What Causes Adrenal Fatigue
The adrenal glands comprise an outer cortex and inner medulla. The cortex is derived from mesoderm and is responsible for the production of steroid hormones (glucocorticoids, mineralocorticoids and sex steroids). The medulla is derived from ectoderm (neural crest) and acts as a part of the autonomic nervous system. It receives sympathetic preganglionic fibres from the greater splanchnic nerves which stimulate the medulla to secrete noradrenaline and adrenaline into the bloodstream. Position the adrenals are small glands which lie in the renal fascia on the upper poles of the kidneys. The right gland lies behind the right lobe of the liver and immediately posterolateral to the IVC. The left adrenal is anteriorly related to the lesser sac and stomach. Blood supply the phrenic, renal arteries and aorta all contribute branches to the adrenal glands. Venous drainage is on the right to the IVC and on the left to the left renal vein.
The adrenal glands are positioned superior to the kidneys and are divided into the adrenal cortex and the medulla. The cortex has three layers. The most superficial layer is the zona glomerulosa, which is deep to the adrenal capsule and responsible for the secretion of mineralocorticoid hormones. The next layer is the zona fasciculata which mainly secretes glucocorticoids, hormones responsible for the breakdown of proteins and lipids and the synthesis of glucose. The zona reticularis is the deepest layer of the cortex and it secretes androgens (male sex hormones) and small amounts of estrogens (female sex hormones) in both sexes. The most prevalent male hormone is DHEA (dehydroepiandrosterone) which is responsible for the development of the sex drive, pubic hair, and axillary hair. The effects of DHEA are minimized in males as the testes secrete greater amounts of testosterone. The adrenal medulla is the deepest part of the adrenal gland and it secretes epinephrine and norepinephrine....
In people (and most other multicellular animals) there are fourteen major tissue types. There are many texts with illustrations and descriptions of the various cell types and tissue, e.g. Kessel and Kardon (1979) which is full of beautiful electron micrographs. Some of these tissue types are familiar bones, muscles, cardiovascular tissue, nerves, and connective tissue (like tendons and ligaments). Other tissues are the constituents of the digestive, respiratory, urinary and reproductive systems. Skin and blood are both distinctive tissue types, made of highly specialized cells. Lymphatic tissue, such as the spleen and the lymph nodes make up the immune system. Endocrine tissue comprises a network of hormone-producing glands (for example, the adrenal gland, source of adrenaline) that exert global control over various aspects of the body as a whole. Finally, epithelium, the most basic tissue type, lines all of the body's cavities, secreting materials such as mucus, and, in the in-
Although AM was first identified in pheochromocytoma tissue arising from adrenal medulla, immunoreactive AM and AM mRNA has been found to be ubiquitously distributed among various tissues (Fig. 6). Notably, high levels of AM mRNA have been detected in such cardiovascular tissues as atrium, aorta, kidney and lung, though the concentrations of immunoreactive AM in aorta, ventricle and kidney were less than 5 of that seen in adrenal gland (Sakata et al., 1993 Sakata et al., 1994, Sugo et al., 1994). It may be that AM biosynthesized in these tissues is rapidly and constitutively secreted into the blood and or utilized as an autocrine or paracrine regulator (Bean et al., 1994). By contrast, AM synthesized in adrenal medulla is thought to be stored in the granules and secreted into a regulatory pathway. Thus, the biosynthetic and secretory systems of AM may be tissue-specific.
Adrenocortical carcinomas account for only 0.05 to 0.2 of all cancers, with an annual incidence of 2 per million. The age of occurrence is bimodal, with the first peak occurring before the age of 5 years and the second peak in the fourth and fifth decades.1 Most series find a slight preponderance in women (4 3). Adrenocortical carcinomas occur equally in the right and left adrenal glands and are bilateral in 2.4 of patients.2 Adrenocortical carcinoma is found in 4 of patients with adrenal incidentalomas and in 10 of adrenal incidentalomas larger than 4 cm.3,4
ACTH and IV steroids aren't ordinarily used together. However, high-dose IV steroids (in 1-gram daily doses) could be used for a 3- to 5-day period in patients who have especially severe attacks to reduce swelling in the optic nerve or spinal cord, with ACTH added to maintain adrenal function (since steroids suppress the adrenal glands) and thereby obtain the benefit of the other actions of ACTH. This would also provide the neuroprotective effect of ACTH.
Weakness and bone injury, may occur with ACTH. Certain hormones induced by ACTH and produced by the adrenal glands, the keto-steroids (like testosterone), have an anabolic (protein building) effect. In other words, as in athletes, anabolic steroids that are induced by ACTH treatment are capable of making muscles somewhat stronger. In contrast, the net effect of steroids is catabolic (protein destroying).
