What Causes Adrenal Fatigue

Adrenal Fatigue Recovery Workbook

This valuable book gives you all of the tools that you need in order to identify, manage, and treat the symptoms of adrenal fatigue syndrome. AFS is a medical problem that most doctors don't really know how to diagnose. The symptoms are often seen as being too vague to mean anything to medical professionals, and therefore people who suffer from this debilitating condition often suffer alone, and without medication. And those that DO get medicated often get put on something useless for this condition such as antidepressants or sleeping pills, which just add issues on to what you are already experiencing. If you are feeling down, tired, or depressed for no reason, there is a good chance that you are suffering from Adrenal Fatigue Syndrome There is no need for you to bear that alone! Why would you want to do that when you have a valuable resource in your hands? This book has everything you need to get help!

Adrenal Fatigue Recovery Workbook Summary


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Drugs And The Adrenal Gland

There are two adrenal glands located near the top of each kidney. The adrenal gland is comprised of two parts the adrenal medulla and the adrenal cortex. The adrenal cortex produces glucocorticoids (cortisol) and mineralocorticoids (aldosterone). Corticosteroids promote sodium retention and potassium excretion. Corticotropin (Acthar) is an ACTH drug that is used to diagnosis adrenal gland disorders. Corticotropin (Acthar) is also used to treat adrenal gland insufficiency and as an anti-inflammatory drug in the treatment of allergic reactions such as anaphy-laxis shock. ACTH given intravenously increases the serum cortisol levels in 30 to 60 minutes if the adrenal gland is properly functioning. ACTH will eventually stimulate cortisol production if pituitary insufficiency causes steroid deficiency. Table 21-2 shows the effects of an adrenal gland that produces too much (hypersecretion) or too little hormone (hyposecretion). Adrenal hyposecretion is called Addison's disease and...

Adrenal Gland

Isg Sagittal

Adrenal carcinoma. (A) Axial T2-weighted breath-hold half Fourier single-shot fast spin-echo image shows 8-cm mass in the right adrenal gland (large arrow). There are gallstones (small arrows). (B) Axial T1-weighted gradient echo image with fat suppression obtained after gadolinium intravenous contrast material shows enhancement of the adrenal mass. (C) Coronal T1-weighted gradient echo image with fat suppression obtained after gadolinium intravenous contrast agent injection shows the mass clearly above the right kidney (arrow), displacing the right kidney medially and laterally. When CT with intravenous contrast is equivocal, chemical shift MR imaging should be performed as chemical shift MR imaging is the most sensitive technique for differentiating adenomas from metastases of the adrenal gland.58 With the chemical shift MR technique, the sensitivity and specificity for differentiating adenomas from metastasis ranges from 81 to 100 and 94 to 100 , respectively.67-70...

The adrenal glands

The two adrenal glands sit like cocked hats over each kidney (Fig. 5.9) (hence their name - additions to the renal organ, or kidney). Each gland has an inner core and an outer layer of cells, the adrenal medulla and adrenal cortex respectively. The cortex (outer layer) makes up about nine-tenths of the bulk of the gland its cells under the microscope are rich in lipid. The medulla stains darkly for microscopy with chromic salts, showing the presence of so-called chromaffin cells, characterised by the presence of catecholamines (such as adrenaline and noradrenaline). Fig. 5.9 The anatomy of the adrenal glands. Fig. 5.9 The anatomy of the adrenal glands. The adrenal medulla develops as part of the nervous system. It is supplied with nerves that are part of the sympathetic nervous system. (They are pregangli-onic fibres whose neurotransmitter is acetylcholine this will be discussed in detail in Section Its secretory activity is controlled directly by the brain through these...

Adrenal Glands

One adrenal gland (uh-DREE-nuhl gland) is located above each kidney, as shown in Figure 50-6. Each adrenal gland has an inner core, the medulla, and an outer layer, the cortex. The medulla and cortex function as separate endocrine glands. Secretion of hormones in the medulla is controlled by the nervous system, whereas hormones in the anterior pituitary regulate secretion of hormones in the cortex.

Hormones Mediating Stressinduced Changes in Blood Leukocyte Numbers

The catecholamines epinephrine and norepinephrine and the glucocorti-coid hormones have been identified as the major endocrine mediators of stress-induced changes in leukocyte distribution (Fauci and Dale, 1974 Schedlowski et al., 1993a, 1993b Dhabhar et al., 1995a Benschop et al., 1996 Dhabhar et al., 1996). Studies have revealed that stress-induced changes in leukocyte distribution are mediated by hormones released by the adrenal gland (Dhabhar et al., 1996 Dhabhar and McEwen, 1999b).Adrenalectomy (which eliminates the corticosterone and epinephrine stress response) has been shown to reduce the magnitude of the stress-induced changes in blood leukocyte numbers. (Dhabhar et al., 1996 Dhabhar and McEwen, 1999b). Cyanoketone treatment, which virtually eliminates the corticosterone stress response, also virtually eliminates the stress-induced decrease in blood lymphocyte numbers, and significantly enhances the stress-induced increase in blood neutrophil numbers (Dhabhar et al., 1996)....

Pulmonary Smooth Muscle

The bronchial tree is innervated by both divisions of the autonomic nervous system. Postganglionic parasympa-thetic neurons innervate bronchial smooth muscle directly and produce bronchoconstriction when stimulated. Sympathetic noradrenergic neurons appear to innervate vascular smooth muscle and parasympathetic ganglion cells. The effect of noradrenergic fibers on ganglion cells is to inhibit their firing. There is some controversy concerning the role of noradrenergic fibers in the regulation of airway smooth muscle tone. There is no doubt, however, that adrenoceptors are present on bronchial smooth muscle and that epinephrine from the adrenal gland and drugs such as epinephrine and iso-proterenol produce bronchodilation of the airway.

Changes In The Incidence Of Orbital Diseases Over Time

Among both males and females,4 but between 1993 and 1998 the increase was confined to females, with an increase of 1.8 per year.5 There is no adequate explanation for this observed increase. A study from Denmark, where a national orbital tumor registry was established in 1974, has also shown a steady increase in the incidence of both benign and malignant orbital tumors over the period 1974 to 1997.6 All tissue specimens derived from the orbit were registered during this time, making the increased incidence observed very likely to be a real increase rather than an artifact. Data are limited on changes in incidence of secondary orbital tumors, but one study from Japan has shown a small but steady increase in orbital metastasis from primary tumors in the lung, liver, and adrenal gland since 1980.7 As the incidence of primary tumors changes over time, it is likely the pattern of orbital metastases will change also.

P45011B1 11Hydroxylase and 11B2 Aldosterone Synthase

RT-PCR studies from Stromstedt and Waterman (14) and Mellon and Deschepper (15) confirmed the presence of P450 11B mRNA in the rat brain cortex. P450 11B2 was detected at low levels all over the brain by Stromstedt and Waterman but could not be detected by Mellon and Deschepper. As was the case with P450scc, the mRNA levels of P450 11B1 were much lower than could be predicted from the protein levels. In addition, the cerebellum and brainstem which were strongly labeled in the immuno-histochemical study of Ozaki et al. (17) had very low or undetectable levels of 11B1 mRNA. The reasons for these discrepancies are not clear. It may be one more indication that the brain regulates its P450 at a post-transcriptional level. However, it cannot yet be ruled out that, in the brain, there is an 11 -hydroxylase enzyme similar enough to be recognized by the antibody raised against adrenal 11B1, yet different enough that it is not detected by PCR primers and or probe specific for 11B1....

Conclusions About Brain Steroidogenesis From The P450 Data

Reliable quantative assessments of the level of catalytic activity and mRNAs of the various steroidogenic enzymes, as well as their localization, is not a purely academic exercise. If regulation of these enzymes is mostly post-transcriptional, mRNA levels would not be expected to reflect changes in catalytic activity and the extremely low levels of the mRNAs might not be so surprising. In the matter of synthesis of steroids from cholesterol, regardless of what the mRNA levels are, the accumulation of preg-nenolone and DHEA in the brain in animals where the gonads and adrenals are removed needs to be explained. The extremely low levels of P450scc and 17 catalytic activity found in the brain in normal animals, is unlikely to account for either the accumulation in the brain or for the maintenance of the relatively high plasma levels of these steroids in the absence of gonads and adrenals. There can only be two possible explanations. Either there is a large increase in P450scc and 17...

