Uso adecuado de las pruebas de laboratorio para la evaluación de la función tiroidea en pediatría / Appropriate use of laboratory tests for evaluation of thyroid function in pediatrics

Las pruebas de función tiroidea (PFT) son esenciales para el diagnóstico preciso y el seguimiento eficaz de la disfunción tiroidea. Existe un incremento progresivo y estable de los pedidos de PFT, incluso se han incorporado las mismas a los exámenes de salud anuales en niños sanos. Representan más del 60% de las pruebas realizadas en el laboratorio de endocrinología, tanto en adultos como en los laboratorios especializados en pediatría. Para hacer un uso eficiente de las PFT, antes de solicitarlas debemos preguntarnos… ¿Para quién? ¿Cuándo solicitarlas? ¿Qué pruebas solicitar? ¿Cómo solicitarlas? y ¿Cómo interpretar correctamente los resultados? Un resultado anormal en las PFT no siempre implica patología tiroidea asociada. Las PFT tienen importante variabilidad intra e interindividual lo que hace más compleja su correcta interpretación. La pesquisa de enfermedad tiroidea neonatal es un importante aporte a la prevención de la deficiencia mental en la infancia, su aplicación obligatoria posibilita un diagnóstico temprano, para asegurar su éxito debe considerarse en el marco de un programa integral de detección con estrategias de confirmación, tratamiento temprano y seguimiento a corto, mediano y largo plazo. No debe hacerse un uso indiscriminado de la prueba de estímulo con TRH en el diagnóstico de la patología tiroidea. En pediatría la estrategia de tamiz de enfermedad tiroidea es conveniente realizarla mediante la medición de por lo menos TSH y T4 libre e incluir la determinación de ATPO en grupos de riesgo, a diferencia de la determinación aislada de TSH como es recomendado en adultos. (AU)

Thyroid function tests (TFTs) are essential for accurate diagnosis and effective monitoring of thyroid dysfunction. There is a progressive and steady increase in requests for TFTs, and they have even been incorporated into annual health examinations in healthy children. They represent more than 60% of the tests performed in the endocrinology laboratory, both in adults and in specialized pediatric laboratories. To efficiently use TFTs, before requesting them we should ask ourselves... For whom? When to request them? Which tests to request? How to request them? and How to correctly interpret the results? An abnormal TFT result does not always imply thyroid disease. TFTs have significant intra- and inter-individual variability, which makes their correct interpretation more complex. Screening for newborn thyroid disease is an important contribution to the prevention of intellectual disability in childhood and its mandatory use enables early diagnosis; however, to ensure the test to be successful, it should be considered within the framework of a comprehensive screening program with strategies for confirmation, early treatment, and short-, medium-, and long-term follow-up. The TRH stimulation test in the diagnosis of thyroid disease should not be used indiscriminately. In children, the screening strategy for thyroid disease should be performed by measuring at least TSH and free T4 and include the measurement of TPO-ab in risk groups, as opposed to the isolated measurement of TSH as recommended in adults. (AU)

New types of localization methods for adrenocorticotropic hormone-dependent Cushing's syndrome.

