[111In]In-CP04 as a novel cholecystokinin-2 receptor ligand with theranostic potential in patients with progressive or metastatic medullary thyroid cancer: final results of a GRAN-T-MTC Phase I clinical trial.

INTRODUCTION: Medullary thyroid cancer (MTC) is a rare malignant tumour of the parafollicular C-cells with an unpredictable clinical course and currently suboptimal diagnostic and therapeutic options, in particular in advanced disease. Overexpression of cholecystokinin-2 receptors (CCK2R) represents a promising avenue to diagnostic imaging and targeted therapy, ideally through a theranostic approach. MATERIALS AND METHODS: A translational study (GRAN-T-MTC) conducted through a Phase I multicentre clinical trial of the indium-111 labelled CP04 ([111In]In-CP04), a CCK2R-seeking ligand was initiated with the goal of developing a theranostic compound. Patients with proven advanced/metastatic MTC or short calcitonin doubling time were enrolled. A two-step concept was developed through the use of low- and high-peptide mass (10 and 50 µg, respectively) for safety assessment, with the higher peptide mass considered appropriate for therapeutic application. Gelofusine was co-infused in a randomized fashion in the second step for the evaluation of potential reduction of the absorbed dose to the kidneys. Imaging for the purpose of biodistribution, dosimetry evaluation, and diagnostic assessment were performed as well as pre-, peri-, and postprocedural clinical and biochemical assessment. RESULTS: Sixteen patients were enrolled. No serious adverse events after application of the compound at both peptide amounts were witnessed; transient tachycardia and flushing were observed in two patients. No changes in biochemistry and clinical status were observed on follow-up. Preliminary dosimetry assessment revealed the highest dose to urinary bladder, followed by the kidneys and stomach wall. The effective dose for 200 MBq of [111In]In-CP04 was estimated at 7±3 mSv and 7±1 mSv for 10 µg and 50 µg CP04, respectively. Administration of Gelofusine reduced the dose to the kidneys by 53%, resulting in the organ absorbed dose of 0.044±0.019 mSv/MBq. Projected absorbed dose to the kidneys with the use of [177Lu]Lu-CP04 was estimated at 0.9±0.4 Gy/7.4 GBq. [111In]In-CP04 scintigraphy was positive in 13 patients (detection rate of 81%) with superior diagnostic performance over conventional imaging. CONCLUSION: In the present study, [111In]In-CP04 was shown to be a safe and effective radiopharmaceutical with promising theranostic characteristics for patients with advanced MTC.

Prevalence of Selected Single-Nucleotide Variants in Patients with Neuroendocrine Tumors-Potential Clinical Relevance.

INTRODUCTION: The genetic basis of neuroendocrine tumors (NETs), whose incidence is continuously increasing, is still not fully defined. The majority of NETs are sporadic, and only a small percentage occur as part of hereditary genetic syndromes. However, the associations of multiple genetic variants have been found as clinically relevant in several neoplasms. The aim of this study was to evaluate whether selected, literature-based genetic variants may have a potential role in NET susceptibility and clinical outcome in Polish patients. MATERIALS/METHODS: A total of 185 patients recruited from one clinical center were enrolled. In the first part of the study, the molecular analysis including four single-nucleotide variants (rs8005354 (DAD1, NM_001344 intronic T/C substitution), rs2069762 (T/G substitution in the promoter region of the IL2 NM_000586), rs3731198 (CDKN2A, NM_000077 intronic A/G substitution), and rs1800872 (C/A substitution in the promoter region of the IL10 NM_000572)) was performed in 107 participants (49 patients with NETs with different primary site NETs and a control group of 58 healthy adult volunteers). In the second stage, the same single-nucleotide polymorphisms (SNPs) were assessed in 127 patients with NET and analyzed in terms of clinical data (primary site, serum CgA concentration, and metastatic disease). RESULTS: The analysis of homozygotes revealed a statistically significant higher prevalence of TT homozygotes of variant rs3731198 in the control group (p = 0.0209). In NET patients, there was a statistically significant higher prevalence of GG homozygotes of variant rs1800872 (p = 0.003). There was a statistically significant correlation between the rs3731198 variant and lymph node metastases (p = 0.0038 with Bonferroni correction). CONCLUSIONS: Our study indicates that GG homozygotes of variant rs1800872 are more often observed in NET patients, while TT homozygotes of variant rs3731198 are less frequent in this group. The rs3731198 variant may be related to an increased risk of lymph node metastasis. Further, larger multicenter studies are warranted to evaluate the potential genetic factors of sporadic NETs.

