The relationship between 25 hydroxy Vitamin D3 and thyroid antibodies with thyroid benign-malign neoplasms.

OBJECTIVE: To study the relationship between vitamin D and thyroid antibodies with thyroid benign-malign neoplasms. MATERIALS AND METHODS: The vitamin D vitamin and thyroid antibodies of 179 patients who underwent thyroidectomy for thyroid nodule were retrospectively reviewed. RESULTS: The mean age of the patients was 44.97 ± 14.139. Vitamin D levels were 14.473 ± 4.9999 ng/ml in women and 19.584 ± 6.1981 ng/ml in men and the mean was 15.016 ± 5.3579 ng/ml. There was a significant relationship between sex and vitamin D level (P < 0, 05). Antithyroglobulin antibody (anti-TGB) had been detected in 95 patients and Antithyroid peroxidase antibody (anti TPO) in 58 patients. There was no significant relationship between vitamin D levels (P: 0, 65), anti-TPO positivity (P: 0, 86), and anti-TGB (P: 0, 12) with benign-malignant neoplasm of thyroid. There was no relationship between vitamin D and metastatic disease (P: 0, 30) as well. In addition, no association was found between malignancy and metastasis (P = 0.068, P = 0.14, P: 0, P = 0, respectively) with thyroid antibody positivity (anti TPO and/or anti TGB) in severe deficiency (<10 ng/ml) and deficiency (<20 ng/ml) of vitamin D. CONCLUSION: Vitamin D deficiency or thyroid autoantibodies did not have any significant effect on thyroid malignancies or metastatic disease separately or together.

Be Aware of the Patient With Benign Follicular Thyroid Lesion Histology and Rising Thyroglobulin Level.

OBJECTIVE: The accurate diagnosis of thyroid follicular/Hürthle cell tumors is challenging and a matter of controversy. We present a series of patients in whom a misclassification of follicular/Hürthle cell thyroid lesions as benign has led to devastating clinical outcomes. METHODS: The Thyroid Cancer Registry of Rabin Medical Center was screened for patients with metastatic differentiated thyroid carcinoma (DTC) who had been initially diagnosed with benign follicular lesion between 1974 and 2015 and treated with hemithyroidectomy. Clinical, pathologic, and outcome data were collected from the medical files. Adequate pathology specimens, when available, were re-evaluated. RESULTS: Seven patients met the inclusion criteria. The original pathologic diagnosis was follicular adenoma in 4 patients and Hürthle cell adenoma in 3 patients. Five patients had bone metastases, of whom one also had lung metastases and one, liver metastases. One patient had both cervical and lung metastases, and 1 patient had only meta-static neck lymph nodes. Six patients had a final diagnosis of encapsulated follicular variant of papillary thyroid carcinoma (EFVPTC), and 1 patient was diagnosed as having follicular thyroid cancer metastasis by bone biopsy. In 3 of the patients, capsular invasion was detected retrospectively; only 1 patient had evidence of vascular invasion. All 7 patients had high levels of thyroglobulin at diagnosis of metastatic DTC. CONCLUSION: Misclassification of follicular thyroid lesions as benign may lead to progressive disseminated DTC. To minimize the clinical risk of misdiagnosis, especially if a thorough evaluation of the specimens by an experienced pathologist is unfeasible, we suggest long-term follow-up of serum thyroglobulin levels. ABBREVIATIONS: DTC = differentiated thyroid carcinoma; EFVPTC = encapsulated follicular variant of papillary thyroid carcinoma; FVPTC = follicular variant of papillary thyroid carcinoma; NIFTP = noninvasive follicular thyroid neoplasm with papillary-like nuclear features; PTC = papillary thyroid carcinoma.

IS MEASUREMENT OF CIRCULATING TUMOR DNA OF DIAGNOSTIC USE IN PATIENTS WITH THYROID NODULES?

