Search

Competing Interests: RP reports personal fees from Bristol Myers Squibb, MSD, Novartis, and Janssen, outside the submitted work. JL reports grants and personal fees from Achilles Therapeutics, Bristol Myers Squibb, MSD, Nektar, Immunocore, Pfizer, Roche, and Novartis; personal fees from AstraZeneca, Boston Biomedical, Eisai, EUSA Pharma, GSK, Ipsen, Imugene, Incyte, iOnctura, Kymab, Merck Sorono, Pierre Fabre, Secarna, Vitaccess, Covance; and grants from Aveo and Pharmacyclics, outside the submitted work. DLM reports personal fees from Bristol Myers Squibb, MSD, and Roche, outside the submitted work.

Context: The relationship between the endocrine system and autoimmunity has been recognized for a long time and one of the best examples of autoimmune endocrine disease is autoimmune hypophysitis. A better understanding of autoimmune mechanisms and radiological, biochemical, and immunological developments has given rise to the definition of new autoimmune disorders including autoimmunity-related hypothalamic-pituitary disorders. However, whether hypothalamitis may occur as a distinct entity is still a matter of debate., Evidence Acquisition: Here we describe a 35-year-old woman with growing suprasellar mass, partial empty sella, central diabetes insipidus, hypopituitarism, and hyperprolactinemia., Evidence Synthesis: Histopathologic examination of surgically removed suprasellar mass revealed lymphocytic infiltrate suggestive of an autoimmune disease with hypothalamic involvement. The presence of antihypothalamus antibodies to arginine vasopressin (AVP)-secreting cells (AVPcAb) at high titers and the absence of antipituitary antibodies suggested the diagnosis of isolated hypothalamitis. Some similar conditions have sometimes been reported in the literature but the simultaneous double finding of lymphocytic infiltrate and the presence of AVPcAb so far has never been reported., Conclusions: We think that the hypothalamitis can be considered a new isolated autoimmune disease affecting the hypothalamus while the lymphocytic infundibuloneurohypophysitis can be a consequence of hypothalamitis with subsequent autoimmune involvement of the pituitary. To our knowledge this is the first observation of autoimmune hypothalamic involvement with central diabetes insipidus, partial empty sella, antihypothalamic antibodies and hypopituitarism., (© The Author(s) 2020. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Endocrinopathies, such as thyroid and parathyroid diseases, disorders of the adrenal axis, and acromegaly are included among the many causes of myopathy. Muscle disturbances caused by endocrine disorders are mainly due to alterations in the protein and carbohydrate metabolisms. Either a deficiency or excess of hormones produced by the glands can cause muscle dysfunction that can be reversed by starting hormone replacement therapy or acting on hormone dysfunction. The diagnosis is usually easy if a muscle disorder occurs in an overt endocrinopathy; however, in few patients, myopathy could be the first manifestation of the underlying endocrinopathy. In this article we discuss pathophysiology, clinical features and management of muscle involvement related to the major endocrine diseases., (©2020 Gaetano Conte Academy - Mediterranean Society of Myology, Naples, Italy.)

Endocrine disorders are associated with various tachyarrhythmias, including atrial fibrillation (AF), ventricular tachycardia (VT), ventricular fibrillation (VF), and bradyarrhythmias. Along with underlying arrhythmia substrate, electrolyte disturbances, glucose, and hormone levels, accompanying endocrine disorders contribute to development of arrhythmia. Arrhythmias may be life-threatening, facilitate cardiogenic shock development and increase mortality. The knowledge on the incidence of tachy- and bradyarrhythmias, clinical and prognostic significance as well as their management is limited; it is represented in observational studies and mostly in case reports on management of challenging cases. It should be also emphasized, that the topic is not covered in detail in current guidelines. Therefore, cardiologists and multidisciplinary teams participating in care of such patients do need the evidence-based, or in case of limited evidence expert-opinion based recommendations, how to treat arrhythmias using contemporary approaches, prevent their complications and recurrence in patients with endocrine disorders. In recognizing this close relationship between endocrine disorders and arrhythmias, the European Heart Rhythm Association (EHRA) convened a Task Force, with representation from Asia-Pacific Heart Rhythm Society (APHRS) and Sociedad Latinoamericana de Estimulación Cardíaca y Electrofisiología (SOLAECE), with the remit of comprehensively reviewing the available evidence and publishing a joint consensus document on endocrine disorders and cardiac arrhythmias, and providing up-to-date consensus recommendations for use in clinical practice.