Adrenal bleeding due to pheochromocytoma - A call for algorithm.

Background: Adrenal hemorrhage is a rare, usually life-threating complication. The most common neoplasm resulting in spontaneous adrenal bleeding is pheochromocytoma and it accounts for nearly 50% of cases. Currently, the recommendations for the diagnosis and management of patients with adrenal bleeding due to pheochromocytoma are unavailable. Materials and methods: We performed a database search for all pheochromocytoma patients, diagnosed and treated from 2005 to 2021 in tertiary endocrinology center. 206 patients were identified, 183 with complete data were included in the analysis. We investigated clinicopathological characteristics, treatment and outcomes of hemorrhagic pheochromocytoma cases and characterize our approach to perioperative diagnosis and medical management. Finally our experiences and data from previously published articles concerning adrenal hemorrhage were analyzed to propose a diagnostic and therapeutic algorithm for hemorrhagic pheochromocytomas. Results: In the whole group, seven patients (4 men and 3 women) with adrenal bleeding were found, (3.8%). Median patient's age was 49 years (range: 36-78 years). The most common manifestation of adrenal bleeding was acute abdominal pain (5/7). Two patients developed shock. Hormonal assessment was performed in five patients, based on 24-hour urinary fractionated metanephrines with urinary 3-methoxytyramine. Normetanephrine was elevated in all patients, metanephrine and 3-methoxytyramine - in four cases (4/5). Most patients (6/7) had symptoms suggesting pheochromocytoma before hemorrhage - most commonly paroxysmal hypertension (4/7). One patient died, before the diagnosis of adrenal bleeding was made. Diagnostic imaging performed in six out of seven patients revealed adrenal tumor, with median largest diameter equal to 7.4 cm (range: 5-11 cm). Five patients had elective surgery, in one case an urgent surgery was performed. In all cases the diagnosis of pheochromocytoma was confirmed in postoperative histopathology or in autopsy. The perioperative survival rate was 85.7%. Conclusions: Diagnosis of pheochromocytoma should be always considered in patients with adrenal bleeding, especially with accompanying abdominal pain, hemodynamic shock and previous history of pheochromocytoma-associated symptoms. Lack of proper diagnosis of pheochromocytoma before surgery is associated with an additional perioperative risk. To improve the decision making in this life-threatening clinical situation, based on our results and literature data, we proposed a diagnostic and treatment algorithm.

Molecular analysis and genotype-phenotype correlations in patients with classical congenital adrenal hyperplasia due to 21-hydroxylase deficiency from southern Poland - experience of a clinical center.

PURPOSE: The prevalence of CYP21A2 gene variants and genotype-phenotype correlations are variable among populations. The aim of this study was to characterize CYP21A2 gene variants in adult patients with classical congenital adrenal hyperplasia (CCAH) from southern Poland and to analyze genotype-phenotype correlations. MATERIALS/METHODS: A total of 48 patients (30 women and 18 men) with CCAH were included in the study. Patients were divided into two clinical subgroups, namely, salt-wasting (SW) - 38 patients and simple virilizing (SV) - 10 patients. A genetic analysis MLPA (multiplex ligation-dependent probe amplification) was performed in all of them. In dubious cases, the analysis was complemented by Sanger sequencing. Genotypes were classified into five groups (depending on the residual in vitro enzymatic activity), namely, null, A, B, C, and D, and correlated with the clinical picture. RESULTS: Molecular defects were investigated and identified in 48 patients. The most common variant in the studied group was I2G, followed by whole or partial gene copy deletion, and I172N. One novel variant c.[878G>T] (p.Gly293Val) was found. In nine patients, a non-concordance between genotype and phenotype was observed. Genotype-phenotype correlations measured by positive predictive value (PPV) were as follows: 100% in group null, 90.5% in group A, and 66.7% in group B. CONCLUSIONS: CYP21A2 variants in the studied cohort were similar to values previously reported in other countries of the region. There was a good correlation between genotype and phenotype in the null and A groups, the correlation being considerably lower in group B.

