Identifying and Healing Adrenal Gland Fatigue

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Adrenal Glands Anatomy

There are two adrenal glands, one situated above each kidney. Both glands have a rich arterial blood supply, mainly from the suprarenal arteries from the aorta, branches from the renal arteries, and branches from the phrenic vessels. The venous drainage is normally by a single vein, on the right side draining directly into the inferior vena cava, and on the left side into the left renal vein.

Pathophysiology Of The Adrenal Glands

The adrenal glands are divisible into the cortex and medulla. The adrenal cortex is essential for life and produces glucocorticoid, mineralocorticoid, and androgenic steroid hormones. The medulla secretes the catecholamines epinephrine and norepinephrine, largely under neural control. No definite clinical condition has been ascribed to hypofunction of the adrenal medulla. Most of the manifestations of adrenal insufficiency occur when the physiologic requirement for glucocorticoid and mineralocorticoid hormones exceeds the capacity of the adrenal glands to produce them.

Adrenal Gland Problems

Your body contains two adrenal glands, one located on top of each kidney. Their function is to produce hormones that control your metabolism, heart rate, blood pressure, and other important body functions. Problems within the adrenal gland can cause increased levels of male hormones (also known as androgens). Even a slight increase of male hormone can interfere with the ovulation process and thus fertility. Signs of increased male hormone include excessive facial hair, hair on the

Adrenal Gland

Lipid depletion of the cortex is an usual but highly unspecific finding in the adrenal glands in sepsis, reflecting stress of the affected organism during protracted Fig. 3.28. Focal hemorrhages in the inner cortex of the adrenal gland in a case of ventilator-associated Pseudomonas aeruginosa sepsis. Fig. 3.28. Focal hemorrhages in the inner cortex of the adrenal gland in a case of ventilator-associated Pseudomonas aeruginosa sepsis. Fig. 3.29. Cut sections of adrenal glands showing intraparenchymal hemorrhage in a case of fatal Waterhouse-Friderichsen syndrome in an adult. Fig. 3.29. Cut sections of adrenal glands showing intraparenchymal hemorrhage in a case of fatal Waterhouse-Friderichsen syndrome in an adult.

Humoral and cellular autoimmune responses

Studies of cellular immunity to adrenal antigens have been based on classical (but now rather outdated) methods to detect delayed hypersensitivity reactions and lymphokine production. In these procedures, peripheral blood lymphocytes from patients were incubated in vitro with the putative antigens, often used as a rather crude suspension. Thus, it has been shown that most patients with Addisons disease have cell-mediated immune reactions to adrenal antigens as determined by the leukocyte migration test. There was no correlation with onset of disease, its duration and the presence of adrenal antibodies. The antigen preparations that have been utilized in leukocyte migration studies were organ-specific, but not species-specific, since monkey and porcine adrenals were used with the same success as human adrenals. In some studies the antigenic activity was localized in the mitochondrial but not the microsomal fraction, whereas in other experiments leukocyte migration inhibition was...

Glandular Extracts Hormones And Enzymes

Glandular extracts, hormones, and enzyme collections are specific to the species, age, and sex of respective animals. Major products such as pepsin, rennin and other digestive enzymes, lipase and trypsin enzymes extracted from the pancreas, bile from the liver, adrenocortical steroids from the adrenal glands, and female reproductive hormones from the ovary are all medically significant products. Though insulin has been referenced as one of the prime pharmaceutical products derived from animal by-products, it is now synthesized by other procedures. This is true for a number of other pharmaceuticals, but reliance on the natural production and extraction is still an important source of medical treatment and prevention compounds.

Neonatal Resuscitation

Normal newborns are equipped with physiologic, pharmacologic, and metabolic responses to enable them to survive the hypoxia that develops as a consequence of asphyxia. Generally, brain injury occurs only when the asphyxia is severe enough to impair cerebral blood flow. Initially the injury is reversible, and only longer periods of ischemia lead to permanent damage. The pattern of injury is strongly influenced by the distribution of blood flow. During asphyxia, blood flow is redirected to the heart, brain, and adrenals at the expense of other organs, such as the kidneys and the gastrointestinal tract. Within the brain, flow is directed to the brainstem at the expense of the high cerebral structures, such as the cortex. In the preterm neonate, the periventricular white matter is susceptible to injury. In the full-term or postterm neonate, the gray-matter regions, such as the overlying parasagittal watershed cortex, are more vulnerable to ischemic injury. When the asphyxial insult is...

Apoptosis in immunity

Express surface CD95 - are induced to undergo apoptosis upon entry into these sites. As elegant proof of this, mice carrying a non-functional CD95-ligand (gld) do not enjoy immune privilege and, in the case of the eye, display marked infiltration upon introduction of a virus (herpes simplex virus type 1, HSV-1) into the anterior chamber of this organ -resulting in keratitis. In stark contrast, introduction of HSV-1 into the eye of wild-type mice results in death of infiltrating lymphocytes and neutrophils and containment of the infiltrating cells to the anterior chamber. Similarly elegant transplantation experiments of testes from lpr and gld mice yielded a similar conclusion that CD95 ligand was responsible for maintaining immune privilege in this organ also. Other studies have demonstrated that CD95L is also abundantly expressed in other immune-privileged sites such as the brain, ovary, uterus, adrenal gland and prostate, suggesting that a similar protective mechanism from immune...

Other endocrine organs

Autoimmunity also develops against other endocrine organs such as the adrenal gland, pancreas islet cells, parathyroid, pituitary and ovary. The autoantibodies are much less prevalent than with thyroid disease but, if present, help in diagnosis. The reactivities, assays and primary associated disorders are summarized in Table 1.

The Range of Androgen Insensitivity Syndromes

AIS occurs in a range of forms, from complete to mild. Most mutations to the testosterone-binding region, and some other types of mutations, cause complete androgen insensitivity syndrome (CAIS). In this form of the syndrome, the XY person is born phenotypically female, and from birth is raised as a girl. Gender identification (the internal sense of being male or female) is female. Sexual orientation is typically heterosexual, and so most CAIS individuals are attracted to males. At puberty, estrogen production by the adrenal glands causes breasts to develop. However, no pubic or armpit hair develops, since in males and females this is controlled by testosterone, and no menstruation occurs. It is at this point that the condition is usually diagnosed. Once discovered, the testes are usually surgically removed to prevent the possibility of testicular cancer, which is more common in people with CAIS. The woman is infertile, but may be able to enjoy sexual relations if the vagina is long...

Reactivation Tuberculosis

While the majority of cases of tuberculosis are pulmonary, up to 15 percent of cases will have extrapulmonary manifestations. 4 Common sites include the adrenal glands, bones and joints, gastrointestinal tract, genitourinary tract, lymph nodes, meninges, pericardium, peritoneum, and pleura.

L Gastrointestinal Function Blood Glucose and Food Intake

One result is the secretion of the hormone adrenaline from the adrenal gland. Control of this secretion is principally via sympathetic nerves, with cell bodies in the thoracic spinal cord, controlled by presympathetic neurons in the rostral ventrolateral medulla oblongata. Neurons in the nucleus tractus solitarius project to the rostral ventrolateral medulla.

Endocrine System And Homeostasis

The adrenal glands are located atop each kidney and also have two main parts. The outer part, or cortex, produces steroid hormones the inner part, called the medulla, produces epinephrine and norepinephrine. Ninety-nine percent of the pancreas serves an exocrine function, producing digestive enzymes. The other 1 performs a critical endocrine function controlling blood glucose.

Laboratory Tests and Ectopic Pregnancy

Progesterone (P) is a steroid hormone secreted by the ovary, adrenal glands, and placenta during pregnancy. During the first 8 to 10 weeks of pregnancy, ovarian production of P predominates and serum levels remain relatively constant. After the tenth week of pregnancy, placental production increases and serum levels rise. Absolute levels of P are lower in pathologic pregnancies and fall when a pregnancy fails. This observation has led multiple authors to propose various P levels as a diagnostic aid in differentiating an early normal from a pathologic pregnancy. As with other diagnostic tests, the sensitivity of P testing increases and the specificity decreases as a lower threshold value is selected. Most pathologic pregnancies have P levels 10 ng mL. For P 5 ng mL, nearly 100 percent of pregnancies will be pathologic there are no normal pregnancies reported with P 2.5 ng mL. Progesterone levels > 25 ng mL have a 97 percent sensitivity for viable IUP. An intermediate value of P 15 ng...

