Levothyroxine Requirements Research Articles

8208 Unexpected And Significant Rise In TSH In The Setting Of Relugolix Use

Abstract Disclosure: A.Y. Groysman: None. A. Poloju: None. P. Majety: None. T. Abraham: None. Background: Relugolix is a gonadotropin-releasing hormone antagonist used as androgen deprivation therapy for metastatic and nonmetastatic castration-resistant prostate cancer that was FDA-approved in December 2020. Common side effects include hot flashes, increased glucose and triglycerides, and decreased hemoglobin. We report a case of Relugolix interference with the absorption of levothyroxine, which has not been reported in the literature. Case: A 79-year-old white man with high-risk, Gleason 9 prostate cancer and Hashimoto’s hypothyroidism presented for evaluation of elevated thyroid stimulating hormone (TSH) level- 52.87 mIU/L (0.28-4.10 mIU/L). He did not have cold intolerance, constipation, fatigue, or weight gain. He was diagnosed with hypothyroidism in 1998 and was on a stable dose of levothyroxine 88mcg daily from 2016 until the time of this presentation. He is adherent and reports following a routine of having breakfast with coffee soon after taking levothyroxine for many years. In June 2022, his TSH was 4.48 mIU/L. In July 2022, he started taking Relugolix along with levothyroxine. Following this, his TSH levels increased to 30.08 mIU/L (FT4: 0.67 ng/dL), 35.43 mIU/L (FT4: 0.57 ng/dL), 52.87 mIU/L (FT4: 0.48 ng/dL) on 2/24/23, 3/3/23, and 3/14/23, respectively. No new medications were reported. His other medications were atorvastatin, tamsulosin, and vitamin D, which he took at night. He did not take calcium or biotin supplements. He had gradual weight gain (8 lbs) over the last 9 months. Levothyroxine dose was increased from 88 to 125 mcg daily and he was instructed to separate Relugolix from levothyroxine so he started taking Relugolix at bedtime. Repeat TSH was low at 0.12 mIU/L. The levothyroxine dose was eventually titrated back to 88 mcg daily and TSH was 5.2 (appropriate for age). Conclusion: Several medications are known to interfere with the absorption of levothyroxine. Our case suggests that Relugolix may be one of them. The significant rise in TSH and levothyroxine requirements months after starting Relugolix and the ability to return to the previous dose of levothyroxine only by separating Relugolix from levothyroxine strongly suggests that there is an interference between these medications that has not been reported. Presentation: 6/2/2024

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.

Congenital hypothyroidism in children with eutopic gland or thyroid hemiagenesis: prognostic factors for transient vs. permanent hypothyroidism.

More than one third of children with congenital hypothyroidism (CH) and thyroid gland in situ(or eutopic gland) have transient hypothyroidism. It remains difficult to determine early on whether hypothyroidism will be transient which may cause overtreatment and its complications in these children. Our primary aim was to determine prognostic factors for transient hypothyroidism in children with congenital hypothyroidism and eutopic gland or thyroid hemiagenesis. We retrospectively reviewed medical records of111 children, born between 1996 and 2017, diagnosed withcongenital hypothyroidism and eutopic gland or hemiagenesis and treated at the Nancy Regional and University Hospital. Fifty four infants (48.6%) had permanent congenital hypothyroidism (PCH) and 57 (51.4%) transient congenital hypothyroidism (TCH). Prognostic factors for TCH included prematurity, twin pregnancy, low birth weight and Apgar score <7, while low FT3 at diagnosis, maternal levothyroxine treatment, a family history of thyroid dysfunction and TSH≥10mUI/L while receiving treatment were associated with PCH. Knee epiphyses on X-ray at diagnosis were absent only in children with PCH. The median levothyroxine dose during follow-up was significantly lower in the TCH group compared to the PCH group. A levothyroxine dose of≤3.95,≤2.56,≤2.19 and≤2.12μg/kg/day at 6months, 1, 2 and 3years of follow-up, respectively, had the best sensitivity-to-specificity ratio for predicting TCH. Even though it remains difficult to predict thecourse of hypothyroidism at diagnosis, we were able to identify several prognostic factors for TCH including perinatal problems and lower levothyroxine requirements that can guide the physician on the evolution of hypothyroidism. Clinical Trial Registration Number: NCT04712760.

