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1.  Effectiveness of Fixed Dose Radioactive Iodine (RAI) for the Treatment of Hyperthyroidism: Experience of a Teaching Hospital in South West Nigeria 
Objective: Using radioactive iodine (RAI) as the first line therapy for Graves’ hyperthyroidism and as the treatment of choice for relapsed Graves’ disease is increasing in recent times. However, there has been little consensus on the most appropriate dose to use. So this study is to determine the response of hyperthyroidism to fixed doses of 370 MBq and 555 MBq RAI therapies and determine the incidence of hypothyroidism at 6 months post therapy.
Methods: Hyperthyroid patients’ case records treated with radioiodine was retrospectively reviewed to determine the response rate of hyperthyroidism to the two fixed dose regimens. Statistical analysis was done with SPSS version 15.0 and the level of statistical significance was taken as p<0.05. Forty subjects, 6 males (15%) and 34 females (85%) received RAI therapy for Graves’ hyperthyroidism, mean age was 49.4 years (range, 25-75years). The thyroid function status at 6 months post therapy was available for all subjects. 24 patients (60%) received 370 MBq while 16 patients (40%) received 555 MBq.
Results: The response for fixed doses of 370 MBq and 555 MBq were similar (100%). Also, the incidence of hypothyroidism in these subjects which was 66.6% with fixed dose of 370 MBq and 62.5% with fixed dose of 555 MBq within 6 months post RAI therapy were similar.
Conclusion: SRAI is highly effective for the treatment of hyperthyroidism, with a cure rate of 100%. However, it has proved impossible to determine a fixed dose regimen for individual patients accurately to guarantee an euthyroid state. This is because hypothyroidism is a natural predictable sequel of RAI therapy.
Conflict of interest:None declared.
PMCID: PMC3759307  PMID: 24003395
I-131; radioisotope therapy; Hyperthyroidism; treatment effectiveness; Nigeria
2.  Comparison of clinical outcome after a fixed dose versus dosimetry-based radioiodine treatment of Graves’ disease: Results of a randomized controlled trial in Indian population 
Two approaches are used to treat Graves’ disease with radioiodine (131I)–the fixed dose approach and the other based on dosimetry. A prospective study was performed to compare the results of these two approaches in a randomized patient population, as such study is lacking in the Indian population till date.
Materials and Methods:
Patients with Graves’ disease were randomized into two groups: (1) Fixed dose group and the (2) Calculated dose group, each comprising of 20 patients. All the patients underwent detailed clinical and biochemical evaluation. Thyroid mass was determined by high resolution ultrasound machine with linear transducer of 7-11 MHz. Patients were given 185-370 kBq (5-10 uCi) of 131I and 24 hr radioiodine uptake (RAIU) was calculated using thyroid uptake probe and thyroid phantom. Fixed dose group patients were administered 185MBq of 131I. Calculated dose group patients were given 131I as per the following formula: Calculated dose = [3700 kBq/g × estimated thyroid wt. (g)] ÷ 24 hr RAIU (%). Success of first dose of radioiodine was defined as clinically/biochemically euthyroid/hypothyroid status at the end of 3 months without the need for further therapy.
In the fixed dose group, eight patients were hyperthyroid, four were euthyroid, and eight were hypothyroid after the first dose at 3 months. Success rate of first dose was 60%. In calculated dose group, seven patients were hyperthyroid, eight were euthyroid, and five were hypothyroid. Success rate of first dose was 65%.
There is no statistically significant difference between the success rates of the two methods at 3 months. Hence, fixed dose approach may be used for treatment of Graves’ disease as it is simple and convenient for the patient. Longer follow-up with higher number of patients should be done to confirm or contradict our findings.
PMCID: PMC4171887  PMID: 25285281
Comparison; dosimetry; empiric dose; Graves’ disease; radioiodine
3.  Radioiodine Thyroid Ablation in Graves’ Hyperthyroidism: Merits and Pitfalls 
Ablative approaches using radioiodine are increasingly proposed for the treatment of Graves′ disease (GD) but their ophthalmologic and biological autoimmune responses remain controversial and data concerning clinical and biochemical outcomes are limited. The aim of this study was to evaluate thyroid function, TSH-receptor antibodies (TRAb) and Graves′ ophthalmopathy (GO) occurrence after radioiodine thyroid ablation in GD. We reviewed 162 patients treated for GD by iodine-131 (131I) with doses ranging from 370 to 740 MBq, adjusted to thyroid uptake and sex, over a 6-year period in a tertiary referral center. Collected data were compared for outcomes, including effectiveness of radioiodine therapy (RIT) as primary endpoint, evolution of TRAb, and occurrence of GO as secondary endpoints. The success rate was 88.3% within the first 6 months after the treatment. The RIT failure was increased in the presence of goiter (adjusted odds ratio = 4.1, 95% confidence interval 1.4–12.0, P = 0.010). The TRAb values regressed with time (r = −0.147; P = 0.042) and patients with a favorable outcome had a lower TRAb value (6.5 ± 16.4 U/L) than those with treatment failure (23.7 ± 24.2 U/L, P < 0.001). At the final status, 48.1% of patients achieved normalization of serum TRAb. GO occurred for the first time in 5 patients (3.7%) who were successfully cured for hyperthyroidism but developed early and prolonged period of hypothyroidism in the context of antithyroid drugs (ATD) intolerance (P = 0.003) and high TRAb level (P = 0.012). On the basis the results of this study we conclude that ablative RIT is effective in eradicating Graves’ hyperthyroidism but may be accompanied by GO occurrence, particularly in patients with early hypothyroidism and high pretreatment TRAb and/or ATD intolerance. In these patients, we recommend an early introduction of LT4 to reduce the duration and the degree of the radioiodine-induced hypothyroidism.