OBJECTIVE: Circulating tumor DNA (ctDNA), a subset of cell-free DNA (cfDNA), is a potential biomarker for thyroid cancer. We determined the performance of a ctDNA panel for detecting thyroid malignancy in patients with thyroid nodules. METHODS: Sixty-six patients with thyroid nodules without a prior history of cancer enrolled in a prospective, 1-year study in which blood was drawn for ctDNA analysis prior to undergoing fine-needle aspiration biopsy (FNAB) of thyroid nodules. The ctDNA panel consisted of 96-mutations in 9 cancer driver genes. The primary outcome measures were the sensitivity, specificity, and positive and negative predictive values (PPV, NPV) of our ctDNA panel for the diagnosis of thyroid malignancy as determined by pathologic and/or molecular tissue examination. RESULTS: Results from 10 subjects could not be determined due to inadequate volume or technical issues. The final classifications of the thyroid nodules were 13 malignant and 43 benign lesions. A KRAS G12V mutation was detected in the plasma of 1 patient with stage IVA papillary carcinoma whose tissue contained the same mutation. Two of the 43 patients with benign lesions also had ctDNA detected, giving a sensitivity of 7.7%, specificity of 95.35%, PPV of 33.33%, and NPV of 77.35%. There were no significant differences between benign or malignant lesions in cfDNA levels. CONCLUSION: Neither cfDNA measurements nor our panel of ctDNA mutations are sensitive or specific enough to provide valuable information over FNAB. An expanded panel and the inclusion of proteomics may improve sensitivity and specificity for thyroid cancer detection. ABBREVIATIONS: cfDNA = cell-free DNA; ctDNA = circulating tumor DNA; FNAB = fine-needle aspiration biopsy; NIFTP = noninvasive follicular thyroid neoplasm with papillary-like nuclear features.

Partial Nephrectomy for Presumed Renal-Cell Carcinoma: Incidence, Predictors, and Perioperative Outcomes of Benign Lesions.

BACKGROUND: The aim of this study was to investigate the incidence of benign histology after partial nephrectomy (PN) in patients with presumed malignancy from preoperative imaging. Furthermore, preoperative predictors of benign lesions and perioperative outcomes were also assessed. METHODS: A series of patients undergoing PN for renal masses was identified using a prospectively maintained database. Patients were excluded for known genetic conditions, if more than one renal mass was resected, or if standard preoperative imaging was not suspicious for renal-cell carcinoma (RCC). Differences in characteristics between patients with benign and malignant pathology were assessed. RESULTS: A total of 916 patients were identified who underwent PN between 2007 and 2015, including 129 (14.1%) patients with a final diagnosis of benign disease. The most common types of benign pathology were oncocytoma (n = 66, 51.2%), angiomyolipoma (n = 37, 28.7%), and complex cysts (n = 10, 7.8%). Low body mass index (BMI) [0.96 (0.92-0.99) p = 0.02], low R.E.N.A.L. score [0.86 (0.76-0.96) p = 0.007], and low preoperative creatinine [0.37 (0.14-0.91) p = 0.04] predicted benign histology in multivariate analysis. Tumor size was a significant predictor in additional modeling [0.81 (0.69-0.94) p = 0.008]. Patients with benign histology had significantly shorter operative times (p < 0.001) and less estimated blood loss (p < 0.001), and there was no difference in complication (p = 0.93) or blood transfusion (0.24) rates. CONCLUSIONS: In this study, the rate of benign pathology after PN for presumed RCC is 14.1%. BMI, R.E.N.A.L. score, and preoperative creatinine are predictive of benign histology, but the ability of different variables to predict benign lesions may be influenced by the distribution of benign tumor subtypes, reflecting potential unidentified selection bias.

Analysis of malignancy predictors for oxyphile thyroid tumors.

