Ovarian function after radioiodine therapy in patients with thyroid cancer.

OBJECTIVE: To assess ovarian function in young women treated with radioiodine. METHODS: The study was conducted on 50 women with thyroid carcinoma aged less than 40 years (mean, 29.8 years), with regular menstrual cycles and normal FSH levels prior to radioiodine therapy. FSH determination was repeated 6 and 12 months after radioiodine therapy (mean, 4.24 GBq iodine-131) and menstrual cycles were monitored during this period. RESULTS: Twenty percent of the patients reported amenorrhea during the first year. FSH levels increased after 6 months (from 5.1 +/- 1.8 to 10.6 +/- 2.2 IU/l, p < 0.00 001) and 28 % of the patients showed elevated values, which had returned to normal by the end of the first year. CONCLUSION: Radioiodine causes transitory alterations in ovarian function even in younger women and after a mean activity of 4.2 GBq (115 mCi).     

Gastric emptying function changes in patients with thyroid cancer after withdrawal of thyroid hormone therapy

BACKGROUND: Hypothyroidism is commonly thought to cause decreased gastric emptying but is mostly associated with autoimmune disease. In the present study the gastric emptying function of thyroid cancer patients with severe hypothyroidism of short duration was evaluated with a radionuclide solid meal gastric emptying study. METHODS: Twenty-two patients who had undergone surgical operation and (131)I ablation for thyroid cancer participated in solid meal gastric emptying studies before the withdrawal of thyroxine and then again 4 weeks after the withdrawal of thyroxine. Eleven patients had an additional gastric emptying study at 6 weeks after withdrawal of thyroxine. Gastric emptying curves and emptying parameters were calculated. Student's paired t-test was used for statistical analysis of data for all cases between the baseline and at 4 weeks after withdrawal. An additional repeated measure anova with multiple comparisons was performed on data between baseline, 4 weeks and 6 weeks after withdrawal for the other 11 patients. All P values presented are two-tailed and the significance level is 0.05. RESULTS: Hypothyroidism status was confirmed by the marked change of the serum thyroxine and thyroid-stimulating hormone 4 weeks and 6 weeks after withdrawal of the thyroxine replacement (P < 0.001). The gastric half-emptying time and emptying rate changed significantly after short-term severe thyroid hormone deficiency (P < 0.005). However, the length of the lag phase did not have a statistically significant change at 4 weeks or 6 weeks after withdrawal of the thyroxin replacement (P = 0.219 and 0.142). CONCLUSIONS: Hypothyroidism following the withdrawal of the thyroxine replacement in thyroid cancer patients preparing for (131)I cancer work-up can significantly prolong gastric half-emptying time and emptying rate.     

Testicular damage after radioactive iodine (I-131) therapy for thyroid cancer

Testicular damage was evaluated in twelve men by determination of sperm counts, serum FSH, LH, and testosterone up to 3 1/2 years after treatment with radioactive iodine (131I) therapy for thyroid cancer. Dose-dependent spermatogenic damage with elevation of serum FSH was evident. Full recovery in one and partial recovery in another patient was documented during 2 1/2 years of follow-up. Serial study in two patients documented a small but significant effect of 50 mCi 131I on serum FSH levels and clinically important effects appear to be restricted to men having multiple doses totalling over 100 mCi.     

Safety of radioiodine therapy in patients with thyroid carcinoma younger than 21 years

We studied 20 patients with differentiated thyroid carcinoma undergoing radioiodine therapy (> or = 100 mCi dose) before the age of 21: 10 patients without distant metastases received a mean dose of 145 mCi and 10 with lung involvement received 270 mCi. One or more years after ablative therapy, xerostomia was present in two patients but was not accompanied by more severe complications such as oral ulcers or fissures, and 99mTcO4- scintigraphy confirmed salivary dysfunction. One patient showed keratoconjunctivitis sicca. Blood counts did not reveal abnormalities caused by radioiodine therapy. FSH was normal in 18 patients. Patients with elevated levels had received radioiodine just over a year ago and repetition of the exam after 6 months showed that FSH had returned to normal. The 6 male patients had normal LH and testosterone levels. Analysis did not reveal signs of pulmonary fibrosis secondary to treatment in the 10 cases with iodine-accumulating metastases in this organ. Our data suggest that ablative therapy employing a dose of 100 to 300 mCi is safe in young individuals, but persistent complications such as salivary dysfunction and conjunctivitis may occur.     