PMCID: PMC3425234  PMID: 22942775
Autoimmunity; Graves’ disease; ophthalmopathy; radioiodine therapy
4.  Outcome of 131I therapy in hyperthyroidism using a 550MBq fixed dose regimen 
The Ulster Medical Journal  2013;82(2):85-88.
Radioiodine is the treatment of choice for relapsed hyperthyroidism although the optimum protocol is uncertain. Fixed dose radioiodine is increasingly popular but responses may vary.
To assess the outcome of 131I therapy in hyperthyroidism using a standard dose regimen in a regional referral centre and to explore factors influencing outcome.
We studied 449 patients (M:F 82:367; age range 13-89y, median 42y) with hyperthyroidism treated between 2003 and 2007 with a standard dose of 550MBq 131I. Patients were classified as either Graves’ disease, toxic multinodular goitre or indeterminate aetiology. Antithyroid drugs were routinely stopped at least 1 week before radioiodine.
One year after radioiodine 334 (74%) were hypothyroid, 85 (19%) were euthyroid and 30 (7%) had required a further dose of 131I. Patients with Graves’ disease were more likely to become hypothyroid than those with toxic multinodular goitre (78% v 37%, p<0.001) and less likely to become euthyroid (11% v 55%, p<0.001). Free T4 >80pmol/L (normal range 9.0 – 19.0 pmol/L) at presentation was associated with an increased failure rate (17% compared with 5% and 3% for 40-79pmol/L and <40pmol/L respectively; p=0.01). Patients with either a small or no goitre were more likely to be successfully treated by a single dose (96%) than those with a medium/large goitre (85%, p<0.001). Anti-thyroid medication was taken by 345 (77%) (carbimazole n=319) patients up to 1 week prior to 131I and was associated with an increased failure rate (8% v 2%, p=0.027) compared to those who had not had antithyroid medication. Logistic regression showed free T4 at presentation to be the only independent risk factor for failure of the first dose of radioiodine (OR 2.5; 95% CI, 1.2–5.1, p=0.012).
A single standard dose of 550MBq 131I is highly effective in treating hyperthyroidism. The aetiology, severity of hyperthyroidism at diagnosis, goitre size and prior antithyroid medication all had a significant effect on outcome.
PMCID: PMC3756864  PMID: 24082285
Radioiodine; hyperthyroidism
5.  Extremely high doses of radioiodine required for treatment of Graves’ hyperthyroidism: a case report 
Cases Journal  2009;2:8479.
Radioactive iodine (131I) is widely prescribed for treatment of Graves’ disease. A dose of 370 to 555 MBq (10 to 15 mCi) is usually enough, but reports of improved remission rates with single doses up to 20-30 mCi, and 38.5 mCi at most, exist.
Case presentation
A 53-year-old male patient was evaluated in September 2005, with symptoms of thyrotoxicosis for 2 years. He presented with tachycardia (130 bpm) and a large goiter. Thyrotropin was <0.01 uIU/ml (0,41-4,5), free thyroxin >7.77 ng/dl (0.9-1.8), anti-thyreoperoxidase antibody: 374 IU/ml (<35) and anti-thyroglobulin antibody: 749 IU/ml (<115). Ultrasound: diffuse goiter, no nodules; right lobe: 7.9 × 3.8 × 3.8 cm; left: 7.7 × 3.5 × 3.8 cm; isthmus: 1.6 cm. Propylthiouracil 300 mg t.i.d. and propranolol were prescribed. Thyroid 99mTc-pertechnetate uptake: 52% (0.35-1.7%) and estimated thyroid volume: 149 mL. After 30 days, he received 555 MBq (15 mCi) of 131I-iodide. Six months after radioiodine therapy, under methimazole 40 mg, thyroid stimulating hormone was 1.5 uIU/ml; free thyroxine 0.54 ng/dl. Methimazole was suspended. In 21 days, thyroid stimulating hormone was 0.03 uIU/ml; free thyroxine 0.96 ng/dl. Methimazole was reintroduced. One year later, thyroid stimulating hormone was <0.01 uIU/ml and free thyroxine >7.77 ng/dl. Thyroid 99mTc-pertechnetate uptake was 45% and estimated thyroid volume 144 mL. A 1110 MBq (30 mCi) radioiodine therpy was administered. He used Methimazole for 8 months, when overt hypothyroidism appeared (TSH: 25.30 uIU/ml; free thyroxine: 0.64 ng/dl). Methimazole was interrupted. Hyperthyroidism returned 6 weeks later (thyroid stimulating hormone <0.01 uIU/ml; free thyroxine >7.77 ng/dl). Thyroid 99mTc-pertechnetate uptake was 25% and estimated thyroid volume 111 mL. Methimazole was prescribed again. In March 2008 he received a 2590 MBq (70 mCi) radioiodine therapy. By may/2008, under methimazole 20 mg, his TSH was 0.07 uIU/ml; free thyroxine 1.31 ng/dl. In October 2008 he presented overt hypothyroidism (TSH 91.6 uIU/ml; free thyroxine 0.34) and was given levothyroxine 75 mcg/day. He remains euthyroid under hormone replacement.
