Filip Gołkowski

Technetium-99m-sestamibi subtraction scintigraphy vs. ultrasonography combined with a rapid parathyroid hormone assay in parathyroid aspirates in preoperative localization of parathyroid adenomas and in directing surgical approach.

Objective  To determine the sensitivity and positive predictive value (PPV) of subtraction scintigraphy (SS) vs. ultrasonography (US) of the neck combined with rapid intact parathyroid hormone (iPTH) assay in US‐guided fine‐needle parathyroid aspirates in preoperative localization of parathyroid adenomas and in directing surgical approach.

Intraoperative parathyroid hormone assay improves outcomes of minimally invasive parathyroidectomy mainly in patients with a presumed solitary parathyroid adenoma and missing concordance of preoperative imaging

Objective  Intraoperative parathyroid hormone assay (IOPTH) is often used during minimally invasive parathyroidectomy (MIP) for primary hyperparathyroidism (pHPT). However, several investigators have reported conflicting outcomes, throwing doubt on the real influence of this adjunct on surgical decision‐making. The aim of this study was to determine the impact of routine use of IOPTH on the success rate of MIP as the primary outcome, and whether it value‐added to surgical decision‐making during the operations at our institution.

Increased prevalence of hyperthyroidism as an early and transient side-effect of implementing iodine prophylaxis

OBJECTIVE To assess the prevalence of hyperthyroidism just after implementation of iodine prophylaxis among adults from an area with iodine deficiency. STUDY DESIGN AND SUBJECTS A total of 1648 adults (age 16 years and older) were sampled from an area of southern Poland during two nationwide epidemiological surveys. Of these, 1424 adults with negative medical history for thyroid disorders qualified for final analysis. The authors compared thyroid dysfunction in participants prior to (1989-1990) and after implementation of iodine prophylaxis (1997-1999). SETTING The southern part of Poland. RESULTS We found an increase in the serum concentration of anti-thyroid microsomal antibodies from 4.9% in the years 1989-1990 to 12.1% after introduction of iodised household salt (P < 0.0001). The prevalence of hyperthyroidism (defined as thyroid-stimulating hormone < 0.4 microU ml- 1) significantly increased in the equivalent period from 4.8 to 6.5% (P = 0.009). CONCLUSIONS We concluded that a sudden rise in iodine intake after implementation of iodine prophylaxis among adults from the area with iodine deficiency may lead to an increase in thyroid autoimmunity and prevalence of hyperthyroidism. Those possible early side-effects appear to be only temporary and are acceptable when compared with the evident benefits of adequate iodine intake.

The current status of intraoperative iPTH assay in surgery for primary hyperparathyroidism

Intraoperative intact parathyroid hormone (iPTH) monitoring has been accepted by many centers specializing in parathyroid surgery as a useful adjunct during surgery for primary hyperparathyroidism. This method can be utilized in three discreet modes of application: (I) to guide surgical decisions during parathyroidectomy in one of the following clinical contexts: (i) to confirm complete removal of all hyperfunctioning parathyroid tissue, which allows for termination of surgery with confidence that the hyperparathyroid state has been successfully corrected; (ii) to identify patients with additional hyperfunctioning parathyroid tissue following the incomplete removal of diseased parathyroid/s, which necessitates extended neck exploration in order to minimize the risk of operative failure; (II) to differentiate parathyroid from non-parathyroid tissue by iPTH measurement in the fine-needle aspiration washout; (III) to lateralize the side of the neck harboring hyperfunctioning parathyroid tissue by determination of jugular venous gradient in patients with negative or discordant preoperative imaging studies, in order to increase the number of patients eligible for unilateral neck exploration. There are many advantages of minimally invasive parathyroidectomy guided by intraoperative iPTH monitoring, including focused dissection in order to remove the image-indexed parathyroid adenoma with a similar or even higher operative success rate, lower prevalence of complications and shorter operative time when compared to conventional bilateral neck exploration. However, to achieve such excellent results, the surgeon needs to be aware of hormone dynamics during parathyroidectomy and carefully choose the protocol and interpretation criteria that best fit the individual practice. Understanding the nuances of intraoperative iPTH monitoring allows the surgeon for achieving intraoperative confidence in predicting operative success and preventing failure in cases of unsuspected multiglandular disease, while safely limiting neck exploration in the majority of patients with sporadic primary hyperparathyroidism. Thus, parathyroidectomy guided by intraoperative iPTH monitoring for the management of sporadic primary hyperparathyroidism is an ideal option for the treatment of this disease entity. However, the cost-benefit aspects of the standard application of this method still remain a matter of controversy.

