Levothyroxine Withdrawal Research Articles

A digital pathology model for predicting radioiodine-avid metastases on initial post-therapeutic 131I scan in patients with papillary thyroid cancer.

Accurate postoperative assessment is critical for optimizing 131I therapy in patients with papillary thyroid cancer (PTC). This study aimed to develop a pathology model utilizing postoperative digital pathology slides to predict lymph node and/or distant metastases on post-therapeutic 131I scan after initial 131I treatment in PTC patients. A retrospective analysis was conducted on 229 PTC patients who underwent total or near-total thyroidectomy and subsequent 131I treatment after levothyroxine (LT4) withdrawal between January 2022 and August 2023. The pathology model was developed through two stages: patch-level prediction and WSI-level prediction. The clinical model was constructed using statistically significant variables identified from univariate and multivariate logistic regression analysis. Of the 229 patients, 19.6% (45/229) exhibited 131I-avid metastatic foci in post-therapeutic 131I scan. Multifactorial analysis identified stimulated thyroglobulin (sTg) as the sole independent risk factor. The AUC of the pathology model in the training and test cohorts were 0.976 (95% CI 0.948-1.000) and 0.805 (95% CI 0.660-0.951), respectively, which were significantly higher than the clinical model (AUC 0.652 and 0.548, Pall < 0.05). This model has the potential to serve as a valuable tool for clinicians in tailoring treatment strategies, thereby optimizing therapeutic outcomes for PTC patients.

High frequency of transient congenital hypothyroidism among infants referred for suspected congenital hypothyroidism from the Turkish National screening program: thyroxine dose may guide the prediction of transients

PurposeWe aimed to determine the frequency of transient congenital hypothyroidism (TCH) in 17 participating centers in Türkiye, evaluate the etiological distribution in permanent congenital hypothyroidism (PCH) cases, and investigate the role of laboratory and clinical findings in predicting TCH.MethodsThis retrospective observational multicenter study included patients from 17 pediatric endocrinology centers identified by “National Newborn Screening Program” (NNSP) who were born in 2015 and followed for 6 years. Demographic, clinical, and laboratory information of the cases were compiled through the database http://cedd.saglik-network.org (CEDD-NET).ResultsOf the 239 cases initially treated for CH, 128 (53.6%) were determined as transient in whom a trial of levothyroxine (LT4) withdrawal was performed at a median age of 36 (34–38) months. Among the patients with PCH (n = 111), thyroid dysgenesis was diagnosed in 39.6% (n = 44). The predictive factors for TCH were: LT4 dose at the withdrawal of treatment, and initial newborn blood screening (NBS)-TSH level. Based on the receiver operating characteristic (ROC) curve analysis to predict optimal cut-offs for TCH predictors, LT4 dose < 2.0 µg/kg/day at treatment discontinuation was predictive for TCH and was associated with 94.5% specificity and 55.7% sensitivity, with an area under the curve (AUC) of 0.802. The initial NBS-TSH level value < 45 µIU/mL was predictive for TCH with 93.1% specificity and 45.5% sensitivity, with an AUC of 0.641. In patients with eutopic thyroid gland only LT4 dose < 1.1 µg/kg/day at withdrawal time was predictive for TCH with 84.7% sensitivity and 40.4% specificity, with an AUC of 0.750.ConclusionAccording to our national follow-up data, the frequency of TCH was 53.6%. We determined the LT4 dose < 2.0 µg/kg/day at discontinuation of treatment and the initial NBS-TSH level < 45 µIU/mL as the best cut-off limits to predict TCH.

Using haematological indices to predict impaired liver function in DTC patients.

In patients with normal liver function, patients with acute or chronic thyroid disease are more likely to develop liver dysfunction. Although the mechanisms underlying this process are not yet fully understood, it has been shown that hypothyroidism can lead to hepatic injury. We evaluated haematological function trends in patients with differentiated thyroid cancer (DTC) at baseline and approximately 4 weeks after l-thyroxine withdrawal before radioactive iodine ablation. This is a retrospective study, and 157 patients were enrolled. Logistic regression analysis was used to find significant predictors. Four weeks after LT4 withdrawal, 64 patients belonged to the group of liver injury, and 93 patients belonged to the group of normal liver function. Univariate analysis determined that platelet count (PC) (P=0.005), mean platelet volume (MPV) (P=0.013), platelet distribution width (PDW) (P=0.039) and absolute lymphocyte count (ALC) (P=0.008) were responsible risk factors for liver injury in DTC patients after withdrawal of levothyroxine (l-thyroxine). Multivariate analysis showed that slight increases in PC (OR: 2.243, P: 0.024) and ALC (OR: 0.398, P: 0.017) were closely associated with liver injury in DTC patients after 4 weeks LT4 withdrawal before radioactive iodine ablation. Our results suggest that PC and ALC are independent predictors of hypo-related liver injury. Our study is the first to suggest that haematological indices can be used for predicting the development and progression of hypo-related liver disorders.