Modifier Role of Common RET Variants in Sporadic Medullary Thyroid Carcinoma.

Background: Although the disease-causing effect of pathogenic variants in the gene RET has been unambiguously identified, there is a lack of consensus regarding the possible impact of common variants in this gene. Our study aimed to test whether variants in exons 10, 11, and 13-16 that are commonly detected during routine diagnostic testing might have any modifying effect on MTC. Methods: In sporadic MTC patients with no pathogenic variants but with or without common variants in RET, the following variants were evaluated: rs1799939 (p.G691S), rs1800861 (p.L769=), rs1800862 (p.S836=), rs2472737 in intron 14, and rs1800863 (p.S904=). Results: After Bonferroni correction, none of the variants were statistically significantly associated with disease outcome when analysed independently. The MTC group was divided into three genetically different clusters by unsupervised k-means clustering. Those clusters differed significantly in the age at diagnosis. A trend towards the association of given clusters with metabolic disorders and with remission state was identified. Conclusions: Although common variants in RET are not responsible for the risk of MTC, their analysis might turn out useful in the prediction of a patient's clinical outcome. Importantly, this analysis would come with no additional cost in laboratories with a diagnostic procedure based on exon sequencing.

Hyperinsulinemic Hypoglycemia in Three Generations of a Family with Glucokinase Activating Mutation, c.295T>C (p.Trp99Arg).

Familial Hyperinsulinemic Hypoglycemia (FHH) is a very rare disease with heterogeneous clinical manifestations. There are only a few reports of heterozygous activating mutations of glucokinase (GCK) attributable to FHH, with no reports describing effects in the course in pregnancy with affected mother/affected child. A large kindred with FHH and GCK:c.295T>C (p.Trp99Arg) pathogenic variant was identified in which four family members from three generations were affected. The clinical follow up in one clinical center lasted up to 30 years, with different times of diagnosis ranging from neonate period to adulthood. The severity of hypoglycemia was mild/severe and fasting was the trigger for hypoglycemia. Response to diazoxide varied from good, in the neonate, to moderate/poor, in childhood/adulthood; however, this was biased by poor compliance. Treatment with somatostatin analogues was discontinued due to side effects. Over time, patients developed clinical adaptation to very low glucose levels. During pregnancy, episodes of severe hypoglycemia in the first trimester were observed, which responded very well to steroids. The clinical course of the GCK:c.295T>C (p.Trp99Arg) mutation varied in the same family, with the development of clinical adaptation to very low glucose levels over time. Treatment with steroids might prevent hypoglycemia during pregnancy in an affected mother.

A rare case of aggressive, hereditary paraganglioma associated with a pathogenic variant in SDHD.

Not required for Clinical Vignette.

fT3:fT4 ratio in Graves' disease - correlation with TRAb level, goiter size and age of onset.

INTRODUCTION: Graves' Disease (GD) is an autoimmune hyperthyroidism occurring mostly in young women. The main pathogenic role of the disease is attributed to TSH receptor antibodies (TRAb), which stimulate the thyroid gland to increase production of the most active thyroid hormone- triiodothyronine (T3). High level of TRAb and a large goiter size are commonly known as poor prognostic factors for the disease and are used to predict relapse. THE AIM: The purpose of our study was to check the correlation between fT3:fT4 ratio with TRAb concentration, total volume of thyroid and age of GD onset. MATERIALS AND METHODS: 114 patients with onset or relapse of GD were analyzed. Those after thyroidectomy or radioiodine therapy were not taken into analysis. The data was retrospectively retrieved from the hospital's records consisting of patients' sex, age, level of TRAb, fT3, fT4 and thyroid volume on ultrasonography. The association between fT3:fT4 and TRAb concentration, thyroid volume and age was evaluated using Pearson correlation coefficient. RESULTS: The group was predominated by women (19.3% men, 80.7% women). The average age was 47.0. The analysis revealed positive correlation between: 1) fT3:fT4 ratio and total volume of thyroid (correlation ratio: 0.37; p <0.05) 2) fT3:fT4 ratio and level of TRAb (correlation ratio: 0.26; p or <0.05) 3) negative correlation between fT3:fT4 ratio and patient's age (correlation ratio: -0.14; p = 0.144). CONCLUSIONS: Positive correlations between fT3:fT4 ratio and TRAb level and total volume of thyroid (poor predictors of GD) may confirm that high level of fT3 can also be a prognostic factor for GD severity.

