Outcome of radioiodine therapy for feline hyperthyroidism: Fixed dose versus individualized dose based on a clinical scoring system.

Background: Hyperthyroidism is the most frequent endocrinopathy in older cats. To date, there is no consensus on how to best calculate the dose of radioiodine to administer to hyperthyroid cats. Aim: The goals of this study were to compare thyroid function, renal function, and survival time between hyperthyroid cats receiving a fixed dose of radioiodine and those receiving an individualized dose calculated using a clinical scoring system. Methods: Medical records of 110 cats treated with radioiodine therapy at the University of Bern between 2010 and 2020 were reviewed. Thyroid function, renal function, and survival of cats treated with a fixed dose of radioiodine (2010-2015; n = 50) were compared to those of cats treated with an individualized dose (2015-2020; n = 60) at different time points after therapy. Results: Treatment with a fixed dose of radioiodine (mean = 168 ± 26 MBq) was associated with 69% of euthyroidism, 19% persistent hyperthyroidism, and 12% hypothyroidism, whereas treatment with an individualized dose (mean = 120 ± 30 MBq) led to 54% euthyroidism, 23% hyperthyroidism, and 23% hypothyroidism (p = 0.73). More than 12 months after treatment, the incidence of azotemia was comparable between cats treated with a fixed dose (37%) and those treated with an individualized dose (31%) (p = 0.77). No factors were found to be predictive of treatment failure (hypothyroidism or hyperthyroidism) after therapy. Median survival time after radioiodine therapy was 44 months. In a multivariate analysis, persistent hyperthyroidism was the only variable independently associated with a shorter survival time (HR = 6.24, p = 0.002). Conclusion: The method of calculating the dose of radioiodine (fixed vs. individualized) to treat feline hyperthyroidism does not appear to be decisive for posttreatment thyroid function, renal function, or survival.

Impact of photobiomodulation therapy on the morphological aspects of submandibular gland submitted to excretory duct ligation and hypothyroidism: an animal study.

The aim of this study was to evaluate the impact of photobiomodulation therapy (PBMT) on histomorphological aspects of submandibular gland (SMG) submitted to salivary gland duct obstruction in hypothyroid rats. Fifty-six male Wistar rats (250 to 300 g) were divided into 4 groups (n = 14): euthyroid (EU), EU + PBMT, hypothyroid (HYPO), and HYPO + PBMT. Duct obstruction of the left submandibular gland (LSMG) was performed in all animals by a ligature procedure. For the induction of hypothyroidism, total thyroidectomy was performed. PBMT groups received irradiation with AlGaInP diode laser (808 nm, 0.04 W, 0.04cm2 spot size, 60 s, 2.4 J per point, 60 J/cm2, 1 W/cm2). Irradiation was performed immediately, 24 h, and 48 h after the obstruction of the salivary gland duct, in one point, extra oral and perpendicular to the gland. Animals were sacrificed after 24 h and 72 h after duct ligature. Our results indicated that salivary duct obstruction and hypothyroidism caused negative modifications on the salivary glands' histomorphology, especially acinar atrophy, after 24 h and 72 h. HYPO + PBMT showed a significant reduction of the inflammatory infiltrate, congested blood vessels, and acinar atrophy in the SMG submandibular salivary gland in 72 h compared to 24 h (p < 0.05). In conclusion, obstruction of the salivary gland excretory duct and hypothyroidism causes severe sialoadenitis with expressive atrophy of the glandular parenchyma. However, PBMT was able to modulate the inflammatory process and delaying acinar atrophy. This study provided insights to better understand the role of the PBMT on the altered salivary gland by duct ligation and associate hypothyroidism.

Improved Patient Dosimetry at Radioiodine Therapy by Combining the ICRP Compartment Model and the EANM Pre-Therapeutic Standard Procedure for Benign Thyroid Diseases.

