EMPATHY: A New Tool for Identifying the Most Suitable Thyroxine Formulation in Hypothyroid Patients.

Background: Therapy of hypothyroidism is based on the administration of appropriate doses of levothyroxine (LT4). A failure to achieve the thyrotropin (TSH) target may be due to poor compliance with the LT4 therapy in about 60% of cases or to malabsorption in about 40% of cases. No tools are available for detecting malabsorption disorders before the choice of the most appropriate therapy. The aim of this study was to validate the Evaluation of Malabsorption in PATients with HYpothyroidism (EMPATHY) questionnaire and to demonstrate its usefulness in indicating the most appropriate therapy. Methods: EMPATHY consists of seven questions that allow the evaluation of several intolerances and allergies. Three hundred (100 males) newly diagnosed hypothyroid patients were enrolled and randomly assigned to complete an EMPATHY questionnaire (150 patients; group 1) or to a control group (150 patients; group 2). The choice of thyroxine formulation and dose for each group was made on the basis of the questionnaire answers or based on the history. Thyroid hormones and TSH were evaluated at enrollment and then every two months for six months; the number of the dose adjustments in the six months for each patient was recorded. Results: Of the 150 patients in each group, 21 (14%) in group 1 and 42 (28%) in group 2 (p = 0.005) needed more than two dose adjustments within six months. After six months of replacement therapy, six (4%) patients in group 1 and 17 (11%) in group 2 (p = 0.03) did not have appropriately controlled hypothyroidism (TSH ≥2.5 mIU/L). A significantly higher LT4 final dose was found in group 2 (148 ± 33 µg/day) than in group 1 (136 ± 28 µg/day; p = 0.003). Conclusions: Validation of EMPATHY provides endocrinologists with a useful tool in clinical practice, permitting a better personalization of LT4 replacement therapy, a more rapid attainment of the target TSH levels, and a decreased need for dose adjustments after initiating therapy.

Diabetes and Aging: From Treatment Goals to Pharmacologic Therapy.

Diabetes is becoming one of the most widespread health burning problems in the elderly. Worldwide prevalence of diabetes among subjects over 65 years was 123 million in 2017, a number that is expected to double in 2045. Old patients with diabetes have a higher risk of common geriatric syndromes, including frailty, cognitive impairment and dementia, urinary incontinence, traumatic falls and fractures, disability, side effects of polypharmacy, which have an important impact on quality of life and may interfere with anti-diabetic treatment. Because of all these factors, clinical management of type 2 diabetes in elderly patients currently represents a real challenge for the physician. Actually, the optimal glycemic target to achieve for elderly diabetic patients is still a matter of debate. The American Diabetes Association suggests a HbA1c goal <7.5% for older adults with intact cognitive and functional status, whereas, the American Association of Clinical Endocrinologists (AACE) recommends HbA1c levels of 6.5% or lower as long as it can be achieved safely, with a less stringent target (>6.5%) for patients with concurrent serious illness and at high risk of hypoglycemia. By contrast, the American College of Physicians (ACP) suggests more conservative goals (HbA1c levels between 7 and 8%) for most older patients, and a less intense pharmacotherapy, when HbA1C levels are ≤6.5%. Management of glycemic goals and antihyperglycemic treatment has to be individualized in accordance to medical history and comorbidities, giving preference to drugs that are associated with low risk of hypoglycemia. Antihyperglycemic agents considered safe and effective for type 2 diabetic older patients include: metformin (the first-line agent), pioglitazone, dipeptidyl peptidase 4 inhibitors, glucagon-like peptide 1 receptor agonists. Insulin secretagogue agents have to be used with caution because of their significant hypoglycemic risk; if used, short-acting sulfonylureas, as gliclazide, or glinides as repaglinide, should be preferred. When using complex insulin regimen in old people with diabetes, attention should be paid for the risk of hypoglycemia. In this paper we aim to review and discuss the best glycemic targets as well as the best treatment choices for older people with type 2 diabetes based on current international guidelines.

Metabolic syndrome and cancer: "The common soil hypothesis".

