Heterogeneity of nuclear DNA pattern and its relationship with cell cycle activity parameters in multinodular goitre.

OBJECTIVE: Recent studies suggest that the malignancy rate in multinodular goitre is not significantly different from that observed in solitary nodules and that chromosomal aberrations are not infrequent in multinodular goitre. To further investigate this topic we determined the DNA pattern in multinodular goitres. DESIGN: DNA ploidy and cell cycle activity parameters were determined in multinodular goitres. PATIENTS: We evaluated 235 patients (185 female, 50 male, mean age 52 +/- 13 years), who had undergone thyroidectomy; 11 of them harboured occult differentiated microcarcinoma. MEASUREMENTS: DNA index (DI), coefficient of variation of G0/G1 phase (CV), percentage of cells in S phase (%S) and in G2+M phase (%G2-M) and proliferative index (PI = %S+%G2-M) were determined by flow cytometric analysis (FCM) in tissue samples taken from 3 different areas of the thyroid gland. RESULTS: Aneuploid DNA was found in 50 goitres without carcinoma (22.3%) and in 5 goitres with carcinoma (45.5%). The mean PI of euploid cells in the goitre without carcinoma was significantly higher in the goitres with an aneuploid component compared to the goitres without aneuploidy (10.8 +/- 1.3 SEM vs 6 +/- 0.32; P +/- 0.001). Also, the percentage difference between maximal and minimal PI found within each goitre (delta PI %) was higher in the former group (373 +/- 49 SEM vs 142 +/- 11.3; P < 0.0001). The PI was significantly higher in goitres with carcinoma compared to the goitres without carcinoma (12.9 +/- 3.2 SEM vs 7.07 +/- 0.40; P < 0.05). CONCLUSIONS: The findings of increased proliferation rate in goitres with an aneuploid or neoplastic component suggests that some factors involved in goitrogenesis could also be responsible for the development of chromosomal aberrations and/or for the selection of cellular clones endowed with high growth potential.

An unusual case of adrenal failure due to isolated metastases of breast cancer.

We describe a patient affected by adrenal insufficiency due to metastases of breast cancer. Adrenal involvement became clinically evident 20 years after radical mastectomy and it was the only secondary localization of the tumor. There is still no evidence of other metastases after a two year follow-up. This case suggests that adrenal function evaluation should be included in periodical follow-ups of patients who underwent radical mastectomy for breast cancer.

[Complications of thyroidectomy: hemorrhage]. / Complicanze della tiroidectomia: l'emorragia.

The authors report their experience in haemorrhage after thyroid surgery. Haemorrhagic complications occurred in 5 cases in a series of 1803 sequential thyroidectomies (incidence: 0.27%). In particular, incidence was 1.9% after interventions for thyroid neoplasias (adenoma and carcinoma) and 0.18% after interventions for non-neoplastic thyroid pathology. Haemorrhage occurred always after "total" operations, even if monolateral. Causative and contributing factors, precautions and measures helpful in reducing the incidence and the potential dangerousness of haemorrhagic complications are discussed.

[Nuclear DNA in neoplastic pathology of the thyroid gland]. / Il DNA nucleare nella patologia neoplastica della tiroide.

We have analysed the nuclear DNA content in a series of 33 thyroid tumours (18 carcinomas and 15 adenomas) and, for comparison, in 189 nodular strumas and 17 tissue samples of normal thyroids, calculating cell cycle parameters and presence of aneuploid DNA. Cell suspensions were prepared for each of three tissue fragments taken for different areas of the surgical specimens. Cell subpopulations with aneuploid DNA content were present in 39% of carcinomas, 27% of adenomas, 20% of strumas, but were absent in the samples from normal thyroids. The presence of hyperdiploid DNA was much more frequent than that of hypodiploid DNA in all pathologic tissues. The mean proliferation index was 14.1 in the carcinomas, 6.6 in the adenomas, 7.1 in the strumas and 6.1 in normal thyroid tissues. The percent of histograms with a coefficient of variation of the G0-G1 peak greater than 5 was highest in the carcinomas (26%). The significance and implications of the reported data are discussed for the interpretation of thyroid neoplastic pathologies.

[Hormonal therapy in differentiated carcinoma of the thyroid gland]. / La terapia ormonale del carcinoma differenziato della tiroide.