THYROID STIMULATING HORMONE EVALUATION BETWEEN THREE AND FOUR WEEKS OF LEVOTHYROXINE WITHDRAWAL IN PATIENTS WITH DIFFERENTIATED THYROID CARCINOMA

Most patients with differentiated thyroid cancer (DTC) would require radioactive iodine (RAI) ablation therapy with I-131. Before RAI ablation therapy, levothyroxine is withheld for four to six weeks to increase TSH to over 30 mIU/L. Most people develop hypothyroidism on levothyroxine withdrawal. Reducing levothyroxine withdrawal from four to three weeks would enhance health and hypothyroidism symptoms. This study aims to evaluate the thyroid-stimulating hormone level after three and four weeks of levothyroxine withdrawal in patients with DTC in the Northern Malaysia population. All DTC patients undergoing RAI ablation therapy from January 2018 to November 2019 were enrolled. TSH levels were evaluated three and four weeks after discontinuing levothyroxine. Clinical data were analysed using IBM SPSS (Statistical Package for the Social Sciences) version 26.0.0. One hundred four patients with a mean age of 47.06 years were recruited. Most patients (77.88%) had papillary thyroid carcinoma (PTC) and were female (80.77%) and Malay (53.85%). By week three of levothyroxine withdrawal, 88.46% of patients had TSH levels above 30 mIU/L, with an average of 66.89 mIU/L, and at week four, 99.04% of patients had TSH levels above 30 mIU/L. Cohen's kappa measurement of the agreement was 0.139 between weeks three and four. A TSH level greater than 30 mIU/L was detected in 88.46% of patients who had discontinued levothyroxine for three weeks and 99.04% after four weeks. It is recommended to review the TSH level at 3 weeks instead of 4 weeks in patients who could not tolerate hypothyroidism symptoms.

Evaluating cognitive function in patients with differentiated thyroid cancer who experienced short- term hypothyroidism by levothyroxine withdrawal using Montreal Cognitive Assessment-Philippines (MoCA-P) tool

Background &amp; Objective: Although there are numerous data studying cognitive dysfunction on hypothyroidism in general, there are limited researches that venture on short-term hypothyroidism. This study aimed to determine the cognitive function of patients with differentiated thyroid cancer (DTC) who experienced short-term hypothyroidism. Methods: This was a prospective study done in a tertiary hospital in Manila that enrolled 16 DTC patients either for radioactive iodine (RAI) therapy or thyroid cancer monitoring, who were followed at baseline before levothyroxine (LT4) withdrawal, during hypothyroid state and post-LT4 treatment. MoCA-P tool was used to objectively assess cognition while HADS-P tool was used to detect anxiety and depression. Mean scores were calculated for each time point and analyzed using paired T-test. Results: There was a decrease in the mean MoCA-P score from baseline to hypothyroid state (25.22 to 22.97, p= 0.032) with improvement post-LT4 treatment (22.97 to 24.93, p= 0.004). Older age was associated with decrease in MoCA-P scores (p= 0.04). Total HADS-P scores were nonsignificant. Visuospatial (3.86 to 3.43, p 0.014) and attention (4.86 to 4.36, p value 0.021) domains declined with hypothyroidism, with reversal of visuospatial function post-LT4 treatment. Conclusion: There is a significant alteration in cognition during short-term hypothyroidism that generally improves with LT4 treatment. It is important to educate patients on specific cognitive domains that can be affected to ensure occupational safety.

Type 2 Deiodinase Thr92Ala Polymorphism and Aging Are Associated with a Decreased Pituitary Sensitivity to Thyroid Hormone.