Secreted by the adrenal glands (located by the kidneys), is needed in small amounts for bone growth. Large amounts of cortisol can interfere with bone growth. The synthetic form of cortisol, or steroids, used in the treatment of some diseases, can cause bone loss. Cortisol, secreted by the adrenal glands (located by the kidneys), is needed in small amounts for bone growth. Large amounts of cortisol can interfere with bone growth. The synthetic form of cortisol, or steroids, used in the treatment of some diseases (see Question 16), can cause bone loss.
There is a 10-fold higher incidence of phaeochromocytoma than in the normal population, so signs of this should be sought, particularly if hypertension is also present. In a study of 18 patients with both conditions, phaeochromocytomas were all associated with the adrenal glands, and each secreted both epinephrine (adrenaline) and norepinephrine (noradrenaline). Convulsions, cardiovascular collapse and death occurred in late pregnancy in a patient with neurofibromatosis who, at autopsy, was found to have a phaeochromocytoma (Harper et al 1989).
Ninety percent of women will live to the climacteric age, compared to only 30 percent 200 years ago. Attrition and aging of ovarian follicles results in termination of the maturation of granulosa cells, which are responsible for estrogen production. Sources of estrogen in the pre-menopausal woman are several fold, including direct production of estradiol by the ovaries as well as the extraglandular aromatization in adipose cells of androstenedione created in the adrenal glands and ovary. The hallmark of menopause is a drop in ovarian production of estriol and testosterone. Peripheral aromatiza-tion of other steroids not produced by the ovaries is an additional source of estrogen in all women. However, this source is not sufficient in most women to prevent the symptoms characteristic of estrogen deprivation.
Severe hypotension characterises the acute adrenocortical insufficiency of Addison's disease, and hypotension may also occur following surgery or trauma in chronic takers of steroids who do not receive supplementation, presumably as a result of suppression of the adrenals' ability to mount a stress response. This has led to the recommendation that all patients on steroid therapy should receive supplementation perioperatively however, the population at risk is uncertain, although most authorities would include all those with more than a week's steroid therapy within the last 3-6 months. The dosage prescribed is often chosen in a heavy-handed and non-scientific manner. If too much steroid is given, there is at least a theoretical risk of increased susceptibility to infection in addition, many patients dislike taking increased doses because depression and other mood changes may be apparent even after a short time, although other side effects typically take longer to occur. Finally, the...
Approximately 6 of androgen excess patients suffer from a specific disorder, including classic and nonclassic 21-hydroxylase deficiencies, the HAIR-AN syndrome, or an ASN, among others (12). In patients clinically suspected of having an ASN, a computed tomography or magnetic resonance imaging scan of the adrenals and transvaginal ovarian ultrasonography should be obtained to assess for adrenal or ovarian masses, respectively. Importantly, measurement of a basal 17-hydroxyprogesterone serum level should be obtained in the follicular phase of the menstrual cycle, preferably in the morning, to exclude 21-hydroxylase-deficient NCAH (39). In patients suspected of having Cushing's syndrome, it will also include a 24-hour urinary free cortisol level or a cortisol level following an overnight dexamethasone (1.0 mg at 11 pm) test. If the HAIR-AN syndrome is suspected, a basal or preferably a glucose-stimulated insulin level should be obtained. Growth hormone levels should be obtained in...
ATC is a systemic disease, with 50 of patients presenting with distant metastases. At least 80 of these patients will present with clinically evident pulmonary metastases, 15 of patients can present with bone metastases, and 13 with brain metastases.10 Distant metastases to the adrenals are seen in 33 and to intra-abdominal lymph nodes in 17 .210 Autopsy studies have shown that metastases are microscopically present in many patients, even when the imaging tests have been negative. One autopsy series showed pulmonary metastases in 100 , bone metastases in 80 , invasion of adjacent cervical soft tissues in 60 , and tracheal invasion in 27 .11 MRI of the brain can detect the presence of occult brain metastases and should be performed as part of the initial staging procedure. Bone scans are also valuable to confirm the presence of metastases in vulnerable weight-bearing areas, whether or not patients have actual symptoms. Positron emission tomography is gaining acceptance as a...
An incidentaloma of the adrenal gland (or adrena-loma) is defined as an adrenal tumor that is discovered incidentally and unexpectedly on radiologic imaging without prior knowledge that the patient has adrenal disease. The widespread use of imaging studies such as computed tomography (CT) (Figure 12-1), ultrasonography, and magnetic resonance imaging (MRI) (Figure 12-2) has increased the detection of adrenal incidentalomas, which range from 0.4 to 2 of abdominal CT scans.1-3 This chapter provides a practical approach to managing patients with adrenal incidentalomas. Incidentalomas comprise a variety of pathologies (Table 12-1). Most incidentalomas are benign cortical adenomas that do not secrete hormones and are termed nonfunctioning tumors. Some tumors, however, are hormonally active and secrete cortisol (Cushing's syndrome), aldosterone (primary hyper-aldosteronism), or catecholamines (pheochromocy-toma). A third group consists of malignant tumors that are either primary...