Lack of impact of radioiodine therapy in tg-positive, diagnostic whole-body scan-negative patients with follicular cell-derived thyroid cancer

Several reports have suggested a benefit from radioactive iodine (RAI) therapy in Tg-positive, whole-body scan-negative patients with follicular cell-derived thyroid cancer, who were said to have high rates of visualization of uptake in metastases after therapeutic doses of RAI. We sought to evaluate the rate of visualization of RAI uptake in these patients and determine the effect of such therapy on tumor progression and Tg levels. We studied 24 consecutive patients who had been treated with high-dose RAI, four of whom had no evidence of metastasis or persistent cancer. Our results showed that four patients had some uptake in posttherapy scans: in the neck, lung, and mediastinal metastases in one patient, in the thyroid remnant in two, and in a possible neck microrecurrence in one. In 13 patients with macrometastases-tumors 1 cm or greater-tumors progressed and serum Tg increased; five have died of thyroid cancer. The disease remained stable in the seven patients with micrometastases. We concluded that in high-risk patients with follicular cell-derived thyroid cancer with high Tg levels and negative diagnostic whole-body scans, only a small number showed meaningful uptake after high doses of RAI. Therefore, widespread use of empiric RAI therapy for such patients who have a large tumor burden should not be encouraged.     

Treatment with lithium prevents serum thyroid hormone increase after thionamide withdrawal and radioiodine therapy in patients with Graves' disease

Serum thyroid hormone concentrations increase after radioiodine (RAI) therapy for Graves' disease. This phenomenon has been ascribed to either antithyroid drug withdrawal before RAI therapy or release of preformed thyroid hormones into the bloodstream from the RAI-damaged thyroid. Lithium blocks the release of iodine and thyroid hormones from the thyroid, thus enhancing the effectiveness of RAI therapy. Changes in serum-free thyroxine (FT4) and triiodothyronine (FT3) levels after methimazole (MMI) discontinuation and RAI therapy were evaluated in a prospective, randomized, control study of 36 patients with Graves' disease. After a 3- to 4-month course of MMI, patients were assigned to one of three groups: G1 (RAI alone); G2 (RAI plus lithium for 6 d starting on the day of RAI therapy); or G3 (RAI plus lithium for 19 d starting on the day of MMI withdrawal). G1-G2 patients had an increase in serum FT4 and FT3 levels from 13.5 +/- 6.5 to 19.8 +/- 9.2 pmol/liter and 5.0 +/- 2.0 to 8.0 +/- 4.8 pmol/liter, respectively (P < 0.0001), 2-5 d after MMI withdrawal, but G3 patients showed no changes. In the 30 d after RAI therapy, mean serum FT4 values increased in G1 patients (P = 0.02), peaking at 3-7 d (P < 0.05) but not in G2 and G3 patients. Serum FT3 levels decreased in G1, G2, and G3 (P = 0.03, P = 0.001, P = 0.02, respectively). Hyperthyroidism was cured in 8 of 12 G1 patients, 11 of 12 G2 patients, and 11 of 12 G3 patients (P = 0.31). Control of hyperthyroidism was prompter in G2 (P = 0.08) and G3 (P < 0.05) than in G1 patients. Patients in the three groups received a similar dose of RAI, but the committed radiation to the thyroid was higher in G3 (563 +/- 174 Gray) and G2 (588 +/- 347 Gray) than in G1 (429 +/- 204 Gray) (P < 0.03). In conclusion, the results of the present study demonstrate that: 1) MMI withdrawal is associated with a slight rise in serum thyroid hormone levels; 2) a further increase occurs after RAI therapy; 3) changes in serum thyroid hormone concentrations are prevented by lithium; and 4) the increased effectiveness of RAI therapy in lithium-treated patients is related to the increased RAI retention in the thyroid gland. Accordingly, a short course of lithium therapy can be considered a useful adjunct to RAI therapy to obtain a prompter control of thyrotoxicosis and avoid its transient exacerbation because of MMI withdrawal and RAI administration.     