Metabolic syndrome (MetS) and cancer share many modifiable risk factors including age, genetic factors, obesity, physical inactivity, unhealthy diet, alcohol, smoking, endocrine disruptors exposure, circadian clock disturbances, and air pollution. MetS is closely linked to cancer, as it increases cancer risk and cancer-related mortality; moreover, cancer survivors have an increased risk of MetS. Elucidating the mechanisms linking MetS to cancer is important to prevent or delay these two conditions. Possible mechanisms explaining the relationship between MetS and cancer include hyperinsulinemia and alterations of insulin-like growth factor system, chronic subclinical inflammation, abnormalities in sex hormones metabolism and adipokines, hyperglicemia, alterations in both gene expression and hormonal profile by endocrine disruptors and air pollution, desynchronization of circadian clock. The common soil hypothesis claims that MetS may be considered a surrogate marker for dietary risk factors of cancer, and a warning sign for susceptible individuals exposed to an unhealthy diet. The common soil hypothesis and the clepsydra of foods represent a theoretical substrate to preventive intervention strategies against the pandemics of MetS and cancer: adherence to healthy dietary patterns is associated with a reduced risk of MetS, and improvement of the quality of diet is consistently associated with a reduction in cancer-related mortality.

Gender-differences in glycemic control and diabetes related factors in young adults with type 1 diabetes: results from the METRO study.

PURPOSE: To describe gender differences concerning glycemic control, cardiovascular risk factors, diabetic complications, concomitant pathologies, and circulating endothelial progenitor cells (EPCs), in a population of young adults with type 1 diabetes. METHODS: We collected data from 300 consecutively patients (168 males and 132 females), aged 18-30 years, among those admitted at Diabetes Unit of University of Campania "Luigi Vanvitelli" (Naples, Italy) from March 2012 to January 2017. Circulating levels of seven EPCs phenotypes were determined by flow cytometry. RESULTS: As compared to men, women with type 1 diabetes had a significantly higher HbA1c levels (%, 8.4 ± 1.3 vs. 8.1 ± 1.3, P = 0.020), body mass index (Kg/m2, 24.8 ± 4.2 vs. 23.9 ± 3.9, P = 0.034), HDL-cholesterol (mg/dL, 61.7 ± 13.7 vs. 54.7 ± 13.9, P < 0.001), and a lower count of both CD133+KDR+ and CD34+KDR+CD133+ EPCs (P = 0.022, P < 0.001, respectively). A higher proportion of women had overweight/obesity, and thyroiditis; smoking and sexual dysfunctions were more prevalent in men than in women. CONCLUSIONS: Young adults with type 1 diabetes present gender differences with regard to glycemic control, prevalence of some cardiovascular risk factors, sexual dysfunctions and circulating levels of EPCs, most often to the detriment of women.

Particulate matter air pollution: individual choices for improving cardiometabolic well-being.

Exposure to small particulate matter (PM2.5) has become the 5th highest ranking risk factor for death, responsible for 4.2 million deaths worldwide. PM pollution is also associated with cardiovascular disease and type 2 diabetes, and may contribute to deteriorate the already poor cardiometabolic outlook of the diabetic patient. Although most sources of outdoor air pollution are well beyond the control of individuals, there is still room for personal action. Health behaviors (smoking cessation, avoiding obesity, and increasing physical activity) may increase the poor life expectancy of individuals in the lowest income quartile of the Western population; moreover, a favorable lifestyle, (no current smoking, no obesity, physical activity at least once weekly, and a healthy diet pattern), may cut by nearly 50% the risk of coronary heart disease among people at high genetic risk. Things seem not immutable, as individual healthy choices do matter.

Lifestyle recommendations for the prevention and management of metabolic syndrome: an international panel recommendation.

The importance of metabolic syndrome (MetS) lies in its associated risk of cardiovascular disease and type 2 diabetes, as well as other harmful conditions such as nonalcoholic fatty liver disease. In this report, the available scientific evidence on the associations between lifestyle changes and MetS and its components is reviewed to derive recommendations for MetS prevention and management. Weight loss through an energy-restricted diet together with increased energy expenditure through physical activity contribute to the prevention and treatment of MetS. A Mediterranean-type diet, with or without energy restriction, is an effective treatment component. This dietary pattern should be built upon an increased intake of unsaturated fat, primarily from olive oil, and emphasize the consumption of legumes, cereals (whole grains), fruits, vegetables, nuts, fish, and low-fat dairy products, as well as moderate consumption of alcohol. Other dietary patterns (Dietary Approaches to Stop Hypertension, new Nordic, and vegetarian diets) have also been proposed as alternatives for preventing MetS. Quitting smoking and reducing intake of sugar-sweetened beverages and meat and meat products are mandatory. Nevertheless, there are inconsistencies and gaps in the evidence, and additional research is needed to define the most appropriate therapies for MetS. In conclusion, a healthy lifestyle is critical to prevent or delay the onset of MetS in susceptible individuals and to prevent cardiovascular disease and type 2 diabetes in those with existing MetS. The recommendations provided in this article should help patients and clinicians understand and implement the most effective approaches for lifestyle change to prevent MetS and improve cardiometabolic health.

