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

Abstract

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.

Thyroid Hormone Withdrawal versus Recombinant Human TSH as Preparation for I-131 Therapy in Patients with Metastatic Thyroid Cancer: A Systematic Review and Meta-Analysis

“…A transient reduction in health-related quality of life was consistently determined [34][35][36][37][38][39]. Some studies also showed an increase in depression and anxiety, and, in other studies, this was observed mainly in patients with predisposing factors [35][36][37][39][40][41]. With previous neuropsychiatric diseases, there is a risk of exacerbation due to hypothyroidism [42].…”

“…Furthermore, a limitation of cognitive abilities is observed [34,43], which is particularly relevant for complex mental requirements. A reduction in cerebral blood flow and glucose metabolism in the short-term hypothyroid in contrast to the rhTSH-stimulated DTC patients was described as a correlate for such limitations using PET [41,44,45]. The reactivity can also be reduced, which can limit the operation of high-speed machines or the ability to drive, or at least make it appear questionable for insurance reasons-although the relevance in this regard has been assessed differently [40,46].…”

Increased Pituitary Fluorine-18-Fluorodeoxyglucose Uptake in Patients with Differentiated Thyroid Cancer in Hypothyroidism versus under Recombinant Human Thyroid-Stimulating Hormone Stimulation

“…Previous studies have demonstrated that thyroid function can impact the metabolic activity of various tissues, as evidenced in 18 F-FDG PET/CT scans [6]. Under physiological conditions, the pituitary gland shows little uptake of 18 F-FDG; incidental findings of pituitary hypermetabolism are unusual, with a reported frequency of 0.8% [7][8][9][10].…”

“…The clinical advantage of rhTSH is that patients continue thyroid hormone substitution, thereby avoiding symptoms of hypothyroidism [2][3][4]. The rationale for performing 18 F-FDG PET/CT at the time of RAI therapy is that the high TSH levels may increase the detection rate of metastatic DTC lesions; similarly, outside RAI therapy, rhTSH may be used to potentially increase the sensitivity of 18 F-FDG PET/CT to detect low-volume disease [5].…”

“…Previous studies have demonstrated that thyroid function can impact the metabolic activity of various tissues, as evidenced in 18 F-FDG PET/CT scans [6]. Under physiological conditions, the pituitary gland shows little uptake of 18 F-FDG; incidental findings of pituitary hypermetabolism are unusual, with a reported frequency of 0.8% [7][8][9][10]. Therefore, pituitary incidentalomas identified on the 18 F-FDG PET/CT merit further diagnostic workup to discriminate between clinically significant pathologic pituitary uptake and nonspecific physiologic pituitary uptake; the most common disease was a primary pituitary tumor, metastatic malignancy, Langerhans cell histiocytosis, and inflammatory hypophysitis [8,9].…”