Identifying and Healing Adrenal Gland 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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Author: Jorden Immanuel
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The writer presents a well detailed summery of the major headings. As a professional in this field, I must say that the points shared in this ebook are precise.

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Adrenal Gland

The adrenal glands are paired structures situated above the kidneys that are approx 2-3 cm wide and 6 cm long and weigh approx 5 g. The glands consists of a yellow, outer cortex that constitutes approx 80 of the adrenal gland and a gray, inner medulla (1). The adrenal cortex consists of three distinct layers or zones of cells. The outermost layer, the zona glomerulosa, is the site of aldosterone synthesis, the principal mineralocorticoid produced by the human adrenal cortex, and corticosterone synthesis. The wider, middle zone is the zona fasciculata, and the innermost layer is the zona reticularis. The two inner zones of the adrenal cortex can be considered a single functional unit, where cortisol, along with some corticosterone, and dehydroepiandrosterone (DHEA) are synthesized. The glucocorticoids have widespread effects on carbohydrate and protein metabolism. Androgens secreted by the adrenal cortex pay a less important role than the androgens, which are secreted by the gonads.

Estrogen Receptors ERa and ER

Although estrogens are mainly produced locally by the ovaries, they exert systemic effects on selected target tissues. The action of the estrogens is mediated by two different estrogen receptors (ERs), ERa and ER 11 . ERa and ERjS are products of different genes and exhibit a tissue- and cell type-specific expression. The ERa is expressed primarily in the uterus, liver, kidney and heart, and sometimes it is co-expressed with the ER in mammary, thyroid and adrenal glands, in bone, and in the brain, where they can form functional heterodimers and where ER in many instances opposes the actions of ERa 11 . ERjS in contrast, is expressed specifically in the ovaries, in prostate, lung, in the gastrointestinal tract, bladder, and in the hematopoietic and central nervous system 11 .

Scientific Foundations

The adrenal glands are two small glands, each sitting on the top of a kidney. These glands have two parts an outer layer called the cortex and an inner region called the medulla. The adrenal cortex releases hormones directly into the blood. Once in the blood stream, these hormones travel to their target cells. The target cells have a special receptor that binds (attaches) to the specific hormone. This ensures that each hormone only communicates with specific cells from nutrients in the liver, thus providing fuel for cells when the body is under stress. When the stressful situation ends, adrenal hormone production returns to normal. The adrenal glands usually produce about 20 milligrams of Cortisol per day, mostly in the morning, but they can produce five times that much when needed. The control of corticosteroid production from the adrenal glands has interested scientists for quite some time. A disease resulting from a lack of circulating corticosteroids was known as early as the...

Tissue distribution and ontogenic development

In the liver and adrenal gland, the activity of EPHX1 was three times higher than that observed in the kidney and lung and could be observed as early as 8 weeks' gestation (Table 4). At 22 weeks, EPHX1 activity had increased to about half that observed in adult liver. EPHX2 is also expressed in the fetus, although fewer ontogenic studies have focused on this isoform. EPHX2 activity was demonstrated as early as 14 weeks in fetal liver with no change in activity occurring with time.25 Adult hepatic activity of EPHX2 was fivefold higher than that observed in the fetus. However, additional studies are needed to examine the change in activity between 30 weeks' gestation and 30 years of age. EPHX2 is also observed in extrahepatic fetal tissue, including the kidney, adrenal glands, intestine, and lungs, but developmental expression in these tissues was less evident.90

Adrenal Medulla Tissue Transplants

The adrenal medulla is the inner part of the adrenal gland, which is found just above the kidneys. The tissue contains fibroblasts, endothelial cells, smooth muscle cells, Schwann cells, neurons, and chromaffin cells (35). The chromaffin cells secrete a variety of factors and neurotransmitters, including dopamine. In general, this type of transplant is an autograft, where the host also serves as the tissue donor. This would normally eliminate the need for immunosuppression, but autologous adrenal transplants in the par-kinsonian primates indicate that immunorejection does occur.