Genetics of medullary thyroid cancer: An overview.

Medullary thyroid carcinoma (MTC) represents 3-5% of thyroid cancers. 75% is sporadic and 25% is the dominant component of the hereditary multiple endocrine neoplasia (MEN) type 2 syndromes. Three different subtypes of MEN2, such as MEN2A, MEN2B, and Familial MTC (FMTC) have been defined, based on presence or absence of hyperparathyroidism, pheocromocytoma and characteristic clinical features. Mutations of the RET proto-oncogene are implicated in the pathogenesis of MTC, but there are many other mutational patterns involved. In MEN2A, Codon 634 in exon 11 (Cys634Arg), corresponding to a cysteine in the extracellular cysteine-rich domain, is the most commonly altered codon. Many other mutations include codons 611, 618, 620. In the genetical testing of RET mutations in MTCs, Next-Generation Sequencing (NGS) is taking an increasingly important role. One of the most important benefit is the comprehensive analysis of molecular alterations in MTC, which allows rapidly to select patients with different risk levels. There is a difference in miRNA expression pathway between sporadic and hereditary MTCs. Among sporadic cases, expression of miR-127 was significantly lower in those who harbor somatic RET mutations than those with wild-type RET. CDKN1B mutations are associated with many clinical pictures of cancers, such as MEN4. V109G polymorphism is associated with sporadic MTCs negative for RET mutations, and might influence the clinical course of the patients affected by MTC. Although surgery (i.e. total thyroidectomy with neck lymph node dissection) is the elective treatment for MTCs, about 80% of patients have distant metastases at diagnosis and in this cases surgery is not enough and an additional treatment is needed. Interesting results come from two large phase III clinical trials with two targeted tyrosine kinase inhibitors (TKIs), vandetanib and cabozantinib. CONCLUSIONS: New genetical testings and therapeutical approaches open new perspectives in MTC management.

Pituitary dysfunction in granulomatosis with polyangiitis.

PURPOSE: Granulomatosis with polyangiitis (GPA) is a multisystem disease, characterized by necrotizing small-vessel vasculitis, which mainly affects the respiratory tract and the kidneys. Pituitary involvement in GPA is rare, present in about 1% of all cases of GPA. To date, only case reports or small case series have been published. Herein we report clinical features, imaging findings, treatment and outcomes in three patients with GPA-related pituitary dysfunction (PD). METHODS: A retrospective analysis of three cases of GPA-related PD was conducted, followed by systematic review of the English medical literature using PubMed. RESULTS: The three cases include three women aged between 32 and 37 years. PD was the presenting feature in one and two developed PD in the course of the disease. All patients had a pituitary lesion on MRI. Conventional treatment with high doses of glucocorticoids and cyclophosphamide led to resolution or improvement of the MRI abnormalities, whereas it was not effective in restoring PD. A systematic review identified 51 additional patients, showing that GPA can lead to partial or global PD, either at onset or, during the course of the disease. Secondary hypogonadism is the predominant manifestation, followed by diabetes insipidus (DI). Sellar mass with central cystic lesion is the most frequent radiological finding. CONCLUSION: GPA should be carefully considered in patients with a sellar mass and unusual clinical presentation with DI and systemic disease. Although conventional induction-remission treatment improves systemic symptoms and radiological pituitary abnormalities, hormonal deficiencies persist in most of the patients. Therefore, follow-up should include both imaging and pituitary function assessment.

Insights into the relationships between diabetes, prediabetes, and cancer.