FNeuropsychiatry Disturbances

Catabolism is the breaking down of the body's complex substances by wear, tear, and age into waste products of simpler composition for elimination. Metabolism and growth then are dependent on the body's receiving enough of the proper foodstuffs in order to supply its needs, in other words, on proper nutrition. Metabolism and growth are further regulated by the vitamins and hormones. The hormones are supplied by the ductless glands of the body (the pituitary, thyroid, parathyroid, pancreas, adrenals, and gonads), and any disorder of these glands will profoundly disturb growth and metabolism. The vitamins are supplied by the diet if the diet or nutrition is unsatisfactory, disturbances in growth and metabolism can result also. Therefore, metabolism, growth, and nutrition are closely related to one another.

Neurosteroid Biosynthesis

In order to examine the activity of the P-450scc present in C6 cells hydroxylated analogs of cholesterol were used, which will freely cross the mitochondrial membranes thus accessing the P-450scc in the inner membrane. Three different hydroxylated cholesterols (25-, 22-, and 20-OH-cholesterol) stimulated mitochondrial production of PREG by three to fivefold. Glial-cell P-450scc activity was also tested with hydroxylated cholesterol analogs in the presence of aminoglutethimide, an inhibitor of adrenal, testis, and ovarian P-450scc. Aminoglutethimide inhibited the PREG formation in a concentration-dependent manner from 25- and 22-OH-cholesterol, but failed to affect the conversion of 20-OH-cholesterol into PREG (55). These findings suggest a functional analogy between adrenal and glial P-450scc. Thus, in addition to the P450scc protein, C6-2B cells also express P450scc activity. More recently, we demonstrated that human glioma cells in culture are also able to synthesize neurosteroids...

Vascular Endothelial Growth Factor

The biological relevance of the FGF signaling system in thyroid cell growth has been further hinted at from genetically altered mice. Mice deficient for FGFRR2-IIIb were generated by placing translational stop codons and an IRES-LacZ cassette into exon IIIb of FgfR2. Expression of the alternatively spliced receptor isoform, FgfR2-IIIc, is not affected in these mice. The FGFR2-IIIb deficient mice, however, show dysgenesis of several non-endocrine as well as endocrine tissues including the thyroid, adrenals, pancreas, and pituitary. These findings are particularly interesting in view of the fact that FGF ligand expression is not altered with normal FGF8, FGF10, Bmp4, and Msx1 in this animal model (45).

Hypothalamic PituitaryAdrenal Axis and Glucocorticoid Responses

The endogenous glucocorticoid in man is cortisol, whereas in rodents it is corticosterone. The expression of corticotrophin releasing hormone (CRH) in the hypothalamic region of the brain is activated by inflammatory or other stimuli. In turn, CRH stimulates the release of adrenocorticotropin hormone (ACTH) into the bloodstream from the anterior pituitary gland. ACTH then stimulates the synthesis and release of glucocorticoids from the adrenal glands. In order to maintain regulation of this axis, glucocorticoids feed back and downregulate the HPA axis at the level of the hypothalamus and pituitary. In addition to regulation of the immune system, glucocorticoids are also essential for the regulation of several homeostatic systems in the body, including the central nervous system, cardiovascular system, and metabolic homeostasis. Glucocorticoid regulation of the immune system will not be discussed in detail here but has been the subject of another recent review (Webster...

DBI in Steroid Neurosteroid Synthesis

In search of a cytoplasmic steroidogenesis-stimulating factor(s), a protein of 8,2 kDa molecular size was isolated from bovine adrenals shown to stimulate transport of cholesterol into mitochondria and transport from the outer to the inner membrane (95). This 8,2 kDa protein was shown to be identical to DBI, except the loss of two amino acids (Gly-Ile) from the carboxy terminus (96), and to have a long-half life (97). We examined the effect of isolated 10 kDa DBI on mitochondria from adrenocortical and Leydig cells (94). Dose-response curves indicated that a threefold stimulation is obtained with low concentrations (0.1-1 M) of DBI, whereas higher concentrations have lower stimulatory effect on PREG formation. The stimulation obtained was similar to those reported for the 8.2 kDa des-(Gly-Ile)-DBI on bovine adrenocortical mitochondria (95,98). Moreover, similar results were obtained using purified rat and bovine testis DBI (18). In order to exclude the possibility that the stimulatory...

Anthrax Lethal Toxin Repression of GR

One unanswered question has been the role of HPA axis glucocorticoid responses during exposure to anthrax lethal toxin. As we have previously described, an intact HPA axis response is essential for survival from a range of proinflammatory, bacterial, and viral insults.We have recently shown that adrenalectomy also enhances sensitivity to LeTx in all mouse strains tested including DBA 2J mice, which are completely resistant to LeTx when the adrenals are intact (Moayeri et al., 2005). However, unlike the studies described earlier, dexamethasone treatment does not prevent this increased mortality rate but rather sensitizes mice to LeTx (Moayeri et al., 2005). Although this data is contrary to what one might initially expect, there is data to demonstrate that the HPA axis needs to be carefully balanced for optimal host responses in bacterial exposures. Perturbations in either direction are detrimental to health. Indeed, prolonged treatment of septic shock with high doses of...

Standard Surgical Technique

At this point, hemostasis is achieved as well as possible. Occasionally, the bare area may require coagulation with the argon beam coagulator and a few hemo-static sutures. Depending on the degree of coagulopathy the new liver may need to be implanted while there is ongoing bleeding from the bare area. The donor liver is prepared for implantation on the back table by removing its diaphragmatic attachments including ligation of phrenic veins, removing the adrenal gland and ligation of the adrenal vein, and preparing the arterial and portal venous structures. The donor liver is then brought onto the operative field and end-to-end anastomoses are constructed using running non-absorbable monofilament su

Stage4S Neuroblastoma

Baby presented at 3 days of age. Bone and bone marrow were normal.The patient received no therapy. a Contrast-enhanced CT scan reveals a partially calcified right adrenal mass (arrow) and a low-attenuation liver metastasis (arrowhead). b Ultrasonography at diagnosis reveals a right adrenal mass (arrowhead) and several hepatic nodules (arrows).c Ultrasonography at 6 months of age demonstrates decrease in size of the right adrenal mass (arrow).d Ultrasonography at 11 months of age shows further decrease in size of the adrenal mass (arrow). The liver metastases have resolved.e Ultrasonography at 2years 3 months shows only a residual hyperechoic area (calcification) in the region of the right adrenal gland (arrow)

Animal pharmacokinetics

14C Nimesulide was found in almost all the organs. The highest concentrations were attained in the fat tissue, the liver, kidneys, lungs, adrenals, gut, and heart between 1-4 h after the administration, whereas the brain showed low concentrations. The tissue-to-plasma concentration ratios for total radioactivity were generally lower than the unity during the entire observation interval (up to 48 h). This finding indicated a low affinity of the drug for tissue components and no accumulation in tissue compartments.

Melatonin And Prenatal Communication Of Circadian Phase

Reppert and Schwartz (52) removed various endocrine organs in an attempt to identify a hormonal signal necessary for entrainment of the rat fetus. Removal of the pituitary, ovaries, adrenals, thyroid parathyroid or pineal (each surgical procedure performed in separate groups of animals) did not disrupt prenatal synchronization (although results with pinealectomy were somewhat unclear). An alternative strategy is to identify stimuli which can entrain the fetal circadian clock when given periodically during gestation to SCN-lesioned dams. Three treatments which can entrain the fetal clock have been identified in this way restricted feeding, timed administration of D1-dopamine receptor agonist, and timed administration of melatonin.

The Hypothalamus PituitaryAdrenal Axis

Glucocorticoid hormones (cortisol in humans and corticosterone in rodents) are the final step of the activation of the hypothalamic-pituitary-adrenal (HPA) axis, one of the major systems implicated in responding to environmental modifications. Activation of the HPA axis is determined by brain inputs to the hypothalamus, which releases corti-cotropin-releasing hormone (CRH) CRH reaches the hypophysis via the hyphophyseal portal system and activates the release of ACTH in the bloodstream, which, in turn, triggers the secretion of glucocorticoids by the cortical part of the adrenal gland (for review, see ref. 1). The secretion of glucocorticoids is characterized by a circadian cycle. Concentrations of these hormones are low during the inactive phase (dark phase in humans and light phase in rodents) and rise during the first hours that precede the active phase (2). The secretion of glucocorticoids is also activated by practically all forms of stress, which induces a rapid and large...

Use of Sex Steroid Metabolites as Therapeutic Regimens After Trauma Hemorrhage

In addition to the use of inhibitors of sex hormone synthesis pathways, studies have also utilized approaches in which animals were treated with sex steroid metabolites such as dehydroepiandrosterone (DHEA) and androstenediol (adiol). Both DHEA and adiol are intermediate metabolites of sex hormone synthesis (Fig. 6.2). DHEA, synthesized in the adrenal glands, is present both as a biologically active free form and as an inactive sulfated form (Nestler et al., 1991 Brown et al., 1999 Baulieu et al., 2000 Jarrar et al., 2000a, 2001). DHEA is the most abundant sex steroid in the circulation and is an intermediate in the pathway for the synthesis of testosterone and estrogen. However, depending on the hormonal milieu, andro-genic and estrogenic effects of DHEA have been reported (Nestler et al., 1991 Jarrar et al., 2001). DHEA has been shown to have immunoenhanc-ing effects on splenocytes harvested from normal animals (Brown et al., 1999 Jarrar et al., 2001). Studies have shown that...