Iodine, Selenium, and Other Trace Elements in Urine of Pregnant Women

The purpose of this work was to determine trace element levels in urine and evaluate possible associations between urinary iodine concentration (UIC), other trace elements (Cr, Cu, Fe, Mn, Na, Se, Zn), toxic elements (Cd, Pb), anthropometrical measures (body weight and height), glycemic indices (serum insulin and glucose), and several parameters related to thyroid function (thyroid stimulating hormone, free thyroxine, antithyroid peroxidase antibodies, thyroid volume, and thyroid echogenicity) in pregnant women. One hundred sixty-nine participants were recruited. The whole study group, originating from Krakow region, comprised three subgroups belonging to three trimesters: I trimester (n = 28), II trimester (n = 83), and III trimester (n = 58). Trace elements were determined using inductively coupled plasma mass/(atomic emission) spectrometry. Partial least square model was used to reveal correlation structure between parameters investigated, as well as a possible causal relationship between dependent parameters and potentially explanatory parameters. Results obtained for trace and toxic elements in urine were comparable with results of other authors, although the study group was not homogenous. We confirmed (1) low iodine excretion in pregnant women, (2) the existence of statistically significant correlation between UIC and urinary selenium, and (3) lack of correlation between latter parameter and typical indices of thyroid function. Urinary selenium correlated with other urinary trace elements, but physiological significance of this finding remains uncertain. The fact that a large number of pregnant women fail to meet dietary recommendations for iodine is the major reason for concern.

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 μg/l vs 93 ug/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 μg/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 νg/l vs 57 μg/l and 86 μg/l vs 114 μg/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.

Dietary patterns as risk factors of differentiated thyroid carcinoma.

UNLABELLED Nutritional factors are known to be important in the development of different metabolic diseases. The history of nodular or diffuse goiter is closely related to risk of thyroid carcinoma. On account of the function of the thyroid gland, many studies focus on iodine intake. The aim of the study was to assess whether dietary patterns could be risk factors of differentiated thyroid carcinoma. MATERIAL/METHODS The case-control study was based on a questionnaire, which included information about dietary patterns and was carried out on 284 patients comprising 30 males (mean age 58.4±13.7 years), and 254 females (mean age 52.1±13.8 years), as well as 345 randomly selected controls: 58 males (mean age 60.2±12 years) and 287 females (mean age 53.4±14.3 years) randomly selected from the Population Register and adjusted by age and gender to the group of TC. The main groups of nutritional products, i.e. starchy foods, meat, dairy products, vegetables, fruits, and beverages, were analyzed. RESULTS Consumption of vegetables, fruits, saltwater fish and cottage cheese was significantly lower in patients with differentiated thyroid carcinoma than in controls, quite the contrary to starchy foods, especially white bread. CONCLUSIONS Dietary patterns appear to modify the risk of thyroid carcinoma. A diet rich in vegetables and fruit, as well as saltwater fish (a source of iodine) and low-fat meat, could be an important protective factor.

Parathyroid transplantation in thyroid surgery

Permanent hypoparathyroidism following thyroid surgery is rare. Its prevalence is reported to be below 1-2% if surgery is performed by experienced thyroid surgeons. Parathyroid identification and preservation in situ with good vascular supply is the mainstay of safe thyroid surgery. However, if the parathyroid glands are damaged, autotransplantation should be undertaken to preserve their function. Parathyroid transplantation can be considered in three distinct modes of application: (I) fresh parathyroid tissue autotransplantation during thyroidectomy in order to reduce the risk of permanent hypoparathyroidism; (II) cryopreserved parathyroid tissue autotransplantation in patients with permanent hypoparathyroidism; (III) parathyroid allotransplantation in patients with permanent hypoparathyroidism when cryopreserved parathyroid tissue is not available for grafting. Nowadays, allotransplantation of cultured parathyroid cells without immunosuppression should be taken into consideration in selected patients as an alternative to calcium and vitamin D3 supplementation in management of permanent hypoparathyroidism. This paper is aimed to provide a review of current status of various parathyroid transplantation techniques in thyroid surgery.

