Neurometabolite Changes in Hyperthyroid Patients Before and After Antithyroid Treatment: An in vivo1H MRS Study

Purpose: Patients with hyperthyroidism have frequent neuropsychiatric symptoms such as lack of attention, concentration, poor memory, impaired executive functions, depression, and anxiety. These neurocognitive impairments such as memory, attention, and executive functions appear to be associated with dysfunction in brain regions. This study was conducted to investigate the metabolic changes in the brain subcortical regions, i.e., posterior parietal cortex and dorsolateral prefrontal cortex (DLPFC), in patients with hyperthyroidism before and after antithyroid treatment using proton magnetic resonance spectroscopy (1H MRS).Materials and Methods: We collected neuropsychological and 1H MRS data from posterior parietal cortex and DLPFC, in both control (N = 30) and hyperthyroid (N = 30) patients. In addition, follow-up data were available for 19 patients treated with carbimazole for 30 weeks. The relative ratios of the neurometabolites were calculated using the Linear Combination Model (LCModel). Analysis of co-variance using Bonferroni correction was performed between healthy controls and hyperthyroid patients, and a paired t-test was applied in patients at baseline and follow-up. Spearman’s rank-order correlation was used to analyze bivariate associations between thyroid hormone levels and metabolite ratios, and the partial correlation analysis was performed between neuropsychological scores and metabolite ratios, with age and sex as covariates, in the patients before and after treatment.Results: Our results revealed a significant decrease in choline/creatine [glycerophosphocholine (GPC) + phosphocholine (PCh)/creatine (tCr)] in both the posterior parietal cortex and DLPFC in hyperthyroid patients, and these changes were reversible after antithyroid treatment. The posterior parietal cortex also showed significantly reduced glutamate/creatine (Glu/tCr), (glutamate + glutamine)/creatine (Glx/tCr), and increased glutathione/creatine (GSH/tCr) ratios in the hyperthyroid patients over control subjects. In DLPFC, only (N-acetyl aspartate + N-acetyl aspartyl-glutamate)/creatine (NAA + NAAG)/tCr was increased in the hyperthyroid patients. After antithyroid treatment, (GPC + PCh)/tCr increased, and Glx/tCr decreased in both brain regions in the patients at follow-up. Gln/tCr in the posterior parietal cortex was decreased in patients at follow-up. Interestingly, (GPC + PCh)/tCr in DLPFC showed a significantly inverse correlation with free tri-iodothyronine (fT3) in hyperthyroid patients at baseline, whereas NAA/tCr showed positive correlations with fT3 and free thyroxine (fT4) in hyperthyroid patients before and after antithyroid treatment, in the posterior parietal cortex. In DLPFC, only (NAA + NAAG)/tCr showed positive correlations with fT3 and fT4 in the patients before treatment.Conclusion: The overall findings suggest that all the brain metabolite changes were not completely reversed in the hyperthyroid patients after antithyroid treatment, even after achieving euthyroidism.

HEMATOLOGICAL DISORDERS OF PROPYLTHIOURACIL IN THYROID PATIENTS AT TERTIARY CARE HOSPITAL OF HYDERABAD

Objective: To find out the frequency of anemia, agranulocytosis and thrombocytopenia in hyperthyroid patients after the use of propylthiouracil. Study Design: Cross sectional study. Place and Duration of Study: Out Door Patients Department and Pathology Laboratory in Liaquat University Medical & Health Sciences, Hospital Hyderabad/Jamshoro, from May 2016 to Apr 2017. Methodology: Two hundred cases, comprising of adult patients were categorized into five groups, age group 15-30 years 79 (39.5%) patients presenting the highest out of total, age group 31-45 years 68 (34%) patients, age group 46-60 years 36 (18%), age group 61-75 years 14 (7%) patients, age group >75 years 3 (1.5) patients. Complete blood count was analyzed on Sysmex Kx21 and thyroid profiles were analyzed on Elecysis 2010 from the Pathology Department. SPSS version 22 was used for data analysis. Result: Out of total patients, 32 (16%) were males and 168 (84%) were females with mean age of 37.44 ± 14.82 years. Majority of patients 68 (34%) were anemic, while 4 (2%) had agranulocytosis and 11 (5.5%) had thrombocytopenia. Headache was reported in 111 (55.5%), exophthalmos in 106 (53%), sore throat in 172 (86%), fever in 136 (68%) and weight loss in 95 (47.5%) patients. Conclusion: Propylthiouracil causes defective hematopoiesis in hyperthyroid patients because propylthiouracil has adverse suppressive effects on bone marrow.

