Effect of percutaneous ethanol injection therapy versus suppressive doses of L-thyroxine on benign solitary solid cold thyroid nodules: a randomized trial

The results of studies using suppressive doses of L-T4 on benign solitary solid cold thyroid nodules have been conflicting. Recently, intranodular injection of absolute ethanol has been proposed as an effective treatment, but has been evaluated only in uncontrolled studies. Our objective was to evaluate the effect of two alternative medical treatment modalities, percutaneous ethanol injection therapy and L-T4, on the benign solitary solid cold thyroid nodule. In a prospective randomized clinical trial, 50 euthyroid patients with a single solid colloid thyroid nodule causing local discomfort were assigned to a single intranodular injection of sterile 98% ethanol (n = 25) or suppressive doses of L-T4 (n = 25). We aimed at an ethanol dose of 20-50% of the pretreatment nodular volume. The initial daily dose of L-T4 was 1.5 microg/kg BW and was adjusted monthly during the first 6 months to reduce serum TSH to subnormal levels (<0.40 mU/L). Thyroid nodule volume and total thyroid volume were assessed by ultrasound, and thyroid function was determined by routine assays before and during follow-up. Symptom scores before and at 12 months were evaluated by a questionnaire rating pressure symptoms and cosmetic symptoms. The median ethanol dose given was 21% [95% confidence interval (CI), 18;25] of the pretreatment nodule volume. In this group, the median reduction in nodule volume was 47% (CI, 33;57; P < 0.0001) compared to 9% (CI, -7;22; P = 0.09) in the L-T4 group. The difference between the two treatment regimens was statistically significant (P < 0.0001). The median reduction in perinodular thyroid volume was 20% (CI, 11;31; P = 0.03) in the L-T4 group, whereas no change was seen in the ethanol group (-2.5%; CI, -18;11; P = 0.9). Fourteen of 25 (56%) patients treated with ethanol injection and 8 of 25 (32%) treated with L-T4 had complete relief of symptoms at 12 months of follow-up (P = 0.09). No major side-effects were seen in either group. Percutaneous ethanol injection therapy administered as a single small dose results in a satisfactory clinical response in approximately 50% of patients by halving the nodule volume. The thyroid nodule-reducing effect of L-T4 suppressive therapy is insignificant, but a subjective satisfactory clinical response is seen in a subgroup of patients, probably explained by the concomitant reduction of perinodular thyroid volume.     

Experimental study of percutaneous hot ethanol injection therapy (PHEIT) by continuous heating device for hepatocellular carcinoma

Percutaneous ethanol injection therapy (PEIT) is widely used as a local treatment for hepatocellular carcinoma (HCC). However, because only a small amount of ethanol can be used in one PEIT session and because the antitumor effect is limited, this modality is indicated only when there are three or fewer tumors and when the tumor diameter is < or = 3 cm. To obtain a more potent and certain antitumor effect, we have devised a new treatment called percutaneous hot ethanol injection therapy (PHEIT), and developed a Continuous Heating Device with which ethanol can be heated and locally injected at a specified temperature. The continuous Heating Device is composed of three major components: a syringe heater, a needle thermocontroller, and a needle tip thermosensor. A disposable syringe filled with liquid is inserted into the syringe heater, which heats the liquid to a desired temperature by adjusting the voltage. The needle thermocontroller is a puncture guide needle to which a heating device has been attached. The needle-tip thermosensor constantly measures, displays and records the temperature of the liquid at the needle tip during injection. Also, because the Continuous Heating Device is a closed-circuit system, there is no risk of accidental a fire, which ensures procedural safety. It is also possible to use this device to safely heat and inject a variety of other liquids, such as physiological saline and anticancer agents and thus contribute to the widespread development of ultrasound-guided injection therapy.     

