Adrenal Fatigue and Exercise
Sometimes hypothyroidism occurs because of a pituitary gland disorder that may interfere with the production of thyroid stimulating hormone (TSH). This is fairly unusual, however. Tumors or cysts on the pituitary gland can also interfere with production of hormones from the gonads and the adrenal glands.
The classic abbreviation experiments compare the micro-behavioral and internal physiological phenomena that appear when a subject is asked to imagine or think about X-ing against what happens during an actual performance of X. In most cases, it transpires that the phenomena that occur during thinking are, basically, abbreviations of the overt movements and physiological phenomena that would be occurring were the action in question being fully and or actually performed. For example, if I am angry, although I may remain motionless, the program of physiological events going on in my body will be a miniature version of the program that would be occurring were I performing some overt aggressive act. If I don't actually make a fist, at least the relevant hand muscles will tense, say, and my adrenal gland will become active. Or, if I am thinking about making a bookcase, I will likely make tiny eye movements consistent with visually inspecting a bookcase, my larynx may exhibit slight muscular
There is some specificity of the effects on BDNF as a function of both anatomical area involved and specific type of neurotrophic factor. Thus, although stress decreases BDNF in the hippocampus, it increases NT-3, and the effects on BDNF are in the opposite direction in the hypothalamic-pituitary-adrenal axis, which hypothetically could contribute to the increased size of the pituitary and adrenal glands in patients with major depression.
Epinephrine Epinephrine, (11.1.2), is obtained from the adrenal glands tissue of livestock 1,2 as well as in a synthetic manner. Epinephrine is synthesized from reaction of which with excess of methylamine gives w-methylamino-3,4-dihydroxyacetophenone (11.1.1). Reduction of this using hydrogen over Raney nickel, or action of aluminum amalgam, or electrolytic reduction gives d,l-epinephrine (11.1.2) 3-9 , which is separated into isomers using (+) tartaric acid 10 .
In humans there is only a single drug-transporting Pgp (MDR1 Pgp), whereas two Pgps are present in mice mdr1a (also called mdr3) Pgp and mdr1b (also called mdr1) Pgp (13). Presumably, the two Pgps in mice jointly fulfill the same function as the single MDR1 Pgp in man (14). The distribution of mdr1a Pgp and mdr1b Pgp in mice is organ specific (15), with mdr1a being the exclusive Pgp at the blood-brain barrier (BBB), in the intestinal mucosa, and at the blood-testis barrier, whereas mdr1b is the only Pgp detected at the blood-placenta and blood-ovary barriers, and in the cortex of the adrenal glands. Both Pgps are expressed in the kidney and the liver. Three strains of knockout mice mdrla ( ) mice, mdrlb ( ) mice, mdrla lb ( ) mice were generated by homozygous disruption of the mdrla or mdrlb gene or both. Under laboratory conditions, all three strains of knockout mice showed normal life expectancy, were fertile, and yielded no abnormal histological or laboratory chemistry findings...
Previously considered a specific marker of depressive illness. It is now recognized as an abnormality in only some subsets of depressed patients, notably psychotic depressives. Also reported is blunted adrenocorticotrophic hormone (ACTH) response to exogenous CRH. More sensitive to detect HPA dysregulation is the combined use of the DST and the CRH stimulation test. In the setting of an abnormal HPA axis test, clinical response appears to best correlate with normalization of the neuroendocrine abnormality. Elevated plasma cortisol following dexamethasone (DEX) predicts a protracted clinical course. The combined DEX CRH test appears to be a useful predictor of increased relapse risk. Recent reports of alterations in cortisol regulation in women with a history of early life trauma or abuse further suggest that HPA axis dysregulation may be an important marker of vulnerability to various types of affective disorders in later life, paralleling studies in rodents and primates (Heim et al.,...
Rarely, thyroid nodules in children turn out to be medullary thyroid cancers, a type of cancer we discuss in Chapter 9. More often, a family is already known to have at least one member diagnosed with medullary thyroid cancer (called an index patient), and the child's blood tests have shown that he or she has a mutation in the RET proto-oncogene responsible for causing this cancer. In this case, it takes only one parent with the mutation to pass it on to a child (called an autosomal dominant mutation). Furthermore, the likelihood that the mutation will cause cancer (known as penetrance) is nearly 100 percent. That means that if an individual has this mutation he or she is expected to develop this cancer at some time in his or her life. Usually, the blood relatives of the index patient should have their blood tested to see if they also have this specific gene mutation. Children in the family should be tested as early as possible. Should these tests show the presence of this mutation,...
