Toxic Nodular Goitre Patients Research Articles

Long-Term Results of Fixed High-Dose I-131 Treatment for Toxic Nodular Goiter: Higher Euthyroidism Rates in Geriatric Patients.

Objective:Geriatric patient population has special importance due to particular challenges. In addition to the increase in incidence of toxic nodular goiter (TNG) with age, it has a high incidence in the regions of low-medium iodine intake such as in our country. The aim of this study was to evaluate the overall outcome of high fixed dose radioiodine (RAI) therapy, and investigate the particular differences in the geriatric patient population.Methods:One hundred and three TNG patients treated with high dose I-131 (370-740 MBq) were retrospectively reviewed. The baseline characteristics; age, gender, scintigraphic patterns and thyroid function tests before and after treatment, as well as follow-up, duration of antithyroid drug (ATD) medication and achievement of euthyroid or hypothyroid state were evaluated. The patient population was divided into two groups as those=>65 years and those who were younger, in order to assess the effect of age.Results:Treatment success was 90% with single dose RAI therapy. Hyperthyroidism was treated in 7±7, 2 months after RAI administration. At the end of the first year, overall hypothyroidism rate was 30% and euthyroid state was achieved in 70% of patients. Age was found to be the only statistically significant variable effecting outcome. A higher ratio of euthyroidism was achieved in the geriatric patient population.Conclusion:High fixed dose I-131 treatment should be preferred in geriatric TNG patients in order to treat persistent hyperthyroidism rapidly. The result of this study suggests that high fixed dose RAI therapy is a successful modality in treating TNG, and high rates of euthyroidism can be achieved in geriatric patients.

Improved quality of life in hyperthyroidism patients after surgery

BackgroundThe most common causes of hyperthyroidism are Graves disease (GD) and toxic nodular goiter (TNG). GD and TNG might influence patients' quality of life (QoL). The aim of our study was to analyze and compare the QoL of patients with GD with that of TNG patients and to evaluate the influence of surgical treatment on their QoL. Materials and methodsA prospective case-control study was conducted at the Center for Endocrine surgery in Belgrade, Serbia. The ThyPRO questionnaire was used in the QoL assessment of the GD and TNG patients (31 and 28, respectively) pre- and post-operatively. ResultsAll patients were receiving antithyroid drugs, and none of the patients were overtly hyperthyroid at the time of completing the preoperative questionnaire. The QoL of the GD patients was worse than that of the TNG patients, with significant differences in eye symptoms, anxiety, and sex life domains (P < 0.001, P = 0.005, and P = 0.004, respectively), preoperatively, and in eye symptoms, anxiety, emotional susceptibility, and overall QoL (P = 0.001, P = 0.027, P = 0.005 and P = 0.013, respectively), postoperatively. The improvement in QoL in the GD patients was significant after surgical treatment in all ThyPRO domains. In the TNG patients, the improvement was significant in all but one ThyPRO domain, sex life (P = 0.066). ConclusionsThe QoL of GD patients is worse than those of TNG patients. Surgery may improve QoL in patients with GD and TNG even if they have achieved satisfying thyroid status with medication treatment, preoperatively.

Effect of stressful life events on the initiation of graves’ disease

Objective. The aim of this study was to investigate the relationship between stressful life events (LESs) and its effect on the initiation of Graves’ disease (GD) and toxic nodular goitre (TNG). Patients and method. Forty-five patients with GD, 24 patients with TNG and 36 healthy control (CG) were included to the study. Graves and TNG patients had diagnosed within the last 12 months, with clinical and biochemical confirmation in Endocrinology Metabolism Outpatient Clinic of Cerrahpasa Medical School. The Holmes–Rahe Stress Scale and the Life Experience Survey (LES) was the psychological evaluation instrument used in this study. Results. There was no significant difference according to Holmes–Rahe scale (Graves & TNG P = 0.329, Graves & Control P = 0.115, TNG and control P = 0.571). According to LES scale when negative event number, positive event number, neutral events and their effects are considered, between Graves and TNG groups no statistically difference was observed (P = 0.139, P = 0.083, P = 0.167, P = 0.162, P = 0.861). The number and impact of negative SLEs were significantly higher in GD compared to CG (P = 0.015, P < 0.001). Conclusion. According to LES scale GD patients has significant difference with respect to CG when negative event number and impact are considered.

