Potentiometric measurement of urinary iodine concentration in patients with thyroid diseases with and without previous exposure to non-radioactive iodine.

BACKGROUND: Extensive application of measurement of urinary iodine concentration (UIC) in several benign and malignant thyroid diseases could profit by the availability of rapid and inexpensive measuring techniques. Aim of this study was to apply a simple and inexpensive commercially available potentiometric method for the quantification of UIC based on iodine-specific ion-selective electrodes (ISE) in patients with thyroid diseases. METHODS: This retrospective study included patients with differentiated thyroid cancer (n=286) and patients with hyperthyroidism of different etiologies (n=203). Within the whole sample (n=489) 20 patients had previously (1 week-6 months) been exposed to iodine overload, either from contrast media (n=8) or amiodarone (n=12). RESULTS: In patients not exposed to iodine, the histogram showed that the distribution of UIC violated normality. The peak of the curve occurred between 5.0 µmol/L and 6.0 µmol/L. Variability was sizeable (percent coefficient of variation, %CV: 66%, 95% confidence interval: 1.48-18.72 µmol/L). The group of exposed patients could be easily distinguished from not exposed patients (median UIC: 47.5 µmol/L vs. 5.42 µmol/L). UIC was significantly correlated to urinary creatinine concentration, but normalization to urinary creatinine increased the inter-subject variability of UIC (%CV=96% vs. 66%). In test-retest studies (n=25) the intra-class correlation coefficient was 0.73 for UIC, 0.82 for creatinine and 0.64 for the UIC: creatinine ratio. CONCLUSIONS: Iodine-specific ISE-based potentiometric methods can be successfully applied as an alternative to existing methods in patients with thyroid diseases. The promising characteristics of the method need to be confirmed in future larger prospective studies.

Prognostic value of stress-gated 99m-technetium SPECT myocardial perfusion imaging: risk stratification of patients with multivessel coronary artery disease and prior coronary revascularization.

BACKGROUND: This study assessed the prognostic value of stress-gated 99mTc-sestamibi myocardial perfusion SPECT (MPS) in patients with multivessel coronary artery disease (CAD) and prior revascularization according to the presence and severity of ischemia. METHODS AND RESULTS: We studied the outcome of 472 patients with multivessel CAD and prior revascularization (coronary angioplasty, 290 patients; bypass surgery, 182 patients), who underwent exercise or dipyridamole 99mTc-sestamibi MPS for evaluation of ischemia. Visual scoring of perfusion images used 20 segments and a 5-point scale. Gated post-stress EF was automatically calculated. Endpoints included hard events: cardiac death (CD) and nonfatal myocardial infarction (MI). During a mean follow-up of 3.0 ± 1.0 years, 37 hard events occurred, including CD in 15 (3%) and MI in 22 (5%) patients. In a risk-adjusted multivariable Cox model, a history of prior MI, diabetes, abnormal MPS, moderate-to-severe ischemia, and post-stress EF <35% were important predictors of cardiac events. Four-year risk-adjusted survival was 97.9% for normal MPS, 87.3% for abnormal MPS with ischemia, and 82.1% for moderate-to-severe ischemia. CONCLUSIONS: Among patients with previous coronary revascularization, stress-gated 99mTc-sestamibi MPS provides prognostic information for the prediction of cardiac events. A normal perfusion scan confers an excellent prognosis and an exceedingly low hard event rate (<1%/year). The presence of moderate-to-severe ischemia or a post-stress EF <35% identifies patients at highest risk of subsequent cardiac events.

Poorly differentiated thyroid carcinomas: how much poorly differentiated is needed?

BACKGROUND: Poorly differentiated (PD) carcinomas of the thyroid are conceptually situated between well-differentiated (papillary or follicular) carcinomas and anaplastic thyroid carcinomas. Although the morphologic criteria for PD tumors are well defined, it is not clear how much of a PD area besides a well-differentiated component in a given tumor is required to allow such a diagnosis. METHODS: We identified 42 patients suffering from thyroid carcinoma with an adverse clinical outcome. Fifty patients with follicular carcinoma were added as controls. We analyzed poorly differentiated areas by applying the Turin criteria of PD carcinomas. These criteria consisted of the presence of a solid/trabecular/insular growth pattern, lack of nuclear features of papillary carcinoma, and presence of 1 of the following features: (1) convoluted nuclei, (2) tumor necrosis, (3) 3 or more mitoses per 10 high-power fields. RESULTS: Using a cutoff value of 10% of PD areas per examined tumor surface, we identified a total of 35 PD carcinomas. Despite using a threshold of 10% of the tumor area as poorly differentiated, the survival data in a Kaplan-Meier analysis were significantly worse than those in the control group (P<0.001) and did not differ from tumors with a PD area >50%. In a multivariate analysis that included age, sex, tumor stage, and PD area >10% against survival data, the only consistent significant factor was PD differentiation (P<0.001). CONCLUSIONS: As even slight amounts of PD areas (≥ 10%) in a thyroid carcinoma affect the prognosis significantly, the presence of such areas may be worth reporting in thyroid carcinomas.