There are currently no empirically validated treatments for HSDD. Sex therapy techniques generally consist of 15 to 45 sessions of cognitive therapy aimed at restructuring thoughts or beliefs that may adversely impact sexual desire (e.g., women should not initiate sexual activities, sex is dirty ) and to address negative underlying relationship issues. Behavioral approaches are utilized to teach patients to express intimacy and affection in both nonsexual (e.g., holding hands, hugging) and sexual ways, to incorporate new techniques into their sexual repertoire that may enhance their sexual pleasure, and to increase sexual communication. Testosterone is effective in restoring sexual desire in women with abnormally low testosterone levels (e.g., secondary to removal of the adrenal glands, bilateral removal of the ovaries, menopause).
This tumour stains positively with NCAM (neural cell adhesion molecule), synaptophysin and chromogranin. Lymphovascular invasion occurs early and distant metastases are common. These are seen in bone marrow, liver, kidney, adrenals, cerebrum, cerebellum, meninges, regional and cervical lymph nodes. After chemotherapy, recurrent tumour may be predominantly squamous or adenocarcinoma.
Sometimes, deficiency of the adrenal gland can cause an insidious and gradually severe fatigue. There are two tests that can be done to check for this. The simplest test is called a cosyntropin (Cortrosyn) stimulation test. Cosyntropin is a drug that is similar to ACTH (adrenocorticotropic hormone), a hormone made by the pituitary gland to stimulate the adrenal gland, much like TSH stimulates the thyroid gland. To do this test, your physician obtains a blood test for cortisol, then gives you an injection of cosyntropin. Your cortisol level is checked after thirty minutes, and then after another thirty minutes (an hour in total). Normal adrenal glands will be able to produce a cortisol level greater than 20 after the cosyntropin injection. If the cortisol level does not rise sufficiently, then it may be necessary to take cortisol replacement therapy for life. Three different steroid drugs can be used for cortisol replacement therapy, the two best being hydrocortisone and cortisone...
Hepatocellular carcinomas have an arterial blood supply but both portal and hepatic veins proliferate alongside, resulting in arterio-venous communications. Consequently, intra- and extrahepatic spread can take place in all directions, commonly to all parts of the liver, via the hepatic veins to the inferior vena cava and the right atrium of the heart and to the stomach and the oesophagus. This vascular spread is characteristic of hepatocellular carcinoma and is always seen in advanced cases at autopsy (Figure 3). Lymphatic spread to portal lymph nodes and beyond occurs in about one-third of cases. Involvement of major bile ducts and dissemination within the peritoneal cavity are much less common. Distant metastases are usually found in the lungs, adrenals, pancreas, kidney, ovary and bone.
Increased thyroid hormone increases the rates of secretion of most other endocrine glands, but it also increases the need of the tissues for the hormones. For instance, increased thy-roxine secretion increases the rate of glucose metabolism everywhere in the body and therefore causes a corresponding need for increased insulin secretion by the pancreas. Also, thyroid hormone increases many metabolic activities related to bone formation and, as a consequence, increases the need for parathyroid hormone. Thyroid hormone also increases the rate at which adrenal glucocorticoids are inactivated by the liver. This leads to feedback increase in adrenocorti-cotropic hormone production by the anterior pituitary and, therefore, increased rate of glucocorticoid secretion by the adrenal glands.
Cortisol decreases the number of eosinophils and lymphocytes in the blood this effect begins within a few minutes after the injection of cortisol and becomes marked within a few hours. Indeed, a finding of lym-phocytopenia or eosinopenia is an important diagnostic criterion for overproduction of cortisol by the adrenal gland. Cortisol increases the production of red blood cells by mechanisms that are unclear. When excess cortisol is secreted by the adrenal glands, polycythemia often results, and conversely, when the adrenal glands secrete no cortisol, anemia often results.
Effect of Fetal Hormones on the Uterus. The fetus's pituitary gland secretes increasing quantities of oxytocin, which might play a role in exciting the uterus. Also, the fetus's adrenal glands secrete large quantities of cortisol, another possible uterine stimulant. In addition, the fetal membranes release prostaglandins in high concentration at the time of labor. These, too, can increase the intensity of uterine contractions.
The combination of an unrelenting headache (+ - low grade fever) with malaise and anorexia and a CSF lymphocytic pleocytosis with a mild decrease in the glucose concentration is suggestive of tuberculous meningitis. The initiation of therapy should not await bacteriological proof of tubercle bacilli by smear or culture. The development of hydrocephalus and the clinical scenario just described is additional strong evidence for tuberculous meningitis. The absence of radiographical evidence of pulmonary tuberculosis and or a negative tuberculin skin test does not exclude the possibility of tuberculous meningitis. The classic Ghon complex refers to Anton Ghon's observation from autopsy specimens that the primary lesion of tuberculosis is in the lung with secondary infection in the tracheobronchial lymph nodes.y In addition to the primary complex, chest radiographic abnormalities suggestive of pulmonary tuberculosis are hilar adenopathy, a miliary pattern, upper lobe...