Changes in radioiodine turnover in patients with autonomous thyroid adenoma treated with percutaneous ethanol injection

In 24 patients with autonomous thyroid adenoma, we studied the hormonal pattern (free thyroxine, free triiodothyronine and thyroid stimulating hormone) and markers of radioiodine turnover before and after nodule ablation with percutaneous ethanol injection. METHODS: The hormonal pattern was studied before treatment and at various intervals after nodule ablation. Changes in radioiodine turnover were studied measuring 131I protein-bound iodine and the biologic half-life of radioiodine in the thyroid (calculated from thyroid uptake at 24 and 48 hr) before and after ethanol treatment. RESULTS: The hormonal pattern was normalized by treatment in all patients and remained normal for the follow-up period. Before treatment, protein-bound 131I was elevated in all patients but 4; after treatment, it normalized in 15 patients with the disappearance of the adenoma on scintigraphy. In the remaining 9 patients with only partial nodule destruction on scintigraphy, protein-bound 131I remained elevated although markedly reduced. Biologic half-life was shortened in 18 of 24 patients before treatment; after treatment, it was normal in 18 of 24 patients (13 of 15 with complete nodule ablation and 5 of 9 with partial ablation). CONCLUSION: Ethanol treatment normalized the hormonal pattern in all patients. Measures of radioiodine turnover were better markers of residual disease in that they normalized in almost all patients with complete nodule ablation, whereas they remained abnormal in a high proportion of patients with incomplete ablation. Thyroid hormones remained normal over a follow-up period of 3-7 yr in all patients.     

Isolated thyroid nodule. Comparative value of cyto-puncture and scintigraphy

OBJECTIVES: Nodular thyroid disease, indicated by the presence of single or multiple nodules within the thyroid gland is a common clinical problem, the main question remains the malignancy. Radionuclide scanning, ultrasonography and fine needle aspiration biopsy have been helpful to distinguish benign from malignant nodules and to select patients for surgery. METHODS: We performed a prospective study to assess the comparative value of fine needle nonaspiration biopsy and thyroid scinti scan in the management of 412 patients operated for solitary thyroid nodule. RESULTS: Sensitivity and negative predictive values were the same for both methods, but specificity of cytology was greater than that of thyroid scinti scan (80.53% vs. 10.47%, p < 0.001). DISCUSSION: Thyroid radionuclide scanning remains valuable in the evaluation of a cytological benign solitary thyroid nodule when TSH value is low, in order to distinguish toxic adenoma from cold nodule in Graves' disease.     

Primary hyperparathyroidism sustained by a giant adenoma of the parathyroid gland

A case of primary hyperparathyroidism sustained by an unusually large parathyroid adenoma is presented. The tumor affected a 45-year-old woman with a 15-year history of nephrolithiasis and presented as a palpable neck mass. On the basis of clinical findings and ultrasound examination, it was initially misdiagnosed as a thyroid nodule. CT scan and transesophageal endosonography gave a correct definition of the tumor, which was located behind the left thyroid lobe and expanded posterior to the pharynx and the esophagus in the prevertebral space. At surgery a parathyroid tumor measuring 8 x 7 x 3 cm and weighing 90 g was successfully removed. No signs of malignancy were observed by both morphological and cell kinetic analyses.     

Percutaneous renal biopsy in children: a 27-year experience

BACKGROUND: The introduction of automated biopsy devices and the localization of the kidney by ultrasound were aimed at optimizing efficacy and safety of the percutaneous renal biopsy procedure. We evaluated these technological advances in our renal biopsies performed in children. METHODS: We sequentially used the Silverman needle (1969-1974), the TruCut needle (1974-1990), and the automated Biopty device (1990-1996). Fluoroscopy was used to localize the kidney until 1985, ultrasound examination prior to biopsy from 1985 to 1992, and direct ultrasound guidance since 1992. A total of 962 native kidney biopsies and 119 allograft biopsies were performed. RESULTS: In the native kidney biopsies, the introduction of the Biopty device and ultrasound guidance were independently associated with fewer passes required to obtain adequate tissue and more glomeruli per specimen. The rate of biopsies yielding more than 9 glomeruli increased from 69 to 92% (p < 0.05). The number of glomeruli harvested per centimeter core length was inversely related to patient age (p < 0.01). More appropriate cortical tissue was retrieved in renal allograft biopsy specimens with the application of the new techniques. The occurrence of macroscopic hematuria (9. 6%) in the native kidney biopsies was not affected by the puncture or localization technique applied, but subcapsular hematomas were documented more often with the Biopty device (42%) than with the TruCut needle (16%), probably due to improved ultrasound equipment. In the whole series 2 patients died, and 3 others required renal surgery and 4 blood transfusions. CONCLUSIONS: The automated ultrasound-guided procedure is a feasible and reliable technique for percutaneous renal biopsy in children. It gives a greater yield of diagnostic tissue without increasing the rate of clinical complications.     