Radioactive iodine is commonly used for the treatment of different thyroid conditions since the 1940s. The EANM has developed a standard pre-therapeutic procedure to estimate patient specific thyroid uptake at treatment of benign thyroid diseases. The procedure which models the time dependent fractional thyroid uptake is based on a two-compartment fitting system, one representing the thyroid and the other the blood. The absorbed dose is however only estimated for the thyroid and not for any other organ in the body. A more detailed biokinetic model for iodine is given by the ICRP and includes an iodide transport in the whole body. The ICRP model has 30 different compartments and 48 transfer coefficients to model the biokinetics of iodide and to model different transfer for inorganic iodide and organic iodine. The ICRP model is a recirculation iodine model, and the optimization is performed on the whole model and not exclusively on the thyroid as in the EANM procedure. Combining the EANM method and the ICRP model gives both patient specific estimations of thyroid uptake and retention and include most organs in the body. The new software gives both an improved patient specific dosimetry for the thyroid and an estimation of the absorbed dose to non-target organs and tissues like kidneys, urinary bladder, stomach wall, and uterus. Using the method described in this paper, the repercussions on the daily routines will be minimal.

Does laser phototherapy influence the proliferation of myoepithelial cells in the salivary gland of hypothyroid rats?

Thyroid hormones influence both development and growth of organs and tissues and guarantee metabolic demands that interfere with the quality of digestive secretions, including those of the salivary glands. Laser phototherapy - LPT can modulate various biological phenomena and its diverse effects permit the action on different cell types. The aim of this study was to evaluate the influence of laser phototherapy on myoepithelial cells of salivary glands of hypothyroid rats. Forty-two albino Wistar rats were divided into two main groups: euthyroid (EU) and hypothyroid (HYPO). Hypothyroidism was induced using propylthiouracil (PTU) for 4weeks. Each group was divided into subgroups: control (without laser) and laser groups (Red/infrared - IR). LPT was used on the submandibular gland and was carried out using a diode laser (λ660 or λ780nm, 40mW, spot size 0.04cm2, irradiation area 1cm2, 300s, 6J/cm2 per gland, 12J/cm2 per session) and started two weeks after PTU treatment. LPT was repeated every other day for two weeks. After animal death, the glands were removed, dissected and processed for immunohistochemical analysis. It was observed an increase in the number of myoepithelial cells of hypothyroid control rats in comparison to euthyroid controls (p=0.001). Visible LPT (λ660nm) caused significant higher proliferation of myoepithelial cells in EU rats when compared to IR LPT (λ 780nm)(p≤0.001).It is concluded that, despite the LPT protocol used did not influence myoepithelial proliferation on hypothyroid rats it significantly increased the proliferation on euthyroid animals.

Leptin and ghrelin concentration in hyperthyroid cats before and after radioactive iodine therapy compared to euthyroid control cats.

OBJECTIVE: Leptin and ghrelin, two peptide hormones with antagonistic effects on satiety and energy balance, could be involved in the pathogenesis of weight loss and polyphagia in cats with hyperthyroidism. Leptin generally decreases appetite and increases energy expenditure, while ghrelin exerts the opposite effects. MATERIALS AND METHODS: Leptin and ghrelin were measured in 42 client owned hyperthyroid cats with a body condition score (BCS) ≤ 5/9 before (T0) and 4 weeks after radioactive iodine treatment (RAIT) (T1). Dependent on the serum total thyroxine concentration concentration at T1, cats were sub-classified as still hyperthyroid (ht-ht) (n = 4), euthyroid (ht-eu) (n = 10) or hypothyroid (ht-hypo) (n = 28). Results were compared to those of 22 healthy, euthyroid control cats with a comparable BCS (≤ 5/9) and age (≥ 8 years) to hyperthyroid cats. RESULTS: At T0, there were no significant differences between hyperthyroid and control cats for leptin (p = 0.06) or ghrelin concentrations (p = 0.27). At T1, leptin significantly decreased in ht-hypo cats compared to T0 (p = 0.0008) despite a significantly increased body weight in this group (p = 0.0001). Serum ghrelin concentrations did not differ between hyperthyroid cats with a history of polyphagia compared to non-polyphagic cats (p = 0.42). After RAIT, ghrelin concentration significantly increased in all hyperthyroid cats (p < 0.0001), as well as in the subgroups ht-eu (p = 0.014) and ht-hypo (p < 0.0001) compared to their respective T0 baseline concentrations. CONCLUSION: Leptin and ghrelin fluctuations may be indicative of changes in metabolic functions in cats with thyroid dysfunction. Leptin fluctuations occurred independently of body weight in different states of thyroid dysfunction; increasing ghrelin concentrations after RAIT suggest a ghrelin-independent mechanism for polyphagia in hyperthyroid cats.

