Color Doppler sonography patterns related to histological findings in Graves' disease.

The aim of this work was to correlate color duplex sonography (CDS) patterns and thyroid histology in hyperthyroid Graves' disease (GD) patients. Sixteen patients with relapsed GD were studied. Before starting a new cycle of medical therapy with methimazole in decreasing doses for 3 to 6 months (baseline study), the patients underwent functional, autoimmune, and CDS studies. The same studies were carried out again just before surgery (presurgical study) after medical therapy had produced a normalization of thyroid hormone serum levels. The thyroid glands were histologically examined and their patterns were compared with CDS patterns. Thirty-three normal subjects were used as a control group. At baseline, 6 patients (group I) had intraparenchymal homogeneous vascular color spots or diffusely distributed over the parenchyma lobe or in areas alternating with avascular zones (CDS-A pattern). In 8 patients (group II) the thyroid had vascular bands with avascular or poorly vascularized parenchymal areas (CDS-B pattern). In 2 patients, the 2 patterns were present in the same thyroid (A-B pattern or mixed pattern). In these 2 patients the histological aspects were more similar to the CDS-B pattern than the CDS-A pattern. The 2 groups of patients differed in the velocity of systolic peak (VP) that was significantly higher in group I than in group II. In the presurgical study, no changes relative to CDS patterns were observed in patient groups I and II. The VP did not show any appreciable modifications in either group of patients. The thyrotropin-stimulating antibodies (TRAb) returned to normal levels in group II, but not in group I. The 2 CDS patterns, observed in the baseline study, were histologically characterized either by a richly vascularized parenchyma with prevalent endothelial hyperplasia (parenchymatous goiter, CDS-A) or by fibrotic septation with prevalent vascular intimal hyperplasia (CDS-B). In conclusion, this CDS study in GD patients showed 2 distinct vascular patterns. The thyroid glands were histologically characterized by either a richly capillary vascularized parenchyma (parenchymatous goiter, CDS-A aspect) or by fibrotic septation with prevalent intraseptal arteriolar-like hyperplasia (fibrous goiter, CDS-B aspect). Such differences may be secondary to a different duration of hyperthyroidism and/or intensity of TRAb thyroid stimulation.

[Comparison between the diagnostic accuracy in diagnosis of thyroid nodules with fine needle biopsy an intraoperative histological evaluation of frozen tissue]. / Raffronto dell'accuratezza diagnostica nella diagnosi dei noduli tiroidei fra biopsia con ago sottile e valutazione istologica intraoperatoria su tessuto congelato.

BACKGROUND: The aim of this study was to compare the diagnostic accuracy of fine needle biopsy (FNB) and intraoperative frozen-section biopsy (FS) regarding the surgical management of thyroid nodules. METHODS: A total of 812 patients with solitary nodule or dominant nodule in a multinodular goiter were evaluated. The patients underwent preoperative FNB and intraoperative FS diagnosis. RESULTS: The definitive histological diagnosis (HD) was: i) 222 malignant lesions (118 papillary, 67 follicular, 16 anaplastic and 8 medullary cancers); ii) 590 benign lesions. FNB accuracy was 90.6%, sensitivity 96.8% and specificity 87.1%. FS accuracy was 97.4%, sensitivity 91.3% and specificity 100%. False negative (FN) were 10 for FNB and 21 for FS. False positive (FP) were 74 for FNB and 0 for FS. FS was less sensitive for the diagnosis of papillary cancer (more FN) and more specific for the diagnosis of follicular thyroid cancers (no FP). CONCLUSIONS: In conclusion, FS is useful in patients undergoing surgery for a thyroid nodule having a "suspicious" cytology. It adds no information in patients with an FNB diagnosis of malignancy and is of limited use in those in whom an FNB benign lesion is diagnosed.

[Doppler color ultrasonography in the diagnosis of diffuse hyperthyroidism]. / L'eco color Doppler nella diagnosi dell'ipertiroidismo diffuso.

