Lose Weight By Controlling The Fat Storage Hormone

Trouble Spot Nutrition

Created by Janet Hradil, Trouble Spot Nutrition is a 3 Phase Hormonal Solution That Melts Away Trouble Spot Fat In Less Than 15 Minutes A Day. Leptin, cortisol, and testosterone all have an influence on our weight issues, but not many of us know it. Janet Hradil has created Trouble Spot Nutrition with the intent of teaching people how their hormones affect their weight loss efforts, and how nutrition can easily correct hormone issues and help fight fat faster than ever before. In each of your fat cells, there is an enzyme, 11 beta-hydroxysteroid dehydrogenase-1 (Hsd), that takes inactive cortisone (a hormone) and turns it into cortisol, a fat storing compound. If you have high amounts of Hsd, you will have high amounts of fat storage. While Hsd is genetically determined, you can use nutrition to reduce levels and stop the unwanted fat storage, even on your trouble spots. Continue reading...

Trouble Spot Nutrition Overview

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Hypercortisolism cushings syndrome epidemiology and etiology

Cushing's syndrome refers to the pathophysiologic changes associated with exposure to supraphysiologic cortisol concentrations (endogenous hypercortisolism) or pharma-cologic doses of glucocorticoids (exogenous hypercortisolism). Cushing's syndrome from endogenous causes is a rare condition, with an estimated incidence of two to five cases per 1 million persons per year.14 Patients receiving chronic supraphysiologic doses of glucocorticoids, such as those with rheumatologic disorders, are at high risk of developing Cushing's syndrome.

Hypercortisolemia Corticotroph Adenomas and Cushings Disease

The first step in diagnosing a patient with hypercortisolemia (Cushing's syndrome) is to find the etiology. In the subset of causes of Cushing's syndrome in the pediatric population, 85 of cases resulted from Cushing's disease.8 Patients diagnosed with Cushing's disease, thus having ACTH-releasing corti-cotroph adenomas, exhibit cushingoid features. Most often, these features in children are short stature, rapid weight gain, menstrual irregularities, skin striae, and mental status changes.9 To demonstrate that hypersecretion of cortisol is present, tests such as the 24-hour urinary free cortisol, 17-hydroxycorticosteroid, and creatinine excretion tests are performed.8 The normal diurnal variation in secretion of cortisol is also lost in Cushing's disease. The high- and low-dose dexamethasone suppression tests are also administered, with the dose of dexamethasone given according to body weight, and these tests have important diagnostic implications. These dynamic tests measure cortisol...

Diencephalic Dysfunction

Disorders of the diencephalon may affect consciousness either directly, by interfering with reticular system function, or indirectly, by producing endocrine disorders. These conditions may develop slowly, as with anterior pituitary syndromes resulting in hypothyroidism or cortisol deficiency, or rapidly, as with osmoregulatory disorders. The lesions producing these problems may also affect the cerebral cortex, as in the case of neoplasms, and produce seizures or other focal neurological disorders. Patients with structural diencephalic lesions may have toxic downward eye deviation, small pupils, decorticate posturing, and Cheyne-Stokes respirations as an archetype, although varying combinations of signs may appear.

The Suprachiasmatic Nucleus

In addition to controlling the circadian variability of the sleep-wake cycle, the SCN creates variability in locomotor activity, food intake, water intake, sexual behavior, core body temperature, and hormonal levels. Thus, cortisol is highest in the early morning hours between 4 00 to 8 00 am, and thyroid-stimulating hormone increases just before sleep. Hormones both influence and are influenced by the circadian clock.

Metabolism of testosterone

Isoforms of5a-reductase exist and isoform 2 is most important because deficiencies of reductase type 2 are correlated with abnormal clinical manifestations (Wilson etal. 1993). To establish a critical steady state concentration ofDHT, not only the activity of the 5a reductase must be high enough, but also the metabolism ofDHT must be low. In the prostate of the dog the activity of the reductive 3a 3 - steroid dehydrogenase activities are low, and this favours the formation ofDHT. The low rate of metabolism through the 3a 3 - dehydrogenase pathway may be the consequence of a low expression of one or both of these enzymes in the prostate, but it may also be possible that within one cell there is a balance between oxidative and reductive actions of two different iso-enzymes. Support for this hypothesis is a report showing that rat and human prostate contain an oxidative 3a-hydroxysteroid dehydrogenase that can convert 5a-androstane-diol back to dihydrotestosterone (Biswas and Russell...

Hormonal regulation of resting metabolism

Insulin stimulates glycogen synthesis in the liver and also promotes liver glucose uptake, but only at an elevated portal vein glucose concentration. Glycogen synthesis in the liver is also directly stimulated by increased vagal nerve activity. Glucagon, on the other hand, stimulates hepatic glycogenolysis as well as lipolysis in adipose tissue. In addition, glucagon stimulates the liver capacity for gluconeogenesis. The effect of glucagon on adipose tissue lipolysis is, however, secondary to the more powerful stimulation by the sympathetic nervous system, cortisol and growth hormone. Several other factors may stimulate hepatic glycogenolysis, including a- and b-adrenergic stimulation and vasoactive intestinal polypeptide, whereas hepatic gluconeogenesis is stimulated by increased precursor (lactate, pyruvate, amino acids, glycerol) availability, secondary to skeletal muscle glycolysis, skeletal muscle proteolysis and adipose tissue lipolysis. During exercise all these processes are...

Hormonal changes with exercise

During exercise, several hormonal systems are activated and increases are seen in plasma concentrations of adrenaline noradrenaline (epinephrine norepinephrine), adrenocorticotrophic hormone (ACTH), cortisol, b-endorphin, growth hormone, renin, testosterone, thyroid hormone and several gastrointestinal hormones (Fig. 1.2.4). Arterial levels of glucagon are unchanged or only marginally increased

Hormonal regulation of carbohydrate metabolism during exercise

Changes in insulin and glucagon have been reported to account for practically all of the increase in hepatic glucose output with exercise 65,66 . It is believed that the decrease in insulin concentration with exercise makes the liver more sensitive to the stimulation by glucagon. Sympathetic nervous stimulation seems to have no role in stimulating hepatic glucose output during exercise in humans, whereas epinephrine has a stimulating effect, additional to that of glucagon, during prolonged exercise, when epinephrine levels are at their highest. In addition, cortisol has an indirect effect on hepatic gluconeogenesis, by increasing the enzymatic potential for this pathway. The catecholamines are important in 'sensitizing' skeletal muscle glyco-genolysis to the stimulating effect of contraction. With exercise leading to hypoglycemia, the compensatory increase in hepatic glucose output is mainly triggered by epinephrine 32 .

Ligand binding domain

To understand the specific recognition of ligands by the human AR, homology models of the ligand-binding domain were constructed based on the crystal structure of the progesterone receptor ligand binding domain. Several mutants in residues potentially involved in the specific recognition of ligands in the hAR were constructed and tested for their ability to bind agonists (Poujol et al. 2000). The homology model AR was refined using unrestrained multiple molecular dynamics simulations in explicit solvent (Marhefka etal. 2001). These models together with the recent crystal structure of the AR, show that the HBD of the AR is similar in structure to the HBD of other nuclear receptors. It is composed of 12 helices and a small (p-sheet arranged in an a-helical sandwich. Depending on the nature of the ligand, agonists or antagonists, the carboxy-terminal helix H12 is found in either one of two orientations. In the agonists-bound conformation, helix H12 serves as a lid to close the...

A role for milk in the control of mammary function in the tammar wallaby

The expression of milk protein genes is regulated concurrently by systemic endocrine factors, by paracrine factors such as the extracellular matrix and by autocrine factors secreted in the milk. Previous studies using a tammar wallaby mammary explant culture model (Nicholas and Tyndale-Biscoe, 1985) have shown that different combinations of insulin, cortisol and prolactin are required for expression of the a- and -casein genes, and whey protein genes including a-lactalbumin and -lactoglobulin (Simpson and Nicholas, 2002). Tammar wallaby mammary explants from late pregnant tammar wallabies can be induced with insulin, cortisol, prolactin, thyroid hormone and oestrogen to express the WAP gene (Simpson et al., 2000). Therefore, the inhibition normally observed in vivo during Phase 2A, and the subsequent induction of WAP gene expression around 100 days post-partum, may be hormonally regulated. In addition, the LLP genes can be down-regulated in mammary explants from Phase 3 tammar...

Reproductive system Male or buck

The bicornuate uterine tract has evolved to produce large litters of young and consists of two long uterine horns, each of which enters the vagina via its own cervix. There is no uterine body. The mesometrium that suspends the tract within the peritoneal cavity contains abundant amounts of fat and is a major fat storage area.

Dermis and hypodermis

The dermis is rich in blood vessels, lymphatic vessels, and nerve endings. An extensive capillary network connects to the systemic circulation with substantial horizontal branching from the arterioles and venules in the papillary dermis. These in turn form plexus and supply capillaries to the hair follicles and the glands. The lymphatic vessels serve to drain the excess extracellular fluid and clear the antigenic materials. The dermis is filled with scattered fibroblasts, macrophages, leukocytes, and mast cells, in addition to the hair follicles, sebaceous glands, and sweat glands. On average, about 10 hair follicles, 15 sebaceous glands, 12 nerves, 100 sweat glands, 360 cm of nerves, and three blood vessels are present in one square centimeter of skin (Barry, 1983). The hypodermis constitutes the deepest layer of the skin, and consists of the subcutaneous tissue filled with fat cells, fibroblasts, and macrophages.