Our presented case of Graves’ disease received a cumulative dose of 4255 MBq (115 mCi). The high uptake could indicate accelerated iodine turnover with 131I short time of action. Impaired hormone synthesis could also be present. We believe the extremely high dose required was due to the initial very high iodine uptake and large thyroid volume.
PMCID: PMC2769445  PMID: 19918435
6.  Radioiodine I-131 For The Therapy Of Graves’ Disease 
Graves’ disease is a common cause of hyperthyroidism. Treatment options for Graves’ disease include antithyroid medication, surgery or radioactive iodine (I-31) or RAI. This review will focus on the approach to RAI therapy; discussing dose selection, patient preparation, and consideration before and after administering RAI, examining aspects of pre-treatment with antithyroid medication as well as discussing possible adverse events including hypothyroidism and possible worsening of thyroid-associated opthalmopathy. Follow-up is lifelong with the aim of ensuring the patient remains euthyroid or on replacement therapy if there is evidence of hypothyroidism. While there are controversies in treatment of thyrotoxicosis with RAI, with appropriate patient selection and regular follow-up, radioiodine is a safe and effective modality in achieving high cure rates.
PMCID: PMC3336179  PMID: 22589645
radioactive iodine; Graves’ disease; thyroid; treatment; medical sciences
7.  Efficacy of Different Protocols of Radioiodine Therapy for Treatment of Toxic Nodular Goiter: Systematic Review and Meta-Analysis of the Literature 
To evaluate treatment success and hypothyroidism following main methods of radioiodine therapy of toxic nodular goiter (TNG); calculated versus fixed dose and high versus low dose of radioiodine.
Evidence Acquisitions:
We searched MEDLINE and SCOPUS databases from inception till July 2013, for clinical trials that compared two different methods of radioiodine administration in TNG. The trials were classified into two groups, those that compared fixed versus calculated dosimetry method and those that assessed high fixed dose versus low fixed dose method. Treatment response was defined as euthyroidism or hypothyroidism, one year after radioiodine administration. We calculated the risk ratio and risk difference of treatment response as well as permanent hypothyroidism as outcome variables. Random effects model was used for data pooling.
The literature search yielded 2538 articles. Two randomized and five non-randomized clinical trials with 669 patients met the eligibility criteria for the meta-analysis. Patients with TNG who were treated according to the calculated method had 9.6% higher cure rate (risk ratio=1.17) and only 0.3% more permanent hypothyroidism compared to patients treated with the fixed dose method. There was no significant difference in the amount of administered radio-iodine in the two groups. Patients treated with fixed high dose had 18.1% more cure rate (risk ratio = 1.2) and 23.9% more permanent hypothyroidism (risk ratio = 2.40) compared to patients treated by fixed low dose protocols.
Calculated radioiodine therapy may be preferred to fixed dose method in patients with TNG. High dose methods are associated with more response and more hypothyroidism.
PMCID: PMC4005974  PMID: 24803943
Thyrotoxicosis; Goiter; Nodular; Iodine; Hyperthyroidism
8.  Low-dose radioiodine given six-monthly in Graves' disease. 
Experience using low-dose radioiodine given six-monthly instead of yearly in hyperthyroid patients with Graves' disease is reported. One hundred and thirty-five patients have been treated over a three-year period with 74 MBq (2 mCi) doses of 131I. Thirty-eight percent were controlled with a single dose. Those patients requiring more than one dose were treated with a further 74 MBq (2 mCi) 131I at six-monthly intervals until euthyroid. Using this approach, 46% were euthyroid one year after starting treatment, and 75% were euthyroid at two years. The incidence of hypothyroidism following treatment was 2.2% at one year, with a yearly incidence thereafter of 4-6%. Six-monthly scheduling of low-dose radioiodine in Graves' disease can reduce the time taken to become euthyroid, compared with conventional yearly low-dose treatments. Further follow up is required to confirm the present low incidence of hypothyroidism following treatment.
PMCID: PMC1289995  PMID: 3840844
9.  Ablative radioiodine therapy for hyperthyroidism: long term follow up study. 
A total of 225 patients were treated for hyperthyroidism with 555 MBq (15 mCi) radioiodine to ablate the thyroid and induce early hypothyroidism. The efficacy of this treatment in eradicating hyperthyroidism and problems of follow up were assessed one to six years later from case records and questionnaires. Information was received from 197 out of 219 live patients (90%) and from 160 doctors concerning 207 patients (92%). Only three patients were not traced and six had died since treatment. The modal time to hypothyroidism was three months, and 64% of patients were hypothyroid at one year; 5.6% had failed to become euthyroid within one year. Ninety five per cent of patients had been seen by the doctor and 82% had had a thyroid test done within the past two years. Most doctors preferred patients to be returned to their care once thyroxine treatment was stabilised. An ablative dose of 131I is recommended as an effective means of treatment which has clear advantages over conventional methods. Good communications and effective follow up should ensure success.
