43 children (age range: 13 to 60 days of life; 22 girls and 21 boys) diagnosed with CH. Children aged 5 to 7 years were examined using the Korean Wechsler Intelligence Scale for Children or the Korean Wechsler Preschool and Primary Scale of Intelligence.ResultsThe patients started treatment between 13 and 60 days of age. The mean intelligence quotient (IQ) of patients tested at age 5 to 7 years was 103.14±11.68 (IQ range: 76–126). None had intellectual disability (defined as an IQ <70). Twenty-one subjects were treated with a low dose (6.0–9.9 µg/kg/day) and 22 with a high dose of levothyroxine (10.0–16.0 µg/kg/day). There was no significant difference in the mean full-scale IQ (FSIQ), verbal IQ (VIQ), and performance IQ (PIQ) scores between the 2 groups. FSIQ, PIQ, and VIQ scores were not significantly correlated with initial dose of L-T4, initial fT4, age at treatment in multivariate analysis.ConclusionIQ scores of subjects with early treated CH diagnosed through a neonatal screening test were within normal range, regardless of etiology, thyroid function, initial dose of levothyroxine, and age at start of treatment.

Study for optimal dose determination of levothyroxine in subclinical hypothyroidism in pregnancy

Context: Subclinical thyroid dysfunction has been associated with pregnancy complications and affects both maternal and fetal outcomes such as impaired neuropsychological development in offspring and adverse obstetric outcomes-including miscarriage, premature birth, gestational hypertension, placental abruption, and fetal death. Endocrine Society guidelines recommend that all pregnant women with subclinical hypothyroidism be treated with Levothyroxine. The American Thyroid Association guidelines recommend that pregnant women with subclinical hypothyroidism and detectable thyroid-peroxidase antibodies receive Levothyroxine. But till date no authority has given any guideline about the initial dose of Levothyroxine. Aims: To formulate a dosage regime of levothyroxine which is optimal for urgent correction of hypothyroid state in pregnancy. Settings and Design: Prospective (longitudinal) study. Subjects and Methods: A total of 42 apparently normal pregnant women, with known last-menstrual period, with no known metabolic or hypertensive disorder who presented to the clinic had thyroid screening using a standardized method. Women with thyroid stimulating hormone (TSH) value in the range to be diagnosed as subclinical hypothyroidism were included in the study. All patients were followed-up till the time of delivery for the obstetric outcome. Levothyroxine was the mainstay of treatment. Levothyroxine dose were adjusted every trimester on the basis of thyroid function tests (TFTs) including free thyroxine (FT4) and TSH values. Anthropometric measurements included height and body weight at baseline. Statistical Analysis Used: Significance is assessed at 5% level of significance. Pearson and Spearmen correlation test used to find out correlation among normally and non-normally distributed data respectively. Analysis of variance (ANOVA) and Kruskal-wallis with distribution free multiple comparison test used to find the significance of study parameters between three or more groups of patients for normally distributed data and non-normally distributed data. Results: 81.25% of subjects achieved euthyroidism in third trimester. The mean levothyroxine dose used in the first trimester was 40.18 ± 13.78 μg. The mean levothyroxine dose used in the third trimester was 58.25 ± 18.57 μg. Significant increase in the mean dose of levothyroxine required in the third trimester (58.25 ± 18.57 μg) as compared to the first trimester (40.18 ± 13.78 μg, P = 0.0012). Conclusions: Significant improvement in the thyroid function as indicated by higher proportion of patients achieving normal TSH values with significant increase in the mean levothyroxine dose used during the course of treatment gives us guideline about the initial starting doses of levothyroxine.

