Thyroid nodules with Hürthle cells: the malignancy risk in relation to the FNA outcome category.

PURPOSE: The aim was to find whether the presence of Hürthle cells (HC) in a smear influences the categorization of FNA results or the risk of malignancy (RoM) of particular categories of cytological diagnosis. METHODS: 25,220 FNA performed in a single center in years 2005-2017 were analyzed. Almost all the examined patients were exposed to moderate iodine deficiency for most of their lives. The distribution of FNA outcome categories was compared between two groups: with or without HC (HC and non-HC). The RoM was evaluated on the basis of postoperative histopathological examination (3082 patients). RESULTS: HC were found in 7.5% of diagnostic FNA. HC nodules were classified into categories II (78.2% vs. 91.9%, p < 0.0000) and VI (0.4% vs. 1.2%, p = 0.0017) less often than non-HC nodules, but more frequently to categories III (14.4% vs. 5.8%, p < 0.0000), IV (11.2% vs. 0.9%, p < 0.0000) and V (1.5% vs. 0.8%, p = 0.0013). There were no significant differences in RoM between HC and non-HC nodules. The RoM in HC and non-HC nodules of particular categories of the Bethesda system was as follows: II: 1.8% vs. 0.8%, III: 9.7% vs. 3.8% when only the last FNA was considered and 10.8% vs. 6.4% when the category III in any performed FNA was considered; IV: 12.7% vs. 10.9%; V: 41.7% vs. 58.2%; and VI: 100% vs. 96.9%. CONCLUSIONS: HC nodules are classified into categories of equivocal cytological outcomes more often than nodules without HC. Nevertheless, the presence of HC in a smear does not significantly affect the RoM of FNA categories.

Effectiveness of the iodine prophylaxis model adopted in Poland.

OBJECTIVE: Most of the Polish territory has been classified as an iodine-deficient and endemic goiter area according to the International Council for Control of Iodine Deficiency (ICCIDD) criteria. In 1997 the obligatory model of iodine prophylaxis was implemented. Our investigations were aimed at the effectiveness of iodine prophylaxis in Poland. METHODS: We assessed urinary iodine excretion and goiter prevalence in 5663 children aged 6-12 yr. The population of children from the same 27 schools was investigated from 1992 to 1994 (1406 girls and 1244 boys) and from 1999 to 2005 (1563 girls and 1450 boys) using identical laboratory and ultrasound methods. RESULTS: We found significant increase in iodine urinary concentration (median 52 microg/l vs 93 microg/l, p<0.001) with accompanying drop in goiter prevalence (29.6% vs 5.2%, p<0.001) after implementation of iodine prophylaxis. Iodine excretion distribution changed significantly after 1997 with an increase in the percentage of children with iodine urinary concentration above 100 microg/l from 10.8% to 45.4%, respectively. A significantly higher iodine urinary concentration was observed in lowlands compared to uplands both before and after implementation of iodine prophylaxis (median, 50 microg/l vs 57 microg/l and 86 microg/l vs 114 microg/l, respectively, p<0.001). The goiter prevalence did not differ between girls and boys from 1992 to 1994 (28.8% vs 30.5%, p=0.35) and 1999 to 2005 (5.5% vs 4.9%, p=0.45). CONCLUSIONS: Implementation of the new model of iodine prophylaxis in Poland in 1997 has led to significant increase in iodine urinary concentration and decrease in goiter prevalence among Polish schoolchildren. In the youngest group of children (6-8 yr olds), prevalence of goiter decreased to 3.2%--i.e. below endemic levels.

Multiparameter analysis of AgNOR in thyroid lesions: comparison with PCNA expression.

The aim of the study was to examine numerous features of argyrophilic proteins related to nucleolar organizer regions (AgNORs) in thyroid tumors, relate them to PCNA expression and evaluate which of these features might be useful in the diagnosis of thyroid lesions. Paraffin sections of 100 thyroid tumors were silver-stained and divided into 9 groups: nodular goiter (NG), simple adenoma (SA), microfollicular adenoma (MFA), follicular carcinoma (FC), follicular variant of papillary carcinoma (PC-F), classical variant of papillary carcinoma (PC-C), Hürthle cell adenoma (HA), Hürthle cell carcinoma (HC), and anaplastic carcinoma (AC). The slides were analyzed with the computerized system for image analysis. A weak correlation was found between PCNA expression and AgNOR size. AC differed significantly from all other examined groups in many features of AgNOR dots. Hürthle cell neoplasms were characterized by the presence of a usually single and relatively large dot. With respect to diagnosing follicular lesions, we found that the evaluation of the total area of dots in the nucleus seemed to be the most useful for discrimination: the assumption of 4.9 micro m2, as a cut-off value, allowed a correct classification of 77% of FC cases. Computer-aided morphometric analysis of AgNORs may be useful in the diagnostics of thyroid lesions.