Context: In honor of the 75th issue of the Journal of Clinical Endocrinology and Metabolism, the author was invited to present his perspectives on genetics in human endocrinology. This paper reviews what the field has achieved in the genetics of common endocrine disease, and offers predictions on where the field will move in the future and its impact on endocrine clinical practice., Evidence Acquisition: The October 2015 data release of the National Human Genome Research Institute-European Bioinformatics Institute (NHGRI-EBI) Catalog of Published Genome-wide Association Studies was queried regarding endocrinologic diseases and traits. PubMed searches were focused on genetic prediction of disease, genetic findings and drug targets, functional interrogation of genetic loci, use of genetics to subtype disease, missing heritability, systems genomics, and higher order chromatin structures as regulators of gene function., Evidence Synthesis: Nearly a quarter of genome wide association study findings concern endocrinologic diseases and traits. While these findings have not yet dramatically altered clinical care, genetics will have a major impact by providing the drug targets of tomorrow, facilitated by experimental and bioinformatic advances that will shorten the time from gene discovery to drug development. Use of genetic findings to subtype common endocrine disease will allow more precise prevention and treatment efforts. Future advances will allow us to move away from the common view of DNA as a string of letters, allowing exploration of higher order structure that likely explains much "missing heritability.", Conclusions: The future will see a greater role of genetics at the bedside, with genetic epidemiologic discoveries leading not only to new treatments of endocrine disease, but also helping us prescribe the right drug to the right patients by allowing subclassification of common heterogeneous endocrine conditions. Future technological breakthroughs will reveal the heritable mysteries hidden in chromatin structure, leading to a more complete characterization of heritability that will propel our ability to translate genetic findings into new preventions and treatments.

Hereditary endocrine diseases are an important group of diseases with great heterogeneity. The current classification for hereditary endocrine disease is mostly based upon anatomy, which is helpful for pathophysiological interpretation, but does not address the pathogenic variability associated with different underlying genetic causes. Identification of an endocrinopathy-associated genetic alteration provides evidence for differential diagnosis, discovery of non-classical disease, and the potential for earlier diagnosis and targeted therapy. Molecular diagnosis should be routinely applied when managing patients with suspicion of hereditary disease. To enhance the accurate diagnosis and treatment of patients with hereditary endocrine diseases, we propose categorization of endocrine diseases into three groups based upon the function of the mutant gene: cell differentiation, hormone synthesis and action, and tumorigenesis. Each category was further grouped according to the specific gene function. We believe that this format would facilitate practice of precision medicine in the field of hereditary endocrine diseases.

Purpose: Rare endocrine-metabolic diseases (REMD) represent an important area in the field of medicine and pharmacology. The rare diseases of interest to endocrinologists involve all fields of endocrinology, including rare diseases of the pituitary, thyroid and adrenal glands, paraganglia, ovary and testis, disorders of bone and mineral metabolism, energy and lipid metabolism, water metabolism, and syndromes with possible involvement of multiple endocrine glands, and neuroendocrine tumors. Taking advantage of the constitution of a study group on REMD within the Italian Society of Endocrinology, consisting of basic and clinical scientists, a document on the taxonomy of REMD has been produced., Methods and Results: This document has been designed to include mainly REMD manifesting or persisting into adulthood. The taxonomy of REMD of the adult comprises a total of 166 main disorders, 338 including all variants and subtypes, described into 11 tables., Conclusions: This report provides a complete taxonomy to classify REMD of the adult. In the future, the creation of registries of rare endocrine diseases to collect data on cohorts of patients and the development of common and standardized diagnostic and therapeutic pathways for each rare endocrine disease is advisable. This will help planning and performing intervention studies in larger groups of patients to prove the efficacy, effectiveness, and safety of a specific treatment.

