Agata Czarnywojtek

The role of sonoelastography in acute, subacute and chronic thyroiditis - a novel application of the method

OBJECTIVE Reports on sonoelastography, which provide an objective estimation of tissue elasticity, are scarce in terms of thyroiditis. The aim of this study was to prospectively assess the applicability of sonoelastography in different types of thyroiditis. DESIGN The study assessed and compared the thyroid tissue stiffness in patients with acute thyroiditis (AT), subacute thyroiditis (SAT), and chronic autoimmune thyroiditis (CAT) with healthy control subjects (CS), followed up for 10 weeks. METHODS The study group consisted of two patients with AT, 18 patients with SAT, 18 patients with CAT, and 40 CS matched for age and gender. Sonoelastography was performed at baseline, at a 4-week follow-up during treatment, and at 10 weeks following diagnosis and treatment initiation. RESULTS Thyroid tissue stiffness was higher in SAT at baseline (214.26 ± 32.5 kPa) in comparison with values recorded at a 4-week follow-up (45.92 ± 17.4 kPa) and at 10 weeks following diagnosis and treatment initiation (21.65 ± 5.3 kPa, P < 0.0001). Baseline thyroid stiffness in SAT was higher than that found in CAT (36.15 ± 18.7 kPa, P < 0.0001) and CS (16.18 ± 5.4 kPa, P < 0.0001). In the remission of SAT, thyroid stiffness was lower than that found in CAT (P = 0.006), while it was higher than that in CS (P = 0.0008). No difference was observed between thyroid stiffness in SAT at 4-week follow-up and in CAT. Patients with CAT presented higher thyroid stiffness than CS (P < 0.0001), which was not influenced by L-thyroxine treatment. Thyroid stiffness in patients with AT was 216.6 and 241.9 kPa at baseline; after treatment, it decreased to 17.93 and 85.348 kPa respectively. CONCLUSIONS Sonoelastography may assist in the diagnosis and treatment monitoring of AT, SAT and CAT, as well as in the differentiation of the various types of thyroiditis.

Increased risk of thyroid pathology in patients with thyroid hemiagenesis: results of a large cohort case-control study

OBJECTIVE Thyroid hemiagenesis (THA) is an anomaly resulting from the developmental failure of one thyroid lobe. Etiopathogenesis, clinical significance, and management of patients in whom THA is diagnosed are still a matter of debate. The aim of the study is to provide the first systematic analysis of a large cohort of subjects with THA. DESIGN Forty patients with THA are described in comparison to a control group of 80 subjects with fully developed thyroid gland. METHODS Serum concentrations of thyrotropin (TSH), free thyroxine (FT(4)), free triiodothyronine (FT(3)), and thyroid autoantibodies were measured. In 37 patients, thyroid ultrasonography and Tc-99m thyroid scintiscan were performed, followed by fine-needle aspiration biopsy if indicated. The remaining archival three cases were diagnosed with the use of I-131 scintiscan under basal conditions and after TSH stimulation. RESULTS Patients with THA, while usually clinically euthyroid, presented with significantly higher levels of TSH and FT(3) as well as with higher FT(3)/FT(4) concentration in comparison to the control group. Furthermore, a higher incidence of associated functional, morphological, and autoimmune thyroid disorders in patients with THA was observed when compared to subjects with bilobate thyroid (P<0.05). CONCLUSIONS Our results revealed that individuals with THA are more likely to develop thyroid pathology. The observed high incidence of associated pathologies is presumably due to long-lasting TSH overstimulation. Therefore, THA diagnosis should be followed by systematic observation and adequate levothyroxine treatment in patients with elevated TSH level.

Risk of Thyroid Nodular Disease and Thyroid Cancer in Patients with Acromegaly – Meta-Analysis and Systematic Review