Study for optimal dose determination of levothyroxine in subclinical hypothyroidism in pregnancy

Context: Subclinical thyroid dysfunction has been associated with pregnancy complications and affects both maternal and fetal outcomes such as impaired neuropsychological development in offspring and adverse obstetric outcomes-including miscarriage, premature birth, gestational hypertension, placental abruption, and fetal death. Endocrine Society guidelines recommend that all pregnant women with subclinical hypothyroidism be treated with Levothyroxine. The American Thyroid Association guidelines recommend that pregnant women with subclinical hypothyroidism and detectable thyroid-peroxidase antibodies receive Levothyroxine. But till date no authority has given any guideline about the initial dose of Levothyroxine. Aims: To formulate a dosage regime of levothyroxine which is optimal for urgent correction of hypothyroid state in pregnancy. Settings and Design: Prospective (longitudinal) study. Subjects and Methods: A total of 42 apparently normal pregnant women, with known last-menstrual period, with no known metabolic or hypertensive disorder who presented to the clinic had thyroid screening using a standardized method. Women with thyroid stimulating hormone (TSH) value in the range to be diagnosed as subclinical hypothyroidism were included in the study. All patients were followed-up till the time of delivery for the obstetric outcome. Levothyroxine was the mainstay of treatment. Levothyroxine dose were adjusted every trimester on the basis of thyroid function tests (TFTs) including free thyroxine (FT4) and TSH values. Anthropometric measurements included height and body weight at baseline. Statistical Analysis Used: Significance is assessed at 5% level of significance. Pearson and Spearmen correlation test used to find out correlation among normally and non-normally distributed data respectively. Analysis of variance (ANOVA) and Kruskal-wallis with distribution free multiple comparison test used to find the significance of study parameters between three or more groups of patients for normally distributed data and non-normally distributed data. Results: 81.25% of subjects achieved euthyroidism in third trimester. The mean levothyroxine dose used in the first trimester was 40.18 ± 13.78 μg. The mean levothyroxine dose used in the third trimester was 58.25 ± 18.57 μg. Significant increase in the mean dose of levothyroxine required in the third trimester (58.25 ± 18.57 μg) as compared to the first trimester (40.18 ± 13.78 μg, P = 0.0012). Conclusions: Significant improvement in the thyroid function as indicated by higher proportion of patients achieving normal TSH values with significant increase in the mean levothyroxine dose used during the course of treatment gives us guideline about the initial starting doses of levothyroxine.

Using Body Mass Index to Predict Optimal Thyroid Dosing after Thyroidectomy

Current postoperative thyroid replacement dosing is weight based, with adjustments made after thyroid-stimulating hormone values. This method can lead to considerable delays in achieving euthyroidism and often fails to accurately dose over- and underweight patients. Our aim was to develop an accurate dosing method that uses patient body mass index (BMI) data. A retrospective review of a prospectively collected thyroid database was performed. We selected adult patients undergoing thyroidectomy, with benign pathology, who achieved euthyroidism on thyroid hormone supplementation. Body mass index and euthyroid dose were plotted and regression was used to fit curves to the data. Statistical analysis was performed using STATA 10.1 software (Stata Corp). One hundred twenty-two patients met inclusion criteria. At initial follow-up, only 39 patients were euthyroid (32%). Fifty-three percent of patients with BMI >30 kg/m(2) were overdosed, and 46% of patients with BMI <25 kg/m(2) were underdosed. The line of best fit demonstrated an overall quadratic relationship between BMI and euthyroid dose. A linear relationship best described the data up to a BMI of 50. Beyond that, the line approached 1.1 μg/kg. A regression equation was derived for calculating initial levothyroxine dose (μg/kg/d = -0.018 × BMI + 2.13 [F statistic = 52.7, root mean square error of 0.24]). The current standard of weight-based thyroid replacement fails to appropriately dose underweight and overweight patients. Body mass index can be used to more accurately dose thyroid hormone using a simple formula.

Fecundity in Young Adults Treated Early for Congenital Hypothyroidism Is Related to the Initial Severity of the Disease: A Longitudinal Population-Based Cohort Study