Graves disease is an organ-specific autoimmune disorder characterized by variable clinical and laboratory patterns and by alternating remissions and relapses. We investigated if a correlation exists between the hypervascular pattern of Graves disease, studied with color Doppler US (CDUS), and the degree of thyroid hyperfunction, estimated according to biohumoral parameters. We also investigated if CDUS can differentiate, with the help of pathologic correlations, the glandular histologic patterns recently reported in the literature in thyroidectomized patients. Forty-five patients with Graves disease were selected and submitted, in the same day, to CDUS and to a clinical biohumoral test, including hormone and antibody assays. Eight of these patients had undergone total thyroidectomy. The following variables were studied in each patient: US structure and glandular thickness, color spot distribution, VP, R1, T3, T4, TRab, Tmab, Tgab and patient's age. Thirty-three normal volunteers were also examined. CDUS demonstrated two patterns: pattern A consisted in many homogeneous and bilobed color spots all over the glandular structure; pattern B consisted in color spots areas and/or vascular bands surrounding avascular areas. Pattern A was seen in 13/45 patients (28.9%) and pattern B in 32/45 (71.1%). The subdivision into two groups showed significant differences from a statistical point of view (0.05 > p > 0.001) in relation to the following indices: Vp, T3 and gland size. Of the 8 patients submitted to total thyroidectomy, 3 had pattern A and 5 had pattern B at CDUS. Histology showed major differences between the two groups: thus, thyroidectomized patients with pattern B had thickened interlobular septa and more nodules. with reduced vascular component. Our study confirms that CDUS can diagnose hyperthyroidism; moreover, this technique seems to be capable of differentiating, with the help of color and flow velocity analyses, two different abnormal patterns, which we called A and B. The early results of this preliminary study seem to indicate that CDUS can show two distinct patterns of Graves disease, which differ from a histologic viewpoint and probably also in clinical aggressiveness.

TGF-beta 1 immunohistochemistry in goiter: comparison of patients with recurrence or no recurrence.

The aim of this work was to establish whether the immunohistochemical pattern for TGF-beta 1 in goiters that recur after thyroid surgery is different when compared with goiters that do not recur postoperatively. Twelve goiters, surgically removed by partial resection between 1977 and 1982, were studied. Ten years after surgery, 6 patients had recurrence of goiter or thyroid nodules (group 1); the others did not have any recurrence (group 2). The presence and location of TGF-beta 1 were evaluated a posteriori by immunohistochemistry in histological samples of the tissue that was removed. In each goiter specimen, 50 randomly selected subcapsular follicles were studied to evaluate the percentage of follicles negative or positive for TGF-beta 1 and the protein's intrathyrocyte location. In the slides of group 1, the percentage of TGF-beta 1-positive follicles was statistically (p < 0.01) greater (93.1%) than in group 2 (71.4%). No difference in the location of TGF-beta 1 was found. The authors found a greater percentage of positive follicles for the TGF-beta 1 protein in group 1 patients. In conclusion, TGF-beta 1 production in goiter is variable, time dependent, and may be a marker of active cellular proliferation due to chronic exposure to a goitrogen stimulus. Thus, the more TGF-beta 1 found, the more the cell is stimulated and, therefore, the greater the risk of relapse.

TGF beta 1 immunostaining patterns and locations in adenoma which later recurred.

To investigate whether the immunohistochemical pattern of TGF beta 1 may be a marker of relapse for adenomatous pathology, 18 follicular adenomas, surgically removed by hemithyroidectomy between 1977 and 1982, were studied. The adenomas were divided into two groups according to the presence (group 1, N = 9) or absence (group 2, N = 9) of nodules recurring in the residual thyroid tissue. The presence and location of TGF beta 1 were evaluated a posteriori by immunohistochemistry in the removed adenoma. Fifty randomly selected subcapsular follicles were studied in each adenoma in order to evaluate the percentage of positive follicles and TGF beta 1 intra-thyrocyte location. In adenoma of group 1, the percentage of positive follicles for TGF beta 1 was lower (80%) than in adenoma of group 2 (84%); this was, however, not statistically significant. The location of TGF beta 1 was mainly at the cell base of the epithelial cells in the microfollicles of group 1, but was dominant at the cell apex in group 2 (p < 0.01). In conclusion, adenoma recurrence is independent of TGF beta 1 production; it may be due to an abnormal TGF beta 1 regulation in response to hyperplasiogenic stimuli.

[Evaluation of the role of repeat needle biopsy in the diagnosis and follow-up of thyroid nodules]. / Valutazione del ruolo della ripetizione dell'agoaspirato nella diagnosi e follow-up del nodulo tiroideo.

