Fine-needle biopsy of thyroid nodules and the contribution of molecular analysis of BRAF and RAS mutations.

BACKGROUND: Thyroid cancer is the most common endocrine malignancy. There is a significant overdiagnosis of thyroid carcinomas that would never clinically manifest, with consequent unnecessary surgical treatment. The fine-needle biopsy and subsequent cytologic examination is of crucial importance in the differential diagnosis of thyroid nodules. On the other hand, a significant portion of the results are indeterminate. OBJECTIVE: To assess the relationship of BRAF/RAS mutations in biopsy specimens to histological characteristics of thyroid nodules in individuals who undergone fine-needle biopsy and surgery. METHODS: This cross-sectional study involves 170 subjects with indeterminate cytology analyzed for BRAF/RAS mutations. RESULTS: Of all 170 patients with indeterminate cytological finding, 103 were indicated for surgery. Of these, 31 were BRAF and 25 RAS positive. Thyroid cancer was diagnosed in 59 patients, while 44 patients had non-malignant thyroid lesions. The BRAF V600E mutation was detected in 30 patients, and the RAS (K-RAS, N-RAS, and H-RAS) mutation in 13 patients with thyroid cancer. In all BRAF-positive nodules, thyroid cancer was histologically confirmed. This means a 100 % positive predictive value of BRAF testing in our study. CONCLUSION: Stratification of thyroid lesions with uncertain results of fine-needle cytology using genetic markers can help to deliver more tailored medical treatment (Tab. 6, Ref. 19).

Influence of autoimmune thyroiditis on the prognosis of papillary thyroid carcinoma.

OBJECTIVES: The association of autoimmune thyroiditis (AIT) with papillary thyroid carcinoma (PTC) has been studied for over 60 years, yet their causal relationship has not been elucidated. Most published papers report a better prognosis of the patients with tumour in the field of thyroiditis. In our work we aimed to find out the differences in the clinical behaviour of PTC depending on the presence of autoimmune inflammation. METHODS: We retrospectively analysed a group of 1,201 patients with PTC dispensed in St. Elisabeth Cancer Institute and Faculty of Medicine from 2000 to 2015. We divided patients with AIT according to the time of diagnosis of inflammation into the AIT1 subgroup, which included patients monitored for AIT before tumour detection. In them, we assumed that the factor of long-term endocrinological monitoring could speed up the diagnosis of the tumour and thus improve the prognosis. The AIT2 subgroup consisted of patients with both tumour and inflammation diagnosed simultaneously, thus eliminating the factor of prior monitoring. RESULTS: PTC in the AIT1 subgroup had better prognostic parameters (TNM stage, persistence, disease remission). Patients in the AIT2 group had all monitored parameters comparable with patients with tumours without autoimmune inflammation. CONCLUSION: AIT alone does not have a protective effect on the course of PTC, the cause of a better prognosis in the AIT1 subgroup is a different pathomechanism of carcinogenesis, as well as previous endocrinological monitoring and earlier detection of malignancy (Tab. 4, Fig. 2, Ref. 27).

An incidental finding of pheochromocytoma in a 33-year-old patient with Lynch syndrome.

Pheochromocytoma is a catecholamine-producing neuroendocrine tumor arising from chromaffin cells of the adrenal medulla. The detection of these tumors is extremely important because they are associated with high cardiovascular morbidity and mortality. Progress in molecular genetics has revealed that up to 35% of pheochromocytomas are inhereted. Lynch syndrome (hereditary nonpolypous colorectal cancer - HNPCC) is an autosomal dominant genetic condition that is associated with a high risk of colorectal cancer or other extracolonic tumors (adenocarcinoma of endometrium, stomach, ovarian carcinoma, carcinoma of urinary tract, small intestine, brain tumors and skin cancer). Foreign medical journals are reporting an increasing number of cases on coexistence of HNPCC and neuroendocrine tumors, including pheochromocytoma. It increases the likelihood that this type of tumor could represent an additional extracolonic manifestation of Lynch syndrome.