The pancreas has a head, neck, body and tail. It is a retroperitoneal organ which lies roughly along the transpyloric plane. The head is bound laterally by the curved duodenum and the tail extends to the hilum of the spleen in the lienorenal ligament. The superior mesenteric vessels pass behind the pancreas, then anteriorly, over the uncinate process and third part of the duodenum into the root of the small bowel mesentery. The inferior vena cava, aorta, coeliac plexus, left kidney (and its vessels) and the left adrenal gland are posterior pancreatic relations. In addition, the portal vein is formed behind the pancreatic neck by the confluence of the splenic and superior mesenteric veins. The lesser sac and stomach are anterior pancreatic relations.
Following unilateral adrenalectomy for primary hyperaldosteronism caused by an adenoma, patients normally do not require corticosteroid or electrolyte replacement. There is usually minimal blood loss during and after the operation, and postoperative fluid imbalances are usually not severe.12 A rare patient will experience transient aldosterone deficiency following adrenalectomy if the normal contralateral adrenal gland was suppressed by the adenoma this can be corrected with administration of exogenous aldosterone (fludrocortisone 0.1 mg d orally). Most patients who have been well prepared with spironolactone prior to operation need to stay in the hospital only overnight.
Dissection is continued by forward mobilization of the spleen, pancreatic tail and splenic flexure of the colon between the mesocolon and Gerota's fascia taking care not to damage the adrenal gland medially or the adrenal vein at its junction with the left renal vein. This left-to-right transperitoneal medial visceral rotation affords excellent exposure of the supraceliac and visceral aorta including the renal arteries (Fig. 8.9). Division of the median arcuate ligament and diaphragmatic crura exposes the distal thoracic aorta without entering the left chest. The left kidney can be brought forward with the rest of mobilized viscera or left in situ.
A 45-year-old woman with a 4-year history of severe hypertension. Workup showed a serum aldosterone level of 86, a renin activity level of 0.4, and a ratio of 215. A thin-cut computed tomographic scan showed a homogeneous 2 cm left adrenal tumor (arrow) and a normal right adrenal gland. A, She underwent a laparoscopic left adrenalectomy. Pathology showed a 2 cm adrenal cortical adenoma with focally prominent zona glomerulosa consistent with an aldosteronoma. B, Her hypertension improved after the operation with no need for medication. Figure 8-1. A 45-year-old woman with a 4-year history of severe hypertension. Workup showed a serum aldosterone level of 86, a renin activity level of 0.4, and a ratio of 215. A thin-cut computed tomographic scan showed a homogeneous 2 cm left adrenal tumor (arrow) and a normal right adrenal gland. A, She underwent a laparoscopic left adrenalectomy. Pathology showed a 2 cm adrenal cortical adenoma with focally prominent zona glomerulosa...
An abdominal computed tomographic scan performed in a 63-year-old woman because of mild right upper quadrant pain. A, The scan shows a 4 cm right adrenal tumor (large arrow) and a normal left adrenal gland (small arrow). B, Subsequent biochemical workup confirmed pheochromocytoma. The patient was a-adrenergic blocked, and the right adrenal tumor was resected laparoscopically. Courtesy of Quan-Yang Duh, MD. Figure 9-10. An abdominal computed tomographic scan performed in a 63-year-old woman because of mild right upper quadrant pain. A, The scan shows a 4 cm right adrenal tumor (large arrow) and a normal left adrenal gland (small arrow). B, Subsequent biochemical workup confirmed pheochromocytoma. The patient was a-adrenergic blocked, and the right adrenal tumor was resected laparoscopically. Courtesy of Quan-Yang Duh, MD.
The procured liver allograft is prepared in the back table just prior to its implantation by removing unnecessary tissues, including diaphragm, adrenal gland, and pericardial remnants. The vena cava, portal vein, and arterial inflow vessels are inspected and prepared for anastomosis to the recipient.
The differential diagnosis for apparent metastases include incidental benign paragangliomas, second pheochromocytomas, multicentric paragan-gliomas, intraperitoneal seeding during surgery, and false-positive 123I-MIBG scanning (see above).86 Malignant pheochromocytomas typically metastasize to bones, retroperitoneal and regional lymph nodes, liver, contralateral adrenal gland, lungs, and, occasionally, brain or muscle. The bones most frequently involved include vertebrae, pelvis and ischium, clavicles, and proximal femurs and humeri metastases to the cranium also occur, with a predilection for the frontal bone. Preverte-bral paragangliomas may cause destruction of adjacent vertebrae. Spinal cord compression can
Excessive hormone release, called hypersecretion, has multiple causes. Some tumors result in the overgrowth of functional endocrine tissue. A pheochromocytoma (FEE-o-CRO-mo-sy-TOE-muh), for example, is a tumor of the adrenal medulla that secretes excessive amounts of epinephrine and norepinephrine (table 17.8). Some tumors in nonendocrine organs produce hormones. For example, some lung tumors secrete ACTH and thus over-stimulate cortisol secretion by the adrenal gland. While certain autoimmune disorders can cause endocrine hyposecretion, others cause hypersecretion. An example of this is toxic goiter (Graves25 disease), in which autoan-
After instillation of a betadine solution through a gastric tube, the duodenum and the jejunum are stapled distal to the pylorus and the ligament of Treitz, respectively. The mesenteric root is transected distally of the pancreas using the GIA stapling device. The splenocolic ligament is taken down and the spleen and the pancreas are freed retroperitoneally. Finally, the IVC is transected at the level of the right adrenal gland, the liver is mobilized by transection of the falciform ligament and the liver-pancreas bloc is removed containing a large diaphragmatic patch.