The goal of the present study was to determine in what percentage of cases was an initial benign cytological diagnosis modified to malignant or suspicion of malignancy by a second aspiration biopsy. The study group consisted of 708 patients, 98 males and 610 females, mean age 46.3 +/- 13.7; FNB was always repeated on the same nodule. The first FNB (cytology I), classified the nodule as: non-diagnostic (group I, 205 cases) or diagnostic (group II, 503 cases); these latter were classified as benign (471) or suspect (32). In 82 cases of group I the second examination after six months (cytology II) was still unable to arrive at a diagnosis; in the remaining 123 cases, it was able to classify 120 as benign and 3 as suspect (the latter being followed up by diagnostic surgery). In group II, cytology II modified the initial diagnosis from benign to suspect (8 cases) or non-diagnostic (7 cases). On the other hand, 29 cases had a change of their initial diagnosis from suspect to benign. The remaining cases of group II repeated a thyroid FNB after one year (cytology III) with a result of benign (486) or non-diagnostic (6). In the 14 cases followed up by diagnostic surgery, due to a second biopsy diagnosis of suspicion, histology showed the presence of Follicular Adenoma in 12 cases and Hashimoto's Thyroiditis in the remaining 2. Based on follow-up surgery, the suspicious lesions seen on the second biopsy turned out to be all non-malignant. However, it is important to underline the greater number of cases where the second examination gave a benign diagnosis when the first examination was judged suspicious. One can conclude that it may be useful to repeat FNB: 1) when the first exam resulted in an inadequate sample, as a second biopsy allows one to classify the nodule 60% of the time; 2) in all cases where there is an initial benign diagnosis, when non-surgical follow-up (clinical and/or echographic) is suspicious.

Enhanced expression of transforming growth factor beta1 in rat thyroid hyperplasia is thyrotropin induced and time dependent.

Forty-three 8-week-old male Wistar rats were studied to evaluate temporal changes of transforming growth factor beta1, (TGF-beta1) mRNA levels in thyroid tissue during pharmacologically induced goiter. Four rats were treated with purified bovine thyrotropin (TSH; Ambinon, 2 mU/day sc) for 7 days before being sacrificed. Thirty-one were treated with propylthiouracil (PTU), added to their drinking water at a concentration of 0.2 g%, and subsequently were sacrificed as follows: five after 1 week (PTU-1): five after 2 weeks (PTU-2); five after 4 weeks (PTU-4); five after 8 weeks (PTU-8); five after 12 weeks (PTU-12). In six rats, after 12 weeks of treatment. PTU was withdrawn for 2 months and subsequently started again in three rats which were sacrificed after 2 weeks (PTU-R); the remaining three rats were sacrificed without any further treatment (PTU-R control). Eight rats (control rats) were never treated and served as controls. After sacrifice, blood was drawn for determination of total thyroxine and the thyroid was excised and subdivided into two lobes. Northern analysis for TGF-beta1 was performed in one lobe. while histological and immunohistochemical studies were performed in the other lobe. Gene expression of TGF-beta1 was induced in TSH- and PTU-treated rats. In TSH-treated rats TGF-beta1 gene expression was less detectable than in PTU-treated rats, where it became evident after 2 weeks and remained through weeks 4-8. Gene expression of TGF-beta1 wits also seen in PTU-R rats, but not in the control and in the PTU-R control. Immunohistochemical analysis showed a different presence and location for the TGF-beta1 protein, which appears to be dependent on the time of exposure to mitogenic stimulus. In conclusion, TGF-beta1 is produced in response to both a direct (TSH by itself) and indirect (TSH induced by PTU-induced hypothyroidism) cellular proliferative stimulus and is not linked to an adaptative phenomenon secondary to hypothyroidism. The immunohistochemical location of TGF-beta1 within the thyrocytes is influenced by mitogen exposure time. A TGF-beta1 immunohistochemical evaluation may be important to define exposure time and activity of goitrogenic stimuli.

[Echo Doppler in the characterization of thyroid nodular disease]. / L'eco Doppler nella caratterizzazione della patologia nodulare tiroidea.