Untreated hypothyroidism is known to impair fecundity. Patients treated early for congenital hypothyroidism (CH) have yet to be evaluated in adulthood, because screening programs have been running for only the last 30 years in most industrialized countries. Our objective was to assess the fecundity of young adults treated early for CH and its determinants. Of the 1748 subjects diagnosed with CH in the first 10 yr after the introduction of neonatal screening in France, 1158 completed a questionnaire on fecundity at a mean age of 25.3 yr. This self-administered questionnaire focused on first attempts to have a child and time to pregnancy. The control group was that used in an analogous study on subjects born between 1971 and 1985. Fecundability hazard ratios (HR) were estimated with Cox regression models and adjusted for known fecundity confounders (age, smoking, and reproductive history). Fecundability was similar for the CH and control groups: HR = 1.14 (0.89-1.47) for women, and HR = 0.98 (0.58-1.66) for men. In women, the most severe initial forms of the disease, athyreosis, absence of bone maturation at the knee epiphyseal ossification centers, and a low serum free T(4) concentration at diagnosis (<5 pmol/liter), were associated with lower fecundity: HR = 0.68 (0.50-0.98) (P = 0.02); HR = 0.65 (0.45-0.94) (p = 0.02) and HR = 0.70 (0.50-0.97) (P = 0.03), respectively. However, fecundability was not associated with age at the start of treatment, initial levothyroxine dose, or the adequacy of hypothyroidism control. There is no evidence that fecundity is generally lower in young adults treated early than in the general population. However, fecundity was lower in women suffering from the most severe form of the disease.

Episodes of Overtreatment during the First Six Months in Children with Congenital Hypothyroidism and Their Relationships with Sustained Attention and Inhibitory Control at School Age

Background/Aims: Contradictory results regarding the optimal initial dose of levothyroxine in children with congenital hypothyroidism (CH) hamper the clinical management of these children during their early infancy. We explore the relationships between the initial dose of levothyroxine and endocrine control during the first 6 months and cognition at school age. Subjects and Methods: Fifty children with CH, 14 boys (10 ± 3.1 years) and 36 girls (9.7 ± 2.6 years), at the Pediatric Endocrine Unit of the Hospital Gregorio Marañón in Madrid were studied. Neurocognitive evaluation was carried out exploring alertness and inhibitory control. The number of episodes of overtreatment during the first 6 months, the initial dose of levothyroxine, etiology and sex were the predictor variables. Results: Inhibitory control was significantly lower in children with CH than in controls. An interaction with gender and etiology was obtained. Alertness had an inverse relationship with the number of episodes of overtreatment with no interaction with gender or etiology. Conclusion: Episodes of overtreatment and not the initial dose of levothyroxine are a risk factor for deficit in alertness whereas subtle inhibitory control deficit seems to be a permanent problem with the current therapeutic approach.

High versus low dose of initial thyroid hormone replacement for congenital hypothyroidism.

Congenital hypothyroidism (CHT) affects approximately one in 3000 to 4000 infants. CHT is one of the most common preventable causes of learning difficulties. Optimal management of CHT requires early diagnosis and prompt treatment to avoid abnormal neurodevelopmental outcome. One of the main issues in the management of CHT relates to the initial dose of levothyroxine to be used in order to achieve optimal results in terms of intellectual development. Currently, it remains unclear whether high dose thyroid hormone replacement is more effective than low dose in the treatment of CHT. Further research is required to determine an appropriate dose that improves mental and psychomotor developmental outcomes. To determine the effects of high versus low dose of initial thyroid hormone replacement for congenital hypothyroidism. Randomised controlled trials were identified by searching The Cochrane Library, MEDLINE and EMBASE and reference lists of published papers. Randomised controlled clinical trials investigating the effects of high versus low dose of initial thyroid hormone replacement for congenital hypothyroidism were included. Both authors independently selected trials, assessed risk of bias and extracted data. The initial search identified 1014 records which identified 13 publications for further examination. After screening the full text of the 13 selected papers, only one study evaluating 47 babies finally met the inclusion criteria. Using the same cohort at two different time periods, the study investigated the effects of high versus low dose thyroid hormone replacement in relation to (1) time taken to achieve euthyroid status and (2) neurodevelopmental outcome. The study reported that a high dose is more effective in rising serum thyroxine and free thyroxine concentrations to the target range and earlier normalisation of thyroid stimulating hormone compared to a lower dose. Similarly, full scale intelligence quotient was noted to be significantly higher in children who received the high dose compared to the lower dose. However, the verbal intelligence quotient and performance intelligence quotient were similar in both groups. Growth and adverse effects were not reported in the included trial. There is currently only one randomised controlled trial evaluating the effects of high versus low dose of initial thyroid hormone replacement for CHT. There is inadequate evidence to suggest that a high dose is more beneficial compared to a low dose initial thyroid hormone replacement in the treatment of CHT.