Background: The DIO2 Thr92Ala polymorphism (rs225014), which occurs in about 15-30% of Caucasian people, determines a less efficient type 2 deiodinase (D2) enzyme. The aim of this study was to determine the impact of DIO2 Thr92Ala polymorphism on the serum thyrotropin (TSH) levels in thyroidectomized patients with hypothyroidism and to evaluate whether TSH levels and aging could be related, at pituitary level, to D2 activity. Methods: This prospective study was performed on 145 thyroid cancer patients, treated with total thyroidectomy, and undergoing radioiodine treatment after 3 weeks of levothyroxine (LT4) withdrawal. A mouse model has been used to determine D2 protein and mRNA levels in pituitary during aging. Results: Genetic analysis identified DIO2 Thr92Ala polymorphism in 56% of participants: 64/145 (44%) patients were homozygous wild type (WT) (Thr/Thr), 64 (44%) heterozygous (Thr/Ala), and 17 (12%) homozygous mutant (Ala/Ala). A significant negative relationship was observed between aging and the rise in serum TSH levels during LT4 withdrawal. However, this negative correlation found in WT was reduced in heterozygous and lost in mutant homozygous patients (Thr/Thr r = -0.45, p = 0.0002, 95% confidence interval [CI] -0.63 to -0.23; Ala/Thr r = -0.39, p = 0.0012, CI -0.60 to -0.67; and Ala/Ala r = -0.30, p = 0.2347; CI -0.70 to 0.20). Accordingly, when we compared the TSH measured in each patient to its theoretical value predicted from age, the TSH did not reach its putative target in 47% of WT patients, in 70% of Ala/Thr, and 76% of Ala/Ala carrying patients (p = 0.0036). This difference was lost in individuals older than 60 years, suggesting a decline of D2 associated with aging. The hypothesis that the pituitary D2 decreases with age was confirmed by the evidence that D2 mRNA and protein levels were lower in pituitary from old versus young mice. Conclusion: An age-related decline in TSH production in response to hypothyroidism was correlated with decreased D2 levels in pituitary. The presence of DIO2 homozygous Ala/Ala polymorphism was associated with a reduced level of TSH secretion in response to hypothyroidism, indicating a decreased pituitary sensitivity to serum thyroxine variation (Institutional Research Ethics board approval number no. 433/21).

ASSESSMENT OF THE RELIABILITY OF THE CRITERIA FOR THE CONSISTENCY OF RADIOIODABLATION

Summary: the article discusses the reasons for the possible ineffectiveness of radioiodablation in patients with differentiated thyroid cancer when using adequate individually calculated activities of 131I. Based on a prospective analysis of post-therapeutic whole-body scintigraphy, laboratory parameters, dosimetric control and clinical manifestations after radionuclide therapy, significant criteria for the possible failure of standard combination therapy are identified and a change in treatment tactics in this group of patients is proposed.Purpose: search for the reasons for unsatisfactory results of radionuclide treatment in patients with differentiated thyroid cancer. Materials and Methods: analysis of 2260 patients with differentiated thyroid cancer who received combined treatment using traditional preparation methods using thyrotropin alpha, from which a group was identified with a high level of 131I. that was unexpected at the pre-therapeutic stage against the background of early radiation diseases and low dosimetry indicators. In patients, laboratory parameters of TSH, thyroglobulin and thyroglobulin antibodies were assessed using radioimmunoassay and clinical manifestations of radiation conditions, taking into account the prescribed therapy; The scintigraphy of the thyroid bed with 99mTc-pertechnetate, post-therapeutic scintigraphy with 131I upon exiting the «closed mode» and dosimetric control under standard conditions every 24 hours after taking the therapeutic activity were performed.Material and methods: prospective single-center analysis of data from 2260 patients with differentiated thyroid cancer who received combined treatment using the traditional preparation method and the use of thyrotropin alfa, from which a group with an unexpected high RP uptake at the pre-therapeutic stage was identified against the background of the absence of early radiation complications and low dosimetry indicators. In patients, laboratory parameters of TSH, TG and AT-TG were assessed using radioimmunoassay and clinical manifestations of radiation reactions, taking into account the prescribed therapy; scintigraphy of the thyroid bed with 99mТс-sodium pertechnetate, post-therapeutic scintigraphy with 131I upon exiting the «closed mode» and dosimetric monitoring with an assessment 48 hours after ingestion of therapeutic activity. Results: analyzed the data of a group of patients in whom there was a marked discrepancy between the usually interdependent results of scintigraphy before and after RIA, which subsequently changed the treatment tactics in their relation. A statistically significant difference was found between the selected groups in terms of the level of stimulated TSH (in patients with predictable (73,9±31,8 mU/L) and unexpected (114,1±30,5 mU/L) uptake of 131I (p=0,0218); by the values of the dose rate 48 hours after the intake of the calculated activity of 131I (p=0,000005). In addition, we additionally analyzed the effect of traditional and drug methods of stimulating thyrotropinemia during preparation for radionuclide ablation. Withdrawal of levothyroxine and with the use of rhTSH, TSH indices were 80,7±27 mU/L and 123,3±75,8 mU/L, respectively (p=0,035), and the levels of stimulated thyroglobulin were 10,2±4,0 ng / ml and 3,2±2,5 ng / ml (p=0,041). Conclusion: the obtained results show that the recommended empirical level of TSH &gt; 30 mU/L is not synonymous with the activation of sodium iodine symporter and the viability of RIA, and also make it possible to distinguish a group of patients with delayed/ partial activation of the symporter. In the continuation of this study, we plan to change the protocol for preparation for radioiodablation and find criteria for pre-therapeutic diagnosis of this group of patients