Hypothyroidism and hyponatremia: data from a series of patients with iatrogenic acute hypothyroidism undergoing radioactive iodine therapy after total thyroidectomy for thyroid cancer.

PURPOSE: The aim of the present study was to evaluate the role of hypothyroidism as a cause of hyponatremia in a clinical model of iatrogenic acute hypothyroidism due to thyroid hormone withdrawal prior to ablative radioactive iodine (RAI) therapy after total thyroidectomy. METHODS: The study group consisted of 101 differentiated thyroid cancer (DTC) patients (77 women and 24 men). Plasma concentration of thyroid-stimulating hormone ([TSH]) and sodium ([Na+]) was evaluated before total thyroidectomy (pre[TSH] and pre[Na+]) and on the day of RAI therapy (post[TSH] and post[Na+]). RESULTS: The frequency of hypothyroidism-associated hyponatremia was 4 % (4/101). Pre[Na+] was significantly higher than post[Na+] (140.7 ± 1.6 vs 138.7 ± 2.3 mEq/L, p = 0.012). Moreover, a linear correlation was identified between pre[Na+] and post[Na+]. CONCLUSIONS: Iatrogenic acute hypothyroidism-related hyponatremia is uncommon. However, because of the significant reduction of [Na+] in the transition from euthyroidism to iatrogenic hypothyroidism, the value of pre[Na+] should be viewed as a parameter to be considered. Since it acts as an independent risk factor for the development of hyponatremia, patients with a pre[Na+] close to the lower limit of normal range may deserve a closer monitoring of [Na+].

Subclinical Hypothyroidism after 131I-Treatment of Graves' Disease: A Risk Factor for Depression?

OBJECTIVES: Although it is well accepted that there is a close relationship between hypothyroidism and depression, previous studies provided inconsistent or even opposite results in whether subclinical hypothyroidism (SCH) increased the risk of depression. One possible reason is that the etiology of SCH in these studies was not clearly distinguished. We therefore investigated the relationship between SCH resulting from 131I treatment of Graves' disease and depression. DESIGN AND METHODS: The incidence of depression among 95 patients with SCH and 121 euthyroid patients following 131I treatment of Graves' disease was studied. The risk factors of depression were determined with multivariate logistic regression analysis. Thyroid hormone replacement therapy was performed in patients with thyroid-stimulating hormone (TSH) levels exceeding 10 mIU/L. RESULTS: Patients with SCH had significantly higher Hamilton Depression Scale scores, serum TSH and thyroid peroxidase antibody (TPOAb) levels compared with euthyroid patients. Multivariate logistic regression analysis revealed SCH, Graves' eye syndrome and high serum TPO antibody level as risk factors for depression. L-thyroxine treatment is beneficial for SCH patients with serum TSH levels exceeding 10 mIU/L. CONCLUSIONS: The results of the present study demonstrated that SCH is prevalent among 131I treated Graves' patients. SCH might increase the risk of developing depression. L-thyroxine replacement therapy helps to resolve depressive disorders in SCH patients with TSH > 10mIU/L. These data provide insight into the relationship between SCH and depression.

Influence of laser photobiomodulation (GaAlAs) on salivary flow rate and histomorphometry of the submandibular glands of hypothyroid rats.

The aim of this study was to analyze the influence of laser photobiomodulation in salivary flow, weight, and histomorphometry of the submandibular glands of hypothyroid rats. Fifty-six male Wistar albino rats were divided in euthyroid group and hypothyroid group, treated with propylthiouracil (PTU) to induce hypothyroidism. Each group was divided into control (without laser) and laser groups (GaAlAs): λ660 nm (40 mW), λ780 nm (40 mW), and λ780 nm (70 mW). The laser application on the submandibular gland occurred after 2 weeks of PTU treatment and repeatedly during 2 weeks every 48 h. The rats were anesthetized, tracheostomized, and the evaluation of the salivary flow rate (µL/min/100 g body weight) was made by the weight of the saliva collected for 15 min from the first drop. After the animals' death, the glands were dissected and processed for histological analysis. There was an evident reduction of the salivary flow of hypothyroid rats in all groups in comparison to euthyroid group (Mann-Whitney test, p < 0.05). No significant difference was found in the salivary flow of rats that received laser photobiomodulation compared with their control groups. Histological analysis revealed a decrease in the parenchyma of the salivary glands of hypothyroid rats, but the laser was not able to reverse this process. Hypothyroid rats irradiated or not with laser showed acini and acinar cells with significantly smaller areas than euthyroid groups. The laser photobiomodulation protocol used was not able to change salivary flow or reverse the acinar atrophy process in the submandibular glands of hypothyroid rats.