Cholesterol Emboli Introduction Clinical Setting

Thus often involve the kidney, skin, gastrointestinal (GI) tract, adrenals, pancreas, and testes. Cholesterol emboli may occur spontaneously or after an invasive vascular procedure. This entity mimics vasculitis clinically, and presents with acute renal failure, new-onset or exacerbated hypertension, and eosinophilia (16-18). In some patients, there is associated presumed secondary FSGS, with proteinuria.

Problems Of The Lungs

(C) For relieving an acute attack of asthma, also stimulate the trigger areas for the adrenal glands (see page 89) and tie small rubber-bands on all toes for 10-12 minutes. During this time, if a toe starts paining or turns black, remove the concerned band for a while (till the normal colour returns) and then reapply it.

Clinical Presentation and Diagnosis

There are no effective serum tumor markers useful in screening patients for differentiated thyroid carcinoma. Initial laboratory evaluation includes the measurement of serum ultrasensitive thyroid-stimulating hormone (TSH), free thyroid hormone levels, antithyroid autoantibodies, and serum calcium to exclude coexistent parathyroid disease which can be found in patients with nodular thyroid disease and thyroid carcinoma. Most patients with thyroid nodules and thyroid carcinomas are biochemically euthyroid, but subclinical or biochemical hyperthyroidism associated with uninodular or multinodular thyroid disease can be detected by laboratory screening. Such patients have a 3-6 incidence of associated thyroid carcinoma. The presence of thyroid autoantibodies suggests Hashimoto's thyroiditis which may raise the suspicion of thyroid dysfunction and identify a controversial risk factor for DTC. Patients with a familial history of thyroid carcinoma should be screened for medullary thyroid...

Age Related Microgravity Effects and Critical Periods

Exposure to gravity deprivation using microgravity or weight unloading techniques gave evidence for the existence of age-related susceptibilities for morphological as well as for physiological and behavioral development. During the 16-day Neurolab mission, the development of various organs in flown neonate rats was strongly modified in the group launched at postnatal day P7. However, the modifications were smaller or absent in pups launched at postnatal day P14. In particular, after the flight, lung, heart, kidney, and adrenal glands of the P7 group were larger than ground controls. Thymus, spleen mesentery, and pancreas were smaller, and the aortic nerve had less unmyelinated fibers. In contrast, in the flight rats from the P14 group, only the kidney was heavier and the ovary lighter than in the ground controls (Miyake et al 2004). These observations clearly identified the second week of life as sensitive to gravity deprivation for morphological organ development.

Anatomic Considerations

Basic to an understanding of the clinical and radiologic criteria is precise knowledge of the anatomy of the extraperitoneal fascial planes, compartments, and relationships. The retroperitoneal space is bounded anteriorly by the posterior parietal peritoneum and posteriorly by the transversalis fascia. It extends from the pelvic brim inferiorly to the diaphragm superiorly. The major organs and structures within it include (a) the adrenal glands, kidneys, and ureters (b) the descending, transverse, and

Step 5 Followup laboratory evaluation

A high serum androgen value may suggest the diagnosis of polycystic ovary syndrome or may suggest an androgen-secreting tumor of the ovary or adrenal gland. Further testing for a tumor might include a 24-hour urine collection for cortisol and 17-ketosteroids, determination of serum 17-hydroxy-progesterone after intravenous injection of corticotropin (ACTH), and a dexamethasone suppression test. Elevation of 17-ketosteroids, DHEA-S, or 17-hydroxyprogesterone is more consistent with an adrenal, rather than ovarian, source of excess androgen.

Treatment of Autonomic Dysfunction

Magnesium sulfate inhibits the release of epinephrine and norepinephrine from the adrenal glands and adrenergic nerve terminals, eliminating the source of catecholamine excess in tetanus19 and providing a rationale for its clinical use.10 Morphine sulfate has also been demonstrated to be effective in treating the autonomic dysfunction in tetanus10 by reducing sympathetic a-adrenergic tone and central sympathetic efferent discharge, and by producing peripheral arteriolar and venous dilatation.9

Physiology Of The Anterior Pituitary Gland

There are six anterior pituitary hormones whose physiologic importance is clearly established. They include the hormones that govern the function of the thyroid and adrenal glands, the gonads, the mammary glands, and bodily growth. They have been called trophic or tropic from the Greek trophos, meaning to nourish,'' or tropic, meaning to turn toward.'' Both terms are generally accepted. We thus have, for example, thyro-trophin, or thyrotropin, which is also more accurately called thyroid-stimulating hormone (TSH). Because its effects are exerted throughout the body or soma in Greek, growth hormone (GH) has also been called the somato-tropic hormone (STH), or somatotropin. Table 1 lists the anterior pituitary hormones and their various synonyms. The various anterior pituitary cells are named for the hormones they contain. Thus we have thyrotropes, corticotropes, somatotropes, and lactotropes. Because a substantial number of growth hormone-producing cells also secrete prolactin, they...

Intraabdominal Masses

Neuroblastomas can arise from adrenal glands or along the sympathetic chain. They often cross to the midline, and the best cure rate is obtained in children under 1 year of age. Computed tomography is the best way to evaluate this tumor. Wilms's tumor is an intrarenal tumor initially and should be considered in children with hematuria. Ultrasound and computed tomography help define this tumor. Bone scan is also needed. Rhabdomyosarcoma occurs in the pelvis or anywhere there is striated muscle, and it is highly malignant.

Metastatic Prostate Cancer

CGI hypermethylation patterns in metastases obtained these specimens from autopsy cases of patients who died from refractory prostate cancer or from the small group of patients undergoing surgical resection of bone metastases to alleviate symptoms or monitor for response to novel therapies. Over a 7 year period, we systematically collected metastatic prostate cancer specimens at autopsy from 28 men who died of refractory prostate cancer. One to six anatomically distinct metastases from a wide array of sites, including bone, lymph node, liver, adrenal gland, intracranial subdural, and intraprostatic, were obtained from each patient (59).

Reflexology In Disorders Of The Endocrine System

Endocrine glands include 1 pituitary, 1 pineal, 1 thyroid, 4 parathyroids, 2 adrenals, 1 thymus, 1 pancreas, 2 ovaries in females or 2 testes in males. The pituitary gland secretes a number of hormones viz. ACTH (controlling the adrenals), TSH (controlling the thyroid), LH + TSH (controllingthe ovaries and the testes) and growth hormone (controlling the growth of the human body). A deficiency of growth hormone results in retarded physical growth (dwarfism).

Clinical Note continued

ACTH secretion therefore remains high and stimulates more pregnenolone production and causes adrenal hyperplasia (Fig. 20). Eventually, the hyperactive adrenals produce enough cortisol for negative feedback to be operative, but at the expense of maintaining a high rate of androgen production. The whole system can be brought into proper balance by giving sufficient glucocorticoids to decrease ACTH secretion and therefore remove the stimulus for androgen production.

Deficient Secretion

Hypoadrenalism (Addison's disease) can be either primary or secondary. Primary hypoadrenalism is caused by a failure of the adrenal cortex as a consequence of auto-immune disease, infection or surgery. As a consequence, ACTH levels are high because of a low circulating cortisol level. Melanocytestimulating hormone (MSH) is secreted in conjunction with ACTH leading to the characteristic pigmentation of the skin and buccal mucosa. Secondary hypoadrenalism results from reduced levels of ACTH following damage to the anterior pituitary. The deficiency in both mineralocorticoids and glucocorticoids results in characteristic clinical features The effects of increased secretion of androgens from the adrenals depends on the sex of the individual affected. The following features may be seen

Infiltrative or Infectious

Adrenal tuberculosis has declined in frequency as a cause of Addison's disease but is still reported to be a cause in 17 to 21 percent of the cases. Fungal infections and other infiltrative processes are infrequent causes of adrenal insufficiency during active, disseminated disease. Adrenal insufficiency as a complication of the acquired immunodeficiency syndrome (AIDS) has been reported. Infectious infiltration of the adrenal glands with Mycobacterium avium or M. intracellular or with cytomegalovirus may have caused the adrenal failure. Metastatic carcinoma in the adrenal glands is a relatively frequent finding at autopsy in patients with certain carcinomas, but it rarely causes adrenal insufficiency.

Bilateral Adrenal Hemorrhage

Bilateral adrenal gland hemorrhage is rare. In general, patients with a serious underlying condition whose adrenal glands are stressed are at risk for this complication. Stress-stimulated adrenal glands are hemorrhage prone. The association between adrenal hemorrhage and anticoagulant therapy with heparin and dicumarol is well established. Adrenal hemorrhage in this setting is most likely to occur between the third and eighteenth day of anticoagulation. Sudden deterioration with hypotension and pain in the flank, costovertebral angle, or epigastrium should suggest this disastrous event. Associated findings may include fever, nausea, vomiting, and disturbed sensorium. Computed tomography (CT) and ultrasound can assist in establishing this diagnosis. Other stressful events that have been associated with adrenal hemorrhage include surgery, trauma, burns, convulsions, pregnancy, and adrenal vein thrombosis. Adrenal crisis as a consequence of adrenal hemorrhage also occurs with...