The influence of non-radioactive iodine (127I) on the outcome of radioiodine (131I) therapy in patients with Graves’ disease and toxic nodular goitre

The aim of the study was to achieve an effective target dose in the thyroid by increasing the effective half-life (Teff) of (131)I by use of iodide ((127)I) two days after (131)I therapy in patients with hyperthyroidism with low Teff. The study was carried out in two groups. Group A - 41 patients, and Group B - 14 patients, all the patients were with hyperthyroidism with Teff less than 3 days qualified for (131)I therapy. Only group A patients received 600 μg of iodide a day for 3 days, two days after (131)I therapy. Radioiodine uptake (RAIU) after 24 and 48 hours, thyroid scintiscan and ultrasonography were done before and after 12 months of (131)I therapy. In group A a significant increase was seen in the Teff (5 days on average) resulting in an increase in the energy target dose by 28% and 37%, in patients with Graves' disease (GD) and toxic nodular goitre (TNG), respectively. After one year of therapy 50% of GD and 93% of TNG patients achieved euthyroidism; 28% of GD and 3% of TNG patients were in hypothyroidism. In Group B, all the patients had radioiodine treatment failure and received a second therapeutic dose of (131)I. Administration of (127)I after (131)I treatment can lead to an increase in its effective half-life. This will also increase the absorbed energy dose in thyroid tissue, thereby improving therapeutic outcome without administration of a higher or second dose of (131)I. This may minimize whole-body exposure to radiation and reduces the cost of treatment.

Iodine-131 Given for Therapeutic Purposes Modulates Differently Interferon-γ-Inducible α-Chemokine CXCL10 Serum Levels in Patients with Active Graves’ Disease or Toxic Nodular Goiter

The mechanism of activation of the immune system after iodine-131 (131I) treatment of hyperthyroidism is still not fully clarified. Serum levels of CXCL10, a prototype of the CXC family of chemokines, are increased in several endocrine autoimmune conditions, and this chemokine plays a role at least in the initial phases of thyroid autoimmune disease and in Graves' disease (GD). OBJECTIVE, DESIGN, AND PATIENTS: The aim of the present study was to measure the serum CXCL10 levels in 20 patients with GD and 10 patients with toxic nodular goiter (TNG) before and 6 months after 131I treatment, when patients had achieved euthyroidism. Forty healthy subjects and 40 patients with autoimmune thyroiditis served as control groups. Before 131I, mean CXCL10 was significantly higher in patients with GD and thyroiditis than controls or those with TNG. Serum CXCL10 levels significantly decreased in GD patients 6 months after 131I treatment, whereas they remained within normal limits in TNG patients after restoration of euthyroidism by 131I. In conclusion, our results demonstrate that high serum CXCL10 levels are associated with the hyperthyroid phase in GD but not TNG, providing further evidence for a minimal role of hyperthyroidism per se in determining high CXCL10 levels and showing a strong association with the autoimmune process. The reduction of CXCL10 levels after 131I treatment in GD only shows that the thyroid gland itself is the main source of circulating CXCL10.

Increase of interferon‐γ‐inducible CXC chemokine CXCL10 serum levels in patients with active Graves’ disease, and modulation by methimazole therapy

CXCL10 plays an important role in the initial phases of Graves' disease (GD) and autoimmune thyroiditis (AT); however, until now, CXCL10 serum levels (sCXCL10) in patients with GD have never been evaluated in relation to thyroid function and treatment. To evaluate sCXCL10 in GD. Cross-sectional. One hundred and three GD, 164 AT, 20 nontoxic multinodular goitre (NTMNG), 16 toxic nodular goitre (TNG) patients and 70 healthy controls (age- and sex-matched). We measured sCXCL10 in patients and controls, to relate this parameter to the clinical phenotype. Mean sCXCL10 in GD and AT patients were comparable (122+/-81 and 133+/-102 pg/ml) and significantly higher (P<0.01) than in controls or NTMNG patients (73+/- 32 and 76+/- 25 pg/ml, respectively). Hyperthyroid GD had significantly higher sCXCL10 than euthyroid or hypothyroid GD (145+/- 92, 107+/- 56 and 105+/- 46 pg/ml, respectively; P=0.01). GD patients with untreated hyperthyroidism had higher sCXCL10 than hyperthyroid or euthyroid GD patients under methimazole (MMI) treatment (166+/-125, 124+/- 41 and 94+/- 35 pg/ml, respectively; P=0.006). Comparable sCXCL10 levels were observed in newly diagnosed untreated hyperthyroid GD patients with respect to untreated patients with relapse of hyperthyroidism after a previous MMI course (176+/-125, 155+/- 97 pg/ml, respectively). GD had similar sCXCL10 to AT and higher than TNG patients or controls (all age- and sex-matched) (144+/- 81, 149+/- 114, 101+/- 27 and 86+/- 44 pg/ml, respectively; P=0.02). sCXCL10 is associated with the active phase of GD in both newly diagnosed and relapsing hyperthyroid patients. The reduction in sCXCL10 in treated patients with GD may be related to the immunomodulatory effects of MMI.