The management of endogenous Cushing's syndrome (CS) typically involves two key steps: (i) confirmation of autonomous hypercortisolism and (ii) localization of the cause to guide treatment. Adrenocorticotropic hormone (ACTH)-dependent CS is most commonly due to a pituitary corticotrope tumor which may be so small as to evade detection on conventional magnetic resonance imaging (MRI). Although biochemical testing (e.g., corticotropin stimulation; dexamethasone suppression) can provide an indication of the likely origin of ACTH excess, bilateral inferior petrosal sinus catheterization offers greater accuracy to distinguish pituitary-driven CS [Cushing's Disease (CD)] from the ectopic ACTH syndrome [EAS, e.g., due to a bronchial or pancreatic neuroendocrine tumor (NET)]. In patients with CD, 40-50% may not have a pituitary adenoma (PA) readily visualized on standard clinical MRI. In these subjects, alternative MR sequences (e.g., dynamic, volumetric, fluid attenuation inversion recovery) and higher magnetic field strength (7T > 3T > 1.5T) may aid tumor localization but carry a risk of identifying coincidental (non-causative) pituitary lesions. Molecular imaging is therefore increasingly being deployed to detect small ACTH-secreting PA, with hybrid imaging [e.g., positron emission tomography (PET) combined with MRI] allowing precise anatomical localization of sites of radiotracer (e.g., 11C-methionine) uptake. Similarly, small ACTH-secreting NETs, missed on initial cross-sectional imaging, may be detected using PET tracers targeting abnormal glucose metabolism (e.g., 18F-fluorodeoxyglucose), somatostatin receptor (SSTR) expression (e.g., 68Ga-DOTATATE), amine precursor (e.g., 18F-DOPA) or amino acid (e.g., 11C-methionine) uptake. Therefore, modern management of ACTH-dependent CS should ideally be undertaken in specialist centers which have an array of cross-sectional and functional imaging techniques at their disposal.

How to Classify and Define Pituitary Tumors: Recent Advances and Current Controversies.

Pituitary tumors are very complex and heterogeneous and have a very wide range of proliferative and aggressive behaviors, and how to define and classify these tumors remains controversial. This review summarizes the epidemiology and progress in the classification and definition of pituitary tumors, as well as controversial issues. Based on the results of radiologic and autopsy studies, the prevalence of pituitary tumors has recently increased significantly. However, the majority of pituitary tumors are incidentally discovered and asymptomatic, and such tumors are called pituitary incidentalomas. Most of these incidentalomas do not induce symptoms, remain stable in size, and do not need treatment. The recent revised classification strategies mainly depend on immunohistochemistry (IHC) to detect pituitary hormones and pituitary transcription factors; therefore, the accuracy of diagnosing pituitary tumors has improved. Although new classification strategies and definitions for pituitary tumors have been presented, there are still some controversies. The term pituitary neuroendocrine tumor (PitNET) was proposed by the International Pituitary Pathology Club, and this terminology can encompass the unpredictable malignant behavior seen in the subset of aggressive pituitary adenomas (PAs). However, some endocrinologists who oppose this change in terminology have argued that the use of tumor in the terminology is misleading, as it gives PAs a harmful connotation when the majority are not aggressive. Such terminology may add new ambiguity to the origin of PAs and unnecessary anxiety and frustration for the majority of patients with benign PAs. The classification of aggressive PAs mainly relies on subjective judgment of clinical behavior and lacks objective biomarkers and unified diagnostic criteria. However, the term "refractory" could more accurately represent the characteristics of these tumors, including their clinical behaviors, radiological features, and pathologic characteristics. Moreover, the diagnostic criteria for refractory PAs are stricter, more objective, and more accurate than those for aggressive PAs. Early identification of patients with these tumors through recognition and increased awareness of the definition of refractory PAs will encourage the early use of aggressive therapeutic strategies.

DIAGNOSIS OF ENDOCRINE DISEASE: Post-pancreatitis diabetes mellitus: prime time for secondary disease.

While most people with diabetes have type 2 disease, a non-negligible minority develops a secondary diabetes. Post-pancreatitis diabetes mellitus (PPDM) is an exemplar secondary diabetes that represents a sequela of pancreatitis - the most common disease of the exocrine pancreas. Although this type of diabetes has been known as a clinical entity since the late 19th century, early 21st century high-quality epidemiological, clinical, and translational studies from around the world have amassed a sizeable body of knowledge that have led to a renewed understanding of PPDM. People have at least two-fold higher lifetime risk of developing diabetes after an attack of pancreatitis than those in the general population without a history of diseases of the exocrine pancreas. PPDM is caused by acute pancreatitis (including non-necrotising pancreatitis, which constitutes the majority of acute pancreatitis) in four-fifth of cases and chronic pancreatitis in one-fifth of cases. Moreover, the frequency of incident diabetes is not considerably lower after acute pancreatitis than after chronic pancreatitis. Recurrent attacks of pancreatitis and exocrine pancreatic dysfunction portend high risk for PPDM, but are not mandatory for its development. Further, young- or middle-aged non-obese men have an increased risk of developing PPDM. In comparison with type 2 diabetes, PPDM is characterised by poorer glycaemic control, higher risk of developing cancer (in particular, pancreatic cancer), younger age at death, and a higher risk of mortality. Metformin monotherapy is recommended as the first-line therapy for PPDM. Appropriate screening of individuals after an attack of pancreatitis, correct identification of PPDM, and apposite management is crucial with a view to improving the outcomes of this secondary but not inappreciable disease.

