Thyroid Diseases: Lind P

Luster M, Clarke SE, Dietlein M, Lassmann M, Lind P, Oyen WJ, Tennvall J, Bombardieri E, Anonymous00011. · Department of Nuclear Medicine, University of Würzburg, Josef-Schneider-Strasse 2, 97080 Würzburg, Germany. · Eur J Nucl Med Mol Imaging. · Pubmed #18670773 No free full text.

Abstract: INTRODUCTION: The purpose of the present guidelines on the radioiodine therapy (RAIT) of differentiated thyroid cancer (DTC) formulated by the European Association of Nuclear Medicine (EANM) Therapy Committee is to provide advice to nuclear medicine clinicians and other members of the DTC-treating community on how to ablate thyroid remnant or treat inoperable advanced DTC or both employing large 131-iodine ((131)I) activities. DISCUSSION: For this purpose, recommendations have been formulated based on recent literature and expert opinion regarding the rationale, indications and contraindications for these procedures, as well as the radioiodine activities and the administration and patient preparation techniques to be used. Recommendations also are provided on pre-RAIT history and examinations, patient counselling and precautions that should be associated with (131)I iodine ablation and treatment. Furthermore, potential side effects of radioiodine therapy and alternate or additional treatments to this modality are reviewed. Appendices furnish information on dosimetry and post-therapy scintigraphy.

Lind P. · No affiliation provided · Eur J Nucl Med. · Pubmed #10436189 No free full text.

This publication has no abstract.

Lind P, Kohlfürst S. · Department of Nuclear Medicine and Endocrinology, PET/CT Center Klagenfurt, Austria. · Semin Nucl Med. · Pubmed #16762610 No free full text.

Abstract: Depending on the iodine supply of an area, the incidence of thyroid cancer ranges between 4 and 12/100,000 per year. To detect thyroid cancer in an early stage, the assessment of thyroid nodules includes ultrasonography, ultrasonography-guided fine-needle aspiration biopsy, and conventional scintigraphic methods using (99m)Tc-pertechnetate, (99m)Tc-sestamibi or -tetrofosmin, and (18)F-fluorodeoxyglucose positron emission tomography (FDG-PET) in selected cases. After treatment of thyroid cancer, a consequent follow-up is necessary over a period of several years. For following up low-risk patients, recombinant thyroid-stimulating hormone-stimulated thyroglobulin and ultrasonography is sufficient in most cases. After total thyroidectomy and radioiodine ablation therapy, thyroid-stimulating hormone-stimulated thyroglobulin should be below the detection limit (eg, <0.5 ng/mL, R: 70-130). An increase of thyroglobulin over time is suspicious for recurrent or metastatic disease. Especially in high-risk patients, aside from the use of ultrasonography for the detection of local recurrence and cervial lymph node metastases, nuclear medicine methods such as radioiodine imaging and FDG-PET are the methods of choice for localizing metastatic disease. Radioiodine imaging detects well-differentiated recurrences and metastases with a high specificity but only moderate sensitivity. The sensitivity of radioiodine imaging depends on the activity administered. Therefore a low activity diagnostic (131)I whole-body scan (74-185 MBq) has a lower detection rate than a high activity post-therapy scan (3700-7400 MBq). In patients with low or dedifferentiated thyroid cancer and after several courses of radioiodine therapy caused by metastatic disease, iodine negative metastases may develop. In these cases, despite clearly elevated levels of thyroglobulin, radioiodine imaging is negative or demonstrates only faint iodine uptake. The method of choice to image these iodine negative metastases is FDG-PET. In recent years the combination of PET and computed tomography has been introduced. The fusion of the metabolic and morphologic information was able to increase the diagnostic accuracy, reduces pitfalls and changes therapeutic strategies in a reasonable number of patients.

Pacini F, Schlumberger M, Harmer C, Berg GG, Cohen O, Duntas L, Jamar F, Jarzab B, Limbert E, Lind P, Reiners C, Sanchez Franco F, Smit J, Wiersinga W. · University of Siena, Siena, Italy. · Eur J Endocrinol. · Pubmed #16260423 links to  free full text

Abstract: OBJECTIVE: To determine, based on published literature and expert clinical experience, current indications for the post-surgical administration of a large radioiodine activity in patients with differentiated thyroid cancer. DESIGN AND METHODS: A literature review was performed and was then analyzed and discussed by a panel of experts from 13 European countries. RESULTS: There is general agreement that patients with unifocal microcarcinomas = 1 cm in diameter and no node or distant metastases have a <2% recurrence rate after surgery alone, and that post-surgical radioiodine confers recurrence and cause-specific survival benefits in patients, strongly suspected of having persistent disease or known to have tumor in the neck or distant sites. In other patients, there is limited evidence that after complete thyroidectomy and adequate lymph node dissection performed by an expert surgeon, post-surgical radioiodine provides clear benefit. When there is any uncertainty about the completeness of surgery, evidence suggests that radioiodine can reduce recurrences and possibly mortality. CONCLUSION: This survey confirms that post-surgical radioiodine should be used selectively. The modality is definitely indicated in patients with distant metastases, incomplete tumor resection, or complete tumor resection but high risk of recurrence and mortality. Probable indications include patients with tumors >1 cm and with suboptimal surgery (less than total thyroidectomy or no lymph node dissection), with age <16 years, or with unfavorable histology.