Patient Selection Indications And Contraindications Indications

Subclinical Cushing's syndrome is present in up to 20 of cortical adenomas (26). It is characterized by loss of the normal cortisol circadian rhythm and resists suppression with dexamethasone, but may have normal 24-hour urinary cortisol levels (26,27). Such lesions may progress to clinical Cushing's syndrome or present with postoperative adrenal crises from unrecognized suppression and may therefore be better removed rather than monitored (24).

In foetal sexual differentiation

Unhindered steroid hormone formation and action is necessary for the development ofthe external genitalia. Furthermore, defects in cholesterol synthesis may also lead to distinct phenotypes including deficiencies of genital development. The first steps of steroid biosynthesis are common pathways for glucocorticoids, mineralo-corticoids, and sex steroids, while the formation of testosterone from androstene-dione via 176-hydroxysteroid dehydrogenase type 3 is probably limited to testis (Hiort etal. 2000). In contrast, further conversion of testosterone to DHT is catalysed in the peripheral target tissues and not within the gonads. Androgen synthesis in the developing testes is controlled during early foetal life by human chorionic gonadotropin (hCG) and only later by the foetal luteinizing hormone (LH) itself.

In puberty and adulthood

Increasing androgenic steroid secretion from the adrenals is defined as adrenarche and precedes puberty. Adrenarche is associated with increased growth of pubic and axillary hair independent of gonadal androgen secretion. Adrenal androgens include mainly dehydroepiandrostendione, its sulfate, and androstendione, but also other adrenal steroids have androgenic potential. Adrenocorticotropic hormone (ACTH) is a potent stimulator of adrenal androgen secretion however, its potency relative to cortisol secretion is much less. Also, substances other than ACTH may modulate adrenal androgen secretion. These include estrogens, prolactin, growth hormone, gonadotropins and lipotropin. None of these appear to be the usual physiological

Circulating factors that influence bone cell function

More recently, a mechanism of hypothalamic control of bone metabolism has been demonstrated. In contrast to the metabolic pathways of PTH and vitamin D, factors are secreted by bone cells and then themselves in turn affect overall bone metabolism through a centrally mediated mechanism. Leptin, a small polypeptide hormone, is secreted by osteoblasts. Its direct effects are thought to be through control of body weight, while its indirect effects may be through modification of gonadal function via interactions within the hypothalamus 1 . In animal studies, mice with leptin deficiency demonstrated obesity, hypo-gonadism, and increased bone formation and bone mass. This newly discovered interrelationship between the central nervous system and bone metabolism offers an exciting new frontier in the understanding and possible treatment of metabolic bone disorders such as osteoporosis.

Preoperative Investigation

Preoperative investigations include radiological imaging to study the anatomical details and endocrinological investigation to determine the functional status. Elevated plasma or urinary aldosterone level indexed against urinary sodium excretion, and measured after sodium loading in combination with previously demonstrated low peripheral renin activity during sodium depletion, is the biochemical hallmark of hyperaldosteronism. Pre- and post-contrast computed tomography scan is the most accurate imaging modality. Conversely, small adrenal lesions are often not well visualized with adrenal magnetic resonance imaging (28). Twenty-four hour urine cortisol and plasma cortisol levels and adrenocorticotrophic hormone after dexamethasone suppression test are the cornerstone of biochemical diagnosis of cortisol-hypersecreting Cushing's adenoma. A 24-hour urine analysis for norepinephrine, epinephrine, and vanillylmandelic acid is mandatory whereas serum norepinephrine and epinephrine levels...

Natural history of MCL injury

The remodeling phase is also marked by tissue remodeling, lasting months and years after the initial injury. It should be noted that an injured MCL never regains the properties of the normal MCL 66-68 . The healed ligaments have elevated numbers of vessels, fat cells and voids and increased water content. The diameter of collagen fibers is smaller with fewer numbers of stable collagen cross-links. The healing MCL also contains elevated type III and V collagens, along with an elevated number of proteoglycans (PG).

Cardiovascular risk factors

Testosterone plays an ambiguous role in relation to cardiovascular risk factors and its respective role has not been fully resolved (see Chapter 10). The interactions between the CAG repeat polymorphism, serum levels of sex hormones, lifestyle factors and endothelium-dependent and independent vessel relaxation of the brachial artery as well as lipoprotein levels, leptin and insulin concentrations and body composition were described in over 100 eugonadal men of a homogenous population. In agreement with previously demonstrated androgen effects on these parameters it was demonstrated that androgenic effects were attenuated in persons with longer CAG repeats while testosterone levels themselves played only a minor role within the eugonadal range. Significant positive correlations with the length of CAG repeats were seen for endothelial-dependent vasodilatation, HDL-cholesterol concentrations, body fat content, insulin and leptin levels. These results remained stable in multiple...

Neuroendocrine Responses to Stress

The hypothalamic-pituitary-adrenal (HPA) axis is one of the most widely studied of the stress responsive systems. This cascade begins with the release of CRH from the parvocellular neurons of the paraventricular nucleus of the hypothalamus into the external zone of the median eminence. From here CRH is carried through the portal blood system to the anterior lobe of the pituitary gland, where it acts as a secretagogue for adrenocorticotrophic hormone (ACTH). ACTH is then released into the systemic circulation and carried through the blood to the adrenal cortex, where it stimulates cells in the zona fasciculata to produce and release glucocorticoids. The glucocorticoid released in response to stress in the rat is corticosterone (CORT), while the human adrenal cortex secretes cortisol. Since corticosterone and cortisol vary only slightly in their chemical structure, both are classified as glucocorticoid hormones and bind to the same receptors in the body with comparable affinity. It is...

Chemistry of Insecure Attachment

Instead of the warm and fuzzy feelings activated by oxytocin, stress chemicals are triggered. Cortisol, the chemical that keeps us alert and helps us deal with stress, seems to be the main culprit at work here. Sometimes cortisol is necessary, for example, in the morning when its concentration is highest to help us wake up. But cortisol's dampening effect on oxytocin is a less positive thing when you wish to be calm and open to human connection. Either of these lifelong positive and negative biochemical patterns begins in baby's first year.

Endocannabinoid Blockers

Wild-type animals, CB1-knockout mice have leaner body composition, but this lean phenotype is not fully explained by changes in food intake. Stimulation of the CB1 receptors in fat cells promotes lipo-genesis and inhibits the production of adiponectin, a cytokine derived from adipose tissue that has potentially important antidiabetic and antiatherosclerotic properties.59 The system may provide a possible treatment target for high-risk overweight or obese patients.

Stressful Life Events

Stressful life events, including childhood trauma, have been associated with the development of som-atization later in life (Campo and Fritsch 1994). Chronic stressors can have an effect on the body's stress response systems, such as the hypothalamic-pituitary-adrenal (HPA) axis. Although elevations of cortisol may be associated with acute stress, prolonged exposure to stress can suppress the HPA axis, resulting in the lowered cortisol levels that are associated with somatic complaints (Lackner et al. 2004). Somatoform symptoms have been linked to traumatic events experienced in both childhood and adulthood (Binzer et al. 1997 Roelofs et al. 2002). Roelofs et al. (2005) have found that the number of traumatic events an individual has experienced is associated with the number of conversion disorder symptoms exhibited. Of traumatic events experienced, those pertaining to relationship and occupational problems are most likely to trigger immediate somatic symptoms in adults (Roelofs et...

Circadian Dysregulation

Dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis is one of the most reproducible biomarkers of major depressive disorder (reviewed in Holsboer, 2000). Increases in urinary cortisol production, levels of corticotropin-releasing hormone (CRH) in spinal fluid (Nemeroff, 1996), and a general disturbance in the normal pattern of cortisol secretion have been identified (Carroll et al., 1981). Blunted suppression of morning cortisol levels following oral dexam-ethasone administration, the so-called dexamethasone suppression test (DST), was 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...

Gross and Microscopic Appearance

Intracranial lipomas appear as dark-yellow lesions on gross inspection. The meninx primitiva contains within it primitive perivascular reticuloendothelium,6 which may become specialized in the storage of fat, and this may account for the histology of intracranial lipomas. Early precapillary parenchyma may also differentiate into fat cells. Microscopic examination reveals that these lesions are composed of mature adipose cells with peripheral, sometimes indented, small bland nuclei. A col-lagenous capsule that is intimately associated with adjacent brain often surrounds the lipoma. In general, no cleavage plane exists between the tumor and surrounding brain tissue. Histo-logically, although mature fat is the predominant element, variable amounts of fibrovascular tissue, bone, and calcification can also be present. Adjacent parenchymal calcifications and bone formation may occur, although the exact percentage of lipomas showing these changes is not well documented. Bone formation within...

Regional and General Anesthesia and Surgical Stress

Of certain stress hormones, like adrenaline and Cortisol, by the adrenal gland. These hormones can be detrimental to the body in a great number of ways when they persist for extended periods. The release of adrenaline alone increases heart rate, blood pressure, and oxygen demands on the heart, which may be harmful or fatal in the patient with advanced heart disease. It also causes elevated blood glucose levels and can impair the immune response, increasing susceptibility to infection.