LBODP105 A Case of Significantly Increased Levothyroxine Requirement With Rifampin Therapy

Abstract Introduction Rifampin has a wide range of drug interactions through increased hepatic microsomal enzyme activity. We are reporting a case of a patient with post-surgical hypothyroidism on stable thyroid hormone replacement therapy who required significantly higher doses of levothyroxine after starting rifampin. Case Report Patient is a 78-year-old woman with history of Papillary Thyroid Cancer (PTC) in remission status post thyroidectomy in 1994 and radioactive iodine therapy in 1997. Patient had been on a stable dose of Levothyroxine of 75-88mcg daily until a visit in January 2013 when her TSH was found to be 39 despite compliance with levothyroxine. Further history revealed that she was diagnosed with Mycobacterium Avium Intracellulare (MAI) infection of the lungs for which she was given rifampin therapy. Her Levothyroxine dose was progressively increased to 150mcg daily. She received rifampin therapy for 18 months, from August 2012 until April 2013. Her Levothyroxine dose was later changed to average 139 mcg /day based on TSH levels and continued to be the same through the rifampin course. In April 2014, and following discontinuation of rifampin, Levothyroxine was decreased to 100mcg daily and subsequently 75mcg daily. During a relapse of MAI in March 2016, her levothyroxine dosage was similarly again increased to 125mcg daily for TSH of 24.58. In June 2017, rifampin was discontinued after completion of second course of MAI treatment, and Levothyroxine dose decreased to 88 mcg daily, and subsequently 75 mcg in September 2017, and average daily 64mcg most recently given age and long-term remission with target mid normal TSH. Discussion Rifampin is used to treat active tuberculosis and MAI infection among other uses. It is a hepatic enzyme inducer which significantly interacts with other drugs. It has been reported previously to cause hypothyroidism in patients with underlying thyroid disorder and increased serum TSH while on levothyroxine, but its impact range on thyroid function has not been clearly described. Our patient was on stable levothyroxine dose following thyroidectomy, and required almost a 100% increase of levothyroxine dose when started on rifampin therapy, returning to baseline levothyroxine requirements off rifampin. This case highlights the severe hypothyroidism and significant impact on levothyroxine dose requirements following rifampin therapy, and the importance of close thyroid function monitoring in patients with hypothyroidism and on rifampin, especially in context of post-surgical hypothyroidism. Presentation: No date and time listed

ODP490 Levothyroxine Dosing Based on BMI and Different Causes of Hypothyroidism

Abstract While several approaches can be used when initiating levothyroxine therapy, it is commonly stated that total levothyroxine dose can be calculated as a function of the person's body weight. 1.6 mcg/kg of body weight. But studies have suggested that other factors must be assessed when trying to calculate a total daily dose. The cause of a patient's hypothyroidism may have an effect on their actual replacement needs. It is not the same to consider a patient with postsurgical hypothyroidism who has had all thyroid tissue completely removed versus Hashimoto's or Radioactive Iodine ablation where some thyroid function may be preserved. It is also important to consider a patient's ideal body weight as studies have shown that ideal body weight rather than actual body weight may be more useful in determining a patient's ultimate levothyroxine requirements. As the prevalence of obesity is increasing in the United States and worldwide, factors such as BMI may start playing a more important role when deciding initiation dosage in these patients. We conducted a retrospective chart review with a total of 260 hypothyroid patients on levothyroxine and with two stable TSH values on the same dose. We divided the patient into three BMI categories. &amp;lt;= 24.9, 25-29.9 and &amp;gt;=30. Patients with BMI &amp;lt;= 24.9 had a levothyroxine mean (SD) dose of 1.5 MCG/KG (0.63), those with a BMI 25-29.9: 1.3MCG/KG (0.44), and those with a BMI &amp;gt;=30: 1.1MCG/KG (0.45). P Value &amp;lt;0. 001. When further subdivided into the cause of hypothyroidism (Hashimoto's, post surgical and radioactive iodine), the effects of BMI on levothyroxine dose seem to also be affected. In postsurgical hypothyroidism, patients with BMI &amp;lt;= 24.9 had a levothyroxine mean (SD) dose of 1.8 MCG/KG (0.47), BMI 25-29.9: 1.5MCG/KG (0.21) and BMI &amp;gt;=30: 1.4MCG/KG (0.38). P Value &amp;lt;0. 001. Patients with Hashimoto's with BMI &amp;lt;= 24.9 had a levothyroxine mean (SD) dose of 1.3 MCG/KG (0.65), BMI 25-29.9: 1.1MCG/KG (0.50) and BMI &amp;gt;=30: 0.9MCG/KG (0.44). P Value &amp;lt;0. 001. In patients with hypothyroidism due to radioactive iodine therapy, the levothyroxine dose for those with BMI &amp;lt;= 24. was 1.4 MCG/KG, BMI 25-29.9: 1.2MCG/KG (0.53) and BMI &amp;gt;=30: 1.2MCG/KG (0.39). P Value 0.883 These results suggest that when initiating levothyroxine therapy, a starting dose of 1.6 MCG/KG is not adequate for all patients and that BMI and cause of hypothyroidism should be considered before making this decision. Presentation: No date and time listed