TABLE 2082 Pathogenesis of Secondary or Tertiary Adrenal Insufficiency

Ihe mechanism of continued adrenal atrophy following discontinuation of exogenous steroids may be a failure of normal diurnal release of CRF. Stress-induced release of ACIH may remain intact, but the atrophic adrenal glands are unable to secrete sufficient cortisol to meet the physiologic requirements in response to stress. Ihe shortest time interval or the smallest dose at which HPA suppression occurs is unknown. As a general rule, there is no suppression regardless of the dose if its duration of use is less than three weeks. In addition, there is no suppression if the dose is < 10 mg of prednisone regardless of the duration unless it is given on an h.s. timetable. Any patient who is on more than 20 mg of prednisone for greater than three weeks is suppressed and should have the necessary precautions taken.

Adrenal Insufficiency And Shock

Adrenal insufficiency may be related to adrenal gland replacement by metastatic tumors or to adrenocortical suppression by therapeutic glucocorticoid administration. In either case, maximal adrenal function may be inadequate to support the individual when stressed by infection, dehydration, surgery, or trauma. Adrenal crisis and shock with vasomotor collapse may be sudden and fatal. The differential diagnosis of cancer patients with fever, dehydration, hypotension, and shock would more frequently include sepsis and hemorrhagic shock. Adrenal crisis is less common than bleeding and sepsis, but the steroid-dependent patient should be empirically given intravenous steroids with both glucocorticoid and mineralocorticoid effect. Normal adrenal glands maximally produce approximately 300 mg per day of hydrocortisone when stressed. This has served as a guideline for replacement therapy. Adrenalectomized individuals are maintained on average doses of 35 to 40 mg of hydrocortisone per day, and...

Mediators of the hypothalamicpituitaryadrenal axis

Hypothalamic dysfunction, hypophysectomy (removal of the pituitary gland) and adrenalectomy, separately or in combination, have dramatic and long-lasting effects on circulating immunocompetent cells. The absence of the pituitary gland eliminates the major source of various neuroendocrine hormones and neuropeptides, including luteinizing hormone, follicle-stimulating hormone, ACTH, prolactin, and growth hormone. The effect of hypophysectomy on the immune response is to alter the numbers of circulating leukocytes, reduce the capacity of both monocytes and macrophages to present antigens, and inhibit cytokine production by immunologically competent lymphocytes. Because the HPA axis is interrupted by removal of either the pituitary or the adrenal gland, glucocorticoids are no longer released into the circulation, thus eliminating a major regulatory factor that controls both the numbers of circulating leukocytes and the ability of these cells to or adrenal gland interrupts the pathway...

Normal Glucocorticoid Levels in Late Gestation

Normally, glucocorticoid production by the fetal adrenal gland is high in early gestation and becomes reduced during mid-late gestation.6,7 Maintenance of these normal low levels of glucocorticoids is essential for normal fetal growth and development. The fetus is usually 'protected' from exposure to circulating maternal Cortisol by the presence of the enzyme 1 lPhydroxysteroid dehydrogenase type 2 (11(3HSD2) in the placenta, which converts active Cortisol to inactive cortisone.

Surgical Treatment of Cushing Syndrome

Surgical treatment of Cushing syndrome involves removing the cause of cortisol excess. Transsphenoidal resection of an ACTH-producing pituitary tumor is successful in 80 percent or more of cases of Cushing disease. Treatment of ectopic ACTH syndrome involves resection of the primary lesion. Primary adrenal causes of Cushing syndrome are treated by removal of the adrenal gland containing the tumor. All patients who undergo adrena-lectomy for primary adrenal causes of Cushing syndrome require perioperative and postoperative glucocorticoid replacement because the pituitary-adrenal axis is suppressed.

Primary Aldosteronism

Primary aldosteronism (Conn syndrome) is a syndrome of HTN and hypo-kalemia caused by hypersecretion of the mineralocorticoid aldosterone. This uncommon syndrome previously accounted for less than 1 percent of unse-lected patients with HTN. However, recent data examining routine screening suggest that aldosteronism may be the cause of up to 15 percent of cases of HTN. An aldosterone-producing adrenal adenoma (APA) is the cause of primary aldosteronism in two-thirds of cases and is one of the few surgically correctable causes of HTN. Idiopathic bilateral adrenal hyperplasia (IHA) causes 30-40 percent of cases of primary aldosteronism. Adrenocortical carcinoma and autosomal dominant glucocorticoid-suppressible aldosteronism are rare causes of primary aldosteronism. Secondary aldosteronism is a physiologic response of the renin-angiotensin system to renal artery stenosis, cirrhosis, congestive heart failure, and normal pregnancy. In these conditions, the adrenal gland functions normally.

Roles Of Progesterone And Estrogens In Sustaining Pregnancy

FIGURE 8 Effects of estrogen on production of placental steroid hormones. By increasing uterine blood flow and inducing low-density lipoprotein (LDL) and the P450 side-chain cleavage (P450scc) enzyme, estrogens increase placental production of pregnenolone, which is used as substrate for androgen production in the fetal adrenals. Uptake of LDL from the maternal circulation may also transfer cholesterol to the fetal circulation. DHEA-S, dehydroepiandrosterone sulfate 16a-DHEA-S, 16a hydroxy-dehydroepiandrosterone sulfate CRH, corticotropin releasing hormone ACTH, adrenocorticotropic hormone hCG, human chorionic gonadotropin. FIGURE 8 Effects of estrogen on production of placental steroid hormones. By increasing uterine blood flow and inducing low-density lipoprotein (LDL) and the P450 side-chain cleavage (P450scc) enzyme, estrogens increase placental production of pregnenolone, which is used as substrate for androgen production in the fetal adrenals. Uptake of LDL from the maternal...

Placental Endocrine Functions

The key enzymes required for the conversion of the 21-carbon progestogenic steroids to the 18-carbon estrogens are 17a-hydroxylase 17,20-lyase and aromatase. There are substantial species differences in the extent to which these enzymes are present in placental tissues. In the sheep and cow, the placenta has low levels of 17a-hydroxylase 17,20-lyase during early pregnancy, thus limiting placental androstenedione production, but there is increased expression of the enzyme during late gestation. Placental androstenedione production may be supplemented by the fetal adrenal gland. Androstenedione may then be aromatized in the placenta to estrogens. In contrast, the rat placenta lacks aromatase. Thus, the placenta produces androgens during late gestation and releases them to the maternal circulation.

Direct Tubular Effects of Diuretics

Once released, renin stimulates the formation of angiotensin II which, in turn, stimulates the release of aldosterone from the adrenal gland. In the absence of diuretics, increased circulating levels of aldosterone induced by a contracted effective circulatory volume are not associated with a marked increase in renal potassium excretion. The kaliuretic effect is blunted because there is a simultaneous reduction in distal Na and fluid delivery as a result of enhanced reabsorption at nephron sites proximal to where aldosterone exerts its principal physiologic effect. In the setting of osmotic agents, carbonic anhydrase inhibitors and loop and thiazide diuretics, distal delivery of salt and water to aldosterone responsive cells in the distal nephron is increased such that the kaliuretic effect of aldosterone is fully expressed. It is increased distal K secretion rather than decreased proximal K reabsorption which accounts for the development of hypokalemia following the use of these...

Corticosteroids Cortisone and Relatives

Besides producing adrenaline, the adrenal glands secrete other hormones that control metabolism and body chemistry. This group of hormones comes from the gland's outer layer, or cortex, and so the principal one is called cortisone. Cortisone and its relatives all have a distinctive molecular structure known as the steroid nucleus (which they share with the male and female sex hormones described below). Pharmacologists have learned to make many semisynthetic drugs with this same structure, starting with raw materials found in certain plants. As a group, these drugs are all called corticosteroids, or simply, steroids, both the endogenous ones and the manmade ones.

Adrenocortical Cancer

Many of the issues related to the diagnosis and preoperative evaluation of the adrenal gland addressed in this chapter are covered in other chapters. Several important factors, such as early diagnosis, are addressed in the chapter on adrenal incidentaloma and in the chapters on the various functional adrenal tumors. This chapter will specifically discuss the epidemiology, diagnosis and treatment of the patient with adrenocortical cancer. Cancers of the adrenal gland make up only 0.05-0.2 of all cancer deaths.1 Adrenocortical cancer has a bimodal age distribution with the first peak prior to age 5, and the second peak between the ages of 40 and 50.2 Those patients who present prior to 5 years of age usually do so with virilization (> 90 ).3 Most patients with adrenocortical cancer are female. In general, men tend to present at an older age. Functional cancers are found more frequently in women, and nonfunctional cancers occur more frequently in men.4 As with most other endocrine...