By contrast, the effects of sodium ion concentration per se and of ACTH in controlling aldosterone secretion are usually minor. Nevertheless, a 10 to 20 per cent decrease in extracellular fluid sodium ion concentration, which occurs on rare occasions, can perhaps double aldosterone secretion. In the case of ACTH, if there is even a small amount of ACTH secreted by the anterior pituitary gland, it is usually enough to permit the adrenal glands to secrete whatever amount of aldosterone is required, but total absence of ACTH can significantly reduce aldosterone secretion.
There is much chemical cross-talk among the neurons on the hypothalamus, and together, these centers coordinate the processes that control eating behavior and the perception of satiety. These nuclei of the hypothalamus also influence the secretion of several hormones that are important in regulating energy balance and metabolism, including those from the thyroid and adrenal glands, as well as the pancreatic islet cells.
The two adrenal glands, each of which weighs about 4 grams, lie at the superior poles of the two kidneys. As shown in Figure 77-1, each gland is composed of two distinct parts, the adrenal medulla and the adrenal cortex. The adrenal medulla, the central 20 per cent of the gland, is functionally related to the sympathetic nervous system it secretes the hormones epinephrine and norepinephrine in response to sympathetic stimulation. In turn, these hormones cause almost the same effects as direct stimulation of the sympathetic nerves in all parts of the body. These hormones and their effects are discussed in detail in Chapter 60 in relation to the sympathetic nervous system.
The zona glomerulosa, a thin layer of cells that lies just underneath the capsule, constitutes about 15 per cent of the adrenal cortex. These cells are the only ones in the adrenal gland capable of secreting significant amounts of aldosterone because they contain the enzyme aldosterone synthase, which is necessary for synthesis of aldosterone. The secretion of these cells is controlled mainly by the extracellular fluid concentrations of angiotensin II and potassium, both of which stimulate aldosterone secretion. In addition to aldosterone and cortisol, other steroids having glucocorticoid or mineralocorticoid activities, or both, are normally secreted in small amounts by the adrenal cortex. And several additional potent steroid hormones not normally formed in the adrenal glands have been synthesized and are used in various forms of therapy. Some of the more important of the corticos-teroid hormones, including the synthetic ones, are the following as summarized in Table 77-1
Stimulation of Aldosterone Secretion by Angiotensin and the Effect of Aldosterone in Increasing Salt and Water Retention
Angiotensin is also one of the most powerful stimulators of aldosterone secretion by the adrenal glands, as we shall discuss in relation to body fluid regulation in Chapter 29 and in relation to adrenal gland function in Chapter 77. Therefore, when the renin-angiotensin system becomes activated, the rate of aldosterone secretion usually also increases and an important subsequent function of aldosterone is to cause marked increase in sodium reabsorption by the kidney tubules, thus increasing the total body extracellular fluid sodium. This increased sodium then causes water retention, as already explained, increasing the extracellular fluid volume and leading secondarily to still more long-term elevation of the arterial pressure.
Sexual desire refers to the broad interest in sexual objects or experiences and is generally inferred by self-reported frequency of sexual thoughts, fantasies, dreams, wishes, and interest in initiating and or engaging in sexual experiences. Definition of this construct is complicated by factors such as attitudes, opportunity partner availability, mood, and health. Relationship factors, individual preferences for sexual variety and emotional intimacy are closely linked to sexual desire. Androgens appear to also play a role. In males, about 95 of androgens (e.g., testosterone) are produced by the testes the remainder is produced by the outer adrenal glands. In females, androgens are produced by the ovaries and adrenal glands in quantities much lower than in males (about 20-40 times less Rako, 1996). In both males and females, decreased testosterone levels due to, for example, orchidectomy (removal of testes) or oophorectomy (removal of ovaries) have been linked to impaired sexual...
The general effects of adult panhypopituitarism are (1) hypothyroidism, (2) depressed production of gluco-corticoids by the adrenal glands, and (3) suppressed secretion of the gonadotropic hormones so that sexual functions are lost. Thus, the picture is that of a lethargic person (from lack of thyroid hormones) who is gaining weight (because of lack of fat mobilization by growth, adrenocorticotropic, adrenocortical, and thyroid hormones) and has lost all sexual functions. Except for the abnormal sexual functions, the patient can usually be treated satisfactorily by administering adrenocortical and thyroid hormones.
Angiotensin II and aldosterone levels are increased two- to threefold in many obese patients. This may be caused partly by increased sympathetic nerve stimulation, which increases renin release by the kidneys and therefore formation of angiotensin II, which, in turn, stimulates the adrenal gland to secrete aldosterone.