The CRF hypothesis and stress

CRF is synthesized in the hypothalamus and elicits the release of adrenocorticotropic hormone (ACTH) from the pituitary. CRF was isolated from sheep hypothalamus and its structure as a 41-amino-acid peptide determined.96 The hypothalamic paraventricular nucleus (PVN) is the major region in the brain of CRF-containing cell bodies and through axonal projections to the capillaries of the median eminence can secrete CRF directly into the portal system where it acts at the pituitary to regulate ACTH secretion into the circulation. The principal role of ACTH is to stimulate the release of cortisol from the adrenal gland, thus completing the HPA axis, a primary component of the neuroendocrine response to stress. Similarly, projections from the PVN to the lower brainstem and spinal cord have been demonstrated to regulate autonomic function and help to further mediate the behavioral responses to stress. High densities of CRF-containing neurons are localized in particular to prefrontal,...

Investigating the pathogenesis of problematic hypoglycaemia

It is important to avoid carrying out hypoglycaemia studies on people with ischaemic heart disease, epilepsy, hypertension, untreated hypothyroidism, hypoadrenalism or unstable diabetic retinopathy. It is crucial not to carry out studies on women of childbearing age if radioisotopes or potentially teratogenic or fetotoxic drugs are to be used, because of the potential risk to any future fetus.

Rationale for the Use of Inhibitors of Releasing Hormones in Cancer Treatment

This process is responsible for producing up to 90 of circulating estradiol, depending on the phase of the menstrual cycle. The aromatisation of androgens by the adrenal glands is responsible for the synthesis of the remaining 10 estradiol in pre-menopausal women and for all estradiol in post-menopausal women (Fig. 17).

Hypoglycaemic stimuli for research Insulin tolerance test

Most experimental hypoglycaemia is induced by insulin. An intravenous insulin challenge, called the insulin tolerance or insulin stress test, was the first test used to determine the effect of hypoglycaemia (Dell'acqua 1951 Hanzlicek & Knobloch 1951). This method was used in early studies that identified the role of the adrenal gland in protective responses to hypoglycaemia (Vogt 1951 De Pergola & Campiello 1953) and has also been used in the past to induce hypoglycaemic seizures as a treatment for severe depression (Mueller et al. 1969) and as a stimulus for gastric acid secretion in the standard Hollander test assessing the completeness of vagotomy (Colin-Jones & Himsworth 1970). It is still used to determine pituitary reserve for growth hormone and cortisol release.

Synopsis Of The Novel

Mond at last bans the insubordinate Bernard and Helmholtz for causing instability. Then he explains the World State to John in a declaration of Huxley's core Brave New World ideology. Science, art, and religion were sacrificed for the common good. Science was first controlled during the Nine Years' War when anthrax bombs threatened the world. Now, when humans need to release residual anger and passion, chemically administered Violent Passion Surrogate stimulates the adrenals. New discoveries in pure science might be subversive and are outlawed. The high art of literature must be sacrificed for conformity. Old books like Shakespeare's tragedy Othello can cause people to feel self-conscious and unlearn new ways. Religion in a youthful and prosperous society, when people are safe, well, and not afraid to die, is unnecessary. God isn't compatible with machinery and scientific medicine and universal happiness. You must make your choice, he says. They live in a utopia where security and...

Putative New Natural Ghrelin Hormones and Companion Receptor Subtypes

Besides the GHRP ghrelin GHS type 1a receptor, the Merck group cloned another related GHS receptor designated type 1b in 1997. The type 1b receptor is a truncated version of the type 1a GHS receptor because only TM-1 through TM-5 domains are encoded. Its function is still unknown. Neither the GHRPs nor ghrelin bind to this receptor and the type 1a and 1b receptors are localised to separate chromosomes. When selective, sensitive hybridisation probes for the type 1a and 1b receptors were utilised, the mRNA distribution in normal human tissues demonstrates the truncated type 1b receptor is widely distributed while the type 1a GHRP ghrelin active receptor is much more restricted, i.e., predominantly in the pituitary gland but also in the thyroid gland, pancreas, spleen, myocardium and adrenal gland. In contrast to the distribution of the active type 1a receptor, the expression of the mRNA distribution of the ghrelin peptide is widespread in human tissues, which suggests that ghrelin may...