ODP491 Levothyroxine Withdrawal Presenting as Myxedema Madness

Abstract Introduction Myxedema coma, a medical emergency, refers to severe hypothyroidism which can be precipitated by several factors including acute infection, myocardial infarction, and hypothermia. Rarely, patients may present with myxedema psychosis which manifests as suicidal ideations, hallucinations and or delusions. Case Presentation A 60-year-old woman with a history of hypertension, hypothyroidism, anxiety disorder and heroin abuse on methadone 50 mg every day presented to the hospital with acute onset of altered mental status. Per the patient, she called 911 for "cardiac arrest and talking about dead bodies". Upon presentation, the patient was hypertensive, 184/124mmHg. Physical exam was notable for active hallucinations. She was alert and oriented to person and place, with an unsteady gait. Laboratory examination was remarkable for hyponatremia 131 mmol/L (137-147 mmol/L). She received workup for acute encephalopathy and ED physicians determined that if the workup was negative, she should be evaluated by Psychiatry. Infectious processes and drug intoxication/overdose were ruled out. Psychiatry determined that the patient's psychosis was due to an organic etiology. Follow-up laboratory showed TSH 155 ulU/mL (0.350-4.80 ulU/mL), free thyroxine 4 &amp;lt; 0.1 ng/dL (0.90-1.8 ng/dL) and thyroid peroxidase antibody 460 IU/ml (&amp;lt;34.9). While in the ICU, she became bradycardic, heart rate 25 bpm, and hypoxic, O2 saturation ∼ 75%. She was placed on nasal cannula with improved oxygenation. Later she experienced two seizures lasting approximately 1 minute. The patient received stress dose steroids intravenously every 8 hours and levothyroxine intravenously. Adrenal insufficiency workup was within normal limits. On hospital day 3, her mental status improved and she was transitioned to oral levothyroxine. The patient was transferred to the medical floor for further care. Upon questioning, she reported she stopped taking her levothyroxine for approximately 6 months. Her delusions decreased and later resolved on hospital day 10. She was discharged home with 100 mcg oral levothyroxine and outpatient follow-up with Endocrinology. Conclusion Our patient presented with a rare manifestation of severe hypothyroidism, myxedema madness. The relationship between psychosis and thyroid dysfunction has long been documented. In the same period, there has only been a few reported cases of myxedema madness in literature, generally reported in Psychiatric journals. This is surprising, given that these are endocrinological emergencies. Importantly, patients with an acute presentation of psychosis, should be tested for thyroid abnormalities, as this is reversible. In our patient's case, she had no previous documented psychiatric history. It is reasonable therefore to conclude that, herlikely myxedema madness resulted from prolonged thyroid replacement non-compliance. Presentation: No date and time listed

Brain [18F]Fluorodeoxyglucose Metabolism Assessment under Hypothyroidism and Recombinant Human Thyroid-Stimulating Hormone in Comparison with Thyroid Hormone Replacement in Patients Submitted to Total Thyroidectomy

Objective: To compare brain metabolism using [18F]fluorodeoxyglucose ([18F]FDG) positron emission tomography/computed tomography (PET/CT) in total thyroidectomy patients during hypothyroidism (levothyroxine withdrawal) or under recombinant human thyroid-stimulating hormone (rhTSH) against levothyroxine intake. Methods: A total of 12 patients were randomly divided into two groups. One group underwent the first [18F]FDG PET/CT brain scan after levothyroxine withdrawal (hypothyroidism condition) and repeated the scan 6 months later during regular levothyroxine intake (replacement condition). The other group underwent the first [18F]FDG PET/CT scan after receiving an rhTSH injection and maintained regular levothyroxine intake (rhTSH condition), and repeated the scan 7 months later during regular levothyroxine intake without rhTSH administration. The intra-group regional brain metabolisms were compared. Results: Under the hypothyroidism condition, brain metabolism was significantly reduced, namely in the bilateral pre-frontal, temporal, anterior cingulate, and primary motor cortices, insula, and striatum (uncorrected voxelwise p &lt; 0.005); No significant differences were found between the rhTSH and replacement conditions. Conclusion: rhTSH administration could be a better option than levothyroxine withdrawal for 131I treatment, serum thyroglobulin measurement, or radioiodine scanning for patient follow-up.

