Sequelae to acromegaly: reversibility with treatment of the primary disease

Acromegalic patients suffer from a number of cardiovascular, metabolic, and rheumatologic problems, and they may also have an increased incidence of malignancy. We reviewed the literature concerning the reversibility of acromegalic complications. Hypertension, myocardial hypertrophy, left ventricular dysfunction and some rheumatologic abnormalities often continue despite successful treatment of the acromegaly. In contrast, glucose intolerance, soft tissue changes, and carpal tunnel syndrome usually resolve when the acromegaly is cured. Studies of the incidence and mortality of cancer in acromegaly are conflicting, but several suggest an increased incidence of colorectal cancer.     

Acromegaly and colorectal cancer: a comprehensive review of epidemiology, biological mechanisms, and clinical implications.

Acromegaly is an endocrine disorder characterised by sustained hypersecretion of growth hormone (GH) with concomitant elevation of insulin-like growth factor (IGF)-I, and is associated with malignancy and premature mortality from cardiovascular and respiratory diseases. In particular, there may be an increased risk of colorectal neoplasia, but the exact extent of this is contentious. Colonoscopy-based studies of adenoma prevalence rates in acromegalic patients are misleading, but population-based studies on colorectal cancer risk are more consistent - a meta-analysis estimated a pooled risk ratio of 2.04 (95 % CI: 1.32, 3.14). Possible mechanisms underlying this increased risk include direct actions as a consequence of elevated levels of circulating GH and IGF-I and/or other perturbations within the IGF system. Other possible mechanisms include altered bile acid secretion, altered cellular immunity, hyperinsulinaemia, shared genetic susceptibility and increased bowel length. However, most explanations only offer indirect evidence, and the expectation of acromegaly as a natural model of colorectal carcinogenesis has not materialised. From a clinical perspective, it seems reasonable to consider a once-only colonoscopic screening at approximately age 55 years, but potential risks and benefits should be balanced.     

The Prevalence of Cancer and Its Relation to Disease Activity in Patients With Acromegaly: Two Centers' Experience

ObjectiveAcromegaly is characterized by increased serum concentrations of growth hormone (GH) and insulin-like growth factor 1 (IGF-1). Although animal studies have demonstrated a relationship between these hormones and cancer risk, the results of human studies evaluating cancer prevalence in acromegaly are inconsistent. We aimed to investigate the prevalence of malignant neoplasms in patients with acromegaly.MethodsCancer risk was evaluated in a cohort of 280 patients (male/female: 120/160; mean age: 50.93 ± 12.07 years) with acromegaly. Patients were categorized into 2 groups according to the presence or absence of cancer. Standard incidence ratios were calculated as compared to the general population.ResultsFrom 280 patients, cancer was diagnosed in 19 (6.8%) patients; 9 (47%) of them had thyroid cancer, which was the most common cancer type. Standard incidence ratios of all cancers were 0.8 (95% CI, 0.5-1.1) and 1.0 (95% CI, 0.8-1.3) in men and women, respectively. Compared to patients without cancer, the current age was higher in patients with cancer (59 [49-65] to 51 [42-59], P = .027). In contrast, the age at diagnosis was similar in both groups. Not only was the time to diagnosis and disease duration similar in both groups but also the basal and current GH and IGF-1 levels. The prevalence of active disease was also similar between the groups (32% to 23%, P = .394).ConclusionOur findings were not consistent with the studies suggesting that patients with acromegaly encounter an increased cancer risk. Furthermore, there were similar basal and current GH and IGF-1 levels in patients with acromegaly, both with and without cancer.     