Thyrotropin (TSH) suppression therapy using thyroid hormone plays an important role in the management of patients thyroidectomized for differentiated thyroid cancer. The rationale for TSH suppression is that differentiated thyroid cancer cells have TSH receptors and show increased adenylate cyclase activity following TSH exposure. L-thyroxine is used for long-term therapy. L-triiodothyronine is preferred when suppressive therapy must be discontinued for radioiodine scan, since its shorter half-life allows more rapid increases of TSH levels. The assessment of TSH suppression is still uncertain. The development of second and third TSH assay generations with progressive improvement in sensitivity has made the TRH test unnecessary and has raised the issue of the TSH level indicative of TSH suppression. In clinical practice TSH values below 0.1 mU/L are considered compatible with appropriate TSH suppression. Serum thyroglobulin is a reliable marker of metastatic disease after total surgical and radioiodine ablation of the thyroid gland and it is useful in the surveillance of patients with differentiated thyroid cancer.

[The cytofluorometric analysis of nuclear DNA in nodular goiter]. / Analisi citofluorimetrica del DNA nucleare nello struma nodulare.

The purpose of this study was to measure the nuclear DNA content of cells in three different areas of multinodular goiter from 15 patients. Diploid DNA was found in the cell samples from 12 patients; the biopsies from one patient contained a clear ipodiploid peak (61%, D.I. 0.75) and those from the remaining 2 had dubious ploidy. The calculation of the mitotic index, including cells in S + G2M phases, evidentiated a large variability between different samples from the same goiter, thus correlating with the cellular heterogeneous composition of the thyroid.

[Recent findings on the etiopathogenesis of multinodular goiter. II. Thyroid growth factors]. / Recenti acquisizioni sull'etio-patogenesi dello struma multinodulare. II. I fattori di crescita della tiroide.

In the last ten years several experimental data have suggested that growth factors may play an important role in modulating thyroid growth and function. Epidermal Growth Factor (EGF) is present in large quantities in thyroid tissue, where it appears to stimulate DNA synthesis and inhibit cellular function. Insulin-like Growth Factors (IGFs), Interleukin I (IL-I) and Fibroblast Growth Factor (FGF) show the same stimulation on cell proliferation. On the contrary Transforming Growth Factor beta (TGF-beta) and somatostatin display inhibitory effects on follicular growth. Therefore it is likely that growth factors' altered production and/or their receptors abnormal expression on the thyroid cells surface might be involved in the development of multinodular goiter and some thyroid neoplasms.

[Recent findings on the etiopathogenesis of multinodular goiter. I. Immunoglobulin stimulation of thyroid growth]. / Recenti acquisizioni sull'etio-patogenesi dello struma multinodulare. I. Le immunoglobuline stimolanti la crescita della tiroide.

This present review of the literature deals with the possible autoimmune genesis of the multinodular goiter. Some investigators have identified an immunoglobulin stimulating specifically the growth of the thyroid gland (TGI) in the sera of patients affected with sporadic goiter, quite different from TSI, involved in Graves' disease. Other authors report divergent results; however there are many methological differences in these studies that give rise to controversies about the evaluation of the data. At present, these studies have failed to demonstrate consistently an autoimmune genesis of multinodular goiter.

[Behavior of TBII (TSH receptor binding immunoglobulins) in multinodular struma]. / Sul comportamento delle TBII (TSH receptor binding inhibitory immunoglobulins) nello struma multinodulare.

The authors consider the behaviour of TBII (TSH receptor binding inhibitory immunoglobulins) in multinodular goiter, in relation to the functional status of the thyroid classified on the basis of T3, FT4, TSH IRMA. The samples were collected from 53 patients with normal T3, FT4 and TSH; 14 patients with T3 and FT4 in normal range and TSH less than 0.15 milli U/l; 8 patients with T3 and/or FT4 above the superior limits of normal range and TSH less than 0.15 milli U/l and from a control group of 10 patients with Grave's disease. TBII was measured by radioreceptor assay and the index resulted less than 15% in all the patients with eufunctioning or hyperfunctioning multinodular goiter. Mean value in biochemically hyperthyroid patients was 6.25% and in euthyroid patients was 5.69%. The difference was statistically not significant. Moreover, significantly elevated levels of TBII were found in 60% of patients with Grave's disease.

[Our experience in the surgical treatment of Arbuthnot Lane disease]. / La nostra esperienza nel trattamento chirurgico della malattia di Arbuthnot Lane.

In the light of their experience, the authors review the data reported in the literature regarding Arbuthnot Lane Disease. The therapeutic indications are examined, and the results of the various types of surgery proposed are compared.

[Synchronous abdomino-perineal amputation (global evaluation of the intervention in our experience)]. / L'amputazione addomino-perineale sincrona (valutazione globale dell'intervento nella nostra esperienza).