Pluripotent stem cells as the target of androgen action

Because testosterone administration has reciprocal effects on muscle mass and fat mass, and increases satellite cell number, we considered the possibility that the target of androgen action might be a precursor cell from which muscle and fat cells are derived. We hypothesized that testosterone regulates body composition by promoting the commitment of mesenchymal pluripotent cells into myogenic lineage and inhibiting their differentiation into adipogenic lineage. To test this hypothesis, we treated pluripotent, mesenchymal C3H 10T1 2 cells with testosterone (0-300 nM) or dihydrotestosterone (0-30 nM) for 0-14 days (Singh et al. 2003). We evaluated myogenic conversion by immunochemical staining for early (MyoD) and late (myosin heavy chain II MHC) myogenic markers, and measurements of MyoD and MHC mRNA and protein (Fig. 8.4). Adipogenic differentiation was assessed by adipocyte counting, and by measurements of PPAR7 2 mRNA, and PPAR7 2 and C EBPa proteins. The number of MyoD+ myogenic...

Hypothalamic PituitaryAdrenal Axis

The HPA axis provides a critical mechanism for regulation of the stress response and its effects on the brain and other organ systems. Several important hormones, including corticotropin-releasing hormone and cortisol regulate the effects of anxiety on the body and provide positive feedback to the brain.15 A cycle of anxiety and sensitization by such feedback could, if unchecked, result in escalation of symptoms. Neuropeptides may provide one mechanism to balance positive and negative feedback, helping to minimize such escalation.

Body Fluids And Compartments

Total body water in males is approximately 60 of total body weight, i.e. 42 L for a 70 kg man. In females, total body water is approximately 10 less, because of the greater proportion of body fat compared with males fat cells have a lower water content than other cells of the body. The water is distributed in various spaces or compartments

Epidemiology and etiology

Adrenal insufficiency generally refers to the inability of the adrenal glands to produce adequate amounts of cortisol for normal physiologic functioning or in times of stress. The condition is usually classified as primary, secondary, or tertiary, depending on the etiology (Table 45-1)2,4-8 The estimated prevalences of primary adrenal insufficiency and secondary adrenal insufficiency are approximately 60 to 143 and 150 to 280 cases per one million persons, respectively. Primary adrenal insufficiency is usually diagnosed in the third to fifth decade of life, whereas secondary adrenal insufficiency is commonly detected during the sixth decade.2,9 Adrenal insufficiency is more prevalent in women than in men, with a ratio of 2.6 12 Chronic adrenal insufficiency is rare.

Treatment and outcome evaluation Chronic Adrenal Insufficiency

Scribed because it most closely resembles endogenous cortisol with its relatively high mineralocorticoid activity and short half-life, and allows the design of regimens that simulate the normal circadian cycle.5 Other glucocorticoids, however, can be used. The pharmacologic characteristics of commonly used glucocorticoids are presented in Table 45-3.4 Since patients with primary adrenal insufficiency can experience DHEA deficiency, DHEA replacement also has been tried. Several small clinical studies, consisting mostly of women, suggest that treatment with DHEA can improve mood and fatigue and provide a general sense of well-being.10-13 Nonetheless, use of DHEA remains controversial and requires further study. The specific management strategies for chronic adrenal insufficiency are as follows2,5,9 For the treatment of primary adrenal insufficiency (Addison's disease), oral hydrocortisone 12 to 15 mg m is typically administered in two divided doses, with two-thirds of the dose given in...

Nonpharmacologic Therapy

Ism can result in prolonged adrenal insufficiency lasting for months after surgery and requiring exogenous glucocorticoid administration. Pituitary irradiation or bilateral adrenalectomy is usually reserved for patients who are not surgical candidates or for those who relapse or do not achieve complete remission following pituitary surgery. Because the response to pituitary irradiation can be delayed (several months to years), concomitant treatment with cortisol-lowering medication may be necessary. Bilateral adrenalectomy is also used for the management of adrenal carcinoma and in patients with poorly controlled ectopic Cushing's disease in whom the ACTH-pro-ducing lesion cannot be localized. Bilateral laparoscopic adrenalectomy achieves an quire lifelong glucocorticoid and mineralocorticoid supplementation. ' Nelson's syndrome may develop in nearly 20 to 50 of patients who undergo bilateral adrenalectomy without pituitary irradiation. This condition presumably results from...

Pharmacologic Therapy

Widely used therapeutic class is the adrenal steroidogenesis inhibitors. Agents in this class include ketoconazole, etomidate, and metyrapone. Steroidogenesis inhibitors can treat hypercortisolism by inhibiting enzymes involved in the biosynthesis of cortisol. Because of their potential to cause adrenal suppression, temporary glucocorticoid re

Adrenal Cortex And Medulla

The cortex consists of three distinct zones. The outer zona glomerulosa, which is made up of whorls of cells, merges into the zona fasciculata formed of columns of cells with prominent venous sinuses. This layer merges into the inner zona reticularis made up of a network of cells (Fig. 28.2). These cells are abundant in lipid, which reflects the fact that they synthesize and secrete lipid hormones. All the cells secrete corticosterone, but the enzymes responsible for aldosterone synthesis are found only in the zona glomerulosa. The enzymes for Cortisol and sex hormone synthesis are found in the zona fasciculata and zona reticularis. The zona glomerulosa also forms the new cortical cells, which allows regeneration. The adrenal medulla cannot regenerate. All the steroids are secreted as the free steroid, except for dehy-droepiandosterone (DHEA) which is conjugated to sulphate. Cortisol and corticosterone are the main glucocorticoids secreted, with a ratio of 7 1. The principal...

Intravenous Local Anesthetics

Have looked at the effect on the stress response. Incisional application of lidocaine with an aerosol provides long-lasting pain relief as well as inhibition of the P-endorphin response.1 Incisional infiltration with bupivacaine may prevent the cortisol and glucose response to herniotomy but may not modify the leukocytic or acute phase response, even in patients whose wounds are cooled to about 15 C.13 No studies are available concerning the use of local anesthetic creams on the wound postoperatively. In summary, the limited data suggest modification of some aspects of the stress response by application of local anesthetics to the wound. However, the effect is small and short-lasting comparable to the short-lasting pain duration.

Associations of endogenous testosterone with cardiovascular risk factors

In men testosterone plasma levels were frequently found to have positive correlations with serum levels of HDL-C as well as inverse correlations with plasma levels of triglycerides, total cholesterol, LDL-C, fibrinogen and PAI-1. However, serum levels of testosterone have even stronger inverse correlations with BMI, waist circumference, waist-hip-ratio (WHR), amount of visceral fat and serum levels of leptin, insulin and free fatty acids. After adjustment for these measures of obesity and insulin resistance, the correlations between cardiovascular risk factors with testosterone but not with visceral fat or insulin lost their statistical significance (Hergenc et al. 1999 Tchernof et al. 1996 Tsai et al. 2000). These findings indicate that a low serum level of testosterone in eugonadal men is a component of the metabolic syndrome, which is characterized by the presence of obesity, glucose intolerance or overt type 2 diabetes mellitus, arterial hypertension, hypertriglyc-eridemia, low...

Adrenal And Renal Hormones And Catecholamines

In studies using rather large volumes of bupivacaine (0.5 ) and a well-described neural blockade, the intra- and postoperative increases in plasma cortisol, aldosterone, and renin, as well as catecholamines, have been inhibited. Although no systematic studies are available, rather large doses of bupivacaine seem to be necessary to achieve eradication of these stress parameters.

Parathyroid Hormone Receptor

To characterize normal and pathologic systemic calcium homeostasis, it is pertinent to clarify some aspects of the cloned PTH receptor.117 Apart from the classic targets of PTH in bone and kidney, the receptor has been demonstrated in fibroblasts, chondrocytes, lymphocytes, smooth muscle cells, and fat cells. This allows PTH to induce hypotension and bowel relaxation and to influence chronotropism and inotropism of the heart in addition to its classic actions on bone turnover and calcium, phosphate, and vitamin D metabolism in the kidney. The receptor also binds PTHrP with similar efficiency. Because PTHrP exerts a variety of hitherto partially clarified functions, studies on the common PTH-PTHrP receptor and its actions are hampered by difficulties in determining the biologically relevant agonist. Activation of the PTH receptor's cAMP-generating capacity requires PTH amino acids 1-24, and PTH 1-34 is essentially as potent as the full-length peptide.118 However, various PTH fragments...

