Needle aspiration techniques in preoperative selection of patients with thyroid nodules: a long-term study.

PURPOSE: Long-term evaluation of the combination of two needle aspiration techniques (NAT) (fine-needle aspiration [FNA] and aspiration needle biopsy [ANB]) in performing an efficient preoperative selection of palpable thyroid nodules. PATIENTS AND METHODS: Eight years of extensive use of surgery for the detection of thyroid cancer was compared with 12 years of preoperative selection of by NAT. RESULTS: A total of 1,140 operations were performed from 1972 to 1979, and 35 malignant nodules were discovered (3.1%). Five thousand four hundred three patients were examined by NAT from 1980 to 1992; 483 (9%) underwent surgery and 158 malignant nodules were excised. The number of malignant nodules identified by NAT was 166 (eight were not excised) (3.1% of the total population examined). The principal clinical and pathologic features were similar in both groups. ANB yielded a definite benign diagnosis in 88 patients with inadequate FNA findings, it correctly identified four malignant nodules diagnosed as benign by FNA, it showed a macrofollicular component in 115 nodules diagnosed by FNA as microfollicular nodules, and it significantly changed the predictive value of 79 suspicions FNA diagnoses. CONCLUSION: Introduction of NAT reduced the number of operations for palpable thyroid nodules from 143 to 40 per year and increased from four to 13 the number of malignant nodules excised without any change in the overall incidence of malignant nodules. The combination of ANB to FNA significantly contributed to the high and efficient preoperative patient selection, principally by reducing the number of indeterminate or suspicious, as well as false-negative, preoperative FNA diagnoses.

Evaluation of triiodothyronine (T3) kinetics in normal subjects, in hypothyroid, and hyperthyroid patients using specific antiserum for the determination of labeled T3 in plasma.

Triiodothyronine (T3) kinetics was evaluated using [125I]T3 and the single injection technique; 5 hypothyroid, 6 hyperthyroid patients, and 10 euthyroid control subjects were studied. Plasma-labeled T3 concentration was measured by means of a new method based on extraction of the hormone on Sephadex G-25 columns followed by elution with the specific antiserum. This technique allows a far better separation of the hormonal radioactivity from the labeled iodide produced from T3 catabolism in comparison with the TCA-precipitation-butanol extraction method. The analysis of the experimental data has been performed using non-compartmental treatment (integral approach); results of mono-compartmental analysis of the same data are also reported for comparison. Average metabolic clearance was 15.3 +/- 0.6 (mean + SEM) liters/day/m2 body surface in normal subjects; it was significantly decreased in hypothyroid patients (11.4 +/- 1.1) and significantly increased (33.4 +/- 4.0) in hyperthyroidism. The total plasma equivalent distribution volume was found significantly enlarged in hyperthyroid patients (22.6 +/- 0.9 liters/m2) in respect to that measured in the control group (15.6 +/- 0.4), whereas it was not different from normal value in hypothyroid patients (17 +/- 1.7). Using plasma concentration of native T3, absolute turnover rate and extrathyroidal pool were also estimated; their values were 6.5, 23.7, and 131.7 micrograms/day/m2 and 10.1, 24.2, and 90.6 micrograms/m2, respectively, in hypothyroid, normal, and hyperthyroid groups.

Peripheral metabolism of thyroid hormones in man. I. Direct measurement of the conversion rate of thyroxine to 3,5,3'-triiodothyronine (T3) and determination of the peripheral and thyroidal production of T3.

