Factors predicting remission in hyperthyroid patients after low-dose I-131 therapy: 20 years retrospective study from a tertiary care hospital.

OBJECTIVE: To assess the therapeutic outcome and factors predicting remission in hyperthyroid patients treated with low-dose I-131 (radioactive iodine) from a tertiary care hospital in South India. METHODS: This 20-year single-institutional retrospective study was carried out on 3891 hyperthyroid adult patients. Only those patients with complete clinical records were audited. Selection criteria were based on patients with scintigraphic diagnosis of either Graves' disease (GD), toxic multinodular goitre (TMNG) or autonomous toxic nodule (ATN) and the records of those who received low-dose I-131 therapy (LDT) between March 2000 and 2020 at Amrita Institute, Cochin were analysed. SPSS 10 software was used for statistical analysis. RESULTS: The records of 3891 hyperthyroid predominantly female patients were analysed. 65% patients had GD, 33% had TMNG and 3% were ATN. High rates of remission as early as 12 weeks (in 61% patients) was observed with a single dose of LDT while on strict iodine-free diet for 3-4 weeks prior to LDT. Study reveals that those with lower free T4 (fT4), small goitre (thyroid volume < 25 cm3), < 15% thyroid trapping function, shorter time duration from onset of hyperthyroidism to LDT, and treatment-naïve patients were factors determining high remission rates. Mann Whitney U test and Chi-square test was used to correlate variables in the remission and relapse groups. We found a positive correlation between fT4, thyroid volume (r = 0.35, p < 0.01) and trapping function (r = 0.34, p < 0.01), which were independent of age, sex, body mass index and TSH levels in our study. CONCLUSION: High therapeutic outcome was observed with a single dose of LDT while on iodine-free diet. Remission with single dose of LDT occurred in 90% patients by 5th month. Of them 56% patients were treatment naive prior to LDT. LDT is thus a safe and effective therapy in hyperthyroid patients and can be recommended as a primary modality of management.

Hyperthyroidism.

Thyrotoxicosis causes a variety of symptoms and adverse health outcomes. Hyperthyroidism refers to increased thyroid hormone synthesis and secretion, most commonly from Graves' disease or toxic nodular goitre, whereas thyroiditis (typically autoimmune, viral, or drug induced) causes thyrotoxicosis without hyperthyroidism. The diagnosis is based on suppressed serum concentrations of thyroid-stimulating hormone (TSH), accompanied by free thyroxine and total or free tri-iodothyronine concentrations, which are raised (overt hyperthyroidism) or within range (subclinical hyperthyroidism). The underlying cause is determined by clinical assessment, detection of TSH-receptor antibodies and, if necessary, radionuclide thyroid scintigraphy. Treatment options for hyperthyroidism include antithyroid drugs, radioactive iodine, and thyroidectomy, whereas thyroiditis is managed symptomatically or with glucocorticoid therapy. In Graves' disease, first-line treatment is a 12-18-month course of antithyroid drugs, whereas for goitre, radioactive iodine or surgery are preferred for toxic nodules or goitres. Evidence also supports long-term treatment with antithyroid drugs as an option for patients with Graves' disease and toxic nodular goitre.

Hyperthyroidism: aetiology, pathogenesis, diagnosis, management, complications, and prognosis.

Hyperthyroidism is a common condition with a global prevalence of 0·2-1·3%. When clinical suspicion of hyperthyroidism arises, it should be confirmed by biochemical tests (eg, low TSH, high free thyroxine [FT4], or high free tri-iodothyonine [FT3]). If hyperthyroidism is confirmed by biochemical tests, a nosological diagnosis should be done to find out which disease is causing the hyperthyroidism. Helpful tools are TSH-receptor antibodies, thyroid peroxidase antibodies, thyroid ultrasonography, and scintigraphy. Hyperthyroidism is mostly caused by Graves' hyperthyroidism (70%) or toxic nodular goitre (16%). Hyperthyroidism can also be caused by subacute granulomatous thyroiditis (3%) and drugs (9%) such as amiodarone, tyrosine kinase inhibitors, and immune checkpoint inhibitors. Disease-specific recommendations are given. Currently, Graves' hyperthyroidism is preferably treated with antithyroid drugs. However, recurrence of hyperthyroidism after a 12-18 month course of antithyroid drugs occurs in approximately 50% of patients. Being younger than 40 years, having FT4 concentrations that are 40 pmol/L or higher, having TSH-binding inhibitory immunoglobulins that are higher than 6 U/L, and having a goitre size that is equivalent to or larger than WHO grade 2 before the start of treatment with antithyroid drugs increase risk of recurrence. Long-term treatment with antithyroid drugs (ie, 5-10 years of treatment) is feasible and associated with fewer recurrences (15%) than short-term treatment (ie, 12-18 months of treatment). Toxic nodular goitre is mostly treated with radioiodine (131I) or thyroidectomy and is rarely treated with radiofrequency ablation. Destructive thyrotoxicosis is usually mild and transient, requiring steroids only in severe cases. Specific attention is given to patients with hyperthyroidism who are pregnant, have COVID-19, or have other complications (eg, atrial fibrillation, thyrotoxic periodic paralysis, and thyroid storm). Hyperthyroidism is associated with increased mortality. Prognosis might be improved by rapid and sustained control of hyperthyroidism. Innovative new treatments are expected for Graves' disease, by targeting B cells or TSH receptors.