Analysis of steroid profiles by mass spectrometry: A new tool for exploring adrenal tumors?

The assay of multiple steroids by mass spectrometry coupled with chromatography, combined with data analysis using an artificial intelligence approach, has become more widely accessible in recent years. Multiple applications for this technology exist for the study of adrenocortical tumors. Taking advantage of the capacity of malignant cortical tumor secretion of non-bioactive precursors, it provides an additional diagnostic approach that can point to the nature of a tumor. These encouraging perspectives have been based to date only on pilot retrospective studies. However, this has changed in 2020 with the publication of data from the EURINE-ACT study. This very large prospective European study provided more nuanced evidence for the benefit of combining the measurement of a panel of steroids with essential imaging tools. This study also facilitated our understanding and provided more precise characterisation of autonomous steroid secretion, particularly in the case of sublinical cortisol-secreting adrenocortical adenomas. This article will focus on our current knowledge on the potential utility of mass spectrometry for diagnosis of both the nature of an adrenal tumors and their secretion.

Evolution of the Primary Aldosteronism Syndrome: Updating the Approach.

CONTEXT: New approaches are needed to address the evolution of the primary aldosteronism syndrome and to increase its recognition. Herein, we review evidence indicating that primary aldosteronism is a prevalent syndrome that is mostly unrecognized, and present a pragmatic and pathophysiology-based approach to improve diagnosis and treatment. METHODS: Evidence was gathered from published guidelines and studies identified from PubMed by searching for primary aldosteronism, aldosterone, renin, and hypertension. This evidence was supplemented by the authors' personal knowledge, research experience, and clinical encounters in primary aldosteronism. INTERPRETATION OF EVIDENCE: Renin-independent aldosterone production is a prevalent phenotype that is diagnosed as primary aldosteronism when severe in magnitude, but is largely unrecognized when milder in severity. Renin-independent aldosterone production can be detected in normotensive and hypertensive individuals, and the magnitude of this biochemical phenotype parallels the magnitude of blood pressure elevation, the risk for incident hypertension and cardiovascular disease, and the likelihood and magnitude of blood pressure reduction with mineralocorticoid receptor antagonist therapy. Expansion of the indications to screen for primary aldosteronism, combined with the use of a pathophysiology-based approach that emphasizes inappropriate aldosterone production in the context of renin suppression, will substantially increase the diagnostic and therapeutic yields for primary aldosteronism. CONCLUSIONS: The landscape of primary aldosteronism has evolved to recognize that it is a prevalent syndrome of renin-independent aldosterone production that contributes to the pathogenesis of hypertension and cardiovascular disease. Expanding screening indications and simplifying the diagnostic approach will enable implementation of targeted treatment for primary aldosteronism.

Multimodal imaging of thyroid cancer.