Methodological Considerations

Although most studies examining the effects of adrenalectomy on the behavioral responses to drugs are consistent, some studies have not observed decreased drug effects following ablation of the adrenal glands. For example, as mentioned previously, adrenalectomy does not decrease sensitization to the locomotor effects of cocaine when it is performed after a sensitizing paradigm (18,19). In addition, adrenalectomy does not reduce cocaine facilitation of brain stimulation (46) or drug-induced reinstatement of seeking behavior (for review, see ref. 43). The nature of this discrepancy is unclear. However, it is important to point out that corticosterone levels at the time of adrenalectomy (i.e., circulating levels of corticosterone at the time when the adrenal glands are removed) could play a fundamental role in determining whether adrenalectomy will or not reduce drug effects. Thus, it has been shown (12,47) that adrenalectomy has no effects on the locomotor response to cocaine or on the...

Hemodynamic alterations

Hemodynamic instability and shock, which is often unresponsive to volume loading and vasopressor agents, are prominent features of acute hypoadrenalism (adrenal crisis). Several mechanisms contribute to cardiovascular failure. Mineralocorticosteroid deficiency resulting in sodium and water loss and subsequent hypovolemia, which may be aggravated by vomiting and diarrhea, is the major pathogenetic factor. However, glucocorticoids are also of prime importance in maintaining adequate cardiovascular function as shock may occur in glucocorticoid deficiency. Glucocorticoid deficiency is associated with reduced myocardial contractility which responds to corticosteroid treatment. Withdrawal of glucocorticosteroid treatment in patients with chronic hypoadrenalism results in a pronounced fall in lymphocyte b 2-adrenergic receptor density, which may reflect changes in cardiovascular b-receptors, and a reduced cAMP response to isoprenaline. This is associated with impaired left ventricular...

Measures to control the effects of hyperthyroidism

Propranolol (80 mg orally or 1-2 mg intravenously as required) blocks the b-adrenoreceptor effects of thyroxine and is particularly useful for reducing sinus tachycardia. It also impairs conversion of thyroxine to tri-iodothyronine and inhibits release of thyroid hormone. Propranolol is contraindicated in patients with cardiac insufficiency or air-flow limitation, although newer more specific b-blockers such as atenolol can be used in patients with congestive cardiac failure, bronchospasm, or peripheral vascular disease. Rapid atrial fibrillation should be managed by standard protocols involving digoxin administration (up to 1.5 mg as a loading dose) following correction of hypokalemia and anticoagulation. Thyrotoxicosis accelerates the metabolism of digoxin. Conversely, patients with thyrotoxicosis are more sensitive to warfarin because vitamin-K-dependent clotting factors are metabolized more rapidly. Verapamil may also be useful in this setting to reduce the ventricular rate....

Psychological Stress and Immunity

Stress can be defined as a state of altered homeostasis resulting from either an external or an internal stimulus. The host's response to stress is designed to restore homeostasis through a variety of adaptive neuroendocrine-mediated mechanisms (Ramsey, 1982). This restoration of homeostasis is accomplished, in part, through the increased synthesis of a variety of neuroendocrine-derived peptides and hormones. For example, the perception of a psychological stressor activates the hypothalamic-pituitary-adrenal (HPA) axis and the sympathetic branch of the autonomic nervous system. This activation culminates in the synthesis of both cortisol (corticosterone in rodents) by the adrenal glands and epinephrine and norepinephrine by the sympathetic nervous system. Interestingly, in addition to their roles in maintaining homeostasis, these and other products of the nervous and endocrine system pathways can also modulate immune function through their binding to specific receptors that are...

Chronic Fatigue Syndrome

Chronic fatigue syndrome is characterized by profound fatigue that is not alleviated by sleep, and a myriad of other symptoms including impairment of memory and concentration, muscle pain, and swollen lymph nodes. There is no single cause of the illness and a physician should be consulted to explore all possibilities. Causes may be a viral infection, adrenal gland dysfunction, chemical sensitivity, autonomic nervous system disorder, or food allergy.

Systemic Side Effects and Complications

Another major concern with the use of corticosteroids is adrenocortical insufficiency. The adrenal gland is an endocrine (hormone-producing) gland located on top of each kidney. The adrenal cortex produces corticosteroidlike chemicals. In adrenocortical insufficiency, there is a decrease or shutdown in the body's natural production of similar substances. Due to physiologic biofeedback, when corticosteroid therapy is used, the body senses the additional drug in the system. The body then decreases natural production in order to bring levels back into balance. When natural production is diminished over time, there may be atrophy (tissue death) of the adrenal cortex. If atrophy occurs, the body can no longer make the normal quantity of chemical itself, causing problems when the therapeutic dose is discontinued.

Familial Adenomatous Polyposis and Turcot and Peutz Jeghers Syndromes

Extracolonic malignancies may be present in individuals with FAP. Duodenum, periampullary area, stomach, pancreas, papillary thyroid, liver, and brain carcinomas are known to occur with greater frequency in FAP patients. Adenocarcinomas of the bile ducts and adrenal glands also have been reported, but the risk of these cancers in individuals with FAP remains low. Carcinomas of the small intestine, predominantly of the duodenum or peri-ampullary area, are seen in 4 to 12 of FAP patients. Gastric adenocarcinoma occurs in 0.5 of FAP patients. Pancreatic and papillary thyroid carcinomas are present in approximately 2 of individuals with FAP. One in 150 children under the age of 5 years with a mutation for FAP will develop hepatoblastoma.1 Tumors of the central nervous system (most commonly medulloblastoma, as seen in Turcot syndrome) occur in less than 1 of individuals with FAP. Individuals with FAP who also have an osteoma, fibroma, or epidermoid cyst have, in the past, been diagnosed...

Biosynthesis and Degradation

Enkephalins are processed by the proteolysis of a high molecular precursor, pro-enkephalin. Pro-enkephalin is also known as pro-enkephalin A, whereas pro-en-kephalin B is not a direct precursor of enkephalins, but the precursor of dynor-phins. The precursor protein was first discovered in 1980, in the adrenal gland by Lewis and coworkers, who unraveled its role in the biosynthesis of enkepha-lins.

What is patients mental status The body does all it can to

Maintain perfusion to heart, brain, and adrenal glands in the face of hypotension or inadequate cardiac output. If mental status is not normal, assume that cerebral perfusion has been compromised. This represents an even more urgent medical emergency and may require immediate attention to airway as fluid resuscitation is occurring.

Endocrinological Factors Hormones

There are a few other hormonal factors that change during pregnancy and are involved in the sleep process. During pregnancy, corticotropin-releasing hormone (CRH), which is normally synthesized by the hypothalamus, is synthesized by the placenta, fetal membranes and decidua and is physiologically identical to that of the mother (Florio, Cobellis, Woodman, Severi, Linton, and Petraglia 2002 Wadhwa, Sandman, Chicz-DeMet, and Porto 1997). CRH is a crucial element in parturition and fetal growth and varying levels have been shown to be involved with preterm labor (Inder et al. 2001 Siler-Khodr, Forthman, Khodr, Matyszczyk, Khodr, and Khodr 2003 Wadhwa et al. 1997). Prolactin is a hormone produced by the anterior pituitary gland with its primary role being initiation and sustenance of lactation. The secretion of prolactin is increased by stress and is dependent upon a woman's estrogen levels. Finally, cortisol, a well-known steroid hormone, is particularly involved in the pregnancy...

Metabolic systems hepatic pancreas endocrine

Experimental work has suggested that many patients with SIRS may have relative deficiency of cortisol. This is often only demonstrated by a direct challenge with a synacthen (ACTH stimulation) test. Resistant hypotension, elevation of blood potassium, and a fall of blood sodium may also indicate hypoadrenalism.

The androgens and oestrogens

Females, too, produce androgens, principally in the follicular theca cells. Androgens are also produced in the adrenals in both male and females. They also likely induce responses in tissues other than the pituitary and gonads. In adults, for example, inhibin is also synthesized by the adrenal glands, spleen and nervous system. Recent studies involving inhibin-deficient transgenic mice reveal a novel role for inhibin as a gonadal-specific tumour suppressor. These mice, in which the a inhibin gene was missing, all developed normally, but all ultimately developed gonadal stromal tumours.