We describe here a new method for the direct measurement of the conversion rate of T4 to T3 in man. The metabolic study was performed in 23 subjects: 13 healthy controls, 7 T4-treated hypothyroids, and 3 sick euthyroid patients. The experimental protocol involved the simultaneous iv bolus injection of [125I]T4 and [131I]T3, and the use of Sephadex G-25 column chromatography to determine the plasma concentrations of [125I]T4, [131I]T3, and [125I]T3 newly formed through 5'-monodeiodination of labeled T4 in the peripheral tissues. The T4 and T3 kinetic parameters were determined by noncompartmental analysis. The conversion rate of T4 to T3 was computed by a method based on the precursor-product relationship, using the [131I]T3 disappearance curve for correcting the concentrations of newly formed [125I]T3 (convolution method). The conversion rate of T4 to T3 was 0.2541 +/- 0.0125 (mean +/- SEM) in the control group and was significantly reduced (0.1283 +/- 0.0204; P less than 0.001) in the sick euthyroid patients, while it was slightly, though not significantly, increased in the T4-treated patients (0.2932 +/- 0.0220). A close agreement was found between the values for the conversion rate obtained by the convolution approach and those derived from the ratio between the serum concentrations of [125I]T3 and [125I]T4 at equilibrium. The conversion rates obtained by the convolution approach were also in good agreement with the values estimated from the molar ratio between the turnover rates of T3 and T4. In the control group, 72.0 +/- 3.6% of the circulating T3 was produced by 5'-monodeiodination of T4 in the peripheral tissues, and 28.0 +/- 3.6% of the circulating T3 derived from direct thyroidal secretion. The sick euthyroid patients showed a significantly smaller proportion of circulating T3 deriving from peripheral conversion of T4 (52.5 +/- 3.9%; P less than 0.025).

The metabolism of human serum albumin in renal failure on conservative and dialysis therapy.

The pathophysiology of albumin metabolism in uremia was investigated by turnover measurements in a large series of uremic patients, either on conservative management or on dialysis therapy. A total of 62 turnover studies were performed in patients on dietary treatment, divided into two groups according to the duration of the low protein diet: 35 subjects from 6 to 30 days, 27 subjects from 6 months to 5 years. Albumin catabolism and distribution were measured by the two-tracer technique (131I-albumin and 125I-iodide, simultaneously injected iv), while albumin synthesis was directly determined in 10 patients by the use of 14C-carbonate and 131I-albumin. Sixteen turnover studies were also performed in a group of end-stage uremics on dialysis therapy by a two-tracer procedure especially designed to determine albumin catabolism in the course of a single peritoneal or hemodialytic treatment. The main features of albumin metabolism observed in the patients on dietary management were: normal intravascular albumin mass, marked reduction of the extravascular and total albumin pools, with proportionally reduced catabolism. No significant turnover difference was found between the short-term diet group and the patients on low-protein diet from 6 months to 5 years. As to the uremics on dialysis therapy, catabolic rate of albumin was 3-fold increased in three patients showing clinical features of "hypercatabolism" in the early phase of uremia, or during relapse from it. Albumin turnover rate returned to normal when measured during clinical steady-state conditions. All these findings suggest that a marked body protein depletion exists in chronic uremia, and that dietary treatment per se is not responsible for such a depleted state. Instead, the depletion of protein stores observed in the steady phase of chronic uremia may have been originated by the exaggerated increased catabolism in the early phase of renal failure, not compensated by a proportional increase of the synthetic rate, due to both the state of uremic intoxication and to the reduced dietary protein intake during the early phase.

Chromatographic identification in serum of endogenously radioiodinated thyroid hormones after iodine-131 whole-body scintigraphy in the follow-up of patients with differentiated thyroid carcinoma.