Schlumberger M, Berg G, Cohen O, Duntas L, Jamar F, Jarzab B, Limbert E, Lind P, Pacini F, Reiners C, Sánchez Franco F, Toft A, Wiersinga WM. · Institut Gustave Roussy, Villejuif, France. · Eur J Endocrinol. · Pubmed #14763906 links to  free full text

Abstract: OBJECTIVE: Because differentiated (follicular and papillary) thyroid cancer (DTC) may recur years after initial treatment, the follow-up of patients with DTC is long term. However, this population has changed, with more individuals being discovered at an earlier stage of the disease, so that previous follow-up protocols based mostly on data from high-risk patients no longer apply. We sought to develop an improved protocol for the follow-up of low-risk patients with DTC based on the findings of recent studies. METHODS: We analysed recent literature on the follow-up of DTC. RESULTS: Recent large studies have produced three important findings: (i) in patients with low-risk DTC with no evidence of disease up to the 6- to 12-month follow-up, diagnostic whole-body scan adds no information when serum thyroglobulin (Tg) is undetectable and interference from anti-Tg antibodies is absent; (ii) use of recombinant human thyroid-stimulating hormone to aid Tg measurement is effective and provides greater safety, quality-of-life and work productivity than does levothyroxine withdrawal with its attendant hypothyroidism; and (iii) ultrasonography performed by an experienced operator is the most sensitive means of detecting neck recurrences of DTC. CONCLUSIONS: We present a revised follow-up protocol for low-risk patients taking into account the above findings. This protocol should help clinicians enter a new era of monitoring characterized by greater safety, simplicity, convenience and cost savings.

Lind P, Kumnig G, Heinisch M, Igerc I, Mikosch P, Gallowitsch HJ, Kresnik E, Gomez I, Unterweger O, Aigner H. · Department of Nuclear Medicine and Endocrinology, PET Center Klagenfurt, LKH Klagenfurt, Austria. · Thyroid. · Pubmed #12487773 No free full text.

Abstract: Until 1963 Austria was an extremely iodine-deficient area with low iodine intake and high goiter prevalence. Therefore, for the first time in 1963, salt iodination with 10 mg of potassium iodide per kilogram of salt was introduced by federal law. Twenty years after this salt iodination, however, investigations in schoolchildren demonstrated iodine deficiency grade I to II according to the World Health Organization (WHO) (urinary iodine excretion, 42-75 microg/g Crea) and goiter prevalence of far more than 10%. In 1990, salt iodination was increased to 20 mg of potassium iodide per kilogram of salt. In 1994, further investigations in schoolchildren demonstrated an increase of urinary iodine excretion (121 microg/g Crea) and a reduction of goiter prevalence below 5%, with the exception of pupils ages 14-19 (12%). In the year 2000, 10 years after the increase of salt iodination in Austria, 430 nonselected adult inhabitants of three communities in Carinthia (a county of Austria) were investigated for iodine excretion, goiter prevalence, and prevalence of thyroid autoantibodies. This study demonstrated that although iodine supply is sufficient now in Austria (males, 163.7 microg of Crea; females, 183.3 microg of iodine per gram of Crea), goiter prevalence is still high in the elderly, who lived for a longer period of iodine deficiency (34.3% in women and 21.3% in men), whereas goiter prevalence in younger people up to age 40 years is below 5%. It could also be shown that the percentage of thyroid autoantibodies is now as high as in other countries with sufficient iodine supply (3.19% in males, 5.17% in females). In addition to the changes of urinary iodine excretion and goiter prevalence because of salt iodination, changes of incidence in hyperthyroidism and histologic types of thyroid cancer are discussed in this paper. In conclusion, the introduction of salt iodination led to an improvement in iodine supply with a marked reduction of goiter prevalence in people who were born after 1963, but also to an increase in hyperthyroidism and autoimmune thyroid diseases as well as changes in histologic types of thyroid cancer.

Lind P. · Department of Nuclear Medicine and Endocrinology, PET Center Klagenfurt, LKH Klagenfurt, St Veiterstrasse 47, 9020 Klagenfurt, Austria. · Eur J Nucl Med Mol Imaging. · Pubmed #12192545 No free full text.

Abstract: Several therapeutic options are available for the treatment of Graves' disease (GD), including long-term antithyroid drug medication (ATD), near-total resection (NTR) and radioiodine therapy (RIT). These treatments are used with different frequencies depending on geographical location, size of the goitre, age of the patient and experience of the physician. It should be noted that RIT is still being applied more frequently in the United States than in Europe. Despite the fact that RIT was introduced as long ago as 1941, several questions are still the subject of debate: Should a fixed dose or a calculated dose be used. If the dose is calculated, how many Grays (Gy) should be delivered to the thyroid? What is the goal of RIT in GD? Which factors, including ATD, influence the outcome of RIT? Is RIT appropriate in GD with Graves' ophthalmopathy (GO)? Although not all these questions have been answered yet, conclusions can be derived regarding a general strategy for use of RIT in GD. As with surgery, the goal of RIT in GD is euthyroidism with or without L-thyroxine medication. There is a clear advantage of dose calculation over use of a fixed dose because the only factor influencing the outcome is the dose delivered to a certain thyroid volume. To minimise recurrent hyperthyroidism, an ablative approach using a delivered dose of 250 Gy is widely accepted. Beside pretherapeutic T(3) levels, thyroid volume and 24-h thyroid uptake, ATD may influence the outcome of RIT. Today it is accepted by most thyroidologists that, if ATD medication is necessary in overt hyperthyroidism, it should be withdrawn at least 2 days before RIT. In patients with GD and GO, RIT may worsen GO. If RIT is performed in GO it should be done under a 3-month steroid medication regimen. In conclusion, RIT can be considered an appropriate and cost-effective therapy in GD, although the decision regarding treatment should be taken on an individual basis, paying due respect to the course and severity of disease, the presence of GO and, last but not least, the wishes of the patient.