Efficacy and Safety of Long-Term Methimazole versus Radioactive Iodine in the Treatment of Toxic Multinodular Goiter.

BACKGRUOUND: This study compared the degree of sustained control of hyperthyroidism in patients with toxic multinodular goiter (TMNG) treated with long-term methimazole (LT-MMI) or radioactive iodine (RAI). METHODS: In this clinical trial, 130 untreated patients with TMNG were randomized to either LT-MMI or RAI treatment. Both groups were followed for 108 to 148 months, with median follow-up durations of 120 and 132 months in the LT-MMI and RAI groups, respectively. Both groups of patients were followed every 1 to 3 months in the first year and every 6 months thereafter. RESULTS: After excluding patients in whom the treatment modality was changed and those who were lost to follow-up, 53 patients in the LT-MMI group and 54 in the RAI group completed the study. At the end of the study period, 50 (96%) and 25 (46%) patients were euthyroid, and two (4%) and 25 (46%) were hypothyroid in LT-MMI and RAI groups, respectively. In the RAI group, four (8%) patients had subclinical hyperthyroidism. The mean time to euthyroidism was 4.3±1.3 months in LT-MMI patients and 16.3± 15.0 months in RAI recipients (P<0.001). Patients treated with LT-MMI spent 95.8%±5.9% of the 12-year study period in a euthyroid state, whereas this proportion was 72.4%±14.8% in the RAI-treated patients (P<0.001). No major treatment-related adverse events were observed in either group. CONCLUSION: In patients with TMNG, LT-MMI therapy is superior to RAI treatment, as shown by the earlier achievement of euthyroidism and the longer duration of sustained normal serum thyrotropin.

Correlation between serum lead and thyroid diseases: papillary thyroid carcinoma, nodular goiter, and thyroid adenoma.

Studies have showed that lead was associated with human health. However, the effects of lead on thyroid functions are inconsistent, and studies based on Chinese population are fragmentary. To evaluate the correlation between lead and thyroid functions of Chinese with different thyroid diseases, we conducted a hospital-based study. Ninety-six papillary thyroid carcinoma (PTC), 10 nodular goiter (NG), and 7 thyroid adenoma (TA) patients were recruited from the First Affiliated Hospital of Wenzhou Medical University, China. Serum triiodothyronine (T3), free triiodothyronine (FT3), free thyroxin (FT4), and thyroid stimulating hormone (TSH) were evaluated with chemiluminescent microparticle immunoassay. Serum lead was assessed with ICP-MASS. Partial correlation was used to explore the correlations of serum lead and thyroid diseases. Compared to PTC, the level of lead was significantly higher in TA, and lower in NG (p < 0.05). This difference remained significant in females when stratified by sex. Serum lead was negatively correlated with TSH (rs =  - 0.27, p < 0.05) in PTC group. T3 was positively related to lead at quartile4 (rs = 0.61, p < 0.05) in PTC group. No significant correlations were observed between lead and FT3 or FT4 in any group. The results suggested that lead might have different etiological roles in these three thyroid diseases.

The impact of high fat diets on physiological changes in euthyroid and thyroid altered rats.