CASE 2 Hypertension And Hypokalemia Case Description

Given the strong family history of hypertension, young age of onset, and appearance of hypokalemia, his physician pursued testing for secondary causes of his hypertension. Twenty-four-hour urine collections for catecholamine and cortisol excretion were normal. Random plasma aldosterone (PA) and plasma renin activity (PRA) levels revealed values of 37.1 ng dL (normal 3.0-35.0 ng dL, normal salt diet) and < 0.1 ng mL h (normal upright value 0.4-8.8 ng mL h, normal salt diet), respectively. Given these data, a diagnosis of primary hyperaldosteronism was made. He was started on spironolactone 50 mg daily, but additionally required labetalol and losartan for blood pressure conrol. Later, his dose of spironolactone was increased to 200 mg daily. A CT scan with 5-mm slices of the adrenal glands showed no evidence of an adenoma, and was reported as normal. Given the patient's extensive family history of early-onset hypertension, it was thought he may suffer from glucocorticoid-remediable...

Meningococcus Meningitis

Infection with gram-negative Neisseria meningitidis has a virulent and fulminant variant with a high mortality (Fig. 6.2). The disease occurs sporadically or in epidemics. The primary infection, a nasopharyngitis, spreads to the brain via the bloodstream. The meningitis is associated with the Waterhouse-Friderichsen syndrome, which is characterized by petechiae and ecchymotic pur-puric lesions in the skin and hemorrhages in the visceral organs, chiefly the adrenals. Disseminated intravascular coagulopathy often complicates the clinical picture.

Pathology biology diagnosis and staging

Because of early dissemination, staging of patients with small-cell lung cancer is more extensive than for patients with NSCLC. It is important to rule out distant metastasis because it will change the role of thoracic radiation in the treatment of these patients. Staging should include a complete history and physical examination, CAT scans of chest and upper abdomen to include the liver and adrenal glands, brain MRI scan, bone scan, complete blood count, and a possible bone marrow aspiration and biopsy.

Neuroendocrine Tumors

Neuroendocrine tumours (NET) constitute a heterogeneous group of neoplasms that originate from endocrine glands, such as the pituitary, parathyroids, and adrenals, as well as endocrine islets within glandular tissue (thyroid or pancreatic) and cells dispersed between exocrine cells, such as the endocrine cells of the digestive and respiratory tracts 31 . NET can be divided into four groups (a) carcinoid tumours, (b) islet cell tumours, (c) chromaffin cell tumours (PHs and paragangliomas), and (d) medullary thyroid carcinoma (MTC).

Use in Prevention and Therapy

Injury, surgery, or chronic illness often leads to rapid and destructive breakdown of body protein. Supplemental arginine reduces protein catabolism and helps maintain protein stores.8 9 In situations of acute stress ar-ginine enhances the release of the stress hormones norepinephrine and epinephrine from the adrenal gland.

Congenital Adrenal Hyperplasia

In CAH, the adrenal glands themselves increase in size because of hyper-plasia of the steroid-producing adrenal cortex. This is because the level of cortisone and hydrocortisone produced by the adrenal gland controls normal pituitary production of ACTH through a negative-feedback mechanism. In variants of congenital adrenal hyperplasia, cortisone production is partially or completely blocked, prompting the pituitary to produce more ACTH in an attempt to increase cortisone production. This continues until the adrenal The total cortisol level in a 24-h urine represents the integrated or mean concentration of free cortisol in plasma over this 24-h period and provides an excellent diagnostic sensitivity and specificity for the detection of the increased secretion of cortisol by the adrenal glands (Cushing's syndrome) (14). In contrast, total serum cortisol levels are not always an accurate measure of an overactive adrenocorticoid function and can be elevated in pregnancy, obesity,...