When large amounts of aldosterone are secreted by the adrenal glands, a mild metabolic alkalosis develops. As discussed previously, aldosterone promotes extensive reabsorption of Na+ from the distal and collecting tubules and at the same time stimulates the secretion of H+ by the intercalated cells of the collecting tubules. This increased secretion of H+ leads to its increased excretion by the kidneys and, therefore, metabolic alkalosis.
Anticipation Angst Allostatic Regulation Adrenal Steroid Regulation of Corticotropin Releasing Hormone
The emotion of fear is regulated by neuroendocrine events in neural circuits that underlie fear-related behavioral and autonomic responses. One brain region critical in the regulation of fear is the amygdala. I suggest that one function of glucocorti-coid hormones is to facilitate the synthesis of the neuropeptide CRH in this nucleus (along with the lateral bed nucleus of the stria terminalis). CRH aids in maintaining and coping with events that are perceived as frightening. Elevated levels of glu-cocorticoids, secreted by the adrenal gland, act on the amygdala and bed nucleus of the stria terminalis to facilitate CRH gene expression (feedforward allostatic mechanisms) and to sustain the central motive state of fear. In this model, long-term fear (chronic angst) is an allostatic state. experimental manipulations (Mason et al., 1957 Mason, 1975a, b Breier et al., 1988). In contexts in which there is loss of control, or the perception of control (worry is associated with the loss of...
Mary adrenal insufficiency manifest signs and symptoms associated with a deficiency or absence of all adrenal cortical hormones including cortisol, DHEA, and aldosterone 283,284 . Women with panhypopituitarism have severe androgen deficiency due to a lack of both ovarian and adrenal androgen production 248 . Pituitary insufficiency can lead to a deficit of DHEA as the zona reticularis of the adrenal gland produces DHEA in response to stimulation by pituitary ACTH, similar to the stimulation of DHEA in the Leydig cell by LH 286 .
Dehydroepiandrosterone (DHEA) is synthesized in the zona reticularis of the adrenal gland partly in response to serum levels of the pituitary, adreno-corticotropic hormone (ACTH). DHEA is sulfated in the adrenal gland via the enzyme sulfo-transferase into DHEA-sulfate (DHEA-S), which is thought to be the storage form of DHEA. However, this concept has recently been challenged and thus so has the idea of DHEA-S reflecting the bioavailabil-ity of DHEA in the tissues. The current thinking has been that there is free interconversion between DHEA and DHEA-S, but recently the reverse conversion of DHEA-S to DHEA has been shown not to occur, at least in liver cells, although the study has been challenged on methodologic grounds 266,267 . DHEA and DHEA-S production follow an age-dependent pattern high levels after birth due to increased synthesis by the fetal adrenal gland, a second
During Chronic Oversecretion of Aldosterone Kidneys Escape from Sodium Retention as Arterial Pressure Rises
Although aldosterone has powerful effects on sodium reabsorption, when there is excessive infusion of aldosterone or excessive formation of aldosterone, as occurs in patients with tumors of the adrenal gland (Conn's syndrome), the increased sodium reabsorption and decreased sodium excretion by the kidneys are transient. After 1 to 3 days of sodium and water retention, the extracellular fluid volume rises by about 10 to 15 per cent and there is a simultaneous increase in arterial blood pressure. When the arterial pressure rises sufficiently, the kidneys escape from the sodium and water retention and thereafter excrete amounts of sodium equal to the daily intake, despite continued presence of high levels of aldosterone. The primary reason for the escape is the pressure natriuresis and diuresis that occur when the arterial pressure rises.
Kidneys may be removed by grasping the surrounding fat and pulling upward while cutting around the organs. The adrenal gland is a small white structure that lies within the perineal fat pad just anterior to the kidneys. It should be left within the fat that clings to the kidney and the two should be presented to histology as a unit. It is important for the pathologist to be able to distinguish between the right and left kidneys. When it comes time to trim the kidneys after fixation, the right kidney should be cut transversely, while the left is cut lengthwise (left long) for histological presentation. A small transverse incision in the right kidney before fixation will allow you to distinguish between the two and improve fixation if left intact.
Infant in her arms and thus gave a reason to uncover the breast as proof of her feminine nature. A very decent solution of a very delicate problem It seems quite obvious that a 52-year-old woman who probably suffered from an androgen-producing tumour ofthe adrenal glands or ovaries would not be able to get pregnant and breastfeed her own infant. In fact, the baby is not sucking. So, de Ribera does not really deceive his spectators, except perhaps those who do not read his Latin explanations. On the other hand, based on observations of relactating grandmothers or even nursing men, she might have been able to breastfeed without having been pregnant
Just as in the general population, pregnant women can develop hypothyroidism or thyrotoxicosis for other reasons, discussed in Chapters 3 and 4. But what does seem clear (at least to thyroid researchers) is that pregnancy increases your body's thyroid hormone requirements. Pregnancy may lead to relative iodine deficiency, which can increase the severity of preexisting hypothyroidism, and worsen preexisting Hashimoto's or Graves' disease. Finally, it can unveil overt hypothyroidism in women who had subclinical hypothyroidism prior to pregnancy. In some rare cases, if there is a great deal of bleeding during delivery, the pituitary may be damaged (Sheehan's syndrome) and result in hypothyroidism, loss of cortisol from the adrenal gland, and infertility.
