Georg Zettinig

Long‐term follow‐up of patients with bone metastases from differentiated thyroid carcinoma – surgery or conventional therapy?

objective Surgery of bone metastases from differentiated thyroid carcinoma seems indicated in individual patients. This study was performed (1) to analyse retrospectively patients with bone metastases from differentiated thyroid carcinoma and (2) to evaluate the impact of surgery of bone metastases on survival.

Positron emission tomography imaging of adrenal masses: 18F-fluorodeoxyglucose and the 11β-hydroxylase tracer 11C-metomidate

Purpose11C-metomidate (MTO), a marker of 11β-hydroxylase, has been suggested as a novel positron emission tomography (PET) tracer for adrenocortical imaging. Up to now, experience with this very new tracer is limited. The aims of this study were (1) to evaluate this novel tracer, (2) to point out possible advantages in comparison with 18F-fluorodeoxyglucose (FDG) and (3) to investigate in vivo the expression of 11β-hydroxylase in patients with primary aldosteronism.Methods Sixteen patients with adrenal masses were investigated using both MTO and FDG PET imaging. All patients except one were operated on. Five patients had non-functioning adrenal masses, while 11 had functioning tumours(Cushing’s syndrome, n=4; Conn’s syndrome, n=5; phaeochromocytoma, n=2). Thirteen patients had benign disease, whereas in three cases the adrenal mass was malignant (adrenocortical cancer, n=1; malignant phaeochromocytoma, n=1; adrenal metastasis of renal cancer, n=1).ResultsMTO imaging clearly distinguished cortical from non-cortical adrenal masses (median standardised uptake values of 18.6 and 1.9, respectively, p<0.01). MTO uptake was slightly lower in patients with Cushing’s syndrome than in those with Conn’s syndrome, but the difference did not reach statistical significance. The expression of 11β-hydroxylase was not suppressed in the contralateral gland of patients with Conn’s syndrome, whereas in Cushing’s syndrome this was clearly the case. The single patient with adrenocortical carcinoma had MTO uptake in the lower range.ConclusionMTO could not definitely distinguish between benign and malignant disease. FDG PET, however, identified clearly all three study patients with malignant adrenal lesions. We conclude: (1) MTO is an excellent imaging tool to distinguish adrenocortical and non-cortical lesions; (2) the in vivo expression of 11β-hydroxylase is lower in Cushing’s syndrome than in Conn’s syndrome, and there is no suppression of the contralateral gland in primary aldosteronism; (3) for the purpose of discriminating between benign and malignant lesions, FDG is the tracer of choice.

Measuring the rate of progression of Parkinson's disease over a 5-year period with β-CIT SPECT

Recent imaging studies suggest a rapid degeneration of the dopaminergic system in early Parkinsons disease (PD), followed by a slowing of the degenerative process in advanced disease. In the present study, a group of early‐stage PD patients underwent three sequential [123I]β‐CIT SPECT studies to assess the decline of striatal dopamine transporter binding over a 5‐year period. Twenty‐one of a cohort of 24 early PD patients who participated in an earlier longitudinal β‐CIT SPECT imaging study [Mov Disord 2002;17:45–53] were included. Scan intervals were 26 ± 11 months (scan 1–2) and 38 ± 15 months (scan 2–3), respectively. The relative annual rate of decline of striatal β‐CIT binding from age‐expected normal values at the time of Scan 1 was used as primary outcome variable. The relative annual decline of striatal binding from Scan 1 to Scan 2 (4.5 ± 4.6%) and from Scan 2 to Scan 3 (3.0 ± 3.0%) was not significantly different. The non‐significant difference in progression rate was due mainly to the rapid early decline of striatal binding in 1 patient who subsequently developed a severe dysexecutive dementia syndrome. These data are not suggestive of substantial change in the course of dopaminergic degeneration in PD within the first 5 to 7 years after symptom onset.

Application of Staging Systems for Differentiated Thyroid Carcinoma in an Endemic Goiter Region With Iodine Substitution