Mikosch P, Gallowitsch HJ, Kresnik E, Lind P. · Abteilung für Nuklearmedizin und spezielle Endokrinologie, PET-Zentrum, Landeskrankenhaus Klagenfurt, St. Veiterstrasse 47, A-9020 Klagenfurt. · Wien Med Wochenschr. · Pubmed #11582990 No free full text.

Abstract: In iodine-sufficient areas any thyroid nodule has to be regarded as potentially malignant, whereas in iodine-deficient areas (endemic goiter areas) thyroid nodules, even multinodular goiter, are frequent. The majority of thyroid nodules in an endemic goiter area can be regarded as being most likely benign and thus not all patients with multinodular goiter have to undergo surgery. The major diagnostic aim and challenge is the selection for surgery of only those patients who suffer from mechanical obstruction due to large goiter and those who present with nodules suspicious of malignancy. Thus, for these cases the question of accurately excluding or verifying malignancy is essential for the patient and the specialist of nuclear medicine or endocrinology. A variety of investigations may be used for the preoperative evaluation of thyroid nodules, although currently sonography and fine-needle biopsy have to be regarded as the key investigations to clarify preoperatively the dignity of thyroid nodules. The article presents the indications and limitations of the different methods in use for the evaluation of thyroid malignancy. The authors present a diagnostic algorithm for the preoperative evaluation of thyroid malignancy with special respect to problems occurring in a(n) (former) endemic goiter area.

Lind P, Kumnig G, Matschnig S, Heinisch M, Gallowitsch HJ, Mikosch P, Kresnik E, Gomez I, Unterweger O. · Department of Nuclear Medicine and Endocrinology-PET Center, Landeskrankenhaus Klagenfurt. · Acta Med Austriaca. · Pubmed #10812462 No free full text.

Abstract: Hypofunctioning nodules on scintiscan using Tc-99m Pertechnetate or I-123 have a higher probability of malignancy compared to eu- or hyperfunctioning nodules. However, in the preoperative assessment of thyroid nodules, ultrasonography and ultrasonography guided fine needle aspiration biopsy play the most important role, especially for papillary thyroid cancer. The problem of differentiating follicular adenoma from highly differentiated follicular carcinoma however remains. Also the additional use of a multi tracer imaging strategy (Tl-201/Tc-99m subtraction scan, Tc-99m Sestamibi, Tc-99m Tetrofosmin dual phase scintigraphy) has not solved this problem. Although it is unlikely, the question whether FDG PET is able to give a better differentiation between benign and malignant tumours in the preoperative assessment of thyroid nodules is not answered up to now. In contrast to preoperative diagnostics, FDG PET is of great value in the postoperative follow up of differentiated thyroid cancer. In case of elevated serum thyroglobulin but negative I-131 WBS FDG PET is the method of choice to detect I-131 negative recurrences and metastases. FDG uptake in metastases from differentiated thyroid cancer is correlated to low differentiation and maybe bad prognosis. There is also evidence that FDG PET may have a role in the follow up of anaplastic and especially in medullary thyroid cancer in the future.

Lind P. · Department of Nuclear Medicine and Endocrinology, PET Center, LKH Klagenfurt, Austria. · Q J Nucl Med. · Pubmed #10568134 No free full text.

Abstract: Iodine-131 is the most specific radionuclide to follow up patients with differentiated thyroid cancer (DTC). However there are some aspects that should be considered if 131I whole body scintigraphy (131I WBS) is performed. 1) Several prior conditions, including a bTSH above 30 mU/l and an urinary iodine excretion below 100-150 micrograms/g Crea, should be fulfilled. 2) Only about two thirds of metastases from DTC accumulate iodine. Therefore, in addition to 131I WBS, there is a need for other nonspecific tracers such as 99mTc Tetrofosmin WBS, 99mTc Sestamibi WBS or F-18 FDG PET to detect also iodine negative recurrences or metastases. There new tracers, especially F-18 FDG PET have demonstrated a very high detection rate of iodine negative metastases with mostly low differentiation. 3) The sensitivity of 131I WBS depends on the administered dose. Whereas the sensitivity of a diagnostic 131I WBS (up to 185 MBq) is below 60%, the value for a post-therapeutic 131I WBS (after 3700-7400 MBq) increases up to 75%. This means that in case of elevated serum thyroglobulin, iodine positive metastases cannot be excluded until WBS after 131I therapy is performed. 4) In patients with elevated serum thyroglobulin and/or known metastases, who are scheduled for 131I treatment, the question arises whether a diagnostic 131I WBS should be performed and if so, which dose should be administered to avoid thyroid stunning. There is evidence in the literature that the dose for a pre-therapeutic diagnostic 131I WBS should not exceed 74 MBq. 5) Despite the high specificity of 131I WBS, several pitfalls of iodine accumulation in non-malignant diseases and malignancies of other origin than thyroid cancer should be taken into account.

Kohlfuerst S, Igerc I, Lobnig M, Gallowitsch HJ, Gomez-Segovia I, Matschnig S, Mayr J, Mikosch P, Beheshti M, Lind P. · Department of Nuclear Medicine and Endocrinology, PET-CT Centre, State Hospital Klagenfurt, Klagenfurt, Austria. · Eur J Nucl Med Mol Imaging. · Pubmed #19169681 No free full text.