PURPOSE: In contrast to other thyroid carcinomas it is difficult to establish a correct preoperative diagnosis for oxyphile carcinoma of the thyroid. In this study we looked for predictive malignancy factors in order to enable surgeons to choose operative treatment and to perform an adequate operation for each patient with an oxyphile neoplasm of the thyroid. METHODS: In this retrospective study we have analyzed the medical files of all patients with oxyphile tumors of the thyroid operated between 1999 and 2008 in our institution. A total of 256 patients were included and divided into oxyphile adenomas (142) and carcinomas (114) on the basis of their definite histopathological diagnosis. The most important demographic and clinical characteristics were analyzed by univariate and multivariate logistic regression analysis. RESULTS: Univariate analysis showed that male gender, thyroglobulin concentrations ≥300 ng/ml and tumor diameter >30 mm were significantly more frequent in patients with oxyphile carcinoma compared to patients with oxyphile adenoma, while coexisting Hashimoto thyreoiditis and positive AntiTPO antibodies appeared significantly less frequent in the carcinoma group. All variables with a p value <0.1 in the univariate test were subjected to multivariate regression analysis in which elevated preoperative thyroglobulin concentrations (≥300 ng/ml) was shown as the only independent predictive factor for oxyphile thyroid carcinomas (OR=5.88, 95% CI 2.78-12.05, p=0.001). CONCLUSIONS: Preoperative thyroglobulin concentration is an independent predictor of malignancy for oxyphile thyroid carcinomas.

Higher body mass index and larger waist circumference may be predictors of thyroid carcinoma in patients with Hürthle-cell lesion/neoplasm fine-needle aspiration diagnosis.

OBJECTIVE: High body mass index (BMI) has been found to be associated with raised thyroid cancer risk, particularly in women. We examined the associations for BMI and waist circumference (WC) with thyroid cancer risk among women with Hürthle-cell lesion/neoplasm (HLN) on fine-needle aspiration biopsy (FNAB) with the hypothesis that BMI and WC could guide the management of these challenging indeterminate lesions. METHODS: This cross-sectional study included 224 women with HLN who underwent thyroidectomy. In all patients, TSH and thyroid auto-antibodies were evaluated, and thyroid nodule features were recorded. Patients were grouped according to BMI (<30 or ≥30 kg/m(2)) and WC (<88 or ≥88 cm). Relationships of thyroid cancer with BMI and WC were assessed using logistic regression analysis. RESULTS: Mean weight, BMI (31·26 ± 5·1 vs 26·47 ± 5·9, P < 0·001), WC (98·23 ± 7·6 vs 86·18 ± 11, P = 0·001), and proportion of patients with high BMI (≥30 kg/m(2)) (65·9 vs 33·8%, P < 0·001) or large WC (≥88 cm) (84·1 vs 47·9%, P < 0·001) were significantly higher in malignant group compared to benign group. In regression analysis, BMI and WC significantly associated with existence of malignancy. Malignancy risk was 3·819-fold higher (95% CI: 2·068-7·054) in BMI≥30 kg/m(2) group compared to BMI<30 kg/m(2), which was independent of TSH and age. Large WC was also associated with increased risk (OR = 5·593, 95% CI: 2·736-11·434). Baseline tumour characteristics were similar according to BMI and WC groups. CONCLUSIONS: A great BMI and large WC were associated with higher thyroid cancer risk in patients with FNAB diagnosis of HLN. Further studies are needed to use BMI or WC in the management of patients with HLN.

Serum thyroglobulin (Tg) monitoring of patients with differentiated thyroid cancer using sensitive (second-generation) immunometric assays can be disrupted by false-negative and false-positive serum thyroglobulin autoantibody misclassifications.