Classification And Clinical Presentation

Cushing's disease, elevated serum ACTH and Cortisol levels Corticotrophic adenomas often present a diagnostic dilemma for clinicians, because their imaging characteristics and laboratory abnormalities are variable. Tumor size appears to have no correlation with severity of hypercortisolism, and the tumor is often not seen on imaging studies before surgery. Thus in all patients a thorough laboratory investigation must be performed to confirm the diagnosis preoperatively, especially where tumor is not obvious on imaging studies. Determinations of serum cortisol, adrenocorticotropic hormone (ACTH), 24hour urine free-cortisol, high- and low-dose dexamethasone

Temperature regulation

A combination of an underdeveloped thermoregulatory system, minimal subcutaneous fat deposits and a high body surface area to volume ratio increases the potential risk of significant heat loss in neonatal patients so maintaining a warm environmental temperature is essential. The temperature for the first 7 days should be 29 C, decreasing to 26 C for

Variation in the androgen receptor

A variable number of CAG repeats in exon 1 of the androgen receptor gene on the X-chromosome, which normally ranges between 9 and 35 encodes for a variable number of glutamine residues in the aminoterminal domain of the receptor and is inversely associated with the transcriptional activity of testosterone-responsive target genes. Abnormal expansion of the CAG repeats beyond the number of 36 leads to Kennedy disease, which is accompanied by signs of hypoandrogenism (see Chapter 2 for details). Within the physiological range of 9 to 35, the number of CAG repeats was shown to be inversely associated with the risk of prostate cancer, benign prostatic hyperplasia, sperm production, and bone density, and depression (Dowsing et al. 1999 Ferro et al. 2002 Seidmann et al. 2001 von Eckardstein et al. 2001 Zitzmann et al. 2001a). With respect to cardiovascular disease it is important to emphasize that the number of CAG repeats is positively correlated with flow-mediated vasoreactivity and...

Clinical implications

Exogenous androgens induce both apparently beneficial and deleterious effects on cardiovascular risk factors by decreasing serum levels of HDL-C, PAI-1 (apparently deleterious) Lp(a), fibrinogen, insulin, leptin and visceral fat mass (apparently beneficial) in men as well as women. However, androgen-induced declines in circulating HDL-C should not automatically be assumed to be pro-atherogenic, since they may reflect accelerated reverse cholesterol transport instead.

Intergenerational Transmission

In a study of risk factors for the development of PTSD, Yehuda and her colleagues examined the association between cortisol and PTSD in children of holocaust survivors. Low cortisol levels were significantly associated with both PTSD in parents and lifetime PTSD in subjects, whereas having a current psychiatric diagnosis other than PTSD was relatively, but nonsignificantly, associated with higher cortisol levels. Offspring with both parental PTSD and lifetime PTSD had the lowest cortisol levels of all study groups. They concluded that parental PTSD is associated with low cortisol levels in offspring, even in the absence of lifetime PTSD in the offspring. They suggested that low cortisol levels in PTSD may constitute a vulnerability marker related to parental PTSD as well as a state-related characteristic associated with acute or chronic PTSD symptoms (Yehuda et al., 2000).

Adrenocortical hypofunction

Clinical features include weakness, weight loss, hyperpigmenta-tion, hypotension, vomiting, diarrhoea and volume depletion. Hypoglycaemia, hyponatraemia, hyperkalaemia and metabolic acidosis are characteristic biochemical findings. The stress of infection, trauma or surgery provokes profound hypotension. Diagnosis is made by measurement of plasma Cortisol concentrations and the response to ACTH stimulation.

Other Phenotypes in the Adrenergic Receptor Knockouts

The D KO had a very interesting increase in daily food and water intake, which might in part have been related to chronic hypotension (17). The B KO had a variety of abnormalities of glucose metabolism, including insulin resistance, increased plasma leptin, increased percentage body fat (with no change in body weight), and glucose intolerance and obesity with a high-fat diet (12). The authors offered an explanation involving increased parasympathetic activity caused by increased hypothalamic neuropeptide Y (12), and certainly further work in this area will be interesting and important. A current clinical paradigm is that a1-antagonists decrease insulin resistance, the opposite of the B KO. INC plasma leptin (12) INC body fat (12) Insulin resistance (12)

Miscellaneous Intramedullary Pathology

Other non-neoplastic entities can occur as intramedullary spinal lesions.33,38 Vascular malformations, particularly cavernous angiomas, may occur in the spinal cord. Inclusion tumors and cysts are rarely intramedullary. Lipomas are the most common dysembryogenic lesion and account for approximately 1 of intramedullary masses. These are not true neoplasms but probably arise from inclusion of mesenchymal tissue within the spinal cord itself. They typically enlarge and produce symptoms in early and middle adult years through increased fat disposition in metabolically normal fat cells. Lipomas are often considered juxtamedullary, because they occupy a subpial location.

Adrenocorticotrophic hormone stimulation test

This is used to aid the diagnosis of Cushing's disease (Fig. 22.14) or of Addison's disease, which is hypoadrenocor-ticalism. Adrenocorticotrophic hormone (ACTH) is normally secreted by the pituitary gland to stimulate the secretion of cortisol from the adrenal cortex. A blood sample is taken and cortisol levels are measured. A synthetic ACTH, e.g. Synathacon, is then administered intravenously and blood cortisol levels are measured again within 60-90 min of the injection.

TABLE 713 ClResistant Metabolic Alkalosis with Hypertension Suppressed Aldosterone Levels Acquired Disorders

Most corticosteroids (specifically cortisol, deoxycorticosterone, and corticosterone) also have significant mineralocorticoid effects and produce hypokalemic metabolic alkalosis Collecting duct cells contain type II 11 3-HSD that degrades cortisol to the inactive metabolite cortisone cortisol secretion in response to ectopic ACTH may be so high, however, that it overwhelms the metabolic capacity of the enzyme in addition, type II 11 fi-HSD may be inhibited by ACTH This chemical inhibits type II 11 -hydroxysteroid dehydrogenase activity and uncovers the mineralocorticoid receptor which is normally protected by this enzyme from glucocorticoid stimulation hydroxysteroid dehydrogenase

TABLE 714 Evaluation of the Patient with Suspected Cushings Syndrome

24 h urinary free cortisol-values greater than 3 times the ULN are highly sensitive and specific. Values between ULN and 3 times ULN require repeat testing and clinical judgment depending on the level of suspicion Overnight dexamethasone suppression test-One mg given between 11 pm and midnight followed by an 8 am serum cortisol. Serum cortisol should suppress to < 1.8 J.g dL in normals Late evening salivary cortisol less than 1.3 ng mL in normals this test is becoming increasingly popular because of its ease of collection and stability of cortisol in saliva at room temperature Late night plasma ACTH and cortisol (11 pm-midnight)-Serum cortisol should be > 15 J.g dL ACTH < 10 pg ml-ACTH-independent process, ACTH > 20 pg ml ACTH-dependent process High dose dexamethasone suppression test-2mg every 6 h with 24 h urines collected for free cortisol and 17-hydroxysteroids suppression is compatible with a pituitary adenoma free cortisol should suppress > 90 and 17-hydroxysteroids...

Physiological Transport Mechanisms for Peptides and Proteins at the Blood Brain Barrier

The concept of saturable, receptor-mediated uptake systems for peptides and proteins at the blood-brain barrier has evolved over the last two decades. There is now combined evidence from in vitro and in vivo studies, at the biochemical and pharmacokinetic levels as well as at the morphological level, that peptides are transported across the endothelial cells. This includes transport of compounds as structurally diverse as insulin and insulin-like growth factors (IGF-I and II) (56), transferrin (57), low density lipoprotein (LDL) (58), and leptin (59). The overall process of transendothelial passage is designated as transcytosis and is composed of binding to a luminal plasma membrane receptor, endocytosis, transfer through the endothelial cytoplasm to the abluminal side, and abluminal exocytosis into brain interstitial space (60). Recently, substantial evidence has been accumulated to support the presence at the BBB of a transport system that is involved in the transcytosis of leptin....

Definition and Pathogenesis

Insulin is also important in maintaining the integrity of proteins, whose amino acids become substrates for hepatic gluconeogenesis when cortisol and glucagon's actions are unopposed by insulin. Insulin insufficiency of diabetic disorders has ubiquitous adverse effects on metabolism of all energy substrates, which contributes to the diverse complications challenging diabetic patients in their activities of daily living.

Adrenal insufficiency

Adrenal insufficiency refers to impaired secretion of cortisol with or without impaired secretion of aldo-sterone. Adrenal insufficiency can result from disorders of the adrenal cortex (primary adrenal insufficiency) or of the hypothalamus or pituitary (secondary adrenal insufficiency) (see Figure 19-2). Symptoms of adrenal insufficiency include weakness, abdominal pain, and hyperpigmentation. Chronic primary adrenal insufficiency, or Addison's disease, usually results from autoimmune adrenali-tis and can be treated with cortisol and aldosterone replacement.

Physiologic Effects of Corticosteroids

Cortisol Cortisol exerts its effect by regulating gene transcription after binding to glucocorticoid receptors within the cell.9 Cortisol has a large number of metabolic effects on several tissues. However, many of the effects of glucocorticoids are based on studies of patients, animals, and cells with non-physiologically high or low levels of glucocorticoids. Glucocorticoids are necessary for maintaining hepatic glycogen stores. They stimulate protein catabolism and lipolysis and cause hyperinsulinemia.1 Cortisol is required for maintenance of normal blood pressure. The effect on immunologic function of glucocorticoids in physiologic levels is not clear, but glucocorticoid excess suppresses both immunologic and anti-inflammatory responses. Glucocorticoids have a weak mineralocorticoid effect and influence calcium homeostasis by decreasing intestinal calcium absorption and increasing urinary calcium excretion.1 In pharmacologic doses, Cortisol causes osteoporosis. The effects of...

