HPA Axis Dysfunction Treatment PDF

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The fetal adrenal gland

The human fetal adrenal gland consists of three zones the inner fetal zone (FZ) which has the enzymes to produce dehydroepiandrosterone sulphate (DHEAS) from early gestation (lacking expression of 3p-hydroxy-steroid dehydrogenase, HSD) the transitional zone (TZ) which contains The fetal adrenal gland is probably under the control of ACTH from the fetal pituitary, but the placenta also produces ACTH and corticotrophin-releasing hormone (CRH). In other species the adrenal gland is involved in the initiation of parturition with a surge in cortisol. A similar role has not been demonstrated in humans, but the subtle changes in metabolism and control of cortisol with increasing gestation make it likely that it plays a part.

Posterior surface of adrenal gland Facies posterior

Upper margin between the anterior and posterior surfaces of the adrenal gland. F Medial margin. Margo medialis. Margin between the anterior and posterior surfaces of the adrenal gland. F Hilum. Site of exit of central vein. It may be directed forward, downward or upward. F Central vein. Vena centralis. Principal vein of the adrenal gland. It exists anterosuperiorly or anteroinferiorly. F Adrenal cortex. Part of the adrenal gland that originally developed from the coelomic epithelium. It is divided into three zones. G Adrenal medulla. Part ofthe adrenal gland that arises from the neural crest. It consists of chromaffin cells, sympathetic ganglion cells and venous sinuses. G Accessory suprarenal glands. Glandulae su-prarenales accessoriae. Scattered adrenal glandular tissue.

Preoperative Assessment

The new patient visit starts with the history. While almost all patients with thyroid cancer are euthyroid, surgery is performed on patients with large goiters who might be hypothyroid and occasionally on patients with hyperthy-roidism who are not amenable to medical control. Any previous neck operations must be understood in detail to elucidate the altered anatomy the surgeon will encounter. Important questions are used to delineate their clinical thyroid status (heat cold intolerance, skin changes, hair changes, cardiovascular status, and bowel changes) and also to investigate for possible multiple endocrine neoplasia (MEN) syndrome with vasoactive tumors of the adrenal glands. For cancer patients, a 1-year history of any excess iodine exposure, especially computed tomography (CT) scans, is obtained to assess how long postoperative radioactive iodine may need to be delayed. This will be checked with 24-hour urine iodine levels prior to administration of 131I. Present medications are...

What to tell parents

A brief explanation of the effects of steroids (maintaining blood glucose, blood pressure, and response to stress), and therefore the problems of adrenal deficiency. Initially it may be difficult to ascertain whether there is a problem with the adrenal gland, but it is important to perform tests (blood cortisol, urine steroid profile, and Synacthen test) that will show how the gland is working. In the interim it may be necessary to give steroid therapy until the results are known.

Pharmacogenetics of Drug Transport

The first polymorphism in the MDR-1 gene was identified by comparing cDNAs cloned from normal human adrenal gland and a cochicine-selected multidrug-resistant cell line derived from an epider-moid carcinoma (152, 153). Nine nucleotide sequence differences were noted, but only two altered the coding sequence. A variation, TT GA at NT544-555 (Gly185Val), was shown to be associated with an enhanced resistance to colchicine relative to other MDR substrates, and was thought to arise during selection of the cells. A second variation, G T at NT2677 (Ser893Ala), was thought to reflect a naturally occurring, nonselected genetic polymorphism. The NT2677 polymorphism was used by Mickley et al. (154) to examine the allelic expression of MDR-1 in normal tissues, in unselected and drug-selected cell lines, and in malignant lymphomas. In normal tissue samples 43 were heterozygous, 42 were homozygous for G, and 15 were homozygous for T (n 83), and expression from each allele was similar. In...