Natriuretic Peptide ReceptorC

NPR-C, or clearance receptor, is structurally distinct from NPR-A and NPR-B. Similar to NPR-A and NPR-B, NPR-C has a large extracellular domain and a membrane-spanning segment. The extracellular domain shares approx 30 primary structure homology with NPR-A and NPR-B. In contrast to the two other receptors, NPR-C is devoid of guanylyl cyclase activity, and the cytoplasmic domain contains only a 37 amino acid tail at the C-terminus having no sequence homology with any known receptor. The truncated intracellular domain and the absence ofguanylyl cyclase activity suggest that NPR-C may function by removing natriuretic peptides from the extracellular compartment (93). Some evidence indicates that NPR-C may also have a signaling function by inhibiting adenylyl cyclase through a Gi-dependent mechanism (94), but a physiological role beyond its function as a clearance receptor remains to be demonstrated in vivo (95). NPR-C is the most abundantly distributed natriuretic peptide receptor and has...

Modulation of Pain by the Hypothalamic PituitaryAdrenal Axis

The hypothalamus is sited at the base of the brain around the third ventricle and above the pituitary stalk, which leads down to the pituitary itself, carrying the hypophyseal portal blood supply. It contains vital centers for functions including appetite, thirst, thermal regulation, and the sleep cycle, and acts as an integrator of many neuroendocrine inputs to control the release of pituitary hormone-releasing factors. Amongst other important influences, it plays a role in the circadian rhythm, menstrual cycle, and responses to stress, exercise, and mood. The pituitary gland is located in the sella turcica at the base of the brain and is around 1 cm in diameter and between 0.5 and 1 g in weight. CRH produced in the hypothalamus induces the release of adrenocorticotropin (ACTH) from specialized cells in the anterior pituitary. This in turn stimulates the release of cortisol from cells in the zona fasciculata and reticularis of the adrenal glands. Figure 4 (See color insert) The...

Zellwegers Disease or Cerebrohepatorenal Syndrome

The cerebral pathology is distinguished by developmental abnormalities, such as disorders of neuronal migration pachygyria and microgyria along the Sylvian fissures, heterotopias of the Purkinje cells, and anomalous dentate and olivary nuclei. Other changes are variable neuronal losses, diminution and or breakdown of myelin, lipid deposits within macrophages, and degeneration of the optic nerves. Common visceral changes include liver fibrosis, often progressing to cirrhosis kidney cysts and lipid-containing striated cortical cells in the adrenals.

Central Tolerance in T Cells

Self proteins are processed and presented in association with MHC molecules on thymic antigen-presenting cells (APCs). The antigens that are present in the thymus include many circulating and cell-associated proteins that are widely distributed in tissues. The thymus also has an unusual mechanism for expressing protein antigens that are typically present only in certain peripheral tissues, so that immature T cells specific for these antigens can be deleted from the developing T cell repertoire. Some of these peripheral tissue antigens are expressed in thymic medullary epithelial cells under the control of the autoimmune regulator (AIRE) protein. Mutations in the AIRE gene are the cause of a multiorgan autoimmune disease called the autoimmune polyendocrine syndrome (APS). This group of diseases is characterized by antibody-and lymphocyte-mediated injury to multiple endocrine organs, including the parathyroids, adrenals, and pancreatic islets. A mouse model of APS has been developed by...

Adrenoleukodystrophies ALDs

Adrenoleukodystrophies (ALDs) (described in detail in section on peroxisomal diseases) are characterized by a failure of degradation of saturated very long-chain fatty acids (VLCFAs), which then accumulate in the cerebral white matter, adrenals, and practically all tissues. Neonatal ALD, is autosomal recessive and results from a disorder of peroxisomal biogenesis. Childhood, juvenile, and adult ALDs are X-linked recessive and result from single-enzyme defects. The pathology, common to all forms, is distinguished by lymphocytic perivascular infiltrations in the demyelinated areas (Fig. 9.10).