Mechanism of action

My own view is that the neuroendocrine system is the most likely agent of change brought about by ECT. Neuroendocrine dysregulation is prominent in patients with the mental disorders for which ECT is effective. Thyroid, adrenal, sex gland, and hypothalamic dysfunction are common in patients with disorders in mood, thought, motor activity, feeding, sleep, sex, growth, and maturation. Indeed, every aspect of body physiology and mental activity is affected by these glands, as seen in the action of the adrenal glands in depressive mood disorders. In the severely depressed patient, the adrenal glands produce too much cortisol. In turn, the high levels in the blood disrupt the normal diurnal rhythms of other glandular discharges, and the glands do not respond to the usual feedback mechanisms. The most prominent features of depression failure to eat, loss of weight, inability to sleep, loss of interest in sex, inability to concentrate thoughts, and difficulties in memory are distortions in...

Jugulotympanic Paraganglioma

Jugulotympanic paragangliomas may also be mul-ticentric or coexist with tumours of other types. They may be bilateral in the same patient and coexist with carotid body paragangliomas that may be bilateral 84 . They may also coexist with adrenal gland pheo-chromocytomas, which can produce hypertension. A familial tendency to grow paragangliomas has been noted particularly in cases with multiple tumours of this type. In families containing patients with head

Pneumocystis carinii Clinical presentation

Extrapulmonary P. carinii have been described from most internal organs post mortem as well as in vivo (Cohen and Stoeckler 1991), including lymph nodes, spleen, liver, bone marrow, bones, adrenal glands, gastrointestinal tract, kidneys, thyroid gland, heart, pleura, pancreas, peritoneum, eyes, ears, and brain (Garcia and Bruckner 1993). Patients taking prophylaxis with aerosolized pentamidin, attaining only the lungs, rather than taking systemic prophylaxis with sulfamethoxazole-trimethoprim (co-trimoxazole), are at particular risk of extrapulmonary infection (Witt et al. 1991).

Organ and systembased theories

The overall performance of mammals is closely related to the levels of efficiency of neuroendocrine mechanisms regulating the output of organs and tissues. Given the central, homeostatic role of these mechanisms, neuroendocrine system failure was suggested as the primary cause of ageing and death. The hypothalamus has been identified as a particular target organ, which, via pituitary function, may modulate the activity of the adrenals, thyroid, and gonads and so exert a causative effect on ageing. However, the pancreas has also been suggested as a probable neuroendocrine target since it is responsible for the maintenance of circulating glucose levels that are known to rise with increasing age.

Other sites of metastases

Primary breast cancer has been reported to metastasize to rare sites, such as the pancreas, with seven reported cases in the literature (92). Patients will clinically present with obstructive jaundice secondary to metastasis of the pancreatic head, with palliative surgical resection, or biliary bypass the mainstay of treatment for patients with a good performance status. Other rare locations for breast cancer metastases include the gall bladder and primary biliary tract, thyroid gland, adrenal gland, colon, small bowel, stomach, and endobronchus, most treated with surgical resection in symptomatic patients (93). Occasionally, patients will present with recurrent breast cancer to the axilla that is unable to be resected due to the rapidity of growth and aggressive nature of the tumor. Such advanced cases can be debilitating to the patient who may experience intractable pain, chronic debilitating lymphedema, and concomitant vascular and neurological dysfunction that leads to a...

NB as a Neural Crest Derivative

Branches of the abdominal aorta, and in the medullary and or ganglionic cells of the adrenal gland (Jaffe 1976). During fetal development, sites of sympathetic nervous system tissue also include neuroendocrine structures with rests of neuroblasts in the adrenal gland and paraganglia adjacent to the sympathetic ganglia.

Neurotrophins in Neural Crest Development

The majority of migrating neural crest cells express TrkC and p75 and may be mitotically active or post-mitotic. A fraction of these also co-express TrkA. In the adrenal gland. The BDNF is expressed in the adrenal cortex during embryogenesis but is restricted to the interface of the adrenal cortex and medulla in the adult. Another TrkB ligand, NT-4, is highly expressed in the adrenal medulla. The majority of neuronal cells in the medulla express TrkA and p75 but not TrkB, although TrkB is restricted to a small number of ganglion cells. Under certain conditions NT-4 activates TrkA and may serve as a physiologic ligand for TrkA expressing chromaffin cells however the neurons of the intermediolateral column of the spinal cord express TrkB and BDNF and innervate adrenal medullary chromaffin cells (Schober et al. 1999).

Pathophysiology Of Depression

Subsequently it was found that the majority of people had a disturbance of HPA axis function during a depressive episode32. Since the HPA axis is a major pathway in mediating stress it was logical to consider that alteration in HPA axis function might be the underlying mechanism giving rise to depression. Here again a problem is that there are people with totally typical depressive illness who do not have alterations in HPA axis function, and some people with increased HPA axis function do not develop depression. Thus, it appears that HPA axis dysfunction cannot provide us with a necessary and sufficient explanation of depression. However, it is clear that the HPA axis does play a role in depression and considering this together with the catecholamine theory, it was postulated that there might be multiple routes which could lead to a depressive illness and there might be a general common final pathway leading to the expression of a depression.

Adrenocorticotropic Hormone

Adrenocorticotropic hormone (ACTH), or corti-cotropin, a peptide of 39 amino acids, is first synthesized as a larger precursor from which ACTH is derived by proteolytic cleavage. ACTH stimulates production of glucocorticoids from the adrenal cortex (see Chapter 60). Release of ACTH depends on diurnal rhythms with serum levels highest in the early morning. Secretion of this peptide also increases under stress. It is easier and less expensive to treat patients having adrenocortical insufficiency with glucocorticoid replacement therapy than it is to use ACTH. Therefore, use of ACTH (Acthar) is restricted to diagnosis a shorter 24-amino acid analogue (Cosyntropin) is also used. Intravenous administration of ACTH should result in peak plasma levels of glucocorticoids within 30 to 60 minutes if the adrenal gland is functional. Prolonged administration of ACTH in a repository form, however, may be necessary to stimulate steroid production, because ACTH has long-term trophic effects on...

Signal Transduction Inhibitors

Perhaps a greater challenge will be identifying agents that are targeted to components of signaling pathways that regulate proliferation and survival. To be of value such models must accurately mimic the cellular metabolic characteristics of the clinical disease, i.e., unless the pathways accurately recapitulate the function in clinical cancer, the models may have limited value in identifying active agents, or in accurately defining the activity of drug combinations. In an attempt to characterize current preclinical models the Cancer Treatment Evaluation Program at the National Cancer Institute has initiated a Project (POPPTAP - Pediatric Oncology Preclinical Tissue Array Project) to molecularly characterize preclinical models by expression profiling and proteomics profiling. The goal of this project is to determine whether expression profiles of xenografts is similar to that of the respective tumor type in children (i.e., do neuroblas-toma xenograft samples cluster with clinical...

Natural Estrogens And Progestins

Peripheral sites of estrogen synthesis include the liver, kidney, brain, adipose tissue, skeletal muscle, and testes. Progesterone is secreted in small amounts by the testes and adrenal gland. The combined estrogen and progestin production by all of these peripheral sites amounts to 10 or less of ovarian synthesis in normal premenopausal women. In postmenopausal women, ovarian steroid synthesis declines and peripheral estrogen biosynthesis accounts for all estrogen produced, both in postmenopausal women and in males.

Characterization Of Plasma Androgens

In males, testosterone is the principal circulating androgen, and the testes are the principal source. Although the adrenals are capable of androgen synthesis, less than 10 of the circulating androgens in men are produced in the adrenals. Testosterone is synthesized by Leydig cells of the testes at the rate of about 8 mg 24 hours, providing a plasma concentration of 0.5 to 0.6 g dL. In females, the ovaries contribute approximately one-third of the total androgens synthesized, while the adrenals contribute the rest.

Patient Preparationanesthesia

There is also no consensus as to the most appropriate procedural anesthesia. In general, renal ablation is less painful than liver ablation due to the retroperitoneal location of the kidneys, but there still may be substantial pain resulting from the procedure. General anesthesia, conscious sedation, or a combination of the two has been utilized with success at different institutions. General anesthesia has significant procedural advantages over conscious sedation, including decreased patient movement during the ablation, decreased patient discomfort, and improved patient monitoring. However, general anesthesia is resource and personnel intensive, and can have risks and complications that are magnified in a medically unfit population. Thus, there is no preferred type of procedural anesthesia and practitioners have had success with both methods. One special circumstance that must be considered is when the tumor is adjacent to the adrenal gland. Heating of the adrenal gland during RF...