Subclinical Hypothyroidism in Pediatric Age: How Important Is Autoimmunity?

BackgroundThe natural history of subclinical hypothyroidism (SHT) is influenced by the underlying etiology, being the most common Hashimoto's thyroiditis (HT) and isolated hyperthyrotropinemia (IH). Additionally, controversy exists surrounding the need for pharmacological treatment.MethodsA retrospective observational study that included patients diagnosed with SHT caused by HT or IH at pediatric age, under levothyroxine therapy and with follow-up at Centro Hospitalar Baixo Vouga between January/2014 and July/2019. Patients with follow-up time <12 months or missing records were excluded. This study aims to compare clinical, analytical and echographic parameters and levothyroxine dose between patients with SHT caused by HT or IH.ResultsSample of 39 patients with 16.5 ± 3.4 years, 22 (56.4%) females. There was a preponderance of females in the HT group and males in the IH (p=0.001). Changes in thyroid ultrasound were more prevalent in the HT group (85.7% vs 16.7%, p<0.001). The median initial and final doses of levothyroxine were higher in the HT group (p=0.016, p=0.011). There was a trend towards a higher levothyroxine discontinuation rate in the IH group (22.2% vs 4.8%, p=0.162).Two positive and statistically significant correlations were found between the level of anti-thyroid peroxidase antibodies (TPOAbs) and both the final levothyroxine dose (ρ=0.544; p=0.004) and the final weight-adjusted levothyroxine dose (ρ=0.434; p=0.027).ConclusionsHT was more common in females and was associated with higher levothyroxine requirements and less likelihood of treatment discontinuation, especially if high TPOAbs levels. These results can be useful in the difficult daily decision of starting therapy, especially in milder forms of SHT.

The Effect of Different Types of Bariatric Surgery on Levothyroxine Requirement in Hypothyroid Bariatric Patients.