Neuroendocrine Control Theory of Aging

The endocrine system evolved to coordinate the activities of cells in different parts of the body by releasing hormones from major endocrine glands and or organs into the bloodstream to be transported to other parts of the body where it affects particular target cells (Chapters 9-13). The major endocrine glands in mammals are the hypothalamus-pituitary-adrenal complex, the thyroid and parathyroid glands, the pancreas, the sex organs, and the adrenal glands (121). The neurological system is inextricably linked to the endocrine system because of the central role of the hypothalamus in synthesizing and realizing hormones (hypophysiotropic hormones) that control the pituitary gland to release hormones that act on target cells throughout the body (Chapters 9-13). Normal functioning requires that nervous and endocrine signals be synchronized and responsive to the needs of the many functions they regulate. However, some of the efficiency of the neurological and endocrine systems decreases...

HPA Axis Alterations in Other Psychiatric Disorders

When depression is comorbid with a variety of other disorders, such as multiple sclerosis, Alzheimer's disease, multi-infarct dementia, Hunting-ton's disease, and others, both CRF hypersecretion and HPA axis hyper-activity are common. In contrast, HPA axis dysfunction has rarely been reported in schizophrenia. Consistent with the role of CRF in both depression-like and anxiety-like behaviours in preclinical animal studies, increased CSF concentrations of CRF have been reported in post-traumatic stress disorder (PTSD) 95 . A recent elegant study that used an in-dwelling cannula in the lumbar space, allowing repeated sampling of CSF several hours after the initial, and presumably stressful, lumbar puncture, demonstrated elevated CSF levels of CRF in combat veterans suffering from PTSD 96 . In contrast, low serum cortisol and urinary free cortisol levels have been repeatedly, yet unexpectedly, detected in PTSD. One possible mechanism that has been proposed by Yehuda et al. 97 suggests...

Orphan Receptors that Bind as Monomers

Nerve growth factor induced gene B (NGFI-B, also called Nurr77, TR3NAK1, TIS1, N10) was originally isolated as a gene induced by nerve growth factor (NGF) in the rat pheochromocytoma cell line PC12. Other family members include Nurr1 (Nur-related factor 1, also called RNR-1, NOT,TINUR, RNR-1) isolated from a mouse brain cDNA library and NOR-1 (neuron derived orphan receptor, also called MINOR, TEC, CHN), identified from cultured rat fetal fore-brain cells. Their genes are rapidly and transiently induced by a wide variety of stimuli and are classified as immediate-early genes. The inducers include chemical stimuli such as cAMP, phorbol esters, pep-tide hormones, growth factors, neurotransmitters, and physical stimuli such as membrane depolarization, mechanical agitation, and a magnetic field. Furthermore, activation of T cells via the T-cell receptor leads to rapid induction of NGFI-B gene expression. NGFI-B and Nurr1 bind to nuclear receptor halfsites as monomers. Receptor activity on...

Androgendependent And Androgenindependent Prostate Growth

Table 47.1 shows the development of the completely endocrine independent cell occurring in four stages. The hormonenaive patient, who has been diagnosed as suffering from prostate cancer that is no longer to be cured by radical prostatectomy or radiotherapy, will respond to the use of monotherapy with androgen receptor antagonists, either steroidal or non-steroidal, or medical or surgical castration. Within a period of 1.5-3 years the cells will show resistance to this monotherapeutic option and require further hormone treatment. In patients who have received monotherapy with an antiandrogen, there will still be normal levels of testosterone in the blood, but in some instances the levels may be slightly elevated. Withdrawal of the patient's own androgens by means of medical or surgical castration will give rise to further response in approximately half of the patients. In patients who have been medically or surgically castrated, there will be a response in approximately 30 to the...

Fetal Breathing Movements

Growth is associated with an increasing capacity of the fetus to sustain prolonged episodes of breathing. Moreover, bouts of breathing become less fragmented. Parallel to this, the intervals between bouts also increase in duration long apneic intervals become a consistent feature of fetal breathing around mid-gestation. It is established that breathing movements are the first movements to disappear in compromised and growth-restricted fetuses, where energy and oxygen consumption have to be spared for more delicate areas 28 . A concomitant increase in blood flow to the brain, heart and adrenals is usually observed in such cases and is taken as a clinical indicator of fetal compromise 28 . The increased spacing between episodes of breathing could also acquire pathological significance in the premature infant and occasionally also in the neonate. In only too many ways a premature infant is a fetus born at an untimely age. Under particular circumstances the premature infant, but also the...

