Adrenal Disorders Supervised by: Dr.Azza Azzo Dr. Rania Aljezani Presented by: Deema Alangari Fatima...

Adrenal Disorders Supervised by: Dr.Azza Azzo Dr. Rania Aljezani Presented by: Deema Alangari Fatima AlHussain Joza AlOtaiby Rawan AlEnzi

Physiology: - The Adrenal gland are: Triangle-shaped organs that weigh approximately 4g. - located: Directly above the poles of the kidney.

- Composed of two physiologically distinct organs: The adrenal medulla and the adrenal cortex. Both of these endocrine organs are responsible for producing substances that aid the body in coping with stress.

The Adrenal medulla: Represent the Innermost portion of the adrenal gland. Secretes: Epinephrine. Norepinephrine. All are related as Catecholamines. The secretion of catecholamines is under control of the sympathetic nervous system.

The Adrenal cortex: represent outer portion, comprises 90% of the adrenal gland. Subdivided into three zones: The outer zona glomerulosa : make up 15% of cortex. The medial zona fasciculata : make up 75% of cortex. The inner zona reticularis : make up 10% of cortex.

Synthesize and secrete : Glucocorticoids : e.g., cortisol, from the zona fasciculata. Mineralocorticoids : aldosterone, from the zona glomerulosa. Sex steroids : androgens and estrogens from the zona reticularis.

Normal physiological effect of adrenaline and noradrenaline : 1. Glycogen broken down to glucose lead to increase blood glucose level. 2. Increase blood pressure (due to vasoconstriction of blood vessel ) 3. Increase breathing grate (due to bronchodilator effect of N) 4. Increase metabolic rate. 5.Change in blood flow patterns, leading to increase digestive and kidney activity.

Normal effect of cortisol: Cortisol's most important job is to help the body respond to stress. Among its other vital tasks, cortisol. - helps maintain blood pressure and cardiovascular function. - helps slow the immune system's inflammatory response. - helps balance the effects of insulin in breaking down sugar for energy. - helps regulate the metabolism of proteins, carbohydrates, and fats. - helps maintain proper arousal and sense of well- being.

Normal effect of and aldosterone: Aldosterone belongs to a class of hormones called mineralocorticoids. It helps maintain blood pressure and water and salt balance in the body by helping the kidney retain sodium and excrete potassium.

Metabolic effects of Glucocorticoids: Glucocorticoid excess causes alteration in the following: 1. protein and carbohydrate metabolism. 2. Distribution of adipose tissue. 3. Electrolytes. 4. The immune system. 5. Gastric secretion. 6. Brain function. 7. Erythropoiesis. 8. suppresses inflammation.

Effect on protein: Glucocorticoid have catabolic effect and antianabolic effects on protein, causing: Decrease in the ability of protein forming cells to synthesize protein. As a consequence, there is loss of protein from tissue such as skin, muscles, bold vessels, and bone.

The skin: The skin atrophies and break down easily; wounds heal slowly. Rapture of elastic fibers in the skin causes purple stretch marks, or striae.

The muscles: - Muscles also atrophy and become weak. - Thinning of blood vessel walls and weakening of perivascular supporting tissue result in easy bruising. This condition can be severe enough for petechiae or even large areas of ecchymosis to appear under the cuff when the patient's blood pressure is taken.

The bone: - There is loss of protein matrix of bone, causing a condition known as osteoporosis, which occur most frequently in the spine, causing vertebral collapse and resultant back pain and loss of height.

Effect on carbohydrate : Glucocorticoid stimulate gluconeogenesis and interfere with the action of insulin in peripheral cells. As a consequence, patients may develop hyperglycemia. In person with an adequate insulin- secreting capacity: The effect of glucocorticoids is countered by increasing insulin secretion that subsequently normalizes glucose tolerance. In patients with diminished insulin- secreting capacity: They are unable to compensate.

Effect on the distribution of adipose tissue: Accumulation of adipose tissue in the central area of the body: - truncal obesity. - moon face: round face. - buffalo hump: supraclavicular fossa fullness and cervicodorsal hump. The truncal obesity and thinning of the upper and lower extremities as a result of muscle atrophy give patients the classic cushingoid appearance.

Effect on serum electrolyte levels: May cause sodium retention and potassium waste, leading to edema hypokalemia, and metabolic alkalosis. Effect on gastric secretion: Gastric secretory activity is increased because steroids alter mucosal protective factors lead to ulcer formation.

Effect on immune response: Glucocorticoids can inhibit immune response. - Immune responses are of two major types: 1. Production of humoral antibodies by B lymphocytes and plasma cells following antigenic stimulation. 2. Depends on sensitized T lymphocytes-mediated reaction. A] Impairment of the immunologic response can occur at each of the stages of this response: 1. initial processing of antigens by cells of the monocyte-macrophage system.