Fortuitously detected Paget’s bone disease in a patient with TENIS syndrome on FDG PET/CT

A 74-year-old lady presented with a complaint of progressive neck swelling for two years. FNAC from the swelling was suggestive of papillary carcinoma thyroid (PCT). She underwent total thyroidectomy with central compartment lymph node dissection. Histopathology revealed multifocal PCT with central compartment lymph node metastases. Her baseline stimulated sTg was 5.3 ng/ml after levothyroxine withdrawal. WBS showed uptake in the operative bed (not shown). She was treated with 100 mCi of I-131 and was kept on a suppressive dose of thyroxin hormone. Her sTg gradually increased (77.5 ng/ml) in follow-up after three years. WBS was negative for metastatic disease. She underwent FDG PET/CT, that revealed cervical and upper mediastinal lymph nodes. Apart from that, multiple pagetic lesions were also noted. The patient had a history of mild localized pain and tenderness over these. Her Serum Alkaline phosphatase level was elevated (269 U/L). The patient refused resurgery for cervical lymph nodes. She is on Zolendronic acid infusion and remains asymptomatic. She is in regular follow-up, and her suppressedsTg remains stable even after two years.

Value of stimulated pre-ablation thyroglobulin as a prognostic marker in patients with differentiated thyroid carcinoma treated with radioiodine.

To determine which Thyroglobulin (Tg) level after levothyroxine (LT4) withdrawal (stimulated thyroglobulin - sTg) measured before radioiodine therapy (RAIT) is able to predict incomplete response to treatment of differentiated thyroid carcinoma (DTC) with greater sensitivity and specificity one year after initial treatment with I131. A chart review was performed in which 375 patients with DTC treated with RAIT were included. The sTg was measured in all patients prior to treatment with I131. Follow up were then performed one year later. Initial sTg levels were associated to DTC outcomes. A receiver operating characteristic (ROC) curve was performed to achieve a sTg level able to predict which patients would have a greater chance of having an incomplete response to RAIT. Incomplete response to treatment was found in 122 patients (32.5%), this group had a mean sTg of 23.2 ng/mL. ROC curve showed that the optimal cut-off sTg level was 4.4 ng/mL. (sensitivity: 72.1%; specificity: 72.3%; accuracy: 72.2%; positive predictive value of 55.7%; and negative predictive value: 84.3%). sTg pre-ablation is a valuable predictor of DTC incomplete response to treatment one year after RAIT. Levels of 4.4 ng/ml or more showed higher accuracy to predict this outcome.

Outcomes of Thyrotropin Alfa Versus Levothyroxine Withdrawal-Aided Radioiodine Therapy for Distant Metastasis of Papillary Thyroid Cancer.

Background: Thyrotropin alfa (rhTSH) is not currently approved by the Food and Drug Administration or European Medicines Agency for the preparation of radioactive iodine therapy (RAIT) in patients with distant metastatic papillary thyroid cancer (PTC). There are only a few studies comparing rhTSH with levothyroxine withdrawal (LTW) in this context. Our main aim was to compare the two methods of RAIT preparation in terms of avidity and structural/biochemical response in distant metastatic PTC. We also intended to evaluate whether the two methods of RAIT preparation represented independent prognostic factors for progression-free survival (PFS) and disease-specific survival (DSS) in this subset of patients. Methods: We performed a retrospective analysis of all patients with PTC treated with RAIT for distant metastatic disease between 2006 and 2018. We included 95 PTC patients-27 (28.4%) had LTW and 68 (71.6%) had rhTSH for RAIT. Results: The two groups presented similar clinicopathological characteristics, except for median age at PTC diagnosis, which was higher in the rhTSH group (p = 0.001), but the median age at first RAIT for distant metastatic disease was not different between the two methods of preparation, 63 years old (interquartile range [IQR] 23) in the LTW group versus 70 (IQR 26.75), p = 0.06. Avidity was similar between the two groups (p = 0.973). Median estimate PFS (p = 0.076) and DSS (p = 0.084) were also similar between LTW and rhTSH. Regarding RAIT-related side effects, only 1 (3.7%) patient and 5 (7.4%) patients in the LTW and rhTSH groups, respectively, reported sialadenitis (p = 0.670). Conclusions: There were no differences between the two methods of RAIT preparation regarding avidity and clinical response. rhTSH may be used as an alternative method of preparation for RAIT in patients with known distant lesions, as it presents similar clinical outcomes to LTW and a good safety profile.