The number of patients with endocrine system diseases increases annually. Widespread introduction of screening programs and improvement of laboratory and instrumental diagnostic is one of the most important causes for this. Treatment of patients with endocrine system diseases within the high-tech medical care leads to perform the unique surgical interventions. It increases survival and patients' life quality.

Aim: Hereditary endocrinopathies in Cyprus exhibit evidence of a founder effect and display the influence of past migration patterns. The genetic frequency and mutation pattern of a specific disorder of sex development (DSD), which is classified as 46,XX DSD or 46,XY DSD, and the non-classic form of congenital adrenal hyperplasia (NC-CAH) outline a type of genetic drift., Results: Not only the high prevalence of the NC-CAH p.V281L mutation but also the rarity of CAH large lesions present a genetic diversity similar to that observed in the Middle Eastern countries. In addition, both the high frequency of the 5-alpha steroid reductase deficiency (5αSRD) IVS1-2A>G mutation and the carrier frequency of the 17-beta hydroxysteroid dehydrogenase 3 (17β-HSD-3) p.R80Q mutation are good examples of a founder effect. p.R80Q can be considered a founder mutation, even though it has been identified in patients of Dutch, Brazilian, and Portuguese origin. This has led to the speculation that it has a Phoenician origin. Phoenicians as ancient traders migrated around 750 BC from present day Syria, Lebanon, and Israel toward Portugal, Spain, and also to nearby Cyprus. While the 5αSRD IVS1-2A>G mutation has already been extensively reported in Turkish patients, it is very common in the Eastern Mediterranean region., Conclusion: This short article portrays clearly, through specific endocrine genetic disorders, the past migration trends in Cyprus that shaped the present-day gene pool of the Greek-Cypriot population.

Hypertension is a major contributor to vascular morbidity and mortality. Endocrine hypertension (EH) refers to secondary hypertension caused by specific endocrine abnormalities. The significance of EH is that the identification of the underlying disorder and its management may lead to partial or complete normalization of blood pressure. When EH is suspected thorough investigation with biochemical and imaging testing are necessary to establish or exclude mineralocorticoid, catecholamine, glucocorticoid, thyroid, parathyroid or growth hormone disorders as well as rare hereditary syndromes. In addition, it is important to differentiate benign from malignant tumors. The present review provides an update on the pathophysiology and clinical presentation of EH. We also discuss the diagnostic work-ups and therapeutic strategies.

The objective of this study was to define the types of disease seen at the only endocrine clinic in Jamaica. The diagnoses of all patients attending the endocrinology clinic of the University Hospital of the West Indies over a 7-year period were analysed. Of the 1503 patients attending 263 weekly endocrinology clinics, 1251 patients had thyroid-related diseases, of which 684 patients had thyrotoxicosis and 233 patients had hypothyroidism. There were 17 pituitary tumours, eight cases of Cushing's syndrome and four of acromegaly. Cases of Sheehan's syndrome (n=11), hypopituitarism (n=17), hypoadrenalism (n=13), hypogonadism (n=9), primary hyperparathyroidism (n=3) and phaeochromocytoma (n=3) were rare. Thyroid disease was the most common diagnosis. New emerging endocrine disorders that are public health problems, such as obesity (n 21) and hyperlipidaemia (n=1), were rare. More traditional diseases, such as Sheehan's syndrome have become rare with improvements in obstetric care.

There is only limited community-based practice safety information available regarding antidepressant use in pediatric patients. This study identifies the factors associated with incident neuroendocrine-related metabolic, digestive, and sexual/reproductive adverse events in children and adolescents treated with antidepressants. A retrospective cohort design evaluating Medicaid medical and pharmacy claims between January, 1996 and December, 2005 was employed for 11970 children and adolescents prescribed an antidepressant medication, and a random sample of 4500 children not treated with psychotropic medications. Incident obesity/weight gain, Type 2 diabetes mellitus, and dyslipidemia were more likely for those prescribed selective serotonin reuptake inhibitors (SSRIs) (OR = 1.49; 1.37; 1.44), whereas Type 2 diabetes mellitus and dyslipidemia were more likely for those prescribed weight-inducing antidepressants (ORs = 1.26; 1.24), and those with pre-existing endocrinopathies (ORs = 3.96; 1.90), controlling for the effects of co-prescribed mood stabilizers or antipsychotics. Incident nausea/vomiting was less likely for those taking SSRIs (OR = 0.78). Females and children under 12 years of age were more likely to develop these adverse effects. Practitioners need to carefully consider the neuroendocrine- related adverse effects of SSRI antidepressant agents in particular, especially in individuals with comorbid endocrine conditions, and those co-prescribed other classes of psychotropic medications.