Sugar levels and also secretes enzymes (exocrine secretions) that break down material in the digestive tract. Hormones are released from endocrine glands and typically travel through the body in blood vessels and reach target areas that have cells receptive to the hormones. Locate and label the pineal gland, pituitary gland, thyroid gland, pancreas, adrenal glands, testes, and ovaries. Color the organs in with different colors for each organ. Answer Key a. Pineal gland, b. Pituitary gland, c. Thyroid gland, d. Adrenal glands, e. Pancreas, f. Ovary, g. Testis
(2) inhibition of androgen production by the ovary or adrenal gland, or (3) in the future, inhibition of androgen metabolizing enzymes in the skin may be possible (see 'Enzyme inhibitors' section below). It is important to note that hormonal therapy is absolutely contraindicated in women who want to become pregnant due to the risk for sexual organ malformation in a developing fetus. Another option in hormone therapy is to block the production of androgens, which can be accomplished through the use of oral contraceptives and low-dose glucocorti-coids. This is most commonly used to treat the patient with late-onset congenital adrenal hyperplasia, which is an inherent defect in the 21-hydroxylase or the 11-hydroxylase enzyme. This defect causes a block in the cortisol biosynthetic pathway, which results in a buildup of precursors for potent androgens. Low-dose prednisone (2.5-5 mg a day, at bedtime) is one option. Dexametha-sone can also be used, but the risk of adrenal suppression is...
Extrinsic narrowing of the colon lumen can be caused by retroperitoneal tumors (kidneys, adrenal glands, pancreas, ovaries, uterine and cervical carcinoma or lymphoma) or by retroperitoneal abscesses (Fig. 17.1). Though peritoneal carcinoma often causes adhesions which especially make endoscope passage in the sigmoid difficult because of lacking compressibility of the abdomen ( splinting technique ) it does not cause narrowing of actual lumen.
Estrogen secretion increases to about 30 times normal by the end of gestation. The corpus luteum is an important source of estrogen for the first 12 weeks after that, it comes mainly from the placenta. The adrenal glands of the mother and fetus secrete androgens, which the placenta converts to estrogens. The most abundant estrogen of pregnancy is estriol, but its effects are relatively weak estra-diol is less abundant but accounts for most of the estro-genic effects in pregnancy.
The differential diagnosis begins with checking ACTH. Values 10 pg mL identify ACTH-inde-pendent Cushing's syndrome, in which case, a CT scan is indicated to evaluate the adrenal glands. If there is more than one lesion, then iodocholesterol scanning may be useful to identify functioning masses. Finally, the response to high-dose dexametha-sone can differentiate the ACTH-dependent forms of Cushing's syndrome, either ectopic or pituitary.42-44
The spleen is then gently and progressively retracted medially with the surgeon's left hand ( B). Using a laparotomy pad under the retracting hand, it is a relatively simple maneuver for the surgeon to identify the peritoneal attachments and provide exposure with the left index finger. The attachments are divided with curved scissors proceeding from the inferior pole to the superior pole and then dividing the splenorenal ligament as the spleen is gradually rotated medially and anteriorly. Care should be taken with any blunt dissection as the splenic capsule is relatively thin and even small tears can result in moderate bleeding. Likewise, care should be taken as proceeding posteriorly around the inferior pole in order to avoid the adrenal gland.
The sympathetic division controls the fight or flight response of the body, shutting down the digestive functions, inhibiting erections, shunting blood away from the kidneys, and dilating the pupils. The sympathetic division increases heart rate, dilates capillaries in the lungs, brain and muscle tissue, and stimulates the adrenal glands. This division is also known as the thoracolumbar division because the nerves exit the CNS in the thoracic and lumbar regions of the spinal cord. There are ganglia associated with the sympathetic division and these are located on either side of the ventral portion of the vertebral column. They are called the sympathetic chain ganglia and the neurons from the thoracolumbar division synapse with nerve cells in these ganglia.