Laparoscopic Adrenalectomy

The adrenal glands are deep retroperitoneal organs. The choice among conventional open methods for adrenalectomy depends on the size, location, and etiology of the adrenal mass and the patient's body habitus and medical condition. The flank or posterior approach through the bed of the twelfth rib avoids transgression of the thoracic and peritoneal cavities. This minimizes postoperative pulmonary problems and paralytic ileus. It is suitable for removing normal sized or hyperplastic glands and tumors up to 5 cm in size.1 However, exposure with the posterior approach is limited and intraabdominal exploration is precluded. Two separate incisions are required for bilateral adrenalectomy. The lateral or transthoracic approach through the bed of the tenth or eleventh rib provides the best exposure and is well suited for tumors larger than 12 cm. The transthoracic approach carries the morbidity of a thoracotomy, allows for only limited abdominal exploration and only one adrenal gland can be...

Stress and the Endocrine System

One function of the central nervous system is to evaluate and identify situations that can qualify as stress situations. The major components in the brain that are involved are the cortex, the limbic system, and the hypothalamus. The hypothalamus is the brain structure that bridges the nervous and the endocrine systems. In stress situations (fight or flight), the body mobilizes all of its energy to deal with the stress. The sympathetic nervous system, which is part of the autonomic nervous system, coordinates the effort to cope with the stress. The signal to activate the sympathetic nervous system is provided by the hormone epinephrine that is released from the medulla of the adrenal gland. A simplified description of the chain of events can be represented as follows Beginning with encountering a stress situation, hypothalamic production of a cortico-releasing factor (CRF) signals the pituitary to release the hormone ACTH (adreno-corticotrophic hormone), which, in turn, acts on the...

The Anti Inflammatory Role of Lipoproteins

Further investigations showed that the LPS was bound to HDL and that a plasma protein aided in the binding. In rabbits, the uptake of LPS by the adrenal glands was increased after LPS binding to HDL, which indicates that binding of LPS to HDL results in a decreased recognition by LPS receptors. Since then, in vivo and in vitro experiments have shown that LPS and LTA bind to and are neutralized by lipid emulsions (90), chylomicrons (91), VLDL (92), LDL (92), 0HDL (92), apoAI (93), apoB (93), and apoE (94).

Robot Assisted Da Vinci Urologic Surgery An Emerging Frontier

First, the feasibility of robot-assisted nephrectomy and adrenalectomy was reported in the pig 36 . Subsequently, the use of robotics has been demonstrated in nephrectomy, partial nephrectomy, and living-donor nephrectomy, with safety, and as an effective alternative to conventional laparoscopic procedures 37-39 . Various authors have also reported safe and effective robot-assisted laparoscopic adrenalectomy in humans 40-42 . Some authors even felt that the da Vinci system enables conventionally trained urologic surgeons to perform complex, minimally invasive procedures with ease and precision. The adrenal gland is small, vascular, and located in a difficult part of the body, and in such a situation the advantages of robotic assistance are tremendous. The biggest challenge, however, has been optimal positioning of the ports.

The Interrelationship Between Psychopharmacology and Psychoneuroimmunology

The adrenal gland secretes glucocorticoids in a pulsatile rhythmical way with the highest plasma concentrations being reached during the day. It has been shown that the lowest plasma concentration of the glucocorticoids coincides with the time at which the lymphocytes respond most actively to antigens. As the hypersecretion of cortisol is a characteristic feature of depression and other psychiatric conditions, it is perhaps not surprising to find that components of the immune system are also abnormal in this condition. All forms of stress result in the activation of the pituitary-adrenal axis, with a consequent rise in circulating catecholamines and glucocorticoid hormones from the adrenal gland. The secretion of ACTH from the pituitary gland, which is controlled by hypothalamic CRF, triggers the secretion of adrenal glucocorticoids, while stress-induced activation of

Sources of Effusions

Renal Fascia Radiology

The cone of renal fascia (arrows) envelops the adrenal gland, kidney (K), and perirenal fat. Medially it blends with the fascia of the psoas muscle (PM). The perirenal fat is particularly abundant in relationship to the lower pole of the kidney. The hepatic angle abuts on pararenal and perirenal fat. L liver Sp spleen. The cone of renal fascia (arrows) envelops the adrenal gland, kidney (K), and perirenal fat. Medially it blends with the fascia of the psoas muscle (PM). The perirenal fat is particularly abundant in relationship to the lower pole of the kidney. The hepatic angle abuts on pararenal and perirenal fat. L liver Sp spleen.

Solid Renal and Juxtarenal Lesions

Vincristine Syringe

Sympathetic nerve cells and may occur anywhere sympathetic tissue is found. However, over 75 are intraabdominal, with 65 of these arising from the adrenal glands (Chandler and Gauderer 2004). Neuroblas-toma is an unusual tumor characterized by its variability in presentation. Well-advanced lesions may regress spontaneously, whereas others may progress despite aggressive therapy.

Well Being Assessment Physiological Criteria

The adrenal glands are not the only ones stimulated by stress. Thyroid-stimulating hormone is released from the pituitary and stimulates release of thyroxine from the thyroid gland. Thyroxine increases metabolic rate and, therefore, calorigenesis. Carbohydrate stores will be utilized first, and then fat stores.

Atrial Natriuretic Peptide

Atrial Natriuretic Peptide Anp

The majority of ANP gene expression occurs in the cardiac atria, but there is low-level expression in extra-atrial tissues, e.g., central nervous system, adrenal gland, kidney, and ventricles. Expression in the latter tissue is generally only observed in early life or during ventricular hypertrophy. Hence, ANP mRNA expression has become a universal marker for ventricular remodeling that results from prolonged hypertension or other forms of cardiovascular insult. Differential processing of ANP in the kidney produces a variant containing four additional amino-terminal amino acids called urodila-tin. It has been reported to be more potent than ANP, possibly because it is less sensitive to proteolytic degradation by neutral endopeptidases (NEPs). Atrial-wall stretch, reflecting increased intravascular volume, is the dominant stimulus for ANP release. However, several hormones and neurotransmitters - such as endothelin, arginine vasopressin, and catecholamines -also stimulate its secretion.

Atrial Natriuretic Peptide and Related Peptides

Three ANP99_126 or natriuretic peptide receptor (NPR) subtypes have been identified. Two, NPR-A and NPR-B, contain cytoplasmic guanylyl cyclase domains which become active, converting GTP to cGMP, when ligand is bound to the extracellular domain. A third subtype, NPR-C, lacks the cytoplasmic guanylyl cyclase domain, and may participate mostly in clearance of bound ANP 1 . Although a lack of specific antisera has hampered localization studies, differential binding and detection of specific mRNAs have localized NPR-A to the renal cortex, including glomeruli, and medulla, while both NPR-A and NPR-B are found in peripheral vasculature and the adrenal gland. NPR-C is present in glomeruli and large renal vessels and absent in the medulla 55, 58 .

Molecular And Structural Characteristics

Adrenal Vasculature

Human PHT2 was found to be widely expressed in various tissues, with mRNA expression demonstrated throughout the gastrointestinal tract, with increased expression in the colon.35 Furthermore, hPHT2 mRNA expression was shown in the brain, colon, heart, kidney, leukocytes, liver, lung, ovary, pancreas, placenta, skeletal muscle, small intestine, spleen, testis, and thymus, which was all confirmed by Southern blot analysis.35 Interestingly, Sakata et al. demonstrated rPHT2 mRNA expression in lung, spleen, and thymus, with lower expression in brain, liver, adrenal gland, and heart by RT-PCR.21 Strong expression was also determined by in situ hybridization in immunocytes, specifically eosinophils, macrophages, and other phagocytes. Further confounding the elucidation of PHT2's function were observations by Sakata et al. suggesting an intracellular localization of PHT2 in the Golgi, lysosomes, autophago-somes, and vacuoles of HEK-293T and baby hamster kidney (BHK) cells.21 Interestingly,...

