The 11th edition of Harrison's Principles of Internal Medicine welcomes Anthony Fauci to its editorial staff, in addition to more than 85 new contributors. While the organization of the book is similar to previous editions, major emphasis has been placed on disorders that affect multiple organ systems. Important advances in genetics, immunology, and oncology are emphasized. Many chapters of the book have been rewritten and describe major advances in internal medicine. Subjects that received only a paragraph or two of attention in previous editions are now covered in entire chapters. Among the chapters that have been extensively revised are the chapters on infections in the compromised host, on skin rashes in infections, on many of the viral infections, including cytomegalovirus and Epstein-Barr virus, on sexually transmitted diseases, on diabetes mellitus, on disorders of bone and mineral metabolism, and on lymphadenopathy and splenomegaly. The major revisions in these chapters and many

Harrison's Principles of Internal Medicine

This article summarizes the phenomenon of cancer overdiagnosis—the diagnosis of a “cancer” that would otherwise not go on to cause symptoms or death. We describe the two prerequisites for cancer overdiagnosis to occur: the existence of a silent disease reservoir and activities leading to its detection (particularly cancer screening). We estimated the magnitude of overdiagnosis from randomized trials: about 25% of mammographically detected breast cancers, 50% of chest x-ray and/or sputum-detected lung cancers, and 60% of prostate-specific antigen–detected prostate cancers. We also review data from observational studies and population-based cancer statistics suggesting overdiagnosis in computed tomography–detected lung cancer, neuroblastoma, thyroid cancer, melanoma, and kidney cancer. To address the problem, patients must be adequately informed of the nature and the magnitude of the trade-off involved with early cancer detection. Equally important, researchers need to work to develop better estimates of the magnitude of overdiagnosis and develop clinical strategies to help minimize it.

Overdiagnosis in Cancer

By definition, an adrenal incidentaloma is an asymptomatic adrenal mass detected on imaging not performed for suspected adrenal disease. In most cases, adrenal incidentalomas are nonfunctioning adrenocortical adenomas, but may also represent conditions requiring therapeutic intervention (e.g. adrenocortical carcinoma, pheochromocytoma, hormone-producing adenoma or metastasis). The purpose of this guideline is to provide clinicians with best possible evidence-based recommendations for clinical management of patients with adrenal incidentalomas based on the GRADE (Grading of Recommendations Assessment, Development and Evaluation) system. We predefined four main clinical questions crucial for the management of adrenal incidentaloma patients, addressing these four with systematic literature searches: (A) How to assess risk of malignancy?; (B) How to define and manage low-level autonomous cortisol secretion, formerly called 'subclinical' Cushing's syndrome?; (C) Who should have surgical treatment and how should it be performed?; (D) What follow-up is indicated if the adrenal incidentaloma is not surgically removed? SELECTED RECOMMENDATIONS: (i) At the time of initial detection of an adrenal mass establishing whether the mass is benign or malignant is an important aim to avoid cumbersome and expensive follow-up imaging in those with benign disease. (ii) To exclude cortisol excess, a 1mg overnight dexamethasone suppression test should be performed (applying a cut-off value of serum cortisol ≤50nmol/L (1.8µg/dL)). (iii) For patients without clinical signs of overt Cushing's syndrome but serum cortisol levels post 1mg dexamethasone >138nmol/L (>5µg/dL), we propose the term 'autonomous cortisol secretion'. (iv) All patients with '(possible) autonomous cortisol' secretion should be screened for hypertension and type 2 diabetes mellitus, to ensure these are appropriately treated. (v) Surgical treatment should be considered in an individualized approach in patients with 'autonomous cortisol secretion' who also have comorbidities that are potentially related to cortisol excess. (vi) In principle, the appropriateness of surgical intervention should be guided by the likelihood of malignancy, the presence and degree of hormone excess, age, general health and patient preference. (vii) Surgery is not usually indicated in patients with an asymptomatic, nonfunctioning unilateral adrenal mass and obvious benign features on imaging studies. We provide guidance on which surgical approach should be considered for adrenal masses with radiological findings suspicious of malignancy. Furthermore, we offer recommendations for the follow-up of patients with adrenal incidentaloma who do not undergo adrenal surgery, for those with bilateral incidentalomas, for patients with extra-adrenal malignancy and adrenal masses and for young and elderly patients with adrenal incidentalomas.

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Management of adrenal incidentalomas: European Society of Endocrinology Clinical Practice Guideline in collaboration with the European Network for the Study of Adrenal Tumors

A 68-year-old woman is incidentally found to have a left adrenal mass, 2.8 cm in diameter, on abdominal computed tomography that was ordered to evaluate right lower abdominal discomfort (which has since resolved). Her medical history is notable only for hypertension that has been well controlled with hydrochlorothiazide, at a dose of 25 mg daily. She reports no sweating, palpitations, headache, weight gain, or proximal muscle weakness. Her physical examination is unremarkable. How should she be evaluated?

/pdf/the-incidentally-discovered-adrenal-mass-588upyq3t5.pdf

The incidentally discovered adrenal mass

https://www.thelancet.com/pdfs/journals/lancet/PIIS0140-6736(05)66736-0.pdf

Congenital adrenal hyperplasia

This National Institutes of Health conference discussed the following aspects of clinically inapparent adrenal masses: causes, prevalence, and natural history; appropriate evaluation; criteria for ...