There is some evidence to suggest that stress is one factor that may contribute toward triggering an autoimmune disorder. Clearly, when you are under unusual or extreme stress, many hormonal changes occur in the body, particularly between the brain and the adrenal glands, which affect your immune system. What is labeled
The majority of autoimmune endocrine diseases are characterized by immune destruction of endocrine tissue leading to glandular dysfunction and hormonal imbalance. Endocrine autoimmune diseases include hypophysitis, Graves' disease, thyroiditis, autoimmune disease of the adrenal gland (Addison's disease), hypoparathyroidism, autoimmune type 1 diabetes mellitus, and autoimmune polyendocrine syndromes. These diseases have complex etiologies, which are unique to each disease, and, to some extent, unique to each patient. With the exception of autoimmune polyendocrine syndrome type I, genetic susceptibility to the development of endocrine autoimmune diseases is associated with multiple polymorphisms in the major histocompatibility complex genes (11). Genetic susceptibility alone, however, is insufficient to elicit autoimmune disease. Studies of autoimmune disease manifestation in identical twins show a lack of concordance, suggesting that specific (environmental or stochastic) immune...
GAS may be brought about by any stressful situation, including chronic physical stress (e.g., from exposure to extreme cold or in times of real physical danger), but it also may occur as a result of continual psychological stress. As originally described by Selye, the physical correlates of GAS include enlarged adrenal glands, with a marked increased in size of the adrenal cortex as its cells respond to the actions of ACTH and attempt to produce ever larger quantities of the glucocorticoids, as well as a shrunken thymus, weight loss, and gastric ulcers. Gastric ulcers are caused by chronic decrease in blood flow to the gut. Substantial rates of blood flow are necessary for maintenance of the mucosal lining that protects the stomach from the digestive acids. As a consequence of chronic activation of the body's stress response, the gut's blood flow is so decreased that its mucosal lining deteriorates, and the stomach's hydrochloric acid produces ulcers.
The metachromatic leukodystrophies (see Ta.bJe30.-6 ), also known as sulfatide lipidoses, are a group of lysosomal storage disorders recognized by the accumulation of excessive amounts of sulfatide. The term metachromatic, as a description of the diseases, derives from the staining properties of the stored lipid sulfatides, which develop a brown or gold hue with toluidine blue rather than the usual blue of myelin. The enzymatic defect involves arylsulfatase-A or cerebroside sulfatase-A. A heat-stable nonenzymatic protein activator is also necessary for the hydrolysis of the sulfatide. The sulfatide is stored in lysosomes of neuronal white matter as well as in other somatic tissues, giving rise not only to signs of the disease in the central and peripheral nervous systems but also to disease in other organs and tissues such as the kidneys, pancreas, adrenal glands, liver, and gallbladder. y
Because of its role in the control of other endocrine glands, the pituitary is often called the master gland of the body. This designation is more appropriately applied to the pitu-itary's anterior lobe than it is to the posterior lobe, as the adenohypophysis manufactures and secretes hormones that regulate the body's most important glands (e.g., the adrenal glands, the thyroid gland, the gonads). In fact, the prefix adeno- means gland. Adrenocorticotropin (ACTH or adrenocorticotropic hormone) stimulates the production and release of hormones by the adrenal cortex (the adrenal glands are above the kidneys). ACTH triggers the release of glucocorticoids (e.g., cortisol), which are important in carbohydrate metabolism and in the body's resistance to stress. ACTH itself is released in response to physical or emotional stress.
The neurotransmitter involved in the activity of the parasympathetic NS is acetylcholine, produced in the cholinergic terminals. The terminals of the sympathetic NS are noradrenergic, that is, they release noradrenaline. The sympathetic NS innervates not only the viscera and blood vessels but also the adrenal gland. Thus adrenaline and to some extent also noradrenaline are secreted from the adrenal gland when activated by the sympathetic NS which, however, in this section is mediated by acetylcholine. Table 4.1 provides summarized information about the functional differences between the sympathetic and parasympathetic branches of the ANS.
The adrenal glands are located superior to the kidneys and consist of two anatomically and chemically distinct structures an outer cortical region in which steroid hormones are synthesized, and an inner medullary area in which cat-echolamines are produced. The cortex is divided into three zones the zona fasciculata, which secretes glucocorticoids the zona reticularis, which is responsible for adrenal androgen production and the zona glomerulosa, which releases mineralocorticoids.