The thyroid-related quality of life measure ThyPRO has good responsiveness and ability to detect relevant treatment effects.

BACKGROUND AND PURPOSE: Patient-reported outcomes have become important endpoints in comparative effectiveness research and in patient-centered health care. Valid patient-reported outcome measures detect and respond to clinically relevant changes. The purpose of this study was to evaluate responsiveness of the thyroid-related quality of life (QoL) instrument ThyPRO in patients undergoing relevant clinical treatments for benign thyroid diseases and to compare it with responsiveness of the generic SF-36 Health Survey. METHODS: A sample of 435 patients undergoing treatment completed the ThyPRO and SF-36 Health Survey (Version 2) at baseline and 6 months after treatment initiation. Responsiveness was evaluated in three thyroid patient groups: patients with hyperthyroidism (n = 66) and hypothyroidism (n = 84) rendered euthyroid after medical therapy, and patients with a clinically detectable nontoxic goiter treated with surgery or radioactive iodine and remaining euthyroid (n = 62). Changes in QoL were evaluated in terms of effect size and compared to the changes predicted by clinical experts. The responsiveness of equivalent scales from ThyPRO and SF-36 Health Survey were compared with the relative validity index. RESULTS: The ThyPRO demonstrated good responsiveness across the whole range of QoL aspects in patients with hyper- and hypothyroidism. Responsiveness to treatment of nontoxic goiter was also demonstrated for physical and mental symptoms and overall QoL, but not for impact on social life or cosmetic complaints, in contrast to clinicians' predictions. For all comparable scales except one, the ThyPRO was more responsive to treatment than the SF-36 Health Survey. CONCLUSIONS: The ThyPRO was responsive to treatment across the range of benign thyroid diseases. We suggest implementing this measurement instrument as a patient-reported outcome in clinical studies and in clinical management.

Low-level laser in the treatment of patients with hypothyroidism induced by chronic autoimmune thyroiditis: a randomized, placebo-controlled clinical trial.

Chronic autoimmune thyroiditis (CAT) is the most common cause of acquired hypothyroidism, which requires lifelong levothyroxine replacement therapy. Currently, no effective therapy is available for CAT. Thus, the objective of this study was to evaluate the efficacy of low-level laser therapy (LLLT) in patients with CAT-induced hypothyroidism by testing thyroid function, thyroid peroxidase antibodies (TPOAb), thyroglobulin antibodies (TgAb), and ultrasonographic echogenicity. A randomized, placebo-controlled trial with a 9-month follow-up was conducted from 2006 to 2009. Forty-three patients with a history of levothyroxine therapy for CAT-induced hypothyroidism were randomly assigned to receive either 10 sessions of LLLT (830 nm, output power of 50 mW, and fluence of 707 J/cm(2); L group, n=23) or 10 sessions of a placebo treatment (P group, n=20). The levothyroxine was suspended 30 days after the LLLT or placebo procedures. Thyroid function was estimated by the levothyroxine dose required to achieve normal concentrations of T3, T4, free-T4 (fT4), and thyrotropin after 9 months of postlevothyroxine withdrawal. Autoimmunity was assessed by measuring the TPOAb and TgAb levels. A quantitative computerized echogenicity analysis was performed pre- and 30 days postintervention. The results showed a significant difference in the mean levothyroxine dose required to treat the hypothyroidism between the L group (38.59 ± 20.22 µg/day) and the P group (106.88 ± 22.90 µg/day, P<0.001). Lower TPOAb (P=0.043) and greater echogenicity (P<0.001) were also noted in the L group. No TgAb difference was observed. These findings suggest that LLLT was effective at improving thyroid function, promoting reduced TPOAb-mediated autoimmunity and increasing thyroid echogenicity in patients with CAT hypothyroidism.

Efficacy of low and high fixed dose radioactive iodine therapy in patients with toxic nodular goiter.