Smoothelin-like Protein 1 Regulates the Thyroid Hor-Mone-Induced Homeostasis and Remodeling of C2C12 Cells via the Modulation of Myosin Phosphatase

The pathological elevation of the active thyroid hormone (T3) level results in the manifestation of hyperthyroidism, which is associated with alterations in the differentiation and contractile function of skeletal muscle (SKM). Myosin phosphatase (MP) is a major cellular regulator that hydrolyzes the phosphoserine of phosphorylated myosin II light chain. MP consists of an MYPT1/2 regulatory and a protein phosphatase 1 catalytic subunit. Smoothelin-like protein 1 (SMTNL1) is known to inhibit MP by directly binding to MP as well as by suppressing the expression of MYPT1 at the transcriptional level. Supraphysiological vs. physiological concentration of T3 were applied on C2C12 myoblasts and differentiated myotubes in combination with the overexpression of SMTNL1 to assess the role and regulation of MP under these conditions. In non-differentiated myoblasts, MP included MYPT1 in the holoenzyme complex and its expression and activity was regulated by SMTNL1, affecting the phosphorylation level of MLC20 assessed using semi-quantitative Western blot analysis. SMTNL1 negatively influenced the migration and cytoskeletal remodeling of myoblasts measured by high content screening. In contrast, in myotubes, the expression of MYPT2 but not MYPT1 increased in a T3-dependent and SMTNL1-independent manner. T3 treatment combined with SMTNL1 overexpression impeded the activity of MP. In addition, MP interacted with Na+/K+-ATPase and dephosphorylated its inhibitory phosphorylation sites, identifying this protein as a novel MP substrate. These findings may help us gain a better understanding of myopathy, muscle weakness and the disorder of muscle regeneration in hyperthyroid patients.

Toxic adenoma: to biopsy or not to biopsy?

Toxic adenoma nodules rarely harbour cancer. Fine-needle aspiration (FNA) is often not done because of the rarity of these lesions being cancer, the difficulty in interpreting cytology in hyperthyroid patients and the rare precipitation of thyrotoxicosis. We present two young, Caucasian female patients aged 29 and 13 years who were each diagnosed with a toxic nodule categorised as benign and indeterminate respectively. They underwent hemithyroidectomy after being rendered euthyroid, however their histology unexpectedly revealed differentiated follicular cancer. Despite thyroid cancer being rare in patients with toxic adenomas, it should be considered when planning treatment, especially if there are risk factors for cancer, or suspicious features on ultrasound examination. A review of the literature shows that compared with adenomas in euthyroid patients, patients in this group are generally younger and predominately female. If an FNA is considered, it should be performed after the patient is rendered euthyroid.

A higher cut-off for Thyroid-stimulating immunoglobulin (TSI) could better predict relapse in Graves’ disease?

Background: TSH receptor (TSHr)-stimulating immunoglobulins (Igs) can be used as diagnostic markers of Graves’ disease (GD). Thyroid-stimulating immunoglobulin (TSI) assays exclusively detect these specific Igs. Materials and Methods: This was a prospective longitudinal study in which hyperthyroid patients with GD and toxic nodular goitres were evaluated at diagnosis. GD patients were also evaluated at antithyroid drug (ATD) withdrawal. An automated chemiluminescent assay measured TSI. According to the manufacturer TSI less than 0.55 IU/L was a non-reactive result. The authors evaluated the Se and Sp of the cutoff point provided by the TSI assay manufacturer, and tested other cutting points through a ROC curve, to assess relapse risk of Graves’ disease. Results: At diagnosis, were evaluated 92 (85.2%) GD patients aged 41.2 ± 2.0 years, and 16 patients (14.8%) with toxic multinodular goiter (TMNG) or toxic adenoma (TA), aged 60.8 ± 4.8 years. They were re-evaluated after 18 ± 4 months with methimazole (MMI) treatment. The follow-up after treatment suspension was of 20 ± 6 months. At diagnosis, the TSI (Se) and (Sp) were 98.9% and 100%, respectively. At ATD withdrawal, despite a high Se (95.5%), Sp was low (59.6%). By adjusting the cut-off to 1.11 (TSI <1.11 IU/L non-reactive), TSI presented the best Sp (89.4%) with a small decrease in Se (93.3%) in predicting GD relapse. Conclusions: TSI had high Se and Sp in GD differential diagnosis with nodular goiters. In the assessment for GD relapse, by raising the cutting point to 1.11 IU/L, a better Sp was obtained at the expense of a small drop in Se. A larger sample is needed to support a higher TSI cut-off point in the clinical routine to assess GD relapse after ATD.

Study on Thyroid Dysfunction in Patients of Dysfunctional Uterine Bleeding

Aim: The purpose of the study was to detect thyroid dysfunction in women who had abnormal uterine bleeding Study Design: Menorrhagia was the most common type of bleeding (36%). Thyroid dysfunction was discovered in 32% of the patients (Subclinical hypothyroidism in 17%, Hyper thyroid is 11% and hyperthyroidism in 4 % of cases). The researchers looked at 100 cases of Dysfunctional Uterine Bleeding that were clinically identified at Sree Balaji Medical College and Hospital between March 2014 and August 2016. The patients in this study ranged in age from under 20 to 45 years old. The number of instances with DUB who were between the ages of 31 and 40 is 38 %. Methodology: The parity of the patients ranged from unmarried to 0-5, with the parity 2 group accounting for 37% of all DUB patients and the following assessments were made. Results: Thyroid dysfunction was most common in cases of polymenorrhagia (42.8%), menorrhagia (33.3%), polymenorrhea (28.5%), and oligomenorrhea. (26%). Thyroid dysfunction was most common in the age group 31-40 years, accounting for 77.5% of the population. In 17 % of cases, the primary thyroid malfunction was subclinical hypothyroidism. 3% of hyperthyroid patients were also oligomenorrhocic. The most prevalent thyroid disorder in metrorrhagic patients was subclinical hypothyroidism.