Introduction Acromegaly is a quite rare chronic disease caused by the increased secretion of growth hormone (GH) and subsequently insulin - like growth factor 1. Although cardiovascular diseases remains the most common cause of mortality among acromegalic patients, increased prevalence of malignant and benign neoplasms remains a matter of debate. The aim of this study is to evaluate the risk of thyroid nodular disease (TND) and thyroid cancer in patients with acromegaly. Materials and Methods PubMed, Cochrane Library, Scopus, Cinahl, Academic Search Complete, Web of Knowledge, PubMed Central, PubMed Central Canada and Clinical Key databases were searched to identify studies containing. Random–effects model was used to calculate pooled odds ratios and risk ratios of TND in acromegaly. Studies which not included control groups were systematically reviewed. Results TND was more frequent in acromegaly than in control groups (OR = 6.9, RR = 2.1). The pooled prevalence of TND was 59.2%. Also thyroid cancer (TC) proved to be more common in acromegalic patients (OR = 7.5, RR = 7.2), prevalence was 4.3%. The pooled rate of malignancy (calculated per patient) was equal to 8.7%. Conclusions This study confirms that both TND and TC occur significantly more often in acromegalic patients than in general population. These results indicate that periodic thyroid ultrasound examination and careful evaluation of eventual lesions should be an important part of follow-up of patients with acromegaly.

Chromogranin A – unspecific neuroendocrine marker. Clinical utility and potential diagnostic pitfalls

Chromogranin A, despite a number of limitations, is still the most valuable marker of neuroendocrine tumors (NETs). Granins belong to the family of acidic proteins that constitute a major component of secretory granules of various endocrine and neuroendocrine cells, which are components of both the classical endocrine glands and the diffuse neuroendocrine system. These cells are a potential source of transformation into neuroendocrine tumors. The awareness of potential causes influencing the false results of its concentrations simplifies diagnosis and treatment. One of the disadvantages of this marker is its non-specificity and the existence of a number of pathological processes leading to an increase in its concentration, which often results in confusion and diagnostic difficulties. The molecular structure is characterized by a number of sites susceptible to the proteolytic activity of enzymes, resulting in the formation of a number of biologically active peptides. Presumably they act as precursors of active proteins. Chromogranin expression correlates with the amount of secretory vesicles in neuroendocrine cells. The peptide chain during biochemical changes becomes a precursor of biologically active proteins with a wide range of activities. There are a number of commercially available kits for the determination of chromogranin A, which differ in methodology. We present the evaluation of chromogranin A as a marker of neuroendocrine tumors in clinical practice and the possible factors that may affect the outcome of its concentration.

Survivin Delta Ex3 Overexpression in Thyroid Malignancies

Context Thyroid cancer incidence has increased significantly during the past decades and is the most common type of endocrine malignancy. Many factors in thyroid cancers were studied as independent predictors of a poor prognosis. Objective The objective of the study was to evaluate survivin expression – BIRC5 and its splice variants: survivin delta Ex3 and survivin 2B in benign and malignant thyroid nodules. Design Thyroid tissues samples from a group of 50 patients consisting of: 29 patients with thyroid cancers (including medullary, papillary, follicular and undifferentiated types), as well as from 21 patients with non-cancerous thyroid tissues (including: 11 benign thyroid lesions and 10 healthy thyroid samples). Main Outcome Measures The analysis of the survivin gene expression and evaluation of the level of splice variants were performed using quantitative RT-PCR. Results A statistically significant higher level of expression of survivin gene – BIRC5 was detected in thyroid malignant nodules, when compared with benign lesions and healthy thyroid samples. Moreover, the comparison of survivin relative expression in different staged tumors (pT1, pT3, and pT4) revealed a much higher amount of BIRC5 transcripts in tumor tissues of pT3/pT4. The comparison of survivin expression between benign thyroid nodules and healthy thyroid did not reveal significant differences. Importantly, high expression rate of the survivin delta Ex3 splice variant characterized thyroid carcinomas. Conclusion The results suggest that survivin, especially survivin delta Ex3 splice variant being overexpress, is a characteristic feature of thyroid malignancy.

The Usefulness of Standardized Uptake Value in Differentiation between Benign and Malignant Thyroid Lesions Detected Incidentally in 18F-FDG PET/CT Examination