Patients with differentiated thyroid cancer (DTC) are conventionally followed with serial 131I whole-body scintigraphy (WBS) and serum thyroglobulin (hTg) assay. Given the 15%-20% incidence of discordant results, we developed a sensitive and specific procedure for monitoring such patients, based on the assumption that 131I uptake, even if too low to be detected by 131I WBS, could be assayed in serum as thyroid products (hTg, T3 and T4) endogenously labeled with 131I. Our study included 125 patients routinely monitored for tumor recurrence or for the persistence of functioning thyroid tissue after complete primary treatment for DTC (surgery and 131I ablation of remnants). A plasma sample, taken 72 hr after administering 131I for WBS was fractionated on a Sephadex-G25 superfine column by first eluting all of the radioactive species except the thyroid hormones and then the radioiodothyronines. The sensitivity and specificity of chromatography in detecting functioning thyroid tissue after primary treatment for DTC were 98.4% and 100% (accuracy 99.2%), respectively, versus 90.6% and 95.1% for 131I WBS (accuracy 92.8%) and 60.9% and 100% for hTg (accuracy 80%). Combining chromatography with serum hTg gave the highest gains in diagnostic performance (100% for all parameters). This chromatographic method can be used in addition to conventional procedures in the follow-up of patients with DTC and represents a highly sensitive test for assessing the results of 131I ablation of postsurgical remnants.

Triiodothyronine turnover studies in euthyroid patients with autonomous thyroid nodules.

Triiodothyronine (T3) kinetic studies were carried out using 126I-T3 and the single injection technique in eight clinically euthyroid patients with autonomous thyroid nodules and the metabolic results were compared to those obtained in a group of 12 healthy control subjects. Plasma labeled T3 concentration was measured by a chromatographic method based on the extraction of the hormone on Sephadex G-25 columns, followed by its elution with a specific anti-T3 antiserum. The analysis of the experimental plasma disappearance curves of the labeled hormone was performed using the noncompartmental method. The results obtained showed a significantly increased metabolic clearance rate of T3 in the patients with autonomous thyroid nodules, as compared to the control group. On the average, the T3 production rates were increased more significantly than the corresponding circulating levels of the hormone, therefore, suggesting that the significant TSH inhibition observed in the euthyroid patients with autonomous thyroid nodules could be related with an increased peripheral utilization of triiodothyronine.

Effect of a single oral dose of L-thyroxine (150 micrograms) on serum thyroid hormone and TSH concentrations in clinically euthyroid goitrous patients.

Serum TT4, FT4, TT3, FT3 and TSH, concentrations were measured before and 0.5, 1, 2, 3, 4, 5 hours after a single oral dose of L-T4 (150 micrograms) in 21 clinically euthyroid goitrous patients on a long-term therapy program. The mean basal TT4 concentration, 8.85 +/- 0.52 micrograms/dl (mean +/- se), increased significantly at the second hour (10.04 +/- 0.52 micrograms/dl, p < 0.001) and reached the highest value at the third hour (10.35 +/- 0.55 microgram/dl, p < 0.001). Subsequently the mean serum TT4 concentration remained elevated until the fifth hour (10.20 + 0.60 microgram/dl, p < 0.001). The mean basal value of FT4 concentration, 8.66 +/- 0.40 pg/ml, increased significantly at 30 minutes (9.19 +/- 0.40 pg/ml, p < 0.01) and reached the highest value at the third hour (11.81 +/- 0.56 pg/ml, p < 0.001). The mean basal serum FT3 concentration, 3.56 +/- 0.10 pg/ml, increased significantly 30 minutes (3.72 +/- 0.11 pg/ml p < 0.05) after L-T4 administration; the mean serum FT3 concentration was significantly higher than the basal level and 1 and 2 hours as well, and reached the highest value at the third hour (3.86 +/- 0.09 pg/ml). The mean serum TT3 concentration did not show any significant change at any time. The mean basal TSH value (2.73 +/- 0.42 microUI/ml) declined progressively. At 30 minutes it decreased significantly (2.29 +/- 0.38 microUI/ml, p < 0.01) and reached the lowest value at the fifth hour (1.39 +/- 0.26 microUI/ml, p < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of long-term low protein diet on albumin metabolism in chronic uremia.

