Comparison of ultrasound-guided fine-needle aspiration biopsy with core-needle biopsy in the evaluation of thyroid nodules.

OBJECTIVE: To compare the diagnostic rate of ultra-sound-guided fine-needle aspiration biopsy (FNAB) with the diagnostic rate of combined FNAB and core-needle biopsy in the evaluation of nodular thyroid disease. METHODS: We performed a retrospective case-control study by reviewing charts of patients who underwent ultra-sound-guided FNAB and core-needle biopsy of the thyroid at a tertiary referral center from January 1999 to December 2001. Results were classified as diagnostic (negative, suspicious, or positive for malignancy) or nondiagnostic. These findings were compared with an age- and sex-matched control group who underwent only FNAB. Complications between the groups were reviewed. RESULTS: The patient group consisted of 320 patients who underwent 340 ultrasound-guided fine-needle aspiration and core-needle biopsies of the thyroid; the control group consisted of 311 patients who underwent 340 FNABs. There was no significant difference in the nondiagnostic rates between groups--12.9% in patients who had FNAB-only compared with 10.9% in patients who had both procedures (proportion difference, -2.1%; 95% confidence interval, -7.0% to 2.9%; P = .41). There was a trend towards an increased incidence of hematoma and infection in the core biopsy group. In the group that underwent FNAB and core-needle biopsies, 10 patients (3.1%) developed biopsy-specific complications (hematomas in 8 patients, biopsy site infections in 2 patients). In the FNAB-only group, 3 patients (1.0%) developed hematomas; there was no incidence of infection. CONCLUSIONS: In the evaluation of thyroid nodules, the addition of core-needle biopsies to FNAB confers little benefit in decreasing the nondiagnostic rates and may be associated with increased complications. Core-needle biopsies should not be routinely performed in the evaluation of thyroid nodules, but rather, patient selection for the more invasive core biopsy should be done judiciously.

Distribution and phylogenetic relationships of Australian glow-worms Arachnocampa (Diptera, Keroplatidae).

Glow-worms are bioluminescent fly larvae (Order Diptera, genus Arachnocampa) found only in Australia and New Zealand. Their core habitat is rainforest gullies and wet caves. Eight species are present in Australia; five of them have been recently described. The geographic distribution of species in Australia encompasses the montane regions of the eastern Australian coastline from the Wet Tropics region of northern Queensland to the cool temperate and montane rainforests of southern Australia and Tasmania. Phylogenetic trees based upon partial sequences of the mitochondrial genes cytochrome oxidase II and 16S mtDNA show that populations tend to be clustered into allopatric geographic groups showing overall concordance with the known species distributions. The deepest division is between the cool-adapted southern subgenus, Lucifera, and the more widespread subgenus, Campara. Lucifera comprises the sister groups, A. tasmaniensis, from Tasmania and the newly described species, A. buffaloensis, found in a high-altitude cave at Mt Buffalo in the Australian Alps in Victoria. The remaining Australian glow-worms in subgenus Campara are distributed in a swathe of geographic clusters that extend from the Wet Tropics in northern Queensland to the temperate forests of southern Victoria. Samples from caves and rainforests within any one geographic location tended to cluster together within a clade. We suggest that the morphological differences between hypogean (cave) and epigean (surface) glow-worm larvae are facultative adaptations to local microclimatic conditions rather than due to the presence of cryptic species in caves.

Image-guided radioiodide therapy of medullary thyroid cancer after carcinoembryonic antigen promoter-targeted sodium iodide symporter gene expression.

In contrast to follicular cell-derived thyroid cancer, medullary thyroid cancer (MTC) remains difficult to treat because of its unresponsiveness to radioiodine therapy, or to conventional chemo- and radiotherapy. We therefore examined the feasibility of radioiodine therapy of MTC after human sodium iodide symporter (hNIS) gene transfer, using the tumor-specific carcinoembryonic antigen (CEA) promoter for transcriptional targeting. NIS gene transfer was performed in vivo in human MTC cell (TT) xenografts, using adenoviral vectors carrying the NIS gene linked to the cytomegalovirus promoter (Ad5-CMV-NIS) or a CEA promoter fragment (Ad5-CEA-NIS). Functional NIS expression was confirmed by immunostaining as well as in vivo (123)I gamma-camera imaging followed by application of a therapeutic (131)I dose. TT cell xenografts in nude mice injected intratumorally with Ad5-CEA-NIS accumulated 7.5 +/- 1.2% ID/g (percentage injected dose per gram tumor tissue; 5 x 10(8) PFU) and 12 +/- 2.95% ID/g (1 x 10(9) PFU) with an average biological half-life of 6.1 +/- 0.8 and 23.6 +/- 3.7 hr, respectively, as compared with accumulation of 8.4 +/- 0.9% ID/g with a biological half-life of 12 +/- 8 hr after application of Ad5-CMV-NIS (5 x 10(8) PFU). After Ad5-CEA-NIS-mediated NIS gene transfer in TT cell xenografts administration of a therapeutic dose of 111 MBq (3 mCi) of (131)I resulted in a significant reduction of tumor growth associated with significantly lower calcitonin serum levels in treated mice as well as improved survival. We conclude that a therapeutic effect of (131)I was demonstrated in vivo in MTC cell xenografts after adenovirus-mediated induction of tumor-specific iodide accumulation by CEA promoter-directed hNIS expression.