PMCID: PMC1442353  PMID: 6432100
10.  Long-term carbimazole pretreatment reduces the efficacy of radioiodine therapy 
Data from several studies suggest that pretreatment with antithyroid drugs (ATD) before 131I increases the risk of treatment failure. This effect has been demonstrated more consistently with propylthiouracil than with carbimazole (CMZ) or methimazole (MMI). Men with Graves’ disease (GD) have a lower rate of remission with 131I compared to women and the impact of long-term ATD pretreatment on the success of 131I is unknown. The objective of our study was to compare the efficacy of fixed doses of radioiodine between patients with and without long-term CMZ pretreatment.
Materials and Methods:
We performed a retrospective study on 335 male patients with GD treated with 131I from 1998 to 2008. 148 patients had been pretreated with CMZ, and the remaining 187 patients received 131I without pretreatment. We compared the success rate of a single dose of 131I, between patients with and without long-term CMZ pretreatment.
The success rate of a single dose of 131I was significantly higher in patients without pretreatment than in patients who were pretreated with CMZ (91.4% vs. 82.3%, P = 0.01). The rate of hypothyroidism in the first 6 months after 131I therapy was significantly higher in patients without pretreatment (55.1% vs. 44.6%, P = 0.05). There was also a trend for higher cumulative rate of hypothyroidism at last follow-up in nonpretreated patients (78.1% vs. 69.7%).
Male patients with Graves’ hyperthyroidism pretreated with CMZ have lower efficacy with 131I therapy compared to nonpretreated patients. CMZ pretreatment given for a prolonged period reduces the efficacy of 131I therapy.
PMCID: PMC4287787  PMID: 25593832
Antithyroid drugs; carbimazole; Graves’ hyperthyroidism; pretreatment; radioiodine
11.  The early development of transient and permanent hypothyroidism following radioiodine therapy for hyperthyroid Graves' disease. 
Canadian Medical Association Journal  1984;130(9):1141-1144.
The outcome in 110 patients first treated with radioiodine (mean dose 6.56 mCi) for hyperthyroid Graves' disease in 1980 was reviewed. In 23% of the patients the disease had not been controlled by the initial dose after 3 months, and 17% were given one or two more doses. Within 2 years 65% of the patients required replacement thyroxine therapy. Although about half of the patients were biochemically hypothyroid 3 months after the last dose of iodine 131, this condition was transient in a third of them; five of these patients even became hyperthyroid again. Patients with transient, as opposed to permanent, hypothyroidism at 3 months tended to be clinically euthyroid but to have residual palpable thyroid tissue and only a modest reduction in the serum thyroxine level. It is therefore recommended that patients not overtly hypothyroid 3 months after treatment with 131I be observed still longer before thyroxine replacement therapy is instituted.
PMCID: PMC1876023  PMID: 6546895
12.  Graves' disease and atrial fibrillation: the case for even higher doses of therapeutic iodine-131. 
Seventy five consecutive patients with Graves' disease complicated by atrial fibrillation were given a large single therapeutic dose of 600 MBq (16.2 mCi) iodine-131 in an effort to control their hyperthyroidism rapidly and thus restore sinus rhythm. Patients were initially followed up every three months after treatment and then at yearly intervals. The mean period of follow up was 3.1 years. A total of 44 of the patients became hypothyroid and 31 euthyroid, and 33 (75%) and 14 (45%) of these patients, respectively, reverted to sinus rhythm (p less than 0.01). Of the 33 who became hypothyroid and reverted to sinus rhythm, 30 had developed the hypothyroidism within six months after treatment. These results are a strong case for increasing the dose of radioiodine in patients with Graves' disease complicated by atrial fibrillation in an effort to speed the onset of thyroid failure and thus maximise the rate of reversion to sinus rhythm.
PMCID: PMC1442420  PMID: 6432116
13.  Radioiodine remnant ablation of differentiated thyroid cancer does not further increase oxidative damage to membrane lipids - early effect 
Thyroid Research  2010;3:7.
Radioiodine (131I) therapy is widely accepted as an essential part of therapeutic regimens in many cases of differentiated thyroid cancer. Radiation-induced oxidative damage to macromolecules is a well known phenomenon. Frequently examined process to evaluate oxidative damage to macromolecules is lipid peroxidation (LPO), resulting from oxidative damage to membrane lipids. The aim of the study was to examine serum LPO level in hypothyroid (after total thyroidectomy) cancer patients subjected to ablative activities of 131I.
Materials and methods
The study was carried out in 21 patients (18 females and 3 males, average age 52.4 ± 16.5 years) after total thyroidectomy for papillary (17 patients) or follicular (4 patients) thyroid carcinoma. Hypothyroidism was confirmed by increased TSH blood concentration (BRAHMS, Germany), measured before 131I therapy. Activity of 2.8 - 6.9 GBq of 131I was administered to the patients orally as sodium iodide (OBRI, Poland). Concentrations of malondialdehyde + 4-hydroxyalkenals (MDA + 4-HDA), as an index of LPO (LPO-586 kit, Calbiochem, USA), were measured in blood serum just before 131I administration (day "0") and on the days 1-4 after 131I therapy. Sera from 23 euthyroid patients served as controls. Correlations between LPO and TSH or 131I activity were calculated.