Metastases to the Thyroid

The majority of metastases to the thyroid remain undetectable in clinical practice 37 . However, incidence in postmortem studies varies between 1.2 and 24 in patients with widespread malignancy 2,38,39 . Based on these figures, thyroid metastases are 10 times more frequent than primary thyroid tumors 40 . This is not surprising given that the thyroid has a rich blood supply, second only to the adrenals. Involvement may arise by direct spread from adjacent structures, hematogenous spread, or retrograde lymphatic spread. Postmortem studies report breast (26 ), lung (25 ), and malignant melanoma (11 ) to be the most frequent cancers to metastasize to the thyroid, with disease usually remaining clinically occult. In contrast, the largest clinical series 41 found that the kidney was the most common primary site (33 ) followed by lung (16 ), breast (16 ), and esophagus (9 ).

Cytochromes P450 Monooxygenase System

Metabolic Activation

Cytochromes P-450 may be found in other organelles as well as the SER including the rough endoplasmic reticulum and nuclear membrane. In the adrenal gland it is also found in the mitochondria, although here adrenodoxin and adrenodoxin reductase are additional requirements in the overall system. Although the liver has the highest concentration of the enzyme, cytochromes P-450 are found in most, if not all, tissues.

Role of Transporters in Drug Distribution

Other tissues with high MDR-1 concentrations include the apical surface of pancreatic duct cells, the adrenal cortex, and the choroid plexus. In the case of secretory glands, MDR-1 may be necessary to protect the gland from its own products and perhaps to assist with their export (e.g., hydrophobic steroids synthesized by the adrenal glands). The choroid plexus is responsible for the secretion of cerebrospinal fluid. It consists of epithelial cells with a basal surface in contact with the blood and an apical surface facing the ventricular space. MDR-1 is located on the apical surface of choroid plexus cells, analogous to its location in other tissues. This location does not put MDR-1 in a position to protect the brain, since transport across the arachnoid membrane separating the CSF and brain cells is thought to be unimpeded. However, choroid plexus cells have been shown to express MRP on their basolateral surface, consistent with a brain-protective role for this transport protein...

Intrauterine growth restriction

Symmetrical IUGR is often familial (one or both parents are short) or a sign of an underlying fetal chromosomal abnormality. PIH causes asymmetrical IUGR with the fetal length and head (brain) growth preserved at the expense of fat and glycogen deposition. PIH stress imposed on the fetus causes an anti-insulin response probably regulated by increased levels of catecholamines. This results in a loss of fat and muscle mass and reduced glycogen stores. Blood flow to essential organs such as the brain, heart and adrenal glands

Relationship of fetal Doppler indices to hypoxemia and acidemia

Mca Doppler Fetal For Antikell

Under hypoxic conditions there is centralization of the fetal circulation with redistribution to preferentially supply the fetal brain, heart, spleen and adrenal glands. An increased amount of umbilical venous blood flow is also directed through the DV to maintain the oxygen tension in the left atrium (Edelstone, 1980). Doppler indices in fetal peripheral arteries are increased consistent with peripheral vasoconstriction. The ability to undergo these physiological adaptations to hypoxemia is likely to be gestation-dependent.

Gambar Infra Orbital Border

Nerve 340.15 ligament of epididymis 162.4 of incus 382.26 of malleus 382.24 lingular bronchus 146.19 segment of upper lobe of left lung 150.18 longitudinal fasciculus 316.16 muscle of tongue 114.23 lymph nodes 264.3 macular arteriole venule 360.12 margin adrenal gland 182.33 cerebral hemisphere 306.10 scapula 34.15 mediastinum 152.25 medullary velum 288.2 mesenteric artery 220.1 ganglion 348.14 plexus 348.28 vein 248.20 nasal

Gene Carrier Treatment

Parathyroid and adrenal gland morphology and function must be assessed and an adequate treatment should be performed if needed. If no abnormalities of these glands are found at the time of diagnosis, their morphology and function should be monitored annually because both hyperparathyroidism and pheochromocy-toma may show up later in life.