This study was aimed at investigating role and efficacy of color-Doppler US in the characterization of thyroid nodules. Eight-three consecutive patients with only one solid thyroid nodule, not smaller than 0.8 cm, were examined. They were submitted to scintigraphy and laboratory tests first and then to color-Doppler US, to fine-needle biopsy and/or to histologic examinations. Color-Doppler US examinations were performed with a 7.5 MHZ linear probe, 5-MHz Doppler frequency, PRF = 0.8 KHz, 40-50 degrees insonation angle, wall filters at the lowest level, 2-5 mm sample volume, color and Doppler gains set at 30-50% and asynchronous data collection. The final diagnosis, made at cytology and/or histology, showed 43 follicular hyperplasias, 19 follicular adenomas and 21 carcinomas. The following US variables were considered: nodule size, site, margins and the possible presence of the "halo sign" pattern, with a special attention paid to micro-/macrocalcifications, signs of invasion of surrounding anatomic structures and possible adenopathies. With color-Doppler US, we studied presence and distribution of nodular vascularization, peak (Vp) and middle (Vm) velocity, resistive index (RI) and Doppler spectrum morphology. In agreement with the current literature, 3 patterns of nodular vascularization were considered: not apparent, or type I (3/83), which was found only in follicular hyperplasia; peripheral, or type II (46/83) and finally, peri- and intranodular, or type III (31/83). Hyperplasias exhibited a type I pattern rarely and exclusively and, if vascularized, they always exhibited Vp < 50 cm/s, Vm < or = 40 cm/s and mostly (39/40 RI < or = 0.75; adenomas were always vascularized, with Vp > 50 cm/s and mostly (18/19) RI < or = 0.75; primary or secondary tumors were always vascularized, with an extremely variable distribution, and if Vp < 50 cm/s, their RI > 0.75, while if Vp < 50 cm/s, their RI was independent of the threshold value of 0.75. These preliminary conclusions seem to confirm that vascular patterns alone are not particularly helpful, compared with B-mode US results, in distinguishing among thyroid nodules. Nevertheless, Vp and RI may be of great usefulness in the characterization of solid nodules and in the selection of the patients to submit to fine-needle biopsy.

Decreased expression of insulin-sensitive glucose transporter mRNA (GLUT-4) in adipose tissue of non-insulin-dependent diabetic and obese patients: evaluation by a simplified quantitative PCR assay.

Impaired cellular uptake and utilization of glucose is the hallmark of non-insulin-dependent-diabetes (NIDDM). We have developed a quantitative assay to probe the expression of glucose-transporter genes in tissues derived from patients with NIDDM. Using the polymerase chain reaction (PCR), we assessed levels of expression of the insulin responsive glucose transporter GLUT-4 in adipose tissue of patients with NIDDM and in obese patients. We report that expression of GLUT-4 is reduced in NIDDM and in obesity associated with hyperinsulinemia and insulin resistance. These results suggest that reduction of GLUT-4 levels in the adipose cell plays an important role in the pathogenesis of insulin resistance, an early feature of NIDDM.

[Treatment of Plummer's adenoma: correlation between ultrasonography-guided percutaneous injection of ethanol and autoimmunity]. / Trattamento dell'adenoma di Plummer: correlazione tra iniezione percutanea ecoguidata di etanolo e autoimmunità.

The authors investigated the value of percutaneous ethanol injection in the treatment of Plummer's adenoma. Ten patients were studied: they exhibited a single, hot and toxic nodule in the thyroid. Thyroid autoimmunization (TSAb; TMAb; TGAb) and function (T3; T4; TSH; FT3; FT4) were studied in all patients, before treatment and at 1 month and 3 months. Scintigraphy with 99Tc was performed at the same time intervals. In the euthyroid stage, alcoholization was preceded by US and cytology. Three-four ml of ethanol 95 degrees were injected once or twice a week, from a minimum of 3 to a maximum of 8 injections. Treatment was successful in 2 cases; partial success was obtained in 4 cases, and in 4 cases treatment failed. In all successful cases antibodies were negative and the nodules had hypoechoic echostructure, with a peripheral hypoechoic halo and no areas of internal colliquation. Thus, US-guided percutaneous alcoholization seems to be capable of correct indications in hypoechoic nodules not exhibiting areas of colliquative necrosis and with negative antibodies. However, the problem of the dose of alcohol to inject to treat the nodule thoroughly is still to be debated.

[Hypothalamic amenorrhea. Different patterns in the pulsatile secretion of LH during 24 hours and different responses to the stimulation test with GnRH]. / Amenorrea ipotalamica. Differente comportamento della secrezione pulsatile di LH nelle 24 ore e differenti risposte al test di stimolo con GNRH.

In 12 patients with hypothalamic amenorrhea and in 5 normal women, plasma gonadotropins (LH and FSH) were assayed before and 20, 30, 60, and 120 minutes after stimulation with 10 mcg GnRH i.v. and 24 hours after stimulation with 100 mcg GnRH i.v. In four patients and in controls the pulsatile secretion of LH was evaluated by blood sampling at 15 minute intervals for the 24-hour period. All patients showed different increases in LH after administration of 10 mcg and 100 mcg at 60 and 120 minutes. In two patients, with decreased LH pulse frequency, the gonadotropin increase is dose-dependent in respect to GnRH. In the other two, with normal LH pulse frequency, no difference was shown. In conclusion, this study suggests that the mechanism responsible for amenorrhea is due to reduced frequency of pulsatile GnRH secretion. However, in some patients LH pulse frequency was within the normal range. The double GnRH test (10 or 100 mcg) may be useful in distinguishing these different forms of amenorrhea.