Diabetes mellitus and cancer are two growing health problems. They have in common many modifiable risk factors including sex, age, obesity, physical activity, diet, alcohol, and smoking, and have a long latency before overtly manifesting. Patients with diabetes experience a roughly 20-25% higher cancer incidence compared to individuals without diabetes, and it depends on cancer site. Moreover, patients with diabetes who further develop cancer have increased early and late mortality in comparison with cancer patients without diabetes. Prediabetes and metabolic syndrome are also related to an increased risk of developing and die from cancer. Possible mechanisms linking diabetes and prediabetes with cancer include hyperglycemia (endogenous or exogenous), hyperinsulinemia, and alterations of insulin-like growth factor system, chronic subclinical inflammation, abnormalities in sex hormone metabolism, and adipokines. It becomes crucial to define the right orientation of the associations between diabetes and cancer in order to identify the modifiable pathogenic mechanisms. The common soil hypothesis claims that prediabetes and diabetes, as well as metabolic syndrome, may be considered a surrogate sign for dietary risk factors of cancer. The clepsydra of foods may help choose foods associated with healthy benefit while avoiding foods associated with harm, including cancer.

Cooling down inflammation in type 2 diabetes: how strong is the evidence for cardiometabolic benefit?

Chronic inflammation is supposed to be an important mediator of cardiometabolic dysfunctions seen in type 2 diabetes. In this mini-review, we collected evidence (PubMed) from randomized controlled trials (through March 2016) evaluating the effect of anti-inflammatory drugs on indices of glycemic control and/or cardiovascular events in people with type 2 diabetes. Within the last 25 years, many anti-inflammatory drugs have been tested in type 2 diabetes, including hydroxychloroquine, anti-tumor necrosis factor therapies (etanercept and infliximab), salsalate, interleukin-1 antagonists (anakinra, canakinumab, gevokizumab, LY2189102), and CC-R2 antagonists. Despite being promising, the observed effects on HbA1c or glucose control remain rather modest in most clinical trials, especially with the new drugs. There are many trials underway with anti-inflammatory agents to see whether patients with cardiovascular diseases and/or type 2 diabetes may have clinical benefit from marked reductions in circulating inflammatory markers. Until now, a large trial with losmapimod (a p38 inhibitor) among patients with acute myocardial infarction, including one/third of diabetic patients, showed no reduction in the risk of major ischemic cardiovascular events. Further evidence is warranted in support of the concept that targeting inflammation pathways may ameliorate glycemic control and also reduce cardiovascular complications in type 2 diabetes.

Revisitation of autoimmune hypophysitis: knowledge and uncertainties on pathophysiological and clinical aspects.

PURPOSE: This publication reviews the accepted knowledges and the findings still discussed on several features of autoimmune hypophysitis, including the most recently described forms, such as IgG4 and cancer immunotherapy- related hypophysitis. METHODS: The most characteristic findings and the pending controversies were derived from a literature review and previous personal experiences. A single paragraph focused on some atypical examples of the disease presenting under confounding pretences. RESULTS: Headache, visual field alterations and impaired pituitary secretion are the most frequent clinical findings of the disease. Pituitary biopsy, still considered the gold diagnostic standard, does not always receive consent from the patients. The role of magnetic resonance imaging is limited, as this disease may generate images similar to those of other diseases. The role of antipituitary and antihypothalamus antibodies is still discussed owing to methodological difficulties and also because the findings on the true pituitary antigen(s) are still debated. However, the low sensitivity and specificity of immunofluorescence, one of the more widely employed methods to detect these antibodies, may be improved, considering a predetermined cut-off titre and a particular kind of immunostaining. CONCLUSION: Autoimmune hypophysitis is a multifaceted disease, which may certainly be diagnosed by pituitary biopsy. However, the possible different clinical, laboratory and imaging features must be considered by the physician to avoid a misdiagnosis when examining a possibly affected patient. Therapeutic choice has to be made taking into account the clinical conditions and the degree of hypothalamic-pituitary involvement, but also considering that spontaneous remissions can occur.

Particulate matter pollutants and risk of type 2 diabetes: a time for concern?