Expectedly, serum LPO level, when measured before 131I therapy, was several times higher (p < 0.00001) in cancer patients than in healthy subjects, which is probably due to hypothyroidism caused by total thyroidectomy. However, we did not observe any differences between LPO levels after and before 131I therapy. LPO did not correlate with TSH concentration. In turn, negative correlation was found between 131I activity and LPO level on the day "2" after radioiodine treatment.
Radioiodine remnant ablation of differentiated thyroid cancer does not further increase oxidative damage to membrane lipids, at least early, after therapy.
PMCID: PMC2964524  PMID: 20925955
14.  Radioactive Iodine for Thyrotoxicosis in Childhood and Adolescence: Treatment and Outcomes 
Objective: The aim of the present study was to evaluate the outcome of radioiodine treatment in thyrotoxicosis in childhood and adolescence.
Methods: This was a retrospective study of 27 patients (ages 7.2- 19.8 years) with a diagnosis of thyrotoxicosis who received iodine-131 (I-131) treatment from January 2007 to December 2011 in the Nuclear Medicine Division, Department of Radiology, Faculty of Medicine, Chiang Mai University. Gender, duration of antithyroid drug (ATD) treatment, 24-hour I-131 uptake, thyroid weight, total dose and number of treatments with I-131, and thyroid status at 6 months after treatment were recorded.
Results: The outcomes of 27 patients (85.2% female, 14.8% male) treated with radioactive iodine were analyzed to assess the effectiveness of therapy as related to dose and gland size. All children and adolescents received 150 µCi of I-131/g of thyroid tissue (n=27). Six 6 months after treatment, 44.5% of the patients were hyperthyroid, 14.8% were euthyroid, and 40.7% were hypothyroid. Of the 12 cases with hyperthyroidism, 2 cases needed a second dose of I-131 treatment, and they finally reached a hypothyroid state. The patients were classified into 2 groups according to treatment success (euthyroid and hypothyroid) and treatment failure (hyperthyroid). There were no significant differences in age, gender, duration of ATD treatment, 2- and 24-hour I-131 uptake, thyroid weight, and total I-131 dose between these two groups.
Conclusions: Radioiodine treatment is safe and effective for thyrotoxicosis in childhood and adolescence. It is suitable as a good second-line therapy for patients with severe complications, those who show poor compliance, and those who fail to respond to ATD treatment. .
Conflict of interest:None declared.
PMCID: PMC3701929  PMID: 23748061
Radioiodine treatment; thyrotoxicosis; children; adolescence; outcome
15.  No impact of dietary iodine restriction in short term development of hypothyroidism following fixed dose radioactive iodine therapy for Graves’ disease 
The increased incidence of autoimmune thyroid disease with increasing dietary iodine intake has been demonstrated both epidemiologically and experimentally. The hypothyroidism that occurs in the first year following radioactive iodine therapy is probably related to the destructive effects of the radiation and underlying ongoing autoimmunity.
To study the outcomes at the end of six months after fixed dose I, 131therapy for Graves’ disease followed by an iodine restricted diet for a period of six months.
Materials and Methods:
Consecutive adult patients with Graves’ disease planned for I131 therapy were randomized either to receive instructions regarding dietary iodine restriction or no advice prior to fixed dose (5mCi) I131 administration. Thyroid functions and urinary iodine indices were evaluated at 3rd and 6th month subsequently.
Forty seven patients (13M and 34F) were assessed, 2 were excluded, 45 were randomized (Cases 24 and Controls 21) and 39 patients completed the study. Baseline data was comparable. Median urinary iodine concentration was 115 and 273 μg/gm creat (p = 0.00) among cases and controls respectively. Outcomes at the 3rd month were as follows (cases and controls); Euthyroid (10 and 6: P = 0.24), Hypothyroid (3 and 5: P = 0.38) and Hyperthyroid (7 and 8: P = 0.64). Outcomes at the end of six months were as follows (cases and controls); Euthyroid (10 and 5: P = 0.12), Hypothyroid (3 and 5: P = 0.38) and Hyperthyroid (7 and 9: P = 0.43). Of the hypothyroid patients 5 (cases 1 and controls 4: P = 0.13) required thyroxine replacement.
There was no statistical significant difference in the outcome of patients with dietary iodine restriction following I131 therapy for Graves’ disease.
PMCID: PMC4287782  PMID: 25593828
Dietary iodine restriction; graves’ disease; radioactive iodine; urinary iodine/creatinine ratios
16.  Effect of 1110 MBq Radioiodine in Reducing Thyroid Volume in Multinodular Goiter: A New Protocol 
There is no consensus on the optimal treatment of multinodular goiter (MNG), but in the past few years, the use of radioiodine has increased. This study’s objective was to evaluate adjuvant methimazole (MMI) therapy to increase and standardize radioiodine uptake (RAIU) with a fixed therapeutic 131I dose of 1110 MBq (30 mCi).
Our study included 5 women with MNG treated with MMI, 10 - 15 mg/day for 2 to 4 months, prior to the administration of 1110 MBq 131I (30 mCi); none of the patients developed hypothyroidism during MMI therapy and had average basal TSH levels of 0.32 ± 0.39 mIU/L that increased to 2.6 ± 0.9 mIU/L (P = 0.07).
RAIU increased from 25.6 ± 8.7% to 49.2 ± 8.3% (P = 0.003). All patients were followed for 12 months: median thyroid volume (TV) decreased from 77.2 mL (32.9 - 124.2) to 48.8 ml (12.4 - 68.9) with an average decrease of 46.4 ± 14.8% (P = 0.01). All patients developed hypothyroidism during the first 6 months after radioiodine therapy.