AIM: The efficacy of low and high fixed dose radioactive iodine (RAI) therapy in patients with toxic nodular goiter was investigated. METHODS: Ninety-three patients (25 males, 68 females) were included into the study (32 patients with toxic adenoma, 61 patients with toxic multinodular goiter). Patients were treated with a fixed dose of 370 MBq (10 mCi) or 740 MBq (20 mCi) RAI. The average follow-up period was 17±10 months. RESULTS: The overall cure rate (eutyhroidism and hypothyroidism) was 81% in patients treated with 740 MBq RAI and 51% in patients treated with 370 MBq RAI (p<0.05). RAI therapy with a dose of 370 MBq and 740 MBq provided the cure in 73% and 91% of the patients with toxic adenoma and 42% and 76% of the patients with toxic multinodular goiter, respectively. No significant difference for gender was observed. Hypothyroidism developed in 4 and 15 patients with a dose of 370 MBq and 740 MBq RAI, respectively. CONCLUSION: A dose of 740 MBq RAI was found to be more effective for the treatment of toxic nodular goiter as compared to a dose of 370 MBq RAI.

Effects of thyroid hormone on A1C and glycated albumin levels in nondiabetic subjects with overt hypothyroidism.

OBJECTIVE: We aimed to determine the effects of thyroid hormone on A1C and glycated albumin (GA) in nondiabetic patients with overt hypothyroidism. RESEARCH DESIGN AND METHODS: A1C levels were measured in 45 nondiabetic patients with overt hypothyroidism and 180 euthyroid control subjects. A1C, GA, fasting blood glucose (FBG), 1,5-anhydroglucitol, and erythrocyte indexes were determined in 30 nondiabetic patients with overt hypothyroidism before and after thyroid hormone replacement. RESULTS: A1C levels were higher in patients with hypothyroidism compared with control subjects. A1C levels were decreased by thyroid hormone replacement. Thyroid hormone replacement increased serum erythropoietin, reticulocyte count, and mean corpuscular hemoglobin (MCH). The change in A1C level was significantly correlated with the change in reticulocyte count or MCH. Thyroid hormone replacement decreased serum levels of albumin and GA. However, FBG and 1,5-anhydroglucitol levels were not altered. CONCLUSIONS: Levels of A1C and GA are spuriously high in nondiabetic patients with overt hypothyroidism.

Primary squamous cell carcinoma of the thyroid years after radioactive iodine treatment.

Primary squamous cell carcinoma (SCC) of the thyroid gland is a rare diagnosis, since there is no squamous epithelium in the thyroid gland. SCC of the thyroid is highly aggressive with a poor prognosis. We present a case of primary SCC of the thyroid: this 88-year-old male patient had a history of hyperthyroidism which was treated with radioactive iodine 25 years earlier. Whether this treatment could be related to SCC of the thyroid is not clear. We treated our patient with thyroidectomy and subsequent intensified radiotherapy. Six months after treatment our patient is doing well and there is no sign of local reoccurrence. Our work-up is described, including the differentiation from metastatic disease. The origin of squamous cell carcinoma in the thyroid is uncertain; we discuss some theoretical considerations. We conclude that after excluding metastatic disease, thyroidectomy combined with radiotherapy is the treatment of choice.

Low-activity (2.0 GBq; 54 mCi) radioiodine post-surgical remnant ablation in thyroid cancer: comparison between hormone withdrawal and use of rhTSH in low-risk patients.