Ectopic ACTH syndrome of different origin-Diagnostic approach and clinical outcome. Experience of one Clinical Centre.

PURPOSE: Ectopic Cushing Syndrome (EAS) is a rare condition responsible for about 5-20% of all Cushing syndrome cases. It increases the mortality of affected patients thus finding and removal of the ACTH-producing source allows for curing or reduction of symptoms and serum cortisol levels. The aim of this study is to present a 20-year experience in the diagnosis and clinical course of patients with EAS in a single Clinical Centre in Southern Poland as well as a comparison of clinical course and outcomes depending on the source of ectopic ACTH production-especially neuroendocrine tumors with other neoplasms. METHODS: Twenty-four patients were involved in the clinical study with EAS diagnosed at the Department of Endocrinology between years 2000 and 2018. The diagnosis of EAS was based on the clinical presentation, hypercortisolemia with high ACTH levels, high dose dexamethasone suppression test and/or corticotropin-releasing hormone tests. To find the source of ACTH various imaging studies were performed. RESULTS: Half of the patients were diagnosed with neuroendocrine tumors, whereby muscle weakness was the leading symptom. Typical cushingoid appearance was seen in merely a few patients, and weight loss was more common than weight gain. Patients with neuroendocrine tumors had significantly higher midnight cortisol levels than the rest of the group. Among patients with infections, we observed a significantly higher concentrations of cortisol 2400 levels in gastroenteropancreatic neuroendocrine tumors. Chromogranin A correlated significantly with potassium in patients with neuroendocrine tumors and there was a significant correlation between ACTH level and severity of hypokalemia. CONCLUSION: EAS is not common, but if it occurs it increases the mortality of patients; therefore, it should be taken into consideration in the case of coexistence of severe hypokalemia with hypertension and muscle weakness, especially when weight loss occurs. Because the diagnosis of gastroenteropancreatic neuroendocrine tumor worsens the prognosis-special attention should be paid to these patients.

Coexistence of neurofibromatosis type 1 with multiple malignant neoplasia.

Neurofibromatosis type 1 (NF1, von Recklinghausen disease) is inherited in autosomal dominant way genetic disorder, with an incidence at birth 1:3000. It is one of the most common congenital disorders. It is characterized by café-au-lait spots, neurofibromas, and less common MPTST and gliomas of the optic nerve. It is caused by germline mutations of the NF1 gene, which acts as tumor suppressor. Inactivation of the gene leads to increased activation of the kinase pathways, and in consequence, uncontrolled proliferation of cells. The disease predisposes to the development of both benign and malignant tumors. Malignant tumors, but not related to the nervous system occur in neurofibromatosis quite rare. The aim of the study is a literature review of NF1, with presentation of a patient with NF1 and coexisting numerous tumors: synchronous somatostatinoma and gastrointestinal stromal tumor with metachronous prostate adenocarcinoma and non-small cell lung carcinoma. And attempt to answer the question if there is a common pathway for oncogenesis of these four tumors.

[The relation between the low T3 syndrome in the clinical course of myocardial infarction and heart failure]. / Wplyw zespolu niskiej trijodotyroniny na przebieg kliniczny zawalu serca oraz rozwój niewydolnosci serca.