BackgroundBariatric surgeries are carried out to improve a patient's quality of life, and to reduce respiratory, cardiac, endocrine, and metabolic complications encountered by those with high body mass index (BMI). A complication associated with high hypothyroidism is weight gain, which may lead to obesity. Here, we explore the effect of different bariatric procedures on thyroid function and levothyroxine dosage. MethodsThis is a retrospective review of 887 patients referred to a tertiary bariatric service between 2008 and 2020 and treated for hypothyroidism at the time of referral.The study identified 57 patients on thyroxine replacement. Of these, 22 underwent restrictive bariatric procedures, 16 underwent restrictive/malabsorptive procedures, and 19 did not undergo operative intervention.Comparisons were made among each group throughout the timeline of interest.ResultsOut of 57 patients, 50 (87.7%) were female. The average age for patients was 47.26+/- 8.89 years. The average BMI at baseline was 48.72+/- 8.68 kg/m2. The mean dose of levothyroxine in controls was 115.8+/- 53.5 mcg while that of surgical patients was 149.8+/- 68.4 mcg.There were no statistically significant differences in levothyroxine doses between surgical and control at T0 (baseline), T1 (one-year post-op in surgical patient, or two-year post referral in control patient), T2 (two-year post-op in surgical patient, or three-year post referral in control patient), and T3 (most recent result available). The surgical group was then categorized further into restrictive and restrictive/malabsorptive. When they were compared with the control group, there were no statistically significant differences in doses.A generalized linear mixed model was applied to assess differences in levothyroxine dose with time as a random variable. This was adjusted for age, sex, BMI, T4 level, and hypothyroid cause. Through this assessment, there were several statistically significant differences in levothyroxine dosage between the groups. Control group required on average 28.06 mcg less levothyroxine than the restrictive/malabsorptive group (p=0.015). Also, the restrictive group required on average 23.57 mcg less levothyroxine than the restrictive/malabsorptive group (p=0.033). There were no statistically significant differences observed between the control group and the restrictive group (p=0.67)ConclusionPatients who have bariatric surgery have changes to their anatomy and physiology which may affect both their thyroid hormone homeostasis and levothyroxine pharmacokinetics. Thus, hypothyroid bariatric patients requiring levothyroxine must have their thyroid function monitored regularly. In this study, it was found that hypothyroid patients who underwent restrictive surgery had an overall statistically significant lower levothyroxine requirement to remain euthyroid as compared to the restrictive/malabsorptive group (p=0.033). Additionally, the control group required statistically significantly less levothyroxine than the restrictive/malabsorptive group (p=0.015). These factors may determine the type of surgery chosen by hypothyroid bariatric patients. However, further studies that are randomized, controlled, and multi-center with a higher population are required.

Significant weight loss resulted in reduced levothyroxine requirements during a tesomet trial of hypopituitary patients with acquired hypothalamic obesity

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Change in levothyroxine requirements after bariatric surgery in patients with hypothyroidism.

Objectives. This study aims to evaluate the need to modify the total and weight-adjusted doses of levothyroxine after bariatric surgery, identify predictors, and assess the influence of the weight loss on the levothyroxine requirements. Methods. A retrospective study in patients with treated hypothyroidism that underwent bariatric surgery. The modification of the levothyroxine dose and its association with the weight loss and other potential predictors were evaluated at 6, 12, and 24 months post-surgery. Results. Among the 63 patients included, 82.54% needed an adjustment of levothyroxine dose during the follow-up. The total weekly dose of levothyroxine (µg) decreased post-surgery at 6 months (β= -49.1; 95%CI-93.7 to -4.5; p=0.031) and 12 months (β=-54.9; 95%CI-102 to -7.8; p=0.022), but did not significantly change at 24 months (p=0.114). The weekly weight-adjusted dose (µg/k) increased at 6 months (β=1.37; 95%CI 0.91 to 1.83; p<0.001), 12 months (β=2.05; 95%CI 1.43 to 2.67; p<0.001), and 24 months (β=2.52; 95%CI 1.74 to 3.30; p<0.001). The weight loss showed association with the weight-adjusted dose (OR=1.07; 95%CI 1.02 to 1.12; p=0.004), but not the total dose (p=0.320). Conclusions. This study shows a significant decrease in the total dose of levothyroxine requirements change after bariatric surgery during the first year of the follow-up and an increase in the weight-adjusted dose over the first two years. No predictors of modification of the total dose of levothyroxine were identified.

Diagnostic Re-Evaluation and Potential Predictor Factors of Transient and Permanent Congenital Hypothyroidism in Eutopic Thyroid Gland.

Background: The incidence of congenital hypothyroidism (CH) has increased over the years, and many predictors for detecting newborns with transient forms (TCH) as early as possible have been considered. Methods: All newborns diagnosed with primary CH and eutopic gland in the Piedmont region of Italy in the period of January 2014–June 2019 were enrolled and re-evaluated at the age of 2 years. Results: 105 newborns were diagnosed with CH during the study period. Dyshormonogenesis was observed in 55/105. At re-evaluation, we found that 52.7% had permanent CH (PCH), while 47.3% had TCH. Male/female rate, TSH levels at diagnosis, levothyroxine requirement at withdrawal and extra-thyroid congenital malformations rate were higher in the PCH group (p = 0.02, p = 0.009, p = 0.02 and p = 0.01), while fT4 levels at diagnosis were lower (p = 0.03). Sensitivity of 72.4% and specificity of 80.7% for serum TSH above 60 mcUI/mL, sensitivity of 73% and specificity of 72.4% for serum fT4 level below 7.2 pg/mL and sensitivity of 66% and specificity of 68% for drug requirement above 2.25 mcg/kg/day were observed in PCH. Conclusions: Demographic, clinical and hormonal data at diagnosis and levothyroxine requirement during the first two years should be adequately monitored to identify infants who are most likely to discontinue therapy after the age of 24 months.