Causal associations of autoimmune thyroiditis and papillary thyroid carcinoma: mRNA expression of selected nuclear receptors and other molecular targets.

Potential causal associations of autoimmune thyroiditis (AIT) and papillary thyroid carcinoma (PTC) have been studied previously. The mRNA expression patterns of thyroid hormone receptors (TR), retinoid receptors (RAR), rexinoid receptors (RXR), dihydroxyvitamin D3 receptors (VDR), and progesterone receptors (PR) in PTC tissue of patients without autoimmune thyroiditis (PTC/AIT-) and in PTC tissue of patients with coexisting AIT (PTC/AIT+) have been investigated in order to judge whether the observed changes may take part in the promotion and progression of thyroid cancer. Tumours with or without AIT were classified histologically and the semiquantitative PCR was performed. The results revealed that there was decreased expression of TRα, TRßα, RARα and PR mRNA in PTC/AIT+ tumours when compared with PTC/AIT- tumours. Decreased expression of RARα in PTC/AIT+ was detected when compared with PTC/AIT- patients. A similar effect of AIT was observed with a decrease in RARγ expression in PTC/AIT+ patients. On the other hand, there was an increased expression of VDR in thyroid tumours (PTC/AIT+) when compared with PTC/AIT-. PR mRNA was decreased in the thyroid tumours of PTC/AIT+ patients when compared with PTC/AIT- patients. In addition, there was an increased expression of MKi67 and complement C3 in PTC of PTC/AIT+ when compared with PTC/AIT-. In the PTC/AIT+ group, a decreased level of IGF-1 mRNA was found when compared with the PTC/AIT- group. According to the significant differences of the studied markers in PTC/AIT+ compared with PTC/AIT-, it was indicated that AIT may be a predisposing factor for the development of PTC.

[The course of differentiated thyroid microcarcinoma in patients treated by different therapeutic strategies]. / Priebeh ochorenia u pacientov s diferencovaným mikrokarcinómom stítnej zlazy pri pouzití rôznych liecebných postupov.

Low risk differentiated thyroid microcarcinoma therapy is a controversial area of thyroid tumor management. Major international medical societies and reputable institutes consider lobectomy to be sufficient therapeutic intervention for the pT1a cN0cM0 stage of papillary thyroid microcarcinoma. However different views and therapeutic strategies exist and result in unnecessary overtreatment and worsening of patients quality of life. We researched the course of the differentiated thyroid microcarcinoma in patients using different therapeutic strategies: lobectomy, total thyroidectomy, total thyroidectomy with central compartment prophylactic lymphadenectomy and total thyroidectomy followed by radioactive iodine treatment. Apart from an excellent prognosis we did not find out any clinically significant differences in the course of the disease. We can conclude that lobectomy is sufficient therapeutic intervention for patients with differentiated thyroid microcarcinoma without known metastases.Key words: differentiated thyroid microcarcinoma - management - overtreatment - the course of the disease.

Ensuring Effective Prevention of Iodine Deficiency Disorders.

BACKGROUND: Programs initiated to prevent iodine deficiency disorders (IDD) may not remain effective due to changes in government policies, commercial factors, and human behavior that may affect the efficacy of IDD prevention programs in unpredictable directions. Monitoring and outcome studies are needed to optimize the effectiveness of IDD prevention. SUMMARY: Although the need for monitoring is compelling, the current reality in Europe is less than optimal. Regular and systematic monitoring surveys have only been established in a few countries, and comparability across the studies is hampered by the lack of centralized standardization procedures. In addition, data on outcomes and the cost of achieving them are needed in order to provide evidence of the beneficial effects of IDD prevention in countries with mild iodine deficiency. CONCLUSION: Monitoring studies can be optimized by including centralized standardization procedures that improve the comparison between studies. No study of iodine consumption can replace the direct measurement of health outcomes and the evaluation of the costs and benefits of the program. It is particularly important that health economic evaluation should be conducted in mildly iodine-deficient areas and that it should include populations from regions with different environmental, ethnic, and cultural backgrounds.

mRNA expression pattern of retinoic acid and retinoid X nuclear receptor subtypes in human thyroid papillary carcinoma.