Prognostic significance of successful ablation with radioiodine of differentiated thyroid cancer patients

OBJECTIVES: Currently, little is known about the prognostic significance of achieving successful ablation with the first dosage of I-131 in patients with differentiated thyroid cancer. This study aimed to assess the following: (i) whether successful or unsuccessful ablation at post-ablation follow-up has prognostic consequences; (ii) possible factors predicting success of ablation in a patient. METHODS: In order to do this, we retrospectively studied 180 patients with a median follow-up of 55 months. Ablation was considered to be successful if 1 year after the initial dosage of I-131 patients fulfilled all of the following criteria: not dead from thyroid cancer, no additional therapy needed for any kind for thyroid cancer within the first year, undetectable thyroglobulin (Tg) levels under TSH stimulation, and negative I-131 scintigraphy. Tg levels at the time of ablation (P < 0.001), lymph node metastasis (P = 0.04) and distant metastasis (P < 0.001) have a significant influence on the success of ablation. P values were calculated by Mann-Whitney U test and Chi-square test, respectively. RESULTS: Patients with successful ablation had a better prognosis than those with unsuccessful ablation: disease-free survival was 87% versus 49% after 10 years; additionally, thyroid-cancer related survival was 93% versus 78%. CONCLUSION: We conclude that the extent of the remaining normal or neoplastic thyroid tissue influences the outcome of ablation, and that successful ablation leads to a better prognosis. It seems that it is very important to achieve complete ablation as soon as possible in order to ensure the best possible prognosis for a patient.     

Testicular function after 131I therapy for hyperthyroidism

OBJECTIVE: Radioiodine-131 is commonly used for treatment of hyperthyroidism but there are few available data on the effects of this treatment on male gonadal function. The untoward effects of (131)I have been mainly studied in male patients treated with high doses for thyroid cancer. In the present work we studied the absorbed radiation dose to the testes and testicular function in hyperthyroid men after (131)I treatment. PATIENTS AND MEASUREMENTS: Nineteen male hyperthyroid patients were enrolled in the study before (131)I therapy. Seventeen of the patients had Graves' disease and two had toxic adenoma. The study was subdivided into two parts: a dosimetric and a clinical study. Six patients were enrolled for the dosimetric study and 13 for the clinical study. The beta dose delivered to the testes was evaluated by the Medical Internal Radiation Dose (MIRD) method. The gamma dose was measured by thermoluminescent dosimeters (TLDs) placed on the skin overlying the inferior poles of the testes for 3 weeks after therapy. The clinical evaluation included hormone determination, ultrasound (US) of the testes and sperm analysis. Patients were followed up for 12 months after (131)I therapy. RESULTS: In the dosimetric study, the beta dose absorbed in the testes was 12.5 +/- 8.8 mGy (range 29-15 mGy) and the gamma dose was 15.8 +/- 5.3 mGy (range 24-11 mGy). The total dose to the testes for administered activity unit was 39 +/- 14 microGy/MBq (range 27-86 microGy/MBq). In the clinical study, FSH did not change significantly after (131)I treatment for the majority of patients. Serum testosterone (T) and the T/LH ratio were significantly reduced 45 days after treatment and returned to basal levels after 12 months. Ten out of 15 hyperthyroid patients (67%) had low sperm motility before treatment. A significant increase in progressive motility was observed after (131)I therapy (Friedman test chi(2) = 12.65, P = 0.01). Conversely, there was no significant variation in sperm concentration and percentage of normal forms after (131)I. CONCLUSIONS: After (131)I therapy, germinal epithelium and Leydig cell function undergo only marginal changes, which may have some significance in subjects with a pre-existing fertility impairment.     