CONTEXT: Reliable thyroglobulin (Tg) autoantibody (TgAb) detection before Tg testing for differentiated thyroid cancer (DTC) is critical when TgAb status (positive/negative) is used to authenticate sensitive second-generation immunometric assay ((2G)IMA) measurements as free from TgAb interference and when reflexing "TgAb-positive" sera to TgAb-resistant, but less sensitive, Tg methodologies (radioimmunoassay [RIA] or liquid chromatography-tandem mass spectrometry [LC-MS/MS]). OBJECTIVE: The purpose of this study was to assess how different Kronus (K) vs Roche (R) TgAb method cutoffs for "positivity" influence false-negative vs false-positive serum TgAb misclassifications that may reduce the clinical utility of reflex Tg testing. METHODS: Serum Tg(2G)IMA, TgRIA, and TgLC-MS/MS measurements for 52 TgAb-positive and 37 TgAb-negative patients with persistent/recurrent DTC were compared. A total of 1426 DTC sera with TgRIA of ≥ 1.0 µg/L had false-negative and false-positive TgAb frequencies determined using low Tg(2G)IMA/TgRIA ratios (<75%) to indicate TgAb interference. RESULTS: TgAb-negative patients with disease displayed Tg(2G)IMA, TgRIA, and TgLC-MS/MS serum discordances (% coefficient of variation = 24 ± 20%, range, 0%-100%). Of the TgAb-positive patients with disease, 98% had undetectable/lower Tg(2G)IMA vs either TgRIA or TgLC-MS/MS (P < .01), whereas 8 of 52 (15%) had undetectable Tg(2G)IMA + TgLC-MS/MS associated with TgRIA of ≥ 1.0 µg/L. Receiver operating characteristic curve analysis reported more sensitivity for TgAb method K vs R (81.9% vs 69.1%, P < .001), but receiver operating characteristic curve cutoffs (>0.6 kIU/L [K] vs >40 kIU/L [R]) had unacceptably high false-negative frequencies (22%-32%), whereas false positives approximated 12%. Functional sensitivity cutoffs minimized false negatives (13.5% [K] vs 21.3% [R], P < .01) and severe interferences (Tg(2G)IMA, <0.10 µg/L) (0.7% [K] vs 2.4% [R], P < .05) but false positives approximated 23%. CONCLUSIONS: Reliable detection of interfering TgAbs is method and cutoff dependent. No cutoff eliminated both false-negative and false-positive TgAb misclassifications. Functional sensitivity cutoffs were optimal for minimizing false negatives but have inherent imprecision (20% coefficient of variation) that, exacerbated by TgAb biologic variability during DTC monitoring, could cause TgAb status to fluctuate for patients with low TgAb concentrations, prompting unnecessary Tg method changes and disrupting Tg monitoring. Laboratories using reflexing should limit Tg method changes by considering a patient's Tg + TgAb testing history in addition to current TgAb status before Tg method selection.

Persistent fever and weight loss due to an interleukin-6-producing adrenocortical oncocytoma in a girl--review of the literature.

UNLABELLED: Adrenocortical oncocytomas are rarely reported, occur almost exclusively in adults, and are mostly nonfunctional. Here, we report an interleukin-6 (IL-6)-producing adrenocortical oncocytoma in an 11-year-old girl presenting with fever, body weight loss, and increased levels of inflammatory markers and serum IL-6. Imaging studies revealed a 4-cm mass in the left adrenal gland. After complete resection, laboratory findings returned to normal. Histology was consistent with adrenocortical oncocytoma, and the tumor cells stained positive for IL-6. CONCLUSION: IL-6-producing adrenocortical oncocytoma should be included in the differential diagnosis and imaging studies should be performed in patients presenting with persistent fever of unknown origin and high levels of inflammatory markers.

Matrix metalloproteinase-2 and -9 in the sera and in the urine of human oncocytoma and renal cell carcinoma.

Matrix metalloproteinases (MMPs) are a family of zinc-dependent endopeptidases, capable of degrading all the molecular components of extracellular matrix. MMPs have been shown to play critical roles in tumor cell invasion and metastasis. We verified the activity of MMPs in the sera and in the urine of patients with kidney carcinoma by gelatin zymography. Of these patients, 16 had clear cell renal carcinoma (ccRCC) and 4 patients had oncocytoma. The sera and the urine of 16 healthy subjects were used as controls. In the sera, zymography analysis showed gelatinolytic bands at 72 kDa (gelatinase A) at 92, 130 and 240 kDa (gelatinase B). MMP-9 activity was slightly enhanced in sera from ccRCC compared with oncocytoma patients. Serum MMP-2 activity was similar in ccRCC and in oncocytoma patients. In the urine, 2 oncocytoma patients and 3 (33%) of the ccRCC patients showed gelatinolytic activity, whereas MMPs could not be detected in the concentrated urine of healthy subjects. The most abundant lytic activity was at 92 kDa, whereas MMP-2 was present in lesser quantities. However, there was broad overlap of the data and we did not find any correlation to type, stage or grade. Therefore, despite previous evidence, MMP-2 and -9 activity in serum and urine may not be useful biomarker for kidney carcinomas.