This new therapeutic protocol using MMI as adjuvant therapy is effective in increasing RAIU as well as the deleterious effects of 131I, without increasing the required dose, but leading to thyroid volume decreases similar to those reported with the use of recombinant human thyrotropin (rhTSH) or higher radioiodine doses.
PMCID: PMC3651074  PMID: 23671549
Methimazole; Radioiodine; Multinodular goiter; Thyroid; Uptake; 131I; Treatment; Hyperthyroidism
17.  Hypothyroidism as a Late Sequela in Patients with Graves' Disease Treated with Antithyroid Agents 
Journal of Clinical Investigation  1979;64(5):1429-1436.
In 1971, thyroid function was evaluated in 15 unselected patients whose only therapy for diffuse toxic goiter was a course of thionamide drug treatment completed 20-27 yr earlier. One patient was frankly hypothyroid by clinical and laboratory criteria. The remaining 14 patients appeared clinically euthyroid and had a normal serum thyroxine (T4) concentration and thyroid radioiodine uptake (RAIU). Nevertheless, only 6 of 14 appeared to be entirely normal according to more refined criteria. The serum thyrotropin (TSH) concentration was markedly elevated in one patient and above the normal range (1.6±2.0; mean±2 SD) in five others. Thyroid stimulation with exogenous TSH revealed subnormal responses of the serum T4I, RAIU, or both, in 7 of 11 patients tested. An abnormal iodideperchlorate discharge test was found in 5 of 10 patients and appeared most abnormal in patients with abnormal RAIU responses to TSH. Fluorescent antimicrosomal antibody was found in the serum of 12 of the 15 patients, in contrast to an expected frequency of 7% in normal individuals of the same age.
By the time a second major follow-up study was completed in 1978, two additional patients had become frankly hypothyroid. A third subject met accepted criteria for subclinical hypothyroidism. One of these subjects had had a clearly elevated serum TSH concentration in 1972, and the remaining two had exhibited the highest responses of serum TSH (36, 26 μU/ml) to thyrotropin-releasing hormone among 10 patients tested in 1972.
One patient developed recurrent thyrotoxicosis in 1978, 25 yr after the onset of his first and only other apparent episode of hyperthyroidism. This patient was the only one who demonstrated a subnormal response to thyrotropin-releasing hormone in 1972. The remaining nine subjects that could be studied in 1978 exhibited varying combinations of abnormalities of thyroid function.
It is concluded that progressive failure of thyroid function is a common occurence in long-standing Graves' disease, and it is suggested that this results from concomitant chronic thyroiditis. We postulate that this inherent tendency toward thyroid failure is exaggerated by surgery or radioactive iodine, explaining the progressive increase in, and inordinate frequency of, hypothyroidism after ablative modes of therapy in diffuse toxic goiter.
PMCID: PMC371292  PMID: 91625
18.  Radioiodine treatment of multinodular non-toxic goitre. 
BMJ : British Medical Journal  1993;307(6908):828-832.
OBJECTIVE--To investigate the long term effect of radioactive iodine on thyroid function and size in patients with non-toxic multinodular goitre. DESIGN--Consecutive patients with multinodular non-toxic goitre selected for radioactive iodine treatment and followed for a minimum of 12 months (median 48 months) after an intended dose of 3.7 MBq/g thyroid tissue corrected to a 100% uptake of iodine-131 in 24 hours. PATIENTS--69 patients with a growing multinodular non-toxic goitre causing local compression symptoms or cosmetic inconveniences. The treatment was chosen because of a high operative risk, previous thyroidectomy, or refusal to be operated on. MAIN OUTCOME MEASUREMENTS--Standard thyroid function variables and ultrasonically determined thyroid volume before treatment as well as 1, 2, 3, 6, and 12 months after treatment and then once a year. RESULTS--56 patients were treated with a single dose of 131I, 12 with two doses, and one with four doses. In 45 patients treated with one dose and remaining euthyroid the median thyroid volume was reduced from 73 (interquartile range 50-106) ml to 29 (23-48) ml at 24 months in the 39 patients in whom this was measured during follow up. The median reduction was 40 (22-48) ml (60% reduction, p < 0.0001), half of which occurred within three months. Patients treated with two doses as well as those developing hypothyroidism and hyperthyroidism had a significant reduction in thyroid volume. Eleven patients developed hypothyroidism (cumulative five year risk 22%, 95% confidence interval 4.8% to 38.4%). Side effects were few: three cases of hyperthyroidism and two cases of radiation thyroiditis. Only one patient was dissatisfied with the result; she was referred for operation six months after treatment. CONCLUSIONS--A substantial reduction in thyroid volume accompanied by a low incidence of hypothyroidism and few side effects makes the use of radioactive iodine an attractive alternative to surgery in selected cases of non-toxic multinodular goitre.
PMCID: PMC1678858  PMID: 8401123
19.  Recombinant TSH and Lithium Overcomes Amiodarone-Induced Low Radioiodine Uptake in a Thyrotoxic Female 
Recombinant human thyroid-stimulating hormone(rhTSH) increases radioactive iodine uptake(RAIU) in selected populations, while lithium is used as an adjunct to radioactive iodine (RAI) therapy in Graves’ disease with low RAIU. In this report, both drugs used in combination, overcame low iodine-131 uptake in a Graves’ patient.