Pituitary Adenylate Cyclase Activating Polypeptide PACAP

Pacap Peptide

Like VIP, PACAP is also distributed ubiquitously and occurs mainly in nerves in the central nervous system, the lungs, and the gastrointestinal tract. PA-CAP has been demonstrated to exert a multitude of effects in these organs, such as relaxation of smooth muscle cells and stimulation of secretion from the pituitary and adrenal glands. In the central nervous system, a neurotrophic action of the peptide has also been reported. The neuropeptide is located in islet nerve terminals and in pancreatic ganglia, and because it is released from the pancreas during electrical activation of the vagal nerves, it is thought to be mainly a parasympathetic neuropeptide. It has, however, also been reported that PACAP is a neurotrans-mitter in sensory nerves. Finally, in one study PACAP has also been reported to be expressed not only in

Laparoscopic Adrenal Surgery

Laproscopy Surgery Adrenalectomy

Since the introduction of laparoscopic adrenalectomy in 19921 its use has become increasingly widespread. The advantages of removing adrenal glands laparoscopically are related to the small incisions used in this procedure, resulting in decreased length of stay, decreased utilization of parenteral pain medication, and earlier return to functional status. The initial imaging test of choice is a computerized tomography CT scan with fine cuts through the adrenal glands.5 This test will detect with a high degree of accuracy tumors greater than or equal to 1 cm, possible involvement of other organs, metastatic disease, and extraadrenal disease. If there is concern of caval involvement, especially in large tumors suspicious for malignancy, a magnetic resonance imaging (MRI) scan should be obtained to rule out this possibility,6,7 which would preclude a laparoscopic approach. The functional status of the tumor can be evaluated by scintiscanning. MIBG (I123-meta-iodobenzylguanidine) scanning...

Nature Of The Catecholaminergic Systems

Catecholamines are relativity small organic molecules that function in the brain and elsewhere in the body, primarily in a regulatory or modulating role, to keep various systems functioning smoothly in response to demands of the internal and external environment. The most familiar of the three natural catecholamines is adrenaline, or epinephrine (Fig. 1). Its effects have been experienced by all of us, for example, in response to a frightening experience. Its release into the bloodstream from the neuronal cell bodies located in the medulla of the adrenal gland regulates heart rate and blood pressure and helps to put us into a readiness state for fight or flight. Norepinephrine, the closest chemical relative of epinephrine, is more prominently localized in the brain than epinephrine, but it is also found in so-called peripheral neurons (those neurons found outside of the brain). In the brain norepinephrine regulates mood and level of emotional arousal and The amount of catecholamines...

Two Major Pathways Of The Stress Response

Another pathway that mediates stress responses in animals is the sympatho-adrenal axis (Fig. 1). Activation of this neurotransmitter axis results in release of ad-renergic hormones (mainly the catecholamines, adrenaline, and noradrenaline) from the medullae of the adrenal glands and from nerves that innervate lymphoid tissues and blood vessels. Catecholamine secretion occurs seconds following perceived threats, enabling rapid increases in heart and respiration rate and constriction of small blood vessels in peripheral tissues to increase blood flow to the brain, liver, and muscles, and enhancing awareness and athletic prowess to facilitate the fight-or-flight response. 4 However, like HPA axis activation, catechol-amine responses may be inappropriate and harmful to immunity and health in the context of exposure to recurring or chronic stressors.

Diffuse Extraperitoneal

Position Diaphragm When Erect

Adrenal glands are shown with striking clarity, much of the extraperitoneal gas is outside the perirenal space. A considerable part undoubtedly enters this compartment through its inferior communication with the iliac fossa, but there is also significant distribution into the posterior pararenal space in particular, outlining the contours of the liver, spleen, upper poles of the kidneys, medial crura of the diaphragm, and subphrenic extraperitoneal tissues (Fig. 8-210). Furthermore, because of the fusion of the renal fascial layers with the diaphragm superiorly, perirenal gas alone does not lead to pneumomedias-tinum and cervical emphysema, whereas gas in the posterior pararenal compartment frequently does. Supine and erect films demonstrate extraperitoneal gas paralleling the lateral borders of the psoas muscles (arrows). Cephalad extension on the left outlines the upper pole of the kidney, the adrenal gland, the medial border of the spleen, the medial crus of the diaphragm, and the...

Spontaneous animal models for organspecific autoimmune diseases

In addition, factors extrinsic to the immune system that also affect immunoregulation are altered in OS chickens, such as a significantly increased serum concentration of corticosteroid-binding globulin (CBG) and, therefore, decreased free, metabolically active glucocorticoids. Furthermore, OS chickens show a malfunctioning immunoendocrine feedback loop injections of antigen or IL-1 do not lead to the surge of blood corticosterone levels observed in normal birds. This altered glucocorticoid response is due neither to a defective production of glucocorticoid increasing factors (mainly IL-1) by the immune system of the OS, nor to a disturbed release of adrenocorticotropic hormone (ACTH) by the pituitary, nor to insufficient responsiveness of the adrenal glands, but can rather be attributed to an altered responsiveness of the hypothalamus to glucocorticoid-increasing factors or of the pituitary to corticotropin-releasing hormone (CRH). found with cell suspensions of other organs, such as...

Box 213 Biochemistry In Medicine

HDL may be taken up in the liver by receptor-mediated endocytosis, but at least some of the cholesterol in HDL is delivered to other tissues by a novel mechanism. HDL can bind to plasma membrane receptor proteins called SR-BI in hepatic and steroidogenic tissues such as the adrenal gland. These receptors mediate not endocytosis but a partial and selective transfer of cholesterol and other lipids in HDL into the cell. Depleted HDL then dissociates to recirculate in the bloodstream and extract more lipids from chylomicron and VLDL remnants. Depleted HDL can also pick up cholesterol stored in extrahepatic tissues and carry it to the liver, in reverse cholesterol transport pathways (Fig. 21-40). In one reverse transport path, interaction of nascent HDL with SR-BI receptors in cholesterol-rich cells triggers passive movement of cholesterol from the cell surface into HDL, which then carries it back to the liver. In a second pathway, apoA-I in depleted HDL in-

The Catecholamines Dopamine Norepinephrine and Epinephrine

The catecholamines, including dopamine (DA), nor-epinephrine (NE), and epinephrine (EPI), belong to a group of neurotransmitters called monoamines. These molecules contain a single amine (-NH2) group, a catechol nucleus (consisting of a benzene ring with two hydroxyl groups), and a side chain consisting of an ethylamine or a closely related derivative. EPI was originally called adrenaline and NE was called nor-adrenaline, as both were initially found in the adrenal gland. Retaining these original names, neurotransmission via EPI and NE is still termed adrenergic and noradrenergic, respectively.

Mediators Which Oppose Renal Salt Retention and Vasoconstriction

The two major systemic dopamine receptors are designated the DAf and DA2 receptors. (These receptors are to be distinguished from the better defined CNS dopamine receptors Dt through D5.) DA, receptors are located in the neuromuscular junctions of blood vessels, in renal tubules, and in sympathetic ganglia. Stimulation of the DAt receptors dilates blood vessels, inhibits renal tubule sodium reabsorption, and reduces postganglion sympathetic outflow. The DA2 receptors are primarily located in postganglionic sympathetic nerve terminals and in the adrenal gland. Activation of the DA2 receptors inhibits norepinephrine release from nerve endings and aldosterone and epinephrine release from the adrenal gland.

The Acute Phase Response and Alzheimer Disease

Elevated plasma levels of cortisol have been found in moderate to severe AD (65,75,132,234,283,313). Orell and O'Dwyer (283) have explained that this may be initiated by excessive cytokine production by injured brain cells which trigger release of corticotropin releasing factor (CRF) from the hypothalamus. CRF stimulates corticotropin release from the pituitary which in turn stimulates glucocorticoid release from the adrenal glands. The activity of this loop is, in part, regulated by the binding of glucocorticosteroid to corti-costeroid receptors in the hippocampus. In animals, aging is acompanied by an impairment in the ability of the hippocampus to inhibit corticotropin release, and is accompanied by a sustained high concentration of steroid production. In persons with AD, there is a delay in the decline of corticotropin concentration after challenge with dexamethasone. It is thought that the excessive and or prolonged cortisol secretion in AD may result in the persistent...

Laparoscopic Surgery in Kidney Cancer

Appropriate treatment of renal tumors is determined almost entirely by the clinical stage at presentation. Surgical resection remains the cornerstone of treatment for renal cell carcinoma. Radical nephrectomy, which includes resection of the kidney, perirenal fat, and adrenal gland was adopted in 1969.6

Therapeutic protocols for feline allergic skin disease

The liver, excessive fat in the kidneys, dystrophic mineralisation of the adrenal glands, degeneration of the testes and hyperkeratosis of the skin. Linoleate therefore has an important role in membrane function in that it influences growth, lipid transport, normal skin and coat condition, and maintenance of the epidermal permeability barrier. The cat is unable to synthe-sise significant quantities of AA and dietary sources are essential.