Retinoids have shown potential for the inhibition of tumour growth and progression. The objective of this study was to investigate retinoic acid nuclear receptor subtypes RAR/RXR and iodothyronine 5'-deiodinase, type I expression pattern in papillary thyroid tumour tissue of 26 patients in order to compare with those of the non-neoplastic thyroid tissue of the corresponding patients. The expression of selected parameters mRNA was examined by semi-quantitative RT-PCR. Papillary thyroid carcinoma (PTC) expressed RXRγ, when compared to non-neoplastic thyroid tissues of the corresponding patients that were lacking expression of RXRγ or its expression was very low. Moreover, we found significantly increased expression of RARα and RARγ in the overall group of PTC. This increase was detected in cases with positive lymph node metastasis (LNM), but not in cases with negative LNM. RARß was significantly reduced in the subgroup of classic variant (CV). We also detected absence or significantly lower expression of hDIO1 mRNA in tumour tissue when compared to non-neoplastic tissue in both overall PTC cases and in the CV subgroup. However, the significantly decreased levels of hDIO1 mRNA were detected in cases with negative LNM but not in cases with positive LNM when compared to corresponding non-tumour tissue in both overall PTC cases and in the CV subgroup. Differences in RAR and RXR subtype mRNA expression patterns in various PTCs may contribute to the immunochemistry data available, and may thus find exploitation in clinical oncology, particularly in the differential diagnosis of thyroid neoplasms.

A prospective, multicentre study to investigate the efficacy, safety and tolerability of octreotide LAR (long-acting repeatable octreotide) in the primary therapy of patients with acromegaly.

OBJECTIVE: To evaluate the efficacy, safety and tolerability of octreotide LAR (long-acting repeatable octreotide) in the primary therapy of acromegaly. DESIGN AND PATIENTS: Ninety-eight previously untreated acromegalics were recruited into this prospective multicentre study. A total of 68 patients successfully completed 48 weeks of the study period, received 12 doses of octreotide LAR 10-30 mg every 4 weeks, and constituted the population used for this analysis. MEASUREMENTS AND RESULTS: A clinically relevant reduction (i.e. to < or = 5 microg/l) in mean GH (mGH) was recorded in 72% of patients after 24 weeks of treatment, and 42% reached a 'safe' GH value (< or = 2.5 microg/l). At week 48, 16 more patients were considered partial GH responders (GH > 2.5 microg/l and < or = 5 microg/l) and 44% had reached a GH level < or = 2.5 microg/l. IGF-1 levels normalized in 38% and 34% of patients after 24 and 48 weeks of treatment, respectively. At study completion, 10 patients (14.7%) who had not normalized their IGF-1 levels had achieved at least a 50% decrement in this marker. In eight microadenoma patients, tumour volume decreased from a mean baseline level of 298 +/- 145 mm3 to 139 +/- 94 mm3 after 24 weeks and to 99 +/- 70 mm3 after 48 weeks of therapy. In 60 patients with macroadenoma, the corresponding values were 3885 +/- 5077 mm3 at baseline and 2723 +/- 3435 and 2406 +/- 3207 mm3 after 24 and 48 weeks, respectively. At weeks 24 and 48, a significant (> 20%) tumour volume reduction was reported in 63% and 75% of patients, respectively. A reduction in the severity of symptoms of acromegaly was observed early in treatment and was maintained throughout the study period. CONCLUSION: Octreotide LAR represents a viable alternative to surgery for primary treatment of acromegaly leading to a progressive regression of tumour volume, a sustained control of biochemical abnormalities and an adequate relief of symptoms of the disease.