The effects of long-term low protein diet on albumin metabolism of uremic patients were evaluated. Studies were performed on 62 patients divided into two groups depending on the duration of the diet (35 subjects from 6 to 30 days, 27 subjects from 6 months to 5 years). All patients received a diet containing at least 20 g of high biological value proteins per day. Albumin catabolism and distribution were measured by the two-tracer technique, after simultaneous i.v. injection of 131I-human serum albumin and of free 125I-iodide. Albumin synthesis was directly determined in 10 patients by two tracers, 14C-carbonate and 131I-albumin, according to the xanthydrol technique for specific activities of urea and albumin guanido carbon in plasma. The main features of albumin metabolism observed in both groups studied were: normal intravascular albumin mass, marked reduction of extravascular and total albumin pools, with proportionally reduced catabolism. No significant turnover difference was found between the first group and the patients on diet from 0.5 to 5 years, thus suggesting that dietary treatment per se is not responsible for the albumin depletion observed in chronic uremia.

The thyroid nodule: diagnostic strategy.

This paper comments on the principal techniques (nuclear imaging echography and needle aspiration) and the most widely used protocols available for preoperative selection of thyroid nodule patients. Successively, the authors report the principles to define a new appropriate protocol based on needle aspiration and hormone assays and evaluate their experience with this new simple protocol. Long term clinical practices shows that surgical excision can be avoided for more than 90% of the nodule patients and that thyroid scintigraphy can be avoided for most of these patients, without appreciable disadvantage.

Basal and stimulated TSH serum concentrations in euthyroid thyroid nodule patients.

Serum TSH concentrations were determined by a sensitive second generation immunoradiometric (IRMA) assay, basally and 20 min after i.v. injection of 200 micrograms of TRH, in 630 consecutive ambulatory clinically and biochemically euthyroid patients with palpable thyroid nodules. The TSH response was defined as normal when the stimulated TSH values was higher than the basal one by at least 2 microU/ml, as suppressed when the difference between the two TSH values was less than 1 microU/ml and as blunted when this difference was between 1 and 2 microU/ml. The TSH response was normal in 511 patients (81.1%), suppressed in 78 (12.4%) and blunted in 41 cases (6.5%). Nodule patients with suppressed responses showed significantly higher mean age (52.7 vs 45.8 years; p < 0.05) and mean serum concentrations of TT4 (9.32 vs 8.71 micrograms/dl; p < 0.05), TT3 (161 vs 137 ng/dl; p < 0.01) and fT3 (4.94 vs 3.86 pg/ml; p < 0.01) than those with normal TSH secretion. Analysis of the distribution of the different TSH responses in the patients grouped according to basal TSH concentration values showed that 50% of the patient group with basal TSH concentration between > 0.2 and 0.3 microU/ml had normal TSH response to TRH. A normal response occurred in 86.5% of patients with basal TSH between > 0.4 and 0.5 microU/ml and in 95.3% of those with basal TSH between > 0.7 and 0.8 microU/ml. The proportion of normal responses in the patients with basal TSH up to 0.1 microU/ml was 15.7% and that of abnormal responses in those with basal TSH > 1.5 microU/ml was 2.7%.(ABSTRACT TRUNCATED AT 250 WORDS)

Long term therapy with a new liquid L-thyroxine preparation: bioequivalence with L-T4 tablets.

Seventy-four euthyroid patients with nodular goiter (55) or primary hypothyroidism (19) were selected for long term treatment with a new preparation containing L-T4 in solution (Tiroxen, Laboratori Baldacci, Pisa, Italy). Each patient underwent, before or after receiving the L-T4 in solution, long term treatment with L-T4 in tablet form at the same dose. The serum concentrations of TSH, TT4, TT3, FT4 and FT3 were measured basally and during therapy with each of the two L-T4 preparations (liquid and tablet). In the golter group, mean serum TSH concentration was 1.4 microUI/ml basally, while it was 0.47 microUI/ml following both L-T4 tablet therapy and L-T4 solution administration. Mean basal TSH value was significantly different from the two values on the therapy (p < 0.001 in each instance). Mean basal serum TT4 concentration was 8.2 +/- 0.25 microgram/dl basally while it was 9.9 +/- 0.28 microgram/dl (p < 0.001) on L-T4 tablet therapy and 9.7 +/- 0.26 (p < 0.001) on L-T4 solution administration. Mean basal serum concentration of TT3, FT4, FT3 was not significantly different from the value on the therapy, either with L-T4 tablet or with L-T4 solution. In the hypothyroid patients the high mean basal serum TSH concentration (23.6 microUI/ml) returned to normal similar values on L-T4 tablet therapy (0.96 microUI/ml; p < 0.01) and on L-T4 solution administration (1.24 microUI/ml; p < 0.01). The serum TSH concentration value during L-T4 therapy varied from unmeasurable level to 3.5 microUI/ml during the tablet administration and to 4.8 microUI/ml during the solution administration.(ABSTRACT TRUNCATED AT 250 WORDS)