Candidate Chemical Mediators

As early as 1949, a role was hypothesized for the adrenal gland in accounting for the effects of LPEB in preventing tumor development,28 and as reported in Reference 12 in comparison to HPEB, LPEB has been shown to increase urinary excretion of immunoreactive adrenal cortical steroids and levels of urinary corticosteroids were reported to be inversely associated with mammary carcinoma multiplicity. These observations were followed by a series of reports by the same laboratory.22,29,30 Briefly, it was shown both in vivo22,29 and in vitro30 that provision of supplemental corticosterone has effects on cell proliferation but not apoptosis

Brief Look at the Endocrine System

There are two types of hormones proteins (which are also known as small peptides) and steroids. Steroids are secreted from the adrenal glands and the gonads. Endocrine glands are ductless glands that include the pituitary (hypophysis), thyroid, parathyroid, adrenals, gonads, and pancreas. Table 21-1 lists endocrine glands, their location, and the hormone(s) secreted by the gland. Adrenal glands

Drugproduced Modulation Of Memory

Systemically administered drugs can also act on peripheral target organs that, in turn, can affect memory-related functions. There is evidence that drugs acting on the adrenal glands can cause the release of epinephrine and glucocorticoids that have memory-modulating effects. Some of these findings are also discussed in this section.

No Regulates Cardiac Betaadrenergic Response

The force and frequency of myocardial contraction and active myocardial relaxation are physiologically regulated by neurotransmitters and hormones. Norepinepherine released by the sympathetic nerves in the heart and epinephrine released into the circulation by adrenal glands increase myocardial contractility and relaxation by acting primarily on beta-adrenergic receptors on heart muscles49 (Figure 18.1). Myocardial responsiveness to beta-adrenergic agonists decreases with age.100 The mechanism is not clear, but the presence of NO in aged myocardium may make some contribution.

CT Protocol for Planning NSS

Adrenals Planning

The first scan phase is a noncontrast CT of the abdomen, including the adrenal glands and both kidneys. The noncontrast CT is essential not only because it helps to plan for the contrast-enhanced portion of the study but also because it provides baseline attenuation values for any detected renal masses and also because it allows for the identification of any calcifications in the urinary tract or in renal lesions.

Metabolic effects of catecholamines

Catecholamine Effects Urine

In the liver, the catecholamines stimulate glycogen breakdown (glycogenolysis) through P2 (adenylyl cyclase-linked) receptors and the 'cascade' mechanism discussed earlier (see Box 2.4). In addition, they can activate glycogenolysis through a second mechanism, via the a1 (phospholipase C-linked) receptors (see Table 5.1) and elevation of the cytoplasmic Ca2+ concentration. (This was mentioned in Box 2.4 one particular situation in which elevation of intracellular Ca2+ concentration stimulates glycogenolysis will be covered in Section 8.4.3 and Fig. 8.8.) The degradation of glycogen, via glucose 1-phosphate, leads to production of glucose, which can be released into the bloodstream. This is a major response to hypoglycaemia (a fall in the blood glucose concentration) and leads to rapid restoration of the glucose concentration provided there is adequate glycogen stored in the liver. There is much experimental evidence that the liver is supplied with sympathetic nerves and that these can...

Clinical manifestation

Cardiovascular collapse (adrenal crisis). Chronic hypoadrenalism The onset of clinical manifestation is usually insidious with gradual development of signs and symptoms, each of which is non-specific alone. Increasing weakness, fatigue, lassitude, anorexia, myalgia, and weight loss are the first symptoms in gradually developing primary hypoadrenalism. Weight loss, which is mostly due to anorexia but can also be caused by dehydration, may be substantial. Vomiting and constipation, apathy, depression, and even psychosis may also occur. Vomiting and abdominal pain often herald an adrenal crisis. In some instances a history of craving for salt or salty foods may be present. Blood pressure is usually low and signs of dehydration are common. Hyperpigmentation, particularly of the lips, buccal mucosa, gingiva, palmar and plantar creases, areolas, and previous scars, is characteristic of primary hypoadrenalism but may be absent in hypoadrenalism of recent onset. Hyperpigmentation may be...

MRI Protocol for Planning NSS

Next, T2-weighted images are obtained to detect and evaluate areas of fluid, including cystic lesions and the renal collecting systems. Single-shot techniques are employed to obtain T2-weighted images in a single breath-hold and to image the entire region of interest with adequate resolution. Twenty slices can be obtained in approximately 20 seconds by utilizing a half-Fourier single-shot technique (HASTE). Thus, the kidneys and adrenal glands can be scanned using a slice thickness of 4 to 5 mm. If desired, axial imaging using the same technique can be performed with slice thickness and positioning corresponding to the in-phase and out-of-phase images.

Endothelial Architecture

Capillary Discontinuous

Pericytes, a type of mural cell associated abluminally with endothelial cells in capillaries and in some postcapil-lary venules, exhibit considerable variability in their relative association with endothelial cells in different tissues (for a review, see Ref. 9 . For example, capillaries of the retina, lung, and skeletal muscle exhibit more pericytes and coverage of endothelial cells than capillaries found in endocrine tissues such as the adrenal gland. Pericyte coverage of newly formed blood vessels is also thought to play a role in the stabilization of these structures the vasculature of tumors is poorly invested with pericytes.

Epidemiology and transmission

Prevalence but also to extrapulmonary P. carinii infections. Prior to the advent of the HIV-1 epidemic, only 16 cases of extrapulmonary Pneumocystosis had been reported in individuals who were immunocompromised by a variety of underlying diseases. Since the beginning of the HIV-1 and related PCP epidemic, at least 90 cases of extrapulmonary pneumocystosis have been reported (Ng et al. 1997). The central role played by CD4 T-lymphocytes is illustrated by the observed relationship between CD4 T-lymphocyte counts and the time of appearance of opportunistic infections. There is a definite clinical association of PCP with low CD4 lymphocyte counts as described above. The major surface glycoprotein of Pneumocystis can induce a protective CD4 T-cellular immunity mediated by IFN-g, which has several identified protective effects. IFN-g has an effect on macrophages, activating them to produce toxic superoxide intermediates and NO which are toxic to Pneumocystis. IFN-g also has an effect on the...

Discovery Of Dopamine As A Neurotransmitter

The discovery that dopamine itself is a neurotransmit-ter, similar to norepinephrine and acetylcholine, proved to be a major scientific breakthrough for the understanding of several neurological and psychiatric diseases, including Parkinson's disease and schizophrenia, but it required another 20 years work to establish this. Dopamine was known to be an intermediate in the synthesis of norepi-nephrine and epinephrine, the product of aromatic amino acid decarboxylase acting on L-dihydroxyphenylalanine. Initially, dopamine was thought to be simply a precursor to norepinephrine and epinephrine, since it was found in extremely low levels and norepinephrine had been shown to be the primary transmitter of the sympathetic nervous system.12 The presence of dopamine in greater than trace amounts was demonstrated by Holtz and von Euler in urine, and in the adrenal gland and the heart of sheep by Goodall.13-15 This began to raise the question of whether dopamine was only a metabolic intermediate....

Food and Drug Administration FDA

Glucocorticoid hormones Steroid hormones that are produced by the adrenal glands in response to stimulation by adrenocorticotropic hormone (ACTH) from the pituitary. These hormones, which can also be manufactured synthetically (pred-nisone, prednisolone, methylprednisolone, betamethasone, dexamethasone), serve both an immunosuppressive and an anti-inflammatory role in the treatment of MS exacerbations they damage or destroy certain types of T-lymphocytes that are involved in the overactive immune response, and interfere with the release of certain inflammation-producing enzymes.

The Roles Of Sf1 In Vivo Knockout Mouse Studies

To define the roles of SF-1 in vivo, targeted gene disruption in embryonic stem cells was used to generate SF-1 knockout mice. Three groups independently produced SF-1 knockout mice, with generally congruent results. SF-1 knockout mice had female external genitalia irrespective of genetic sex, and died shortly after birth from adrenocortical insufficiency (23,24), supporting an essential role for SF-1 in androgen and corticosteroid biosynthesis. Surprisingly (Fig. 2), their adrenal glands and gonads were completely absent, revealing obligatory roles for SF-1 in the development of the primary steroidogenic tissues. Developmental studies showed that the earliest stages of adrenal and gonadal development still occurred in the absence of SF-1 subsequently, these structures manifested features characteristic of programmed cell death, and degenerated. The expression of SF-1 in the anterior pituitary and hypothalamus suggested that the SF-1 knockout mice might also exhibit abnormalities at...