In the light of their experience, the Authors examine the validity of synchronous abdomino-perineal resection. Their study population consists of 224 such operations. On the basis of the results achieved, the conclusion is reached that there is still no realistic alternative today to synchronous abdomino-perineal resection for the treatment of malignancies whose lower borders lie at a distance of less than 6.5 cm from the anal margin.

[Postoperative hypothyroidism]. / L'ipotiroidismo postoperatorio.

The author consider the problem of hypothyroidism after thyroid surgery for Basedow's disease and multinodular, toxic and nontoxic, goitre. In the behavior of such surgical complication, in addition to thyroid remnant size and technique employed many others biological factors, whose nature up to today is not well defined, are the cause. This multifactorials genesis makes very unforeseeable, in each case, the long term result of surgery in the form of hypothyroidism. However, the hypothyroidism after surgery may be the consequence of a phase of functional adjustment, and then to start substitution therapy immediately after surgery may have opposite effect.

[Behavior of thyroglobulin after fine needle aspiration of the thyroid]. / Comportamento della tireoglobulina dopo agoaspirazione tiroidea con ago sottile.

The authors report the behaviour of serum concentration of thyroglobulin (TG) after fine needle aspiration biopsy of the thyroid. Compared with the basal level, serum concentration of thyroglobulin increase of 70% three minutes and of 341% sixty minutes after this maneuver. The authors agree with those who believe an interval of 10-15 days between fine needle aspiration biopsy of the thyroid and determination of serum concentration of thyroglobulin is necessary.

[Surgical therapy of Basedow's disease]. / La terapia chirurgica del morbo di Basedow.

The authors, in the light of the data of the literature, study the problem of the surgical treatment of Basedow disease. Besides those who suggest the total thyroidectomy as an ultimately curative intervention, most of surgeons prefer the subtotal thyroidectomy. However, the result of such operation is doubtful as to postoperative hypo- and hyperthyroidism, due to the operativeness of factors of not only biological, but also technical nature. In order to make the therapeutical result as satisfactory as possible, the literature suggests some particular surgical solutions, such as ligature of thyroid artery, limited subtotal thyroidectomy and modified subtotal thyroidectomy, which seem to obtain satisfactory results from the clinical standpoint.

[Behavior of creatine kinase-isoenzyme BB in the nodular pathology of the thyroid (preliminary note)]. / Comportamento della creatinakinasi-isoenzima BB nella patologia nodulare della tiroide (nota preliminare).

The literature indicates the presence of the BB isoenzyme of creatinakinase in the thyroid tissue. The CKBB, therefore, was dosed with radioimmunologic method in a group of 79 patients bearing nodular pathology of thyroid (12 carcinomata, 42 nodular strumata, 25 adenomata), to check whether such parameter could be used as marker in the thyroid neoplasms. The CKBB, however, did not show a statistically different behaviour in the three classes of pathology considered.

[Initial therapeutic evaluations of 141 patients with carcinoma of the breast under 40 years of age]. / Prime valutazioni terapeutiche su 141 pazienti affette da carcinoma della mammella con età inferiore a 40 anni.

The Authors, considering 141 cases of patient women under 40, suffering from breast cancer, analyse the prognostic factors in relation to the different therapeutical approach, histologic type, dimensions of T, and presence or absence of metastases at the axillary lymph nodes. They, moreover, appraise the actuarial global survival with no disease (NED) of this group of patients as compared with the survival of women in more advanced age.

[Rare complication of calculosis of the gallbladder: Bouveret's syndrome]. / Una rara complicanza della calcolosi della colecisti: la sindrome di Bouveret.

The authors report a case, they had the opportunity to observe, of pyloric stenosis, secondary to the migration of two big gall-stones into stomach through a cholecysto-gastric fistula. As the event is extremely rare, they discuss some clinical, diagnostical and therapeutical aspects of same.

[Behavior of antithyroglobulin and antimicrosomal antibodies in thyroid pathology]. / Sul comportamento degli anticorpi antitireoglobulina e antimicrosomiali in patologia tiroidea.

The Authors report the behaviour of antithyroid and antimicrosomial antibodies in a group of 394 patients suffering from nodular struma, thyroid adenoma and carcinoma, Hashimoto's thyroiditis, other thyroidites and Basedow's disease. The autoimmune pathology (Hashimoto's thyroiditis and Basedow's disease) is joined to a higher frequency of positive titles for both antibodies. In such pathology we also meet the highest titles. In the non-autoimmune pathology the antimicrosomial antibodies are more frequently positive than the antithyroid ones. If one considers the behaviour of both antibodies, the specificness about the diagnosis of thyroiditis increases.