Double isotope measurement of peritoneal clearance of iodide and albumin loss during peritoneal dialysis in man (labelled albumin loss in peritoneal dialysis).

131I-labelled Human Serum Albumin and 125I-sodium iodide were used to measure protein loss from the peritoneum and peritoneal clearance of iodide in a group of 8 uraemic patients, each one being studied after a different number of dialyses. Both albumin loss and iodide clearance reached a maximum at about the 10th dialytic treatment and then tended towards the initial levels. Protein loss as determined isotopically was markedly lower than indicated by direct radioimmunoassay measurements performed in three cases. Fitting experimental points by a model which assumes direct passage of protein from plasma to peritoneal cavity suggests the presence of a "delay" pool between plasma and the peritoneal cavity itself (extravascular sites adjacent to peritoneum?). The shorter retention time of the dialysis solution in the abdomen (4-8 minutes) seemed to us to cause lower protein losses than reported by authors using longer retention times.

Comparison of the effect of a single oral L-thyroxine dose (150 micrograms) in tablet and in solution on serum thyroxine and TSH concentrations.

150 micrograms of L-thyroxine were administered to each of 14 euthyroid goitrous patients orally between 7:30 and 8:30 a.m. after fasting overnight. The L-T4 dose given was one and half tablets of the drug "Eutirox" (L-T4 tablet of 100 micrograms distributed by Bracco, Milan, Italy) or one and half ml of the solution "Tiroxen" (solution containing 100 micrograms/ml of L-T4 distributed by Laboratori Baldacci, Pisa, Italy). Two studies (one with tablet and one with solution) were performed on each patient. The tablet or the liquid form of L-T4 were administered in random order. In each study a blood sample for serum hormone determination was drawn immediately before L-T4 administration, then 30 minutes later and every hour up to the fifth hour after. The second study was performed in similar fashion later. The mean serum TT4 concentration value at any time was very similar in the two studies, thus showing the same time course after the administration of solution and the tablet formulation. The mean basal TT4 value (9.07 +/- 0.56 and 8.90 +/- 0.73 micrograms/dl respectively) increased significantly at the first and second hours. The highest value was reached at the second and at the third hour after the solution (11.15 +/- 0.58 micrograms/dl) and the tablet (11.81 +/- 0.78 micrograms/dl) respectively. Subsequently, the mean TT4 values remained significantly higher than basally over the entire 5 hours. The FT4 mean serum concentration at all times were very similar in the two studies and showed the same time course.(ABSTRACT TRUNCATED AT 250 WORDS)

[SPECT in the study of pathology of the temporomandibular joint. The authors' personal experience]. / La SPECT nello studio della patologia dell'articolazione temporo-mandibolare. Esperienza personale.