Central and nutritional control of adaptive thermogenesis

Female Male Zone Adrenal

Ingredients) to combat obesity (see references 47 and 48). On the one hand, there are a number of food components (e.g. caffeine, catechin polyphenols, ephedrine) known to stimulate the activity of the sympathoadrenergic system or the release of noradrenaline from the adrenals (e.g. capsaicin). On the other hand, certain nutrients foods - such as vitamin A, carotenoids, olive oil, medium-chain triacylglycerols, polyunsaturated fatty acids (PUFAs) and dietary protein - have been shown to have the potential to stimulate the expression of the UCPs in tissues. For instance, rats adapted to medium and high protein exposure have increased expression levels of UCP2 in liver and UCP1 in BAT, this correlating with a higher energy expenditure and oxygen consumption in the dark period and a lower feed energy efficiency.49 Replacement of habitual foods with others that may enhance energy expenditure may be a practical way to maintain a stable body weight or to help achieve weight loss. The...

The search for nonintentional causal explanations

Some supporting evidence comes from Cushing's Syndrome. Here the pituitary gland at the base of the brain produces excess adrenocorticotrophic hormone (ACTH) that stimulates the adrenal gland to produce excess corti-costeroids. There is a non-intentional cause of the increased steroids. Depression is seen in roughly half the cases of Cushing's Syndrome and usually remits after treatment for the disease (Kelly et al. 1980). Thus increased corti-costeroids may have a causal role in depression, but given that Cushing's Syndrome is a very rare cause of depression, unless there exists a more covert form of the disease, it is not the usual explanation.

Hormone Receptor Targeted Therapies

Normal prostate cells and tumor cells are sensitive to androgens, which are produced by two major sources the testicles, which produce testosterone (95 of all androgens), and the adrenal glands, which produce dehydroandrosterone, dehy-droandrosterone sulfate, and androstenedione. Both are under the influence of luteinizing hormone (LH), which in turn is controlled by GnRH produced by the hypothalamus. Testosterone levels have a negative feedback effect on GnRH release from the hypothalamus. Targeted endocrine medical treatment of prostate cancers aims to decrease the activity of androgens on the AR, either with antiandrogens (i.e., nonsteroidal agents such as flutamide, biclutamide) that competitively block dihydrotestosterone (DHT) binding to AR, and subsequent activation of AR-regulated genes, or by suppression of LH secretion (i.e., using specific LH agonists that ultimately inhibit LH secretion, thus reducing androgen production).

Acute adrenal insufficiency adrenal crisis

Acute adrenal insufficiency is a true endocrinological emergency. It usually presents as shock in a previously undiagnosed patient with (primary) hypoadrenalism who has been subjected to major stress or in a patient with established hypoadrenalism who does not or is not able to increase glucocorticoid replacement during an intercurrent illness or injury. A febrile illness, bacterial infection, trauma, surgery, dehydration, or any other intercurrent illness in these patients can trigger acute adrenal failure as the diseased adrenal cortex is unable to respond adequately to this type of stress. Acute hypoadrenalism can also result from bilateral adrenal

Steroidogenic Cytochromes P450

The synthesis of neurosteroids probably proceeds through pathways both similar to and different from those used in the adrenals, gonads, and placenta. The brain contains additional steroid metabolizing enzymes that convert classic steroid hormones to a variety of neuroactive compounds, shown in Fig. 2. Pregnenolone (PREG), dehydroeplandrosterone (DHEA), and metabolites of progesterone (PROG) and 20a hydroxyprogesterone have been identified in the brains of many species. These metabolites include 5a dihydroprogesterone and 3a,5a-tetrahydroprogesterone (allopregnanolone), suggesting that the brain metabolizes PROG in a fashion different from adrenals and gonads. Just as in the adrenals, gonads, and placenta, the expression of the steroidogenic enzymes in the central and peripheral nervous systems is develop-mentally, regionally, and cell-specifically regulated, ensuring the regulated synthesis of specific neurosteroids.

Autonomic nervous system

The increased basal sympathetic tone may manifest as tachycardia and alteration of bladder function and bowel motility. Episodes of marked sympathetic overactivity occur, with increased vascular resistance, increased central venous pressure, increased cardiac output, hypertension, pallor, cyanosis of the digits, pyrexia, and sweating. These sympathetic crises are thought to be mediated by loss of spinal inhibition of the adrenal glands. Therefore epidural anesthesia may attenuate or eliminate them.

Location of the Autonomic Ganglia

The sympathetic ganglia consist of two chains of 22 seg-mentally arranged ganglia lateral to the vertebral column. The preganglionic fibers leave the spinal cord in adjacent ventral roots and enter neighboring ganglia, where they make synaptic connections with postgan-glionic neurons. Some preganglionic fibers pass through the vertebral ganglia without making synaptic connections and travel by way of splanchnic nerves to paired prevertebral ganglia in front of the vertebral column, where they make synaptic connections with postgan-glionic neurons. In addition, some sympathetic pregan-glionic fibers pass through the splanchnic nerves into the adrenal glands and make synaptic connections on the chromaffin cells of the adrenal medulla.

Adrenalectomy and hypophysectomy

Learning that the adrenal gland is a source of steroid production in postmenopausal women, surgical adrenalectomy as well as hypophy-sectomy (depriving ACTH) were considered treatment options for postmenopausal women (14, 15). At this time, the general belief was that postmenopausal estrogens together with androgens were synthesized and directly secreted by the adrenals later, it was discovered that circulating androgens, mainly of adrenal but with a potential small contribution of testosterone from the postmenopausal ovaries (16-18), were converted into estrogens in different tissue compartments by the aromatase enzyme (Fig. 1), Both treatment options revealed significant antitumor effects but at considerable morbidity and even mortality. This led to the subsequent invention of medical adrenalectomy in an attempt to achieve similar antitumor effects at the cost of lower toxicity. However, treatment with glucocorticoids in moderate doses (prednisone prednisolone 5-10 mg daily) was...


Little is known about the mechanisms regulating neurosteroid formation. Both cAMP and glucocorticosteroids have been shown to enhance PREG formation from 3H meva-lonate, precursor of cholesterol, in mixed glial cell cultures, but these effects might be related to an acceleration of cell differentiation in vitro (45). Cholesterol side-chain cleavage activity is regulated in the C6 glioma cell line by the mitochondrial benzodiazepine receptor, which is involved in intramitochondrial cholesterol transport, thereby increasing the substrate availability to P-450 as previously described for adrenals and gonads (46).


There is a close correlation between pantothenic acid tissue levels and function of the adrenal glands. The adrenals are, for example, important in responding to stress. Pantothenic acid is a part of the energy cycle and the production of acetyl-choline, a neurotransmitter. It is involved in cholesterol and hormone synthesis. The vitamin is widely available in almost all natural foods however, food processing destroys substantial amounts. Fifty percent of pantothenic acid is lost in the milling of grains and 37 in meat during cooking.


Certain essential oils have antiviral properties, act as expectorants for respiratory ailments, have sedative and antispasmodic qualities, and give support to the immune system. Some oils have an effect on the autonomic nervous system, moderating an overactive sympathetic system. In a clinical study, 80 of the participants reported positive improvement for symptoms affecting the nervous system including depression, tension, headache, fatigue, insomnia, and loss of appetite.6 Some oils have shown in studies to have an anti-inflammatory effect by stimulating the adrenal glands and releasing cortisone-like substances. Brain waves were shown to be altered on another group who experienced improved visual search tasks.


If we start with the P450s in Table 2, i.e., those P450s in families involved in well known physiological pathways, the most unique of these is P4507B. Unlike the other P450s in Table 2, it is predominantly expressed in the brain and neither its substrate nor its function is known. This P450 and was cloned from a rat hippocampal cDNA library in 1995 (19). By sequence comparison, it was found to be most similar to P4507A, the 7a hydroxylase of cholesterol, but it was different enough to be put into a new subfamily. It is not detectable in the adrenals or gonads. It is possible that because of the similarity to P4507a, cholesterol or one of its derivatives might be natural substrates. One question that arose immediately upon the cloning of P4507B was whether this represented the cDNA of 3 -diol hydroxylase. When the distribution of P450 7B mRNA in the rat brain was examined with Northern blot analysis, a high level of expression in the hippocampus and much lower levels in other brain...


Glucocorticoids occur naturally in the body as cortisone and hydrocortisone. These hormones are produced by a pair of organs called the adrenal glands, which are situated next to the kidneys. The adrenal glands are organized into two discrete tissue types, somewhat confusingly called the medulla and cortex. These have nothing to do with their namesakes in the brain. Cortisone and hydrocortisone are produced in the adrenal cortex in response to the release of a regulatory hormone called adrenocorticotrophic hormone (ACTH), which is manufactured in both the pituitary gland in the brain and the adrenal cortex. ACTH is naturally secreted in response to a variety of stress factors including fear, anxiety, pain, exercise, infection, and very low levels of blood glucose.