ObjectiveTo evaluate and compare staging systems for differentiated thyroid carcinoma and predicted outcome in an endemic goiter region with iodine substitution and to examine the risk profile of differentiated thyroid carcinoma and compare it against nongoiter regions. Summary Background DataDifferentiated (papillary or follicular) thyroid carcinoma has a favorable prognostic outcome. In numerous studies prognostic factors have been identified and staging systems created, particularly in Anglo-American centers (nonendemic goiter regions), to evaluate individual prognostic outcome. MethodsIn a retrospective study, the authors assessed 440 patients with differentiated thyroid carcinoma (papillary, n = 293; follicular, n = 147) and a long-term follow-up of median 10.6 years to determine the predictive accuracy of nine staging systems applicable to the study population; the systems were compared by calculating the proportion of variation explained. ResultsWith regard to cause-specific mortality, the difference between the respective stages and/or risk groups was highly significant for every staging system. By means of calculating the proportion of variation explained, MACIS scoring supplied the most reliable prognostic information for differentiated thyroid carcinoma (relative importance 16.93%). EORTC and UICC/AJCC systems had a relative importance of 16.34% and 13.96%, respectively, also a high level of accuracy; this implies that they are superior to the other six staging systems. If we separate papillary and follicular carcinoma, for the former the MACIS score with a relative importance of 15.05% is clearly superior to the other staging systems, whereas for the latter the EORTC score and the UICC/AJCC staging system, with relative importance of 17.04% and 16.58%, respectively, yield the best prognostic information. ConclusionsBy applying staging systems in an endemic goiter region with iodine substitution, the best prognostic information for papillary thyroid carcinoma has been achieved with the MACIS score, while for follicular thyroid carcinoma the EORTC score and the UICC/AJCC system have the best prognostic accuracy. Because of the individual factors, which are easy to obtain and generally available (age, T, N, M classification), the uncomplicated handling, and the widespread use and the good predictive accuracy, the UICC/AJCC classification is the staging system of choice for comparing published results.

Increased prevalence of sublinical brain perfusion abnormalities in patients with autoimmune thyroiditis: evidence of Hashimoto's encephalitis?

objectives  Hashimotos encephalitis is a term which describes encephalopathy associated with autoimmune thyroiditis, but it is not based on evidence, whether Hashimotos encephalitis is a distinct clinical entity by itself. In previously reported cases of Hashimotos encephalitis, abnormal brain perfusion studies have been reported. The aim of this study was to evaluate the prevalence of brain perfusion abnormalities in euthyroid patients with autoimmune thyroiditis.

[ 123 I]- β -CIT SPECT Imaging Shows Reduced Thalamus–Hypothalamus Serotonin Transporter Availability in 24 Drug-Free Obsessive-Compulsive Checkers

Numerous findings indicate alterations in brain serotonin systems in obsessive-compulsive disorder (OCD). We investigated the in vivo availability of thalamus–hypothalamus serotonin transporters (SERT) in patients with DSM-IV OCD who displayed prominent behavioral checking compulsions (OC-checkers). Four hours after injection of [123I]-2β-carbomethoxy-3β-(4-iodophenyl)tropane ([123I]-β-CIT), single photon emission computed tomography (SPECT) scans were performed in 24 medication-free non-depressed OC-checkers and 24 age- and gender-matched healthy controls. For quantification of brain serotonin transporter availability, a ratio of specific to non-displaceable [123I]-β-CIT brain binding was used (V″3=(thalamus and hypothalamus−cerebellum)/cerebellum). Drug-free non-depressed OC-checkers showed an 18% reduced brain serotonin transporter availability in the thalamus and hypothalamus, as compared with healthy control subjects (1.38±0.19 vs 1.69±0.21; p<0.001). There was a strong negative correlation between severity of OC symptomatology (Y-BOCS scores) and SERT availability (r=−0.80; p<0.001). Moreover, we found a significant positive correlation between illness duration and serotonin transporter availability (r=0.43; p<0.05). This first report of significantly reduced [123I]-β-CIT binding in the thalamus–hypothalamus region in OC-checkers suggests reduced brain serotonin transporter availability, which is more pronounced with increased severity of OC symptomatology and short duration of illness. The results provide direct evidence for an involvement of the serotonergic system in the pathophysiology of OCD.

‘Suppressed’ Double Adenoma – A Rare Pitfall in Minimally Invasive Parathyroidectomy

Since the introduction of a quick intraoperative parathyroid hormone (QPTH) assay, complete removal of hyperfunctioning parathyroid tissue can be proven during surgery. We report on a scintigraphically and biochemically documented patient with persistent primary hyperparathyroidism (PHPT) caused by suppressed hyperfunctioning parathyroid tissue. A left lower enlarged parathyroid gland was resected by minimally invasive open parathyroidectomy. QPTH measurements confirmed complete resection of hyperfunctioning tissue and histology showed a tumorous enlarged left lower parathyroid gland. The patient was normocalcemic until 1 month after surgery, when serum calcium increased again. A MIBI scan 6 months after surgery showed no evidence of hyperfunctioning parathyroid tissue. After an increase of PTH, a third MIBI scan another 3 months later was performed. Increased tracer uptake behind the lower pole of the right thyroid lobe was seen and confirmed by ultrasonography. Another tumorous enlarged parathyroid gland was removed. These findings support the hypothesis that smaller yet abnormal parathyroid glands can be suppressed and may become hypersecretory if left in situ after surgical removal of the larger gland.