It has been proven that either excess or deficiency of thyroid hormones has harmful influence on the cardiovascular system function. On the other hand, severe systemic conditions like myocardial infarction or severe heart failure may affect thyroid hormones secretion and their peripheral conversion, leading to low T3 syndrome. Amongst many mechanisms causing T4 to T3 conversion disturbances, important role plays decreased activity of D1 deiodinase and increased activity of D3 deiodinase. The animal research confirmed that thyroid hormones influence cardiomiocytes phenotype and morphology. They inhibit inflammation, apoptosis and cardiac remodelling after myocardial infarction. It was also proven that free triiodothyronine similarly to brain natriuretic peptide predict long-term prognosis in chronic and acute heart failure patients. Potential influence of low T3 syndrome on the course of myocardial infarction and heart failure may have significant impact on the future research on individualization of myocardial infarction and heart failure treatment depending on patient's thyroid status.

Current Approaches to the Diagnosis of Classical form of Congenital Adrenal Hyperplasia.

Congenital adrenal hyperplasia (CAH) is one of the most common diseases transmitted in an autosomal recessive manner and is caused by mutations of enzymes which are responsible for the process of adrenal steroidogenesis. According to the impairment of enzymes involved in steroidogenesis, several types of CAH can be distinguished. The most common type is associated with mutations in the CYP21A2 gene, encoding 21-hydroxylase enzyme and has different clinical forms: Classical (in which there are two types: salt wasting and simple virilization) and non-classical, characterized by less severe symptoms and late onset. CAH is characterized by a strong correlation between the genotype and the phenotype. Mutations in the CYP21A2 gene can cause different degrees of loss of 21-hydroxylase enzyme activity which result in a wide spectrum of clinical pictures. Several methods used to diagnose CAH (such as determining steroids in serum or urine) have been known from the 70's. Modern diagnosis of CAH is based primarily on the use of genetic testing, which is the subject of numerous constantly updated patents. In this paper the most recent patents on the diagnosis of CAH were assessed.

Noninsulinoma pancreatogenous hypoglycaemia in adults--a spotlight on its genetics.

Hyperinsulinaemic hypoglycaemia (HH) is also classically referred to as "nesidioblastosis". Heterogeneous clinical manifestation of the disease causes risk of late diagnosis or even misdiagnosis. In infants and children, it can lead to serious and permanent damage to the central nervous system, which leads to the manifesting mental retardation. HH is characterised by unregulated insulin secretion from pancreatic ß-cells. This effect has been correlated with nine genes: ABCC8, KCNJ11, GCK, GLUD-1, HADH1, SLC16A1, HNF4A, HNF1A, and UCP2. Mutations in these genes were found in approximately 48% of cases. The genetic background of the remaining cases is unknown. Understanding the genetic basis of familial hyperinsulinism has changed the early look at the disease. It has allowed for the differentiation of specific types of the disease. Depending on which of the nine disease-associated loci bears a pathogenic mutation, they differ in phenotype and pattern of inheritance. This review provides a brief overview of the genetic mechanisms of HH and its possible clinical presentations.

[Influence of selected endogenous and environmental factors on the course and complications of Grave's disease]. / Wplyw wybranych czynników biologicznych oraz srodowiskowych na przebieg i wystapienie powiklan u pacjentów z choroba Gravesa-Basedowa.

UNLABELLED: Graves' disease (GD) is an autoimmune thyroid disease with complex and not fully established etiology. It occurs when environmental factors influence people genetically prone to this illness. The aim of this study was to determine the impact of selected factors (endogenous and environmental) on the course and complications of disease in patients with recurrent GD. MATERIALS AND METHODS: Two hundred and four patients with relapsed GD, treated in the Clinical Department of Endocrinology in University Hospital in Cracow in years 2004-2006 and then in 2011 were retrospectively analyzed. Patients who agreed to participate in the study were sent questionnaire to complete. Demographic and clinical data were collected and entered into a database. Patient data included: gender, place of living, lifestyle (smoking), family history of autoimmune diseases, the course of the disease, its symptoms and the treatment strategy. Furthermore the medical documentation was analyzed. Descriptive statistical analyses were made. RESULTS: The study showed a significant difference in the frequency of appearance of ophthalmopathy between men and women (80% and 37.14%, respectively, p = 0.041), between smokers and nonsmokers (61.9% and 21.05%, respectively, p = 0.022) and between the age of patients with positive and negative family history of autoimmune diseases (37.6 years and 50.5 years respectively, p = 0.002). CONCLUSIONS: 1. Male gender is a risk factor for ophthalmopathy in GD. 2. Cigarette smoking affects the risk of Graves' ophthalmopathy. 3. A positive family history of thyroid diseases and/or autoimmune diseases promotes the development of GD at a younger age.