Abstract: PURPOSE: The purpose of this prospective study was to determine the diagnostic impact and influence on patient treatment of posttherapeutic (131)I SPECT-CT when the findings on planar posttherapeutic whole-body scintigraphy (ptWBS) were inconclusive. MATERIALS AND METHODS: A total of 53 SPECT-CT scans were performed in 41 patients with thyroid cancer after high-dose (131)I therapy (2.944 to 7.526 GBq (131)I) because of diagnostic uncertainty on ptWBS. Physiological uptake in the salivary glands, gastric mucosa, gut, nasal mucosa, urinary tract and liver were considered to be normal. Any other foci of increased (131)I uptake, except iodine uptake clearly located in the thyroid bed, were considered to be abnormal. The data were evaluated on a lesion and a patient basis. RESULTS: Regarding neck lesions, SPECT-CT provided a diagnostic impact in 26/90 lesions (28.9%) and confirmed the diagnosis in 64/90 lesions (71.1%). On a patient basis, SPECT-CT changed N status in 12/33 patients (36.4%), provided a diagnostic impact in 21/33 patients (63.6%) and led to a treatment change in 8/33 patients (24.2%). Regarding lesions distant from the neck, SPECT-CT confirmed the diagnosis in 62/71 lesions (87.3%) and had a diagnostic impact in 9/71 lesions (12.7%). On a patient basis, SPECT-CT changed M status in 4/19 patients (21.1%), had a diagnostic impact in 14/19 patients (73.7%) and led to a treatment change in 2/19 patients (10.5%). Considering all patients, SPECT-CT led to a treatment change in 10/41 patients (24.4%). CONCLUSION: Integrated SPECT-CT is a useful tool, especially in cases of diagnostic uncertainty and helps to individualize patient management.

Kohlfuerst S, Igerc I, Gallowitsch HJ, Gomez I, Kresnik E, Matschnig S, Lind P. · Department of Nuclear Medicine, and Endocrinology, PET-CT Center Klagenfurt, LKH Klagenfurt, Klagenfurt, Austria. · Thyroid. · Pubmed #17123338 No free full text.

Abstract: INTRODUCTION: The aim of our study was to determine whether treatment with a long-acting somatostatin-receptor analogue is effective in patients with (131)I-negative but somatostatin-receptor-positive metastases from dedifferentiated and anaplastic thyroid cancer. MATERIALS AND METHODS: Twelve patients were screened for the study. All of them showed progressive disease confirmed by radiologic evaluation, increasing serum thyroglobulin (Tg), and negative diagnostic or posttherapeutic (131)I whole-body scans (WBS). Eight of 12 patients (4 males and 4 females; age range, 57-89 years; 1 papillary thyroid cancer; 4 poorly differentiated follicular thyroid cancer; 1 follicular and anaplastic thyroid cancer; 2 anaplastic thyroid cancer) showed positive somatosatin-receptor expression in Tc-99m depreotide WBS/SPECT (Tc-99m Dep.WBS). Initially, in all patients fluorine-18 2-fluoro-2- D-glucose-positron emission tomography-computed tomography ((18)F-FDG-PET-CT), Tc-99m Dep.WBS, and Tg measurements were performed. In the case of positive receptor scintigraphy, patients were treated with 20mg Sandostatin LAR (Novartis Pharmaceuticals, Basel, Switzerland) once per month intramuscularly over a period of 6 months followed by repeated (18)F-FDG-PET-CT, Tc-99m Dep.WBS, and Tg measurement to determine metabolic activity and tumor size. In case of tumor progression, the dose was increased to 30mg of Sandostatin LAR once per month. RESULTS: Only 3 patients were able to undergo long-term treatment. Two patients were treated with octreotide long-acting release (LAR) for 1 year and 1 patient for 1(1/2) years. All patients showed progressive disease during the treatment: an increase of serum Tg on one hand and an increase in the number of lesions and extent in tumor size visible on FDG-PET-CT and Tc-99m Dep.WBS on the other. During the treatment there was no change in receptor expression, nevertheless, clear tumor progression under therapy with a somatostatin analogue was visible in FDG-PET-CT and in Tc-99m Dep.WBS. CONCLUSION: Our data demonstrate that all of our patients treated with a somatostatin analogue showed clinical progression and that our attempt to achieve a stabilization of the disease failed.

Mikosch P, Kerschan-Schindl K, Woloszczuk W, Stettner H, Kudlacek S, Kresnik E, Gallowitsch HJ, Lind P, Pietschmann P. · Department of Internal Medicine II, Klagenfurt State Hospital, Klagenfurt, Austria. · Thyroid. · Pubmed #18302515 No free full text.

Abstract: BACKGROUND: Thyroid hormone administration is associated with low bone density in some studies. The aim of the present study was to evaluate the influence L-thyroxine, in doses used to treat patients with a history of thyroid carcinoma, on serum cathepsin K and other markers of bone metabolism. Cathepsin K is thought to have a role in osteoclast mediated bone resorption. METHODS: A group of male patients with differentiated thyroid cancer (DTC) on suppressive L-thyroxine therapy (DTC-group; n = 51; mean age 57 years; TSH < 0.1 mU/L) was selected as a model for hyperthyroidism. The results were compared to a group of healthy euthyroid men (control-group; n = 50; mean age 58 years; TSH 1.5 +/- 0.9 mU/L). RESULTS: In the DTC-group the median value of cathepsin K was 6.9 pmol/L, in the control group 4.8 pmol/L (p = 0.0052; highly significant [h.s.]). There was a significant negative correlation of cathepsin K with age (r = -0.279, p = 0.028). The analysis of various bone associated parameters revealed an increase of serum crosslaps in the DTC-group versus euthyroid controls (p = 0.03). A significant correlation could be found for cathepsin K and osteoprotegerin (p = 0.002). CONCLUSION: Cathepsin K is increased by a suppressive L-thyroxine therapy and decreases with increasing age. The increased cathepsin K levels seen in DTC-patients on suppressive L-thyroxine therapy are likely to contribute to accelerated bone degradation in these patients.