Serum thyroglobulin is a poor diagnostic biomarker of malignancy in follicular and Hurthle-cell neoplasms of the thyroid.

BACKGROUND: Serum thyroglobulin (Tg) is the most accurate biomarker for thyroid cancer recurrence. However, some clinicians measure preoperative Tg as a diagnostic cancer marker despite lack of supporting evidence. We examined whether Tg accurately predicts malignancy in follicular or Hürthle-cell neoplasms. METHODS: We reviewed 366 patients who underwent thyroidectomies for follicular/Hürthle-cell neoplasms. We compared Tg in malignant versus benign tumors by univariate and receiver-operator characteristic analyses. We also examined several Tg-derived indices that normalized Tg to known confounding factors including nodule size, thyroid function, and type of Tg assay. RESULTS: Thirty-nine patients met inclusion criteria for analysis. There were no differences between malignant (n = 16) and benign (n = 23) lesions in Tg or any of the normalized indexes. Receiver-operator characteristic analysis revealed an area under the curve of .59. Lesions with Tg levels greater than 500 mug/L had a positive predictive value of .75. CONCLUSIONS: Tg has poor accuracy for predicting malignancy in follicular or Hürthle-cell thyroid neoplasms.

Clinical usefulness of positron emission tomography-computed tomography in recurrent thyroid carcinoma.

OBJECTIVES: To determine the efficacy of combined positron emission tomography-computed tomography (PET-CT) in identifying recurrent thyroid cancer and to elucidate its role in the clinical management of thyroid carcinoma. DESIGN: Retrospective study. SETTING: Tertiary care referral academic center. PATIENTS: One hundred twenty-four patients with previously treated thyroid carcinoma who underwent PET-CT. MAIN OUTCOME MEASURES: PET-CT images were correlated with clinicopathologic information. The influence of PET-CT findings on disease status determination and the treatment plan was evaluated. RESULTS: Among 121 patients undergoing iodine I 131 ((131)I) imaging (an (131)I image was unavailable for 3 patients), 80.6% had negative findings on (131)I imaging before undergoing PET-CT. Among 75 patients who had positive findings on PET-CT, 71 were true positive results. Among 49 patients who had negative findings on PET-CT, 32 were true negative results. Therefore, PET-CT demonstrated a sensitivity of 80.7%, specificity of 88.9%, positive predictive value of 94.7%, and negative predictive value of 65.3%. A significant difference was noted in the mean serum thyroglobulin levels between patients with positive vs negative PET-CT findings (192.1 vs 15.0 ng/mL, P = .01) (to convert thyroglobulin level to micrograms per liter, multiply by 1.0). Overall, distant metastases were detected in 20.2% of patients using PET-CT. There was an alteration of the treatment plan in 28.2% of patients as a result of added PET-CT information, and 21.0% of patients underwent additional surgery. CONCLUSIONS: PET-CT is usually performed in patients with thyroid cancer having elevated thyroglobulin levels but non-(131)I-avid tumors and has high diagnostic accuracy for identifying local, regional, and distant metastases. Additional information from PET-CT in patients with (131)I-negative and thyroglobulin-positive tumors frequently guides the clinical management of recurrent thyroid carcinoma.

Effectiveness of peripheral thyrotropin receptor mRNA in follow-up of differentiated thyroid cancer.