Other drug complications

Most drugs have undesirable side-effects. For example, etomi-date inhibits Cortisol synthesis and can increase mortality in critically ill patients when used continuously for sedation. Nitrous oxide interferes with methionine synthesis and haemopoiesis. In addition nitrous oxide diffuses into gas-filled spaces. For example, the use of 70 nitrous oxide for 2 h doubles the volume of bowel gas and may compromise gut blood supply, reduce surgical access and increases the incidence of postoperative nausea and vomiting. Nitrous oxide also increases the size and or pressure in gas-filled spaces such as a pneumothorax.

Clinically Inapparent Adrenal Mass Incidentaloma or Adrenaloma

Recently, at a State of the Science Conference at the National Institutes of Health Conference, the term clinically inapparent adrenal mass was coined.3 The widespread teaching is that most adrenalomas are indolent tumors, nonfunctioning and asymptomatic, causing no harm to the patient.4 5 Recent studies, however, have shown that a high percentage of these tumors can be subclinically functioning, causing symptoms milder than those encountered in the well-known adrenal-hyperfunctioning syndromes but still harmful to the patient.614 Thus, the screening tests of serum potassium, urinary vanillylmandelic acid (VMA), and serum Cortisol do not suffice and more detailed and in-depth laboratory investigation is necessary. The fear of adrenal carcinoma that dictated the approach to these tumors in the past (with the main emphasis on the size of the tumor) should be changed to the fear of the subtle function of these usually benign adrenal cortical adenomas with coexistent metabolic pathology...

The Goal of Evaluation

Chiodini and coworkers14 performed a longitudinal study evaluating the rate of spinal and femoral bone loss levels in 24 women with clinically inapparent adrenal masses. They were divided into two groups on the basis of the median value of urinary Cortisol excretion. The group with higher Cortisol values (subclinical Cushing levels) had more lumbar trabecular bone loss than those with low Cortisol secretion (not hypersecreting tumors). Depending on the amount of glucocorticoids secreted, the clinical significance of subclinical Cushing's syndrome ranges from slightly attenuated diurnal Cortisol rhythm to atrophy of the contralateral adrenal gland, a dangerous condition after unilateral adrenalectomy if appropriate therapeutic measures are not taken early enough.37 The best screening test for autonomous Cortisol secretion is the short dexamethasone suppression test. A 2- or 3-mg dose is better than the usual 1-mg dose to reduce false-positive results. A suppressed serum Cortisol (< 3...

Regression Require Commensurate Vascular Remodeling

Studies were conducted using a monogenetic strain of mice (C57BL 6J, ob ob), which develops morbid obesity because of the inability to synthesize leptin (Zhang et al. 1994), a hormone that regulates appetite and metabolism (Pelleymounter et al. 1995 Camp field et al. 1996 Spiegelman and Flier 1996 Halaas et al. 1997). Leptin-deficient (ob ob) mice can gain (or lose, if dieted) nearly 1.0 g d of weight, principally in the form of fat tissue. This far exceeds the average weight changes of 0.1 g d, which are typical of wild-type mice. The substantial shifts in fat mass in ob ob mice provide an opportunity to study the mechanisms coordinating tissue and vascular remodeling. pose tissue loss (Fig. 3). Previous studies showed similar findings (Crandall et al. 1997 Cohen et al. 2001). We further found that the shift from endothelial proliferation to apoptosis occurred under a variety of weight-loss conditions, such as angiogenesis inhibitors, diet restriction, or leptin. This suggests that...

Not broken but not working properly

If this were the case, it would be difficult to understand why antidepressant drugs that raise monoamine levels quickly take several weeks to have a significant effect on depressive symptoms. This delay suggests that antidepressants work indirectly and that depression is caused by biochemical dysfunction that is only distantly linked to monoamine function. Indeed, in their search for new targets for antidepressant drugs, pharmaceutical companies are now exploring alternative biochemical pathways, such as those associated with the regulation of the brain's stress hormone cortisol. Growing concerns about the safety and side effects of the monoamine uptake inhibitors are a driving force behind the search for more effective new treatments for this baffling illness of the brain.

How Distress Aggravates Pain and Illness

There is little doubt that emotional distress can lower a person's pain threshold and increase pain. Stress also takes a serious physical toll many studies show that stress causes muscles to tighten, disturbs appetite and sleep habits, and triggers the production of stress hormones. These hormones, such as adrenaline and Cortisol, increase heart rate, blood pressure, muscle tension, and blood sugar and, over time, can lower one's pain threshold and weaken the immune response.

Genetics vs Lifestyle

Single-gene mutations related to obesity often involve leptin and melanocortin. Leptin is a protein produced in adipose tissue that provides negative feedback to appetite control centers. Obesity may reflect lack of hormone production or a lack of leptin receptors. There are leptin-deficient animal models, and rarely, this deficiency has been identified in humans. In leptin-deficient people, weight loss results when leptin is replaced. Leptin supplementation in non-leptin-deficient obese subjects does not result in weight loss (Bray, 2002). Many hormonal factors are involved in appetite, as well as in the absorption, storage, and use of calories. Factors providing input to the brain include leptin levels, vagal afferent activity, Central obesity suggests increased visceral fat deposits, likely caused by increased production of peptides and other metabolic messengers. Hormonal influences most likely play a role in the distribution of fat. Central obesity is believed to result partly...

Research Evidence to Date

University-based research found that laughing lowers blood pressure and increases muscle flexibility in addition to releasing endorphins. Endorphins not only reduce pain they also induce a degree of euphoria, and therefore may further enhance the positive effects of laughter. There is also evidence indicating that laughter increases immune activity, and that it can reduce levels of cortisol, a stress hormone associated with suppressing the immune system.

Role of pAdrenergic Receptors in the Regulation of Fat Metabolism

When fed a standard chow diet, P1P2P3-AR-KO mice had a small increase in fat stores when compared with wild-type mice. However, a calorically dense diet, high in fat and sucrose, induced massive obesity in P1P2P3-AR-KO mice. The observed weight gain of 25 g in 8 wk represents the development of extreme obesity and is similar to that observed in leptin-deficient ob ob mice. The marked obesity observed in high calorie-fed P1P2P3-AR-KO mice is caused entirely by a defect in diet-induced thermogenesis (31). These findings establish that P-ARs are required for diet-induced thermogenesis, and that this pathway plays a critical role in the body's defenses against diet-induced obesity. The target tissue mediating sympathetically driven diet-induced thermogenesis is unknown. Although brown adipose has been proposed as the primary target, data from mice lacking UCP1 strongly argue against this. In brown adipose, UCP1 is a downstream component in the generation of heat following sympathetic...

Obstructive Sleep Apnea

Although obstructive sleep apnea (OSA) is not always associated with obesity, excessive weight is a major risk factor. About 70 of OSA patients are obese. Among obese persons, the incidence of OSA is approximately 40 (Poulain et al., 2006). The increased risk may be related to increased neck circumference and pharyngeal fat deposits. Often unrecognized, OSA has significance beyond daytime somnolence and the spousal impact of disruptive snoring and has been associated with systemic effects as well, such as pulmonary hypertension, right-sided CHF, and erectile dysfunction. Weight loss may benefit the OSA patient. Conversely, a patient with mild OSA who has a 10 increase in body weight then has a sixfold increased risk of progressing to moderate or severe sleep apnea (Caples et al., 2005).

Epidemiology and Pathogenesis

Cushing's syndrome account for only 0.2 of all causes of arterial hypertension in the general population, with a prevalence of 1 to 10 cases per million per year.2 Corticotropin-dependent Cushing's syndrome is found in more than 80 of patients. Chronic corticotropin hypersecretion results in hyperplasia of the reticularis and fasciculata zones of the adrenal cortex, with hyperproduction not only of Cortisol but also of deoxycorticosterone and androgens. Two forms of Cushing's syndrome result from increased corticotropin levels pituitary-dependent Cushing's syndrome and ectopic Cushing's syndrome. The second type is corticotropin-independent Cushing's syndrome. Cushing's syndrome may be caused by a unilateral cortisol-secreting adrenocortical adenoma (10 ) or carcinoma (10 ). Primary adrenal hyperplasia is a rare cause of corticotropin-independent Cushing's syndrome. Because adrenocortical tumors secrete increased amounts of Cortisol, corticotropin production is suppressed. In patients...

Diagnostic Procedures

When Cushing's syndrome is suspected and iatrogenic causes have been excluded, the diagnosis should be confirmed by both an overnight dexamethasone suppression test (1 mg of dexamethasone is given at 11 pm, and a plasma Cortisol measurement is obtained in the morning) and the 24-hour urinary free Cortisol measurement. When the dexamethasone suppression test is normal (plasma Cortisol < 50 mmol L) and the urinary free Cortisol is normal (< 135 nmol 24 hours), the patient does not have Cushing's syndrome. False-positive tests may occur as a result of (1) chronic intake of certain drugs (barbiturates, phenytoin, rifampicin) or alcohol (which accelerates Cortisol metabolism) (2) the presence of a serious illness or stressful event, chronic diseases (renal failure), or major depressive states (which stimulate the secretion of glucocorticosteroids) and (3) obesity and highestrogen states (estrogen therapy, pregnancy), but in the obese patients the urinary free Cortisol is usually...