Are posttherapy radioiodine scans informative and do they influence subsequent therapy of patients with differentiated thyroid cancer?

Posttherapy scans (PTS) with a gamma camera are typically used after therapeutic doses of 131I to visualize metastases that may not be seen with lower dose diagnostic scans. During a 16-month period, we studied 81 patients (64 with papillary thyroid cancer and 17 with follicular thyroid cancer), who had both a diagnostic whole-body scan (131I dose 3 mCi) and a PTS. A total of 117 PTS were evaluated. At the time of PTS, clinical or radiologic evidence of metastatic or residual disease was present in 68 patients (84%). The anatomic sites of known disease included, neck (63), mediastinum (23), lung (35), bone (14), trachea (16), esophagus (5), and brain (2). PTS showed focal areas of abnormal uptake not seen in diagnostic scans in 15 scans (13%). Areas with abnormal new uptake included: neck (5), lung (5), mediastinum (4), bone (2), and adrenal (1). In 7 patients (9%) the PTS results impacted future decisions regarding plans for subsequent diagnostic scanning and 131I therapy or changed the patient's risk group category. In conclusion: (1) 13% of 117 PTS demonstrated abnormal foci of 131I uptake not seen on pretherapy scans and (2) PTS changed management strategy in 9% of the studied patients.     

Retinoic acid in patients with radioiodine non-responsive thyroid carcinoma

De-differentiated thyroid carcinoma is characterized by loss of thyroid-specific functions and properties. The therapeutic options for this type of thyroid cancer are limited and generally not efficient. Recent studies with retinoic acid (RA) have shown that this drug can induce re-differentiation of the thyrocyte and tumor regression after 131I therapy. The aim of the present study was to assess the effects of RA therapy in patients with extensive thyroid tumor involvement, which lost radioiodine uptake ability. A total of 5 patients (1 follicular carcinoma, 3 papillary carcinomas and 1 poorly differentiated carcinoma) were treated with isotretinoin (1.0 to 1.5 mg/kg/day) for 5 weeks and then submitted to radioiodine therapy. Three parameters for assessment of RA effects were established: a) reduction of serum thyroglobulin levels; b) increment of the post-therapeutic dose radioiodine uptake; c) tumor size regression after therapy. All patients completed the treatment and the most frequent side effects were dry skin and lips and hypertriglyceridemia. One patient showed satisfactory response (2 or more of the 3 criteria were reached) and a new cycle of RA was given. In two, just a partial response (1 criterion) was seen and the other patients did not respond. Based on these results, isotretinoin might be an option for de-differentiated thyroid cancer, with low rate of severe side effects, especially when compared with cytotoxic drugs. Aggressive thyroid cancer frequently needs multimodal adjuvant therapy.     

Hypothalamo-hypophyseal thyroid and gonadal function before and after erythropoietin therapy in dialysis patients.

We examined the effects of administration of two hypothalamic neurohormones, TRH and GnRH, for 3 days in five anemic male dialysis patients and five age-matched normal male volunteers. Patients on chronic hemodialysis have abnormal hypothalamo-hypophyseal thyroid and gonadal functions, including blunted TSH response to TRH, hyperprolactinemia, elevated basal levels of LH with exaggerated response to GnRH, and depressed FSH secretory response to GnRH. After correction of anemia with exogenous erythropoietin, these dialysis patients were given a single injection of the same hypothalamic hormones. The repeat studies after the correction of anemia showed normalization of 1) the TSH response to TRH, 2) basal GH and PRL levels, and 3) the FSH response to GnRH. Although these patients appear to have biochemical evidence of testicular failure, the gonadotropin response (FSH) to GnRH was not exaggerated. In addition, there was no increase in total T4 and free T4 after TRH administration. Although a free T3 response to TRH was present, it was remarkably blunted compared to that of controls. At the present time, it is not known whether these hormonal responses after the correction of anemia are due to better oxygenation or a trophic action of the erythropoietin.     