PURPOSE OF REVIEW: Thyroid cancer is the most common endocrine cancer in adults with rising incidence. Challenges in imaging thyroid cancer are twofold: distinguishing thyroid cancer from benign thyroid nodules, which occur in 50% of the population over 50 years; and correct staging of thyroid cancer to facilitate appropriate radical surgery in a single session. The clinical management of thyroid cancer patients has been covered in detail by the 2015 guidelines of the American Thyroid Association (ATA). The purpose of this review is to state the principles underlying optimal multimodal imaging of thyroid cancer and aid clinicians in avoiding important pitfalls. RECENT FINDINGS: Recent additions to the literature include assessment of ultrasound-based scoring systems to improve selection of nodules for fine needle biopsy (FNB) and the evaluation of new radioactive tracers for imaging thyroid cancer. SUMMARY: The mainstay of diagnosing thyroid cancer is thyroid ultrasound with ultrasound-guided FNB. Contrast-enhanced computed tomography and PET with [F]-fluorodeoxyglucose (FDG) and MRI are reserved for advanced and/or recurrent cases of differentiated thyroid cancer and anaplastic thyroid cancer, while [F]FDOPA and [Ga]DOTATOC are the preferred tracers for medullary thyroid cancer.

Central diabetes insipidus in children: Diagnosis and management.

Central diabetes insipidus (CDI) is a complex disorder in which large volumes of dilute urine are excreted due to arginine-vasopressin deficiency, and it is caused by a variety of conditions (genetic, congenital, inflammatory, neoplastic, traumatic) that arise mainly from the hypothalamus. The differential diagnosis between diseases presenting with polyuria and polydipsia is challenging and requires a detailed medical history, physical examination, biochemical approach, imaging studies and, in some cases, histological confirmation. Magnetic resonance imaging is the gold standard method for evaluating the sellar-suprasellar region in CDI. Pituitary stalk size at presentation is variable and can change over time, depending on the underlying condition, and other brain areas or other organs - in specific diseases - may become involved during follow up. An early diagnosis and treatment are preferable in order to avoid central nervous system damage and the risk of dissemination of germ cell tumor, or progression of Langerhans Cell Histiocytosis, and in order to start treatment of additional pituitary defects without further delay. This review focuses on current diagnostic work-up and on the role of neuroimaging in the differential diagnosis of CDI in children and adolescents. It provides an update on the best approach for diagnosis - including novel biochemical markers such as copeptin - treatment and follow up of children and adolescents with CDI; it also describes the best approach to challenging situations such as post-surgical patients, adipsic patients, patients undergoing chemotherapy and/or in critical care.

Contemporary evaluation and management of tall cell variant of papillary thyroid carcinoma.

PURPOSE OF REVIEW: The purpose of this review is to describe the contemporary evaluation and management of tall cell variant of papillary thyroid carcinoma with an emphasis on the clinical features. RECENT FINDINGS: Tall cell variant of papillary thyroid carcinoma is the most common aggressive subtype. Within the last few years, the diagnostic criteria for this entity have evolved. Studies have elucidated a better understanding of the clinical implications and pathophysiology of this variant. In this review, the studies presented reflect cumulative and aggregated data from metaanalyses, systematic reviews, and large database investigations utilizing the current diagnostic criteria. SUMMARY: Overall, tall cell variant of papillary thyroid carcinoma represents an aggressive subtype of well-differentiated thyroid carcinoma with more prevalent high-risk features and a poorer clinical outcome.

Contemporary Thyroid Nodule Evaluation and Management.

CONTEXT: Approximately 60% of adults harbor 1 or more thyroid nodules. The possibility of cancer is the overriding concern, but only about 5% prove to be malignant. The widespread use of diagnostic imaging and improved access to health care favor the discovery of small, subclinical nodules and small papillary cancers. Overdiagnosis and overtreatment is associated with potentially excessive costs and nonnegligible morbidity for patients. EVIDENCE ACQUISITION: We conducted a PubMed search for the recent English-language articles dealing with thyroid nodule management. EVIDENCE SYNTHESIS: The initial assessment includes an evaluation of clinical risk factors and sonographic examination of the neck. Sonographic risk-stratification systems (e.g., Thyroid Imaging Reporting and Data Systems) can be used to estimate the risk of malignancy and the need for biopsy based on nodule features and size. When cytology findings are indeterminate, molecular analysis of the aspirate may obviate the need for diagnostic surgery. Many nodules will not require biopsy. These nodules and those that are cytologically benign can be managed with long-term follow-up alone. If malignancy is suspected, options include surgery (increasingly less extensive), active surveillance or, in selected cases, minimally invasive techniques. CONCLUSION: Thyroid nodule evaluation is no longer a 1-size-fits-all proposition. For most nodules, the likelihood of malignancy can be confidently estimated without resorting to cytology or molecular testing, and low-frequency surveillance is sufficient for most patients. When there are multiple options for diagnosis and/or treatment, they should be discussed with patients as frankly as possible to identify an approach that best meets their needs.