Rsk Reduction in Women with Inherited Predisposition to Breast cancer

Affected patients have a 50 risk of developing cancer by age 35 years and a 90 lifetime risk. The syndrome is characterized by pediatric bone or soft tissue sarcoma, early-onset breast cancer, and other cancers including those affecting the brain, lung, and adrenals, and leukemia. Cowden's syndrome is caused by a mutation in the PTEN gene on chromosome 10 84 . Affected patients have multiple hamartomas and an increased risk of developing breast or thyroid carcinoma at a young age.

Feedforward Control in Muscle Cells

In fact, muscles can begin to break down glycogen even before the message goes out from the brain to tell them to contract. When the brain realizes that we are in a dangerous situation and might be going to have to run, it causes the release of the hormone adrenaline from the adrenal glands above the kidneys. Adrenaline binds to an integral membrane protein of the skeletal muscle cells called the j-adrenergic receptor. This causes the production of the intracellular messenger cyclic AMP (cAMP) within the cytosol of the muscle cell. This topic is dealt with in more detail in Chapter 16. cAMP then activates cAMP-dependent protein kinase, which is given the short name of protein kinase A (Fig. 13.15). Glycogen phosphorylase kinase, the enzyme that phosphorylates glycogen phosphorylase, is itself phosphorylated by protein kinase A, and is then active even when cytosolic calcium is low.

Pineal Gland and Cancer

From an endocrinological view, these apparently contradictory finding could be explained if the cancer-induced changes in the circadian pattern of melatonin availability were manifested over a period of time > 24 h, i.e. just as different patterns of cortisol incretion are characteristic of different adrenal-gland diseases.

The Renin AngiotensinAldosterone System

Aldosterone plays a crucial pathophysiological role in CHF (20). It is a steroid hormone synthesized from cholesterol in the mitochondria of the zona glomerulosa of the adrenal glands' cortex. Recent research demonstrated extraadrenal sites of aldosterone production, such as in cardiovascular tissue (see above). Adrenal glands do not store aldosterone but are capable of rapidly synthesizing it. Angiotensin II is the most important stimulus to aldosterone synthesis. Renin converts angiotensinogen, which is formed mainly in the liver and to a lesser extent in the kidneys and vascular endothelium, into angiotensin I. ACE is the major pathway that converts angiotensin I into angiotensin II. As a negative feedback, aldosterone and angiotensin II inhibit renin release. Apart from aldosterone secretion angiotensin II stimulates VP release and norepinephrine release. It is also a potent vasoconstrictor.

Sex Differences That Arise During Development

The hypothalamus, pituitary gland, and adrenal glands of both males and females produce the same hormones in similar amounts it is the hormones secreted by the ovaries and testes that determine biological sex differences. Once a fetus develops either testes or ovaries they produce hormones that influence the development of other structures involved in reproduction.

The Kidneys As The Main Effectors Of Sodium And Water Retention In

The renal excretion of sodium and water normally parallels sodium and water intake, so that an increase in intravascular fluid volume is associated with increased renal sodium and water excretion. In CHF sodium and water are paradoxically retained. From 1940 through 1960 HF was thought to result primarily from renal hypoperfusion, and also in the current HF model the kidneys are the main effectors of sodium and water retention in CHF (11,27). When, irrespective of the CHF etiology, cardiac output or effective circulating volume falls below physiologically acceptable limits, extrarenal and renal baroreceptors sense arterial underfilling (Fig. 2), which sets in motion a vicious cycle through a continuous stimulation of the RAAS. Arterial underfilling triggers the release of catecholamines, angiotensin II, endothelin, and VP. Subsequently, renal vascular resistance rises and renal plasma flow is reduced relatively more than the glomerular filtration rate, which leads to an increase in...