Working Model For The Neural Circuitry Of Anxiety Disorders

Neural Circuits Anxiety Disorders

A biological model to explain pathological human anxiety should involve both brain stem circuits and cortical and subcortical regions involved in memory and modulation of emotion. The evidence is consistent with chronically increased function of neurochemical systems (CRF and NE) that mediate the fear response in anxiety disorders. Although it is clear that activity at the central portion of the HPA axis is increased, responses at other portions of the HPA axis, including the pituitary and adrenals, and the long-term effects on the hormonal final product (cortisol), are less clear. Increased NE and CRF released in the brain act on specific brain areas, including hippocampus, mPFC, temporal and parietal cortex, and cingulate, that are dysfunctional in human anxiety disorders. Other neurochemical systems, including Bzs, opiates, dopamine, CCK, and NPY, also play a role.

Adrenal Incidentaloma

Obtaining a thorough history and physical examination should be the first step in evaluating the patient found to have an adrenal incidentaloma. Functional tumors, primary adrenocortical cancers, or metastases to the adrenal gland can often be diagnosed on the basis of a detailed history and physical examination alone. Questions should therefore be directed to rule out these entities. The patients should be asked about excessive weakness, extremes of mood, or recent unexplained weight changes. Females should be asked about a deepening of their voice, recent growth of hair on their face, chest, or arms, or changes in menstruation. Likewise, males should be questioned about breast enlargement or impotence. All of these questions are directed at identifying benign or malignant functioning adrenocortical tumors that can secrete steroid hormones such as cortisone, aldosterone, or sex hormones. In addition, the presence of symptoms associated with a pheochromocytoma, such as hypertension,...

Native Americans Early Uses of Animals

Products in medical treatment has not received the same attention. Animal products were used in a number of medical remedies in many Native American nations. Moose and bear fat were used by the Ojibwa to treat skin wounds and to ensure healthy skin in the extreme temperatures. Deer tendons were used as suture material by numerous tribes. The Yukon treated scurvy by ingestion of the animal adrenal glands. Fish oil, because of its high iodine content, was used to treat goiters in Eskimo and Aleut nations. Some South American nations treated epilepsy through shock treatment'' with electric eels. A type of injection device was used by some Native American nations well before the invention of the syringe in 1904. Such devices were constructed from the bladder of a deer or duck connected to a reed or quill of the porcupine. These syringes were used to clean wounds or to inject herbal medicine into the wound.

Relevance Of The Autonomic Innervation Of The Pancreatic Islet

Another important function of the parasympathetic nerves is to stimulate glucagon secretion during hypoglycemia, which provides a mechanism for the recovery of circulating glucose. The protection against hypoglycemia is also achieved by other mechanisms, for example, the secretion of adrenaline and cortisol from the adrenals as well as direct stimulation of the release of glucose from the liver, but the primary involvement of glucagon in this respect has been established. The glucagon response to hypoglycemia is due to direct stimulation of glucagon secretion by the low glucose level and by the reduced intraislet concentration of insulin, and several studies have shown that the autonomic nerves also contribute to a major degree. Thus, ganglionic blockade is associated with more than 75 inhibition of the glucagon response to hypoglycemia in conjunction with lowered responses of markers for parasympathetic activation, as demonstrated both in humans and in experimental animals. In...

Selyes Theorymodel Of Stress

The Austrian-born Canadian endocrinologist and psychologist Hans Selye (1907-1982) was one of the first modern psychologists to examine systematically the construct of stress and its effects on the organism, although medical and theoretical interest in stress goes back to the Greek physician Hippocrates (460-377 B.C.). In the 1920s, the American physiologist Walter B. Cannon (1871-1945) verified for stress theory that the stress response is part of a unified mind-body system, where a variety of stressors (such as lack of oxygen, extreme cold, emotional states) trigger the flow of adrenaline and noradrenaline that, in turn, enter the bloodstream from sympathetic nerve endings in the inner portion of the adrenal glands. Such physiological events help to prepare and adapt the body for what Cannon called the flight or fight syndrome, or what is known today as Cannon's emergency syndrome. Hans Selye spent 40 years of research on stress and expanded Cannon's findings to the extent that...

Pentose Phosphate Pathway of Glucose Oxidation

In other tissues, the essential product of the pentose phosphate pathway is not the pentoses but the electron donor NADPH, needed for reductive biosynthesis or to counter the damaging effects of oxygen radicals. Tissues that carry out extensive fatty acid synthesis (liver, adipose, lactating mammary gland) or very active synthesis of cholesterol and steroid hormones (liver, adrenal gland, gonads) require the NADPH provided by the pathway. Erythrocytes and the cells of the lens and cornea are directly exposed to oxygen and thus to the damaging free radicals generated by oxygen.

The Hypothalamus And Neuroendocrine Regulation

Neurohumoral Regulation

A role for hypothalamic timing mechanisms in neuroendocrine regulation is predicted by the rhythmic profiles of hormone release by the anterior pituitary and its target organs. This is clearly exemplified by the temporal profile of cortisol secretion by the adrenal gland. Release of plasma corticosteroids is under control of the hypothalamic-pituitary-adrenal (HPA) axis and exhibits a circadian profile, with peak levels occurring at the end of the dark phase in humans and the end of the light phase in rat. Although the temporal relations of these peaks differ between the two species, the temporal association of the peaks to activity is the same. Release of corticosteroids from the adrenal is under the control of corticotropin-releasing factor (CRF) neurons in the paraventricular hypotha-lamic nucleus. Release of CRF into the portal plexus at the median eminence elicits the synthesis and release of adrenocorticotropin hormone from the anterior pituitary, which subsequently stimulates...

Meat and meat products

The target antigens used in most studies on meat and meat products are blood or serum proteins, such as albumin. Some authors also used muscle proteins, preparations of adrenals, and sarcoplasmatic extracts to produce specific polyclonal antisera in rabbits, goats, and sheep. So far, in only a few studies were mice immunised for the production of monoclonal antibodies. The proteins used for the immunisation procedure cover a wide range of animal species, such as horse, cattle, pig, sheep and exotic species like impala and topi. Usually reliability and sensitivity of these assays decreases with increased heating of the samples, even when relatively stable proteins, such as myoglobulin (Hayden, Autoclaved muscle extract (pig) Heated adrenals and muscles

Characteristics of Diuretic Induced Hypokalemia

The decline in the serum potassium concentration usually develops within the first 2 weeks of therapy and then stabilizes as a new steady state is achieved. Thereafter, the serum potassium concentration should remain stable. Further declines in the serum potassium concentration are prevented by several factors which serve to decrease renal potassium secretion. Increased reabsorption of sodium in the proximal nephron as a result of the diuretic-induced decreases in extracellular fluid volume serves to dampen sodium and fluid delivery to the distal nephron. In addition, a progressive increase in mineralocorticoid activity is prevented as the development of hypokalemia tends to inhibit release of aldosterone from the adrenal gland. Chronic hypokalemia is also associated with a direct cellular effect leading to decreased distal nephron K excretion. Finally, K reabsorption is stimulated in the collecting duct under conditions of chronic hypokalemia as a result of increased activity of the...

Autoimmune features of vitiligo

Vitiligo can be found in autoimmune families in association with Addison disease, alopecia areata, pernicious anemia, or mucocutaneous candidiasis, with an incidence 10-15 times higher than in the general population. Antibodies to thyroid, adrenal gland and gastric parital cells can be demonstrated in vitiligo patients using modern techniques, antibodies reactive with melanocytes have been consistently-found in vitiligo patients' sera. The levels of these antibodies are greatest in patients with actively progressing disease and in vitiligo patients with other autoimmune disease. Both melanocyte-specific antibodies and antibodies reactive to other cells in addition to melanocytes have been identified. Some of these antibodies are specific for proteins involved in melanization such as tyrosinase and tyrosinase-related protein 1. Antibodies to a melanocyte-specific 85 kDa antigen have been described in dogs, cats and horses with vitiligo. Similar antibodies are found in a chicken model...


Figure 1 (A) Adrenal gland from patient with Addisons disease, showing atrophy of the cortex and infiltration with mononuclear cells. (B) Another area from same adrenal gland, photographed at higher magnification. (See also color Plate 6.) Figure 1 (A) Adrenal gland from patient with Addisons disease, showing atrophy of the cortex and infiltration with mononuclear cells. (B) Another area from same adrenal gland, photographed at higher magnification. (See also color Plate 6.) thelium is present, it is not arranged in three different zones, but in strands or rows of irregular size, contour and direction. There is loss of cellular outline, swelling and vacuolar appearance. Some cells are extremely large, with granular or vacuolated cytoplasm, others are small. In addition, both hyperplasia and hypertrophy can be observed in adrenals from patients with idiopathic Addisons disease. Scattered islands of cells may be seen in the cortex as well as large well-circumscribed adenoma-like...