Disease monitoring of Primary Aldosteronism.

Primary aldosteronism (PA) is a highly prevalent cause of arterial hypertension featuring excess cardiovascular events. A timely diagnosis and treatment of PA cures hyperaldosteronism and can provide resolution or improvement of arterial hypertension, even when the latter is resistant to drug treatment. Accordingly, strategies to screen early and widely the hypertensive patients for PA by means of simplified diagnostic algorithms are justified. Such strategies are particularly beneficial in subgroups of hypertensive patients, who are at the highest cardiovascular risk. Broadening of screening strategies means facing with an increased number of patients where monitoring the disease becomes necessary. Hence, after identification of the surgically and non surgically curable cases of PA and implementation of targeted treatment physicians are faced with the challenges of follow-up, which are scantly discussed in the literature. Hence, the purpose of this paper is to provide some recommendations on how to optimize the monitoring of patients in whom the PA subtype has been diagnosed and treatment, either with unilateral laparoscopic adrenalectomy or medically, has been instituted.

Controversies and advances in adrenal venous sampling in the diagnostic workup of primary aldosteronism.

Adrenal venous sampling (AVS) is a key part of the diagnostic workup of primary aldosteronism, distinguishing unilateral from bilateral disease and determining treatment options. Although AVS is a well-established procedure, many aspects remain controversial, including optimal patient selection for the procedure and exactly how AVS is performed and interpreted. Despite the controversies, a growing body of evidence supports the use of AVS in most patients with primary aldosteronism, though some specific patient groups may be able to forego AVS and proceed directly to treatment. Although AVS remains a difficult procedure, success rates may be improved with the use of advanced CT imaging techniques and/or rapid cortisol assays. New advances in nuclear imaging and steroid profiling may also offer alternatives or adjuncts to AVS in the future.

Hypophysitis: An update on the novel forms, diagnosis and management of disorders of pituitary inflammation.

Hypophysitis is a heterogeneous condition that leads to inflammation of the sella and/or suprasellar region, potentially resulting in hormonal deficiencies and/or mass effects. A preponderance of hypophysitis subtypes have an underlying autoimmune aetiology. The overall incidence and prevalence of hypophysitis has dramatically increased over the past decade, mainly due to increased awareness of the condition in the medical community, improvements in imaging techniques, and a rise in the occurrence of certain forms of hypophysitis such as IgG4 hypophysitis (IgG4Hy) and immune checkpoint inhibitor induced hypophysitis (ICIHy). The clinical presentation varies from an asymptomatic condition to a fatal disease often as a result of electrolyte abnormalities due to glucocorticoid deficiency in the context of adrenal crisis from central adrenal insufficiency. Milder forms of hypophysitis are treated with replacement of deficient hormones while more acute presentations with mass effects require glucocorticoid therapy, immunosuppressive therapy or surgery. Timely diagnosis and interventions are keys to prevention of the lethal complications of this disease. In this review, we provide an update on the recent advances in the field of pituitary autoimmunity, with an emphasis on autoimmune hypophysitis and novel forms of hypophysitis such as anti-PIT1 hypophysitis, IgG4Hy and ICIHy.

Acromégalie : améliorer la prise en charge: Acromegaly: improving care.