Effect of Laparoscopic Sleeve Gastrectomy vs. OAGB on Thyroid Function Tests in Patients with Morbid Obesity and Subclinical or Clinical Hypothyroidism.

As one of the major problems for the health sector, morbid obesity is associated with many hormonal dysfunctions, including thyroid hormone disorders. Few studies have been performed on improving subclinical and clinical hypothyroidism following bariatric surgery. Therefore, we designed and conducted this study to evaluate the effect of various types of bariatric surgery on thyroid hormone levels and to assess the change of levothyroxine requirement in these patients. The data of all patients who underwent either sleeve gastrectomy (SG) or one-anastomosis gastric bypass (OAGB) surgery in the 5years from 2016 to 2020 at our hospital were analyzed retrospectively. From 1486 patients (792 cases of SG and 694 cases of OAGB), 281 patients had preoperative abnormal thyroid function tests: subclinical hypothyroidism (102 patients) and clinical hypothyroidism (179 patients). The T4 level did not change significantly in any of the groups and subgroups. However, the TSH level at the end of the sixth month after SG and OAGB in both groups significantly lowered. Nevertheless, there is no significant difference between the effect of SG and OAGB surgical procedures on the rate of TSH and T4 alterations in both subclinical and clinical hypothyroid patients. In the sixth month after surgery, 49% of clinically hypothyroid patients in the SG group (n = 179) reduced or stopped taking the medication. Whereas bariatric surgery reduces TSH levels, it does not significantly alter T4 levels. Furthermore, there is no apparent difference between subclinical and clinical hypothyroidism and different types of bariatric surgery.

Increasing levothyroxine requirements in a patient with previously stable hypothyroidism

Increasing levothyroxine requirements in a patient with previously stable hypothyroidism

Transdermal Absorption of Methimazole- a Cat’s Tale

Introduction: In modern civilization different kinds of animals live with us as pets. These pets have different diseases and are on medications. Close contact with animals can cause medication adverse reactions or may worsen pre-existing conditions in humans. Here we present an interesting case of hypothyroidism worsened by transdermal absorption of methimazole administered for feline hyperthyroidism. Case History: 66-year-old Caucasian female with past medical history of postoperative hypothyroidism s/p total thyroidectomy secondary to multinodular goiter due to Hashimoto’s thyroiditis with a 0.2 cm papillofollicular microcarcinoma and 0.7 cm follicular adenoma presented for follow up. She complained of weight gain, lethargy and dry skin for the past 4 months. She was on a stable dose of levothyroxine 112 mcg daily for the past year. She took her pill correctly and did not miss any doses. Her other medical problems were impaired fasting glucose, osteopenia and B12 deficiency. Her repeat thyroid function tests showed TSH 11.2 mc IU/ l (0.4 -4) (TSH - 0.538 mc IU/ L 6 months back), T4 - 6.8 mcg/ dl (4.5 - 12) (T4 8.9 6 months back). She had a measurable serum thyroglobulin of 0.4 ng/ml with antithyroglobulin antibody 11 IU/ml (<115) consistent with some residual thyroid tissue despite her history of a “total thyroidectomy”. Due to recent worsening of her symptoms with elevated TSH on background of previous stable levothyroxine requirement, further detailed history was taken. She reported that her cat was suffering from hyperthyroidism, treated with methimazole 10 mg daily. The patient used to cut the pill in half with bare hands and fed it to her pet. She also used to handle wet methimazole that her cat coughed up. Her levothyroxine dose was continued at 112 mcg daily. The patient was advised to use gloves before feeding and wash her hands after feeding her cat. Her symptoms resolved after she took precautions and TSH normalized to 1.170 mc IU/ l with T4 7.6 two months later. Conclusion: Absorption of methimazole by transdermal administration has been shown in cats1. A study by Kasraee et al showed safety of a 5% topical methimazole application for treatment of post inflammatory hyperpigmentation in humans with no change in thyroid function tests2. Our case contradicts this study and indicates that methimazole might be absorbed transdermally in humans. To conclude, more studies are needed to study the effect of transdermal administration of methimazole in humans.