Fibromyalgia (FM) and migraine are common chronic disorders that predominantly affect women. The prevalence of headache in patients with FM is high (35%-88%), with migraine being the most frequent type. A particular subgroup of patients with FM (approximately half) presents with a combined clinical form of these two painful disorders, which may exhibit a different manner of progression regarding symptomatology and impact on daily activities. This article reviews several common aspects of the pathophysiology regarding pain control mechanisms and neuroendocrine dysfunction occurring in FM and migraine, particularly in the chronic form of the latter. We also discuss the participation of hypothalamic and brainstem centers of pain control, the putative role played by neurotransmitters or neuromodulators on central sensitization, and changes in their levels in the cerebrospinal fluid. Understanding their mechanisms will help to establish new treatment strategies for treating these disabling brain disorders.

Rationale: Considerable confusion exists regarding nomenclature, classification, and management of pediatric diffuse lung diseases due to the relative rarity and differences in the spectrum of disease between adults and young children., Objectives: A multidisciplinary working group was formed to: (1) apply consensus terminology and diagnostic criteria for disorders presenting with diffuse lung disease in infancy; and (2) describe the distribution of disease entities, clinical features, and outcome in young children who currently undergo lung biopsy in North America., Methods: Eleven centers provided pathologic material, clinical data, and imaging from all children less than 2 years of age who underwent lung biopsy for diffuse lung disease from 1999 to 2004., Measurements and Main Results: Multidisciplinary review categorized 88% of 187 cases. Disorders more prevalent in infancy, including primary developmental and lung growth abnormalities, neuroendocrine cell hyperplasia of infancy, and surfactant-dysfunction disorders, constituted the majority of cases (60%). Lung growth disorders were often unsuspected clinically and under-recognized histologically. Cases with known surfactant mutations had characteristic pathologic features. Age at biopsy and clinical presentation varied among categories. Pulmonary hypertension, presence of a primary developmental abnormality, or ABCA3 mutation was associated with high mortality, while no deaths occurred in cases of pulmonary interstitial glycogenosis, or neuroendocrine cell hyperplasia of infancy., Conclusions: This retrospective cohort study identifies a diverse spectrum of lung disorders, largely unique to young children. Application of a classification scheme grouped clinically distinct patients with variable age of biopsy and mortality. Standardized terminology and classification will enhance accurate description and diagnosis of these disorders.

Objective: The determination of the plasma aldosterone (PAC) to the plasma renin concentration (PRC) ratio is an accepted screening tool for primary hyperaldosteronism (PHyperA)., Design: To assess the diagnostic significance of this ratio for other disorders of the renin-aldosterone-system (RAS), we examined 60 patients with different adrenal diseases, 32 patients with essential hypertension and 76 normotensive healthy volunteers. The aldosterone (pmol/L) and renin (mU/L) concentrations were measured in one plasma sample by an automated chemiluminescence assay (Nichols Advantage)., Results: Patients with PHyperA (n=31) had a PAC/PRC ratio between 105 and 2328 and could be distinguished without overlap from the essential hypertension group (ratio: range 2.7-49) and normal healthy volunteers (ratio: range 0.9-71). Fourteen patients with primary hypoaldosteronism showed low PAC/PRC ratios (range 0.21-0.98) and low PAC values (range: 42-100). Seven patients with secondary hypoaldosteronism had normal PAC/PRC ratios (range 2.8-23.2) and low PAC values (range: 42-116). Eight patients with secondary hyperaldosteronism had normal PAC/PRC ratios (range 7.8-67.9) and elevated PAC values (range: 803-2917). The graphic presentation of these data allowed the differentiation of all major disorders of the RAS., Conclusions: The measurement of PAC/PRC ratios using this automated system provides a sensitive and rapid screening method for PHyperA. Moreover, the measurement of both the PAC and the PAC/PRC ratio allows differentiation of other disorders of the RAS.