The cause(s) of autoimmune Addisons disease is(are) still unknown. Expression of MHC class 11 antigens, suggested as a key event in the initiation and or maintenance of organ-specific autoimmunity, occurs in normal adrenals and, therefore, is unlikely to be the primary etiologic event of Addisons disease. Defects in HLA-DQ(3 chain, found in IDDM, have not been reported in patients with Addisons disease. On the other hand, a deficiency of T suppressor cell activity was noted by some authors. To date, restricted T cell receptor (TCR) usage, alterations of the idiotype-anti-idiotype network and changes in the balance of the cytokine network have not been demonstrated in autoimmune Addisons disease.


Multiple cases of pernicious anemia have been reported in families, often for several generations, and this frequency may be as much as 20 times greater than in the normal population. There is a raised but not absolute concordance of pernicious anemia in monozygotic twins and there are intrafam-ilial aggregations of the autoimmune diseases associated with pernicious anemia, namely the thyroid antoimmune diseases, insulin-dependent diabetes mellitus and primary Addison's disease of the adrenal gland which may be expressed as frank or subclinical disease marked by the presence of autoantibodies specific to these diseases. The prevalence of gastric parietal cell antibodies in first-degree relatives of patients with pernicious anemia is 20 which is three times higher than that found in normal controls and the frequency of autoantibodies to thyroid, pancreatic islet cells and adrenal cortical cells is also higher among relatives.


Autoimmune diseases are usually diagnosed according to the functional deficits that ensue in affected organs, rather than by their immunological features per se. This applies to autoimmune disease affecting the thyroid gland, adrenal gland, pancreatic islets, stomach, liver, kidney, muscles, neural transmitters, etc. However, testing for the disease-relevant autoantibody will in many instances provide specific and decisive diagnostic information, exemplified by testing for the antiglobulin reaction in hemolytic anemia, and for autoantibodies to acetylcholine receptor in myasthenia gravis, adrenal cortical cells in Addison's disease, dsDNA in SLE, mitochondrial pyruvate dehydrogenase enzyme complexes in primary biliary cirrhosis, or to the combination of nuclei and F actin in type 1 autoimmune hepatitis. An interesting application of modern sensitive and automated tests for autoantibodies, utilizing recombinant autoantigens, is screening for presymptomatic autoimmune disease, e.g....

Endogenous Ouabain

In the 1960s and 1970s, de Wardener and colleagues developed evidence for the existence of various natriuretic factors, which could stimulate salt excretion in the setting of volume expansion by inhibition of tubule Na K ATPase 16 . While numerous extracts of plasma and urine from volume expanded animals inhibited Na K ATPase activity and reduced transepithelial Na+ transport in a number of renal model epithelia, the identity of these factors remained unclear 16 , Recent studies have provided strong evidence that at least one of these factors may closely resemble ouabain itself 8 , The structure of ouabain is shown in Fig. 7. Similar compounds have been found in extracts of numerous plant species, most prominent of which is digitalis, an extract of the foxglove plant (Digitalis purpurea). Ouabain binds to the a subunit of Na K ATPase and inhibits pump activity. Ouabain was shown to be present in high concentrations in the adrenals of rats, cows, and humans and has been measured at...

The NPY Y1 Receptor

The NPY Y1 receptor is pharmacologically characterized by its high affinity for Pro34 NPY and D-Arg25 NPY its low affinity for N-terminally truncated NPY analogues and its high affinity for nonpeptide antagonists such as 1229U91, BIBP3226, and BIBO3304 (Table 1, Figure 1). Structurally, the receptor is related to the NPY Y4 and NPY y6 receptors (Figure 2). NPY Y1 receptor mRNA is expressed at highest levels in brain (especially cortex, hippocampus, thalamus, and hypothalamus), vascular smooth muscle, heart, kidney, spleen, skeletal muscle, lung, testis, adrenal gland, placenta, bone marrow, and gastrointestinal tract. NPY Y1 receptor protein distribution mirrors mRNA distribution fairly closely with the notable exception that low levels of receptor are detected in most hippocampal regions. The NPY Y1 receptor is coupled to multiple signal transduction pathways via pertussis toxin sensitive G proteins (Gi and or Go), including reduction of cyclic AMP (cAMP) formation, an increase in...

Prenatal Development

The placenta also has important endocrine functions. Soon after implantation, chorionic gonadotropin (CG) is produced. This maintains the corpus luteum so that progesterone production is continued. Progesterone maintains the thick endometrium. After month three or four of the pregnancy, CG drops sharply and the placenta produces progesterone itself the corpus luteum is allowed to degrade. The placenta also produces large amounts of estrogens, especially estriol, from testosterone produced by the fetal adrenal glands. The high levels of progesterone and estrogen are thought to contribute to the morning sickness'' experienced by some pregnant women. The hormone human placental lactogen, placental prolactin, plus maternal hormones prolactin and thyroid hormones prepare the mammary glands for milk production and has other effects similar to growth hormone. The peptide hormone relaxin prepares for birth by causing dilation of the cervix and suppressing oxytocin production by the...

Why Accommodate

Not accommodating livestock needs, which thus results in distress, can also impair animal health. When animals enter a state of distress, their bodies attempt to cope with this stress by increasing glucose availability, altering blood flow, and altering behavior. The hormones responsible for these alterations, often termed stress hormones, can impair the immune system and other functions of the body such as reproduction. Glucocorti-coids are key hormones in the stress response. When an animal is stressed, a cascade of events, starting in the hypothalamus and culminating at the cortex of the adrenal gland, causes the release of glucocorticoids, which are then able to increase glucose availability in order for the animal to effectively respond to the stressor. However, glucocorticoids are also known to be immunosuppressive. Thus, chronic exposure to stress (for example, due to crowding) can allow the animal to succumb to pathogens in the environment, becoming sick and possibly dying. In...

Response To Stress

Fig. 1 The hypothalamic pituitary adrenal (HPA) axis and the sympatho adrenal (SA) axis are activated in response to a stressor. CRH, corticotropic releasing hormone ACTH, adrenocortico tropic hormone. CRH causes the release of ACTH, which causes the release of glucocorticoids from the cortex of the adrenal gland (the HPA response). Sympathetic activation of the autonomic nervous system causes the release of epinephrine from the medulla of the adrenal gland (the SA response). (View this art in color at Fig. 1 The hypothalamic pituitary adrenal (HPA) axis and the sympatho adrenal (SA) axis are activated in response to a stressor. CRH, corticotropic releasing hormone ACTH, adrenocortico tropic hormone. CRH causes the release of ACTH, which causes the release of glucocorticoids from the cortex of the adrenal gland (the HPA response). Sympathetic activation of the autonomic nervous system causes the release of epinephrine from the medulla of the adrenal gland (the SA...

Other Organs

In neonate rats that had reached stage P7 at launch, several organs revealed remarkable differences in size compared to their ground siblings after the Neurolab 16-day spaceflight. Lung, heart, kidney, and adrenal glands became significantly larger by microgravity while thymus, spleen mesentery, and pancreas were smaller. Furthermore, the aortic nerve had a smaller number of un-myelinated fibers in flight neonates (Miyake et al 2004).

DNA viruses

Burkitt's lymphoma first presented as a maxillary tumour, initially believed to be a localized granuloma or round-cell sarcoma, but with recognition that deposits were present also in kidneys, adrenals and ovaries, the condition was identified as an unusual form of lymphoma. The tumour occurs only in a belt north and south of the equator where there is a high rainfall and very high levels of malarial infections. The discovery of EBV in cells cultured from Burkitt's lymphoma suggested that this was the causative agent, but the disease can occur in its absence. Furthermore, EBV infection affects > 95 of the world population. The restricted geographical distribution of Burkitt's lymphoma implicates a cofactor and this is believed to be constant antigen stimulation from malarial infection stimulating the continuous recruitment of new B-cells which, under the influence of virus, avoid programmed cell death.


Cortisol and glucose provide developmental regulation, while adrenaline (epinephrine) and gluca-gon provide acute and more variable regulation. Experimentally, cortisol infusion decreases glyco-gen content of the liver while deficiencies in hypothalamic-pituitary regulation of the adrenal gland leads to cortisol deficiency and glycogen deficiency. Insulin acts synergistically with glucose to increase hepatic glycogen stores. Glucose also acts independently to activate glycogen phosphorylase and glycogenolysis to keep hepatic glycogen content constant at higher glucose concentrations.