Clinical Case:
A 39-year old female with Graves’ disease, acquired thionamide-induced agranulocytosis, and severe hypokalemia, subsequently went into cardiorespiratory arrest. On resuscitation, she had ventricular tachyarrhythmias which were cardioverted using amiodarone. She was subsequently placed on IV hydrocortisone amiodarone and propranolol. On admission, she was normotensive, tachycardic, and afebrile. She had fine tremors, hyper reflexia, and diffuse, non-tender thyromegaly. Initial investigations showed normal complete blood count, hypokalemia and elevated alanine transaminase levels. Levels of thyroid stimulating hormone were low (0.03 uIU/L, N = 0.27-3.75). Thyroid ultrasound showed diffuse thyromegaly with uniform echopattern and normal color flow Doppler, radioiodine uptake showed low uptake at 0400h and 2400h (6% and 7%, respectively). In preparation for RAI therapy, she was given lithium 900mg/day for 12 days to increase RAI retention. To increase iodine-131 uptake, two doses of 0.9mg rhTSH were injected intramuscular, 24 hours apart, before RAI therapy. Repeat RAIU after the second dose of rhTSH showed more than a 5-fold increase in 0400h uptake compared with the baseline (32% vs. 6%). Exactly 24 hours after the second dose of rhTSH, she was given 25mCi of iodine-131. Thereafter, the patient’s clinical and biochemical markers continued to improve. She became hypothyroid and is currently on levothyroxine replacement therapy.
This case demonstrates the efficacy of combining rhTSH and lithium to overcome amiodarone-induced low iodine-131 uptake in Graves’ disease.
PMCID: PMC3693641  PMID: 23843834
rhTSH; Lithium; Amiodarone
20.  Long-term outcome of low-activity radioiodine administration preceded by adjuvant recombinant human TSH pretreatment in elderly subjects with multinodular goiter 
Thyroid Research  2009;2:6.
Large multinodular goiter (MNG) in elderly people is a common finding which can require intervention. The long-term effect of radioiodine therapy on thyroid volume (TV) and function after recombinant human (rh) TSH pre-treatment was evaluated.
After baseline evaluation, 40 subjects over 60 years old with a large MNG were treated with 131I up to the activity of 600 MBq. Nineteen patients were pretreated with rhTSH (0.1 mg on 2 consecutive days; group 1) while 21 subjects underwent treatment without rhTSH pretreatment (group 2). TV was monitored every 6–12 months by ultrasonography. The median follow-up period was 36 months.
At the baseline, the groups matched in terms of TV, 24-h radioiodine uptake (RAIU), urinary iodine and neck complaints. The number of subjects pretreated with anti-thyroid drugs was significantly (P = 0.01) greater in group 2 than in group 1; TSH was more suppressed (P = 0.003) and f-T3 was more elevated (P = 0.005) in group 2 than in group 1 patients. RhTSH increased 24-h RAIU in group 1 up to the baseline level observed in group 2. The 131I activity administered was similar in both groups. Adverse events were slight and similar in both groups. A permanent post-radioiodine toxic condition was reported only in 2 patients in group 2. After radioiodine therapy, hypothyroidism was observed in significantly more group 1 patients than group 2 patients (P = 0.002). While TV was reduced in both groups, the percentage TV reduction recorded at the last examination was significantly higher (P = 0.03) in group 1 than in group 2. MNG-related complaints were significantly reduced in both group 1 (P = 0.0001 vs baseline) and group 2 (P = 0.001) patients.
Low radioiodine activities after pretreatment with low-dosage rhTSH are able to reduce TV and improve MNG-related symptoms in elderly subjects.
PMCID: PMC2713215  PMID: 19566933
21.  Impact of lithium on radioactive iodine therapy for hyperthyroidism 
Radioactive Iodine (RAI) is a common therapy for hyperthyroidism. However hyperthyroidism recurs or persists in 15-18% of patients after RAI. Studies report variable percentage of failure after RAI therapy depending on several variables including I131. Lithium enhances efficacy of treatment by increasing RAI retention in the thyroid.
To evaluate the efficacy of Lithium to RAI therapy in terms of cure, reduction of mean thyroid volume, and its safety.
Settings and Design:
A prospective comparative study.
Subjects and Methods:
Forty hyperthyroid patients were assigned to two groups, RAI alone and RAI plus lithium and followed for 1 year. Lithium was given in a dose of 900 mg/day in three divided doses for 6 days starting on the day of RAI therapy. Total T3, total T4, and thyroid-stimulating hormone (TSH) were done at baseline, 2,4,6,9, and 12 months. Ultrasound of thyroid was done at baseline and at the end of 1 year. Monitoring was done for side effects of lithium and RAI therapy.
Statistical Analysis:
Cure rate and time to cure were assessed by Chi-square test. Mean change in thyroid volume was compared by student's t-test. P < 0.05 was considered significant.
RAI combined with lithium had a trend towards better cure rate (90%) compared to RAI alone (70%) (P 0.11). Mean time taken to cure was 4.69 months in RAI plus lithium and 7.12 months in RAI alone (P 0.001). Mean change in thyroid volume was similar in both the groups (P = 0.75). There were no side effects of Lithium or RAI.