Localizing Procedures

And magnetic resonance imaging (MRI) scanning. Radiocholesterol scintigraphy is very useful in patients with Cushing's syndrome because it evaluates both adrenals simultaneously.8 9 In patients with adrenocortical hyperplasia resulting from a corticotropin-dependent syndrome, scintigraphy shows bilateral uptake (Fig. 70-4A). In the presence of a cortisol-secreting adenoma, focal uptake is observed, and scintigraphy accurately depicts the suppression of the contralateral adrenal gland (Fig. 70-4B). When an adrenal tumor is present, either CT or MRI scanning localizes the tumor and documents the size of the mass and its relationship to the surrounding structures (Fig. 70-4C and D). In selected patients with a unilateral adrenal mass, image-guided fine-needle aspiration cytology may be performed when requested for surgical planning.10

Anterior Pituitary Function

Role in the stress response complicate interpretation of the changes seen in its levels after BSD.121429 Levels of adrenocorticotropic hormone (ACTH) remain within the normal laboratory range after BSD.121430 Cortisol levels may also be 'normal' for non-stressed patients but this may indicate a relative deficiency, which might be uncovered with stress testing (short synacthen test). No relationship between cortisol levels and severe hypotension has been demonstrated.14

Mutations That Raise Blood Pressure

Glucocorticoid-remediable aldosteronism (GRA) is an autosomal dominant trait featuring early onset of severe hypertension caused by a novel gene duplication produced by unequal crossing over between two genes involved in adrenal steroid biosynthesis (Lifton et al. 1992a,b). One of these genes encodes aldosterone synthase, whose enzymatic activity is the rate-limiting step in aldosterone biosynthesis in the adrenal glomerulosa and is normally regulated there by signaling via angiotensin II. The other encodes steroid 11-P hydroxylase, which is employed in cortisol biosynthesis in adrenal fasciculate and whose expression is regulated by adrenocorticotropic hormone (ACTH). These two genes have recently evolved from a common ancestor and are 95 identical in DNA sequence they are tightly linked on chromosome 8, arranged in a head-to-tail orientation. The chimeric gene duplications that cause GRA fuse ACTH-responsive regulatory elements from 11-hydroxylase onto coding sequences that result...

Altered neuroendocrine regulation

From the latter studies it can be concluded that alteration in LH secretion in elderly men is not due to increased endogenous opioid tone, whereas the possibility of a relative leptin deficiency as underlying cause has also been excluded (Van Den Saffele etal. 1999). At present, the mechanisms underlying the apparent deficiency of GnRH secretion in elderly men remain to be fully elucidated. The observed changes in LH secretion with decreased mean LH pulse amplitude can be expected to have

Evidence Based Treatments

Field et al. (1997) conducted a randomized trial in which youth with mild to moderate JRA who either were massaged by their parents 15 minutes a day for 30 days or engaged in progressive muscle relaxation with their parents daily for 30 days. Findings revealed that the youth in the massage group experienced both psychosocial- and pain-related improvements. Massage immediately reduced parental anxiety, diminished child anxiety based on behavioral observations, and lowered salivary cortisol levels. Long-term massage effects included less frequent pain, lower severe pain, and fewer words for pain. Parent reports indicated less severe pain during the evening and fewer pain episodes limiting vigorous activity, whereas physician reports revealed less pain and less morning stiffness.

Preoperative Preparation

Patients undergoing adrenal surgery require thorough preparation. Such preparation is especially necessary when one uses an open approach. Venous thromboembolism is not uncommon postoperatively, so intermittent pneumatic compression of the legs or some other method of preventing deep venous thrombosis should be considered. Caution is necessary when using anticoagulants because of the risk of retroperitoneal hemorrhage postoperatively. A modified bowel prep using a clear liquid diet and cathartics should be given the day before surgery so the large intestine will not be filled with feces. The effects of excess hormone secretion should be reversed whenever possible. Patients with aldosteronomas should have potassium deficits corrected. Preoperative use of spironolactone or amiloride may facilitate this. The adverse effects of Cortisol excess can be blunted by giving metyrapone, ketoconazole, or mitotane. Vitamin A can counteract some of the poor wound healing that is seen in Cushing's...

Summary and future directions

Androgens circulate in appreciable amounts in women. Female serum testosterone levels rely on a complex interplay of hormonal secretion and bioconversion of peripheral prehormones. Testosterone levels are proportional to ovarian and adrenal secretion and peripheral bioconversion of the adrenal androgens DHEAS and DHEA, the predominant circulating androgens. Adrenal androgen secretion attenuates with age in a cortisol-independent fashion due to involution of the reticularis zone of the adrenal cortex. As a result, as women age, less testosterone is produced from peripheral bioconversion of DHEAS and DHEA. With the onset of menopause, while ovarian folliculogenesis ceases, the remaining theca and stroma respond to the elevated, menopausal levels of LH by greatly increasing ovarian testosterone secretion. This compensatory mechanism attenuates the age decline in serum testosterone levels from declining adrenal androgens. The combined effects create a subtle decline in serum testosterone...

Adrenal Neoplasia and Hyperplasia

Thirty-five percent to 40 of MEN 1 patients harbor adrenocortical lesions, and these are clearly overrepresented in the MEN 1 syndrome.1517 Most lesions are hyperplastic, bilateral, and nonfunctioning. Aldosterone- and cortisol-secreting adenomas, however, have been reported.1517 Hypercortisolism in MEN 1 can be the result of an ACTH-secreting pituitary process, a cortisol-secreting adenoma carcinoma or, rarely, due to an adrenocorticotropic hormone (ACTH)- or corticotropin-releasing factor-producing islet cell tumor or thymic carcinoid.25 Adrenocortical carcinomas have also been described in MEN 1 patients, most often in association with insulin-producing islet cell tumors.1725172 This raises the possibility of a shared underlying genetic cause or a trophic effect of insulin on adrenocortical cells.

Effects on the Developing Brain

The hypothalamic-pituitary-adrenal axis refers to the glands that release substances, such as cortisol, that are known to be elevated in abused children. These substances are also suspected to cause abnormalities in behaviors or phobias such as sleep disturbances and anxiety disorders.

DHEA secretion and age

Levels remain very low until they gradually increase between the sixth and tenth years of age owing to increasing DHEA(S) production by the zona reticularis, a phenomenon termed adrenarche (Reiter et al. 1977 Sklar et al. 1980). DHEA(S) concentrations peak during the third decade, followed by a steady decline with advancing age so that levels during the eighth and ninth decade are only 10-20 of those in young adults (Orentreich et al. 1992). This decline has been termed adrenopause in spite of unchanged or even increased cortisol secretion (Laughlin and Barrett-Connor 2000). The age-related decline in DHEA(S) levels shows high interindividual variability and is associated with a reduction in size of the zona reticularis (Parker Jr. etal. 1997). DHEA secretion follows a diurnal rhythm similar to that of cortisol while DHEA(S) does not vary throughout the day. Liu et al. (1990) observed an age-associated attenuation of the diurnal rhythm and the pulse amplitude of DHEA secretion....

Psychosocial Adjustment

Craniopharyngiomas are benign, slow-growing tumors that develop from remnants of the craniopha-ryngeal duct. They are relatively rare and grow in close proximity to the hypothalamus and pituitary. As a result, the tumor disrupts both the endocrine and autonomic nervous systems. Injury to the hypothalamus can produce changes in eating, sleeping, reproduction, and body temperature. Affected connections from the hypothalamus to the limbic system can lead to increased emotionality. Psychiatric disorder is also a consequence of resulting changes in endocrine functioning, as are the alterations in sleeping, eating, and autonomic functioning that frequently accompany hypothalamic injury. Following surgery for craniopharyngioma, nearly 60 of patients experience obesity due to hypothalamic in-sensitivity to endogenous leptin release (Roth et al. 1998). The extent of hypothalamic damage, assessed on magnetic resonance imaging, correlates with the postoperative body mass index. These patients...

Is The Checking Of Other Hormone Levels Postictally Worthwhile

Other hormones show less consistent postictal changes. Serum Cortisol is elevated after both bona fide and simulated generalized seizures.39 The Cortisol rise follows that of corticotropin, beta-endorphin, and beta-lipotropin, all products of a common precursor molecule, proopiomelanocortin.6 Elevated vasopressin after seizures has also been reported.60 Because all these hormones are secreted in response to stress, their postictal elevation may not be specific to epileptic seizures. Inconsistent findings of postictal changes in LH and FSH have been revealed by different authors.33-34 60 No consistent significant postictal change has been seen in serum levels of growth hormone or TSH.34,60 Thus, postictal testing of hormones other than prolactin is at present not clinically useful.