Several clinical observations point to the importance of androgens in acne. The development of early acne in the prepubertal period has been associated with elevated serum levels of dehydroepiandrosterone sulfate (DHEAS), a precursor of testosterone 9, 10 . For example, acne occurs near the time of puberty. In fact, investigators have demonstrated that acne begins to develop at the time of adrenarche when the adrenal gland begins to produce large quantities of DHEAS 9, 10 . This hormone can serve as a precursor to the production of more potent androgens within the sebaceous gland. The rise in serum DHEAS in prepubescent children is associated with an increase in sebum production and the development of comedonal acne. Androgen Metabolism within the Skin Dehydroepiandrosterone sulfate (DHEAS) is produced in large quantities by the zona reticularis of the adrenal gland. It circulates in the bloodstream in high levels in relatively high levels compared to other hormones with the exception...
(2) The adrenal gland, which is acted upon by adreno-corticotrophic hormone (ACTH), also secreted by the pituitary, to produce dehydroepiandrosterone (DHEA) that can then be metabolized into more potent androgens such as androstenedione and testosterone. An elevated level of DHEAS would indicate that the source of androgens is the adrenal gland. Patients with a serum DHEAS greater than 800 g dl may have an adrenal tumor and should be referred to an endocrinologist for further evaluation. Values of DHEAS in the range of 400800 g dl may be associated with congenital adrenal hyperplasia which is most commonly a partial deficiency in the 21-hydroxylase or 11-hydroxylase enzyme in the adrenal gland. Such an enzyme deficiency results in the shunting of steroids into the pathway resulting in increased androgen production.
A very small percentage of women (1 ) experience natural menopause before the age of 40. It is not known why these people stop having their periods. Idiopathic ovarian insufficiency or premature ovarian failure is a condition that usually occurs in women under the age of 40 and causes menopause. Idiopathic ovarian insufficiency is usually caused by autoimmune and genetic disorders, Addison's disease (disorder of the adrenal glands, which manufacture steroid hormones), or hypothyroidism (an underactive thyroid gland).
The initial focus was dictated by clinical observations. Remarkably, the first observation was made in 1895 and published in 1896 by Beatson who detected the regression and then recurrence of a breast lump in a 33-year-old Glasgow woman following removal of her ovaries. The temporary effect led Beatson to opine that We must look in the female to the ovaries as the seat of the exciting cause of carcinoma, certainly of the mamma, (Beatson, 1896). Some 40 years after the Beatson report, clinicians were administering either androgens or estrogens and or removing the adrenals or pituitary in women with breast cancer (Haddow et al., 1944 Huggins and Bergenstal, 1952 Loeser, 1938 Ulrich, 1939).
Preclinical or subclinical Cushing's syndrome is caused by autonomous glucocorticoid secretion in patients who may have no overt, or only minimal, clinical signs and symptoms of full-blown Cushing's syndrome. Subclinical hypercortisolism has been reported in 5 to 20 of patients with adrenal inci-dentalomas. Depending on the amount of glucocor-ticoid secreted by the tumor, the clinical spectrum can vary considerably. Diagnostically, patients often have a slightly attenuated diurnal rhythm of cortisol secretion. They may also have a suppressed contralateral adrenal gland. Removing the hypersecret-ing adrenal gland, even without removing the normal gland, may result in life-threatening acute adrenal insufficiency. The natural history of this condition is unclear because long-term prospective studies are lacking. Subclinical Cushing's syndrome may progress to overt Cushing's syndrome. Some patients with subclinical Cushing's syndrome have subtle biochemical abnormalities that are reversed...
AM was initially discovered in human pheochromocytoma by monitoring the cAMP activity in rat platelets (Kitamura et al.,1993a). AM mRNA is highly expressed not only in pheochromocytoma but also in normal adrenal medulla, kidney, lungs, and ventricle (Kitamura et al., 1993b). However, whether these organs secrete AM into circulation or not was not initially fully understood. To investigate the sites of production and clearance of AM in humans, we took samples of both arterial and venous blood across the adrenal gland, kidney, lung, and heart and measured plasma AM concentrations by radioimmunoassay (Nishikimi et al., 1994). There was no step-up of plasma AM concentration in the coronary sinus, renal vein, or adrenal vein. There were no significant differences in plasma AM concentrations among the various sites of the right side of the heart including the inferior portion of the inferior vena cava, superior portion of the inferior vena cava, superior vena cava, right atrium, right...
Most pheochromocytomas are located in the adrenal glands (90 in adults and 70 in children), occurring more frequently on the right than on the left. In one series, right-sided pheochromocytomas have been described as producing paroxysmal hypertension more often than sustained hypertension, whereas the opposite is true for tumors arising from the left adrenal gland.18 Adrenal pheochromocytomas are bilateral in about 10 of adults and 35 of children. They may present at any age but are more common in the fourth and fifth decades.