The association of adverse health with high fat intake has long been recognized. However, the lack of research focusing on the interrelationship of thyroid and liver function, and the pathogenesis of a high fat diet leaves these topics poorly understood. The objective of this study was to evaluate and compare the physiological changes in euthyroid and thyroid altered animal model fed saturated and unsaturated high fat diets. To achieve this objective adult male Sprague Dawley rats (n = 100) were fed one of five diets; a control or one of four test diets containing 25% saturated or unsaturated, and 37% saturated or unsaturated fats for a period of eight weeks. Each experimental group consisted of ten euthyroid and ten thyroid altered animals. An altered thyroid state was chemically induced with the addition of 0.05% propylthiouracil (PTU) in the drinking water. Euthyroid animals fed high fat diets increased in body weights and body lengths, compared to thyroid altered animals (P < 0.05). Alanine aminotransferase (ALT) and asparte aminotransferase (AST) levels increased across all experimental groups. HbA1C values and urinary glucose values were within normal range for all animals. Liver morphology showed increased hepatic stellate (ito) and vacuole cells in thyroid altered animals. These findings suggest that altered thyroid status negatively impacts growth and weight gain, and simultaneously affected lipid metabolism, resulting in abnormal liver morphology.

A case series of paediatric hearing preservation cochlear implantation: a new treatment modality for children with drug-induced or congenital partial deafness.

OBJECTIVE: To investigate the use of hearing preservation cochlear implantation in children with partial deafness. PATIENTS AND METHODS: Five children with either drug-induced or congenital partial deafness were enrolled in a pilot study. The patients ranged in age from 13 months to 14 years. Implantation was performed using a hearing preservation technique. A Flex EAS electrode (MED-EL, Innsbruck, Austria) was used in all full insertions. RESULTS: Low frequency hearing was preserved in all patients with postoperative bone conduction within 10 dB of the preoperative hearing levels. These changes were preserved over the follow-up period of 12 months. There were significant improvements in speech perception. CONCLUSION: Hearing preservation cochlear implantation is a new effective modality in children with partial deafness.

Radioiodine treatment of Plummer and multinodular toxic and nontoxic goiter disease by the first approximation dosimetry method.

The aim of this study was to assess the efficacy of mean radioiodine activities of 12.6 MBq/mL in order to achieve a successful treatment of hyperthyroidism with a single radioiodine dose and a low incidence of hypothyroidism. We evaluated 51 patients with Plummer disease, 41 patients with multinodular toxic goiter, and 9 patients with compressive toxic and nontoxic goiter, after a short suspension of antithyroid drugs, with the exclusion of patients with critical cardiovascular conditions, an expanded iodine pool, and a nodular volume larger than 120 mL. Target volume was measured by ultrasonography and calculated by the ellipsoid method. All the patients underwent a thyroid uptake test with 1.85 MBq of (131)I and measurements on the neck and thigh at 2, 6, and 24 hours. Target volume was 21.5 +/- 21.4 mL for group 1, 15.4 +/- 10.7 mL for group 2, and 56.4 +/- 12.8 mL for group 3. The 24 hours uptake (mean % +/- standard deviation) was 43.1 +/- 19.9, 48.5 +/- 15.4, 56.4 +/- 12.8, respectively, for groups 1, 2 and 3. Mean follow-up was group 1: 23 +/- 17 months; group 2: 23 +/- 14 months; and group 3: 28 +/- 20 months. First approximation dosimetry took into account thyroid volume and the 24-hour uptake percentage. A euthyroidism condition was reached in 40 of 51 patients (78.4%) of group 1, 35 of 41 patients (85.4%) of group 2, and 6 of 9 patients (66.7%) of group 3. Hypothyroidism was observed in 13 of 101 patients (12.9%). Only 9 of 101 (8.9%) patients were subclinically hyperthyroid at the end of follow-up. The over-all efficacy of treatment was 91.1%. Reduction (%) of nodule volume was 66 +/- 23, 57 +/- 18, and 79 +/- 13, respectively, in groups 1, 2, and 3, with scintigraphic disappearance of hot nodules or persistence of cold nodules with the recovery of extranodular thyroid tissue in 76 patients.

Combination of minimally invasive thyroid surgery and local anesthesia associated to iopanoic acid for patients with amiodarone-induced thyrotoxicosis and severe cardiac disorders: a pilot study.