As with the other tissues described, the differentiation of cells produced by breast stem cells is strictly controlled. Unlike the haematopoietic system where differentiation is controlled mainly by paracrine and autocrine secretions, the breast is also subject to control by circulating hormones secreted by the pituitary, ovary and adrenal glands. For example, during each menstrual cycle at about the time of ovulation, there is an increase in lobular size and epithelial cell vacuolization under the influence of oestrogens and rising progesterone. When menstruation occurs, the fall in hormone levels causes lobular regression. Similarly in pregnancy, oestrogens and progesterone stimulate proliferation and development, and prolactin released by the pituitary gland activates the production of alveolar cells. Additionally, lactation is triggered by the release of oxy-tocin, which causes contraction of the smooth muscle components of the myoepithelial cells surrounding the alveoli leading...
Dietary intakes of vitamin C are absorbed in the upper small intestines by active transport mechanisms at physiological intakes (50-200 mg day). Large intakes (gram doses) of the vitamin may be absorbed by passive diffusion. Most (80-90 ) of a physiological dose will be absorbed. However, this absorbance value may drop to 10-20 for megadoses. Vitamin C is found in high concentrations in the adrenal glands, pituitary gland, white blood cells, the lens of the eye and brain tissue.6-10
The adrenal gland also has two parts. Its outside is the cortex. Releasing hormones from the pituitary stimulate cells of the adrenal cortex to release either mineralocorti-coids or glucocorticoids. Mineralocorticoids such as aldosterone work on the kidney to enable conservation of salt and water. Glucocorticoids are involved in the body's response to stress. The inside of the adrenal gland is the medulla. Its cells are the target of preganglionic sympathetic axons from the spinal cord and release adrenalin and noradrenalin into the bloodstream.
FGFR-1 (fig) mRNA is highly expressed in human fetal brain, skin, growth plates of developing bones and calvarial bones with lesser amounts in other tissues. FGFR-2 (bek) mRNA is expressed in brain, choroid plexus, liver, lung, intestine, kidney, skin, growth plates of developing bone and calvarial bone. FGFR-3 mRNA is expressed in brain, lung, intestine, kidney, skin, growth plates of developing bones and calvarial bone. FGFR-4 mRNA is expressed in human fetal adrenals, lung, kidney, liver, pancreas, intestine, striated muscle and spleen.
The molecular weight determined from amino acid composition of a rat clone is approximately 73 kDa and the human is 78.5 kDa28. Most preparations fall within a 70-85 kDa range. This includes rabbit skeletal muscle (74 kDa),29 rat testis (70 kDa)31, rat epidermis (80 kDa) , bovine brain (75 kDa) , chicken liver (80 kDa)31, human brain (85 kDa)17, monkey brain (80 kDa)34 35, and others. The high molecular weight form was seen in bovine dental follicle and adrenal gland (220 kDa)927 and rabbit serum10. Human erythrocytes showed a molecular weight of 75 kDa36. In addition, numerous lower molecular weight forms have been seen. Most of these center around 50 kDa. Indeed, the first size determination of Pz-peptidase by Aswanikumar and Radhakrishnan from monkey kidne was 56 kDa4. Other tissue sizes were human brain (55 kDa),3437 monkey brain (55 kDa)35 human testis (55) , rat brain (43)39, etc. There have also been many lower molecular weight bands noted in the 20-30 kDa range, however, it is...
Aldosterone Is the Major Mineralocorticoid Secreted by the Adrenals. Aldosterone exerts nearly 90 per cent of the mineralocorticoid activity of the adrenocortical secretions, but cortisol, the major glucocorticoid secreted by the adrenal cortex, also provides a significant amount of mineralocorticoid activity. Aldosterone's mineralo-corticoid activity is about 3000 times greater than that of cortisol, but the plasma concentration of cortisol is nearly 2000 times that of aldosterone.
The normal diurnal rhythm of urinary output is abolished or even reversed in chronic renal disease, adrenal gland insufficiency and in the presence of oedema. This leads to nocturia which may also occur if there is bladder outflow obstruction, due, for instance, to prostatic hypertrophy, or with diuretic treatment.
The second portion of the duodenum is retroperitoneal and fixed in position through fusion of its lateral visceral peritoneum to the parietal peritoneum of the lateral abdominal wall. By dividing the peritoneum at the right lateral edge of the segment (Kocher's maneuver), one mobilizes the descending duodenum to render surgically accessible the retroduodenal and intrapancreatic bile ducts. The right kidney and its hilar structures, the adrenal gland, and the vena cava lie posterior to the second portion of the duodenum (Fig. 2-3 (Figure Not Available) ). Horizontally across the descending mid point of the duodenum, folds of peritoneum come together from above and below to form the mesocolon. At the superior duodenal flexure, the descending second portion of the duodenum forms an acute angle with the first portion and descends about 7 to 8 cm to the inferior duodenal flexure. The transverse colon crosses it anteriorly and may or may not possess a mesocolon at this point. One must...