2. induction and proliferation of immunocompetent lymphocytes and release of cytokines. 3. antibody production. 4. the inflammatory reaction. B] glucocorticoid also suppress delayed hypersensitivity reactions. C] The glucocorticoid-mediated inhibition of cellular immunity is probably important in suppressing transplant rejection.

On Cardiovascular : Hypertension. due to (increase aldosterone cause Na and water retention and edema), increase cardiac out put by effect of cortisone, and Because sensitivity of blood vessel to chatecolamine is increased.

Effect on brain function: -emotional liability. -euphoria. -insomnia. -episodes of transient depression. Erythropoiesis : -Involution of lymphoid tissue. -stimulation of neutrophil release. -enhancement of erythropoiesis.

Suppresses inflammatory response : It is the most important and clinically useful pharmacologic effect of glucocorticoids. -inhibit hyperemia. -extravasation of cells. -cellular migration. -capillary permeability. -inhibit the release of vasoactivekinins. -suppress phagocytosis.

By their effect on mast cells, glucocorticoids inhibit histamine synthesis and suppress the acute anaphylactic reaction based on antibody-mediated hypersensitivity. Also decrease serum calcium levels hypocalcaemia.

Regulated and stimulated by :

Hypothalmic-Pitutary gland- Adrenal Feedback system: During stress, plasma Adrenocorticotropic hormone (ACTH) is elevated, and then cortisol is produced and released by the adrenal cortex. ACTH is secreted by the anterior pituitary gland under the regulatory control of corticotrophin- releasing factor (CRF), which is secreted by the hypothalamus. Catecholamines and vasopressin also simulate the release of ACTH.

In stressful situations, ACTH secretion increases to many time the basal rate and increase cortisol production and secretion. As cortisol level increase in response to ACTH stimulation. CRF release from the hypothalamus is turned off. The decrease in CRF then leads to a reduction in further ACTH and cortisol secretion.

Conditions that Stimulate ACTH and Cortisol Secretion Hypoglycemia Cold exposure InfectionPain TraumaAnxiety ToxinsHemorrhage DepressionExercise AlcoholismStarvation

Circadian Rhythm: It is factor which influences cortisol secretion. This circadian, or diurnal, rhythm : is the cyclic release of cortisol occurring throughout a 24-hr period as a result of intrinsic endocrine function. Minimal secretion of cortisol occurs just before and in the initial hours of sleep; maximal secretion of cortisol occurs just before and in the initial hours of wakefulness. During the rest of the day; intermittent secretion of cortisol occur.

Hyperfunction of the adrenal gland

Cushing's Syndrome: Cushing's syndrome may result from: - long-term administration of pharmacologic doses of glucocorticoids (iatrogenic). -excessive cortisol secretion caused by a disturbance in the hypothalamic-pituitary- adrenal axis (spontaneous).

Iatrogenic Cushing's syndrome: is seen in patients with conditions such as rheumatoid arthritis, asthma, lymphoma, and generized skin disorders who receive synthetic glucocorticoids as anti-inflammatory agents. Spontaneous Cushing's syndrome: Adrenocortical hyperfunction develops either as a result of excessive stimulation by ACTH or as a consequence of adrenal pathology leading to abnormal production of cortisol.

Cushing's syndrome can be divided into two types: ACTH- dependant: Its etiologies based on chronic hypersecretion of ACTH, account for approximately 80% of all cases of spontaneous Cushing's syndrome. Elevated ACTH levels lead to overstimulation of the adrenal zona fasciculata and zona reticularis and therefore, to increase secretion of cortisol and androgens.

*ACTH-dependant causes include the following: 1.pituitary microadenomas resulting in an increased release of ACTH (Cushing's disease). 2. ectopic, malignant ACTH-secreting tumors (e.g., small cell carcinoma of the lung islet- cell tumor, thymoma, and bronchial adenoma). 3. ectopic CRF-secreting tumors.

ACTH- independent: ACTH- independent etiologies involve cortisol secreting tumors, which lead to elevated serum cortisol levels and secondarily to suppressed ACTH release. Accounting for fewer than 20% of patient with Cushing's syndrome.

* ACTH- independent causes include the following: 1. nodular hyperplasia of the adrenal cortex. 2. adrenal cortical tumors. may be: a- Benign (adenomas): may lead to severe Cushings syndrome, but they usually develop slowly, and symptoms may be present for several years before the diagnosis is finally made. b- Malignant (carcinoma): develop rapidly and may lead to metastasis and early death.

3. ectopic production of cortisol. N.B: Female having 3.5 times higher risk than males and having a propensity to developing pituitary microadenmas (Cushing's disease) as the cause of Cushing syndrome.