Zoller M, Kohlfuerst S, Igerc I, Kresnik E, Gallowitsch HJ, Gomez I, Lind P. · Department of Nuclear Medicine and Special Endocrinology, PET/CT Centre, Landeskrankenhaus Klagenfurt, St. Veiter Str. 47, 9020, Klagenfurt, Austria. · Eur J Nucl Med Mol Imaging. · Pubmed #17103166 No free full text.

Abstract: PURPOSE: 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) is a well-established method in the follow-up of patients with differentiated thyroid carcinoma (DTC), elevated thyroglobulin (Tg) and negative 131I scans. This retrospective clinical study was designed to evaluate the impact of computed tomography (CT) and that of FDG-PET in combined FDG-PET/CT examinations on the restaging of DTC patients. METHODS: Forty-seven FDG-PET/CT scans of 33 patients with a history of DTC, elevated Tg levels and negative 131I uptake or additionally suspected 131I-negative lesions were studied. PET and CT images were analysed independently by an experienced nuclear medicine specialist and a radiologist. Afterwards a final consensus interpretation, the gold standard in our department, was provided for the fused PET/CT images and, if available, for supplementary investigations. RESULTS: Thirty-five investigations (74%) revealed pathological FDG-PET/CT findings. In summary, 25 local recurrences, 62 lymph node metastases and 122 organ metastases (41 lung, 60 bone, 21 other organs) were diagnosed. In 36 out of 47 examinations (77%), the original PET diagnoses were modified in the final consensus interpretation owing to the CT assessments. In 8 of the 35 pathological FDG-PET/CT examinations (23%), the final consensus interpretation of the PET/CT images led to an alteration in the treatment plan. CONCLUSION: PET/CT is a powerful fusion of two pre-existing imaging modalities, which not only improves the diagnostic value in restaging DTC patients with elevated Tg and negative 131I scan, but also provides accurate information regarding subsequent treatment options and may lead to a change in treatment management.

Mikosch P, Igerc I, Kudlacek S, Woloszczuk W, Gallowitsch HJ, Kresnik E, Stettner H, Grimm G, Lind P, Pietschmann P. · Department of Nuclear Medicine and Special Endocrinology, Klagenfurt State Hospital, Klagenfurt, Austria. · Eur J Clin Invest. · Pubmed #16893379 No free full text.

Abstract: BACKGROUND: Suppressive thyroid hormone therapy is generally a lifelong treatment for patients with differentiated thyroid cancer (DTC). However, long-standing thyrotropin (TSH) suppression is a risk factor for osteoporosis. Osteoprotegerin (OPG) and receptor activator of nuclear factor kappaB ligand (RANKL) are central regulators of bone turnover. The aim was to analyze the effects of a suppressive thyroid hormone therapy in males with DTC on the OPG/RANKL system and on bone metabolism. PATIENTS AND METHODS: The OPG and soluble RANKL (sRANKL) were determined in 40 men (mean age, 53.2 years) with DTC on suppressive thyroid hormone therapy (TSH; 0.053 +/- 0.037 mU L(-1), duration 5.7 +/- 4.4 years) and 120 healthy controls matched for age. The markers of bone metabolism were C-terminal telopeptide of type I collagen in serum (sCTx) and osteocalcin (OC). RESULTS: The control group had OPG values (mean +/- SD) of 1.9 +/- 1.0 pmol L(-1) and sRANKL values of 0.40 +/- 0.62 pmol L(-1). In patients with DTC, results for OPG were 3.03 +/- 1.04 pmol L(-1) (P < 0.05) and for sRANKL were 0.13 +/- 0.16 pmol L(-1) (P < 0.05). The control group presented values for sCTx of 2669 +/- 1132 pmol L(-1) and for OC of 17.89 +/- 6.5 ng mL(-1). Patients with DTC on suppressive thyroid hormone therapy had increased sCTx values of 3810 +/- 2020 pmol L(-1) (P = 0.03) but comparable OC values of 19.21 +/- 7.67 ng mL(-1) (NS). CONCLUSIONS: Suppressive thyroid hormone therapy in men with DTC increased bone degradation and induced significant changes in the OPG/RANKL system. These changes include, besides the risk of osteoporosis, possible negative effects on the vascular function and an increased risk of cardiovascular disease.

Lind P, Igerc I, Kohlfürst S. · Abteilung für Nuklearmedizin und Endokrinologie, PET/CT Zentrum Klagenfurt, Landeskrankenhaus Klagenfurt, Klagenfurt, Austria. · Wien Med Wochenschr. · Pubmed #16424998 No free full text.