Approximately 15-20 mg of cortisol is secreted daily. Corticotropin releasing hormone (CRF) from the hypothalamus is carried to the anterior pituitary gland in a portal venous system and stimulates release of ACTH. The ACTH circulates to the adrenal cortex where it stimulates synthesis and release of cortisol (very little cortisol is actually stored in the adrenal gland). Approximately 95 of glucocorticoid circulates bound to an a-globulin and the remainder is free steroid. A negative feedback effect from the free cortisol inhibits release of both CRF from the hypothalamus and ACTH from the anterior pituitary gland. There is a normal diurnal variation in glucocorticoid levels in 24 h with a trough at approximately 4 a.m. The main actions of glucocorticoids are

Adrenal medulla

Catecholamines are not essential for life but are essential for reaction to acute stress (preparation for 'flight or fight'). The sympathetic nervous system stimulates the adrenal medulla to release catecholamines directly into the circulation. In view of the anatomical position of the adrenal glands, this is directly into the upper inferior vena cava and directly to the heart for immediate effect. The main actions of catecholamines are


ACTIONS AND PHARMACOLOGY This is a highly selective angiotensin II receptor antagonist that blocks the vasoconstrictor and aldosterone-secreting effects of angiotensin II. It selectively blocks the binding of angiotensin II to specific receptors found in vascular smooth muscle and the adrenal gland. 18 It undergoes substantial first-pass metabolism by cytochrome P-450 enzymes and is converted to an active metabolite. The half-life of losartan is about 2 h and of the metabolite is about 6 to 9 h. Peak concentrations of losartan and its active metabolite are reached in 1 h and in 3 to 4 h, respectively.


The pituitary gland has usually been thought of as the ''master gland'' because its hormone secretions control the growth and activity of three other endocrine glands the thyroid, adrenals, and gonads. Because the secretory activity of the master gland is itself controlled by hormones that originate in either the brain or the target glands, it is perhaps better to think of the pituitary gland as the relay between the control centers in the central nervous system and the peripheral endocrine organs. The pituitary hormones are not limited in their activity to regulation of endocrine target glands they also act directly on nonendocrine target tissues. Secretion of all of these hormones is under the control of signals arising in both the brain and the periphery.

Healthy lifestyle

Obesity is associated with an increased risk of breast cancer in post-menopausal women, the mechanisms of which may be hormonal. It has been demonstrated that obese women metabolise androstenedione (from the adrenal gland) into oestrogen in the adipocytes. The circulating levels of oestrone are higher in obese post-menopausal women than non-obese individuals. In pre-menopausal women obesity may be associated with a reduced risk of breast cancer, although the reasons for this difference are unclear.

Adrenal Cortex

Adrenal cortical hormones have been divided into two categories based on their ability to protect against these two causes of death. The so-called mineralocorti-coids are necessary for maintenance of sodium and potassium balance. Aldosterone is the physiologically important mineralocorticoid, although some deoxycor-ticosterone, another potent mineralocorticoid, is also produced by the normal adrenal gland (Fig. 2). Cortisol


Androgens are steroid hormones produced in the gonads (ovaries in women, the testes in males) and in the adrenal glands. In women, androgens are produced in two locations The adrenals and the ovaries (in males, they are produced in the adrenals and testes). Cortisol production in the adrenals Where zonas fasciculata and reticularis Regulated by ACTH Derived from Cholesterol DHEA and DHEAS are androgen products from the adrenals. Increased levels of these indicate that the source is adrenal.


The major glucocorticoid is cortisol, which is secreted in response to direct stimulation by adrenocorticotropic hormone (ACTH) from the anterior pituitary gland. Secretion of ACTH is governed by the hormone corticotropin-releasing factor (CRF) from the hypothalamus. This normally occurs with a diurnal rhythm, with the highest levels in the morning and the lowest levels in the late evening. On stimulation by ACTH, the adrenal glands respond in minutes to secrete cortisol in direct proportion to the ACTH concentration. Cortisol is normally secreted at the rate of 20 to 25 mg day. Through negative feedback inhibition, the plasma cortisol level acts to suppress ACTH release.


Primary adrenal insufficiency, or Addison's disease, is due to disease or destruction of the adrenal cortex and has a wide variety of causes ( IabJ,e,,,,2 0.8.- 1 ). Approximately 90 percent of the adrenal cortex must be involved before clinical manifestations of adrenal failure result. Idiopathic atrophy of the adrenal glands is the leading cause of chronic adrenal insufficiency. Idiopathic adrenal insufficiency has been further divided into autoimmune (70-75 percent) and truly idiopathic (25-30 percent).


In children, adrenal insufficiency is due to rare congenital causes or to acquired lesions of the hypothalamus, pituitary or adrenal cortex. By far, the most common cause of acquired chronic adrenal insufficiency is autoimmune destruction of the adrenal glands. Type I autoimmune polyendocrinopathy manifests with chronic mucocutaneous candidiasis, hypoparathyroidism and Addison's disease. Type II autoimmune disease presents with adrenal failure in association with thyroid disorder or insulin dependent diabetes mellitus. Infections account for approximately 20 percent of the cases of pediatric adrenal insufficiency. Among those are infiltrative destruction of the gland by fungal infections and tuberculosis. Hemorrhage into the adrenal glands may occur in the neonatal period as a consequence of a complicated labor or asphyxia. Another cause of adrenal gland hemorrhage is the Waterhouse-Friderichsen syndrome resulting from meningococcemia and producing shock. Finally, about one-third of...

Adrenal Crisis

Adrenal crisis is an acute, life-threatening emergency that must be suspected and treated based upon clinical impression. It is due primarily to cortisol insufficiency and to a lesser extent, aldosterone insufficiency, and occurs when the physiologic demand for these hormones exceeds the capacity of the adrenal glands to produce them. Adrenal reserve may be exhausted in patients with chronic adrenal insufficiency when they are subjected to intercurrent illness or stress. These patients should be taught to respond to minor febrile illness or stress by increasing their glucocorticoid dose by 2 to 3 times the usual dose for a few days during the illness. Mineralocorticoid dose does not need to be changed. During an emergency from severe trauma or stress, dexamethasone 4 mg IM can be self-administered. A variety of conditions may precipitate crisis these include major or minor infections, trauma, surgery, burns, pregnancy, hypermetabolic states such as hyperthyroidism, and drugs,...


If the patient has primary adrenal insufficiency, all plasma cortisol levels are low (< 15 pg dL), and the urinary 17-OHCS is also low, confirming the inability of the adrenals to respond to ACTH stimulation. An adequate rise in the plasma cortisol level excludes the diagnosis of adrenal insufficiency. A response indicative of partially intact adrenocortical reserve excludes the diagnosis of primary adrenal failure in favor of secondary adrenal insufficiency, but further testing is required to confirm this diagnosis. Other methods for simultaneous diagnosis and treatment have been described.

Gross anatomy

Anteriorly, the right kidney is covered on its medial aspect by the second part of the duodenum and the liver overlying the upper pole and hepatic flexure of the colon covering the lower part of the anterolateral aspect. The left kidney has the tail of the pancreas together with the edge of the greater curve of the stomach separated by the lesser sac on its medial aspect, the spleen lateral to this and the lower half of the kidney related to the splenic flexure of the colon. Both kidneys have the adrenal glands superomedially.


Adenocarcinoma of the kidney (also known as renal cell carcinoma) is the most common type of renal tumour. It can occur at any age, but is commonest in the sixth and seventh decade. About 60 of cases occur in men. Presenting symptoms can include haematuria, loin pain or a palpable mass. However, an increasing number of renal tumours are now diagnosed as incidental findings on CT or ultrasound scan, following investigation for other conditions (Fig. 19.6). Occasionally, a tumour will present with a paraneoplastic phenomena, such as thromboembolism, polycythaemia or anaemia. The primary tumour may metastasize directly to adjacent lymph nodes and the adrenal gland or distantly to the lungs and occasionally bone. Treatment of renal cell carcinoma depends on its stage, at presentation. If the tumour is confined to the kidney, radical nephrectomy (removing the kidney, perinephric fat and adrenal gland) is frequently curative. The operation can be


Causing ACTH-dependent hypercortisolism. Patients with ACTH-independ-ent hypercortisolism require thin-section CT scan or MRI of the adrenal gland, both of which identify adrenal abnormalities with more than 95 percent sensitivity. Patients with ACTH-dependent hypercortisolism and either markedly elevated ACTH or a negative pituitary MRI should have CT scan of the chest to identify a tumor-producing ectopic ACTH.

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