BACKGROUND AND AIMS: Amiodarone-induced thyrotoxicosis is a life-threatening condition. A prompt control of thyrotoxicosis is obtained by thyroidectomy. Preparation with iopanoic acid proved to be very effective in reducing cardiovascular complications. Nevertheless, general anesthesia and extensive surgery may affect negatively patients also after adequate preparation. Safety and efficacy of minimally invasive video-assisted thyroidectomy performed under regional anesthesia (bilateral modified deep cervical block) in patients with amiodarone-induced thyrotoxicosis was evaluated. PATIENTS AND METHODS: Eight patients with amiodarone-induced thyrotoxicosis (three with type I and five with type II), mean age 66.2 years, were prepared with iopanoic acid. There were five men and three women. Three patients had dilatative cardiomyopathy, three had heart failure secondary to severe myocardial infarction, and two had refractory unstable rhythm disorders. RESULTS: Minimally invasive video-assisted thyroidectomy was performed under regional anesthesia. Mean operative time was 55.5 min. During surgery, lung and heart function remained well and no surgical complications occurred. After surgery, all patients remained on amiodarone therapy and two patients were subsequently removed from the checklist for heart transplantation. CONCLUSION: Minimally invasive video-assisted thyroidectomy under regional anesthesia can be proposed as resolution of amiodarone-induced thyrotoxicosis in high risk patients with severe cardiac disorders, after preparation with iopanoic acid.

Developmental toxic effects of chronic exposure to high doses of iodine in the mouse.

Chronic exposure to high doses of iodine induces thyroid dysfunction, but effects of chronic exposure to high amounts of iodine on pregnancy and fetal outcome are uncertain. In the present study, Balb/C mice were given different doses of iodine at the levels of 0 (sterile water), 1,500, 3,000, 6,000, 12,000 and 24,000 micro g/L in drinking water for 4 months, then were mated and the developmental toxicity and teratogenicity were evaluated. An obvious colloid goiter was observed, and serum total thyroxine (TT4) levels increased and serum total triiodothyronine (TT3) levels decreased significantly in dams when iodine dose reached 3,000 micro g/L. Maternal effect was evident by the reduction of average daily food consumption in higher doses of iodine groups. Embryotoxicity and teratogenicity were mainly indicated by the reduced body weight in female fetuses, the decreased number of live fetuses, and the increased incidence of resorptions, and especially skeletal variations. These results suggest that exposure to maternally toxic doses of iodine may have a potential developmental toxic effect.

[Lithium and its effects on the endocrine system, bones and peripheral nerves--a current review]. / Lithium und seine Wirkungen auf das Endokrinium, den Knochen und den peripheren Nerv--eine aktuelle Ubersicht.

Controlled studies in 1990-1992 with Danish, Sardinian, and Hongkong-Chinese patients consistently revealed a prevalence of goiter of about 50% in lithium treated patients. This is far beyond the frequency generally assumed for Germany, the whole country still known to be an endemic goiter area. Hypothyroidism as a side effect of lithium occurs in a clearly different group of patients and is much less frequent, the overall incidence being not substantially different from the incidence in the general population. But the risk of becoming hypothyroid as well as hyperparathyroid during lithium prophylaxis is markedly higher in women over 45 years of age, who in the general population are also prone to both endocrine dysfunctions. Lithium is considered to have a provoking role. Lithium is known to be accumulated in the bone and an impact on bone metabolism was shown in animal studies. The data reviewed prohibit the use of lithium during lactation and enforce strict indication in children. In adults the effect of lithium on bone should be considered only in osteomalacia and severe osteoporosis. This review is illustrated by the case of a 60-year-old woman, who after 4 years of successful treatment with lithiumcarbonate because of schizoaffective psychosis, developed a syndrome of hypercalcemia. Exstirpation of a parathyroid adenoma rendered her normocalcemic. Moreover, a pre-existing diffuse goiter had grown to a large nodular goiter within the course of her 5-year treatment. As she finally became paraparetic, she was admitted to our rehabilitation center for the diseases of the spinal cord. Her paraparesis may have been caused not only by the lithium-induced primary HPT, but in part by lithium itself. There are a few reports on lithium causing peripheral neuropathy at toxic levels. A transient deterioration of a pre-existing neuropathy, as in our case study, may have happened at lithium serum levels not far beyond the upper limit of 0.8 mmol/l.

[Lithium and hyperthyroidism]. / Lithium und Hyperthyreose.

The development of hypothyroidism and the forming of a goiter are well-known complications associated with lithium medications. But there are also occasional references to cases of hyperthyroidism in the wake of both continual and of discontinued lithium medication. In the case being reported on here of a lady patient aged 64 and suffering from a toxic adenoma not recognized at the time, thyrotoxicosis accompanied by above-normal FT-3 results and the characteristic clinical symptoms developed when lithium medication was discontinued. Medical literature consulted in the context discussed pharmacological mechanisms which may be responsible for the said complications.