The Mind Body Connection

Documenting the relations between stress, emotion, and physiology. Shortly after this work was published, Selye began reporting his experiments on the effects of cold and fatigue on the physiology of rats. These physical stressors produced enlarged adrenal glands, small thymus and lymph glands (involved in immune system functioning), and increased ulcer formation.

Mechanisms Of Parturition Parturition

Signals for myometrial activation also come from the fetal HPA axis (Liggins and Thor-burn, 1994). It is currently thought that once fetal maturity has been reached (as determined by as yet unknown mechanisms), the fetal hypothalamus and or the placenta (see below) increase the level of CRH secretion, which in turn stimulates adrenocorticotropic hormone (ACTH) expression by the fetal pituitary and cortisol and androgen production by the fetal adrenals. Fetal an-drogens are then aromatized into estrogens by the placenta. Ultimately, this initiates a biological cascade that leads to a common pathway of parturition characterized by uterine contractility, cervical ripening and decidual fetal membrane activation seen in Phase 2 of parturition. Estrogens. Unlike the placentas of most other species, the human placenta cannot convert progesterone to estrogen because it is deficient in 17-hydroxylase, which is required for this conversion. Estrogen production in the placenta depends largely on...

Pathogenesis And Clinical Significance

Tubule cells and renal blood vessel endothelium bladder prostate liver. Not intestine Epithelium (tubule cells) and endothelium of kidneys, adrenal glands, trachea myocytes of heart macrophages of brain, heart, urinary bladder, spleen and lymph nodes (suggestive of phagocytosis after release from other cells) (Mertens et al, 1997) epithelium of duodenum (transiently) and conjunctiva and detected in sputum, urine and stool (Franzen et al., 1995) liver peritoneum Corneal stroma (Shadduck et al., 1990) urinary system (Deplazes et al., 1998). In experimentally infected Disseminated, especially involving myocytes (myocardium, muscularis of gastrointestinal tract, walls of arteries in urinary bladder, kidney, liver, adrenals, heart and diaphragm) but also present in adrenal cortical epithelium, kidney tubules and foci of hepatocytes (Margileth et al., 1973) Cornea (Visvesvara et al., 1999)

Nervous System Endocrine System Interactions

The link between the nervous and endocrine systems lies in two glands located between the cerebrum and the brain stem, the hypothalamus and the hypophysis (the pituitary gland). Electrical impulses from neurons in the cerebral cortex may activate the hypothalamus to release hormones that activate the hypophysis to release its hormones, which in turn activate or inactivate other endocrine glands throughout the body. These glands include the thyroid, parathyroids, thymus, pancreas, adrenals, and reproductive organs. This entire system operates by negative feedback homeostasis so that, once information is transferred and specific bodily functions are achieved, nervous or hormonal signals travel back to the hypothalamus to terminate any further action. If the pituitary gland releases adrenocorticotropic hormone (ACTH), the adrenal glands will be activated to release their hormones. The adrenal cortex produces and secretes a variety of hormones, such as aldosterone, which regulates the...

HPA Axis Abnormalities in Depression

A combined dexamethasone CRF test has also been developed. In this test, 1.5 mg dexamethasone is administered orally at night (11 p.m.) and subjects receive an intravenous bolus of 100 g hCRF at 3 p.m. the following day. Patients with HPA axis dysfunction display a paradoxically increased release of ACTH and cortisol relative to controls. These abnormalities, which are frequently encountered in depressed patients, disappear following remission of depressive symptoms, and normalization of HPA axis function seems to precede full clinical remission 61, 62 . The combined Structural changes in the components of the HPA axis have also been documented in depressed patients. Perhaps in part due to the trophic effects of CRF, pituitary gland enlargement has been documented in depressed patients as measured by magnetic resonance imaging (MRI) 64 . Enlargement of the adrenal glands, presumably due to ACTH hypersecretion, has repeatedly been demonstrated both in depressed patients post mortem 65,...