Fine needle aspiration cytology in non-neoplastic non-toxic recurrent nodular goitre.

The aim of the study was to examine whether evaluation of anisokaryosis is helpful in the cytological diagnosis of focal lesions in non-toxic recurrent goitre (NRG) after thyroidectomy for non-malignant goitre. Karyometric analysis was performed in routine cytological smears obtained from 80 females: 40 with focal lesions in non-toxic primary goitre (NPG) and 40 with NRG (postoperative histopathological examination revealed nodular goitre in both groups in all cases). We found that the level of anisokaryosis was significantly (P<0.005) higher in NRG than in NPG. There were no significant differences between the two lesions, in cellular composition or thyroid follicular cell arrangement. Thus, isolated anisokaryosis, a feature of malignancy in patients without a prior thyroidectomy, has limited diagnostic value in recurrent goitre.

Iodine-induced hyperthyroidism--an epidemiological survey several years after institution of iodine prophylaxis in Poland.

In 1997, the obligatory model of iodine prophylaxis was introduced in Poland in order to correct the existing status of mild and/or moderate iodine deficiency. In order to monitor possible side-effects of increased iodine supply, studies on iodine-induced hyperthyroidism were initiated by establishing several regional registers of hyperthyroidism. In the present paper, the results of a two-year monitoring (2000-2001) have been summarized. There are no epidemiological data on hyperthyroidism prior to starting the iodine prophylaxis, but the obtained current data are comparable to observations in other countries, made after iodine supplementation. The incidence of iodine-induced hyperthyroidism did not exceed the acceptable level, thus confirming--together with previous observations on the effectiveness of iodine prophylaxis--the adequacy of applied dose of KI (30 microg/kg NaCl), used for salt iodization in Poland.

Correlation between PCNA expression and AgNOR dots in pituitary adenomas.

Nucleolar organizer regions are segments of DNA associated with argyrophilic proteins (AgNORs). Our previous findings showed that the number, the area, and the intranuclear localization of AgNOR dots differ according to tumor aggressiveness and to the hormone-immunopositivity of pituitary adenomas. Proliferating cell nuclear antigen (PCNA) is a nuclear protein, whose expression is correlated with cell proliferation. The aim of the present paper was to examine PCNA-labeling indexes in pituitary adenomas and to correlate them with AgNOR dots in various immunohistochemical types of the tumors. Histological slides from 32 pituitary tumors and one normal pituitary were silver-stained and analyzed with a computerized system for microscopic image analysis. We found that the percentage of PCNA-positive cells did not differ significantly among examined groups of monohormonal adenomas. However, tumors immunopositive for alpha-subunit (alpha-SU) showed a significantly higher (p < 0.05) PCNA index than adenomas immunonegative for that unit. PCNA index in recurrent tumors was significantly higher than in primary adenomas. There was a moderate positive correlation between the PCNA index and the mean area of AgNOR dots and a similar correlation between the PCNA index and the area of the biggest dot in the nucleus. The obtained results reveal that the PCNA indexes and estimated parameters of AgNOR dots differ according to tumor aggressiveness.

Effects of octreotide on propylotiouracil-induced goiter in rats: a quantitative evaluation.

To evaluate the possible antigoitrogenic effect of somatostatin, the influence of long-acting somatostatin analog--octreotide--on experimental goiter developed in rats treated with propylthiouracil was examined. Goiter formation was assessed by measurement of the main histological compartments of the thyroid as well as by morphometric analysis of the vascularization and blood supply of the gland. Although treatment with octreotide did not prevent the goiter formation, it clearly reduced blood supply and vascularization of the thyroid and counteracted propylthiouracil-induced increase in the relative volume of follicular epithelium. To conclude, the somatostatin analog--octreotide--is effective in reduction of goiter vascularisation. This finding provides a rationale for the clinical trials of the treatment of hypervascular goiter by somatostatin analogs.

Thymidine Kinase (EC 2.7.1.21) Activity in Homogenates of Human Thyroid Tissue, Following the Exposure to Epidermal Growth Factor (EGF) in vitro.