Thyroid cancer in hyperthyroidism: Incidence rates and value of ultrasound-guided fine-needle aspiration biopsy in this patient group

Three hundred and thirty-three hyperthyroidism cases were retrospectively investigated to provide information about the association between hyperthyroidism and thyroid cancer. There were 112 cases of toxic multinodular goiter (TMNG), 77 cases of toxic nodular goiter (TNG) and 144 cases of Graves' disease (GD). All nodules detected in GD patients, all nodules greater than 1 cm diameter in nodular goiter patients, nodules 5-10 mm size diameter if they had calcification were fine-needle biopsied (FNAB) under ultrasound guidance (US-guided), and a total of 612 such biopsies were performed. The biopsy samples were cytologically assessed as benign (no.=552; 90.2%), suspicious (no.=6; 1.1%), malignant (no.=13; 2.1%), or inadequate for diagnosis (no.=41; 6.7%). All patients with a biopsy diagnosis of malignant or suspicious nodules underwent surgery. Histological examination confirmed the diagnosis of thyroid cancer in all 13 (2.1%) patients with malignant FNAB findings. Papillary thyroid carcinoma (PTC) was identified in 2 patients with TMNG (%1.8), 5 with TNG (%6.5) and 5 with GD (%3.5). Metastatic follicular thyroid carcinoma (FTC) was identified in a patient with TNG. Thyroid malignancy (micro- or macrocarcinoma) was diagnosed pre-operatively in all 13 cases by US-guided FNAB. Thyroid cancer was diagnosed in 6 (5.5%) of the 109 nodules detected in the TNG group, 2 (0.44%) of the 452 nodules detected in the TMNG group, and 5 (9.8%) of the 51 nodules detected in the GD group. Two (2.6%) of the 77 functioning nodules in the TNG patients were malignant, but none of the 402 functioning nodules in the TMNG patients was malignant. In patients with hyperthyroidism, US-guided FNAB is useful for detecting thyroid cancer in nodules greater than 5 mm diameter before radioiodine therapy or surgery.

High serum osteoprotegerin levels in patients with hyperthyroidism: effect of medical treatment

This study was aimed at evaluating serum osteoprotegerin (OPG) concentrations in a cohort of patients with hyperthyroidism before and after methimazole (MMI) treatment. One hundred fourteen hyperthyroid patients [93 with Graves disease (GD) and 21 with toxic nodular goitre (TNG)] and 68 matched for sex and age healthy subjects were evaluated for serum free-thyroxine (FT4), free-triiodiothyronine (FT3), thyrotropin (TSH), TSH receptor antibodies (TRAb), bone alkaline phosphatase (BALP), C-telopeptides of type-1 collagen (CrossLaps), OPG levels, and bone mineral density (BMD). In hyperthyroid patients, the biochemical evaluations were performed before and after 6 and 12 months of MMI treatment, whereas BMD was measured at baseline and after 12 months of treatment. Hyperthyroidism was more severe in GD than TNG patients. Serum OPG levels were found to be significantly higher in hyperthyroid patients than in the healthy subjects (4.3 pmol/l, range: 1.6–12.0, vs. 2.2 pmol/l, range: 1.4–6.0; P < 0.001), the values being higher in GD patients than TNG. A significant correlation between serum OPG levels and age was found in the healthy subjects ( r: 0.48; P < 0.001) but not in hyperthyroid patients ( r: −0.03; P = 0.8). In the healthy subjects, serum OPG levels were also positively correlated with both serum FT4 ( r: 0.23; P = 0.03) and FT3 ( r: 0.24; P = 0.04) levels. In hyperthyroid patients, however, serum OPG was still correlated with FT3 levels ( r: 0.38; P < 0.001), whereas the correlation with serum FT4 was lost ( r: 0.19; P = 0.06). In hyperthyroid patients, but not in the healthy subjects, serum OPG levels were correlated positively with CrossLaps ( r: 0.20; P = 0.03) and negatively with BALP ( r: −0.24; P = 0.01) and BMD ( r: −0.33; P = 0.01). After 6 months of MMI treatment, serum OPG concentrations decreased significantly in TNG patients (from 3.5 pmol/l, range: 1.6–8.0, to 2.3 pmol/l, range: 1.0–4.3; P < 0.001), whereas a not significant change in OPG levels occurred in GD patients (from 4.8 pmol/l, range: 1.8–12.0, to 4.2 pmol/l, range: 1.0–14.0; P = 0.7). At Month 12 of treatment, serum OPG concentrations were significantly lower than those measured at baseline in both TNG (2.5 pmol/l, range: 1.0–3.1, vs. 3.5 pmol/l, range: 1.6–8.0; P < 0.001) and GD (2.1 pmol/l, range: 1.0–8.6, vs. 4.8 pmol/l, range: 1.8–12.0; P < 0.001). At this time, no significant differences in serum OPG, CrossLaps, and BALP values were found between patients and control subjects. At the end of follow-up, BMD was higher than those measured at baseline but still significantly lower than those measured in the control subjects. This study shows that hyperthyroid patients have serum OPG concentrations significantly higher in comparison with euthyroid subjects, in relation to thyroid hormone excess and high bone turnover. Medical treatment of hyperthyroidism normalizes serum OPG levels in temporal relationship with the normalization of bone metabolism markers, even in presence of persistent abnormal bone structure as determined by ultrasonography.