Evaluation of fecal mutagenicity and colorectal cancer risk

Colorectal cancer is one of the most common internal malignancies in Western society. The cause of this disease appears to be multifactorial and involves genetic as well as environmental aspects. The human colon is continuously exposed to a complex mixture of compounds, which is either of direct dietary origin or the result of digestive, microbial and excretory processes. In order to establish the mutagenic burden of the colorectal mucosa, analysis of specific compounds in feces is usually preferred. Alternatively, the mutagenic potency of fecal extracts has been determined, but the interpretation of these more integrative measurements is hampered by methodological shortcomings. In this review, we focus on exposure of the large bowel to five different classes of fecal mutagens that have previously been related to colorectal cancer risk. These include heterocyclic aromatic amines (HCA) and polycyclic aromatic hydrocarbons (PAH), two exogenous factors that are predominantly ingested as pyrolysis products present in food and (partially) excreted in the feces. Additionally, we discuss N-nitroso-compounds, fecapentaenes and bile acids, all fecal constituents (mainly) of endogenous origin. The mutagenic and carcinogenic potency of the above mentioned compounds as well as their presence in feces, proposed mode of action and potential role in the initiation and promotion of human colorectal cancer are discussed. The combined results from in vitro and in vivo research unequivocally demonstrate that these classes of compounds comprise potent mutagens that induce many different forms of genetic damage and that particularly bile acids and fecapentaenes may also affect the carcinogenic process by epigenetic mechanisms. Large inter-individual differences in levels of exposures have been reported, including those in a range where considerable genetic damage can be expected based on evidence from animal studies. Particularly, however, exposure profiles of PAH and N-nitroso compounds (NOC) have to be more accurately established to come to a risk evaluation. Moreover, lack of human studies and inconsistency between epidemiological data make it impossible to describe colorectal cancer risk as a result of specific exposures in quantitative terms, or even to indicate the relative importance of the mutagens discussed. Particularly, the polymorphisms of genes involved in the metabolism of heterocyclic amines are important determinants of carcinogenic risk. However, the present knowledge of gene-environment interactions with regard to colorectal cancer risk is rather limited. We expect that the introduction of DNA chip technology in colorectal cancer epidemiology will offer new opportunities to identify combinations of exposures and genetic polymorphisms that relate to increased cancer risk. This knowledge will enable us to improve epidemiological study design and statistical power in future research.     

Luminal iron levels govern intestinal tumorigenesis after Apc loss in vivo

It is clear from epidemiological studies that excess iron is associated with increased risk of colorectal cancer; however, questions regarding the mechanism of how iron increases cancer risk, the source of the excess iron (circulating or luminal), and whether iron reduction represents a potential therapeutic option remain unanswered. In this study, we show that after Apc deletion, the cellular iron acquisition proteins TfR1 and DMT1 are rapidly induced. Conversely, restoration of APC reduces cellular iron due to repression of these proteins. To test the functional importance of these findings, we performed in vivo investigations of the impact of iron levels on intestinal tumorigenesis. Strikingly, depletion of luminal (but not systemic) iron strongly suppressed murine intestinal tumorigenesis, whereas increased luminal iron strongly promoted tumorigenesis. Taken together, our data definitively delineate iron as a potent modifier of intestinal tumorigenesis and have important implications for dietary iron supplementation in patients at high risk of colorectal cancer.     

Diet and colorectal cancer prevention

The majority of cancers are sporadic and epidemiological estimates suggest that up to 80% of colorectal cancer is attributable to diet. Epidemiologically, cross-sectional comparisons, case-control studies and trends in food intake show high rates of colorectal cancer in populations consuming diets high in meat and fat, and low in starch, NSP (non-starch polysaccharides, fibre) and vegetables. In general, prospective studies tend to support these findings although estimates of relative risk are not high. Existing prospective studies have however used crude indices of diet subject to substantial measurement error, and interactions with genetic polymorphisms in, for example, phase-I and -II enzymes have been studied only rarely. The association between meat consumption and colorectal cancer is usually attributed to the formation of heterocyclic amines in meat when it is cooked. In addition, in humans high-meat diets increase the level of nitrosatable material entering the colon so that faecal N-nitroso compounds (NOCs) increase in a dose-responsive manner following endogenous synthesis in the colon. Some of the mutations and guanine adducts accumulated during colorectal cancer progression are characteristic of alkylative damage, which would be compatible with NOC exposure. To date, NSP, resistant starch and vegetables have not reduced faecal NOC levels.     