[Growth hormone after baclofen in normal and acromegalic subjects]. / Ormone della crescita dopo baclofene in soggetti normali ed acromegalici.

Serum growth hormone (GH) levels in basal conditions (two samples) and 30, 60, 90, 120, 150 and 180 minutes after oral administration of baclofen (20 mg) were evaluated in 6 healthy subjects and in 6 acromegalic patients. The effect of cimetidine (400 mg i.v.) administrated 45 minutes after baclofen (20 mg by mouth) were evaluated in 9 healthy women. Baclofen was able to significantly rise serum GH levels in normal subjects but no in acromegalic patients. Cimetidine suppress GH increase induced by baclofen. It was concluded that: 1) baclofen, GABAb receptor agonist, stimulate GH secretion by inhibition of GIF secretion or by stimulation of GRF secretion; 2) istamine, through H2 receptors in the hypothalamus, is important to mediate GH release induced by stimulation of GABAb receptors.

[Prolactin after baclofen in healthy subjects and prolactinoma patients]. / Prolattina dopo baclofene in soggetti normali e con prolattinoma.

Serum prolactin (PRL) levels in basal conditions (two samples) and 30, 60, 90, 120, 150 e 180 minutes after oral administration of baclofen (20 mg) were evaluated in 6 healthy subjects and in 10 patients with prolactinoma. The effect of baclofen (20 mg by mouth) on the PRL secretion cimetidine (400 mg i.v.) or domperidone (20 mg i.v.) induced were evaluated in 9 healthy women by administration of baclofen 60 minutes before cimetidine or domperidone. Baclofen was unable to significantly rise serum PRL levels in healthy subjects and in patients affected by prolactinoma and furthermore did not interfere with PRL rise domperidone induced. On the contrary baclofen decreased PRL rise cimetidine induced. It was concluded that: in basal condition, GABAb receptor don't play an obvious role in modulation of PRL secretion; when H2 istaminergic inhibition on PRL secretion is blocked (at an hypothalamic site), a GABA inhibition, b receptor mediated, on PRL secretion became more clear; the domperidone blockade of hypophysial dopaminergic receptors suggests that GABAb modulation of prolactin secretion don't obtain itself by dopaminergic pathways.

[Neurohypophyseal diabetes insipidus. Anatomo-clinical correlations]. / Diabete insipido neuroipofisario. Correlazioni anatomo-cliniche.

Eighteen patients aged between 14 and 60 years suffering from diabetes insipidus were studied. Diabetes insipidus was diagnosed by means of Robertson's test. All patients underwent C.T. scanning and evaluation of PRL basally and after TRH (200 mcg e.v.). Twelve patients (66%) showed neurological lesions (secondary central diabetes insipidus). Six of these patients had hyperprolactinaemia. Our data suggest that most of central diabetes insipidus are associated with central system nervous (S.N.C.) damage. In same cases the presence of hyperprolactinaemia suggests a brain damage. Therefore neuroradiological study is very important in all cases of neurohypophyseal diabetes insipidus.

[Evaluation of TSH secretion after GnRh in patients with primary hypothyroidism]. / Valutazione della secrezione di tsh dopo GnRH in pazienti con ipotiroidismo primario.

6 women (mean age 38 years) with high Thyroid Stimulating Hormone (TSH) serum levels because affected from primary hypothyroidism were studied. 6 healthy women (mean age 31 years) represented the control group. All subjects underwent evaluation of serum TSH, Follicle Stimulating Hormone (FSH), Luteinizing Hormone (LH), basally and 20, 30, 60, 120 minutes after administration of Gonadotropin Releasing Hormone (GnRH: 100 meg. IV). Seric FSH and LH show a large increase 30 minutes after GnRH either in healthy or in hypothyroid subjects. TSH is unresponsive to GnRH in normal condition, while shows a clear decrease (-78%) 30 minutes after GnRH in primary hypothyroidism. Rarely the hypothalamic releasing hormones possess an inhibitory effect on anteipophyseal secretions. Previously a GnRH inhibitory effect on prolactin (PRL) release from PRL secreting tumors in rat. The GnRH inhibitory effect on TSH release in pathological conditions such as primary hypothyroidism is difficult to explain: it may be that GnRH acts on Central Nervous System or at pituitary level: in the last case it could bind sites which are not quite different in the different glycoprotein secreting cells.