Refined use of scintigraphy in the evaluation of nodular thyroid disease

BACKGROUND: Scintigraphy has been advocated in patients with a thyroid nodule when fine needle aspiration biopsy (FNAB) is not definitive. The purpose of this study was to determine the incidence of hyperfunctioning nodules in patients without a definitive FNAB, the correlation of serum thyrotropin (TSH) levels with the functional status of a nodule, and whether a sensitive TSH assay can be used in lieu of scintigraphy. METHODS: From 1990 to 1996, patients with a thyroid nodule were evaluated with FNAB and serum TSH measurement. Iodine-123 scintigraphy was reserved for patients without a definitive FNAB and was correlated with TSH levels. RESULTS: Of 356 patients with a thyroid nodule, 102 did not have a definitive FNAB. A hyperfunctioning nodule was diagnosed in 14 of the 102 patients. A low TSH level was detected in 12 (86%) of 14 patients with a hyperfunctioning nodule (mean = 0.04 +/- 0.38 microIU/mL) and only 20 (23%) of 88 patients with a hypofunctioning nodule (mean = 0.87 +/- 4.11 microIU/mL) (P < .05). Only 2 of 70 (2.8%) patients with a normal or increased TSH level had a hyperfunctioning nodule. CONCLUSIONS: A 14% incidence of hyperfunctioning nodules in patients without a definitive FNAB warrants the use of scintigraphy but only when serum TSH levels are low, thus avoiding unnecessary scans in 91% of patients with a thyroid nodule.     

Ectopic thymic carcinoid masquerading as a thyroid nodule

A 26-year old woman presented with a thyroid nodule. Ultrasound and scintigraphy confirmed the presence of a 3.5-cm non-functioning mass in the left lobe. A fine needle aspiration demonstrated unusual, malignant-appearing cells, and thyroidectomy was performed. At gross pathological sectioning, the lesion was clearly attached to, but not part of, the thyroid. Microscopic features indicated an atypical carcinoid arising in a cervical remnant of the thymus. This appears to be the first case of ectopic thymic carcinoid presenting as a thyroid nodule.     

Thyroid disease among the Rongelap and Utirik population--an update

In 1954, 253 Marshallese were accidentally exposed to fallout radiation from the hydrogen bomb, BRAVO. The Marshall Islands Medical Program (MIMP) was established by the Department of Energy in 1955 to monitor and treat radiation-related disease pursuant to this accident. Medical teams from Brookhaven National Laboratory, a federal institution, regularly visit the Marshall Islands to give medical care to the exposed population. The most significant complication of the exposure has been found to be thyroid disease due to the ingestion of radioactive iodides from the fallout. In 1963 the first thyroid nodules were found in Rongelap subjects and in 1969 in Utirik. Non-neoplastic adenomatous nodules were associated with higher doses of radiation and neoplastic nodules developed in individuals receiving lower doses of radiation. Women were more susceptible to the development of palpable thyroid nodules than men. In 1994 the MIMP initiated examination of the thyroid by ultrasound to supplement the clinical examination. One hundred and sixty-four patients were evaluated. No significant differences were found in the incidence of thyroid nodules or the mean nodule count between the three groups of Rongelap and Utirik exposed and a comparison patient population. There was no significant difference in the incidence of thyroid nodules in males vs. females. Five exposed patients were referred for surgical excision of a nodule detected only by ultrasound. These ultrasound findings are unexpected in that females are known to have a higher incidence of thyroid disease than males and we expected that the incidence of ultrasound nodules would be higher in the exposed population.     