Abstract: For early diagnosis of thyroid cancer, ultrasonography (US) and US-guided fine-needle aspiration biopsy are the methods of choice. Thyroid scintigraphy using Tc-99m pertechnetate can underline the necessity of surgery in case of hypofunctioning nodules. Treatment of thyroid cancer includes total thyroidectomy and staging lymphadenectomy, in the case of lymph node metastases, radical neck dissection of the ipsilateral side. Four weeks after surgery, if TSH exceeds a value of 50 mU/l, with the exception of papillary thyroid cancer pT1a (TNM 1997), radioiodine remnant ablation using activities between 2960 and 3700 MBq I-131 is performed in all other cases. As growth of benign and malignant thyroid cells depends on TSH stimulation, thyroid hormone therapy using TSH suppressive doses (TSH, <0.03 mU/l) follows radioiodine remnant ablation. Additional fractionated external radiation therapy (50 Gy) may be administered in advanced cases (e.g., pT4 N1M0; TNM 1997). Standard follow-up of differentiated thyroid cancer includes measurement of serum thyroglobulin, US of the neck and I-131 whole-body scintigraphy (I-131 WBS). With about 98% the sensitivity of thyroglobulin is very high under TSH stimulation. In case of elevated thyroglobulin, US is the method of choice to detect local recurrences and lymph node metastases of the neck. At defined intervals of follow-up or in case of increasing thyroglobulin, I-131 WBS will be performed under TSH stimulation. With the availability of recombinant TSH (exogenous TSH stimulation) the need to withdraw thyroid hormone over a period of 3-4 weeks (endogenous TSH stimulation) is no longer necessary to perform I-131 WBS. However, in about 20-40% of cases or in the course of disease after several radioiodine therapies, recurrences or metastases may be or become iodine negative. In this case, cationic complexes such as Tc-99m Sestamibi or Tc-99m Tetrofosmin are available to detect less differentiated metastases. In the course of dedifferentiation of malignant thyroid cells, the ability of iodine uptake decreases and uptake of glucose increases. This elevated glucose metabolism can be imaged using FDG PET. Today the combination of PET (metabolic imaging) and CT (morphologic imaging) using PET/CT fusion imaging is the method of choice to image iodine-negative metastases.

Kohlfuerst S, Igerc I, Lind P. · Department of Nuclear Medicine and Endocrinology, PET Center, LKH Klagenfurt, St. Veiterstrase 47, 9020 Klagenfurt, Austria. · Thyroid. · Pubmed #15876162 No free full text.

Abstract: There is no doubt that the availability of recombinant human thyrotropin (rhTSH) is one of the milestones in the management of patients with differentiated thyroid cancer (DTC). It offers the opportunity to obtain representative serum thyroglobulin (Tg) levels and diagnostic whole-body scanning (Dx WBS) with 131I under adequate TSH elevation, while the patient continues to receive thyroid hormone. But rhTSH is also used with success in the treatment of local recurrences and distant metastases. In this retrospective analysis we were able to show that our excellent clinical experiences with the use of rhTSH (rare side effects and high compliance) could also be demonstrated by sufficiently elevated TSH levels and representative stimulated Tg measurements. Since April 2001 most of the patients with thyroid cancer in our hospital have undergone diagnostic examination (205 patients underwent 319 examinations) and 131I therapy (a total of 68 treatments) with rhTSH stimulation excluding the first radioiodine ablation of remnants after initial thyroidectomy. Our results show that under rhTSH stimulation 83.5% (diagnostic group) and 88% (therapy group) of our patients with DTC obtained a TSH level of greater than 80 mU/L after two injections of rhTSH (Thyrogen, Genzyme Corp., Cambridge, MA) 0.9 mg intramuscularly 24 hours and 48 hours before the administration of 131I. Only 2.3% (diagnostic group) and 0% (therapy group) demonstrated TSH levels less than 50 mU/L. Serum Tg levels under rhTSH-stimulated conditions showed that in 81.2% the serum Tg maximum was obtained on day 5. Because of the costs associated with periodically rhTSH-assisted Tg testing and based on the data of other studies we are now testing mainly on day 5 to identify residual tumor mass and to compare these Tg levels in the follow-up. Our experience demonstrates that the administration of rhTSH is a safe, effective, and-from an economic point of view- valuable tool in the management of patients with DTC.

Schlumberger M, Pacini F, Wiersinga WM, Toft A, Smit JW, Sanchez Franco F, Lind P, Limbert E, Jarzab B, Jamar F, Duntas L, Cohen O, Berg G. · Service de Médicine Nucléaire, Institut Gustave Roussy, 94805 Villejuif, France. · Eur J Endocrinol. · Pubmed #15538930 links to  free full text

Abstract: As differentiated (follicular and papillary) thyroid cancer (DTC) may recur years after initial treatment, follow-up of patients with DTC is long term. However, this population has changed, with more individuals being discovered at an earlier stage of disease, so that previous follow-up protocols based mostly on data from high-risk patients no longer apply. We have proposed, in a previous issue of this Journal, an improved protocol for the follow-up of low-risk patients with DTC based on the findings of recent studies. We report here the case of a paradigmatic patient with papillary thyroid carcinoma, with the goal of illustrating the benefits of applying this algorithm in routine clinical practice. We also offer expanded and additional comments on various issues in the management of DTC.

Gomez Segovia I, Gallowitsch HJ, Kresnik E, Kumnig G, Igerc I, Matschnig S, Stronegger WJ, Lind P. · Department of Nuclear Medicine and Special Endocrinology-PET Center, General State Hospital, Klagenfurt, Austria. · Thyroid. · Pubmed #15142361 No free full text.

Abstract: INTRODUCTION: The aim of the study was to investigate the current thyroid carcinoma (TC) incidence in Carinthia, a former iodine-deficient, goiter-endemic region in Austria with approximately 550,000 inhabitants from 1984 to 2001. Using age-cohort analysis we analyzed the TC incidence under the impact of two regional risk factors: the contamination of Austrian soils by the radioactive fallout in from Chernobyl 1986 and the increased iodination of table salt in a general program of goiter prophylaxis begun in 1991. To evaluate the characteristics of TC incidence, we compared the results of the periods 1984-1989, 1990-1995, and 1996-2001. RESULTS: A total of 734 TC cases were diagnosed. Papillary, follicular, medullary, oxyphilic, and anaplastic TC accounted for 76%, 18%, 3%, 1%, and 2%, respectively. The female to male ratio was 3:1. The annual incidence rate increased by 8.05% in females and 11.6% in males. TC cases younger than 40 years of age accounted for 22.6%, with a rate increase of 18% per year in young males, the female-to-male ratio decreased from 8.3, 6.1, 2.7 younger than 40 in the compared periods. Along with a further increase in papillary TC incidence and papillary thyroid carcinoma (PTC) follicular thyroid carcinoma (FTC) ratio in the adult population, the ratio tended to decrease in the younger than 40-year-old population. T4 class TC and loco-regional lymph node involvement increased significantly. Interpretation: The observed changes in TC incidence, particularly in the young population, as in adults, could be linked to the abovementioned risk factors involved in the initiation and early growth of TC, and iodine may play a role in stimulating overall thyroid activity.