The World Health Organization estimates that worldwide in 2012 around 7 million deaths occurred prematurely due to air pollution, which is now the world's largest single environmental health risk. The higher premature mortality associated with air pollution is due to exposure to small particulate matter of 10 microns (PM10) or less in diameter. Exposure to air pollution has also been suggested as a contributing to diabetes incidence and progression. There are a number of possible biological pathways linking air pollutants to diabetes, including endothelial dysfunction, dysregulation of the visceral adipose tissue through inflammation, hepatic insulin resistance, elevated hemoglobin A1c level, elevated blood pressure, and alterations in autonomic tone, which may increase insulin resistance. The risk of future diabetes associated with exposure to 10 µg/m(3) increase of PM2.5 has been quantified in the range of 10 to 27%; the risk of diabetes mortality associated with PM2.5 appears to be quite lower, around 1% for each increment exposure of 10 µg/m(3) of both PM2.5 and PM10. Limitations of the current epidemiological evidence include the complex mixture of pollutants, the different design of the studies, the limited data available for non Western populations, and the lack of demonstration that improvement of air quality is associated with a decrease incidence of type 2 diabetes. Although the most sources of outdoor air pollution are well beyond the control of individuals, people should be informed that there are means to reduce the burden of air pollutants on diabetes risk, including avoidance of passive smoking, adoption of an healthy diet, and increasing leisure-time physical activity.

Longitudinal behavior of autoimmune GH deficiency: from childhood to transition age.

BACKGROUND: Some cases of apparently idiopathic GH deficiency (GHD) may be caused by pituitary autoimmunity. OBJECTIVE: To study the variations in pituitary function and antipituitary antibodies (APA) from childhood to transition age in patients with apparently idiopathic GHD. DESIGN: We conducted a longitudinal study. PATIENTS AND METHODS: Pituitary function and APA detection by immunofluorescence were investigated in 24 childhood patients with isolated GHD before starting recombinant GH therapy and after the stopping of this therapy in transition age. Sera of patients positive for APA were processed by double immunofluorescence to identify their pituitary target. RESULTS: At diagnosis, 16 out of 24 patients were APA positive targeting only somatotrophs (group 1), while the remaining eight were APA negative (group 2). When retested off therapy, 12 out of 16 patients in group 1 persisted being APA positive, while the remaining four became negative with recovery of pituitary function. All patients in group 2 persisted being APA negative but still showing GHD. Of the 12 patients persistently APA positive, eight with confirmed GHD showed APA still targeting somatotrophs, whereas four showed APA targeting only gonadotrophs associated with isolated hypogonadotropic hypogonadism (HH). CONCLUSION: Patients with APA at middle but not at high titer in childhood may show a remission of autoimmune GHD in childhood after GH replacement therapy. As APA may shift their target in transition period, an early characterization of APA by double immunofluorescence is advisable in APA positive GHD patients showing delayed puberty, to allow an early diagnosis and an appropriate therapy, thus preventing the progression toward HH.

Sexual dysfunction in women with cancer: a systematic review with meta-analysis of studies using the Female Sexual Function Index.

Cancer may impair sexual function in women. We provide an overview of studies that address Female Sexual Dysfunction (FSD) in women with cancer with a meta-analysis of observational studies that used a validated diagnostic tool. Searches included MEDLINE, Scopus, and Google Scholar for studies published from January 2000 to 31 December 2014. Every included study had to involve at least 30 cancer patients, to investigate FSD based on the Female Sexual Function Index (FSFI), and to have been published in peer-review journals. Duplicate independent data extraction and quality assessment were performed. Data were pooled using a random effects model if statistical heterogeneity was present. The main outcomes were FSFI total score and FSD prevalence. FSFI is a 19-item self-report instrument for assessing key dimensions of female sexual function. A value less than 26.55 is consistent with FSD. Thirty-five studies met the inclusion criteria. Among these, 27 reported FSFI scores, and 16 FSD prevalence. Most studies (56 %) had low to moderate quality. The mean value of FSFI was lower than 20 at all cancer sites: 16.25 (pooled random effect, 95 % CI 14.91-17.58, I 2 = 14.5 %) for colorectal cancer, 18.11 (95 % CI 14.45-21.77, I 2 = 97.8 %) for gynecological cancer, and 19.58 (95 % CI 17.64-21.53, I 2 = 90.9 %) for breast cancer. FSD prevalence was higher than 60 % at all cancer sites, with the highest value for gynecological cancer (78.44 %, 95 % CI 68.36-88.52 %, I 2 = 94.1 %). Women with cancer showed low FSFI scores with a high prevalence of FSD.

Circulating endothelial progenitor cells in type 1 diabetic patients with erectile dysfunction.