The XK Gene Family

Databank analysis demonstrates that the human XK gene belongs to a gene family with several different members 3, 24 . Sequence similarity searches identify a family of nine full-length human genes related to ced-8, as well as a series of eight Y chromosome-linked partial sequences. Sequence comparisons confirm that previously identified highly conserved motifs in ced-8 and XK are shared with the related genes. Several residues in these motifs are identical between ced-8 and other family members, but not conserved with XK 24 . Recently, two cDNAs, XPLAC and XTES, have been cloned. XPLAC, like XK, has three exons and is located on X-chromosome at q22.1, while XTES has four exons and is located at 22q11.1. Whereas XK is ubiquitously expressed, XPLAC is expressed predominantly in placenta and adrenal gland, and XTES is exclusively expressed in primate testis 3 .


In conclusion, one may suggest that a physico-chemical defence mechanism, which is based on the detergent action of bile acids, provide the body with a general defence, which is not limited to bacterial endotoxins, but is also effective against other agents (e.g., viruses) that possess lipoprotein or lipid structures. This novel mechanism may be added to the known defence mechanisms, which are based on bile acids produced in the liver and present in the enterohepatic circulation. It is interesting to note in this respect that bile acids are the most important products of cholesterol metabolism, which are reusable end products that affect the production of steroid hormones (by the adrenal gland and gonads). It is possible that bile acids play a role also in the pathophysiology of endocrine and reproductive abnormalities, which remains to be elucidated

Further Sugar Damage

What do these wide swings of insulin and glucose do to the body In a word, aging. Any biological system that is chronically run faster than it is designed to run will wear down more quickly, be diseased longer, and die sooner. The pancreas, testes, ovaries, adrenals, thyroid, and pituitary are all glands whose functions are intimately interrelated. Other lesser known glands are also involved as well. When the body is subjected to wide swings of insulin and glucose, these glands burn out. Eventually, the body loses its ability to deal with environmental stresses, including toxicity, as well as with the poor nutrition that makes the toxicity worse.


Ectopic meningiomas are exceedingly rare and likely arise from rests of arachnoid tissue trapped in ectopic locations during development. These must be distinguished from the equally rare extracranial metastases of malignant meningiomas that occur in less than 0.1 of all meningiomas. Primary cutaneous meningiomas are the most common and typically occur in the scalp of frontal and occipital regions. Other reported locations of primary ectopic meningiomas include paranasal sinuses, eyelids, parotid gland, temporalis muscle, temporal bone and zygoma, as well as some distant sites, such as the lungs, mediastinum and adrenal gland.


About half of all patients with major depression have a raised cortisol output, which tends to return to normal on recovery. It is most consistently associated with an 'endogenous' pattern of illness (Chapter 4.5.i3). While cortisol is always regarded as a 'stress' hormone, and is secreted in response to various types of acute stress, the stresses that commonly result in long-term hypercortisolaemia are poorly understood. The idea that there is a relatively specific link between chronic high cortisol levels and mood disorder is notably persistent. In major depression there is peripheral hypertrophy of the adrenal glands, measurable in MRI body scans, and an enhanced response to corticotropin. The MRI change, like the hypercortisolaemia itself, reverses on recovery. (29)

Host pathogenicity

An infected host may die from necrosis of the intestine and mesenteric lymph nodes before other organs are severely damaged (Dubey and Frenkel 1973), or focal necrosis may develop in many organs. The clinical picture is determined by damage to different organs, especially organs such as the eye, the heart, and the adrenals. Necrosis is caused by the intracellular growth of tachyzoites. Toxoplasma gondii does not produce a toxin.


Androgens, secreted by the female's adrenal cortex, have a concentration 10 times less than those in the male. The variation of the androgen levels in the plasma during the menstrual cycle is small and it is the free androgen level that must be taken into account. Androgens maintain the adult female pubic and axillary hair, clitoris, and probably labia and periurethral glans. The role of androgens in female sexuality is controversial and not clear cut. (38) Some propose that, as in the male, it is the major hormonal influence on the female libido. Removal of the adrenals has been shown to reduce desire and ability to reach orgasm. Excess androgens stimulates libido but in pharmacological not physiological doses. Such doses affect the structure and sensitivity of the clitoris (an androgen-sensitive tissue), so the effects on sexuality might not be brain mediated.


Activity was not affected, whereas cholesterol under the identical experimental conditions suppressed the activity of this enzyme by 53 .121 In rats fed or infused with phytosterols, HMG-CoA reductase activity was not decreased.122123 These findings indicate that the cholesterol-lowering action of phytosterols is not via suppressing endogenous cholesterol synthesis. Labeled sitosterol and campesterol were found in adrenal glands, ovary, and testis of animals, providing evidence that plant sterols follow similar metabolic pathways to that of cholesterol.74

Systemic effects

A decrease in oxygen delivery in the immediate postburn period coupled with increased cellular demands for oxygen can result in an oxygen debt. Simultaneously, a massive catecholamine release from both the adrenal gland and the autonomic nervous system contributes to profound metabolic sequelae. This catecholamine discharge, coupled with resuscitation-associated edema in the bowel mesentery, results in a generalized ileus associated with burns covering more than 20 per cent of the body surface area.

Laboratory tests

A complete blood cell count, coagulation and serum chemistries (creatinine, liver and pancreatic enzymes, lactate dehydrogenase, lactate, creatine phosphokinase, glucose, and electrolytes) should be drawn. Rapid serum potassium and glucose determination is crucial, as is blood gas analysis. The arterial blood gas should be analysed without temperature correction. Drug and or alcohol screening and thyroid or adrenal gland function tests are obtained as indicated. Blood, urine, and sputum cultures should be obtained if sepsis is suspected. Radiography, including CT scanning, is performed as indicated. A baseline ECG is obtained.

Cushings syndrome

Hypersecretion of cortisol by the adrenal gland can result in Cushing's syndrome. Cushing's syndrome can also be due to exogenous ACTH or glucocorticoid administration, or endogenous hyperproduction of these hormones. Because a physiological release of cortisol occurs during periods of stress or duress, it is not surprising to see elevations of serum cortisol during the courses of many psychiatric disorders, including major depressive disorder, alcoholism, anorexia nervosa, panic disorder, and psychoactive substance-withdrawal syndromes. The more common clinical signs and symptoms of Cushing's syndrome include fat redistribution, menstrual irregularities, dysphoria, thin skin, moon facies, increased appetite, sleep disturbances, hypertension, hypercholesterolaemia, hypertriglyceridaemia, poor concentration, impaired memory, euphoria, glucose intolerance, striae, and hirsutism. (73>

Endocrine changes

The placenta is an endocrine organ, secreting both steroid and polypeptide hormones. Some of the hormonal changes occurring during pregnancy have a specific function relating to preservation of the corpus luteum, placentation, protection and growth of the fetus, and parturition. Others are the consequences of physiological adaptive processes in different systems. Although total levels of both thyroxine and cortisol are increased secondary to rises in hepatic synthesis of thyroid-binding globulin and corticosteroid-binding globulin respectively, levels of free thyroxine are not substantially altered by pregnancy. However, levels of free urinary and serum cortisol are raised up to threefold since cortisol production rate is increased. Therefore it is possible that a cortisol level falling within the normal non-pregnant range is indicative of hypoadrenalism in pregnancy. The placenta secretes both corticotrophin-releasing hormone and ACTH.

Heart Attack

What happens mechanically at the time of death from a heart attack is ventricular fibrillation, an erratic heartbeat that interrupts delivery of oxygenated blood to the brain. The determining factor of whether the death of a portion of the heart muscle actually results in the whole heart expiring may depend on the condition of the autonomic nervous system that governs involuntary actions like breathing, digestion, and heartbeat. If the autonomic nervous system is in sympathetic mode, which has a contractility effect, as opposed to the parasympa-thetic, which is relaxing, fibrillation is more likely to happen. In some cases, death from heart attack is due to an artery spasm. Artery spasms occur when the sympathetic nervous system is dominant and the adrenals are overactive. Heart arrythmias or irregular heartbeats can be the result of an activated sympathetic system as well. Genetic predisposition can play a role in heart disease but no matter what condition the arteries are in, heart...

Stress and health

A range of behavioural and emotional responses are shown by individuals as they attempt to cope with stressful situations and these are accompanied by autonomic, neuroendocrine, and immunological changes. During stressful episodes, releasing factors from the brain cause the pituitary to release ACTH which gives rise to the release of corticosteroids from the cortex of the adrenal glands. In addition to producing a number of well-known changes associated with the mobilization of both short- and longer-term physical resources (e.g. release of adrenaline (epinephrine)or noradrenaline (norepinephrine), release of glucose, activation of endorphins encephalins, etc.), these steroids can also have effects on the immune system. Thus, fairly acute stressors, such as examinations, and more chronic stressors, such as caring for a dependent elderly relative, can lead to deleterious immunological changes with adverse effects on health. fy.1.,12,) For example, chronic stress has been found to slow...