The activity of thymidine kinase (TK - EC 2.7.1.21) was measured in human thyroid tissue homogenates incubated in vitro. This enzyme functions as a part of the pyrimidine salvage pathway involved in DNA synthesis. The thyroid tissue was obtained from the thyroids of patients thyroidectomized at the Department of Endocrine Surgery, Medical University of lodz because of: 1. non-toxic nodular goiter (NTNG): tissue macroscopically unchanged, woman 46 yrs; 2. non-toxic adenoma (NTA), woman 37 yrs; 3. toxic adenoma (TA), woman 45 yrs. The tissue was incubated for 4 hours in RPMI 1640 medium (Gibco), containing Hepes buffer, 15 % FCS and the examined substance - epidermal growth factor (EGF) - used in five different concentrations (0.1 ng/ml, 1 ng/ml, 10 ng/ml, 100 ng/ml, 1000 ng/ml). The TK activity was measured according to Cheng and Prusoff (1974) as modified by Greger and Draminski (1989). The reaction products were separated by ascending chromatography. It was found that: 1. TK activity in thyroid tissue from NTNG and NTA did not significantly differ from control incubations without EGF, while it was significantly higher in the thyroid tissue from TA; 2. in the range of concentrations from 1 ng/ml to 1000 ng/ml, EGF increased TK activity in the macroscopically unchanged tissue from NTNG; 3. the incubation of the tissue from NTA with EGF resulted in the increase of TK activity in a concentration-dependent manner; 4. EGF stimulated TK activity in the tissue from TA, but the difference was significant only after the lowest EGF concentration. The obtained results suggest a possible role of EGF in the pathogenesis of NTNG, as well as of NTA and TA in humans.

Usefulness of computer-aided karyometric examination in preoperative differentiation of Hürthle cell lesions.

We have previously reported that there is a significant difference in the mean size of thyrocyte nuclei among patients with nodular goiter, follicular adenoma, and follicular carcinoma. In the present study, we have examined karyometric parameters of Hürthle cells in smears collected from 41 patients with Hürthle cells adenomas, Hürthle cells carcinomas, nodular goiter, and lymphocytic thyroiditis. The karyometric evaluation was performed with the image analysis computer system-Karyometry Manager 1.2. We measured the mean volume, the mean intersection area, and the mean perimeter of 100 nuclei in each routine smear. We found that the sizes of Hürthle cell nuclei could be arranged in the ascending order from the nodular goiter, through lymphocytic thyroiditis to Hürthle cell neoplasms, but those differences did not reach a border of statistical significance.

Multifarious system for quantitative analysis of histologic compartments.

A system is presented for measuring relative volumes of histologic compartments in microscopic slides. The computer program for that system was written by us as an MS windows 3.x application. The applied method of measurements, based on the "point-counting" technique, requires the recognition of the compartments, corresponding to the selected points of an image. The neural network was employed to facilitate the process of classification of the examined points. Nine descriptors of an image were selected as an input to the network (a pattern). Error-free compartment recognition was not always achieved because of some overlapping of the pattern classes. Nevertheless, the semi-automation of the assignment of the examined points to histologic compartments makes the measurements less laborious and time-consuming.

Karyometric analysis in the cytologic diagnosis of thyroid lesions.

OBJECTIVE: To assess the possible role of karyometry in improving the diagnostic value of fine needle aspiration biopsy (FNAB) of the thyroid. STUDY DESIGN: Thyrocyte nuclei were evaluated in routine slides obtained from 229 patients. The cytologic specimens were divided into seven groups according to the results of corresponding postoperative histopathologic examinations. Karyometric measurements comprised assessment of nuclear volume intersection area and perimeter as well as level of anisokaryosis, evaluated as standard deviations of those parameters in single slides. The karyometric evaluation was performed with a computerized image analysis system. RESULTS: The size of thyrocyte nuclei increased from nontoxic nodular goiters through follicular adenomas, toxic nodular goiters treated with antithyroid drugs, lymphocytic thyroiditis, papillary and follicular carcinomas to anaplastic carcinomas. The observed differences between those groups were statistically significant, but there was marked overlapping. Our data indicate also that the age and sex of the patient influence the cytologic picture of nodular goiter. The evaluation of anisokaryosis increases the usefulness of karyometry in differentiating malignant neoplasms from benign lesions. CONCLUSION: Karyometric analysis increases the probability of a correct diagnosis with FNAB examination.

INFLUENCE OF EGF ON THE RELATIVE VOLUMES OF COLLOID, EPITHELIUM AND STROMA AND ON THYROCYTE NUCLEI SIZE IN RAT THYROID LOBES IN VITRO.