Coronary Vasoreactivity in Subjects with Thyroid Autoimmunity and Subclinical Hypothyroidism Before and After Supplementation with Thyroxine

BACKGROUND The association of subclinical hypothyroidism (SCH) with increased risk for cardiovascular disease is still controversial. This study aimed to examine coronary vascular reactivity by positron emission tomography (PET) in asymptomatic patients with SCH before and after levothyroxine (LT4) supplementation. METHODS Ten patients (7 women and 3 men; mean age 43±15 years) with untreated autoimmune SCH, defined by elevated levels of thyroid-stimulating hormone (mean TSH: 16.9±11.3 μU/mL), normal levels of free thyroxine (0.9±0.1 μg/mL), free triiodothyronine (3.2±0.4 pg/mL), and positive thyroid peroxidase antibodies were studied. Eight euthyroid subjects with similar low-risk cardiovascular risk profile served as controls. Myocardial blood flow (MBF) and coronary flow reserve (CFR) were quantitatively assessed with rest/stress N-13 ammonia PET at baseline and after 6 months of LT4 replacement therapy (given only to patients). RESULTS At baseline, stress MBF and CFR corrected (c) for rate pressure product (RPP) and myocardial vascular resistance (MVR) during stress were significantly reduced in SCH compared with controls (stress MBF: 2.87±0.93 vs. 4.79±1.16 mL/g/min, p=0.003; CFR: 2.6±0.73 vs. 4.66±1.38, p=0.004; MVR: 40.14±18.76 vs. 20.47±6.24 mmHg/mL/min, p=0.02). Supplementation therapy with LT4 normalized TSH in all subjects and was associated with an increase in CFR (2.6±0.73 vs. 3.81±1.19, p=0.003) and with a tendency toward a decrease in MVR. Differences in CFR between SCH and controls were also seen after correction of resting MBF for RPP. CONCLUSIONS In asymptomatic subjects with SCH due to thyroid autoimmunity, coronary microvascular function is impaired and improves after supplementation with LT4. This may partially explain the increased cardiovascular risk attributed to SCH.

Comparison of three different purification methods for the routine preparation of [11C] Metomidate

PET with (R)-[O-methyl-11C] metomidate ([11C] MTO) is an attractive method for the characterisation of adrenal masses discriminating lesions of adrenal cortical origin from noncortical lesions. [11C] MTO was prepared by the reaction of [11C] methyliodide with the corresponding free acid. Three purification methods have been compared. The method of choice uses preparative HPLC with a ready-to-use weak acidic solvent.

Diencephalic Serotonin Transporter Availability Predicts Both Transporter Occupancy and Treatment Response to Sertraline in Obsessive-Compulsive Checkers

BACKGROUND To our knowledge, no studies have investigated the predictive value of central serotonin transporter (SERT) availability for treatment response to serotonin reuptake inhibitors (SSRIs) in patients with obsessive-compulsive disorder (OCD). This study used brain imaging to examine the relationship between pretreatment SERT availability and transporter occupancy as well as treatment response by sertraline in patients displaying prominent behavioral checking compulsions (OC checkers). METHODS Single photon emission computed tomography (SPECT) was used to measure thalamic-hypothalamic SERT availability with [(123)I]-2beta-carbomethoxy-3beta-(4-iodophenyl)-tropane in 28 nondepressed OC checkers at baseline and after 14 weeks of treatment with sertraline (175 mg daily). SERT availability was correlated with OC severity and treatment response as assessed with the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS). Associations between individual transporter occupancies and clinical parameters were investigated. RESULTS 1) Correlation analyses between thalamic-hypothalamic SERT availability and OC severity showed significant negative associations at baseline and after treatment with sertraline. 2) Pretreatment SERT availability correlated significantly with both transporter occupancy and treatment response; in addition, a positive association was found between transporter occupancy and treatment response directly. 3) Using multivariate statistical models, the data demonstrated that higher pretreatment SERT availability significantly predicted higher occupancy rates as well as better treatment response 14 weeks later. CONCLUSIONS Higher pretreatment thalamic-hypothalamic SERT availability may predict both higher occupancy rates and better treatment response to sertraline. The data suggest a strong connection between transporter occupancy and treatment response.