Hepatic infarction following percutaneous ethanol injection therapy for hepatocellular carcinoma

We report on two patients who developed hepatic infarction after undergoing percutaneous ethanol injection therapy (PEIT) for hepatocellular carcinoma (HCC). In both cases, liver function parameters deteriorated immediately after the ethanol injection, and enhanced computed tomography images showed a wedge-shaped avascular low-density area due to hepatic infarction. In one patient, PEIT was performed for a nodule treated with transcatheter arterial infusion (TAI) using a suspension of styrene maleic acid neocarzinostatin (SMANCS) 4 weeks before. In the other patient, TAI with SMANCS had been carried out 14 months previously for a different nodule in the same segment where the nodule treated with PEIT was located. When PEIT is used for patients with HCC who have previously undergone TAI, especially with SMANCS, PEIT may induce hepatic infarction.     

Papillary Hürthle cell carcinoma (Warthin-like tumor) of the thyroid. Report of a case with fine needle aspiration findings

BACKGROUND: Papillary Hürthle cell carcinoma with lymphoplasmacytic stroma is a newly recognized variant of papillary carcinoma of the thyroid gland. Fine needle aspiration findings reveal some points that have not been reported previously. CASE: A 50-year-old female presented with a left lobe thyroid mass. Fine needle aspiration of the nodule yielded cellular smears, mostly in large and small papillary clusters of Hürthle cells, with nuclear grooves and rare nuclear inclusions in a lymphoplasmacytic background. Isolated Hürthle cell and multinucleated giant cells were also seen. Histopathologic examination of the 3-cm-diameter nodule showed papillary Hürthle cell carcinoma with lymphocytic stroma, or "Warthin-like tumor" of the thyroid, with capsular invasion. CONCLUSION: The presence of papillary clusters with nuclear features of papillary carcinoma and oxyphilic cytoplasm in a lymphoplasmacytic background should raise the diagnosis of Warthin-like tumor of the thyroid.     

Complications of percutaneous ethanol ablation

Percutaneous ethanol injection therapy performed with sonographic visualization is a steadily growing therapeutic method that can be used in the ablation of solid and cystic masses in a variety of anatomic locations. Ethanol has been used for many years as an angiographically administered agent for vascular embolization of tumors such as hepatic and renal neoplasms. It was first used as a percutaneously injected agent for the sclerosis of renal cysts. Local infiltration or intravascular injection of ethanol leads to cell death by causing cell membrane lysis, protein denaturation, and vascular occlusion. Because of the initial success in the sclerosis of renal cysts, percutaneously injected ethanol is now used in the ablation of hepatic cysts and solid tumors, such as hepatocellular carcinomas. As a treatment agent, ethanol combines the benefits of being widely available, inexpensive, efficacious, and relatively easy to administer. Optimal results require that the radiologist have considerable experience in ultrasonographic scanning techniques and facility with percutaneous needle insertion under real-time visualization. Alternatively, the radiologist may choose CT as a method to visualize needle placement. Percutaneous ethanol injection therapy usually is an effective alternative to conventional surgical resection of liver lesions and has a low complication rate. We present two patients in whom hypotensive complications occurred during percutaneous ethanol injection therapy and discuss the likely causative mechanisms.     

Iatrogenic urinary tract infection with Pseudomonas cepacia after transrectal ultrasound guided needle biopsy of the prostate

In response to an unexplained development of Pseudomonas cepacia cystoprostatitis after transrectal ultrasound guided prostate biopsy, a retrospective review of records and biopsy protocol was performed at our institution. Between June 5, 1990 and January 9, 1991 no documented infections occurred in 272 patients undergoing transrectal ultrasound and prostate biopsy. During the next 6 months, however, 9 of 110 patients (8.2%) presented again with infectious symptomatology after transrectal ultrasound guided needle biopsy of the prostate. Culture of a majority of the specimens (67%) yielded P. cepacia. Two additional asymptomatic patients became colonized with P. cepacia. Environmental investigations revealed the ultrasound transmission gel as the source of the contamination. The proposed mechanism of infection was direct prostate or bladder seeding of contaminated transmission gel used to prepare the ultrasound transducer probe. Infections developed in immunocompetent patients despite adequate antimicrobial prophylaxis most likely secondary to underlying bladder outlet obstruction and significant direct inoculum of organisms. We currently recommend use of individualized sterile packets of transmission gel in addition to appropriate antimicrobial prophylaxis and povidone-iodine cleansing enemas when performing transrectal sonographic guided biopsies of the prostate.     