As SCC grows, it extends longitudinally and circumferentially in the tracheal wall, and may penetrate extraluminally to involve adjacent structures. Tumors may occur at any level of the trachea or carina. Adjacent recurrent laryngeal nerves and the esophagus may be invaded directly. The most common sites of metastases are adjacent peritracheal lymph nodes. Hematogenous metastases to the lung, bone, liver, or adrenals are less common initially. Age and gender incidences of SCC of the trachea are similar to those of carcinoma of the lung (Table 7-2), with peak incidence between 50 and 70 years, predominating in males. The etiologies seem to be identical. Except in 4 cases, every patient we have seen with SCC of the trachea has been a cigarette smoker, usually for many years. One exception had received arsenicals for dermatolog-ic treatment in youth and suffered multiple squamous skin cancers on exposure to sunlight. Another had worked for many years with a multitude of organic chemicals...
An attempt to simplify the evaluation of the hypo-thalamic-pituitary-adrenal axis led to the development of the one-hour ACTH test (or high-dose ACTH test), which consists of the administration of ACTH (250 pg m2) by intravenous infusion during a one-minute time frame 55 . Serum Cortisol is measured an hour later and is normally greater than 20 pg dl (552 nmol l). Patients with complete ACTH deficiency (in whom the adrenal glands have not been exposed to ACTH for 4-10 weeks) fail to respond with a one-hour serum cortisol concentration of more than 20 pg dl (552 nmol l) 64 . In contrast, patients with partial ACTH deficiency or recent onset of complete ACTH deficiency may have a normal serum cortisol response to this dose of ACTH, and ACTH deficiency may not be detected by this test.
HYPOADRENALISM Pathogenesis and Pathophysiology. The adrenal gland is the effector organ of the hypothalamic-pituitary-adrenal (HPA) axis and secretes cortisol in response to stimulation by pituitary-derived corticotropin (adrenocorticotropic hormone ACTH ). Pituitary function, in turn, is under the control of corticotropin-releasing hormone from the hypothalamus. Dysfunction anywhere in the HPA axis may result in adrenal insufficiency. Primary adrenal insufficiency (PAI), is due to bilateral adrenal gland destruction and secondary adrenal insufficiency (SAI) results from hypothalamic or pituitary dysfunction. The most frequent cause of adrenal insufficiency is iatrogenic SAI following the withdrawal of exogenously administered steroids. The fatigue and weakness associated with hypoadrenalism reflect the associated hypotension as well as the water and electrolyte disturbances. The role of glucocorticoids in catabolic energy mobilization likely also contributes. worldwide), and the...
Behaviorally, puberty marks the onset of human genital sexuality. Puberty begins between approximately 10 and 14 years of age for females and between 12 and 16 years of age for males. Hypothalamic stimulation of the pituitary gland causes secretion of pituitary hormones, including those directed to the gonads (gonadotropic) and to the adrenal glands (adrenocorticotropic). These glands, in turn, secrete the hormones responsible for the physical changes at puberty a rapid increase in growth, the development of secondary sex characteristics, and the development of the reproductive capacity. James Tanner outlined the chronological sequence of the appearance of secondary sex characteristics (often referred to as Tanner stages). In addition, the individual experiences an increase in sexual awareness and a heightening of sexual drives. Sexual activity, including kissing, petting, and even intercourse, is a frequent component of the adolescent experience.
Addison's disease is caused by your adrenal glands failing to make cortisol and other steroid hormones the adrenal products your body needs to function properly. This is rare among thyroid patients, but it tends to occur more frequently in a person with pernicious anemia, discussed later, which is commonly found in thyroid patients. Addison's disease is an autoimmune destruction of the adrenal glands however, loss of adrenal function can be consequent to trouble with the pituitary gland.
Families with the inherited form of medullary thyroid cancer have one of three different patterns of inherited disease. The first type, multiple endocrine neoplasia type 2a (MEN2a), is medullary thyroid cancer that is inherited along with a tumor of the adrenal gland that makes adrenaline (pheochromocytoma) and a tumor of the parathyroid gland that results in high calcium levels (hyperparathyroidism). The second type, multiple endocrine neoplasia (MEN2b), is medullary thyroid cancer that is inherited along with pheochromocytoma and unusual body features, such as elongated fingers and toes or bumps on the tongue. The third type is just inherited medullary thyroid cancer without the other associated problems.