Differences in Muscle Mass

Testosterone released by the testes at puberty results in the increased size of muscle fibers, long cells that contract when stimulated by nerve impulses. Testosterone also increases the total amount of muscle on the body, or muscle mass, because it promotes retention of the dietary nitrogen used to synthesize muscle proteins. Males have more testosterone than females, although the ovaries and adrenal glands do release small quantities of this hormone, and the difference in muscle mass accounts for an overall difference in strength between males and females. In sports that require brute strength, such as football, men have an advantage, but in sports like baseball, where success depends more on agility and hand-eye coordination, sex differences are reduced.

Adenosine A Receptor Agonists

The endogenous nucleoside adenosine exerts a variety of physiological effects via interactions with a family of G protein-coupled receptors consisting of four subtypes the adenosine A1, A2A, A2B, and A3 receptors.49 The A1 receptor is the most comprehensively studied adenosine receptor subtype and has been cloned from a number of species, including humans. A1 receptors are believed to act mainly via the Gi o family of G proteins and are widely expressed in the brain, spinal cord and a variety of peripheral tissues such as adipose tissue, heart, eye, adrenal gland, liver, kidney, salivary glands, and GI tract.49 Despite this widespread distribution, A1 knockout mice develop normally and display relatively subtle differences compared to wild-type animals, suggesting that adenosine A1 receptors are particularly important under pathophysiological conditions.50

Fibroblast Growth Factor

Originally, two FGF-like polypeptides were purified to homogeneity and characterized 247 the FGF from bovine pituitary, called basic FGF, and an acidic FGF from bovine brain. Basic FGF has also been isolated from a variety of other tissues, including adrenal gland, corpus luteum, retina, and kidney. There is significant amino acid sequence homology between the two polypeptides, and they are potent mitogens for diverse cell types including capillary endo-thelial, vascular smooth muscle, adrenocortical, bone, and ovarian granulosa cells. There is significant sequence homology among these receptors and overlap in their binding specificity for various FGFs. For instance, one isoform of FGFR1 binds FGF1 and FGF2 with slightly different affinities. An isoform of FGFR2 binds FGF1, -2, and -4 but not FGF5 or -7, whereas an FGFR2 splice variant binds FGF1 and -7, but not FGF2. FGFR3 can bind FGF1, -2, -4, and -5. FGFR4 binds FGF1 with high affinity and FGF4 and FGF5 with 10fold lower affinity....

CASE 1 A Rapidly Expanding Adrenal Mass Case Description

A 43-yr-old male initially presented to his primary care physician with the complaint of 3 d of right-sided abdominal pain. The pain was dull, located diffusely in the right upper quadrant of his abdomen and flank, and at times penetrated to the back. He denied any relation of the pain to food intake. In addition, he denied any jaundice, nausea, vomiting, fevers, or chills. His exam was unremarkable with the exception of mild right upper quadrant abdominal pain with moderate palpation. His physician was concerned with the possibility of gall bladder pathology, and pursued an abdominal ultrasound of the right upper quadrant. The ultrasound revealed no evidence of biliary disease, but an incidental finding of a right adrenal mass, measuring approximately 2 cm, was noted (see Fig. 1). No further testing was performed, and the patient's pain resolved without therapy. Approximately 3 yr later, the patient again presented with pain located in his right upper abdomen, similar to his previous...

CASE 1 Cushings Disease Difficulties In Diagnosis Case Description

Computed tomography (CT) of the abdomen showed a 4-cm mass in the right adrenal gland and the left adrenal gland appeared normal. A cystic area of 2 cm was noted on the Another late-night salivary cortisol level was 4.9 nmol L (0.3-3.6) and a dexametha-sone corticotropin releasing hormone (CRH) test was performed. The results are shown in Table 1. After these studies, the pituitary neurosurgeon agreed to operate on this woman. Transsphenoidal surgery demonstrated a 2-mm left corticotroph microadenoma, which was successfully removed and was followed promptly by secondary adrenal insufficiency. Within 24 mo, her pituitary-adrenal axis recovered. Subsequent CT of the adrenals showed regression of the 4-cm adrenal nodule. The patient lost 60 lbs and is very pleased with her clinical outcome.