Acromegaly is characterized by increased release of growth hormone (GH) and, consequently, Insulin-Like Growth Factor I (IGF-I), most often by a pituitary adenoma. Prolonged exposure to excess hormone leads to progressive somatic disfigurement and a wide range of systemic manifestations that are associated with increased mortality. Transsphenoidal adenomectomy is the treatment of choice of GH-secreting pituitary tumors but surgical cure is not achieved in around 50% of patients, then adjuvant treatment is necessary. Mortality in acromegaly is normalized with biochemical control and has decreased in the last decade with the increased use of adjuvant therapy. Both GH and IGF-I are currently biomarkers for assessing disease activity in patients with acromegaly. However, discordance between GH and IGF-I results is encountered in a quarter of treated patients. The impacts of such a discrepancy over mortality and morbidity and the risk of biochemical and/or clinical recurrence are unclear. Moreover, despite a good biochemical control, some symptoms persist, leading to a decreased quality of life. Back pain due to vertebral fractures seem to be frequent in these patients and underdiagnosed. In patients with acromegaly, bone mineral density is not a reliable predictor of fracture risk. A more accurate evaluation of bone microstructural alterations associated with GH hypersecretion and vertebral fractures may be provided by new radiological devices analyzing alteration of trabecular microarchitecture, leading to a better prevention. © 2019 Published by Elsevier Masson SAS. All rights reserved. Cet article fait partie du numéro supplément Les Must de l'Endocrinologie 2019 réalisé avec le soutien institutionnel de Ipsen-Pharma.

Trend, projection, and appropriate body mass index cut-off point for diabetes and hypertension in Bangladesh.

BACKGROUND: Rapid increasing of high body mass index (BMI) is a global health concern. Population with high BMI predicts an increased risk of diabetes and hypertension. The objective of the present study is to estimate the trend and prediction of diabetes and hypertension in Bangladesh, to examine the association of BMI with risk of diabetes and hypertension, and to ascertain an appropriate BMI cut-off point for screening diabetes. METHODS: We searched PubMed from inception to August 2016 and identified studies reporting diabetes and hypertension prevalence in Bangladesh. Bangladesh Demographic and Health Survey 2011 data was also included in this study. Bayesian model was used to estimate trend and projection in diabetes and hypertension prevalence by sex and residence. Receiver operating characteristic curves was used to determine the optimal BMI cut-off point for screening diabetes. FINDINGS: Of 535 articles reviewed, 35 studies reported prevalence of diabetes and hypertension. Prevalence of diabetes (95% credible interval) increased between 1992 and 2015 from 3.2% (2.2-4.3) to 12.1% (9.1-15.4) in men, and from 2.5% (1.8-3.5) to 13.4% (9.7-17.6) in women. Diabetes prevalence in 2030 is expected to reach 23.6% (13.6-36.3) for men and 33.5% (19.9-50.9) for women. Hypertension prevalence increased between 1992 and 2015 from 11.0% (8.6-13.7) to 20.4% (18.4-22.4%) in 2015 in men, and from 14.0% (10.3-19.0) to 21.3% (19.0-23.6) in women. Annual average rate of change for diabetes prevalence was higher among women and in rural areas, while for hypertension prevalence it was higher in men and urban areas. Adults with BMI of 22.5kg/m2 or above had a higher risk of diabetes and hypertension in this study. The optimal BMI cut-off point for screening diabetes was 23kg/m2 for overall population, 22kg/m2 for men, and 23kg/m2 for women. INTERPRETATION: Diabetes is more prevalent among women and rural population groups, while hypertension is more prevalent among men and urban population groups in Bangladesh. A BMI of 22.5kg/m2 or more is risk factors for developing diabetes and hypertension. Screening for diabetes may be considered for all Bangladeshi adults with a BMI of ⩾23kg/m2.

Current biomarkers of invasive sporadic pituitary adenomas.