[Symptoms and early diagnostic possibilities of pancreatic endocrine cells hyperplasia (nesidioblastosis)]. / Symptomatologia i mozliwosci wczesnej diagnostyki hiperplazji kom6rek dokrewnych trzustki (nesidioblastosis).

Nesidioplastosis in adults is one of a rare causes of hyperinsulinemic hypoglycemia. Symptoms include chronic or recurrent hypoglycemias, often with neurological signs. Due to the looses of consciousness with coexisting seizures, in many cases patients are treated on epilepsy. Right diagnosis is usually late established, when the damages in the central nervous system (CNS) are irreversible. Early diagnosis of the disease and appropriate treatment might help to avoid serious disability in these patients. The aim of the study was to asses modern diagnostics of the nesidioblastosis with an emphasis on the biochemical and hormonal tests and imaging modalities. Patients enrolled to the study were aged between 18 and 72 years of age, and had chronic or recurrent hypoglycemia caused by hyperinsulinemia. In all patients fasting glucose and fasting insulinemia tests were performed, as well as the fasting blood test or in the 24-hour profile tests. Several techniques were used including ultrasound (US), abdominal computer tomography (CT), in two patients magnetic resonance imaging, scintigraphy of somatostatin receptors in seven patients, and in two patients scintigraphy with glucagone-like peptide-1 (GLP-1) analogue-labeled marker was done. In the performed tests low values of the blood glucose were found, whereas insulin levels, however not adequate to the blood glucose, were nearly always within the normal range. In the standard imaging only in one patient tumor lesion in the pancreatic tail was revealed, though not confirmed in the intraoperative histology. In the scintigraphy examination with the somatostatin analogue in one patient slightly increased collection of the marker in whole pancreas was reported and in the other patient focal collection in the pancreatic tail was observed. Scintigraphy with GLP-1 analogue revealed focal collection of the marker in one case. Five patients were underwent surgical treatment. In the histopathology in all operated patients hyperplasia of the endocrine pancreatic cells with positive immuno. histochemic reaction on the insulin was found. In the three cases despite hyperplasia of pancreatic islets, small sizes insulinomas were detected as well. 1. The diagnosis of nesidioblastosis should be taken into consideration in all patients with unclear-cause hypoglycemias, in whom simultaneously insulin blood level is inadequate to the level of glucose. 2. Widely available imaging examinations: US, CT, MRI are useless in the diagnosis of nesidioblastosis. 3. Among the imaging methods in preoperative diagnostics of hypoglycemia with concomitant hyperinsulinemia somatostatin receptor scintigraphy seems to have specific, though limited role - it is valuable only in the severe, diffused lesions. 4. Recurrent hypoglycemias after 70% excision of the pancreas may indicate the possibility of coexistence of pancreatic islets hyperplasia and insulin secreting insulinoma.

Are RECIST criteria sufficient to assess response to therapy in neuroendocrine tumors?

MATERIAL AND METHODS: Within the group of 47 patients treated with peptide receptor radionuclide therapy (PRRT), four patients were chosen: three with inoperable tumors without liver metastases and one with two lesions in the pancreas and metastases. RESULTS: In all patients, after PRRT, the changes in the sum of the longest diameters of tumors were between -1% and -21%, resulting in stable disease reported [strict Response Evaluation Criteria in Solid Tumors (RECIST)]. But the measurements of tumor volume and attenuation in computed tomography and the tumor to nontumor ratio in somatostatin receptor scintigraphy resulted in different response assessments. CONCLUSIONS: The RECIST standard may be not sufficient to properly assess the therapy response in patients with neuroendocrine tumors.

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.