Papillary Thyroid Carcinoma With Axillary Lymph Node Metastasis

Papillary thyroid carcinoma (PTC) is typically known to be a non-aggressive form of thyroid follicular epithelial-derived cancer. It is characterized histologically by classic and variant forms. Metastases are uncommon and spread mainly via lymphatic channels to cervical lymph nodes and less commonly via hematogenous spread to lungs and bone. Axillary lymph node (ALN) metastasis is a rare sequela of disease presentation. A 59-year-old female presented for evaluation of shortness of breath and chest pain for one week. She had a longstanding history of hypothyroidism due to chronic lymphocytic thyroiditis which was stable on levothyroxine. Her physical exam revealed a firm mass on the inferior aspect of the left neck. Computed tomography (CT) angiogram ruled out pulmonary embolism but noted a superior mediastinal mass and significant left axillary and subpectoral adenopathy. Mammogram was negative for breast malignancy. Left axillary ultrasound showed a 1.1 x 1.8 x 1.9 cm enlarged lymph node. Thyroid ultrasound showed a 3 mm nodule on the left lower pole and a 3.7 x 2.9 x 2.1 cm heterogeneous and irregular mass in the left neck. Positron emission tomography/CT showed increased uptake in left lower paratracheal, left supraclavicular and axillary lymph nodes. Fine needle aspiration of the left neck mass and left ALN confirmed metastatic papillary carcinoma. She underwent total thyroidectomy, left modified neck, central neck, and left ALN dissection along with partial esophageal wall excision. Intraoperatively, she was found to have a multifocal tumor in the left thyroid lobe with the largest dimension of 1 cm. Surgical pathology noted that the primary tumor in the left thyroid was classic type of papillary carcinoma, and the metastatic tumor in the lymph nodes was of tall cell variant. I-123 thyroid uptake and scan after surgery showed low residual thyroid uptake of 0.6%. She underwent adjuvant ablation with 155 millicuries (mCi) of radioiodine (RAI or I-131) following levothyroxine withdrawal protocol. Post ablation therapy thyroid uptake and scan showed no radiotracer uptake within the thyroidectomy bed. According to the American thyroid association (ATA) risk stratification system, she was categorized as high risk. This case illustrates that PTC may exceptionally spread to axillary lymph nodes. Physiologic flow is centripetal to the jugulosubclavian junction and there is no communication between cervical and axillary lymphatics. However malignant tumors can alter and partially block lymphatic pathways, resulting in ALN metastasis in a retrograde direction. This case also demonstrates that PTC can be transformed into aggressive forms associated with worse prognosis such as tall cell variant. Further comprehensive monitoring and management approaches are needed to plan treatment and gauge prognosis of patients with PTC who present with ALN metastasis.

Abnormal Brain Glucose Metabolism in Papillary Thyroid Cancer Patients 4 Weeks After Withdrawal of Levothyroxine: A Cross-Sectional Study Using 18F-FDG PET/CT.

BackgroundThere is no doubt that thyroid dysfunction is associated with psychiatric disorders. A large amount of thyroid carcinoma patients displayed mood disorders after the withdrawal of levothyroxine (LT4). However, it is unclear whether the disorders are related to the transient withdrawal of LT4, and if yes, what the possible underlying mechanism is. This study aims to investigate the abnormal regional cerebral glucose metabolism (rCMRglu) in a group of papillary thyroid cancer (PTC) patients without LT4 for 4 weeks and prove the relationship between the abnormal rCMRglu with depression and anxiety.MethodsBrain 18F-FDG PET/CT data of 38 consecutive PTC patients with high/intermediate-risk from June 2016 to December 2017 have been analyzed. Of the 38 patients, 23 are in the LT4 withdrawal group (WG) and 15 in the LT4 replacement group (RG). These patients were also evaluated for depressive and anxiety symptoms within 24 h after the scans based on the Hamilton Depression Rating Scale (17 items, HRDS-17) and the Hamilton Anxiety Rating Scale (HAMA) respectively.ResultsThirty-eight patients (12 men, 26 women; age range, 25–69 years; mean age, 45.8 years) were selected in the study. Compared with the RG, patients in WG showed depression and anxiety with higher total scores of HRDS-17 and HAMA (14.7 ± 5.8 vs 3.8 ± 5.5, t = −5.74, p = 0.00; 9.3 ± 4.3 vs 2.7 ± 4.1, t = −4.74, p = 0.00, respectively). In the brain glucose metabolism analysis, the WG patients showed lower rCMRglu in Occipital_Mid_R and Postcentral_L. On the other hand, data illustrated significant rCMRglu increases in the Frontal_Sup_Orb_L. Compared with the healthy group (HG), the rCMRglu of the Postcentral_L and Precuneus_L showed hypoactivity, but the Hippocampus_R and the Temporal_Inf_L showed hyperactivity. This analysis yielded a significant correlation between abnormal rCMRglu with the free thyroxine level, the serum thyroid-stimulating hormone level, HRDS-17, and HAMA scores.ConclusionsThe findings showed that more PTC patients exhibited depression and anxiety after LT4 withdrawal for 4 weeks. More attention should be paid to these hypothyroid patients while they were in the hospital. Such a short-term LT4 withdrawal also likely induced abnormal rCMRglu. Our study attempts to explain the possible mechanism of mood disorders related to transient hypothyroidism.