When a pheochromocytoma is suspected on clinical and biochemical grounds, the patient can be imaged with full abdominal CT scanning, from the diaphragm through the pelvis. Thin sections are obtained through the adrenals (Figure 9-5). Glucagon should not be used because it may provoke a hypertensive crisis. Hypertension should be treated prior to CT scanning because intravenous contrast can also cause hypertensive crisis. If no mass is dis-
ACTH (or corticotrophin) is a hormone that is made in the brain and is stored in the pituitary gland, which is situated at the base of the brain. This hormone is normally released in miniscule amounts during the early hours of the morning to stimulate the adrenal glands' production of steroid hormones. Cortisol, the active form of cortisone, is one product of ACTH stimulation. Dr. Leo Alexander began using ACTH a half-century ago at Harvard Medical School. He showed in a series of studies that it speeded recovery from MS attacks. Later, a national study, published in 1970, proved that it did indeed significantly speed the recovery for patients with acute exacerbations of MS. an endocrine gland about the size of a pea at the base of the brain. The pituitary gland secretes hormones regulating a wide variety of bodily activities. Adrenal glands the primary steroid hormone produced by the adrenal gland. It is the biologically active soluble form of cortisone. Cortisone
The adrenals and ovaries contribute variably to the circulating levels of androgens in adult women (15). Generally, it is thought that A4 is derived in roughly equal amounts from the ovary and the adrenal, while testosterone is derived approximately 25 from the adrenal, 25 from the ovary, and 50 from the peripheral conversion of A4. DHT is produced in peripheral tissues from testosterone and circulates at levels about one-third to one-half that of testosterone. DHEA and DHEAS are almost exclusively of adrenal origin. DHEA is secreted in a pulsatile manner and demonstrates a diurnal rhythm similar to that of cortisol in young women (16). Because of the low metabolic clearance rate (MCR) of DHEAS, however, there are only minor changes in its concentration throughout the day. Androstenedione and testosterone levels also exhibit a diurnal rhythm (15), although less variable than that of DHEA and cortisol.
Distant metastases to the liver, lung, adrenal glands, and bone occur with large primary lesions. In a study from a Swedish registry, it was noted that MTC patients with a palpable mass in the neck had distant metastatic disease in 20 of cases, regardless of heritability.3 Furthermore, occult remote micrometastases are most likely the cause of most cases of persistent hypercalcitoninemia after extensive lymph node dissection.
Norepinephrine in storage vesicles can diffuse into the cytoplasm. In certain cells (particularly the adrenal medulla), norepinephrine is converted to epinephrine in the cytoplasm, catalyzed by (PNMT). (Once formed, epinephrine may then return to the vesicle, diffuse from the cell, or undergo catabo-lism.) The expression of PNMT is enhanced by cortisol, which is present in high concentrations in areas of the adrenal medulla, owing to venous blood flow from the adjacent adrenal cortex. This accounts for the fact that, in the normal human adrenal medulla, about 80 of the catecholamine content is epinephrine, whereas only 20 is norepinephrine. Serum epinephrine concentrations fall dramatically after resection of both normal adrenals, whereas norepi-nephrine concentrations do not decline.1
Overview of the renin-angiotensin-aldosterone system 8,9 . Angiotensinogen (or renin substrate) is a 56-kD glycoprotein produced and secreted by the liver. Renin is produced by the juxtaglomerular apparatus of the kidney, as shown in Figures 2-8 and 2-9. Renin cleaves the 10 N-terminal amino acids from angiotensinogen. This decapeptide (angiotensin I) is cleaved by angiotensin converting enzyme (ACE). The resulting angiotensin II comprises the 8 N-terminal amino acids of angiotensin I. The primary amino acid structures of angiotensins I and II are shown in single letter codes. Angiotensin II increases systemic vascular resistance (SVR), stimulates aldosterone secretion from the adrenal gland (indicated in gray), and increases sodium (Na) absorption by renal tubules, as shown in Figures 2-15 and 2-17. These effects decrease urinary Na (and chloride excretion UNaV).
Adrenomedullin significantly decreases blood pressure in vivo, directly acts on vascular smooth muscle cells, and increases cAMP levels. Adrenomedullin also acts on vascular endothelial cells and activates endothelial NOS by increasing intracellular Ca2+ levels. Thus, adrenomedullin reduces blood pressure indirectly. Strong expression of adrenomedullin mRNA is found in vascular smooth muscle cells and endothelial cells. Its expression in these cells is 20 times higher than that in the adrenal gland. Thus, adrenomedullin is produced and secreted from vascular walls and acts as an autocrine and paracrine factor involved in the regulation of vascular tonus. Furthermore, recent studies suggest a role of adrenomedullin in the pathogenesis of arteriosclerosis.
Adrenal and gonadal maturation are not functionally interdependent. In adult women, the adrenals and ovaries contribute variably to the circulating levels of androgens, although in general A4 is derived in roughly equal amounts from the ovary and the adrenal, whereas testosterone is derived approximately 25 from the adrenal, 25 from the ovary, and 50 from the peripheral conversion of A4. DHT is produced in peripheral tissues from testosterone and circulates at levels of about one-third to one-half that of testosterone. DHEA and DHEAS are almost exclusively of adrenal origin. DHEA is secreted in a pulsatile manner and demonstrates a diurnal rhythm that is similar to that of cortisol in young women.