Etiologies of Cushings Syndrome

Clinical Manifestation: An overall change in appearance and increased total body fat are classic initial finding. -Obesity is common, and fat is redistributed to central areas of the body, resulting in truncal or centripetal obesity with a protuberant abdomen and wasted extremities.

-moon faces: rounding of the face. -buffalo hump. -the skin of the patient is fine and translucent (why?), because of atrophy of the epidermal layer and connective tissue beneath it.

-florid complexion. -vascular striae. -easy bruising and poor wound healing are results of hypercortisolemic atrophy. -Hyperpigmentation: from the stimulatory action of cortisol on melanocytes may be seen

-growth of lanugo facial hair. -increase in androgen levels. In female patients: Hirsutism (abnormal growth of hair). Acne. Seborrhea. Amenorrhea. In male patients: Decrease in libodo. Decrease in body hair. Testicular atrophy.

-On Muscle: * muscles wasting and myopathy (why?). because of the catabolic effect of cortisol on muscle tissue. * Proximal muscle weakness. * Primarily of the lower extremities, is often exhibited as difficulty in climbing stairs and standing up from a sitting position.

-effect on the metabolic functions of bone: * inhibition of osteoblasts by cortisol may cause osteopenia and ultimately osteoporosis. * Hypercalciuria: result in kidney stone formation. * In Adults: bone pain and fractures. * In children: premature closure of the long epiphyses, leading to stunted growth and short stature.

-Hypokalemia. -Psychiatric disturbance: include mood liability, euphoria, increased anxiety, crying, insomnia, and decreases in memory and concentration. -Immunosuppresion: which leads to a predisposition for bacterial and opportunistic infections ranging in severity from fungal skin infections to Pneumocystis carinii pneumonia and cryptococcal meningitis.

Diagnosis: 1. 24-Hour Urinary Free cortisol Level (free scanning): This is the most specific diagnostic test. The patient's urine is collected over a24-hour period and tested for the amount of cortisol. Once Cushing's syndrome has been diagnosed, other tests are used to find the exact location of the abnormality that leads to excess cortisol production. Normal value: 20 100 mg/24 hrs, when it is greater than 100 to 125 mg/24 hr. Cushing syndrome is likely.

2. Dexamethasone Suppression Test: This test helps to distinguish patient with excess Production of ACTH due to pituitary adenomas from those with ectopic ACTH- producing tumors. Dexamethasone is a man-made (synthetic) steroid that is similar to cortisol. It reduces ACTH release in normal people. Therefore, taking dexamethasone should reduce ACTH levels and lead to decreased cortisol levels. Cushing syndrome related to ectopic ACTH-producing tumor: there is no response. Cushing syndrome caused by pituitary tumor (Cushing's disease) there is a response to dexamethason suppression test.

3. CRH Stimulation Test: This test helps to distinguish between patients with Pituitary adenomas and those with ectopic ACTH Syndrome or cortisol-secreting adrenal tumors. Patients are given an injection of CRH Rise in blood levels of ACTH and cortisol in patients With ectopic ACTH syndrome. No response in patients with cortisol- secreting adrenal tumors.

4. Direct Visualization of the Endocrine Glands (Radiological Imaging): Imaging test sreveal the size and shape of the pituitary and adrenal glands and help determine if a tumor is present.

Treatment: -Surgical treatment. -Medical treatment: Medical treatment for Cushing's syndrome is reserved for intractable cases of Cushing's syndrome or situations in which there will be a delay in surgery. Two types of medication are used: 1.medications that inhibit the pituitary secretion of ACTH (e.g., Bromocriptine). 2.medications that inhibit the adrenocorticol secretion of cortisol (e.g., Metyrapone).

Aldosteronism: Aldosteronism results from excessive production of aldosterone, The mineralocorticoid steroid hormone of the adrenal cortex. N.B: Aldosterone enhances proximal renal tubule reabsorption of sodium and causes potassium and hydrogen ion excretion.

The clinical consequence of aldosterone excess: -Sodium and water retention. -expansion of the extracellular fluid volume. -hypertension. -hypernatremia. -hypokalemia. -metabolic alkalosis.

There are two types of aldosteronism: Primary Aldosteronism (Conn's syndrome): The excessive production of aldosterone occurs as a result of tumor or hyperplasia of the adrenal cortex. Most aldosterone-secreting tumors are benign and small 0.5 to 2.0 cm. It is a form of endocrine hypertension and probably affects 1% to 2% of patients with hypertension.

Secondary Aldosteronism: Occurs in conditions in which afferent arteriolar pressure in the renal glomerulus decreases, leading to stimulation of the rennin-angotensin system. Angotensin stimulates aldosterone production. It is seen in: -Congestive heart failure. -Cirrhosis of the liver. -Kidney disease. These conditions in which edema is prominent clinical feature.