Introduction In the last decade, (18)F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET and PET/CT) has become one of the major diagnostic tools used in oncology. A significant number of patients who undergo this procedure, due to non-thyroidal reasons, present incidental uptake of (18F-FDG) in the thyroid. The aim of the study was to compare the SUVmax (standardized uptake value) of thyroid focal lesions, which were incidentally found on PET/CT, in relation to the results of thyroid fine-needle aspiration biopsy (FNAB) and/or histopathological evaluation. Materials and Methods Patients referred for PET/CT examination, due to non-thyroidal illness, presented focal 18F-FDG uptake in the thyroid and were advised to undergo ultrasonography (US), hormonal evaluation, FNAB and/or total thyroidectomy at our institution. Results 6614 PET/CT examinations performed in 5520 patients were analyzed. Of the 122 patients with focal thyroid 18F-FDG activity, 82 patients (67.2%) underwent further thyroid evaluation using FNAB. Benign lesions were diagnosed in 46 patients, malignant - in 19 patients (confirmed by post-surgical histopathology), while 17 patients had inconclusive results of cytological assessment. Mean SUVmax of benign lesions was 3.2±2.8 (median = 2.4), while the mean SUVmax value for malignant lesions was 7.1±8.2 (median = 3.5). The risk of malignancy was 16.7% for lesions with a SUVmax under 3, 43.8% for lesions with a SUVmax between 3 and 6, and 54.6% for lesions with a SUVmax over 6. In the group of malignant lesions, a positive correlation between the lesion’s diameter and SUVmax was observed (p = 0.03, r = 0.57). Conclusions Subjects with incidental focal uptake of 18F-FDG in thyroid are at a high risk of thyroid malignancy. A high value of SUVmax further increases the risk of malignancy, indicating the necessity for further cytological or histological evaluation. However, as SUVmax correlated with the diameter of malignant lesions, small lesions with focal uptake of 18F-FDG should be interpreted cautiously.

Familial syndromes associated with neuroendocrine tumours.

Neuroendocrine tumours may be associated with familial syndromes. At least eight inherited syndromes predisposing to endocrine neoplasia have been identified. Two of these are considered to be major factors predisposing to benign and malignant endocrine tumours, designated multiple endocrine neoplasia type 1 and type 2 (MEN1 and MEN2). Five other autosomal dominant diseases show more heterogeneous clinical patterns, such as the Carney complex, hyperparathyroidism-jaw tumour syndrome, Von Hippel-Lindau syndrome (VHL), neurofibromatosis type 1 (NF1) and tuberous sclerosis. The molecular and cellular interactions underlying the development of most endocrine cells and related organs represent one of the more complex pathways not yet to be deciphered. Almost all endocrine cells are derived from the endoderm and neuroectoderm. It is suggested that within the first few weeks of human development there are complex interactions between, firstly, the major genes involved in the initiation of progenitor-cell differentiation, secondly, factors secreted by the surrounding mesenchyme, and thirdly, a series of genes controlling cell differentiation, proliferation and migration. Together these represent a formula for the harmonious development of endocrine glands and tissue.

Incidental 18 F-FDG uptake in the thyroid in patients diagnosed with PET/CT for other malignancies

BACKGROUND The value of PET/CT imaging in diagnosis of different cancers has been widely described. PET/CT may contribute to visualization of additional findings that were not the indication to the study and did not refer to initial diagnosis. In a small number of PET/CT scans an incidentally found focal ¹⁸F-FDG uptake in the thyroid gland is found. The goal of the study was to estimate the prevalence and evaluate the clinical significance of incidental thyroid ¹⁸F-FDG uptake in a cohort of patients diagnosed for different malignancies. MATERIAL AND METHODS 2478 PET/CT scans using ¹⁸F-FDG were performed in 1925 subjects for evaluation of different, non-thyroid malignancies. For PET/CT examination, a Discovery ST (General Electric) PET/CT scanner was used. Patients with focal ¹⁸F-FDG activity were further evaluated by means of fine needle aspiration biopsy (FNAB). If cytological examination disclosed malignancy or suspicion of malignancy, thyroidectomy was performed. Both cytological and histopathological results were then analyzed. RESULTS Focal increased ¹⁸F-FDG uptake was found in 71 patients (3.7%), and cytological or histopathological results were evaluable in 20 of them. In general, 8 cases of thyroid cancer were found, which accounts for 40% probability of malignancy. The predominant histopathological diagnosis was papillary thyroid carcinoma (5 out of 8 cases). Additionally, in one case (5%) thyroid metastasis of lung cancer was detected. Diffused ¹⁸F-FDG activity in both thyroid lobes was observed in 120 subjects (6.2%)--in most cases chronic thyroiditis was confirmed. CONCLUSIONS The probability of malignancy of focal thyroid incidentalomas in ¹⁸F-FDG PET/CT scans is rather high. Therefore, thorough evaluation of such lesions is highly recommended in each case. Most thyroid malignancies incidentally detected in PET/CT are papillary carcinomas.