Transition from cold to hot thyroid nodules

We report three cases of autonomously functioning thyroid nodules (AFTNs) that appeared hypofunctioning at radioactive iodine (131I) thyroid scan carried out at initial observation. Since at that time thyroid hormones and thyrotropin (TSH) were also normal, they were initially classified as "cold" nodules and treated with levothyroxine (LT4). The correct diagnosis of AFTN was made years later when a thyroid scintigraphy was repeated. In two of these patients, re-evaluation of the nodule was done because of the development of LT4 intolerance. A possible explanation is that these AFTNs had undergone hemorrhagic/cystic degeneration when they were first studied, but in subsequent years, proliferation of residual AFTN tissue caused the recurrence of a typical functioning nodule.     

Two-dimensional electrophoretic analysis of membranous protein from human thyroid tissues and cancer cell lines

Thyroid neoplasm is the most commonly encountered neoplastic disorder in endocrine clinics. Thyroid scan, ultrasonography, and fine needle aspiration cytology (FNAC) are used as diagnostic tools to differentiate a malignant nodule from a benign lesion. There are certain limitations and pitfalls in FNAC, especially in the diagnosing of follicular tumors. The lack of characteristic findings or a specific tumor marker are the most common problems in the preoperative diagnosis of thyroid follicular carcinoma. Although serum thyroglobulin level has been used as a tumor marker for post-operative, well-differentiated thyroid cancer, the assay cannot be used for preoperative diagnosis of thyroid carcinoma. In this study, various thyroid tissues and cancer cell lines including CGTH W-1, CGTH W-3, RO 82 W-1, SW 579 cell lines were used for the investigation of tumor markers. Specific spots were identified in the area near the 60 kDa molecular mass protein and isoelectric point (pI) 5.9 of the CGTH W-1 cell line. These spots could not be found in the papillary or anaplastic thyroid cancer cell lines. Another spot with a molecular weight of about 9.8 kDa with a low pI of 4.8 was present in the CGTH W-1 and RO 82 W-1 cell lines. This spot appeared to be a tumor marker of follicular cancer cells. This spot could not be found in the papillary and anaplastic cancer cell lines and other benign thyroid tissues. Specific proteins that were identified in this study may be useful as tumor markers for follicular thyroid carcinoma.     

Hürthle cell tumor dwelling in hot thyroid nodules: preoperative detection with technetium-99m-MIBI dual-phase scintigraphy

Single injection dual-phase scintigraphy (early and late acquisitions) with 99mTc-MIBI was used to differentiate benign and malignant hot thyroid nodules. METHODS: Thirteen euthyroid and two hyperthyroid patients displaying a hot thyroid nodule on the 99mTc scan due to an autonomously functioning thyroid nodule (AFTN) underwent early (15-30 min) and late (3-4 hr) thyroid scintigraphy after the administration of 740-1000 MBq 99mTc-MIBI. Visual scoring was done to assess nodular tracer uptake and retention. In addition, the nodular-to-thyroid (N/T) uptake ratio in the early and late image and the washout rates (WO) from the nodule and thyroidal tissue were measured. All patients underwent thyroid surgery. RESULTS: Histopathology revealed a Hürthle cell tumor in three nodules, a benign adenoma with oxyphilic metaplasia in two nodules and a benign adenoma without oxyphilic cells in the remaining 10 nodules. The Hürthle cell tumor nodules displayed intense and persistent uptake of 99mTc-MIBI (N/T was 2.81 +/- 0.52 and 5.53 +/- 1.06 in early and late images, respectively; WO from the nodule was 12.33 +/- 0.47, WO from the thyroidal tissue was 22.00 +/- 3.56). The benign nodules showed intense uptake in the early image and intense uptake to absent retention in the late image (N/T was 2.94 +/- 1.31 and 1.62 +/- 0.50 in the early and late images, respectively; WO from the nodule was 20.25 +/- 2.92, WO from the thyroidal tissue was 20.33 +/- 2.92). CONCLUSION: Single injection dual-phase 99mTc-MIBI scintigraphy of the thyroid with AFTN can identify nodules as a result of the activity of a Hürthle cell tumor, since these tumors cause intense and persistent tracer uptake in contrast with a benign AFTN.     