Prothymosin-alpha and Ki-67 expression in pituitary adenomas.

INTRODUCTION Prothymosin alpha (PTMA), a nuclear oncoprotein involved in cell cycle regulation, is used as a prognostic marker in many cancers. The histopathology of pituitary carcinomas and locally invasive adenomas is indistinguishable from that of benign tumors. A new marker is needed to differentiate these lesions. We evaluated PTMA in pituitary adenomas to determine its usefulness as a prognostic factor of tumor proliferation. MATERIAL/METHODS We conducted a retrospective analysis of a group of 27 patients, including 15 females (56%) and 12 males (44%) with a mean age of 58.6±12 years, who underwent pituitary tumor surgery between 2003 and 2012. The Ki-67 and PTMA-nuclear (PTMA-n) and PTMA-cytoplasmic (PTMA-c) indices were determined by immunohistochemical staining. We studied histopathological features, clinical symptoms, and magnetic resonance imaging or computed tomography performed before surgery and one year following surgery to evaluate tumor size and progression. RESULTS The expression of Ki-67 was revealed in 77.8% of adenomas, PTMA-n in 81.5% and PTMA-c in 92.6%. The mean value of the Ki-67 index was 1.8%, PTMA-n was 1.84%, and PTMA-c was 35.6%. There was a significant positive correlation between Ki-67 and PTMA-n (p=0.009). We did not find any correlation between Ki-67, PTMA-c, and tumor progression. PTMA-n was found to be correlated with tumor size (p=0.045) and was higher in the case of gonadotropinomas (p=0.026). CONCLUSIONS The positive nuclear expression of Ki-67 and PTMA was observed in the majority of pituitary adenomas. Neither the expression of Ki-67 nor that of PTMA-c was related to tumor recurrence or local invasion.

Topoisomerase 2 alpha as a prognostic factor in pituitary tumors

Introduction: In pituitary tumors markers of proliferation and progression essential for treatment and follow-up are searched Objectives: We studied topoisomerase 2 alpha (Topo2A) expression in different types of pituitary adenomas in order to evaluate its prognostic potential in patients with hypophyseal tumors. Patients and methods: In a retrospective study of 60 patients of mean age 46.7±17.6 years who underwent pituitary tumor surgery, expression of Topo2A, by immunohistochemistry, was analysed quantitatively with respect to histopathology, tumor features, clinical symptoms, MR imaging and post-operative recurrence/progression of disease. Results: Topo2A was expressed in 73% of (44/60) pituitary adenoma. The highest Topo2A indices were observed in ACTH-secreting pituitary tumors (median:1.13% [0.37-1.21]), followed by silent-ACTH tumors (0.94%[0.89-1.0]), and hormone immunonegative adenomas (0.8%[0.65-1.55]). No differences in expression with respect to patient age or gender were observed. Statistically significant relations were found between Topo2A index and tumor size, its invasiveness, pathological ocular tests and recurrence of tumor growth in postoperative observation. In patients with Topo2A index >1% the relative risk of tumor recurrence is higher by a factor of 3.5 (95%CI:1.8-6.9), P<0.001. After pre-treatment acromegaly patients with somatostatin analogues decrease in median Topo2A expression was observed, compared with untreated patients (0.0% [0.0-0.22] vs 0.71%[0.17-1.0], P<0.05). Conclusions: In our study group, Topo2A index exceeding 1% was found to be a prognostic factor for recurrence/progression of tumors, especially in patients with hormonally inactive adenomas, to be selected for intensive postoperative treatment. In acromegaly, application of somatostatin analogues inhibits Topo2A expression, providing molecular evidence of the effectiveness of these analogues.