[Subtotal thyroid resection in severe, iodine-induced hyperthyroidism]. / Die subtotale Schilddrüsenresektion bei schwerer, jodinduzierter Hyperthyreose.

Iodine-induced thyrotoxicosis due to iodine application in high amounts in patients with circumscript or disseminated thyroid autonomy, is complicated by a prolonged course, mainly due to a resistance to conservative therapy with thiourea derivates. We therefore decided to perform an early subtotal thyroidectomy in 24 thyrotoxic patients. This measure is in contrast to the common opinion that surgery should only be performed after normalization of thyroid hormones. In all 24 patients with severe hyperthyroidism, including three patients with thyroid storm, hormone levels decreased within a few days after surgery to normal or subnormal values and the clinical picture of thyrotoxicosis disappeared. In the case of thyroid storm the signs of disorientation normalized within 1-3 days. One patient died five weeks after surgery due to severe concomitant diseases. One patient exhibited transitory respiration distress and another had postoperative hypocalcemia. In 13 patients L-thyroxine replacement became necessary due to subclinical or clinical hypothyroidism. Surgery as a early treatment for thyrotoxicosis should be reserved for patients with severe illness where conservative treatment has been shown to be ineffective. In rare selected cases, when a rapid normalization is required, surgery without preoperative treatment seems to be justified. The effect of surgery was impressive in all our cases and there were only minor perioperative complications.

[Operative indications and surgical procedure in iodine-induced hyperthyroidism]. / Operationsindikation und chirurgisches Vorgehen bei jodinduzierten Hyperthyreosen.

Clinical course, indications for surgical treatment, and results of treatment in 8 female patients with iodine induced thyrotoxicosis (IIT) are reported. The diagnosis of IIT could be established in all patients by a) clinical hyperthyroidism, b) increased T3 and T4 serum concentrations, and c) previous iodine contamination. Sources of iodine were radiographic contrast agents for urography (n = 4), oral cholecystography (n = 3), intravenous cholangiography (n = 1), phlebography (n = 1), and cranial computer tomography (n = 1). The onset of hyperthyroidism occurred 1-8 weeks after iodine exposure. Indications for surgical treatment of IIT were: 1. autonomous nodular goiter (n = 6), and 2. iodine exacerbation of preexisting thyrotoxicosis in patients with Graves' disease (n = 2). Corresponding to the different pathogenesis of autonomous and immunogenetic goiter the following surgical treatment is recommended: Enucleation of solitary autonomous adenomas or unilateral lobectomy in case of large adenomas, subtotal bilateral lobectomy in toxic multinodular goiter or, preferentially, unilateral lobectomy combined with subtotal resection of the contralateral thyroid lobe; "Near-total" thyroidectomy in Graves' immunopathy.

Current incidence of thyrotoxicosis and past prevalence of goitre in 12 British towns.

The incidence of thyrotoxicosis was determined in a collaborative study in 12 towns in England and Wales. Cases were ascertained prospectively through biochemistry laboratories carrying out routine thyroid function tests. The annual incidence varied from 9.7 to 49.2 per 100 000. Reassay of sera at a reference laboratory showed that this variation did not result from inter-laboratory differences in the techniques for measuring thyroid function. The incidence of thyrotoxicosis was strongly correlated with the previous prevalence of endemic goitre in the towns. Current high dietary intakes of iodine--largely the result of milk contamination--may cause toxic nodular goitre in people made susceptible by a lack of iodine early in life. They may also contribute to the occurrence of Graves' disease.

[Danger of iodine drugs in the pregnant woman]. / Dangers des médicaments iodés chez la femme enceinte.

The authors draw attention to the fact that the possible effects of drugs containing iodine are often neglected during pregnancy. As an example, they report the following observation : "A young woman with benign asthma, treated for 14 years Asthmasedine and Asthmaligne, gave birth, on the 36th week of pregnancy, to a child apparenty dead but who was able to be reanimated. The child showed two types of signs : respiratory distress due to higher neurological disorders and a multinodular, non-compressing goiter. These two complications were caused by a congenital hypothyroidism corroborated by laboratory tests and due to the prolonged absorption of iodinated drugs by the mother". In conclusion, in cases of women receiving during pregnancy high doses of drugs containing iodine (250 such drugs are recorded in the Vidal), it is desirable to control the effect on the fetus and to propose an intra-amniotic therapy with L-Thyroxine, thus allowing a cerebral development close to normal.