Pgp Inhibition as an Adjunct to Treating Chemotherapy Resistant Cancers

An extensive survey of MDR-1 mRNA expression levels in cancer patient tissue samples and normal controls suggested that three types of MDR-1 behavior may be distinguished in different cancer cells (121, 122) (1) MDR-1 is normally expressed in transporting epithelium, liver, colon, kidney, pancreas, and adrenal gland. Expression of MDR-1 remains high in cancers derived from these tissues. (2) Cancer cells derived from other tissues that normally do not express MDR-1 may be induced to express it when selected by drug treatment, and promoter analysis has shown that P-gp expression is induced by a variety of xenobiotics. This appears to result from clonal selection for resistant cells during the initial phase of drug treatment and leads to patient relapse following an initially successful response to therapy. Such relapses are commonly seen in leukemias, lymphomas, breast, and ovarian cancers. (3) Cancer cells that normally do not express MDR-1 may acquire expression in the absence of...

Sources for Further Study

Hormones and Human Behaviour. New York Cambridge University Press, 1985. An excellent compilation of the information available on hormones and behavior up to 1985. Uses technical language, but one who reads on a high-school level and has had some exposure to science will find the book informative and interesting. Focuses on the pituitary, the gonads, and the adrenals, and their effect on human behavior.


A central right non-small cell lung cancer with extensive ipsilateral mediastinal metastasis (a) in a 61-year-old man who was otherwise well. Staging by abdominal CT and bone scan showed 1.5 cm enlargement of the right adrenal gland and no other evidence of distant metastasis, and neoadjuvant therapy and resection were being considered. PET scan showed metastasis in the right adrenal gland( ) (b), left upper quadrant of the abdomen (S) (a) and the liver ( ) (c) (arrows) and management was changed to palliative radiation and chemotherapy. (Reproduced from Valk PE, Bailey DL, Townsend DW, Maisey MN. Positron Emission Tomography Basic Science and Clinical Practice. Springer-Verlag London Ltd 2003, p. 527.) Figure 1.1. A central right non-small cell lung cancer with extensive ipsilateral mediastinal metastasis (a) in a 61-year-old man who was otherwise well. Staging by abdominal CT and bone scan showed 1.5 cm enlargement of the right adrenal gland and no other evidence of...

The Amygdalas

In response to anxiogenic stimuli, the central nucleus of the amygdala solicits, either directly or indirectly through the BNST, the hypothalamic paraventricular nucleus (PVN) and the locus coeruleus. This latter is essential for the production of noradrenaline, which raises blood pressure, accelerates heart rate, and-with the nucleus accumbens-activates a motor reaction the PVN then produces corticotropin-releasing factor (CRF), which stimulates the pituitary (PIT) to release adrenocorticotrop-ic hormone (ACTH), which is carried in the bloodstream to the adrenals. Cortisol, a hormone secreted by the capsules, then returns to the brain in the bloodstream, regulating pituitary stimulation. The body thus finds the sympathetic system activated and can prepare itself-or at least predispose itself-to attack or to flee. The amygdala is part of a system of reciprocal regulation with the adrenals, as it is sensitive to the adrenaline and noradrenaline they produce, and governs the acquisition...


P-glycoprotein is an ATP-dependent transporter which is capable of transporting an extremely wide variety of drugs out of the cell. The potential role for P-glycoprotein for determining the oral bioavailability of some drugs has only recently been appreciated66. P-glycoprotein is expressed in a variety of normal human tissues including the liver, brain, adrenal gland, kidney and intestinal tract epithelia67. This suggests a common role as a protective mechanism. In the small intestine it is localised in the apical membranes of the cell, but is not detectable in crypt cells. It is composed of two blocks each containing six trans-membrane regions and a site for binding ATP on each half (Figure 6.12).

Spinal Cord

The locus ceruleus, which is situated in the pons, is one the the two pigmented areas of the brain (the other is the substantia nigra in the midbrain). The locus ceruleus is a norepinephrine-producing nucleus that sends widespread excitatory projections to many brain areas, but inhibitory projections to others, and may be important in facilitating wakefulness and attention, as well as the active (REM) phase of sleep. It has been called the adrenal gland of the brain.