Antithyroid drugs as a factor influencing the outcome of radioiodine therapy in Graves' disease and toxic nodular goitre?

There is controversy over the factors that may influence the outcome of radioiodine therapy for benign thyroid diseases. Antithyroid medication has been claimed to negatively influence the effectiveness of radioiodine therapy in Graves' disease. In a longitudinal study, we assessed the influence of sex, age, antithyroid drugs, target radiation dose, target mass, applied activity, delivered dose, interval between last meal and application, and TSH, FT3 and FT4 levels on the outcome of radioiodine therapy. One hundred and forty-four patients (111 female, 33 male) suffering from Graves' disease (GD) and 563 patients (434 female, 129 male) with toxic nodular goitre (TNG) were entered in the study and followed up until 8 months after therapy. Treatment was defined as successful when the TSH level was found to be normal or elevated. Ninety-eight GD patients and 418 TNG patients were successfully treated. Forward stepwise multiple regression analysis models retained only the target mass in GD and the applied activity in TNG as significantly associated with the outcome of therapy. The predictive value of all variables involved was extremely low in both disease groups. Whereas concomitant antithyroid medication had no influence in GD, it adversely influenced radioiodine therapy of TNG. This effect may be attributed to a radioiodine "steal phenomenon" induced by TSH-stimulated normal thyroid tissue, which causes overestimation of the uptake in toxic nodules.

Clinical outcome of radioiodine treatment of hyperthyroidism: a follow‐up study

To study the clinical outcome of treatment of hyperthyroid patients with radioiodine. Records of patients treated for hyperthyroidism with radioiodine from 1989 to 1992 were examined in 1994, and a questionnaire was sent to patients < or = 70 years with Graves' disease (GD) and toxic nodular goitre (TNG) to obtain information regarding thyroxine substitution, smoking habits and present state of health. Outpatients in a thyroid unit; follow-up by primary care. Seven hundred and fifty-four patients with hyperthyroidism treated with radioiodine, 327 receiving the questionnaire, 72% response rate. Radioiodine treatment using a delivered absorbed dose method, aiming at an absorbed dose to the thyroid of 100-120 Gy. Statistical analysis of clinical records and results from questionnaire. Only 10% of the patients needed more than one treatment. At the time of follow-up, thyroxine supplementation was given to 178 (93%) of the GD and to 21 (47%) of the TNG patients. Smoking was more common in GD patients than in the general population (44% vs. 26%; P < 0.001). Smoking GD patients experienced eye discomfort more often than smoking TNG patients (53% vs. 7%; P < 0.001). Weight gain after therapy was a problem in 79% of the hyperthyroid individuals. Few patients needed retreatment and most of the GD patients had thyroxine after 1-5 years after therapy. Smoking patients, especially those with GD, had more eye symptoms. At follow-up, the euthyroid patients still consider themselves having a poorer health than individuals in the general population.

Diminished lymphocytic cortisol metabolism-enhancing effect in endogenous thyrotoxicosis.

A study was carried out to determine the effect on lymphocytic cortisol metabolism (LCM) of plasma from 62 patients with diffuse thyrotoxic goitre (DTG), 14 patients with toxic nodular goitre (TNG) and ten hypothyroid patients. Plasma of 33 healthy donors served as controls. A known concentration of human lymphocytes was incubated with cortisol in media containing 50% phosphate-buffered saline (PBS) and 50% of one of the following additions: (1) PBS, (2) homologous plasma (HP), (3) heterologous plasma, (4) plasma from DTG patients, (5) plasma from TNG patients, (6) plasma from hypothyroid patients, (7) PBS and HP to which L-thyroxine (T4) and triiodothyronine (T3) had been added separately and as a mixture up to a concentration ten times the normal, (8) boiled HP and (9) boiled DTG plasma. Plasma from hypothyroid patients gave an LCM-enhancing effect (LCMEE) similar to that of HP. The plasma of DTG and TNG patients had a markedly lesser effect on LCM than did HP. The T4 and T3 had no additional effect when added to PBS or HP. Boiling of HP and DTG plasma resulted in a similar decrease in LCMEE. The findings of this study raise the possibility of the existence of a factor inhibiting LCMEE in the plasma of thyrotoxic patients.