Von Hippel-Lindau disease (VHL) organ involvement. VHL is an autosomal-dominant multisystem disorder with a prevalence rate of roughly 1 in 40,000 32, 35 . It is characterized by the development of tumors, benign and malignant, in various organs. VHL-associated tumors tend to arise at an earlier age and more often are multicentric than the sporadic varieties. Morbidity and mortality are mostly related to central nervous system hemangioblastoma and renal cell carcinoma. Involvement of cerebellum, retinas, kidneys, adrenal glands, and pancreas is illustrated (see Figures 9-37 to 9-41).
Normal renal tubular function is controlled by a delicate balance of humoral mediators. Thus, a tumor-induced inappropriate concentration of a hormone that normally contributes to the modulation of this balance may result in a profound disturbance of tubular function, thereby causing impairment of fluid and electrolyte balance as well as other homeostatic defects. A tumor product appears to be the basis for renal phosphate loss in some cases, in that the resultant hypophosphatemia regresses when the tumor is removed 75 . Hyponatremia occurs frequently in the patient with cancer it is frequently caused by the syndrome of inappropriate antidiuretic hormone secretion (SIADH). Bronchogenic carcinoma is the most frequent cause of this syndrome. A number of other tumors have also been reported to cause SIADH. Disappearance of the syndrome on removal of the tumor or improvement following successful chemotherapy has been observed frequently 76 . Cancer is a common cause of central diabetes...
Pituitary Cushing's disease results from excessive production of adrenocorticotropic hormone (ACTH), typically owing to a benign adenoma. Excess ACTH stimulates both adrenals to produce excessive amounts of cortisol and results in bilateral adrenal hyperplasia. The increased cortisol production does not suppress ACTH release, however, because the pituitary tumor is unresponsive to the normal feedback suppression of increased cortisol levels. The diagnosis usually is made by demonstration of elevated levels of ACTH in the face of elevated cortisol levels, particularly in the afternoon or evening, representing loss of the normal circadian rhythm (see Fig. 4-4). Radiographic studies of the pituitary (computed tomographic scan and magnetic resonance imaging) will likely demonstrate the source of increased ACTH production. When the pituitary is the source, surgery and irradiation are therapeutic options.
The adrenal gland is involved in the production of a variety of steroid hormones and catecholamines that influence blood pressure. Thus, it is not surprising that several adrenal disorders may result in hypertension. Many of these disorders are potentially curable or responsive to specific therapies. Therefore, identifying adrenal disorders is an important consideration when elevated blood pressure occurs suddenly or in a young person, is severe or difficult to treat, or is associated with manifestations suggestive of a secondary form of hypertension. Because these occurrences are relatively rare, it is necessary to have a high index of suspicion and understand the pathophysiology on which the diagnosis and treatment of these problems is based.
The sympathetic nervous system tends to have longer-lasting effects than the parasympathetic. After ACh is secreted by the parasympathetic fibers, it is quickly broken down by acetylcholinesterase (AChE) in the synapse and its effect lasts only a few seconds. The NE released by sympathetic nerve fibers, however, has various fates (1) Some is reabsorbed by the nerve fiber and either reused or broken down by the enzyme monoamine oxidase (MAO). (2) Some diffuses into the surrounding tissues, where it is degraded by another enzyme, catechol-O-methyltransferase (COMT). (3) Much of it is picked up by the bloodstream, where MAO and COMT are absent. This NE, along with epinephrine from the adrenal gland, circulates throughout the body and exerts a prolonged effect.
A 47-year-old woman had a 2 cm right adrenal tumor discovered incidentally 2 years ago and had a negative biochemical workup. A, A follow-up abdominal computed tomographic scan 2 years later showed the right adrenal tumor (large white arrow) to have grown to 3.5 cm. The left adrenal gland (small white arroW) was normal. Biochemical workup again showed no hyper-function. She underwent a laparoscopic right adrenalectomy. B, Pathology showed it to be a adrenocortical adenoma. Figure 12-7. A 47-year-old woman had a 2 cm right adrenal tumor discovered incidentally 2 years ago and had a negative biochemical workup. A, A follow-up abdominal computed tomographic scan 2 years later showed the right adrenal tumor (large white arrow) to have grown to 3.5 cm. The left adrenal gland (small white arroW) was normal. Biochemical workup again showed no hyper-function. She underwent a laparoscopic right adrenalectomy. B, Pathology showed it to be a adrenocortical adenoma. Laparoscopic...