Example 102

The endocrine system comprises glands that secrete messenger ligands, known as hormones, into the intercellular fluid. These ligands regulate the behavior of distant cells by binding to receptor proteins embedded in the membranes or interior of the target cell, forming a complex that triggers the target cell to express a characteristic biological response. Major endocrine glands include the thyroid, parathyroid, pituitary, and adrenal glands the pancreas and the testes and ovaries. The hormones secreted by the endocrine glands regulate a wide variety of bodily functions related to growth, reproduction, digestion, excretion, calcium homeostasis, and others. These hormones are dissolved within plasma and transported by the circulatory system to target cells. At the target cell, receptor proteins can be found in the membranes, within the cellular body, or within the nucleus. Hormones that are not fat-soluble cannot diffuse through the cellular membrane and therefore interact with...


Figure 4.4 Overview of the feedback mechanisms of the hypothalamic-pituitary-adrenal axis. Following relevant stimuli, including stress, corticotropin-releasing factor (CRF) is released from the hypothalamus into hypophyseal portal vessels, where it is transported in high concentrations to the pituitary gland. CRF then promotes the release of adrenocorticotropin (ACTH), which in turn promotes the release of cortisol from the adrenal glands. Cortisol acts as an inhibitory signal at both the hypothalamus and pituitary, preventing further CRF and ACTH release, respectively. Mounting evidence suggests that chronic overactivity of the axis, and particularly overproduction of CRF, may contribute to the pathophysiology of depression. Reproduced from 82 with permission

Initial Treatment

Hormone replacement therapy with L-thyroxine (L-T4) should be started immediately after thyroidectomy. Unlike papillary and follicular thyroid tumors, medullary carcinoma is not dependent on TSH for both growth and function, thus there is no need to treat patients with L-T4 suppressive therapy the daily dose should be tailored by measuring serum FT3, FT4, and TSH aiming to keep their values within the normal range. Unilateral or bilateral adrenalec-tomy must be performed before total thyroidec-tomy, when a pheochromocytoma has been documented, because of the risk of a life-threatening hypertensive crisis during the induction of anesthesia for the neck surgical treatment. Preoperative screening for pheochro-mocytoma should be conducted in all patients with a diagnosis of medullary thyroid carcinoma since the patient may be an index case of a familial form, presented as apparently sporadic. Although pheochromocytoma is usually bilateral, a 10-year interval is the mean period between the...

Renal carcinoma 171

Stage 1 Confined to renal parenchyma. Stage 2 Extends to adrenal glands and perinephric fat. Stage 3 Involves local vessels or nodes. Stage 4 Spreads to adjacent or distant organs. M Surgical Transabdominal or loin radical nephrectomy is the standard treatment with resection of perinephric fat, Gerota's fascia and ipsilateral adrenal gland. Partial nephrectomy ('nephron-sparing') may be appropriate to some patients. Radiotherapy and chemotherapy RCC is notoriously resistant to chemother-apeutic agents radiotherapy may be used for metastatic lesions. Immunotherapy Interleukin-2 and 7-interferon have limited response rates (15-20 ).

The Transition

Resulting in permanent loss of fertility. However, the ovarian stroma continues to produce androstenedione and testosterone in significant amounts. As estrogen levels decline into the postmenopausal range, estradiol is no longer made by the follicle, but by peripheral conversion of estrone, testosterone, and, most importantly, androstenedione. The major estrogen sources throughout this period are the adrenal glands via the conversion of androstenedione to estrone in adipose tissue. In addition, the adrenals continue to secrete testosterone and small amounts of estrogen, as well as dihydroepiandrostenedione (DHEA) and dihydroepiandrostenedione-sulfate (DHEAS). However, with increasing age, the adrenals produce smaller amounts of androgen, which also results in diminished peripheral estrogen production over time.