Mechanisms linking obesity and cancer

The incidence of obesity in US adults has been steadily increasing over the past few decades. Many comorbidities associated with obesity have been well-established such as type 2 diabetes and cardiovascular diseases. However, more recently an epidemiological relationship between obesity and the prevalence of a variety of cancers has also been uncovered. The shift of the paradigm surrounding white adipose tissue function from purely an energy storage tissue, to one that has both endocrine and metabolic relevance, has led to several mechanisms implicated in how obesity drives cancer prevalence and cancer deaths. Currently, there are four categories into which these mechanisms fall — increased lipids and lipid signaling, inflammatory responses, insulin resistance, and adipokines. In this review, we examine each of these categories and the mechanisms through which they drive cancer pathogenesis. Understanding the relationship(s) between obesity and cancer and especially the nodal points of control in these cascades will be essential in developing effective therapeutics or interventions for combating this deadly combination. This article is part of a Special Issue entitled Lipid Metabolism in Cancer.     

The association of diet,gut microbiota and colorectal cancer: what we eat may imply what we get

Despite the success of colonoscopy screening and recent advances in cancer treatment, colorectal cancer (CRC) still remains one of the most commonly diagnosed and deadly cancers, with a significantly increased incidence in developing countries where people are adapting to Western lifestyle. Diet has an important impact on risk of CRC. Multiple epidemiological studies have suggested that excessive animal protein and fat intake, especially red meat and processed meat, could increase the risk of developing CRC while fiber could protect against colorectal tumorigenesis. Mechanisms have been investigated by animal studies.Diet could re-shape the community structure of gut microbiota and influence its function by modulating the production of metabolites. Butyrate, one of the short-chain fatty acids (SCFAs), which act as a favorable source for colonocytes, could protect colonic epithelial cells from tumorigenesis via anti-inflammatory and antineoplastic properties through cell metabolism, microbiota homeostasis, antiproliferative, immunomodulatory and genetic/epigenetic regulation ways. In contrast, protein fermentation and bile acid deconjugation, which cause damage to colonic cells through proinflammatory and proneoplastic ways, lead to increasedriskofdevelopingCRC.In conclusion, abalanced diet with an increased abundance of fiber should be adopted to reduce the risk and prevent CRC.     

Molecular genetics of early-onset colorectal cancer

Early-onset colorectal cancer (EOCRC) has been rising in global prevalence and incidence over the past several decades. Environmental influences, including generational lifestyle changes and rising obesity, contribute to these increased rates. While the rise in EOCRC is best documented in western countries, it is seen throughout the world, although EOCRC may have distinct genetic mutations in patients of different ethnic backgrounds. Pathological and molecular characterizations show that EOCRC has a distinct presentation compared with later-onset colorectal cancer (LOCRC). Recent studies have identified DNA, RNA, and protein-level alterations unique to EOCRC, revealing much-needed biomarkers and potential novel therapeutic targets. Many molecular EOCRC studies have been performed with Caucasian and Asian EOCRC cohorts, however, studies of other ethnic backgrounds are limited. In addition, certain molecular characterizations that have been conducted for LOCRC have not yet been repeated in EOCRC, including high-throughput analyses of histone modifications, mRNA splicing, and proteomics on large cohorts. We propose that the complex relationship between cancer and aging should be considered when studying the molecular underpinnings of EOCRC. In this review, we summarize current EOCRC literature, focusing on sporadic molecular alterations in tumors, and their clinical implications. We conclude by discussing current challenges and future directions of EOCRC research efforts.     

