The endocrine system during sepsis

Endocrinopathy during sepsis can manifest as hyperglycemia and insulin resistance or as insufficient production of either adrenal corticosteroids or vasopressin. The results of a recent large clinical trial have demonstrated that tight glycemic control with insulin can confer survival benefit to selected intensive care unit patients. Relative impairment of adrenocortical reserve has been suggested to be an important contributor to the pathogenesis of shock in sepsis. Replacement doses of glucocorticoids and mineralocorticoids have been associated with improved survival in the subset of patients with blunted results on adrenocorticotropin hormone stimulation tests. Posterior pituitary production of vasopressin is diminished in septic shock while sensitivity to its vasopressor effects is enhanced. Clinical trials are underway to determine whether administration of vasopressin can improve outcomes in patients with septic shock. Whether the euthyroid sick syndrome represents an adaptive or a maladaptive response to severe illness remains unclear.     

骨钙素介导的骨内分泌系统

骨为新型的内分泌器官,具有内分泌功能。目前发现骨分泌2种激素:成纤维细胞因子23(FGF23)和骨钙素(OCN)。成骨细胞/骨细胞分泌的FGF23主要作用于肾脏调节磷代谢;成骨细胞/骨细胞分泌的OCN存储于骨基质,经破骨细胞的吸收脱羧后以低羧化形式(ucOCN)释放入血,最终作用于胰岛β细胞、脂肪细胞和睾丸间质细胞。ucOCN和靶器官之间形成反馈节环,调控能量代谢和雄性生殖功能。     

The pleura and the endocrine system

The functioning of the pleura and the endocrine system are not entirely independent of each other. Some hormones can reach a greater concentration in the pleural exudate than in the blood. However, the clinical significance of this finding remains unknown. In some circumstances, hormonal changes are responsible for pathological manifestations in the pleura. Hypothyroidism is one of the most common diseases that can cause a pleural effusion, likely resulting from alterations in capillary permeability. The presence of ectopic endometrial tissue within the lung parenchyma, pleura, pericardium or diaphragm is known as thoracic endometriosis and is one of the causes of catamenial pneumothorax and /or catamenial hemothorax, which can affect women of childbearing age and arises within 72 h from the onset of menstruation. Treatment and prevention of recurrent catamenial pneumothorax / hemothorax usually requires an approach that combines surgery and hormone therapy. Malignant pleural effusion from breast cancer may contain estrogen receptor-positive cells. In such a case, endocrine treatment may be effective in reducing the amount of pleural fluid and the associated symptoms. Thyroid cancer and lymphangioleiomyomatosis (LAM) are further hormone-sensitive malignancies in which pleura is frequently involved. The solitary fibrous tumor of pleura (SFPT) is an example of a pleural disease that can cause hormonal balance disorders. It can lead to a rise in the releasing factor for growth hormone (GHRH), human beta chorionic gonadotropin (Beta-hCG), and insulin-like growth factor 2 (IGF2). The consequence of such hormonal imbalance include hypertrophic pulmonary osteoarthropathy, gynecomastia, and refractory hypoglycemia, respectively.     

The endocrine system in diabetes mellitus

The pathophysiology of diabetes mellitus is complex and not fully understood. However, it emerges as an abnormal metabolic condition associated with a systemic damage to the vascular bed. Cumulative evidence also reveals that the endocrine system is not intact in patients with diabetes mellitus. It is not clear whether the changes observed in the endocrine system represent a primary defect or reflect the effects of the impaired insulin action and abnormal carbohydrate and lipid metabolism on the hormonal milieu. Review of the literature reveals that the function of the entire endocrine system including the functions of hormones from the hypothalamus, pituitary, adrenal, thyroid, parathyroid, the vitamin D system, the gonads, and the endocrine function of the adipose tissue, is impaired. Good metabolic control and insulin treatment may reverse some of these abnormalities. It remains unanswered as to what extent these changes in the endocrine system contribute to the vascular pathologies observed in individuals affected by diabetes mellitus and whether part of the abnormalities observed in the endocrine system reflect a basic cellular defect in the diabetic syndrome.     