Observed to be relatively abundant in liver, adipose tissue, and pancreatic islets, as expected, but also in heart, kidney, spleen, thymus, and stomach. Low levels were found in adrenal glands, small intestine, thyroid, and skeletal muscle. No expression was observed in testes, lung, large intestine, or brain ( 39).


'Neurotransmitter' is a term nowadays in use not only by neuroscientists but also by the lay person citing from the popular science columns. Yet both the concept and the term were nonexistent only a century ago. At that time it was thought that nerve-nerve and nerve-muscle communication is always electrical (synapse). The first to propose explicitly that a chemical substance, adrenaline, is liberated from the sympathetic nerve terminal to act upon its muscle target, was Elliott (1904). But the story actually starts earlier. The mere idea that a nerve may release a chemical substance for communicating with other cells was proposed by ou Bois-Reymond in 1877 (cited in Dale 1938). The first hints of evidence were provided by an English physician, George Oliver, who spent his leisure time inventing clinical instruments and testing them on his own family members (Dale 1948). One of these instruments was designed to measure the thickness of an artery under the skin. Oliver (how horrible)...

Steroid Biosynthesis

Although the adrenal cortex is primarily involved in the synthesis and secretion of corticosteroids, it is also capable of producing and secreting such steroid intermediates as progesterone, androgens, and estrogens. The adrenal gland synthesizes steroids from cholesterol, which is derived from plasma lipoproteins via the low-and high-density lipoprotein pathways. Additionally, cholesterol is enzymatically released extramitochondri-ally from cholesterol esters catalyzed by a cholesterol


Ketoconazole (Nizoral), an orally effective broad-spectrum antifungal agent (see Chapter 52), blocks hy-droxylating enzyme systems by interacting with cy-tochrome P450 at the heme iron site to inhibit steroid and or androgen synthesis in adrenals, gonads, liver, and kidney. The most sensitive site of action appears to be the C17-20 lyase reaction involved in the formation of sex steroids. This explains the greater suppressibility of testosterone production than with cortisol. Cholesterol side-chain cleavage and 11p 18-hydroxylase are secondary sites of inhibition.

Table 1413

Testosterone, with a basic structure as a steroid ring, is the natural endogenous androgen.97-99 Testosterone is synthesized primarily in the Leydig cells of the testes in males and by the ovaries and adrenal glands in females. Healthy adult men produce 3 to 10 mg d, yielding plasma concentrations ranging from 300 to 1000 J.g dl.93-95 Testosterone acts on the cell androgenic receptors found mainly in skin, muscle, and male sex glands. It has both androgenic or masculinizing properties and anabolic properties. Androgenic effects are present to some degree in all anabolic steroids. Androgenic affects include development of male sex glands, male hair growth pattern, increased libido, and assertiveness (Table 14.14). Most testosterone analogs or anabolic steroids have androgenic properties much lower than testosterone


A number of factors can influence oxytocin release and a most prominent inhibitory effect is delivered by acute stress. For example, oxytocin neurons are repressed by catecholamines, which are released from the adrenal gland in response to many types of stress reactions, including fright.

Subject Index

ACTH 120, 139, 144-148, 165, 173, 192, 194, 196, 233, 239, 258, 266-269, 271, 276, 315, 318-319, 359-360, 362, 370 adenohypophysis 246, 319 adenosine 12, 33, 100, 320-321, 325, 337 adenylate cyclase 10, 12, 53-54, 67-69, 102, 119, 129, 138, 145, 152, 155, 181, 192, 195, 202, 208, 212, 231, 244, 246, 268, 276, 311, 321-322, 329, 337, 349, 351-352, 359, 371 ADP 320-322, 370 adrenal cortex 146, 197, 268 adrenal gland 125, 144, 148, 218, 250, 269,

Liver Procurement

The heart and or lungs are removed first. This allows time for perfusion and topical cooling. Liver recovery begins with an incision of the pericardium surrounding the intrapericardiac inferior vena cava. The suprahepatic vena cava is freed completely. This requires an incision of the diaphragm over the esophageal hiatus. Care should be taken not to enter the esophagus. The right diaphragm is incised with a wide margin away from the liver. During this dissection, pulling the liver or the right kidney forcefully can cause tears in the liver capsule. The peritoneum overlying the infrahepatic vena cava and right kidney is incised. The right kidney is retracted laterally and caudally to allow the surgeon to encircle the inferior vena cava with index finger. The left renal vein is identified and the inferior vena cava is transected above the left renal vein. The right adrenal gland is divided leaving half of the gland with the liver and the other half with the right kidney. Using the right...

Anaplastic Carcinoma

Anaplastic Thyroid Carcinoma

Anaplastic or undifferentiated carcinoma accounts for 5 to 10 of all primary malignant tumors of the thyroid (192) but in many centres this is decreasing with earlier detection of disease. These tumors are rapidly growing, with massive local invasion that usually overshadows the early metastases, most frequently to lung, adrenals and bone (4,5). They are highly lethal with a 5 year survival rate of 7.1 (193) and a mean survival period of 6.2 to 7.2 months (193,194).

MRI Abdomen

Both adrenal glands are normal in position and size, and the adrenal crura are normally developed. The adrenal compartment is unremarkable. Adrenal glands Adrenal glands (variable) Splenic index DxWxL between 160 and 440 Adrenal glands (variable) Other visualized upper abdominal organs, especially the adrenal glands, show no abnormalities. Adrenal glands Adrenal Glands Both adrenal glands present normal size and position with normally developed crura. There is no evidence of a mass or circumscribed expansion. Both adrenal glands appear normal. Adrenal glands Paired Signal characteristics of normal adrenals (T1 slightly hypointense to liver T1 fat-saturated isointense T2 hypointense T2 fat-saturated hyperintense) 1 Adrenal glands (variable) T2-weighted axial image through the adrenal glands T2-weighted axial image through the adrenal glands


When the mind perceives a threat, whether real or imagined, the brain instantly and automatically evaluates the situation. Then the subconscious begins to prepare the body for a response. The sympathetic system causes the blood to flow to the muscles, the muscles and blood vessels constrict, and the body is flooded with hormones from the pituitary and adrenal glands. Heart rate increases and oxygen consumption accelerates. Production of digestive juices is reduced and blood sugar levels increase as the liver releases glucose into the bloodstream. This process becomes harmful when it remains a perpetual state with few periods of full relaxation or full release of the tension. After years pass, many illnesses can develop, including an artery spasm that can result in a heart attack.

HDL metabolism

Lcat Membrane Domain

A receptor that is a member of a large family of receptors known as scavenger receptors, because their role is generally to remove 'debris' by phagocytosis (especially in macrophages). This particular receptor is known as scavenger receptor (SR)-BI and is expressed in the liver and also in steroidogenic tissues (e.g. adrenal gland and ovary). 'Docking' of HDL particles with SR-BI is followed by off-loading of their cholesteryl ester content. The cholesteryl esters enter the cellular pool and may be hydrolysed by lysosomal hydrolases as shown for LDL-receptor mediated uptake (Box 9.3). This process is fundamentally different from the uptake of LDL particles by the LDL-receptor, however, and has been called 'selective lipid uptake'. The difference is that the particle itself is not internalised and the cholesterol-depleted particle leaves the receptor to re-enter the cycle of the HDL pathway.

Biogenic Amines

Norepinephrine and dopamine are the strongest inducers of breast carcinoma cell migration 11 , and norepinephrine stimulates the migration of human colon 12 and prostate carcinoma cells 11 as well. In athymic BALB c nude mice, nor-epinephrine enhances the development of lumbar lymph node metastases from prostate carcinoma cells injected in the thighs 13 . In combination with the above-mentioned fact, that noradrenergic nerve fibers are present in the lymph organs, i.e. spleen, thymus, bone marrow, and lymph nodes 2 , one might even argue that the localization of metastases can be driven by neurotransmitters. This view is supported by the clinical observation that certain tumors, such as the small cell lung carcinoma, frequently develop metastases in the relatively small, catecholamine-producing adrenal glands 14, 15 , and in the brain 16, 17 . Interestingly, in both the immune system and in tumor cells, the effects of norepinephrine are mediated via -adrenoceptors 18, 19 . Thus...


A loading dose of 70 mg kg magnesium sulfate followed by an infusion of 1 to 4 g h to keep serum levels between 2.5 and 4 mmol l reduces systemic vascular resistance, pulse rate, and to a small extent cardiac output. The release of epinephrine (adrenaline) from the adrenal gland and norepinephrine (noradrenaline) from