Health outcomes of children fathered by patients treated with radioiodine for thyroid cancer

Context and objectives  Radiation is known to be mutagenic. The present study analyses birth outcomes and the health of offspring from men previously exposed to ¹³¹I treatment for thyroid carcinoma.
Methods  Data on 493 pregnancies (356 from 173 untreated fathers, 23 from 17 patients who have undergone surgery alone and 114 from 63 fathers who received ¹³¹I) were obtained by interviewing male patients treated for thyroid carcinoma who had not received significant external radiation to the testes. Among these pregnancies, 73 were conceived from fathers who had received more than 370 MBq.
Results  The mean activity for the 114 pregnancies fathered by 63 patients was 3993 MBq leading to an estimated radiation dose of 9·2 cGy to the testes (MIRD committee coefficient). No significant differences between untreated and treated fathers were found for any adverse outcome.
Conclusion  There was no evidence that exposure to radioiodine affects the outcome of subsequent pregnancies and offspring, whatever the event considered. As our study is underpowered, the question of whether testicular irradiation, fractionated or not, is linked to impaired fertility or consequences on offspring remains to be established.     

Reciprocal changes in parathyroid hormone and thyroid function after radioiodine treatment of hyperthyroidism

Hyperthyroidism is associated with negative calcium balance, normal to increased serum calcium concentrations, and decreased cortical bone mass. There is no agreement concerning serum PTH levels in such patients. In this study, we measured serum PTH concentrations using a newly developed sensitive 2-site immunoradiometric assay in 17 hyperthyroid patients before and after radioiodine therapy. The mean serum PTH and calcium concentrations were 28 +/- 15 (+/- SD) ng/L (normal range, 12-65 ng/L) and 2.4 +/- 0.5 mmol/L (normal range, 2.1-2.6 mmol/L) before therapy. After therapy serum PTH concentrations increased in 16 of the 17 patients. The increase in serum PTH was greater in the 9 patients who became hypothyroid rapidly (29 +/- 15 to 75 +/- 29 ng/L) compared with that in the 8 patients who became euthyroid gradually (26 +/- 16 to 45 +/- 24 ng/L). Serum PTH rose along with TSH as the patients became hypothyroid after radioiodine, and both serum PTH and TSH fell when L-T4 therapy was given. The reciprocal changes in serum PTH concentrations and thyroid function over time suggest a strong association of bone mineral metabolism and thyroid status.     

Use of recombinant human thyrotropin before radioiodine therapy in patients with advanced differentiated thyroid carcinoma

The use of 131I for radioablative therapy in patients with differentiated thyroid cancer (DTC) requires a sufficient serum concentration of TSH for efficient thyroid tissue uptake of iodine. We describe the use of recombinant human TSH (rhTSH) in conjunction with ablative radioiodine therapy (RIT) in 11 patients (16 total treatments) with advanced and/or recurrent DTC (5 papillary, 6 follicular) for whom withdrawal of thyroid hormone suppression therapy (THST), the standard method to increase serum TSH, was not an option. Indications for rhTSH use in these patients included inability to tolerate withdrawal of thyroid hormones due to very poor physical condition or inability to achieve sufficient serum TSH levels after THST withdrawal. Ten patients had undergone thyroidectomy, and most (9 of 11) had received prior ablative RIT after THST withdrawal. Baseline thyroglobulin levels ranged from 25 to nearly 30,000 ng/mL, reflecting the heterogeneity of the patient population. In 7 cases (5 patients), posttherapy thyroglobulin levels assessed at a mean of 4.3 months (range, 2-10 months) after 131I therapy were decreased by at least 30% compared to pretherapy levels. In follow-up visits, an additional 3 patients showed marked clinical improvement or decreased or stabilized tumor burden in whole body scans compared to pretherapy scans. Three patients died of progressive disease within 2 months of therapy before follow-up assessments occurred. No adverse events were reported among the 8 surviving patients. The results suggest that rhTSH offers a promising alternative to THST withdrawal to allow ablative RIT after effective TSH stimulation in patients with advanced recurrent DTC who would not otherwise be able to receive this treatment. This therapeutic indication extends the clinical potential of this new agent, already demonstrated to be effective for use with 131I for diagnostic purposes.     