Hormonal activity

Growth factors stimulated by androgens, and by a combination of these mechanisms.66 Approximately 7000 mg of testosterone is secreted daily by the testes of which only 7 is converted into DHT in peripheral tissues.66 The testes produce 95 of androgens in men, while the adrenal gland accounts for the remaining 5 of hormone.67 Testosterone, as well as precursors to androgens, such as androstenedione, dehydroepiandrosterone (DHEA) and DHEA sulfate, originate in the adrenal gland and are likewise converted to DHT in peripheral tissues. Approximately 40 of prostatic DHT originates from steroids of adrenal origin.68 Androgen-dependent prostate cancer contains androgen receptors that bind DHT and transmit proliferative signals to the nucleus.69

Clinical picture

The majority (up to 98 ) of patients with systemic ARL present with extensive disease and systemic (B) symptoms. Extranodal lymphoma is very common, occurring in the majority of patients at presentation frequently, the disease is exclusively extranodal. The most common extranodal sites of lymphoma in HIV patients are gastrointestinal tract, liver, meninges (up to 20 ), lung, bone marrow (approximately 20 ) and oropharynx. Lymphoma in unusual sites such as the heart, adrenals, kidneys, skin, testes, mouth, muscle, soft tissue, anus and rectum occur more frequently in HIV-infected patients.

Hereditary Forms

About 50 of MEN2A and 40-45 of MEN2B patients develop pheochromocytoma, which shares the same characteristics in both syndromes. Contrary to the sporadic form of pheochromocytoma, the adrenal tumors of MEN syndromes are usually bilateral and mul-ticentric. However, the two adrenal glands are rarely simultaneously involved and a mean period of 10 years usually elapses between the development of the tumor in the two glands.


Technical progress has permitted new methodologies to be developed to facilitate detection and quantitative measurements of metastatic spread. This issue is of special importance because the majority of spontaneous metastases of CaP are microscopic. Yang et al. (86) used bits of green fluorescent protein-labeled PC-3 tumors that had been implanted orthotopically in nude mice. Metastases were detected in various organs, including liver, lung, kidney, pleural membrane, and adrenal gland. Interestingly, this approach resulted in skeletal micrometastases as well. Luciferase-labeled PC-3 cells grown intramuscularly were also used to monitor trafficking of these cells to lymph nodes (83).

Hormonal Effects

As well as the sex hormones already mentioned (see above) many other hormones seem to affect the metabolism of foreign compounds and therefore may have effects on toxicity. A number of pituitary hormones may directly, as well as indirectly, affect metabolism, for example growth hormone, follicle stimulating hormone, adrenocorticotrophic hormone, luteinizing hormone and prolactin. Thus, hypophysectomy in male rats results in a general decrease in metabolism, but the effects of some of the individual hormones may depend on the sex of the animal and the particular enzyme or metabolic pathway. For example, ACTH administration decreases oxidative metabolism in males but increases N-demethylation in female rats. Removal of the adrenal gland reduces metabolism, such as ethylmorphine demethylation and aniline 4-hydroxylation, and this can be partly restored by the administration of corticosteroids. However, there are probably many factors involved as well as the loss of a particular hormone....

Pituitary gland

Hans Selye, a Canadian scientist, proposed a direct connection between the endocrine system and behavior. In 1946, he described physiological events that were triggered by stress. This set of bodily changes became known as the general adaptation syndrome. The syndrome involved the mobilization of the autonomic nervous system, the adrenal glands, and the anterior lobe of the pituitary.


All vertebrates (animals with backbones) have a well-developed and highly organized endocrine system. The system consists of the following glands the pituitary, the pineal, the thyroid, the thymus, the pancreas, a pair of adrenals (each adrenal actually acts as two glands the adrenal cortex produces unique hormones and functions independently of the adrenal medulla), a pair of parathyroids, and a pair of ovaries or testes. Endocrine tissue in the gastrointestinal tract readies the system for the digestive process. During a pregnancy, the placental tissue assumes an endocrine function. Although the kidneys do not produce a hormone directly, they release an enzyme which converts a blood protein into a hormone that stimulates red blood cell production.

Shuin Lin Yang

In preparation for implantation, the kidney is unpackaged and transferred from the preservation fluid container to a backtable basin full of icy Ringer's lactate solution. The preservation fluid is cultured, as a guide for potential latent infection therapy at a later date. The perirenal fat and the adrenal gland are dissected off the kidney. The surgeon then checks and ligates all open ends from small branches of vessels and lymphatics, to avoid postreperfusion bleeding and posttransplant lymphocele formation.