Comparison of therapeutic radioiodine dose to ablation response in differentiated thyroid cancer patients with cut-off serum thyroglobulin level after two weeks of levothyroxine withdrawal

Comparison of therapeutic radioiodine dose to ablation response in differentiated thyroid cancer patients with cut-off serum thyroglobulin level after two weeks of levothyroxine withdrawal

Renal Function and Plasma Renin activity as Potential Factors Causing Hyperkalemia in Patients with Thyroid Carcinoma Undergoing Thyroid Hormone Withdrawal For Radioactive Iodine Therapy

Objective: Hypothyroidism is not commonly considered a cause of hyperkalemia. We previously reported that hyperkalemia was observed mainly in elderly patients treated with renin-angiotensin-aldosterone system (RAS) inhibitors when levothyroxine treatment was withdrawn for the thyroidectomized patients with thyroid carcinoma to undergo radioactive iodine treatment. Here, we investigated whether acute hypothyroidism causes hyperkalemia in patients who were not treated with RAS inhibitors. We also investigated factors influencing potassium metabolism in hypothyroid patients. Methods: We conducted a single-center, prospective cohort study of 46 Japanese patients with thyroid carcinoma undergoing levothyroxine withdrawal prior to radioiodine therapy. All patients were normokalemic before levothyroxine withdrawal. Blood samples were analyzed 3 times: before, and at 3 and 4 weeks after levothyroxine withdrawal. We investigated factors that may be associated with the elevation of serum potassium levels from a euthyroid state to a hypothyroid state. Results: None of the patients developed symptomatic hyperkalemia. The mean serum potassium level was significantly higher at 4 weeks after levothyroxine withdrawal compared to baseline. The serum sodium levels, the estimated glomerular filtration rate (eGFR), and the plasma renin activity (PRA) decreased significantly as hypothyroidism advanced. In contrast, the plasma levels of adrenocorticotropic hormone, cortisol, aldosterone, and antidiuretic hormone were not changed, while serum thyroid hormone decreased. At 4 weeks after their levothyroxine withdrawal, the patients' serum potassium values were significantly correlated with the eGFR and the PRA. Conclusion: Acute hypothyroidism can cause a significant increase in the serum potassium level, which may be associated with a decreased eGFR and decreased circulating RAS. Abbreviations: ACTH = adrenocorticotropic hormone; ADH = antidiuretic hormone; ATPase = adenosine triphosphatase; eGFR = estimated glomerular filtration rate; HbA1c = glycated hemoglobin; K+ = potassium; Na+ = sodium; PRA = plasma renin activity; RAS = renin-angiotensin-aldosterone system; T4 = thyroxine; TSH = thyroid-stimulating hormone.

Partial withdrawal of levothyroxine treated disease leads to brain activations and effects on performance in a working memory task: A pilot study.

Hypothyroidism is associated with memory impairments. The present study aimed to evaluate the effects of partial withdrawal of levothyroxine on working memory tasks and brain function. Fifteen subjects under long-term levothyroxine substitution as a result of complete hypothyroidism participated in the present study. Functional magnetic resonance imaging (MRI) was performed using a working memory task (n-back task) and neuropsychological tests were performed before and 52-54 days after the induction of subclinical hypothyroidism by reducing the pretest levothyroxine dosage by 30%. Reaction time of subjects under partial levothyroxine withdrawal was significantly longer and less accurate with respect to solving the working memory tasks. Functional MRI revealed significant activation changes after medication withdrawal in the cerebellum, insula, parietal, frontal, temporal and occipital lobes, lingual gyrus, and the cuneus. Partial withdrawal of levothyroxine may lead to deficits in a working memory task and to an activation of brain areas associated with working memory ability.

Recombinant human thyrotropin (rhTSH) versus Levo-thyroxine withdrawal in radioiodine therapy of differentiated thyroid cancer patients: differences in abdominal absorbed dose.

In DTC patients, 131-radioiodine therapy has routinely been used for many years for thyroid remnant ablation after thyroid surgery. To date, two different strategies can be used to achieve sufficient TSH stimulation on thyroid remnant: (I) Levo-thyroxine withdrawal or (II) rhTSH stimulation. The aim of our study was to compare the abdominal absorbed dose ratio between differentiated thyroid cancer patients who underwent thyroid remnant ablation after either L-T4 withdrawal or rhTSH stimulation. We reviewed the records of 63 patients affected by differentiated thyroid cancer. All patients underwent thyroid remnant ablation after either L-T4 withdrawal or rhTSH stimulation. A post-therapy whole-body scan was obtained 5 days after 131-radioiodine therapy. Qualitative and quantitative image analysis was performed. Quantitative analysis was performed by drawing seven regions of interest on the abdomen (anterior and posterior views) to estimate both the activity ratio (AR) and absorbed dose ratio (DR) obtained in patients treated in hypothyroidism or after rhTSH stimulation. The values of the activity and absorbed dose ratios obtained on each abdomen region (liver, stomach, ascending colon, transverse colon, descending colon, rectum, and small intestine) were always higher in patients treated after L-T4 withdrawal than after rhTSH stimulation with p-values of 0.000, 0.000, 0.001, 0.000, 0.022, 0.007, and 0.002, respectively. DTC patients treated with 131-radioiodine after rhTSH stimulation have lower abdominal radioiodine activity than hypothyroid patients. Our data could be of practical relevance in terms of patient management. The potential impact on rare radioiodine-related gastrointestinal side effects is to be established in specifically designed prospective studies.