AHR Over-Expression in Papillary Thyroid Carcinoma: Clinical and Molecular Assessments in a Series of Italian Acromegalic Patients with a Long-Term Follow-Up

Aim

Acromegaly reportedly carries an increased risk of malignant and benign thyroid tumors, with a prevalence of thyroid cancer of around 3–7%. Germline mutations in the aryl-hydrocarbon receptor (AHR) interacting protein (AIP) have been identified in familial forms of acromegaly. The molecular and endocrine relationships between follicular thyroid growth and GH-secreting pituitary adenoma have yet to be fully established. Our aim was to study the prevalence of differentiated thyroid cancer (DTC) in acromegaly, focusing on the role of genetic events responsible for the onset of thyroid cancer.

Methods

Germline mutations in the AIP gene were assessed in all patients; BRAF and H-N-K RAS status was analyzed by direct sequencing in thyroid specimens, while immunohistochemistry was used to analyze the protein expression of AIP and AHR. A set of PTCs unrelated to acromegaly was also studied.

Results

12 DTCs (10 papillary and 2 follicular carcinomas) were identified in a cohort of 113 acromegalic patients. No differences in GH/IGF-1 levels or disease activity emerged between patients with and without DTC, but the former were older and more often female. BRAF V600E was found in 70% of the papillary thyroid cancers; there were no RAS mutations. AIP protein expression was similar in neoplastic and normal cells, while AHR protein was expressed more in PTCs carrying BRAF mutations than in normal tissue, irrespective of acromegaly status.

Conclusions

The prevalence of DTC in acromegaly is around 11% and endocrinologists should bear this in mind, especially when examining elderly female patients with uninodular goiter. The DTC risk does not seem to correlate with GH/IGF-1 levels, while it may be associated with BRAF mutations and AHR over-expression. Genetic or epigenetic events probably play a part in promoting thyroid carcinoma.     

Germline mutations in the MYH gene in Swedish familial and sporadic colorectal cancer

Biallelic germline mutations in the base excision repair gene MYH have been shown to predispose to a proportion of multiple colorectal adenomas and cancer. To evaluate the contribution of MYH mutations to non- FAP, non-HNPCC familial colorectal cancer, 84 unrelated Swedish individuals affected with colorectal cancer from such families were screened for germline mutations in the coding sequence of the gene. None of the cases was found to carry any pathogenic sequence change. We then determined the prevalence of the two most common pathogenic MYH mutations found in Caucasians, Y165C and G382D, in 450 Swedish sporadic colorectal cancer cases and 480 Swedish healthy controls. The frequency of both variants in Swedish cases and controls was similar to those previously reported. In addition, we found that previously unknown sequence variations at the position of amino acid 423 (R423Q, R423P, and R423R) appear to occur more frequently in cases than in controls (p = 0.02), a finding that warrants future studies.     

Extract of Lactobacillus plantarum strain 06CC2 induces JNK/p38 MAPK pathway-mediated apoptosis through endoplasmic reticulum stress in Caco2 colorectal cancer cells

Colorectal cancer is a multi-factorial disease involving genetic, environmental and lifestyle risk factors. In recent years, many changes in the bacterial composition of the intestinal microflora have been reported in colorectal cancer, suggesting the involvement of the intestinal microflora in the development and progression of colorectal cancer. Along with these reports, research on lactic acid bacteria that have a beneficial effect on the human body for the purpose of improving the intestinal environment and treating intestinal diseases has advanced. Among these studies, biogenics (defined as a component derived from lactic acid bacteria that acts directly on diseases regardless of the state of intestinal microflora) is a recent concept derived from the work on probiotics. Based on this concept, it is important to evaluate the effectiveness of various components derived from lactic acid bacteria in the treatment to diseases from and apply them in prevention and treatment. In this study, we investigated the antitumor effect of an extract obtained from Lactobacillus plantarum strain 06CC2 on colorectal cancer cells. In in vitro experiments, the extract derived from Lactobacillus plantarum 06CC2 significantly suppressed the proliferation of Caco2 colorectal cancer cells in comparison to control and non-cancer cells. Furthermore, we found that endoplasmic reticulum stress and the JNK/p38 MAPK signaling system are involved in the induction of apoptosis. These findings indicate the direct antitumor effect of the Lactobacillus plantarum 06CC2 extract on Caco2 colorectal cancer cells, and that this extract may have potential application as a biogenics.     