Circulating endothelial progenitor cells (EPCs) are bone marrow-derived stem cells able to migrate to sites of damaged endothelium and differentiate into endothelial cells, thereby contributing to vascular repair. Recent studies demonstrated a reduction of EPCs in patients with diabetes mellitus or erectile dysfunction (ED). The aim of this study was to evaluate the circulating levels of different EPCs phenotypes and their relation with testosterone levels in young type 1 diabetic patients with ED. We studied 118 consecutively type 1 diabetic patients and 60 age-matched healthy controls. Erectile function was assessed by completing the International Index of Erectile Function (IIEF-5) and EPCs levels by flow cytometry. Testosterone concentrations were evaluated in all the study population. We identified 38 diabetic patients with ED (Group 1) and 80 patients without ED (Group 2). CD34+KDR+CD133+ cells were significantly lower in patients in Group 1 as compared with those in Group 2 [median and interquartile range, n/10(6) events, 12 (6-16) vs. 18 (13-22), P < 0.001)]. In all participants in the study, there was a significant correlation between circulating CD34+KDR+CD133+ cells and testosterone levels (r = 0.410, P < 0.001), which was highest in Group 1, intermediate in Group 2, and lowest in Group 3 (controls). There was a significant correlation between IIEF-5 score and both CD34+KDR+ (r = 0.459, P = 0.003) and CD34+KDR+CD133+ (r = 0.316, P = 0.050) cells among patients of Group 1, as well as between testosterone levels and most of the EPCs phenotypes. Finally, multivariate regression analysis identified levels of circulating CD34+KDR+ cells as an independent risk factor for ED (ß-coefficient 0.348, P = 0.007). In conclusion, type 1 diabetic patients with ED show reduced levels of CD34+KDR+CD133+ cells, whose number correlates with IIEF. Further studies are needed to fully understand the exact mechanisms by which testosterone regulates vascular homeostasis.

Remission of type 2 diabetes: is bariatric surgery ready for prime time?

There is mounting evidence that bariatric surgery leads to higher remission rates of type 2 diabetes than any conventional medical treatment, lifestyle intervention, or medically supervised weight loss program. Although remission rates of type 2 diabetes may be as high as 66.7 % after gastric bypass and 28.6 % after gastric band, very few bariatric surgery studies report long-term results with sufficient patient follow-up to minimize biased results. Hence, trials that directly compare bariatric surgery procedures with medical and lifestyle intervention for patients with type 2 diabetes are the best candidate for assessing the role of bariatric surgery in diabetes remission. Three randomized controlled trials and one prospective study have so far been published comparing the effect of Roux-en-Y gastric bypass (RYGB) procedure against optimal medical therapy, with a follow-up ranging from 1 to 6 years: the percentage of diabetic patients in remission (hemoglobin A1C < 6-6.5 % without medications) ranged from 38 to 75 % at the end of follow-up. Intensive lifestyle intervention is also superior to conventional treatment for inducing remission of type 2 diabetes, with remission rates of type 2 diabetes between 10 and 15 % at 1 year of follow-up. Bariatric surgical procedures, especially RYGB, are more effective at inducing initial type 2 diabetes remission in obese patients, but more information is needed about the long-term durability of comorbidity control and complications after bariatric procedures. In the meantime, all efforts should be directed toward primary prevention of type 2 diabetes, given the encouraging results of lifestyle intervention studies.

Unhealthy diets: a common soil for the association of metabolic syndrome and cancer.

The association between metabolic syndrome and cancer continues to be acknowledged. Metabolic syndrome is a common long-term complication in cancer survivors; on the other hand, findings from several recent meta-analyses suggest that the presence of metabolic syndrome is associated with increased risk of future cancer at specific sites. Approximately one-third of cancer deaths occurring in the USA each year may be caused by unhealthy lifestyle habits, including poor nutrition. Worldwide, diets low in fruits rank third for deaths attributable to individual risk factors. Metabolic syndrome may be a surrogate marker for dietary risk factors for cancer, a sentinel for the deleterious effect of unhealthy diet in susceptible individuals, who may first manifest metabolic consequences (visceral obesity, dysglycemia, hypertension, and dyslipidemia), and then an increased risk of cancer. From the standpoint of preventive oncology, people with the metabolic syndrome should be encouraged, more than sex- and age-matched counterparts, to undergo appropriate cancer screenings.