Thyroid cells in peripheral circulation have been linked to thyroid cancer (TC). These cells express thyrotropin receptor (TSHR) messenger RNA (mRNA), which has been studied as a marker of initial TC diagnosis. We examined the utility of TSHR mRNA in long-term follow-up of TC patients. From 2002 to 2007, TSHR mRNA was prospectively measured by quantitative reverse-transcription polymerase chain reaction (RT-PCR) from peripheral blood samples in 259 patients, and those followed > or =3 months since initial thyroidectomy were studied. TSHR mRNA levels were correlated to thyroglobulin (Tg), imaging studies, and disease status during follow-up. Thirty-four patients underwent 20 +/- 14 months median follow-up for papillary (n = 31, 91%), follicular (n = 2) or Hurthle cell (n = 1) TC. Advanced-stage disease occurred in 24% at presentation, and 11 (32%) developed cervical node metastases or recurrence requiring reoperation during follow-up. Of 52 simultaneous TSHR mRNA and serum Tg measurements, 52% were concordant. TSHR mRNA missed disease in 21% patients, but was better than Tg in 27%, including all those with Tg antibodies. TSHR mRNA concurred with whole-body scan detectable disease for 11/14 patients (79%) and accurately predicted overall TC disease status in 77% patients. In discordant cases, TC recurrence was apparent from other imaging modalities [positron emission tomography (PET) scan or ultrasound]. TSHR mRNA in conjunction with Tg diagnosed TC recurrence with 90% sensitivity and 94% specificity. We conclude that TSHR mRNA demonstrates high concordance rates with present methods of detecting TC recurrence, and appears to be more accurate in patients with Tg antibodies. As a novel adjunct, TSHR mRNA may enhance long-term management of TC patients.

Preoperative undetectable serum thyroglobulin in differentiated thyroid carcinoma: incidence, causes and management strategy.

BACKGROUND: In recent years serum thyroglobulin (Tg) measurement during thyroxine (T4) treatment and/or after stimulation by endogenous TSH or recombinant human TSH (rhTSH) has eclipsed other diagnostic procedures in managing patients with differentiated thyroid cancer (DTC). However, preoperative undetectable Tg was reported in up to 12% of patients affected by DTC and recurrences of DTC with no increase in serum Tg have also been described. Clearly, a negative Tg measurement may falsely reassure both the patient and the clinician in these cases. AIM: We retrospectively evaluated the incidence of undetectable or reduced preoperative serum Tg in a group of 436 patients affected by DTC. Additionally, we evaluated the role of Tg retesting by two different immunoassays in patients with low Tg at first measurement. METHODS: We retrospectively selected 17 patients with undetectable (i.e. less than functional sensitivity of assay method) or reduced Tg (i.e. between functional sensitivity and minimum normal value) among 436 patients with histologically proved DTC. The remaining 419 patients were used as control cases. Frozen sera from all patients were retested by two different Tg immunoassays. RESULTS: Globally, 17 out of 436 (3.8%) patients showed undetectable (n = 5, 1.1%) or reduced (n = 12, 2.7%) preoperative Tg. The Tg level was above the minimum normal value in 3 and 4 out of 5, and 8 and 9 out of 12 of these patients, respectively, when two different immunoassays were employed. On the other hand, undetectable or reduced Tg levels were found in 3.0%-5.1% of control cases when different immunoassays were used. CONCLUSIONS: Regardless of the method employed, 3.0-5.1% of patients with DTC showed undetectable or reduced preoperative Tg. This fact must be recognized, as Tg cannot be used as a benchmark for DTC follow-up in these cases. However, Tg retesting with different immunoassays seems to be useful in ruling out these pitfalls in a large majority of patients, and also indicates the most effective assay to be employed in these cases.

Detection of carbonic anhydrase-9 gene expression in peripheral blood cells predicts risk of disease recurrence in patients with renal cortical tumors.