Population-Attributable Causes of Cancer in Korea: Obesity and Physical Inactivity

Background

Changes in lifestyle including obesity epidemic and reduced physical activity influenced greatly to increase the cancer burden in Korea. The purpose of the current study was to perform a systematic assessment of cancers attributable to obesity and physical inactivity in Korea.

Methodology/Principal Findings

Gender- and cancer site-specific population-attributable fractions (PAF) were estimated using the prevalence of overweight and obesity in 1992–1995 from a large-scale prospective cohort study, the prevalence of low physical activity in 1989 from a Korean National Health Examination Survey, and pooled relative risk estimates from Korean epidemiological studies. The overall PAF was then estimated using 2009 national cancer incidence data from the Korea Central Cancer Registry.Excess body weight was responsible for 1,444 (1.5%) and 2,004 (2.2%) cancer cases among men and women, respectively, in 2009 in Korea. Among men, 6.8% of colorectal, 2.9% of pancreatic, and 16.0% of kidney cancer was attributable to excess body weight. In women, 6.6% of colorectal, 3.9% of pancreatic, 18.7% of kidney, 8.2% of postmenopausal breast, and 32.7% of endometrial cancer was attributable to excess body weight. Low leisure-time physical activity accounted for 8.8% of breast cancer, whereas the PAF for overall cancer was low (0.1% in men, 1.4% in women). Projections suggest that cancers attributable to obesity will increase by 40% in men and 16% in women by 2020.

Conclusions/Significance

With a significantly increasing overweight and physically inactive population, and increasing incidence of breast and colorectal cancers, Korea faces a large cancer burden attributable to these risk factors. Had the obese population of Korea remained stable, a large portion of obesity-related cancers could have been avoided. Efficient cancer prevention programs that aim to reduce obesity- and physical inactivity-related health problems are essential in Korea.     

A Nested Case–Control Study of Metabolically Defined Body Size Phenotypes and Risk of Colorectal Cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC)

BackgroundObesity is positively associated with colorectal cancer. Recently, body size subtypes categorised by the prevalence of hyperinsulinaemia have been defined, and metabolically healthy overweight/obese individuals (without hyperinsulinaemia) have been suggested to be at lower risk of cardiovascular disease than their metabolically unhealthy (hyperinsulinaemic) overweight/obese counterparts. Whether similarly variable relationships exist for metabolically defined body size phenotypes and colorectal cancer risk is unknown.ConclusionsThese results support the idea that individuals with the metabolically healthy/overweight phenotype (with normal insulin levels) are at lower colorectal cancer risk than those with hyperinsulinaemia. The combination of anthropometric measures with metabolic parameters, such as C-peptide, may be useful for defining strata of the population at greater risk of colorectal cancer.     

Mouse models for unraveling the importance of diet in colon cancer prevention

Diet and genetics are both considered important risk determinants for colorectal cancer, a leading cause of death worldwide. Several genetically engineered mouse models have been created, including the Apc^Min mouse, to aid in the identification of key cancer related processes and to assist with the characterization of environmental factors, including the diet, which influence risk. Current research using these models provides evidence that several bioactive food components can inhibit genetically predisposed colorectal cancer, while others increase risk. Specifically, calorie restriction or increased exposure to n-3 fatty acids, sulforaphane, chafuroside, curcumin and dibenzoylmethane were reported protective. Total fat, calories and all-trans retinoic acid are associated with an increased risk. Unraveling the importance of specific dietary components in these models is complicated by the basal diet used, the quantity of test components provided and interactions among food components. Newer models are increasingly available to evaluate fundamental cellular processes, including DNA mismatch repair, immune function and inflammation as markers for colon cancer risk. Unfortunately, these models have been used infrequently to examine the influence of specific dietary components. The enhanced use of these models can shed mechanistic insights about the involvement of specific bioactive food and components and energy as determinants of colon cancer risk. However, the use of available mouse models to exactly represent processes important to human gastrointestinal cancers will remain a continued scientific challenge.     