The epidermal growth factor (EGF) is believed to be a potent growth factor for the thyroid gland. In the present study, we have examined the relative volumes of the main histological compartments (colloid, epithelium and stroma) and the size of thyrocyte nuclei (the mean volume, the mean intersection area and the mean perimeter) in the rat thyroid lobes incubated in vitro for 18 hrs with EGF, applied in 5 different concentrations: 0.1, 1.0, 10, 100 and 1000 ng/ml. Morphometric evaluation was performed, using a computer image analysis system, developed by us. We found that EGF - in concentration of 100 ng/ml - increased the relative volume of stroma when compared to controls, as well as to all the other groups incubated in exposure to that growth factor (used in different concentrations); at the same time, EGF decreased the relative volume of epithelium in the thyroid gland (statistical significance has been recorded only vs. EGF concentrations of 10 ng/ml and 1000 ng/ml). On the other hand, we observed that EGF - in concentration of 100 ng/ml - significantly increased the mean nuclear volume and the mean intersection area of thyrocyte nuclei when compared to the controls, as well as to EGF in concentrations of 1 ng/ml and 1000 ng/ml. With regards to the mean perimeter, a significant increase of its length was noted in the EGF(100 ng/ml)-exposed group vs. the group incubated with an addition of EGF (1 ng/ml).

Size of thyrocyte nuclei in aspirates from follicular adenomas: correlation with patients' ages.

OBJECTIVE: To determine whether the size of thyrocyte nuclei in aspirates from follicular adenoma correlates with the age of patients. STUDY DESIGN: The karyometric parameters were evaluated in routine aspirates, obtained from 27 patients with follicular adenoma as diagnosed in postoperative histopathologic examinations. The ages of the patients ranged from 11 to 70 years (36.8 +/- 16.3, x +/- SD). The cytologic examination of all the aspirates before surgery revealed "follicular neoplasms." The karyometric evaluation was performed with Karyometry Manager, version 1.2, an image analysis computer system. RESULTS: Neither the mean nuclear volume, mean nuclear intersection area nor mean nuclear perimeter correlated with the ages of the patients. CONCLUSION: These results suggest that in contrast to nodular goiter, in the cytologic examination of follicular neoplasms, the ages of patients should be disregarded when interpreting the size of thyrocyte nuclei.

Interactions between atrial natriuretic factor (ANF) and thyrotropin or somatostatin in their effects on thyroid growth processes; studies in vitro and ex vivo in vitro.

The goal of our present study has been to examine the effects of the atrial natriuretic factor (ANF) on the growth processes in rat thyroid lobes. In the initial in vitro experiment, thyroid lobes were preincubated with rat ANF (Sigma) for 30 min in RPMI 1640 medium with 3H-thymidine (2 microCi/ml), and later on 15% fetal calf serum (FCS), Hepes buffer and the remaining tested substances [TSH 20 mIU/ml, somatostatin (SS) 10(-7)M] were added. Preincubations with ANF were not conducted in the controls and in the group exposed to TSH alone. Incubations of all the examined groups (controls, TSH alone, ANF alone, ANF together with TSH or ANF together with SS) with 3H-thymidine were carried out for 4 hours. We obtained the following results: at none of the examined concentrations (10(-5)M, 10(-7)M, 10(-9)M), did ANF significantly affect the rate of 3H-thymidine incorporation in vitro. Neither did TSH alone nor ANF with TSH jointly significantly influence the process in question. However, we observed increased rates of the 3H-thymidine uptake, following the joint exposure of thyroid lobes to ANF (10(-7)M or 10(-9)M) and SS (10(-7)M), when compared to ANF alone. In the ex vivo in vitro experiment, direct intrathyroidal microinjections of ANF alone or jointly with TSH or SS, were carried out. Twenty four (24) hours after the microinjections, all the animals were sacrificed by decapitation, the thyroid lobes being collected and incubated for 4 hours with 3H-thymidine (2 microCi/ml).(ABSTRACT TRUNCATED AT 250 WORDS)

Age-related changes in the size of thyrocyte nuclei in aspirates from nontoxic nodular goiter.

It is believed that the size of thyrocyte nuclei correlates with the age of the patient in both normal thyroid tissue and nodular goiter. Therefore, we examined karyometric parameters in aspirates obtained from 38 patients ranging from 18 to 79 years (48.8 +/- 15.2, mean +/- SD). Routine cytologic evaluation revealed nodular goiters in all the patients. Subsequently, the same smears were analyzed with a computer system for karyometric measurements. The mean volume, intersection area and perimeter of nuclei of thyrocytes from nodular goiters correlated positively with age. The results suggest that the age of the patient should be considered when interpreting thyrocyte nuclear size during cytologic examination.

Melatonin-induced decrease of the size of thyrocyte nuclei in rat thyroids incubated in vitro.