OBJECTIVES: To present extended follow-up on a cohort of patients with renal cortical tumors treated with partial or radical nephrectomy and preoperatively assess for carbonic anhydrase 9 tumor marker expression in the peripheral blood. METHODS: All patients were originally enrolled in an institutional review board-approved study assessing the role of a reverse-transcriptase polymerase chain reaction peripheral blood assay designed to detect the tumor-specific gene carbonic anhydrase-9 (CA9). A total of 41 patients with renal cortical tumors confined to the kidney were enrolled at a single institution and assessed preoperatively with peripheral blood test for CA9 expression before undergoing partial or radical nephrectomy. A Kaplan-Meier estimated survival analysis and log-rank test were performed to determine whether detection of peripheral blood cells expressing the CA9 gene influences disease-free and disease-specific survival. RESULTS: The median follow-up was 4.3 years. The median age was 71 years. Of the 41 patients, 26 were men and 15 were women. The estimated 5-year disease-free survival for patients with detectible expression of the CA9 gene in the peripheral blood was 39.5% compared with 88.1% for patients without detection of the CA9 gene (P = 0.048). On bivariate analysis, disease-free survival correlated with histologic type, tumor diameter, and tumor grade. CONCLUSIONS: The expression of the tumor-specific marker CA9 in the peripheral blood is associated with decreased disease-free survival in patients with renal cortical tumors. This is the first study reporting on the prognostic value of this peripheral blood-based tumor marker for kidney tumors.

Staging and treatment of differentiated thyroid carcinoma with radiolabeled somatostatin analogs.

In patients with progressive metastatic (or recurrent) differentiated thyroid carcinoma that either do not take up radioiodine or are unresponsive to continued radioiodine therapy, staging is difficult and treatment options are few. However, in most of these patients uptake of radiolabeled somatostatin analogs is evident on somatostatin-receptor scintigraphy (SRS). Using SRS, patients with sufficient uptake of radiolabeled somatostatin analogs can be selected for high-dose peptide receptor radionuclide therapy (PRRT) as an alternative targeted-treatment option. PRRT with the beta-particle-emitting radionuclides (90)yttrium ((90)Y) and (177)lutetium ((177)Lu) gives the best results in terms of objective tumor response. Promising, novel, radiolabeled somatostatin analogs that have a broader receptor affinity profile and, thus, a potentially wider therapeutic range are being tested clinically.

Elevated basal calcitonin levels in a patient with a hurthle-cell carcinoma of the thyroid and neuroendocrine differentiation: report of a case.

A thyroid nodule with elevated plasma levels of calcitonin is usually suggestive of a medullary thyroid carcinoma (MTC); however, thyroid and extrathyroid conditions have been reported with elevated plasma calcitonin levels in the absence of MTC. We report the case of a patient with a thyroid nodule and an elevated basal plasma calcitonin level of 315 pg/ml (normal value <100 pg/ml) who underwent a left hemithyroidectomy. Interestingly, histopathological examination revealed a Hurthle-cell carcinoma with positive neuroendocrine (NE) markers such as calcitonin and synapthophysin, but not with chromogranin staining. Thus, we discuss the phenomenon of non-NE tumors showing positivity for NE markers.

Oxyphil parathyroid adenoma: a malignant presentation of a benign disease.

Functioning parathyroid adenomas of the oxyphil cell type are rare, and the clinical characteristics of patients with these tumors have not been well defined. We describe two cases of severe primary hyperparathyroidism (PHPT) caused by benign oxyphil parathyroid adenomas. The patients' clinical presentations mimicked parathyroid carcinoma. Both had very large tumors associated with marked elevations in PTH and serum calcium levels. Skeletal manifestations were also atypical for benign PHPT, with severe osteoporosis in one patient and osteitis fibrosa cystica in the other. These cases also highlight the remarkable capacity of the skeleton to recover after successful parathyroidectomy, previously reported in other forms of severe PHPT. Bone mineral density improved dramatically 1 yr after parathyroidectomy, with increases of 51% at the lumbar spine, 36% at the total hip, and 11% at the distal one third radius. Most of the increases occurred in the first postoperative months. Consistent with this early and accelerated skeletal response, markers of bone turnover were increased 2 months after surgery and normalized by 8 months postoperatively. In patients with PHPT who present with severe or atypical clinical features, oxyphil adenoma should be considered.

Factors influencing the basal and recombinant human thyrotropin-stimulated serum thyroglobulin in patients with metastatic thyroid carcinoma.