A "smart needle" to facilitate difficult vascular access in pediatric patients

A new Doppler probe inside a needle was evaluated in a group of infants and children to assess its suitability for subclavian venous access. While the efficient use of this device required learning a new technique, we found the device useful to accurately locate the subclavian vein and differentiate it from the artery in all patients weighing more than 3 kg. This device will be most helpful in cases of difficult access, eg, scar from previous access, obesity, or edema.     

Value of color-coded Doppler sonography in the differential diagnosis of nodular thyroid gland changes

AIM: The incidence of functional autonomous adenomas, detected in every second nodular goiter by scintigraphic methods is very high in an area of iodine deficiency. The color-coded Doppler sonography (CCDS) as a diagnostic tool in differentiating thyroid nodules is discussed controversially. METHODS: In this prospective study we investigated the value of CCDS in 200 patients with nodular thyroid alterations compared with 99m-Technetium (Tc) scintigraphy. RESULTS: Focal maximas of Tc-uptake were detected in 22.5% of all patients, and 44.5% of the thyroid nodules showed increased vascularity. There was no correlation between nodular vascularity and thyroid 99m-Tc uptake (TcTU). In contrast to this we could demonstrate a significant relation between vascularity and the diameter of the nodule (p < 0.0001). The results are discussed in the context of method specific limitations of ultrasound examinations. CONCLUSION: Our results confirm that CCDS has no great importance in the differentiation of thyroid nodules. Scintigraphy remains the diagnostic method of choice to assess the topographic thyroid function.     

Methods for providing probe position and temperature information on MR images during interventional procedures

Interventional magnetic resonance imaging (MRI) can be defined as the use of MR images for guiding and monitoring interventional procedures (e.g., biopsy, drainage) or minimally invasive therapy (e.g., thermal ablation). This work describes the development of a prototype graphical user interface and the appropriate software methods to accurately overlay a representation of a rigid interventional device [e.g., biopsy needle, radio-frequency (RF) probe] onto an MR image given only the probe's spatial position and orientation as determined from a three-dimensional (3-D) localizer used for interactive scan plane definition. This permits 1) "virtual tip tracking," where the probe tip location is displayed on the image without the use of separate receiver coils or a "road map" image data set, and, 2) "extending" the probe to predict its path if it were directly moved forward toward the target tissue. Further, this paper describes the design and implementation of a method to facilitate the monitoring of thermal ablation procedures by displaying and overlaying temperature maps from temperature sensitive MR acquisitions. These methods provide rapid graphical updates of probe position and temperature changes to aid the physician during the actual interventional MRI procedures without altering the usual operation of the MR imager.     

Diffusion-weighted MR imaging in a case of dissociative amnesia

BACKGROUND: Management of thyroid cancer in pregnancy is controversial, as evidenced by disagreement in recommendations cited in leading obstetrics textbooks. Most thyroid carcinomas are well differentiated and pursue an indolent course. Many physicians recommend delay in surgical therapy until after delivery because of operative morbidity. CASE: A 27-year-old primigravida was found to have a solitary thyroid nodule at her initial obstetrics appointment. Fine needle aspiration was consistent with papillary carcinoma. Although detected at 8 weeks' estimated gestational age (EGA), the decision was made to defer surgical therapy until postpartum. The patient was referred to a tertiary care facility at 24 weeks' EGA secondary to rapid growth of the nodule. Surgery performed at that time revealed invasive disease. CONCLUSION: Review of the literature suggests that delay in definitive therapy stems from early reports of fetal loss related to surgery, but contemporary data suggest that the risk of fetal loss related to surgery is minimal.