Mikosch P, Obermayer-Pietsch B, Jost R, Jauk B, Gallowitsch HJ, Kresnik E, Leb G, Lind P. · Department of Nuclear Medicine and Special Endocrinology, Klagenfurt State Hospital, Austria. · Thyroid. · Pubmed #12804103 No free full text.

Abstract: AIM: Patients with differentiated thyroid carcinoma (DTC) must receive suppressive levothyroxine (LT(4)) therapy for the rest of their lives. The literature, however, presents conflicting results on how this affects bone metabolism. The aim of this study was to assess the influence of the estrogen status and LT(4) therapy, in particular LT(4) dosage in micrograms per kilograms (microg/kg), on bone metabolism in female patients with DTC. MATERIAL AND METHODS: Three markers of bone metabolism (C-terminal telopeptide of type I collagen in serum [SCTx]; N-terminal telopeptide of type I collagen in urine [U-NTx]; and osteocalcin [OC]) were investigated in four groups: group REF (healthy premenopausal female controls), group DTC-ES (premenopausal women with DTC and normal estrogen levels), group DTC-ED (postmenopausal women with DTC and estrogen deficiency), and group DTC-HRT (postmenopausal women with DTC undergoing hormone replacement therapy [HRT]). All patients with DTC were on a well-adjusted suppressive LT(4) therapy with TSH levels 0.1 mU/L or less. RESULTS: In group DTC-ES bone turnover was comparable to group REF, whereas in group DTC-ED, all three markers were significantly increased as compared to groups REF and DTC-ES. In group DTC-HRT, the HRT normalized U-NTx and OC. However, in this group S-CTx was not completely normalized by HRT in all patients, although also significantly lowered compared to group DTC-ED. The analysis of LT(4 )dosage per kilogram showed that premenopausal DTC-patients had increased markers of bone metabolism if LT(4) dosage exceeded 2.6 microg/kg. Estrogen-deficient patients with DTC, however, had a much lower critical LT(4) dosage, above which increased markers of bone metabolism were seen. CONCLUSION: A well-adjusted suppressive LT(4) therapy of less than 2.6 microg/kg and normal estrogen levels do not seem to increase bone metabolism in estrogen-sufficient patients with DTC. The normalization of an estrogen deficiency by HRT or other antiresorptive therapies and minimal suppressive dosages of LT(4) are attempts to optimize the care of patients with DTC. In postmenopausal patients with DTC and patients with DTC who require LT(4) dosages in excess of 2.6 microg/kg, the information provided by markers of bone metabolism may help to prevent bone damage.

Kresnik E, Gallowitsch HJ, Mikosch P, Stettner H, Igerc I, Gomez I, Kumnig G, Lind P. · Department of Nuclear Medicine, Institute of Mathematics, University of Klagenfurt, Klagenfurt, Austria. · Surgery. · Pubmed #12660642 No free full text.

Abstract: BACKGROUND: The aim of this study was to evaluate the usefulness of fluorine-18-fluorodeoxyglucose positron emission tomography ((18)F-FDG PET) in the preoperative assessment of suspicious thyroid nodules. METHODS: A total of 43 patients were examined before surgical resection. In all patients, imaging was obtained at 70 minutes after the intravenous administration of 180 MBq (18)F-FDG. Standard uptake values (SUVs) were calculated. RESULTS: A total of 16 patients with thyroid carcinomas (11 papillary, 3 follicular, 2 anaplastic), 23 thyroid adenomas (11 microfollicular, 10 Hurthle cell, 2 macrofollicular), and 4 patients with degenerative goiter were found. (18)F-FDG uptake in Hurthle cell adenoma, thyroid cancer, microfollicular adenoma, degenerative goiter, and macrofollicular adenoma was 4.4 +/- 2.2, 3.7 +/- 1.9, 1.6 +/- 0.3, 1.2 +/- 0.2, and 0.9 +/- 0.1, respectively. Significant differences were observed between thyroid carcinomas and both microfollicular adenomas and degenerative goiters (P < 0.05), and between Hurthle cell adenomas and both microfollicular adenomas as well as degenerative goiter (P < 0.05). For diagnosis of thyroid carcinoma, 100% sensitivity, 63% specificity, and 100% negative predictive value was found when a cutoff value for SUV of 2 was used. CONCLUSIONS: Our results indicate that thyroid carcinomas, in contrast to most benign thyroid nodules, demonstrate significantly increased glucose metabolism. (18)F-FDG PET is unlikely to differentiate successfully all benign tumors from malignant tumors, but it can help select patients who need surgery, especially if cytology is inconclusive or malignancy cannot be excluded.

Mikosch P, Würtz FG, Gallowitsch HJ, Kresnik E, Lind P. · Department of Nuclear Medicine and Special Endocrinology, PET-Center, Klagenfurt State Hospital, St. Veiterstrasse 47, A-9020 Klagenfurt. · Wien Med Wochenschr. · Pubmed #12658970 No free full text.