Though pituitary adenomas (PA) are considered benign, some of them exhibit invasive behaviors such as recurrence and low rate of total surgical resection. Reliable prognostic biomarkers for invasive PA are highly desired; however they remain to be identified. In this review, we summarize the current controversial findings of biomarkers for invasive sporadic PA, and we discuss the possible reasons for the controversies.

Future directions in the diagnosis and medical treatment of adrenocortical carcinoma.

Adrenocortical carcinoma (ACC) is a rare disease with a poor prognosis. Discrimination between ACCs and adrenocortical adenomas (ACAs) remains challenging, with the current gold standard being the Weiss score, consisting of several histopathological characteristics. However, new markers like Ki67, a marker for proliferation, and the staining of reticulins are promising not only as it comes to identifying malignancy but also as prognostic markers in patients with ACC. Currently, surgery is still the only curative treatment for ACC. Mitotane, an adrenolytic drug, is used in the adjuvant setting and in case of metastatic or advanced disease. Patients with progressive disease are frequently treated with mitotane, alone or in combination with etoposide, doxorubicine and cisplatin. Radiotherapy is indicated in selected cases. The low response rates and high toxicity of the systemic therapies emphasize the need for markers that enable the identification of responders and non-responders. Consequently, research is focusing on predictive factors varying from the expression of DNA repair genes to clinical patient characteristics. Subgroups of ACC with different prognosis have been identified based on transcriptome characteristics. As a conclusion from large molecular studies, ACCs appear to harbor many abnormalities compared to ACAs. Altered pathways driving ACC pathogenesis include the IGF, TP53 and the Wnt signaling pathway, allowing these as new potential targets for medical therapy. However, despite efforts in preclinical and clinical studies investigating efficacy of targeting these pathways, most novel therapies appear to be effective in only a subset of patients with ACC. New treatment concepts are therefore urgently needed.

Sheehan's syndrome: new insights into an old disease.

Sheehan's syndrome (SS) is a parturition-related pituitary disease resulting from severe postpartum hemorrhage and can present with varying degrees of pituitary insufficiency. Pathological and clinical findings of SS were first described by Harold L. Sheehan in the previous century. Although his definitions are still valid, various studies and reports including new data have subsequently been published. Additionally, the diagnosis of SS has often been overlooked and thus delayed for long years due to its nonspecific signs and symptoms. Therefore, a large number of patients may be remained undiagnosed and untreated. SS is not as rare as assumed in developed countries, probably due to migrant women and unawareness of physicians regarding the syndrome. In this review, we provide a detailed review of the epidemiology, etiopathogenesis, clinical, laboratory and radiological features, new diagnostic criteria, differential diagnosis, and treatment of SS.

Changes in incidence, survival and mortality of prostate cancer in Europe and the United States in the PSA era: additional diagnoses and avoided deaths.

BACKGROUND: We describe changes in prostate cancer incidence, survival and mortality and the resulting impact in additional diagnoses and avoided deaths in European areas and the United States. METHODS: Using data from 12 European cancer registries and the Surveillance, Epidemiology and End Results program, we describe changes in prostate cancer epidemiology between the beginning of the PSA era (USA: 1985-1989, Europe: 1990-1994) and 2002-2006 among patients aged 40-64, 65-74, and 75+. Additionally, we examine changes in yearly numbers of diagnoses and deaths and variation in male life expectancy. RESULTS: Incidence and survival, particularly among patients aged <75, increased dramatically, yet both remain (with few exceptions in incidence) lower in Europe than in the United States. Mortality reductions, ongoing since the mid/late 1990 s, were more consistent in the United States, had a distressingly small absolute impact among patients aged 40-64 and the largest absolute impact among those aged 75+. Overall ratios of additional diagnoses/avoided deaths varied between 3.6 and 27.6, suggesting large differences in the actual impact of prostate cancer incidence and mortality changes. Ten years of remaining life expectancy was reached between 68 and 76 years. CONCLUSION: Policies reflecting variation in population life expectancy, testing preferences, decision aids and guidelines for surveillance-based management are urgently needed.