Dysfunction of the thyroid gland during amiodarone therapy: a study of 297 cases

Aim This study aims to explore and compare the efficacy of radioiodine treatment (RIT) in hyperthyroid and euthyroid patients who have been treated with amiodarone (AM) in the past or are currently undergoing AM treatment. Clinical observation of a group of patients with amiodarone-induced hypothyroidism during a 12-month follow-up period was used for comparison. Design This was a observational, two-centered study. Patients were assessed at baseline and at 2 months, 6 months, 8 months, and 12 months after RIT. Patients Group A: At baseline (61 males [M] and 17 females [F], mean age 50±19 years), there were 78 euthyroid patients with cardiac arrhythmias, who were treated with AM and developed amiodarone-induced thyrotoxicosis, and currently require retreatment with AM. Group B: Hyperthyroid patients (92 M and 26 F, mean age 72±11.8 years) after AM therapy in the past. Group C: Hyperthyroid patients (66 M and 13 F, mean age 63.9±13.2 years) currently treated by AM. Group D: Hypothyroid patients (6 M and 16 F, mean age 61.4±10.4 years) after AM therapy. The patients from Groups A, B, and C were retreated with AM after ~3–6 weeks of RIT. Results In Group A, after 12 months of RIT therapy, recurrent thyrotoxicosis was observed in six (7.7%) cases, and persistent hypothyroidism was diagnosed in 42 (53.8%) cases. In Group B, hyperthyroidism occurring during treatment with AM was found in 40 (33.9%) patients, and permanent hypothyroidism was observed in eleven (12.5%) cases. After annual follow-up in Group C, nine (11.4%) patients were diagnosed with hypothyroidism, while 27 (34.1%) patients were diagnosed with hyperthyroidism. In Group D, all patients had permanent hypothyroidism and when the concentration of serum thyroid-stimulating hormone was >10 µIU/mL, l-thyroxine was applied. Conclusion Our study showed that radioiodine administration is advisable in certain circumstances, even in euthyroid patients. It allows for continuation of further long-term AM treatment. Additionally, RIT allows for the reintroduction of AM therapy that was previously terminated. Hence, it can help control life-threatening tachyarrhythmias and decrease episodes of thyrotoxicosis.

Management of the hormonal syndrome of neuroendocrine tumors

Gastroenteropancreatic neuroendocrine tumors (GEP/NET) are unusual and rare neoplasms that present many clinical challenges. They characteristically synthesize store and secrete a variety of peptides and neuroamines which can lead to the development of distinct clinical syndrome, however many are clinically silent until late presentation with mass effects. Management strategies include surgery cure and cytoreduction with the use of somatostatin analogues. Somatostatin have a broad range of biological actions that include inhibition of exocrine and endocrine secretions, gut motility, cell proliferation, cell survival and angiogenesis. Five somatostatin receptors (SSTR1-SSTR5) have been cloned and characterized. Somatostatin analogues include octreotide and lanreotide are effective medical tools in the treatment and present selectivity for SSTR2 and SSTR5. During treatment is seen disapperance of flushing, normalization of bowel movements and reduction of serotonin and 5-hydroxyindole acetic acid (5-HIAA) secretion. Telotristat represents a novel approach by specifically inhibiting serotonin synthesis and as such, is a promising potential new treatment for patients with carcinoid syndrome. To pancreatic functionig neuroendocrine tumors belongs insulinoma, gastrinoma, glucagonoma and VIP-oma. Medical management in patients with insulinoma include diazoxide which suppresses insulin release. Also mTOR inhibitors may inhibit insulin secretion. Treatment of gastrinoma include both proton pump inhibitors (PPIs) and histamine H2 – receptor antagonists. In patients with glucagonomas hyperglycaemia can be controlled using insulin and oral blood glucose lowering drugs. In malignant glucagonomas smatostatin analogues are effective in controlling necrolytic migratory erythemia. Severe cases of the VIP-oma syndrome require supplementation of fluid losses. Octreotide reduce tumoral VIP secretion and control secretory diarrhoea.