Pathogenesis of colorectal carcinoma and therapeutic implications: the roles of the ubiquitin-proteasome system and Cox-2

Pathways of the molecular pathogenesis of colorectal carcinoma have been extensively studied and molecular lesions during the development of the disease have been revealed. High up in the list of colorectal cancer lesions are APC (adenomatous polyposis coli), K-ras, Smad4 (or DPC4-deleted in pancreatic cancer 4) and p53 genes. All these molecules are part of important pathways for the regulation of cell proliferation and apoptosis and as a result perturbation of these processes lead to carcinogenesis. The ubiquitin-proteasome system (UPS) is comprised of a multi-unit cellular protease system that regulates several dozens of cell proteins after their ligation with the protein ubiquitin. Given that among these proteins are regulators of the cell cycle, apoptosis, angiogenesis, adhesion and cell signalling, this system plays a significant role in cell fate and carcinogenesis. UPS inhibition has been found to be a pre-requisite for apoptosis and is already clinically exploited with the proteasome inhibitor bortezomib in multiple myeloma. Cyclooxygenase-2 (Cox-2) is the inducible form of the enzyme that metabolizes the lipid arachidonic acid to prostaglandin H2, the first step of prostaglandins production. This enzyme is up-regulated in colorectal cancer and in several other cancers. Inhibition of Cox-2 by aspirin and other non-steroidal anti-inflammatory drugs (NSAIDs) has been found to inhibit proliferation of colorectal cancer cells and in epidemiologic studies has been shown to reduce colon polyp formation in genetically predisposed populations and in the general population. NSAIDs have also Cox-independent anti-proliferative effects. Targeted therapies, the result of increasingly understanding carcinogenesis in the molecular level, have entered the field of anti-neoplastic treatment and are used by themselves and in combination with chemotherapy drugs. Combinations of targeted drugs have started also to be investigated. This article reviews the molecular pathogenesis of colorectal cancer, the roles of UPS and Cox-2 in it and puts forward a rational for their combined inhibition in colorectal cancer treatment.     

Type 2 diabetes mellitus as risk factor for colorectal cancer

Colorectal cancer occurs more frequently in patients with type 2 diabetes mellitus. The hyperinsulinemia-hypothesis suggests that elevated levels of insulin and free IGF-1 promote proliferation of colon cells and lead to a survival benefit of transformed cells, ultimately resulting in colorectal cancer. In patients with type 2 diabetes mellitus, epidemiological studies show an increased risk for colorectal cancer and an even higher risk if patients are treated with sulphonylureas or insulin. Moreover, tumour progression at hyperinsulinemia is more rapid and tumour-associated mortality is increased. Colorectal cancer can be avoided by screening. Recommendations for colorectal cancer screening should employ the recent epidemiologic evidence. All patients with type 2 diabetes mellitus should be recommended to undergo colonoscopy before starting insulin therapy, and screening intervals should not exceed 5 years. For this concept, a review of the evidence is presented, and a screening algorithm for colorectal cancer in patients with type 2 diabetes mellitus is proposed.     

Determination of insulin-like growth factor-I in the monitoring of growth hormone treatment with respect to efficacy of treatment and side effects: should potential risks of cardiovascular disease and cancer be considered?