The gastroenteropancreatic endocrine system and related tumors

Up to 16 types of endocrine cells have been characterized morphologically (and most of them also functionally) in the gastroenteropancreatic area. Four main groups of pancreatic endocrine tumors (with several subtypes) have been identified: islet cell, ectopic, nonfunctioning, and poorly differentiated tumors. A detailed classification system that combines cytologic and clinicopathologic patterns has been developed for the study of 132 pancreatic tumors. Among a large series (more than 120 cases) of endocrine tumors arising in the gastrointestinal tract, serotonin-producing argentaffin carcinoids have been separated from hindgut trabecular carcinoids, producing glucagon- and pancreatic polypeptide-related peptides, paragangliomas, somatostatin cell tumors, gastrinomas, and argyrophil ECL cell carcinoids. The clinicopathologic profile of the various pancreatic and gastrointestinal tumor entities has been delineated and involvement in the multiple endocrine neoplasia syndrome has been analyzed in detail.     

The renin-angiotensin system in the endocrine pancreas

Experimental data suggest that a tissue renin-angiotensin system is present in the pancreatic islets of several species, including man. However, the physiological role for this local renin-angiotensin system remains largely unknown. In vitro findings argue against a direct effect of angiotensin II on alpha- and beta-cells. In contrast, when the influence of angiotensin II on the pancreatic islets has been evaluated in the presence of an intact vascular system either in vivo or in the perfused pancreas, a suppression of insulin release has been observed, also in man. These discrepancies may be explained by the profound effects of the renin-angiotensin system on pancreatic islet blood perfusion. Alterations in the systemic renin-angiotensin system and an increased vascular sensitivity for its components have been observed in diabetes mellitus and hypertension. Whether changes occur also in the pancreatic islet renin-angiotensin system during these conditions remains unknown. Future research may help to provide an answer to this question, and to elucidate to what extent the renin-angiotensin system may contribute to beta-cell dysfunction in these diseases.     

The endocrine system and connective tissue disorders

The face of many endocrine diseases is rapidly changing as early detection and intervention is achieved. Nevertheless, certain musculoskeletal symptoms can suggest a possible endocrinopathy. The clinician can expect the appearance of particular rheumatic problems during the course of a chronic endocrine disorder. This is especially germaine for diabetes and acromegaly, in which the disorder is controlled but not cured. Clearly hormones play a critical role in the development and expression of immunologic disease. Sex hormones and calcitriol have a direct effect on basic immunobiology (3). The rheumatoid synovium responds to parathyroid hormone and calcitriol in concert with local signals such as prostaglandins, interleukins, and interferon (2,77). Finally, the immune system plays a central role in the pathogenesis of several endocrine diseases. The thyroid diseases, Graves' disease and Hashimoto's disease are best studied. The mechanisms of Ia expression leading to immune destruction and lymphocytic infiltration of the gland will be applied to other endocrine disorders.     

The endocrine system in chronic nitric oxide deficiency

The experimental model of chronic inhibition of nitric oxide (NO) production has proven to be a useful tool to study cardiovascular and renal lesions produced by this type of hypertension, which are similar to those found in human hypertension. It also offers a unique opportunity to study the interaction of NO with the humoral systems, known to have a role in the normal physiology of vascular tone and renal function. This review provides a thorough and updated analysis of the interactions of NO with the endocrine system. There is special focus on the main vasoactive factors, including the renin-angiotensin-aldosterone system, catecholamines, vasopressin, and endothelin among others. Recent discoveries of crosstalk between the endocrine system and NO are also reported. Study of these humoral interactions indicates that NO is a molecule with ubiquitous function and that its inhibition alters virtually to all other known regulatory systems. Thus, hypothyroidism attenuates the pressor effect of NO inhibitor N-nitro-L-arginine methyl ester, whereas hyperthyroidism aggravates the effects of NO synthesis inhibition; the sex hormone environment determines the blood pressure response to NO blockade; NO may play a homeostatic role against the prohypertensive effects of mineralocorticoids, thyroid hormones and insulin; and finally, NO deficiency affects not only blood pressure but also glucose and lipid homeostasis, mimicking the human metabolic syndrome X, suggesting that NO deficiency may be a link between metabolic and cardiovascular disease.     