Suppressibility of parathyroid hormone in primary hyperparathyroidism.

OBJECTIVE: To describe an unusual case of pathologically confirmed primary hyperparathyroidism in a patient presenting with severe hypercalcemia and an undetectable parathyroid hormone (PTH) level. METHODS: We present a detailed case report and outline the serial laboratory findings. In addition, the possible causes of low serum PTH levels in the setting of primary hyperparathyroidism are discussed. RESULTS: A 16-year-old female patient presented with severe epigastric pain, found to be attributable to acute pancreatitis. At hospital admission, her serum calcium concentration was high (14.0 mg/dL); the patient also had a normal serum phosphorus level of 3.6 mg/dL and an undetectable PTH level (<0.2 pmol/L). An evaluation for non-PTH-mediated causes of hypercalcemia revealed a partially suppressed thyroid-stimulating hormone concentration and a below normal 1,25-dihydroxyvitamin D level, consistent with her suppressed PTH. One week after the patient was dismissed from the hospital, repeated laboratory studies showed a serum calcium value of 11.1 mg/dL, a serum phosphorus level of 2.8 mg/dL, and an elevated PTH concentration of 11.0 pmol/L, consistent with primary hyperparathyroidism. A repeated 1,25-dihydroxyvitamin D measurement was elevated. A parathyroid scan showed a parathyroid adenoma in the left lower neck area, and she subsequently underwent successful surgical resection of a pathologically confirmed parathyroid adenoma. CONCLUSION: This case demonstrates that the serum PTH level can be suppressed in patients with primary hyperparathyroidism. Moreover, it emphasizes the need for careful evaluation of the clinical context in which the PTH measurement is determined. Consideration should be given to repeating measurement of PTH and serum calcium levels when the initial laboratory evaluation of hypercalcemia is unclear because dynamic changes in calcium metabolism may occur in the presence of secondary contributing factors.

A novel therapeutic strategy for medullary thyroid cancer based on radioiodine therapy following tissue-specific sodium iodide symporter gene expression.

CONTEXT: In contrast to papillary and follicular thyroid cancer, medullary thyroid cancer (MTC) remains difficult to treat due to its unresponsiveness to radioiodine therapy and its limited responsiveness to chemo- and radiotherapy. OBJECTIVE: To investigate an alternative therapeutic approach, we examined the feasibility of radioiodine therapy of MTC after human sodium iodide symporter (hNIS) gene transfer using the calcitonin promoter to target hNIS gene expression to MTC cells (TT). DESIGN: TT cells were stably transfected with an expression vector, in which hNIS cDNA was coupled to the calcitonin promoter. Functional hNIS expression was confirmed by iodide accumulation assays, Northern and Western blot analysis, immunostaining, and in vitro clonogenic assay. RESULTS: hNIS-transfected TT cells showed perchlorate-sensitive iodide uptake, accumulating 125-I about 12-fold in vitro with organification of 4% of accumulated iodide resulting in a significant decrease in iodide efflux. NIS protein expression was confirmed by Western blot analysis using a monoclonal hNIS-specific antibody, which revealed a major band of a molecular mass of 80-90 kDa. In addition, immunostaining of hNIS-transfected TT cells revealed hNIS-specific immunoreactivity, which was primarily membrane associated. In an in vitro clonogenic assay, 84% of NIS-transfected TT cells were killed by exposure to 131-I, whereas only about 0.6% of control cells were killed. CONCLUSIONS: A therapeutic effect of 131-I has been demonstrated in MTC cells after induction of tissue-specific iodide uptake activity by calcitonin promoter-directed hNIS expression. This study demonstrates the potential of NIS as a therapeutic gene, allowing radioiodine therapy of MTC after tissue-specific NIS gene transfer.