Symptomatic temporomandibular joint dysfunctions may affect about 25% of the adult population, with a smaller though significant percentage of patients experiencing severe impairment. From 1986 through 1991, 107 patients with severe temporomandibular joint symptoms and with various temporomandibular joint disorders were evaluated with conventional radiology and with closed/open-mouth temporomandibular joint tomograms. Single-photon emission-computed tomography (SPECT) and planar imaging were performed on 32 patients using a rotating gamma camera equipped with a general purpose collimator. Transaxial, coronal and sagittal tomoscintigrams were reconstructed. Increased radiotracer uptake in the temporomandibular joint was regarded as a positive finding, and the intensity of temporomandibular joint activity was compared with that of adjacent calvarium using regions of interest. In the 32 patients submitted to scintigraphy, conventional radiology showed no pathologic patterns, while SPECT showed pathologic findings in 31 patients (97% of cases). The patient with normal temporomandibular joint findings on SPECT exhibited abnormal maxillary isotope uptake, ipsilateral to the symptoms. Our results indicate that SPECT is a simple, noninvasive, inexpensive and very sensitive screening test relative to the internal derangement of the temporomandibular joint. Moreover, it provides information which is not available by means of routine bone scans or X-ray studies. Thus, SPECT appears to be the modality of choice for patients whose clinical findings are equivocal or whose symptoms are unclear, and it can guide treatment strategies and be useful in the follow-up.

Percutaneous injection of ethanol to treat autonomous thyroid nodules.

OBJECTIVE: The aim of this study was to evaluate the efficacy and safety of sonographically guided percutaneous injection of ethanol for treating autonomous thyroid nodules in order to assess that technique's feasibility as an alternative to traditional ablative (radionuclide and surgical) therapies. SUBJECTS AND METHODS: Thirty-two patients with autonomous thyroid nodules were included in the study: seven had thyrotoxicosis, and 25 were in the pretoxic clinical phase. Ethanol was injected percutaneously on an outpatient basis once or twice a week for a total of three to 10 injections per nodule, mainly depending on the nodule's size. Scintigrams obtained 3 months after the end of treatment were used to assess response to this therapy. The follow-up period was from 3 to 30 months. RESULTS: Thyroid scintigraphy 3 months after percutaneous injection of ethanol showed complete recovery of function in extranodular tissue in 26 patients (81%), partial recovery in five patients (16%), and no recovery in one patient (3%). In all patients, the volume of the nodules decreased by more than 50% after treatment. In three of five patients in whom scintigraphy showed only partial recovery of function in extranodular tissue, a second percutaneous injection of ethanol was given after 15 months. The therapy was well tolerated, and after a total of 216 injections, no patient had permanent side effects. CONCLUSIONS: Our experience shows that percutaneous injection of ethanol is a practical alternative to traditional treatments for autonomous thyroid nodules and that it is an option for treating pretoxic adenoma.

[The echo-guided percutaneous injection of ethanol: a therapeutic alternative in the "autonomous thyroid nodule". Our experience]. / Iniezione percutanea ecoguidata di etanolo: alternativa terapeutica del "nodulo tiroideo autonomo". Nostra esperienza.

The authors report their experience on the therapeutic value, in terms of efficacy and tolerance, of percutaneous ethanol injection (PEI) in the treatment of autonomous thyroid nodules (ATN). A group of 15 patients, 13 in clinical pretoxicity and 2 in initial thyrotoxicosis, were submitted to fine-needle ethanol injection (95%) performed under US guidance. The amount of injected alcohol was measured on the basis of the volume and diffusion of alcohol itself within the nodule, in the whole of 79 injections given. Follow-up lasted 3-15 months. Thyroid scanning demonstrated a complete or partial recovery of extranodular parenchymal function in 80% and 20% of cases, respectively. In all cases a volume reduction greater than 50% was obtained, with an initial sharp fall, already after the first month, thanks to early alcohol cytotoxicity. In the 2 patients with toxic ATN serum, normal values of free hormones have been observed ever since the third weekly injection. Good tolerance to treatment was observed, and no permanent complications. In agreement with other authors, we believe our experience to show that PEI represents a new therapeutic approach in patients with ATN. PEI will certainly play a preferential role, relative to other conventional therapies, in the management of clinical pretoxic ATN, regarding which no uniform treatment protocol exists yet.