Management of the clinically inapparent adrenal mass ("incidentaloma").

This review supports the U.S. Preventive Services Task Force recommendations on genetic counseling and BRCA testing for susceptibility to breast and ovarian cancer.

Genetic risk assessment and BRCA mutation testing for breast and ovarian cancer susceptibility: systematic evidence review for the U.S. Preventive Services Task Force.

This review supports the U.S. Preventive Services Task Force recommendation on routine genetic screening for hereditary hemochromatosis.

Screening for hereditary hemochromatosis : A systematic review for the U.S. preventive services task force

Context Breast cancer is the second most common cancer in women in the U.S. and is the second leading cause of cancer death. Although less common, ovarian cancer is associated with high morbidity and mortality. Both breast and ovarian cancer are associated with a family history of these conditions and, in some families, the pattern of cancers suggests the presence of a dominantly inherited cancer susceptibility gene. Two genes, BRCA1 and BRCA2, have been identified as breast cancer susceptibility genes, and clinically significant mutations are estimated to occur in about 1 in 300 to 500 of the general population. Objective Screening for inherited breast and ovarian cancer susceptibility is a two-step process that includes an assessment of risk for clinically significant BRCA mutations followed by genetic testing of high-risk individuals. The evidence synthesis describes the strengths and limits of evidence about the effectiveness of selecting, testing, and managing patients in the course of screening in the primary care setting. Its objective is to determine the balance of benefits and adverse effects of screening based on available evidence. The target population includes adult women without preexisting breast or ovarian cancer presenting for routine care in the U.S. Data Sources Relevant studies were identified from multiple searches of MEDLINE® (1966 to October 1, 2004), Cochrane Library databases, reference lists of pertinent studies, reviews, editorials, and websites, and by consulting experts. Study Selection Investigators reviewed all abstracts identified by the searches and determined eligibility by applying inclusion and exclusion criteria specific to key questions about risk assessment, mutation testing, prevention interventions, and potential adverse effects including ethical, legal, and social implications (ELSI). Eligible studies had English-language abstracts, were applicable to U.S. clinical practice, and provided primary data relevant to key questions. Data Extraction All eligible studies were reviewed and data were extracted from each study, entered into evidence tables, and summarized by descriptive and statistical methods as appropriate. Two reviewers independently rated the quality of studies using USPSTF criteria. Data Synthesis A primary care approach to screening for BRCA genetic susceptibility for breast and ovarian cancer has not been tested. No studies directly evaluated whether screening by risk assessment and BRCA mutation testing leads to a reduction in the incidence of breast and ovarian cancer and cause-specific and/or all cause mortality. Assessment tools that estimate the risk of clinically significant BRCA mutations are available to clinicians, but have not been widely evaluated in primary care settings. Several referral guidelines have been developed for primary care, but there is no consensus or gold standard for use. Trials reported that genetic counseling may increase accuracy of risk perception, and decrease breast cancer worry and anxiety. Estimates of breast and ovarian cancer occurrence, based on studies of BRCA mutation prevalence and penetrance, can be stratified by family history risk groups that are applicable to screening. However, studies are heterogeneous and estimates based on them may not be reliable. Studies of potential adverse effects of risk assessment, genetic counseling, and testing reported decreased rather than increased distress. A meta-analysis of chemoprevention trials in women with unknown mutation status indicated statistically significant effects of selective estrogen receptor modulators in preventing breast cancer and estrogen receptor positive breast cancer, and significantly increased risks for thromboembolic events and endometrial cancer. Observational studies of prophylactic mastectomy and oophorectomy indicated reduced risks of breast and ovarian cancer in BRCA mutation carriers. Studies of patient satisfaction with surgery had mixed results; cancer distress improved, but self-esteem, body image, and other outcomes were adversely affected in some women. Applying this evidence to an outcomes table indicated that the numbers needed to screen to prevent one case of breast (4,000–13,000) or ovarian cancer (7,000) are high among women with an average risk of having a clinically significant BRCA mutation, and decrease as risk increases. Adverse effects also increase as more women are subjected to prevention therapies. Conclusions The evidence base for genetic risk assessment and BRCA mutation testing for breast and ovarian cancer susceptibility as a screening strategy is limited by lack of studies demonstrating effectiveness, biases inherent in studies conducted in highly selected populations, and incomplete information on adverse effects. Keywords Genetic risk assessment, genetic testing, BRCA1 and BRCA2 mutations, breast cancer, ovarian cancer.

Emily L Harris

Papers

Management of the clinically inapparent adrenal mass ("incidentaloma").

Genetic risk assessment and BRCA mutation testing for breast and ovarian cancer susceptibility: systematic evidence review for the U.S. Preventive Services Task Force.

Screening for hereditary hemochromatosis : A systematic review for the U.S. preventive services task force

Genetic Risk Assessment and BRCA Mutation Testing for Breast and Ovarian Cancer Susceptibility

Screening for Hereditary Hemochromatosis