Are Any Other Hormonal Systems Clinically Affected By Partial Seizures

The function of the hypothalamo-pituitary-adrenal axis may be altered chronically as well as acutely in seizure patients.39,60 Cortisol has been shown to be elevated interictally in some studies61 but not in others.31 Corticotropin is also elevated interictally in patients with temporal lobe seizures,61 a finding that appears to be related specifically to abnormal functioning of the anterior temporal lobe,61 where the amygdala is located, and to be limited to TLE that involves the amygdala. For instance, stimulation of the amygdala in TLE patients62 as well as in animals63 leads to a rise in serum corticosteroids and corticotropin, but stimulation of the hippocampus inhibits their secretion.62 Corticotropin is secreted by the anterior pituitary in response to corticotro-pin-releasing hormone (CRH) produced by neurons in the paraventricular nucleus of the hypothalamus. These neurons receive a direct input from CRH-containing neurons in the amygdala.64 Postictal and interictal elevation...

Effects on Acute Phase Response and Cytokines

In a prospective randomized study of laparoscopic versus small-incision open cholecystectomy, Squirrell et al. (20) demonstrated significantly lower C-reactive protein levels following laparoscopic cholecystectomy. However, they found no differences in serum cortisol levels between the two groups and concluded that the neuro-endocrine component of the metabolic response, i.e., cortisol, was not influenced by the type of surgical access (20). These findings were contradicted by McMahon et al. (16), who found no differences in the levels of C-reactive protein or other acute-phase response proteins such as albumin and transferrin between laparoscopic and minilaparotomy cholecystectomy. Because open cholecystectomy in this study was performed through a much smaller incision than would normally be used for open surgical procedures, these results indicate that the trauma of abdominal access influences immunological function. Other studies of laparoscopic versus small-incision...

Efficacy Of Neuraxial Block

Despite the potential benefits of regional anesthesia on patient outcome, few data exist that link inhibition of surgical stress by neuraxial anesthesia and analgesia to patient outcome. Use of epidural anesthesia and analgesia in high-risk surgical patients results in decrease in urinary cortisol excretion, incidence of cardiovascular failure, major infectious complications, and overall postoperative complications.112 Patients receiving neuraxial anesthesia for lower extremity vascular surgery have lower norepinephrine levels and less incidence of graft failure.12 In addition, neuraxial anesthesia may improve patient outcomes through attenuation of the stress response-induced potentiation of postoperative hypercoagulability and immunosuppression.02 Thus, suppression of the stress response after surgery may result in improved outcomes in many areas, including cardiovascular, coagulation, and immune systems.

Efficacy Of Peripheral Nerve Block

By interrupting neural input into the CNS, peripheral nerve blocks may also minimize the surgical stress response after surgery. For instance, patients receiving regional anesthesia (interscalene block) for shoulder surgery have significantly lower serum epinephrine levels in the immediate postoperative period.122 Unlike those receiving general anesthesia, patients receiving regional anesthesia (retrobulbar block) for cataract surgery do not have a significant increase in catecholamines, glucose, and cortisol.112 112 Peripheral blocks of the sympathetic nervous system (paravertebral and celiac plexus block) may also blunt but not abolish the stress response.112 112 Systemic absorption of local anesthetic is not likely to be responsible for any suppression of the stress response in the immediate postoperative period.112 Intercostal, intraperitoneal, or intrapleural administration of local anesthetics is not effective in attenuating the stress response.122 1521 152 152 152 Although...

Hypertensive blood pressure values in acute ischemic stroke

Several observations have demonstrated spontaneous elevation of blood pressure in the first 24-48 hrs after stroke onset with a significant spontaneous decline after a few days 1-3 . Several mechanisms may be responsible for the increased blood pressure, including stress, pain, urinary retention, Cushing effect due to increased intracranial pressure and the activation of the sympathetic, renin-angiotensin and ACTH-cortisol pathways. Despite the increased prevalence of hypertension following stroke, optimal management has not been yet established. Several arguments speak for lowering the elevated BP risks of hemor-rhagic transformation, cerebral edema, recurrence of stroke and hypertensive encephalopathy. On the other hand, it may be important to maintain the hypertensive state due to the damaged autoregulation in the ischemic brain and the risk of cerebral hypoperfusion exacerbated by the lowered systemic blood pressure.

Complications of Radiation Therapy

Radiation therapy results in endocrine dysfunction and visual defects similar to those observed following surgery, but the severity of these complications, particularly with respect to diabetes insipidus, appears to be reduced. In a retrospective study of 72 patients at UCSF from 1972 to 1999 treated for initial disease, 32 had visual deficits after subtotal resection followed by irradiation, although 81 of these had visual deficits before treatment, and 72 retained the same functional status. For 36 patients treated for recurrent disease, only 53 retained the same functional status with no difference associated with extent of surgical resection, whereas 78 had permanent deficits. A majority of patients had impaired endocrine function. Sixty-four percent required thyroid hormone replacement, 56 required cortisol, 44 required sex hormones, 17 had diabetes insipidus, and 1 had elevated prolactin levels. The endocrinologic sequelae of radiation therapy are comparable with other series...

Table 463 Overview Of Immune Function

Cortisol and epinephrine may reduce neutrophil chemotaxis and decrease NK cell activity. 3 Also, perioperative administration of morphine diminishes NK cell and lymphocyte activity. In animal studies, morphine induces a decrease in lymphoid organ weight and inhibits ability to combat active infections. Immunosuppression is not reversed with administration of naloxone. Inhalational anesthetic agents may also inhibit interferon stimulation of NK cell activity. The effect of anesthetic agents on human immune response is unclear and may be clinically significant however, the effects resulting from surgical trauma are probably more important than those of anesthetic agents on postoperative immunosuppression.1

Can Hormones Be Used To Treat Epilepsy

Endocrine treatment of seizures may rationally be aimed at those endocrino-logic aspects of seizures that act either to exacerbate or to ameliorate them. As already discussed, progesterone may have an anticonvulsant effect, whereas estrogen, CRH, and Cortisol may have proconvulsant effects. Thus, treatment with progesterone, estrogen antagonists, and medications that suppress the activity of the hypothalamo-pituitary-adrenal axis may prove to be useful adjunctive treatments in appropriate patients. As mentioned previously, we have seen three patients with refractory seizures and hypercortisolemia whose seizures became controlled upon normalization of the patients' Cortisol levels by ketoconazole.65 Wider use of ketoconazole and other potential enzymatic inhibitors of Cortisol synthesis has not been explored.

Etiology and Pathology

Years, noted only a few consistent postmortem findings that might at some time help explain the nature of SIDS. These include, according to one SIDS researcher (Guntheroth 1989), intrathoracic pete-chiae, patchy pulmonary edema and emphysema, indicative of respiratory problems histopathology suggesting pre-existing hypoxia, such as changes in pulmonary arteries and right ventricle, smaller thymus, extra-medullary erythropoiesis, increased peri-adrenal brown fat cells, and enlarged adrenal chromaffin cells and neuropathological changes such as astroglial proliferation in brain stem, leu-komalacia, and delayed loss of dendritic spines in reticular substance, consistent with underdevelopment or a subtle chronic disorder. The pathological changes so far discovered fail to provide enough information for medical scientists to understand the etiology or mechanism behind SIDS deaths.

Weight Management Motorize Your Metabolism

Weight management is at a crisis level in our country. It is estimated by the U.S. Centers for Disease Control and Prevention that one-third of Americans are 20 percent or more overweight, which qualifies them as being obese. National surveys show that 25-50 percent of adults are on diets and spend about 30 billion each year on them. Unfortunately, a lot of that money goes to waste without the proper lifestyle changes. Two-thirds of those who lose weight will gain it back during the next three to five years. The average human body has 30-40 billion fat cells, which are genetically geared for helping you store unused calories. It's simple Use those calories, or they go into storage visible storage

The Population Health Perspective

Caldwell's skepticism notwithstanding, a growing number of demographers have been turning their attention toward a broader definition of health beyond simply counting the dead (or living). Without going to the opposite extreme of admitting everything under the WHO definition, health demographers have increasingly turned to more complex outcomes such as cause-specific mortality, disability, self-rated health, health services use, and health behaviors. Problems remain with the accuracy of self-reported health outcomes, but in many large-scale population-based surveys, both demographers and epidemiologists have begun to complement self-reports with biological markers of physiological change (Goldman 2001). Some of these biomarkers (such as salivary cortisol measurements) have only recently become widely available.

Integrating Biological Markers and Psychosocial Pathways

Including Cortisol, noradrenalin, epinephrine, and dihydroepiandrosterone (DHEA) (McEwen and Seeman 1999). These primary mediators have widespread influences throughout the body that potentially account for the differential resilience and vulnerability of individuals in response to adverse social circumstances. For example, cortisol is a quintessential stress hormone'' associated with activation of the hypothalamus-pituitary-adrenal (HPA) axis. The dysregulation of cortisol secretion is implicated in a wide range of disease processes, from elevated blood pressure and higher central adiposity to glucose intolerance, immune suppression, and cognitive decline (McEwen 1998). Cortisol measurement has been incorporated into surveys and study designs via 12-hour urine collections and, more recently, noninvasive and relatively inexpensive saliva specimens. In contrast to biological markers like cortisol (which represents one of the primary mediators of the allostatic process), biomarkers of...