Consistent with evidence of HPA axis dysregulation, there is also a growing interest in the role of the central corticosteroid receptor (CR) in the pathogenesis of major depression (Nemeroff, 1996 Holsboer, 2000). Increased CRH has been measured in the CSF of actively depressed patients. Also described in postmortem samples are increases in the number of CRH-secreting neurons in the hypothalamus and decreased CRH-binding sites in frontal cortex, presumably a compensatory response to increased CRH secretion. These brain findings are complemented by neuroendocrine function tests described previously and supported by a number of rodent and primate studies of psychological stress (Lopez et al., 1999 Sanchez et al., 2001). Central CRH-1 and CRH-2 receptors are the focus of ongoing pharmacological studies, with CRH-1 antagonists seen as potential novel antidepressants or antianxiety medications.
Somatostatin and its long-acting analogs have been proven as drugs of first choice in the reliable control of hormone - mediated symptoms.3,8 SST acts on various targets including the brain, pituitary, pancreas, gut, adrenals, thyroid, kidney and on the immune system to regulate a variety of physiological functions. Its actions include inhibition of endocrine and exocrine secretions, modulation of neurotransmission, motor and cognitive functions, inhibition of intestinal motility, absorption of nutrients and ions, vascular contractility and cell proliferation.9 Prolonged-release formulations now allow drug administration every 2 to 4 weeks. Both octreotide and lanreotide have been shown to be efficacious in managing symptoms and tumor progression compared with standard doses of short-acting SST analogs.1,10
Increased Extracellular Potassium Ion Concentration Stimulates Aldosterone Secretion. In negative feedback control systems, the factor that is controlled usually has a feedback effect on the controller. In the case of the aldosterone-potassium control system, the rate of aldosterone secretion by the adrenal gland is controlled strongly by extracellular fluid potassium ion concentration. Figure 29-5 shows that an increase in plasma potassium concentration of about 3 mEq L can increase plasma aldosterone concentration from nearly 0 to as high as 60 ng 100 ml, a concentration almost 10 times normal.
Stress can affect body chemistry as well as emotional responses. During the well-known fight or flight reaction to threat, the adrenal glands respond by producing the hormone adrenaline. Adrenaline in turn causes the breakdown of glycogen (the form of glucose that is stored in the liver) to glucose, which can be used for producing ATP in muscle cells. Energized by the ATP, the arm and leg muscles can contract to strike an enemy or beat a hasty retreat. Adrenaline also affects the digestive system, inhibiting the digestion and absorption that can await a quieter time.
An important hormone system in the body called the adrenergic system is formed from parts of the brain, nervous system, and adrenal glands (small glands that sit on top of each kidney). The hormones released by the adrenergic system are called catecholamines. Two of these hormones are adrenaline (also known as epinephrine) and noradrenaline (norepinephrine). You might remember that adrenaline is a fight or flight hormone, released when you are scared, shocked, or highly excited. When this happens you feel jittery or nervous, your heart beats very fast, you sweat profusely, and your eyes appear wide open because your lids are pulled back (retracted). Just like with many other hormones, special receptors are present in the body's cells that stick to these hormones to stimulate the cells. Two types of these adrenergic receptors are alpha receptors, which make blood vessels squeeze together tightly and raise the blood pressure, and beta receptors, which make the heart beat faster. Many of...
It's important to note another cause of fatigue common in people with thyroid disease there's a real risk that exhaustion may be caused by problems with your adrenal glands. The adrenal glands, located above each of your kidneys, make cortisol, the steroid hormone essential for life. They also make adrenaline and related hormones. Just as the thyroid gland is often afflicted by autoimmune disease, causing Hashimoto's thyroiditis or Graves' disease, the adrenal gland is sometimes similarly afflicted by the immune system, causing the adrenal gland to make too little cortisol. This can cause a profound fatigue, known as Addison's disease. Likewise, if hypothyroidism is caused by pituitary or hypothalamic disease, since these organs also control the adrenal gland, trouble here can also cause loss of adrenal gland function. Specific tests must be done to test for this if it's suspected. This is discussed later in this chapter.
Another endocrine gland susceptible to destruction by autoimmunity, infection, and bleeding is the adrenal gland. Because oral replacement of cortisol does not accurately reproduce the pattern of cortisol secretion by the native adrenal gland, the generation of adrenal cells from stem cells would be of therapeutic benefit. (47). It is expressed in a variety of tissues, including the adrenal cortex, testis (Sertoli cells), ovary (granulosa and theca cells), the placenta, and the pituitary and hypothalamus. During development, SF-1 is expressed in the urogenital ridge as early as embryonic day 9 in mice, and its role in the differentiation of steroidogenic tissues is demonstrated by the absence of adrenal glands and gonads in mice with a null mutation of the SF-1 gene (48,49). In humans, mutations in SF-1 are associated with hypogonadism and hypoadrenalism (47). Among the targets of SF-1 are the genes that encode the steroidogenic cytochrome P450 enzymes (47).