Effects of Short-Term Hypothyroidism on the Lipid Transfer to High-Density Lipoprotein and Other Parameters Related to Lipoprotein Metabolism in Patients Submitted to Thyroidectomy for Thyroid Cancer

Elevation of low-density lipoprotein (LDL) cholesterol is the hallmark of the dyslipidemia observed in hypothyroidism, but alterations on high-density lipoprotein (HDL) plasma levels and metabolism are less understood. The aim of this study was to explore aspects of HDL metabolism and enzymes that act on HDL after a short period of overt hypothyroidism. Eighteen women (age 44 ± 11 years; body mass index 27.9 ± 5.2 kg/m2) were studied before total thyroidectomy for thyroid cancer, when they were euthyroid, and after thyroidectomy, in overt hypothyroidism for three weeks, following levothyroxine withdrawal for performance of a whole-body scan. Thyrotropin and free thyroxine confirmed hypothyroidism; low thyroglobulin and radioiodine uptake indicated near absence of thyroid tissue. LDL cholesterol (125 ± 35 vs. 167 ± 40 mg/dL; p = 0.0002), HDL cholesterol (HDL-C; 39 ± 8 vs. 46 ± 10 mg/dL; p = 0.0025), non-HDL-C (149 ± 38 vs. 201 ± 46 mg/dL; p < 0.0001), unesterified cholesterol (53 ± 10 vs. 70 ± 16 mg/dL; p = 0.0003), apolipoprotein (apo) A-I (1.32 ± 0.19 vs. 1.44 ± 0.22 g/L; p < 0.04), and apo B (0.97 ± 0.25 vs. 1.31 ± 0.28 g/L; p < 0.0001) plasma concentrations were all higher in hypothyroidism compared to values in the euthyroid state, but triglycerides and Lp(a) were unchanged. There were no changes in HDL particle size and lipid composition, cholesteryl ester transfer protein and lecithin cholesterol acyltransferase concentrations and in paraoxonase-1 activity. Regarding the in vitro assay to estimate lipid transfer to HDL, there were no changes when comparing the euthyroid to the hypothyroid state, but when adjusted for HDL-C, the unesterified cholesterol (0.14 ± 0.03 vs. 0.11 ± 0.02; p < 0.0001), triglycerides (0.11 ± 0.02 vs. 0.09 ± 0.02; p < 0.0001), phospholipids (0.44 ± 0.09 vs. 0.40 ± 0.07; p = 0.0205), and esterified cholesterol (0.14 ± 0.03 vs. 0.13 ± 0.03; p = 0.0043) transfer to HDL were all diminished in hypothyroidism. In short-term hypothyroidism, HDL-C increased, but this did not increase the capacity of the HDL fraction to receive lipids or the activity of paraoxonase-1, the anti-oxidation enzyme associated to HDL.

Experimentally induced subclinical hypothyroidism causes decreased functional connectivity of the cuneus: A resting state fMRI study

ObjectiveThe aim of this study was to experimentally evaluate the effects of subclinical mild hypothyroidism on brain network connectivity as determined by resting state fMRI (rsfMRI) which serves as a proxy for global changes in brain function. MethodsFifteen otherwise healthy patients with complete hypothyroidism under stable, long term levothyroxine substitution volunteered for the study. They reduced their pretest levothyroxine dosage by 30% for 52–56 days. Basally and after partial levothyroxine withdrawal, rsfMRI along with a neuropsychological analysis was performed. RsfMRI was subjected to graph-theory-based analysis to investigate whole-brain intrinsic functional connectivity. ResultsThe desired subclinical hypothyroidism was achieved in all subjects. This was associated with a significant decrease in resting-state functional connectivity specifically in the cuneus (0.05 FWE corrected at cluster level) which was mainly caused by a weaker functional connectivity to the cerebellum and regions of the default mode network, i.e. the medial prefrontal cortex, the precuneus and the bilateral angular gyri. The decrease in cuneus connectivity was correlated to the increase in TSH serum levels. A working memory task showed a slightly longer reaction time and less accuracy after partial levothyroxine withdrawal. ConclusionEven short-term partial levothyroxine partial withdrawal leads to deficits in working memory tasks and to a weaker integration of the cuneus within the default mode network.