Clinical Trial Methods

Immediate responses that disappear within a short period of time. This includes the fast bronchodilating effect of -agonists, responses to various provocations and specific systemic effects that are measured by markers in the blood (like plasma cortisol for glucocorticosteroids and serum potassium for However, there are caveats with crossover studies. The primary caveat is the possible presence of carry-over effects (in fact, non-equal carry-over effects), which might bias treatment comparisons. When deciding if a crossover design is appropriate for a particular study, we therefore must convince ourself, beforehand, that we can get rid of possible carry-over effects by separating the various treatment periods with washout periods during which no treatment is given. For a single-dose short-acting j2-agonist trial a washout period need in general only be a few days. A trial which studies cortisol depression after short periods of GCS administration should have washout periods of 1 -2...

Treatment of Special Populations

Glucocorticoids play a significant role in bone remodeling. Exogenous glucocorticoid administration results in an increase in bone resorption, inhibition of bone formation, and change in bone quality. Glucocorticoids (e.g., prednisone, hydrocortisone, methyl-prednisolone, and dexamethasone) promote bone resorption through reduced calcium absorption from the GI tract and increased renal calcium excretion. Bone formation is reduced through inhibition of osteoblasts. They also decrease estrogen and testosterone production.

Abnormal HPG Regulation

Although several mechanisms that parallel obesity to infertility have been proposed, many remain ambiguous and relatively undefined. Studies indicate that the central factor linking the mechanisms associated with obesity and infertility is an abnormal regulation of the HPG axis, as well as the previously discussed OS. The HPG axis responds to fluctuations in hormones causing a range of widespread and local effects on the body and aspects of reproduction. Excess fat accumulation can impair the feedback regulation of the HPG axis and be a contributing factor to abnormal semen quality. Since sex steroids and glucocorticoids control the interaction between the hypothalamic-pituitary-adrenal (HPA) and the HPG axes, any imbalance may in turn affect spermatogenesis and male reproductive function. The abnormal endocrine changes observed in obese, infertile men are not similar to men with either obesity or infertility alone. Therefore, simultaneous irregular hormonal profile and...

Acute Adrenal Insufficiency Related to Bilateral Adrenal Hemorrhage

Veins Fragile Adrenal

Stress may lead to bilateral adrenal hemorrhage or may cause acute adrenal insufficiency without hemorrhage. The burn patient is an example of this dual situation apparently related to a similar stress. Among 807 patients treated at Parkland Hospital over the previous 6 years, Murphy and colleague28 found 3 patients in whom acute adrenal insufficiency developed. They reviewed the existing theories of the pathophysiology of adrenal insufficiency in the burn patient. Vaughan and associates demonstrated Cortisol levels three to four times higher than normal in patients with burns greater than 30 . These patients lost their diurnal rhythm. Burn size correlated with Cortisol but not corticotropin levels.29 Hemorrhagic cortical necrosis is the most common pathologic finding associated with this acute adrenal insufficiency.28 The clinical picture is that of sudden and rapid cardiovascular collapse, which is frequently interpreted as sepsis. When the diagnosis of adrenal insufficiency is...

Neuropeptides In Psychiatric Disorders

Among the better explored connections is the role of CRH in stress-related disorders, including depression (Holsboer, 2001a,b Harro and Oreland, 2001 De Souza and Grigoriadis, 2002). Levels of CRH in the CSF have been found to be higher and CRH receptor densities lower in some populations of depressed patients, and the number of CRH-expressing neurons in the hypothalamic paraventricular nucleus is higher. Recurrence of depression can be fairly well predicted on the basis of enhanced cortisol response to CRH after dexamethasone-induced feedback inhibition of anterior pituitary (Reul and Holsboer, 2002). Several nonpeptide antagonists of the CRH1 receptor subtype have recently been developed. There is preliminary evidence that such drugs may be efficient against anxiety and depression (Zobel et al., 2000).

Mecanism Of Centripetal Lipid Accumulation Supraclavicular Fat And Face

Corticotroph cells produce ACTH and constitute 10 to 20 of the anterior lobe. Corticotrophs are concentrated in the central third of the gland but are also found in the lateral wings of the adenohypophysis and in the pars intermedia. Cortisol secretion is regulated by the hypothalamic-pituitary-adrenal axis. Corticotropin-releasing hormone (CRH) made by the par-aventricular neurons in the hypothalamus stimulate the release of ACTH. ACTH is synthesized as part of the precursor proopiomelanocortin (POMC), which is cleaved into pro-ACTH and b-lipotropin (PLPH). Further processing of pro-ACTH yields ACTH, corticotrophin-like intermediate lobe peptide (CLIP), endorphin, lipotropin, and melanocyte-stimulating hormone (MSH). The major role of ACTH is to stimulate steroidogenesis in the adrenal cortex, which results in the syn thesis and release of cortisol. Cortisol exerts negative feedback at the pituitary and the hypothalamus. Regulation of cortisol by the brain is through CRH release and...

Androgen dynamics in women

The three sources from which androgens in women arise from are the adrenal cortex, the ovarian theca (and to a lesser degree, ovarian stromal cells), and by peripheral bioconversion of circulating androgenic prohormones. The adrenal gland produces about 95 of circulating serum dehydroepiandrosterone (DHEAS, the production rate of which is 19 mg day in young women) and 50 of dehydroepiandrosterone (DHEA, the production rate of which is 16 mg day). The rest of circulating DHEA is produced by peripheral conversion of DHEAS (30 ) in addition to a small ovarian contribution (20 ) (Burger 2002). DHEAS circulates unbound to protein, has virtually no androgenic action, and has a half-life of 10 hours it serves as a circulating prohormone for production of DHEA and the more potent downstream androgens both in the circulation and in peripheral tissues. Twenty-eight percent of DHEA comes from hydrolysis of DHEAS, and about 31 of DHEA is sulfated to DHEAS (Haning etal. 1989 Bird etal. 1978). The...

Regulation Of Srebp Isoform Expression

Plasma Fplc

Taken together, the above evidence suggests that SREBP-lc mediates insulin's lipogenic actions in liver. This observation led to the discovery that SREBP-lc contributes to the development of hepatic steatosis or fatty liver associated with diabetes, obesity, and the metabolic syndrome. Hepatic steatosis is the most commonly encountered liver abnormality in the United States, owing to its strong association with obesity and insulin-resistant diabetes mellitus (Mokdad et al. 200l). Conservative estimates indicate that 40-60 of individuals with obesity or diabetes develop fatty livers. A subset of patients with fatty liver will subsequently develop fibrosis, cirrhosis, and liver failure. Data initially obtained in mice indicate that the fatty liver associated with insulin resistance is caused, in part, by increased SREBP-lc expression. The increased SREBP-lc expression occurs in response to the high insulin levels present in insulin-resistant states. Thus, SREBP-lc levels are elevated in...

Results Clinical data

Of 28 patients diagnosed between 1951 and 1959, 16 died of cortisol insufficiency precipitated by concurrent illnesses. In contrast, only two patients died in the group diagnosed between 1960 and 1970. This marked decrease in mortality was secondary to a better and regular follow-up and an improvement in their education regarding the nature and life-endangering risks of the disease. The salient clinical features are summarized in Table 3. Gonadal insufficiency was present in 94 of the patients, cortisol insufficiency in 96 and thyroid insufficiency in 88 . The earliest sign of pituitary failure was the inability to lactate. Three patients had scanty menses for Cortisol insufficiency Cortisol reserve was studied in all patients before replacement therapy. The basal urinary hydroxycorticosteroids ranged from undetect-able values to 1.0 mg day in the patients who did not show pituitary reserve. The response to ACTH, 40 units twice a day for 4 days (ACTHAR gel) was arbitrarily classified...

Temperament and Personality

One of the earliest indicators of vulnerability to the development of anxiety is behavioral inhibition, characterized by increased physiological reactivity or behavioral withdrawal in the face of novel stimuli or challenging situations (Kagan and Reznick, 1986). Behavioral inhibition may be a manifestation of a biological predisposition characterized by both overt behavioral (e.g. cessation of play, reluctance to interact in the presence of unfamiliar objects and people) and physiologic indicators (e.g. low heart rate variability, accelerated heart rate, increased salivary cortisol level, pupillary dilation, increased cortisol level). There is an increased frequency of behavioral inhibition among children of parents with anxiety disorders compared to those of normal controls (Biederman et al., 1991 1993 Beidel and Turner., 1997 Turner et al., 1987 Rosenbaum et al., 1991 1993 1988 Sylvester et al., 1988). The link between childhood allergies, eczema and...

Addisons Disease and Acute Adrenal Hemorrhage

The adrenal gland produces glucocorticoids and miner-alocorticoids. Glucocorticoid production is regulated by the hypothalamic-pituitary-adrenal axis. In response to a variety of stimuli from within the brain, corticotropin-releasing factor (CRF) is released into the portal circulation of the pituitary, which in turn stimulates the secretion of adreno-corticotropin (corticotropin). Corticotropin then enters the systemic circulation, where it stimulates the production and secretion of glucocorticoids and, to a lesser extent, miner-alocorticoids. In the adrenal cortex, corticotropin stimulates the conversion of cholesterol to corticosteroids. Adequate circulating levels of corticosteroids returning to the brain inhibit the production of CRF and corticotropin. Cortisol, corticotropin, and CRF are secreted with a diurnal variation, with levels higher in the morning than in the afternoon. Plasma Cortisol levels are highest at 8 am and lowest between 10 pm and 2 am. Stress disrupts the...

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