OBJECTIVE: (a) To compare the efficacy of low-activity (2 GBq; 54 mCi) (131)I ablation using l-thyroxine withdrawal or rhTSH stimulation, and (b) to assess the influence of thyroid remnants volume on the ablation rate. DESIGN: Patients underwent neck ultrasound, (131)I neck scintigraphy and radioiodine uptake. Post-therapy whole body scan (WBS) was acquired after 4-6 days. Ablation was assessed after 6-12 months by WBS, Tg and TgAb following l-thyroxine withdrawal. METHODS: Group A: preparation by L-T(4) withdrawal (37 days); 21 patients received (131)I (2.02+/-0.22 GBq; 54.6+/-5.9 mCi) and on the day of treatment, TSH, Tg, TgAb were measured; Group B: stimulation by rhTSH; 21 patients received (131)I (1.97+/-0.18 GBq; 53.2+/-4.9 mCi) 24 h after the second injection of rhTSH (0.9 mg) and TSH, Tg and TgAb were measured after 2 days. RESULTS: At follow-up, 90.0% of patients from group A and 85.0% of patients from group B had Tg levels <1 ng/ml; no uptake was observed in 95.2% and in 90.5% of patients from group A or B respectively, with no statistical differences for both ablation criteria. Before (131)I treatment, small thyroid remnants (<1 ml) were detected by US in <25% of all patients. CONCLUSIONS: The use of rhTSH for the preparation of low-risk patients to ablation therapy with low activities of (131)I (2 GBq; 54 mCi) is safe and effective and avoids hypothyroidism. The presence of thyroid remnants smaller than 1 ml at US evaluation had no effect on the ablation rate.

Radioactive iodine (131I) effects on male fertility.

PURPOSE OF REVIEW: Radiometabolic therapy with radioactive iodine (I) is the standard treatment for differentiated thyroid cancer and is also currently the treatment of choice for Graves' disease in the United States. and in most countries. Men younger than 40 years of age represent about 10% of all radiometabolic treatments. Thus, the question arises whether I therapy is able to induce a damage to the fertility potential. RECENT FINDINGS: The different effects caused by I therapy employed in cancer and hyperthyroid patients are reviewed. Most articles about the first category of patients show a damage to the germinal epithelium directly related to the cumulative dose delivered. Although the small amounts used in hyperthyroidism are usually well tolerated in terms of sterility risk, the impairment caused by hyperthyroidism per se is probably higher than that caused by I treatment. SUMMARY: Young cancer patients, particularly those with node or lung metastases, who will probably undergo repeated treatments should be aware of the potential risks to their fertility. An evaluation of testicular function is thus advisable. When an impairment of fertility potential is already present, the option of freezing semen should be considered. The available studies concerning I therapy in hyperthyroidism suggest that this treatment does not cause a worsening of semen analysis but an amelioration in affected patients.

Licensee over-reliance on conservatisms in NRC guidance regarding the release of patients treated with 131I.

Medical licensees are required to comply with U.S. Nuclear Regulatory Commission (NRC) regulations pertaining to the release of patients administered radioactive material. However, use of the associated NRC guidance expressed in NUREG-1556, Volume 9, is completely optional and has been shown to be overly conservative. Rigid adherence to the guidance recommendations has placed an undue burden on nuclear medicine therapy patients and their families, as well as licensees responsible for ensuring compliance with NRC requirements. More realistic guidance has been published by other responsible professional societies and will be presented in this work. These more realistic calculations allow for higher releasable activity levels than the widely adopted NUREG levels, particularly for thyroid cancer patients. The guidance-suggested releasable activity limit is similar to our calculational result for hyperthyroid patients, 2.1 GBq (57 mCi) compared to 2.3 GBq (62 mCi), but is significantly lower for thyroid cancer patients, 6.6 GBq (179 mCi) vs. 16.9 GBq (457 mCi) using the regulatory definition of the total effective dose equivalent (TEDE). Higher limits are both possible and reasonable, if the permissible extra-regulatory definition of the TEDE is used in which the effective dose equivalent (EDE), rather than the deep-dose equivalent (DDE), is determined. We maintain that professionals evaluating compliance with the NRC requirements for patient release, pursuant to 10 CFR 35.75, should use the procedures presented here and not rely automatically on the NUREG.

[Where does subclinical hypothyroidism start? Implications for the definition of the upper reference limit for thyroid stimulating hormone]. / Wo beginnt die subklinische Hypothyreose? Implikationen zur Definition der oberen Referengrenze für Thyreotropin.