RAI therapy combined with lithium showed a trend towards higher cure rate, safe and time to cure was less than RAI alone. Hence RAI combined with lithium is a better option in the management of hyperthyroidism than RAI alone.
PMCID: PMC4171890  PMID: 25285284
Hyperthyroidism; lithium; Radioactive Iodine
22.  Hyperthyroidism and radio-iodine therapy in a district general hospital. 
A retrospective analysis was performed of 48 patients with hyperthyroidism (41 women aged 35-80, mean 56.6 years; 7 men aged 31-77, mean 52.1 years) treated with a fixed dose of 550 MBq 131I during a 12 month period May 1991-April 1992. Weight loss was common at presentation but 28.57% of women aged 35-49 years weighed over 80 kg compared to 9.98% in a standard UK population P < 0.05. Patients treated with carbimazole (73%) prior to 131I had higher FT3 levels at presentation (14.0 +/- 4.4 pmol/l) compared to those (27%) who were considered not to require such treatment (8.9 +/- 1.4 pmol/l, P < 0.001). Four months following radio-iodine, 67% were hypothyroid, 25% were euthyroid and 8% remained thyrotoxic and were retreated. Another patient became hypothyroid during 1 year of follow-up. Pre-treatment with carbimazole did not protect against the development of hypothyroidism (carbimazole treated 69% hypothyroid at 4 months, untreated 62% hypothyroid at 4 months). Patients with continuing thyrotoxicosis had very high FT3 levels at presentation (18.6, 21.1, 20 and in one patient reported only as > 10 pmol/l). A rationalized programme of follow-up assessments at 2, 3, 4, 8 and 12 months is suggested for patients treated with this dose of radio-iodine.
PMCID: PMC1294843  PMID: 7966101
23.  Thyrotoxicosis and radioiodine therapy: Does the dose matter? 
There are 3 treatment options for thyrotoxicosis: Antithyroid drugs, Surgery and radioiodine. The choice of treatment varies geographically. Radioiodine therapy is preferred in the United States. The aim of radioiodine is to destroy sufficient thyroid tissue to cure the hyperthyroidism. There is a lack of consensus towards what dose of radioiodine should be used. Several methods are used to determine the dose. In our practice we administer 400 MBq to patients with Graves and in patients with large multinodular goiter, we would administer 800 MBq.
PMCID: PMC3603012  PMID: 23565364
Thyrotoxicosis; radiodine therapy; Dose
24.  Evaluating the Efficacy of Primary Treatment for Graves' Disease Complicated by Thyrotoxic Periodic Paralysis 
Objective. Thyrotoxic periodic paralysis (TPP) is a potentially life-threatening complication of Graves' disease (GD). The present study compared the long-term efficacy of antithyroid drugs (ATD), radioactive iodine (RAI), and surgery in GD/TPP. Methods. Sixteen patients with GD/TPP were followed over a 14-year period. ATD was generally prescribed upfront for 12–18 months before RAI or surgery was considered. Outcomes such as thyrotoxic or TPP relapses were compared between the three modalities. Results. Eight (50.0%) patients had ATD alone, 4 (25.0%) had RAI, and 4 (25.0%) had surgery as primary treatment. Despite being able to withdraw ATD in all 8 patients for 37.5 (22–247) months, all subsequently developed thyrotoxic relapses and 4 (50.0%) had ≥1 TPP relapses. Of the four patients who had RAI, two (50%) developed thyrotoxic relapse after 12 and 29 months, respectively, and two (50.0%) became hypothyroid. The median required RAI dose to render hypothyroidism was 550 (350–700) MBq. Of the 4 patients who underwent surgery, none developed relapses but all became hypothyroid. Conclusion. To minimize future relapses, more definitive primary treatment such as RAI or surgery is preferred over ATD alone. If RAI is chosen over surgery, a higher dose (>550 MBq) is recommended.
PMCID: PMC4131447  PMID: 25147568
25.  Effects of hypothyroidism on bronchial reactivity in non-asthmatic subjects. 
Thorax  1990;45(12):947-950.
The effect of hypothyroidism on non-specific bronchial reactivity was studied in 11 patients without pulmonary disease (mean age 40 (SD 13) years) who had had a total thyroidectomy and radioiodine treatment for thyroid cancer 41 (36) months before the study. All patients when mildly hyperthyroid while having long term thyroxine replacement treatment and once when hypothyroid two weeks after stopping triiodothyronine for the purpose of screening for metastases. Bronchial reactivity was assessed by measuring specific airways conductance (sGaw) after increasing doses of inhaled carbachol (45-1260 micrograms). The dose producing a 35% decrease in sGaw (PD35) was determined from the cumulative log dose-response curve by linear regression analysis. Mean baseline sGaw values were similar when the patients were hypothyroid and when they were hyperthyroid (1.35 (0.36) and 1.41 (0.56) s-1 kPa-1). The interstudy coefficients of variation of baseline sGaw were higher in the thyroid patients than in a euthyroid control group (14% versus 8%). Geometric mean PD35 was lower when the patients were hypothyroid (97 micrograms) than when they were mildly hyperthyroid (192 micrograms). It is concluded that acute hypothyroidism increases non-specific bronchial reactivity in nonasthmatic subjects.
PMCID: PMC462844  PMID: 2281429

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