Cardiovascular mortality is significantly increased among patients with end-stage renal disease. The commonly observed vascular calcification in such patients has been considered as one of the causative factors. In patients undergoing dialysis, the incidence of coronary artery calcification is 2-5 times higher compared to patients with normal renal function and angiographically demonstrated coronary artery disease. Moreover, epidemiological studies have revealed a significant correlation of the extent of coronary artery calcification with the severity of underlying atherosclerotic lesions. Vascular calcification was initially considered as a passive process of hydroxyapatite deposition due to elevated plasma concentrations of calcium and phosphate. Nevertheless, there is a growing body of evidence that vascular calcification is an actively regulated and cell-mediated process. This phenomenon includes phenotypic alterations of vascular smooth muscle cells mainly resulting from an imbalance between promoters (such as increased Ca x P product) and inhibitors (fetuin-A, GLA protein, osteoprotegerin) of mineral deposition. With regard to the therapeutic approach, despite the evident effectiveness of both traditional and innovative remedies in the management of metabolic and electrolytic abnormalities of patients with end-stage renal disease, an individualized intervention based on etiopathogenesis is really required.

Polycystic ovary syndrome (PCOS), the most common endocrinopathy in women (with a prevalence of 5-10 %), is characterized by hormonal and metabolic imbalance. Complexity of symptoms of close relatives of women with PCOS and genetic autosomal trait initiated a hypothesis about the existence of a male equivalent of PCOS. Premature alopecia was suggested as one of the signs of a male phenotype of this syndrome. The present study investigated a group of 30 men, in which premature hair loss started before 30 years of age. In all patients, their hormonal profile was determined. It was possible to form two subgroups. The first one showed similar hormonal changes as women with PCOS, the other had either no anomalies in steroid spectrum or just only lower level of sexual hormones binding globulin (SHBG). Both subgroups did not differ in either BMI or age. In all men with premature alopecia insulin tolerance test was also carried out and the occurrence of allele 3 INS VNTR was investigated, which is one of the candidate genes for PCOS. The subgroup with hormonal changes resembling those of women with PCOS showed a significantly higher insulin resistance than the group without these changes. About one third of the premature balding men showed the combination of hormonal shifts and higher insulin resistance. This frequency corresponds to the prevalence of PCOS in women. There was no significant difference between the two subgroups in the occurrence of allele 3 INS VNTR.

Background: Most causes of fatigue are ill defined, self limiting or elude diagnosis. Many endocrine disorders present with nonspecific features including fatigue, so are difficult to differentiate on clinical grounds. However, avoiding diagnostic delay is vital to prevent significant morbidity and mortality. Thus, a high index of suspicion and knowledge of appropriate investigations is important. Endocrine disorders predispose the individual to developing related disorders; fatigue may be one sign of associated comorbidity., Objective: This article discusses the endocrine disorders that commonly present with or develop fatigue as a prominent feature, with emphasis on particular challenges for diagnosis, investigation or management. Screening recommendations for comorbid disease was generated by an extensive review of current evidence., Discussion: The identification of endocrine disorders can be both challenging--due to patterns of presentation--and rewarding for doctors and patients alike, due to importance and effectiveness of treatment.

Autoimmune Polyendocrine Syndromes (APS) were initially defined as a multiple endocrine gland insufficiency associated to an autoimmune disease in a patient. Neufeld & Blizzard (1980) suggested a classification of APS, based on clinical criteria only, describing four main types. APS-1 is characterized by presence of chronic candidiasis, chronic hypoparathyroidism, Addison's disease. It is a very rare syndrome interesting young subjects correlating to different mutations of AIRE (AutoImmuneRegulator) gene on chromosome 21. APS-2 is characterized by presence of Addison's disease (always present), autoimmune thyroid diseases and/or type 1 diabetes mellitus. It is a rare syndrome interesting particularly adult females and associated to a genetic pattern of HLA DR3/DR4. Autoimmune thyroid diseases associated to other autoimmune diseases (excluding Addison's disease and/or hypoparathyroidism), are the main characteristics of APS-3. The different clinical combinations of autoimmune diseases not included in the previous groups are characteristics of APS-4. In this paper criteria for defining a disease as autoimmune are presented. Furthermore, the classification, epidemiology, pathogenesis, genetic, animal models, clinical features, laboratory's tests, imaging, therapy, recent progresses in understanding the APS and a detailed analysis of large group of our patients affected by different types of APS are proposed and discussed.