Development Of Ectodermderived Organs

The neural crest is an embryonic structure derived from the ectoderm. It contains stem cells that can differentiate into a number of specified cell types and tissues. These include the peripheral ganglionic neurons and glial cells, Schwann cells, sympathetic and parasympathetic neurons, medulla of the adrenal gland, epidermal pigment cells, facial bones and cartilages, corneal endothelial cells, tooth papillae, connective tissue cells and smooth muscle cells in the aortic arch, and connective tissue cells in the salivary and thyroid glands. Since these cells and structures are distributed through the entire body, the neural crest cells must migrate from the ectodermal neural crest to the periphery for a long distance. The control of the migration pattern and destination of neural crest cells as well as the specification and differentiation of these cells are major topics of developmental research. Adrenal gland cells Adrenal gland cells Migration of Neural Crest...

Ketoconazole and Low Dose Prednisone

These observations led us to the hypothesis that ketoconazole administration on a long-term basis might slow the progression of renal failure. One problem with this concept is the well-known escape phenomenon When cortisol production is inhibited, adrenocorticotrophic hormone (ACTH), derived from the pituitary gland, increases and stimulates the adrenal gland to produce more cortisol. We have found that this escape can be prevented by administering a low dose (2.5 mg per day) of prednisone (a synthetic glucocorticoid) at the same time. ACTH levels do not rise, and the block in cortisol synthesis persists.

Tissue distribution

Early studies on P450 enzymes focused on the liver as the main drug-detoxifying organ and the adrenal gland for the metabolism of endogenous substrates, but it was soon recognized that other organs, notably those that serve as portals of entry to the body, such as the respiratory and the gastrointestinal tracts, also express P450s and other biotransformation enzymes. Each organ or tissue has its own profile of P450 enzymes that will determine the sensitivity of that tissue to a xenobiotic. It should be noted that most extrahepatic P450 enzymes are also present in the liver, often at a higher concentration, but can be regulated differently in different tissues, leading to altered xenobiotic exposures. Table 3 summarizes the tissue distribution of P450 enzymes that are commonly detected at either the mRNA (or, less commonly, the protein) level in various human organs.

Case Description

A 24 h collection for urinary catecholamines, vanillylmandelic acid, and metanephrines revealed an epinephrine level of 115.8 g (normal < 20), norepinephrine level of 180.6 g (normal < 80), dopamine level of 187.6 g (normal 88-420), vanillylmandelic acid level of 15.0 mg (normal 2-10), and metanephrine level of 1.6 g (normal 44-300). MRI showed a right adrenal mass with a characteristic high signal intensity on T2 weighted images (see Fig. 3). Meta-iodobenzylguanidine (MIBG) scintigraphy localized uptake in the right adrenal gland. These findings were all compatible with a diagnosis of pheo-chromocytoma.

Staging

All patients with esophageal cancer should be staged with computed tomography (CT) scans of the chest and abdomen. These can be used to identify bulky disease invading mediastinal soft tissue (T4). CT scanning can also identify those patients with distant disease to lung, liver, or adrenal glands who would then not be considered candidates for aggressive therapies but rather should focus primarily on palliative measures of symptom relief. Unfortunately, CT scans are unable to differentiate between T1-3 diseases. Moreover, lymph node metastasis and length of tumor involvement are missed in almost half the cases. Endoscopic ultrasound can determine T status with almost 80-90 accuracy (6-8). Although it is able to identify lymph nodes, it is difficult to distinguish benign from malignant nodes without tissue confirmation. With the addition oftransesophageal lymph node biopsy to endoscopic ultrasound, regional lymph node status is correctly diagnosed in almost 90 of patients (9)....