Sialoadenitis following ablative therapy with high doses of radioiodine for treatment of differentiated thyroid cancer

We analyzed eight-three patients who received 3.7 GBq (100 mCi) or 7.4 GBq (200 mCi) after total thyroidectomy for thyroid cancer. This study consisted in clinical and lab analysis (amylase serum level), followed by iodine whole body scan. The sialoadenitis was defined by hyperamylasemia (> 200 U/L). Eleven (13.25%) patients referred spontaneous local pain or after mastication post I 131 ablative therapy. Hyperamylasemia was detected in 31 (37.3%) patients in the second day after treatment. After seven days, serum amylase levels were in normal values in all patients. The symptomatic sialoadenitis was detected more frequently in patients with residual cervical uptake who received I-131 7.4 GBq (70%). The uptake in topography of salivary glands was present in 93.5% of sialoadenitis cases (p < 0.05). Significant statistical correlation was detected between absent of distance metastases and higher incidence of sialoadenitis (p < 0.05). No correlation was demonstrated between this complication and cervical remnants or I-131 dose administered. The sialoadenitis post high dose ablative therapy is a relative common complication with low clinical repercussion. The absent of distance metastases is directly correlated to this complication.     

Differentiation between healthy thyroid remnants and tumor tissue after radioiodine therapy in patients with differentiated thyroid carcinoma using in vitro phosphorus-31 magnetic resonance spectroscopy

BACKGROUND: The growth and spread of many tumors are triggered by changes in cell membrane metabolism, which can lead to systemic alterations in levels of phospholipids. We sought to determine whether plasma levels of several phospholipids could differentiate between healthy remnants of thyroid tissue and residual tumor tissue or metastases in patients with thyroid carcinoma. METHODS: We measured plasma phospholipid levels by phosphorus-31 magnetic resonance spectroscopy (31P-MRS) in blood samples from 30 patients with thyroid cancer who had been rendered hypothyroid in preparation for diagnostic or therapeutic administration of iodine-131. All patients had undergone total thyroidectomy. Iodine-131 whole-body scintigraphy and measurements of thyroglobulin values during up to 3 years of follow-up were used to distinguish patients in remission from those with only healthy thyroid remnants and those with tumor tissue or metastases. RESULTS: Mean (+/- SD) levels of sphingomyelin (0.33 +/- 0.06 mmol/L vs. 0.46 +/- 0.03 mmol/L, P <0.0001) and phosphatidylcholine (1.34 +/- 0.19 mmol/L vs. 2.15 +/- 0.33 mmol/L, P <0.0001) were significantly lower in patients with metastatic thyroid cancer (n = 8) than in patients (n = 12) who were in remission. Patients with only remnants of thyroid tissue (n = 10) also had significantly lower phospholipid levels than did patients in remission, but significantly greater levels that did patients with tumor tissue or metastases. CONCLUSION: These preliminary results suggest that 31P-MRS may be useful in helping to differentiate the presence of tumor tissue, remnants of thyroid tissue not requiring further treatment, and remission in patients with thyroid cancer.