Besides the adrenal gland, the mRNA of AM is widely expressed in cardiovascular tissues. The cultured cells such as fibroblasts, vascular endothelial cells and smooth muscle cells have been shown to express AM mRNA prominently (Sugo et al, 1994a Sugo et al, 1994b Tomoda et al, 2001). We examined the promoter activity of the human AM gene in cultured human aortic endothelial cells (HAEQ (Ishimitsu et al, 1998). First, the transcription start site was determined by the primer extension method using total RNA extracted from HAEC as the template. As framed in Figure 2, two transcription start sites were identified, both at the cytosine nucleotides. These are 21 and 25 bases downstream from the TATA box and 19 and 23 bases upstream from the 5'-end of the human AM cDNA sequence determined by Kitamura et al. (Kitamura et al, 1993b). Hereafter, the upstream transcription start site at nucleotide C is assigned the nucleotide number 1.
Menopausal woman, androstenedione, synthesized in the adrenal gland, is the principal estrogen precursor following the decline of ovarian function. Increased conversion of androstened-ione to estrone by fat cells that results in elevated levels of this predominant postmenopausal estrogen is reputed to be the underlying explanation for the increased risk of breast cancer seen in obese postmenopausal women.47-52 In contrast, in premenopausal obese women, derangement of the estrogen-progesterone balance and subsequent menstrual disturbances result in a decreased risk of breast cancer.50,53
Steroid hormones are all derived from cholesterol. Hence, they are all lipid-soluble and diffuse from the blood through the cell membranes of the target cells, where they act as transcription factors and initiate important cellular responses. Cortisol is a steroid hormone secreted from the adrenal gland, and it plays a significant role in processes as diverse as human development, metabolic response to stress, energy metabolism, and aging. Cortisol acts through two intracellular receptors the mineralocorticoid receptor and the glucocorticoid receptor (Nishi and Kawata, 2006). Both receptors can be found in the cytoplasm of target cells and are rapidly translocated into the nucleus when bound to their ligand, cortisol. However, some studies have also reported the presence of these corticosteroid receptors in the nucleus even in the absence of its ligand.
Tionship to the pancreatic ducts, the portal vein, the common bile duct, and the superior mesenteric vessels. This helps in removal of the tumor and decreases the risk of a postoperative fistula. The body and tail of the pancreas are mobilized by incising the peritoneum at the inferior border of the gland and gradually dissecting beneath its entire posterior surface. This is also the approach that is frequently used to expose the left adrenal gland.
The adrenal gland is one of the frequent sites of metastases, and virtually any malignancy may spread to it. A metastatic tumor should be highly suspected in the setting where an imaging study detects an adrenal mass in a patient with a known history of malignant disease. Common cancers that metastasize to the adrenal gland are from the lung, kidney, breast, gastrointestinal tract, and melanoma. Occasionally, an adrenal metastasis is discovered with an undetermined primary origin thus, a thorough history and physical examination are essential for all patients (Figures 12-3 and 12-4). For example, melanomas can recur many years after previous surgical excision. The clinical assessment suggests what investigations are required to confirm the diagnosis, such as a chest radiograph and bronchoscopy for lung cancer or a mammogram and biopsy for breast cancer. Figure 12-1. A 46-year-old woman had nonspecific right-sided abdominal discomfort and palpitation. An abdominal computed tomographic...
The skin and other structures are in the integumentary system and the digestive system involves the breakdown and absorption of food with organs such as the esophagus and stomach. The endocrine system is made of the glands that secrete hormones such as the thyroid gland and the adrenal glands. The respiratory system involves the transfer of oxygen and carbon dioxide between the air and the blood. The respiratory system consists of organs such as the trachea and lungs. Stomach Adrenal glands Lungs Answer Key a. Skin, b. Integumentary, c. Esophagus, d. Stomach, e. Digestive, f. Thyroid gland, g. Adrenal gland, h. Endocrine, i. Trachea, j. Lung, k. Respiratory
The pathogenetic mechanisms of neonatal acne are still unclear. A positive family history of acne supports the importance of genetic factors. Familial hyperandroge-nism including acne and hirsutism give the evidence that maternal androgens may play a role through transplacen-tal stimulation of sebaceous glands 4 . There is a considerable sebum excretion rate during the neonatal period which decreases markedly to almost not detectable levels following the significant reduction of sebaceous gland volume up to the age of 6 months 5-7 . There is a direct correlation between high maternal and neonatal sebum excretion suggesting the importance of maternal environment on the infant sebaceous glands 8 . Neonatal adrenal glands produce a certain amount of P-hydroxysteroids that prepare the sebaceous glands to be more sensitive to hormones in the future life 1 . In males from 6 to 12 months there are increasing levels of luteinizing hormone (LH) and as a consequence of testosterone these...
Hyperkalaemia is a dangerous condition. Although the normal range extends up to 5-5 mmol l it is rare to get arrhythmias below 7-5 mmol l. The most common cause of hyperkalaemia is renal failure - either acute or chronic. Hyperkalaemia can also result from potassium overload, loss of potassium from cells due to acidosis or cell lysis, hypoaldosteronism and hypoadrenalism.