Wolmans Disease

Wolman's disease, a rare autosomal disorder of infants, is caused by a deficiency of the lysosomal enzyme acid lipase. As a result, triglycerides and cholesteryl-esters accumulate in the visceral organs, lymph nodes, bone marrow, and adrenals, which often show cortical calcifications. The brain shows lipid-containing foamy cells in the choroid plexus and leptomeninges. Death occurs in the first year of life. A milder form of the disease affects adults and presents with hepatomegaly, premature atherosclerosis, and hyperlipoproteinemia.

The Endocrine System

Adrenal glands Figure 12.1 Endocrine organs involved in the production of sex differences. There are many organs in the endocrine system. Those involved in the production of sex differences include the hypothalamus and pituitary gland of the brain, the adrenal glands that sit on the kidneys, the testes in males, and the ovaries in females. Many organs are involved in the endocrine system. Five of these organs are involved in the production of biological sex differences the hypothalamus, the pituitary gland, the adrenal glands, the ovaries, and the testes (Figure 12.1). Adrenal Glands An adrenal gland sits atop each kidney. These glands secrete the hormone adrenaline in response to stress or excitement, but they also secrete androgens, masculinizing hormones such as testosterone, as well as estrogens, which are feminizing hormones. Because estrogen and testosterone are responsible for many of the anatomical sex differences in males and females, these hormones are called sex hormones....

Cyp2c Cyp2j

The RAS contributes to the development and maintenance of hypertension and mediates renal injury by inducing systemic and glomerular hypertension. Synthesis of angiotensin II (AT-II) depends on the release of renin, primarily by juxtaglomerular cells in the kidney (Figure 5). The release of renin is regulated by the hydrostatic pressure sensed at the glomerular afferent arterioles, AT-II levels, and the quantity of sodium delivered to the macula densa. Plasma potassium, atrial natriuretic peptide, and endothelin levels also affect renin synthesis and release. Renin acts to cleave the liver angiotensinogen to angiotensin I (AT-I). ACE then converts AT-I to AT-II. This proteolytic enzyme is found in the endothelial cells of the lung, vascular endothelium, and cell membranes of the kidneys, heart, and brain. ACE also degrades vasodilator bradykinin to inactive fragments. Non-renin and non-ACE pathways also exist in the body allowing the production of AT-II either directly from...

Multiple Messengers

Many cells use more than one intracellular messenger at once. Skeletal muscle cells are a good example (Fig. 16.4). In the excitement before a race, the runner's adrenal glands release adrenaline into the blood. This binds to a receptor on skeletal muscle cells called the j-adrenergic receptor. The complex of adrenaline plus j-adrenergic receptor can now activate Gs and hence adenylate cyclase. This in turn generates cAMP, which activates cAMP-dependent protein kinase. This enzyme, which is given the short name of protein kinase A, phosphorylates glycogen phosphorylase kinase and turns on the latter enzyme even when cytosolic calcium is low (see Fig. 13.15 on page 305). The end result is that even before the runner begins to run, the muscles break down glycogen and make the glucose-6-phosphate (page 288) they will need once the race begins.

Active form

The natriuretic peptides incite their action through binding to high-affinity receptors mainly on endothelial cells, vascular smooth muscle cells, and other target cells. Three distinct natriuretic peptide receptors (NPRs) have been identified in mammalian tissues NPR-A, -B, and -C (28). NPR-A and -B are structurally similar, with a 44 homology in the ligand-binding domain (29,30). A single membrane-spanning portion bridges the intracellular and extracellular segments of these receptors. Both types of receptors utilize a cGMP signaling cascade (28). NPR-B is mostly found in the brain, whereas NPR-A is more commonly located in large blood vessels (28). Both receptor types are also found in the adrenal glands and kidneys. NPR-A binds preferentially to ANP, but also binds to BNP. On the other hand, CNP is the natural ligand for B receptors (28).