Abstract: We report on the case of a 86-year-old male patient with a rapidly growing nodule within the right lobe of the thyroid gland, which after hemithyroidectomy, turned out to be a mucosa-associated lymphoid tissue (MALT) lymphoma of the thyroid gland. In addition, Hashimoto's thyroiditis was reported in the thyroid tissue adjacent to the MALT lymphoma. During follow-up a second nodule emerged within the left lobe and, because of evidence of MALT lymphoma recurrence, F-18-FDG-PET was performed. F-18-FDG-PET imaged a clearly increased accumulation within the whole left lobe and isthmus. Thus, no differences in the degree of hypermetabolism could be imaged between the nodule and the adjacent thyroid tissue. To our knowledge, this is the first report about F-18-FDG-PET in a patient with MALT lymphoma of the thyroid. Literature search revealed only a few cases of MALT lymphomas in locations other than the thyroid gland that were studied with F-18-FDG-PET. In no case was F-18 FDG accumulation seen in the MALT lesions. However, clear F-18 FDG accumulation was reported in some patients with Hashimoto's thyroiditis. It is concluded that the intensive F-18-FDG accumulation within the whole left lobe and isthmus of the presented case was due to the coexisting Hashimoto's thyroiditis. Consequently, F-18-FDG-PET imaging does not seem to be indicated in a patient with MALT lymphoma and known Hashimoto's thyroiditis in order to evaluate the status of the MALT lymphoma.

Lind P. · Department of Nuclear Medicine and Endocrinology, PET Center Klagenfurt, LKH Klagenfurt, St. Veiterstrasse 47, 9020 Klagenfurt, Austria. · Eur J Nucl Med Mol Imaging. · Pubmed #12583362 No free full text.

This publication has no abstract.

Lind P, Kresnik E, Kumnig G, Gallowitsch HJ, Igerc I, Matschnig S, Gomez I. · Department of Nuclear Medicine and Endocrinology, PET Centre Klagenfurt. · Acta Med Austriaca. · Pubmed #12558561 No free full text.

Abstract: Differentiated thyroid cancer is a rare tumour with an incidence of 4 - 9/100,000/year. For preoperative assessment of thyroid nodules, ultrasonography (US) and US-guided fine needle aspiration biopsy are the methods of choice to detect thyroid cancer. The value of preoperative fluorine-18 fluorodeoxyglucose positron emission tomography (18F-FDG-PET) in differentiating malignant from benign nodules, especially in cases of follicular proliferation, has not yet been evaluated. After thyroidectomy and radioiodine remnant ablation, several methods are used to follow patients with differentiated thyroid cancer, including serum thyroglobulin, ultrasonography of the neck, iodine-131 (131I) whole body scintigraphy (WBS) and scintigraphy with nonspecific tracers such as technetium-99 m ((99m)Tc) Tetrofosmin or Sestamibi. Whereas the specificity of 131I-WBS is high, sensitivity is low, especially if one takes into account that only two-thirds of recurrences or metastases store iodine. With the introduction of 18F-FDG in oncology, it is also used for the detection of local recurrences and metastases of differentiated thyroid cancer. Elevated thyroglobulin but negative 131I-WBS belongs to the 1a indications for 18F-FDG-PET in oncology according to the German Consensus Conference 2000. The sensitivity for detecting 131I-negative metastases with 18F-FDG-PET can be increased by elevated thyroid-stimulating hormone (TSH) after withdrawal of thyroid hormone therapy or after intramuscular injection of recombinant TSH. Most of the 131I-negative metastases demonstrate 18F-FDG uptake, which represents rapid tumour growth and poor differentiation, whereas most of the 131I-positive metastases are 18F-FDG negative. The combination of 131I-WBS and 18F-FDG-PET leads to an increase in the detection rate to more than 90 - 95 % in cases of elevated thyroglobulin, because well- and less-differentiated cancer cells may be present in one patient. In rare cases, a recurrent tumour or metastasis may accumulate 131I as well as 18F-FDG. In these patients, it may be possible that well- and less-differentiated cells are present in one metastasis. The early use of 18F-FDG-PET in patients with elevated thyroglobulin, especially in the case of negative 131I-WBS, changes the therapeutic strategy in up to half of the patients (surgery, external radiation).

Heinisch M, Kumnig G, Asböck D, Mikosch P, Gallowitsch HJ, Kresnik E, Gomez I, Unterweger O, Lind P. · Department of Nuclear Medicine and Special Endocrinology, PET Centre, State Hospital Klagenfurt, Austria. · Thyroid. · Pubmed #12481947 No free full text.

Abstract: The objective of this epidemiologic study was to determine the volume of the thyroid gland as well as urinary iodine excretion in dependence on age and gender in a population from an area of low natural iodine supply now receiving iodine prophylaxis. In 430 persons from three communities in the province of Carinthia, Austria, we determined thyroid volume via sonography as well as urinary iodide excretion. As in numerous other European countries, natural iodine supply is insufficient in Austria. Therefore, to reduce goiter incidence, iodization of common salt with 10 mg potassium iodide (KI) per kilogram of NaCl was made mandatory in Austria in 1963 by federal law. In 1990, the amount of iodine addition was increased to 20 mg KI per kilogram of NaCl. Our results show that mean urinary iodide excretion in the persons investigated was altogether satisfactory (males: 163.7 microg of iodine per gram of creatinine; females: 183.3 microg of iodine per gram of creatinine). Goiter prevalence was 34.3% in women and 21.3% in men. An increase in goiter occurrence with age was noted in both genders. The increase in goiter prevalence was particularly obvious in the age group older than 40, i.e., among those participants who had spent at least a certain span of their lives in an area of iodine deficiency. Thus, the most likely reason for the persistently high goiter prevalence is not current iodine deficit but rather the high number of goiters that had developed previously at the time of iodine deficiency and were unable to undergo regression in spite of today's comparatively good iodine supply situation.