[Differentiated thyroid carcinoma--essential for the practitioner]. / Das differenzierte Schilddrüsenkarzinom--das Wichtigste für die Praxis.

Differentiated thyroid carcinoma (DCT) is a rare carcinoma (incidence 8-12/100,000) with an excellent prognosis (five year survival of papillary thyroid carcinoma 95%). The presenting symptom of DCT is most frequently an indolent thyroid nodule, often discovered by chance at the occasion of a routine clinical examination. Rarely, DCT presents with a fixed ipsilateral cervical lymph node enlargement or a newly developed hoarseness of the voice. Patients at risk are those who have had irradiation of the head or neck, those with rapid enlargement of a thyroid nodule or patients with rare familiar tumour syndromes. Treatment is most frequently accomplished with total thyroidectomy followed by radioiodine ablation with or without suppressive levothyroxine therapy. In special situations, several radioiodine therapies are needed. All patients need regular long term follow up by neck sonography, measurements of thyroglobuline levels and control of thyroid hormone replacement therapy. DCT may relapse many years (>10) after initial therapy. Patients should ideally be followed by specialized interdisclipinary centres.

Exacerbation of erythropoietic protoporphyria by hyperthyroidism.

Erythropoietic protoporphyria (EPP) is a hereditary disorder caused by deficiency of ferrochelatase, the last enzyme in the heme biosynthetic pathway. The majority of EPP patients present with a clinical symptom of painful phototoxicity. Liver damage, the most serious complication of EPP, occurs in <5% of the patients. This report describes a case of an EPP patient who complained of worsening cutaneous symptoms, nervousness, and insomnia. Laboratory tests showed highly increased protoporphyrin concentration in erythrocytes and elevated serum transaminases that are indicative of EPP-related liver damage. The subsequent finding of decreased serum thyroid-stimulating hormone (TSH) and increased free triiodothyronine (FT3) and free thyroxine (FT4) concentrations, as well antibodies against both thyroid peroxidase (TPO) and TSH receptors, led to the diagnosis of Graves' disease. The patient received 500 MBq of radioiodine (I(131)). Three months after the radioactive iodine therapy, the thyroid volume was reduced to 30% of pretherapeutic volume. Although the patient was slightly hypothyroidic, his liver enzymes returned to normal, his erythrocytic protoporphyrin concentration dropped fivefold, and his skin symptoms improved dramatically. The coexistence of Graves' disease and EPP is a statistically rare event as, besides our patient, there was one additional case reported in the literature. Although the exact mechanism whereby Graves' disease interacts with EPP is yet to be explored, we recommend testing thyroid function in EPP patients with liver complication to exclude hyperthyroidism as a potential cause.

Tumor response and clinical benefit in neuroendocrine tumors after 7.4 GBq (90)Y-DOTATOC.

UNLABELLED: The aim of this prospective phase II study was to evaluate the tumor response of neuroendocrine tumors to high-dose targeted irradiation with 7.4 GBq/m(2) of the radiolabeled somatostatin analog (90)Y-1,4,7,10-tetra-azacyclododecan-4,7,10-tricarboxy-methyl-1-yl-acetyl-D-Phe-Tyr(3)-octreotide (DOTATOC). In addition, we investigated the clinical benefit of (90)Y-DOTATOC regarding the malignant carcinoid syndrome and tumor-associated pain. METHODS: Thirty-nine patients (mean age, 55 y) with progressive neuroendocrine gastroenteropancreatic and bronchial tumors were included. The treatment consisted of 4 equal intravenous injections of a total of 7.4 GBq/m(2) (90)Y-DOTATOC, administered at intervals of 6 wk. After each treatment cycle, a standardized clinical benefit assessment using the National Cancer Institute grading criteria (NCI-CTC) was performed. RESULTS: The objective response rate according to World Health Organization (WHO) criteria was 23%. For endocrine pancreatic tumors (13 patients), the objective response rate was 38%. Complete remissions were found in 5% (2/39), partial remissions in 18% (7/39), stable disease in 69% (27/39), and progressive disease in 8% (3/39). A significant reduction of clinical symptoms could be found in 83% of patients with diarrhea, in 46% of patients with flush, in 63% of patients with wheezing, and in 75% of patients with pellagra. The overall clinical benefit was 63%. All responses (both clinical benefit and WHO response) were ongoing for the duration of follow-up (median, 6 mo; range, 2-12 mo). Side effects were grade 3 or 4 (NCI-CTC) lymphocytopenia in 23%, grade 3 anemia in 3%, and grade 2 renal insufficiency in 3%. CONCLUSION: High-dose targeted radiotherapy with 7.4 GBq/m(2) (90)Y-DOTATOC is a well-tolerated treatment for neuroendocrine tumors, with remarkable clinical benefit and objective response.