The mean volume, intersection area and perimeter of thyrocyte nuclei in rat thyroid lobes incubated with melatonin (Mel), thyrotropin (TSH) or with both substances together, were investigated. The measurements were carried out using a computer system for karyometric examination. Melatonin in concentrations of 10(-8) M, 10(-10) M and 10(-12) M significantly decreased the mean nuclear volume and intersection area of thyrocytes (p < 0.01); the mean perimeter of thyrocyte nuclei was significantly decreased by melatonin in concentrations of 10(-10) M and 10(-12) M (p < 0.01). TSH (20 mIU/ml), when applied alone, significantly decreased the mean volume, intersection area and perimeter of thyrocyte nuclei (p < 0.01). TSH generally did not counteract the melatonin-induced decrease of thyrocyte nuclei except for 10(-10) M melatonin concentration when TSH increased the mean nuclear perimeter (p < 0.01) and slightly enlarged the mean volume (p < 0.05), compared with Mel alone. The results suggest an inhibitory influence of melatonin on thyroid follicular cell activity, and are in compliance with earlier observations.

[Effect of melatonin on the function of the pituitary-gonadal axis in food restriction states]. / Wplyw melatoniny na czynnosc osi przysadkowo-jajnikowej w stanach ograniczenia pozywienia.

The effects of melatonin (25 micrograms s.c. daily in the late afternoon during ten days) on the ovarian morphometry and the gonadotropin secretion were investigated in food-restricted and fed ad libitum rats. It was found that in food-restricted rats melatonin produced the significant decrease of the surface area of the whole ovary and of zona granulosa. Moreover melatonin treatment of food-restricted rats resulted in significant decrease of the relative areas of graafian follicles and zona granulosa estimated in relation to the whole ovary cross-section surface area. On the other hand melatonin did not produced significant alterations of the morphometric indices of the ovary in fed ad libitum rats. Melatonin administration was found to inhibit the effects of gonadotropin release in food-restricted but not in normally fed rats. These findings suggest that food restriction sensitizes the pituitary ovarian axis to antigonadotropic melatonin action.

The usefulness of computer-aided karyometric examination in preoperative differentiation of follicular neoplasms of the thyroid gland.

Fine-needle aspiration biopsy (FNAB) is the most important procedure in preoperative diagnosis of thyroid neoplasms. However, routine cytological examination is insufficient for differentiation between follicular adenoma and follicular carcinoma. Therefore, we decided to assess the usefulness of karyometric analysis in the examination of aspirates from these neoplasms. Morphometric analysis was performed with the use of the computer system for karyometric measurements--"Karyometry Manager" ver. 1.2. We examined cytological smears derived from 26 patients. In 10 of them a nodular goitre was diagnosed in both cytological and histopathological examinations. In the other 16 patients, "follicular neoplasms" were found in cytological examination. These proved to be follicular adenomas (8 cases) and follicular carcinomas (8 cases) on histopathological examination. The following morphometric parameters were measured in 100 nuclei per smear: volume, intersection area, perimeter, convexity coefficient and shape coefficient. We found that: 1) the mean volume and the mean intersection area of thyrocyte nuclei from follicular carcinomas were significantly (p < 0.001) greater than those of nuclei from adenomas or nodular goitres; 2) the mean perimeter of thyrocyte nuclei from follicular carcinomas was significantly greater than the mean perimeter of thyrocyte nuclei from follicular adenomas (p < 0.025) and nodular goitres (p < 0.001); 3) the mean nuclear area of thyrocytes from follicular adenomas was significantly greater than that of thyrocytes from nodular goitres (p < 0.05). Our results show that karyometric analysis can be useful in cytological differentiation of follicular neoplasms.

Occurrence of goitre in relation to iodine deficiency in school children in Lódz City, the Lódz metropolitan area and in Piotrków, Sieradz, Plock, Wloclawek, Radom and Skierniewice Voivodships (Lódz coordinating center).

This paper presents the results of studies performed within the Applied Project of the Ministry of Health and Social Welfare and of the Committee for Scientific Research: "Studies on Iodine Deficiency in Poland", including the school children in Lódz City and seven voivodships of the Central Poland. According to the results, the analyzed regions can be regarded as areas of goitrous endemia of a moderate degree (the goitre was found in 32.7% of examined population); the same regions can also be classified among the regions of mild iodine deficiency (the mean iodide concentration in urine was 64.0 micrograms/l). The obtained results prove the to-date's iodine prophylaxis to be not entirely efficient in the areas of interest, demanding an effective model of iodine complementation in diet to be designed.