UNLABELLED: The upper limit of the TSH reference range is currently under discussion. In its recent guidelines, the National Academy of Clinical Biochemistry (NACB) recommended the use of approximately 2.5 mIU/L, rather than approximately 4 mIU/L, due to the fact that reference populations, on which the definition of the reference range is based, contain persons undergoing an initial phase of autoimmune thyroid disease. This will skew the upper reference limit of TSH. Ultrasonography, in addition to measurement of thyroid autoantibodies, should be used to exclude these persons. OBJECTIVE: The present study investigates whether the NACB recommendation also applies for a region of mild iodine deficiency. METHODS: According to NACB criteria, a reference population (713 persons) was defined out of a total study population of 1442. The TSH reference range was calculated in this reference group and in further subgroups by percentiles. The results were compared with the total study population and the NACB recommendation. All assays used were provided by BRAHMS Diagnostica AG, Hennigsdorf, Germany. RESULTS: As expected, all median TSH values, excluding the median of the group with a hypoechogenic thyroid were close to 1.2 mIU/L. The 97.5th percentile in the reference population was 3.35 mIU/L. However, there was no difference compared to the total study population. CONCLUSION: The upper reference limit for TSH based on a reference population according to NACB criteria came down to 3.35 mIU/L, but not to approximately 2.5 mIU/L. Interestingly, there is no difference compared to the total study population.

[Combined radioiodine (I131) treatment and radio-guided surgery for recurrent cervical well-differentiated thyroid cancer].

Local recurrence and cervical lymph node involvement are relatively common in patients with well-differentiated thyroid carcinoma. Since these patients are young and have a good prognosis, their treatment is challenging. Therapeutic doses of radioiodine (I131) are seldom curative and include a long period of discomfort--stopping the replacement therapy. Most patients will require surgery to eradicate the recurrent disease. However, when performed, excision of all involved tissue should be complete and accomplished in a single procedure since repeated cervical surgery is technically difficult, carries a high morbidity rate and yields bad cosmetic results. This study aims to combine radioiodine (I131) treatment and radio-guided surgery to improve the completeness of surgical excision without wide resections of cervical tissues. The combined treatment protocol was described previously and includes preparation of the patient for radioiodine (I131) treatment, administration of a therapeutic dose of 3.7 GBq of radioiodine (I131) in the hypothyroid state and using the radio-activity as a marker for identifying tumor aggregates intraoperatively using a hand held gamma probe. Both patients treated show complete removal of all neoplastic foci with radioiodine uptake. Moreover, in both patients the intraoperative probe identified additional metastatic foci that were not shown by the preoperative scan. Although our experience is limited (only two patients), and a larger series with a longer follow-up period is needed, we believe radio-guided surgery for recurrent or persistent cervical well-differentiated thyroid cancer offers an important therapeutic tool.

Thyroid disease and female reproduction.

OBJECTIVE: To review the menstrual function and fertility in thyroid disease, mainly in hyperthyroidism and hypothyroidism. Also to register the consequences of (131)I therapy, which is used widely in the treatment of Graves' disease and thyroid cancer, on subsequent pregnancies and on fertility in these patients. DESIGN: A MEDLINE computer search was used to identify relevant studies. The type of menstrual disturbances and the status of fertility were recorded from all the studies found. Also, the fertility and genetic hazard of female patients with Graves' disease and thyroid cancer who were treated with (131)I were registered. RESULT(S): Both hyperthyroidism and hypothyroidism may result in menstrual disturbances. Menstrual abnormalities are less common now than in previous series. In a recent study, we found that only 21.5% of 214 thyrotoxic patients had some type of menstrual disturbance, compared to 50 to 60% in some older series. The most common manifestations are hypomenorrhea and oligomenorrhea. According to the results of endometrial biopsies, most thyrotoxic women remain ovulatory. Moreover, the genetic hazard incident to radioiodine therapy in Graves' disease and thyroid carcinoma is very small; exposure to (131)I does not cause reduced fecundity, and the risk of loss of fertility is not a contraindication for its use in these patients. mIn hypothyroidism, the frequency of menstrual irregularities has very recently been reported to be 23.4% among 171 hypothyroid patients studied. This is much less than that reported in previous studies, which showed that 50 to 70% of hypothyroid female patients had menstrual abnormalities. The most common manifestation is oligomenorrhea. Severe hypothyroidism is commonly associated with failure of ovulation. Ovulation and conception can occur in mild hypothyroidism. These pregnancies are, however, often associated with abortions, stillbirths, or prematurity. The latter may be of greater clinical importance in infertile women with unexplained infertility. CONCLUSION(S): These new data, mainly concerning menstrual abnormalities in hyperthyroidism and hypothyroidism, are inconsistent with what is generally believed and written in the classic thyroid textbooks and indicate that such opinions should be revised.