The place of the spleen in the endocrine system

While the evidence for an endocrine function of the spleen is meagre and theexact nature of this action is not clear it does seem to be fairly well established thatthe spleen must be considered as an important part of the mechanism whereby anormal corpuscle, and possibly platelet, content of the circulating blood is maintained.

This regulation seems to be due to the production by the spleen of one or morehormones.

These hormones appear to affect the processes of the bone marrow and also mayact upon the corpuscles in the circulating blood.

The conception of hyperactivity of the spleen in the human being seems to befirmly established but little is known of the clinical appearance of its hypoactivity.

     

Metabonomics and the endocrine system

Proton-NMR-based metabonomics offers a rare opportunity as a definitive screening technique for biofluids and tissue biopsies. The procedure is extraordinary in that it allows the 'complete biochemical picture' to be examined at one time and is able to detect subtle but repeatedly consistent disparities that may be occurring in different, and perhaps unrelated, biochemical pathways. Such metabolic responses to an initial perturbation in homeostasis may be followed over a sequential time-course to their eventual dissipation or consequent sequelae. The application of this technique is beginning slowly to filter into the area of endocrine research and has been used to examine long-term and diffuse physiological alterations that may occur following such events as anabolic steroid treatment of cattle and the exposure of endometrial cells to tamoxifen. Although only modest inroads have been made so far, this technique promises immense potential for future researches within the endocrine field.     

Age and the endocrine system

The pattern of age-induced changes in each endocrine system is unique. Both hormone levels and target organ responsivity are altered in the aging endocrine-cardiovascular system. Serum levels of vasopressor hormones both increase (norepinephrine) and decrease (renin, aldosterone). Target organ responses to beta-adrenergic stimulation in the heart and probably also in vascular smooth muscle decrease due to postreceptor changes. These effects contribute to the clinical problems of hypertension and orthostatic hypotension which characterize the elderly. Aging produces mild carbohydrate intolerance and a minimal increase in fasting serum glucose in healthy, nonobese individuals, primarily due to decreasing postreceptor responsiveness to insulin. Aging decreases the metabolism of thyroxine, including its conversion to triiodothyronine, but clinically significant alterations of thyroid hormone levels do not occur. Changes in the end-organ response to thyroid hormones, however, significantly alter the clinical presentation of thyroid diseases. Aging shifts the serum vasopressin-serum osmolality relationship toward higher serum vasopressin levels probably due to altered baroreceptor input, probably contributing to the tendency toward hyponatremia in the elderly. Aging slows the metabolism of cortisol, but glucocorticoid levels in the human are essentially unaltered by age. However, recent data indicate that delta-5 adrenal steroids decrease markedly in both men and women. Nodules in the anterior pituitary, the thyroid, and the adrenal increase in frequency with aging. Finally, the reproductive system is primarily altered by endocrine cell death, by unknown mechanisms, resulting in decreased estrogen and testosterone levels in women and men. This most obvious age-related endocrine change turns out to be incompletely understood and is not representative of most age-related endocrine changes. Despite characterization of these many age-related alterations in endocrine systems, therapeutic issues often remain unexplored, and more data are needed in many areas.     

The coagulation system in endocrine disorders: A narrative review

Endocrine disorders can influence the haemostatic balance. Abnormal coagulation test results have been observed in patients with abnormal hormone levels. Also unprovoked bleeding or thrombotic events have been associated with endocrine disease. The aim of the present review is to summarise the available evidence on the influence of common endocrine disorders on the coagulation system, and their possible clinical implications. We focus on thyroid dysfunction, hyper- and hypocortisolism and growth hormone disturbances, while other endocrine disorders are only briefly discussed. In the published literature a clear bleeding diathesis has only been associated with overt hypothyroidism, mainly mediated by an acquired von Willebrand syndrome. A clinically relevant hypercoagulable state may be present in patients with hyperthyroidism, hypercortisolism or abnormal growth hormone levels, but adequate prospective clinical studies are lacking. Also effects of pheochromocytoma, hyperprolactinaemia and hyperaldosteronism on the coagulation system have been described. It is apparent that unprovoked bleeding and thrombotic episodes can be secondary to endocrine disorders.