Many atypical forms of sarcoidosis have been described. mediastinum-lung involvement, observed in 90% of the cases, may cause atypical manifestations: hemoptysis, chest pain, predominant pleural or proximal bronchial involvement. Diffuse "unpolished glass" images or air cavities may be observed on the chest x-ray. A rigorous diagnostic work-up is necessary for these atypical forms. Pathological confirmation is mandatory: non-caseous tuberculoid granuloma. A very wide range of extra-thoracic localizations have been described with variable clinical manifestations. In cases with no mediastinum-lung involvement, pathology data must be confronted with the notion of multiple organ dissemination to reach diagnosis.

This article describes extensively and systematically oral mucosa diseases. Macroscopical aspects are particularly described in order to give the dentist all important elements of differential diagnosis. This nosological description is based on a clinical approach: white and pigmented lesions are distinguished from ulcerated and benign so as malignant tumoral lesions. Specifically on the oral mucosa located lesions and oral mucosa lesions of systemic diseases are described.

Resistance to thyroid hormone encompasses a clinically heterogeneous group of conditions characterized by reduced responses of target tissues to a supply of thyroid hormone that under normal circumstances would be excessive. The syndrome of resistance to thyroid hormone is first suspected when serum thyroid hormone levels are found to be elevated in the presence of nonsuppressed serum thyrotropin (TSH). Clinical confirmation of the diagnosis requires the demonstration of the failure of full replacement doses of thyroid hormone to produce the expected suppressive effect on the secretion of TSH and a failure to induce appropriate responses in peripheral tissues.

The acquired immunodeficiency syndrome (AIDS) is a severe disease. Lung, brain and digestive complaints that result in opportunistic infections and neoplasms are the most documented. The endocrine disorders, the description of which is recent on the basis of post-mortem data, motivated some authors to undertake studies in order to evaluate endocrine function in patients infected with human immunodeficiency virus (HIV). An increase in serum cortisol level due to stress adaptation in the early stage of the disease is reported, whereas peripheral adrenal insufficiency, although unusual, appears in the late stage. Hypogonadism is common in men with HIV infection but its origin is discussed, central or peripheral. The thyroid function is generally preserved, but low T3 syndrome which correlates with bad prognosis may be observed. Anterior hypopituitarism, which is rare, hyponatremia more frequent because of its etiopathogenic factors in AIDS, constant and precocious hyperprolactinemia, are noticed. The episodes of asymptomatic or severe hypoglycemia may be explained by inanition and side effects of drugs. The non-specificity of the clinical manifestations of endocrine dysfunction masked by the classic signs of AIDS, shouldn't make forget the systematic search of glandular abnormalities as soon as an evocative symptomatology is conspicuous. The mechanisms of endocrine complications are badly known, but opportunistic infections, drugs, particularities related to the structure of HIV and interleukin 1 (IL1) surely play a role. The recognition of endocrine disorders is essential for optimal therapy because, unknown, their evolution is dramatic.