Insulin-like growth factor (IGF)-I has proven to be important in the diagnosis of childhood-onset growth hormone (GH) deficiency (GHD). However, the variability of IGF-I should be taken into account before it can be used in a clinical setting. GH replacement therapy in GHD patients increases IGF-I into the normal range, although there is a large variation. Excessively high (supranormal) GH-induced IGF-I levels are associated with increased prevalence of side effects in adults with GHD. Consequently, at most centres, GH doses are titrated according to IGF-I levels in GHD adults. Whether or not this should also be done in children has not been established. Due to the known variability of IGF-I, individual changes in IGF-I must exceed approximately 35% to be sufficiently significant to warrant a dose adjustment. Novel epidemiological studies have suggested that higher IGF-I levels are associated with an increased risk of prostate, breast and colorectal cancer compared with lower IGF-I levels in otherwise healthy subjects. Consequently, life-time exposure to IGF-I should be considered in all patients treated with GH, and IGF-I should preferably be kept within normal age-related ranges in children as well as in adults.     

Accelerated Telomere Shortening in Acromegaly; IGF-I Induces Telomere Shortening and Cellular Senescence

Objective

Patients with acromegaly exhibit reduced life expectancy and increased prevalence of age-related diseases, such as diabetes, hypertension, and cardiovascular disease. However, the underlying mechanism has not been fully elucidated. Telomere shortening is reportedly associated with reduced life expectancy and increased prevalence of these age-related diseases.

Methods

We measured telomere length in patients with acromegaly using quantitative PCR method. The effect of GH and IGF-I on telomere length and cellular senescence was examined in human skin fibroblasts.

Results

Patients with acromegaly exhibited shorter telomere length than age-, sex-, smoking-, and diabetes-matched control patients with non-functioning pituitary adenoma (0.62 ± 0.23 vs. 0.75 ± 0.35, respectively, P = 0.047). In addition, telomere length in acromegaly was negatively correlated with the disease duration (R ² = 0.210, P = 0.003). In vitro analysis revealed that not GH but IGF-I induced telomere shortening in human skin fibroblasts. Furthermore, IGF-I-treated cells showed increased senescence-associated β-galactosidase activity and expression of p53 and p21 protein. IGF-I-treated cells reached the Hayflick limit earlier than GH- or vehicle-treated cells, indicating that IGF-I induces cellular senescence.

Conclusion

Shortened telomeres in acromegaly and cellular senescence induced by IGF-I can explain, in part, the underlying mechanisms by which acromegaly exhibits an increased morbidity and mortality in association with the excess secretion of IGF-I.     

Benign and Malignant Nodular Thyroid Disease in Acromegaly. Is a Routine Thyroid Ultrasound Evaluation Advisable?

Data on the prevalence of benign and malignant nodular thyroid disease in patients with acromegaly is a matter of debate. In the last decade an increasing incidence of thyroid cancer has been reported. The aim of this study was to evaluate the prevalence of goiter, thyroid nodules and thyroid cancer in a large series of patients with acromegaly with a cross-sectional study with a control group. Six Spanish university hospitals participated. One hundred and twenty three patients (50% men; mean age 59±13 years; disease duration 6.7±7.2 years) and 50 controls (51% males, mean age 58±15 years) were studied. All participants underwent thyroid ultrasound and fine needle aspiration. Cytological analysis was performed in suspicious nodules between 0.5 and 1.0 cm and in all nodules greater than 1.0 cm. Goiter was more frequently found in patients than in controls (24.9 vs. 8.3%, respectively; p<0.001). Nodular thyroid disease as well as nodules greater than 1 cm were also more prevalent in acromegalic patients (64.6%, vs. 28.6%, p<0.05 and 53.3 vs. 28.6%, respectively; p<0.05), and all underwent fine needle aspiration. Suspicious cytology was detected in 4 patients and in none of the controls. After thyroidectomy, papillary thyroid carcinoma was confirmed in two cases (3.3% of patients with thyroid nodules), representing 1.6% of the entire group of patients with acromegaly (2.4% including a case with previously diagnosed papillary thyroid carcinoma). These data indicated that thyroid nodular disease and cancer are increased in acromegaly, thus justifying its routine ultrasound screening.