Changes in levothyroxine pharmacokinetics following bariatric surgery in obese hypothyroid patients

Aim: Levothyroxine (L-T4) requirements in obese hypothyroid patients receiving L-T4 therapy decrease following bariatric surgery. L-T4 absorption is also thought to decrease after surgery. The purpose of this study was to evaluate L-T4 requirements in hypothyroidism cases before and after weight loss through bariatric surgery. Methods: Seventy-six cases of hypothyroidism receiving L-T4 replacement therapy and with a body mass index over 40 kg/m2 were included in the study. Patients losing at least 10% of basal body weight following bariatric surgery were assessed in terms of thyroid hormone levels and L-T4 requirements over follow-up of at least one year. The L-T4 requirements of patients in whom euthyroidism was achieved were compared in terms of bariatric surgery procedures and hypothyroidism etiology. Results: Seventy-six patients (56 women, 20 men) with a mean age of 38 years (18-51) were included in the study. Mean weight before bariatric surgery was 121.6 ± 6.8 kg, and mean body mass index was 49.5 ± 1.6 kg/m2. Euthyroidism was confirmed at pre- and post-bariatric surgery evaluation. No statistically significant postoperative changes were determined in thyroid-stimulating hormone or free thyroxine-3 and -4 (p > 0.05). A statistically insignificant decrease was observed in L-T4 dosages after surgery in cases of Hashimoto’s thyroiditis (p = 0.064). A statistically significant decrease was determined in L-T4 dosages in cases of non-Hashimoto hypothyroidism (p = 0.001). L-T4 requirements decreased in both surgical procedures (p = 0.001) Conclusion: Postoperative L-T4 requirements decrease with weight loss. In addition, no decrease appeared to occur in L-T4 absorption following the surgical procedures in this study.

Levothyroxine and insulin requirement in autoimmune polyglandular type 3 syndrome: a real-life study

PurposeTo evaluate factors influencing the insulin and levothyroxine requirement in patients with autoimmune polyglandular syndrome type 3 (APS-3) vs. patients with type 1 diabetes mellitus (T1DM) and autoimmune hypothyroidism (AH) alone, respectively.MethodsFifty patients with APS-3, 60 patients with T1DM and 40 patients with AH were included. Anthropometric, clinical and biochemical parameters were evaluated in all patients. Insulin requirement was calculated in patients with APS-3 and T1DM, while levothyroxine requirement was calculated in APS-3 and AH.ResultsPatients with APS-3 showed higher age (p = 0.001), age of onset of diabetes (p = 0.006) and TSH (p = 0.004) and lower total insulin as U/day (p < 0.001) and U/Kg (p = 0.001), long-acting insulin as U/day (p = 0.030) and U/kg (p = 0.038) and irisin (p = 0.002) compared to T1DM. Patients with APS-3 had higher waist circumference (p = 0.008), duration of thyroid disease (p = 0.020), levothyroxine total daily dose (p = 0.025) and mcg/kg (p = 0.006), triglycerides (p = 0.007) and VAI (p = 0.010) and lower age of onset of thyroid disease (p = 0.007) than AH.At multivariate analysis, levothyroxine treatment and VAI were associated with insulin and levothyroxine requirement in APS-3, respectively. VAI was independently associated with insulin requirement in T1DM. Circulating irisin levels were independently associated with levothyroxine requirement in AH.ConclusionPatients with APS-3 show lower insulin requirement and higher levothyroxine requirement than T1DM and AH alone, respectively. Levothyroxine treatment and VAI affect insulin and levothyroxine requirement, respectively, in APS-3. In T1DM, adipose tissue dysfunction, indirectly expressed by high VAI, is associated with an increased insulin requirement, while circulating irisin levels influence the levothyroxine requirement in AH.