The serum thyroglobulin (Tg) level is the most sensitive marker for detecting residual thyroid carcinoma. We hypothesized that the basal and TSH-stimulated Tg levels in patients with metastatic thyroid carcinoma would reflect tumor volume, histological subtype, and location of metastatic lesions. A retrospective review of 417 thyroid cancer survivors undergoing evaluation for residual disease with the assistance of recombinant human TSH (rhTSH) was performed. In 169 patients with metastatic disease, we found that the basal Tg level directly correlated with the number of lesions, and that it was highest in patients with follicular and lowest in those with papillary thyroid carcinoma. The basal Tg level was highest in patients with bone metastases and lowest in those with cervical metastases. The fold increase in the serum Tg after rhTSH treatment was highest in papillary thyroid carcinoma and lowest in Hurthle cell carcinoma. The fold increase in Tg was not influenced by tumor volume or by the site of metastatic lesions. Multivariate analysis showed multiple interactions between factors, but did not identify one factor that significantly influenced basal Tg or fold increase. We conclude that the location and volume of metastases influence basal Tg, but not its responsiveness to rhTSH, whereas the histological type of carcinoma influences both basal Tg and responsiveness to rhTSH.

Sonography in the diagnosis of cervical recurrence in patients with differentiated thyroid carcinoma.

OBJECTIVE: To determine the sensitivity of thyroglobulin (Tg), iodine scanning, and sonography in the diagnosis of cervical recurrence of thyroid cancer. METHODS: This prospective study assessed 81 patients with cervical metastases or extrathyroid invasion at first appearance who underwent clinical examination, scanning, measurement of Tg after thyroxine withdrawal, and sonography about 8 months after thyroidectomy followed by radioiodine treatment. Only patients without distant metastases and without anti-Tg antibodies were included. RESULTS: Fifty patients showed persistence of the disease in the cervical region, with only 16% of them having had a suspicion on clinical examination, 33 with Tg levels of 2 ng/mL or greater (66% sensitivity), and 29 with positive scan findings (58% sensitivity). A combination of the 2 methods detected disease in 40 (80%) of 50 patients but failed to show 20% of cases that were identified by sonography and confirmed by fine-needle aspiration. Sonography had sensitivity of 96%. Specificity values for Tg, iodine scanning, and sonography were 80.6%, 90.3%, and 87%, respectively. CONCLUSIONS: Classic follow-up methods may not detect cervical disease in some patients with differentiated thyroid carcinoma, and sonography is necessary even in patients apparently free of the disease.

Outcome in patients with differentiated thyroid cancer with negative diagnostic whole-body scanning and detectable stimulated thyroglobulin.

BACKGROUND: Management of patients with differentiated thyroid carcinoma with negative diagnostic radioiodide scanning and increased serum thyroglobulin (Tg) concentrations is a widely debated problem. High-dose iodine-131 treatment of patients who have a negative (131)I diagnostic whole-body scan (WBS) is advocated. However, the therapeutic benefit of this "blind" treatment is not clear. OBJECTIVE: To investigate the course of serum Tg during thyroid hormone suppression therapy (Tg-on) and clinical outcome in patients with negative diagnostic (131)I scanning and increased serum Tg concentrations during thyroid hormone withdrawal (Tg-off), after treatment with high-dose (131)I. DESIGN: Retrospective single-center study. METHODS: Fifty-six patients were treated with a blind therapeutic dose of 150 mCi (131)I. Median follow-up from this treatment until the end of observation was 4.2 Years (range 0.5-13.5 Years). RESULTS: The post-treatment WBS revealed (131)I uptake in 28 patients, but none in the remaining 28 patients. In this study the Tg-on values did not change after treatment in either the positive or the negative post-treatment WBS group. During follow-up, 18 of the 28 patients with a positive post-treatment WBS achieved complete remission, compared with 10 of the 28 patients with a negative post-treatment WBS. Nine patients in the negative group died, but no patients died in the positive post-treatment group (P=0.001). CONCLUSIONS: High-dose iodine treatment in diagnostically negative patients who have a negative post-treatment scan seems to confer no additional value for tumor reduction and survival. In patients with a positive post-treatment scan, high-dose iodine treatment can be used as a diagnostic tool to identify tumor location, and a therapeutic effect may be present in individual cases.