Autoimmune endocrinopathies belong to so-called organ specific autoimmune diseases. These diseases combine very often and from the polyglandular autoimmune endocrine syndrome (PAES), where autoantibodies either destroy or stimulate individual endocrine glands or hormone receptors in target tissues. Thus a wide range of combinations of hypofunctional or hyperfunctional clinical syndromes develops. PAES is a good natural model of endocrine polyautoaggressiveness. In its development the following aetiopathogenetic factors participate: 1. Hereditary familial disposition, expressed e.g. by certain inherited HHS genes (e.g. A1, B8, DR 3, 4). 2. Aberrant expression of these DR genes on endocrine organs due to bacterial or viral infections, pregnancy, stimulation of the thyroid gland by TSH or immunoglobulins (TSIg). 3. Antigenic mimicri and the presentation of autoantigens to immunocompetent cells. 4. Impaired immunoregulation--antigen specific insufficiency of suppressor T lymphocytes. 5. Local and general amplification reaction to an autoimmune process. 6. The development and autoreproduction of organ specific autoimmune endocrine disease and its development into the final stage of endocrine disease where autoantibodies may disappear. The diagnosis of PAES in clinical practice is difficult. Common immunological tests are not very conclusive. To assess a polyglandular affection we found useful the multiaxial synchronous test where stimulation of several hypothalamic releasing hormones combined with a hypoglycaemic stimulus is used. Autoimmune lymphocytic hypophysitis is part of PAES. In clinical practice this syndrome is therefore frequently incorrectly diagnosed and then incorrectly treated.

A series of 267 gastroenteropancreatic endocrine tumours has been revised from the point of view of histopathologic diagnosis, hormonal profile and clinical behaviour. Results of this investigation, together with revised concepts on the histogenesis of gastroenteropancreatic endocrine growths, allowed to develop detailed classification systems which proved useful for precise tumour diagnosis and for clinicopathologic correlation, with special reference to tumour function, prognosis and therapy. Among 132 pancreatic growths, various types of islet cell tumours (61 cases), with (45 cases) or without (16 cases) hyperfunctional syndrome, were separated from different types of gut-related (38 cases) and 'ectopic' (three cases) tumours, as well as from 25 non-functioning, locally symptomatic tumours, three small cell carcinomas and two mixed endocrine-exocrine tumours. Among 97 intestinal tumours, 39 argentaffin EC cell carcinoids, mostly from the appendix and ileum, were separated from 23 hindgut-type carcinoids, mostly from the rectum, 22 gastrin cell tumours, mainly from the duodenal bulb, five somatostatin cell tumours, mostly from the periampullary region of the duodenum, and two gangliocytic paragangliomas. Among 38 gastric tumours, five small cell 'neuroendocrine' carcinomas were separated from three gastrin cell tumours and 30 argyrophil carcinoids, 27 of which arose in the body fundus, 16 associated with chronic atrophic gastritis and four with combined Zollinger Ellison/Multiple Endocrine Neoplasia Syndrome.

The autoimmune polyglandular syndrome is characterized by the association of 2 or more endocrine disorders of autoimmune origin which may coexist with autoimmune disorders in other organs. Roughly 25% of patients with an autoimmune endocrinopathy show evidence of autoimmune disease elsewhere. We report 21 patients with autoimmune polyglandular syndrome classified according to Neufeld.

Autoimmune polyglandular syndromes are classified into three types. Type I occurs in childhood and is characterized by at least two of the following: chronic mucocutaneous candidosis, adrenal failure and hypoparathyroidism. There is also an association with chronic active hepatitis. Type II usually develops in adulthood and is characterized by adrenal failure plus hypothyroidism or diabetes mellitus, or both. Type III consists of thyroid disease and one other organ-specific autoimmune disorder. This classification has potential usefulness in patient management and family screening for autoimmune endocrine diseases.

Dysfunction of multiple endocrine glands may develop as the result of hypopituitarism, various infiltrative disorders, or an organ-specific autoimmune mechanism. When dysfunction of two or more endocrine glands occurs in association with circulating organ-specific antibodies directed against the involved glands, the term polyglandular autoimmune syndrome is applied. Characteristics of polyglandular autoimmunity include specific patterns of disease association and frequently a family history of similar involvement. The principal endocrine components of these syndromes are adrenal insufficiency, autoimmune thyroid disease, insulin-dependent diabetes mellitus, and premature gonadal failure. In addition, primary hypoparathyroidism is a key feature of one form of polyglandular autoimmunity that occurs in children. Several nonendocrine organ-specific autoimmune disorders are also associated with polyglandular autoimmunity, of which pernicious anemia is the most frequent. The underlying abnormality responsible for polyglandular autoimmunity is most likely a defect in T suppressor cell function, but there is evidence that aberrant expression of HLA DR antigens also plays an important role in the pathogenesis of these disorders.