Magnitude of increase in levothyroxine requirements during pregnancy in women with pregestational hypothyroidism in navarra (Spain)

Magnitude of increase in levothyroxine requirements during pregnancy in women with pregestational hypothyroidism in navarra (Spain)

Protocolo diagnóstico y tratamiento de la patología tiroidea en la mujer embarazada y en el posparto

A common cause of medical consultancy in pregnancy is thyroid pathology, specifically thyroid function disorders. Physiological changes during pregnancy: a) cause an increase in levothyroxine requirements; b) narrow TSH reference values, mainly in the first trimester, increasing scenarios compatible with hyperthyroidism and primary hypothyroidism and c) facilitate clinical changes in autoimmune hyperthyroidism. Mismanagement or ignorance of these features over fetus well-being can result in negative effects on the health of the mother and the fetus/child. In postpartum, typical pregnant immune tolerance is lost, treatment has to be adjusted, appearing characteristic disorders like silent thyroiditis.

SUN-007 Elevated Levothyroxine Requirements Post-Partum as Initial Presentation of Placenta Accreta

Introduction: It is well known that estrogen plays an important role in thyroid regulation. We report an unusual case of post-partum placenta accreta causing pathologic estrogen secretion leading to increased levothyroxine (LT4) requirements and inability to lactate. Case: A 36-year-old woman with history of Hashimoto’s hypothyroidism presented post-partum day 11 after a normal vaginal delivery with inability to produce breast milk and mildly elevated TSH levels. Prior to her pregnancy, she required an equivalent dose of 142 mcg of LT4 supplementation daily, which increased appropriately to 171 mcg during pregnancy. After delivery, LT4 was decreased to 150mcg in anticipation of normalization of levothyroxine requirements to pre-pregnancy level. However, she had difficulty lactating and was found to have elevated prolactin, estradiol, and TSH levels. The following day, she presented to her obstetrician for persistent vaginal bleeding and was found to have placenta accreta requiring dilation and curettage (D&C). Her LT4 requirements eventually dropped to 125 mcg with decreasing beta-HCG and estrogen levels after successful D&C treatment. She was also then able to produce sufficient breast milk for lactation. Discussion: This case highlights the effect of estrogen on LT4 requirements during physiologic pregnancy and postpartum with placenta accreta. It is expected that hypothyroid patients have approximately 25-50% increased thyroid replacement requirements during pregnancy, which normalizes soon after delivery.1 Estrogen increases thyroxine-binding globulin and lowers circulating free thyroxine2,, which causes higher thyroid replacement requirements. Estrogen is also known to inhibit lactation. Our patient demonstrates that this holds true even in a pathologically high estrogen state from placenta accreta. Our case uniquely demonstrates a temporal association between estrogen levels and LT4 requirements in the post-partum hypothyroid patient. Patients with inappropriately high TSH levels after delivery should prompt investigation into pathologic causes of elevated estrogen-states, as levothyroxine requirements are expected to normalize immediately post-partum.

SAT-509 Sudden Onset of Malabsorption

Celiac disease (CD) is an immune-mediated enteropathy caused by a reaction to gliadin which responds to a restriction to dietary gluten. It has been traditionally recognized in children and young adults, although, recently, detection in the elderly population has increased. CD occurs in 2–5% of patients with autoimmune hypothyroidism, and is more prevalent in this group than in the general populationAn 82-year-old Caucasian woman with primary hypothyroidism and a BMI of 16 is referred to our endocrinology clinic for help with the management of hypothyroidism. She had a history of well controlled hypothyroidism on weight-dosed levothyroxine for many years until several months prior when she developed sudden onset of diarrhea and weight loss. Since then, her thyroid function tests showed an elevated TSH despite medication adherence. Her levothyroxine dose was steadily increased to 300 mcg daily and yet, her TSH still remained elevated. Laboratory work up was done which revealed elevated transglutaminase antibodies, suggesting the diagnosis of CD. The patient refused an endoscopy for a tissue diagnosis. Even though the patient has been diagnosed with CD, she has trouble following a gluten free diet and still has intermittent diarrhea and high levothyroxine requirements.Although lack of medication adherence is common, it is important to exclude gastric or intestinal causes of malabsorption in patients with high thyroid replacement requirements. Elderly patients often have paucity of symptoms, so high clinical suspicion is necessary to diagnose these patients.

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.