Reduced Gene Expression of Peroxisome Proliferator-Activated Receptor Gamma Coactivator-1α in Whole Blood in Euthyroid Patients One Year After Hemithyroidectomy for Benign Euthyroid Goiter.

We have previously reported decreased thyroid function within the laboratory reference range and changes in mitochondrial function after hemithyroidectomy. Peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α) and coactivator-1ß (PGC-1ß) are key regulators of mitochondrial biogenesis and function. The aim was to examine the influence of hemithyroidectomy on the longitudinal change in mRNA expression of these genes. In addition, we measured longitudinal changes in mRNA expressions of the mitochoncrial-related genes nuclear factor erythroid-derived 2-like 2 (NFE2L2), mitochondrial transcription factor A (TFAM), and sodium dismutase 2 (SOD2). Twenty-eight patients were examined before and 1, 3, 6, and 12 months after hemithyroidectomy for benign euthyroid goiter. Thyroid stimulating hormone (TSH) and thyroid hormones were measured, and whole blood gene expression of PGC-1α, PGC-1ß, NFE2L2, TFAM, and SOD2 was examined by reverse transcription quantitative Polymerase Chain Reaction. We used mixed effect regression models to investigate changes in gene expression with time. Averaged over all follow-up visits, TSH increased (p=0.001), tT3 declined (p=0.01), and fT4/tT3 ratio increased (p=0.03) over one-year follow-up, but fT4 remained unchanged. Averaged over all follow-up visits, whole blood PGC-1α levels (p<0.001) and SOD2 (p=0.009) levels declined, but PGC-1ß, TFAM, and NFE2L2 did not change over one-year follow-up. The study demonstrates significant downregulation of whole blood PGC-1α and SOD2 gene expressions in hemithyroidectomized patients with a concomitant increase in TSH concentration within the reference range. Thus, hemithyroidectomized patients may likely have impaired mitochondrial function.

Long-term outcomes after total thyroidectomy.

INTRODUCTION: The aim of this study was to assess the complication rates of total thyroidectomy in a regional hospital setting in Denmark for permanent hypoparathyroidism, recurrent laryngeal nerve palsy and post-operative bleeding. Furthermore, the long-term outcomes in the management of hypoparathyroidism were investigated. METHODS: This was a retrospective study of 114 consecutive patients undergoing total thyroidectomy due to benign thyroid disease. RESULTS: A total of 0.9% suffered from permanent recurrent laryngeal nerve palsy, whereas temporary nerve palsy was seen in 1.8%. Post-operative bleeding occurred in 5.4%. The frequencies of temporary and permanent post-operative hypocalcaemia were 22.8% and 17.4%, respectively. Autotransplantation of parathyroid tissue was performed in 23.7%. Unintentional parathyroidectomy occurred in 8.7%. Serum ionized calcium was significantly lower preoperatively in the group that developed hypocalcaemia (p = 0.03). CONCLUSIONS: The incidence of recurrent laryngeal nerve palsy was similar to that reported in other published studies. Post-operative bleeding was more common than in other studies. The high frequency of permanent post-operative hypocalcaemia is a cause for concern. We need to consider implementing a guideline to facilitate outfacing calcium and vitamin D supplements as an attempt to phase out was not attempted in all patients. FUNDING: not relevant. TRIAL REGISTRATION: The study was approved by the Danish Data Protection Agency, but has not been registered due to its register-based design.

Weight Gain and Serum TSH Increase within the Reference Range after Hemithyroidectomy Indicate Lowered Thyroid Function.

Background. Weight gain is frequently reported after hemithyroidectomy but the significance is recently discussed. Therefore, the aim of the study was to examine changes in body weight of hemithyroidectomized patients and to evaluate if TSH increase within the reference range could be related to weight gain. Methods. In a controlled follow-up study, two years after hemithyroidectomy for benign euthyroid goiter, postoperative TSH and body weight of 28 patients were compared to preoperative values and further compared to the results in 47 matched control persons, after a comparable follow-up period. Results. Two years after hemithyroidectomy, median serum TSH was increased over preoperative levels (1.23 versus 2.08 mIU/L, P < 0.01) and patients had gained weight (75.0 versus 77.3 kg, P = 0.02). Matched healthy controls had unchanged median serum TSH (1.70 versus 1.60 mIU/L, P = 0.13) and weight (69.3 versus 69.3 kg, P = 0.71). Patients on thyroxin treatment did not gain weight. TSH increase was significantly correlated with weight gain (r = 0.43, P < 0.01). Conclusion. Two years after hemithyroidectomy for benign euthyroid goiter, thyroid function is lowered within the laboratory reference range. Weight gain of patients who are biochemically euthyroid after hemithyroidectomy may be a clinical manifestation of a permanently decreased metabolic rate.

Persistent cellular metabolic changes after hemithyroidectomy for benign euthyroid goiter.

BACKGROUND: The significance of perturbations of thyroid-stimulating hormone (TSH) and thyroid hormones within the laboratory reference ranges after hemithyroidectomy is unknown. Our aim was to examine changes in TSH and thyroid hormones after hemithyroidectomy for benign euthyroid goiter, focusing on tissue response by examining the mitochondrial membrane potential (MMP) of peripheral blood mononuclear cells (PBMCs) and basal oxygen consumption (V˙O2). MATERIALS AND METHODS: In a prospective study on 28 patients and controls, we examined serum TSH and thyroid hormones before hemithyroidectomy and 1, 3, 6 and 12 months after hemithyroidectomy for benign euthyroid goiter. In the hemithyroidectomy group, flow cytometry was used to measure the MMP of tetramethylrhodamine methyl ester (TMRM)- and MitoTracker Green (MTG)-stained PBMCs, and V˙O2 was measured by an Oxycon Pro apparatus. RESULTS: One year after hemithyroidectomy, TSH had increased from a median of 0.97 mIU/l (interquartile range, IQR: 0.69-1.50 mIU/l) to 2.10 mIU/l (IQR: 1.90-3.00 mIU/l; p < 0.001); free thyroxine (fT4) had decreased from a median of 16.0 pmol/l (IQR: 14.9-17.0 pmol/l) to 14.8 pmol/l (IQR: 14.1-16.4 pmol/l; p = 0.009), whereas total triiodothyronine variations did not differ from those in controls. Concomitantly, the MMP of TMRM- and MTG-stained PBMCs was increased by 58% (p < 0.001) and 22% (p = 0.008), respectively. V˙O2 was increased by 14% (p = 0.01). CONCLUSION: Hemithyroidectomy for benign euthyroid goiter induced persistently increased TSH and decreased fT4, sustained mitochondrial hyperpolarization and increased V˙O2. Our results demonstrate a decrease after hemithyroidectomy of the metabolic state to which the individual is adapted, with persistent cellular metabolic changes in a hemithyroidectomized patient group which is normally considered clinically and biochemically euthyroid.