* Congestive heart failure exemplifies the way secondary aldosteronism may develop (How?): Patients in congestive heart failure cannot pump blood normally and develop a fall in cardiac output. Perfusion pressure to the afferent arteriole of the renal glomerulus decreases. The fall in pressure is sensed by stretch receptors in the juxtaglomerular apparatus. Rennin is secreted in increased amounts.

Rennin activates angiotensin production. Angiotensin stimulates aldosterone secretion by an otherwise normal adrenal cortex. The increased production of aldosterone promote sodium and water reabsorption, expansion of the extracellular fluid compartment, and possibly an increase in afferent arteriolar pressure. N.B.: Secondary aldosteronism can also develop in conditions in which a partial occlusion of the renal artery occurs, leading to renal vascular hypertension.

Diagnosis: Is based on: 1.the measurement of increased levels of aldosterone in plasma. 2. the measurement of increased levels of aldosterone in urine. 3.Special blood test called: plasma rennin activity (PRA): is measured to distinguish between primary aldosteronism (low PRA) and secondary aldosteronism ( high PRA).

4.Computered Tomography scanning and Nuclear photoscanning: also help detect and localize an adrenal lesion in patient with primary aldosteronism. If a tumor cannot be localized, samples of adrenal venous blood may be obtained by selective catheterization of the right and left adrenal veins. A higher concentration of aldosterone on the side suspected of harboring a tumor helps confirm the presence of the lesion.

Treatment: Treatment of primary aldosteronism includes unilateral adrenalectomy through a laparoscopic approach, with resection of the aldosterone-secreting hormone. Patient with adrenal hyperplasia are treated by the administration of aldosterone antagonists such as sipronolactone.

Syndromes of Androgen Excess: Androgen Physiology: Both men and women normally secrete various androgen.

The three major types of androgen are: 1. dehyroepiandrosterone. 2. delta 4-androstenedione. 3. testosterone.

- the adrenal gland is the main source of it. - its metabolite DHEA sulfate - weak androgens. - can be measured in the urine as 17- ketosteroids. Dehyroepiandroste rone (DHEA) - It is a stronger androgen product than DHEA but weaker than testosterone. - The adrenal cortex & ovary also produce Delta 4-androstenedione. Delta 4- androstenedione - It is the most potent of the three androgen compound. - There are several source of testosterone including in: Adrenal cortex, the ovary, the testes,and the peripheral tissue. - Testosterone circulates in the plasma partially bound to a carrier protein: sex hormone binding globulin (SHBG), a small fraction is unbound. Testosterone

Hirsutism : One of the most common problem seen by the endocrinologist among young women is Hirsutism, which is usually a manifestation of androgen excess.

What is the hirsutism? Hirsutism is excessive growth of body hair in the female in a characteristic masculine distribution over the facial, periareolar,abdominal and sacral area. It may be associated with baldness or temporal recession of the hairline.

Hirsutism may be present alone or as a part of the a virilizing syndrome. Women with hirsutism usually have abnormalities in testosterone secretion, transport and metabolism. For example; hirsute women have less testosterone binding, higher free testosterone level, and more active metabolic clearance tests than women without hirsutism.

Although in normal women testosterone is extracted and metabolized almost completely by the liver. Hirsutism is seen in disorder such as porphyria and congenital ectodermal dysplasia or in areas of the body that have been either immobilized or placed in a body cast.

Adrenal Virilism: Virilism, excessive secretion of androgens from the adrenal gland, is more commonly seen in females, with hirsutism being the dominant feature. Women who present with hirsutism also may have: -voice deepening. -increased muscle mass. -menstrual abnormalities. -clitoral enlargement. While Virilism me be easy to diagnose based on clinical symptoms, making the diagnosis on a biochemical basis difficult.

The most common etiology of virilism involves one of many possible congenital enzymes defects. Depending on the enzyme deficiency, accumulation of a variety of androgens, notably testosterone, can develop. Hirsutism, often without any other signs of virilism but frequently accompanied by irregular or absent menstrual period and acne, is a common clinical entity and associated with polycystic ovary syndrome (PCOS). When hirsutism is present alone and without virilization or menstrual irregularity, women are thought to have simple or idiopathic hirsutism.

Differential diagnosis of androgen Excess: Five major categories of conditions are associated with androgen excess: 1. Polycystic ovary syndrome ( PCOS). 2. Adrenocortical or ovarian tumors. 3. Late- onset or non classical adrenocortical hyperplasia. 4. Simple or idiopathic hirsutism. 5. Miscellaneous states.

1. Polycystic ovary syndrome ( PCOS): Hirsutism is frequently associated with infertility, amenorrhea, obesity, and enlarged ovaries. It have sustained elevations of serum luteinizing hormone (LH). In these patients testosterone production rates are responsible for the manifestations of androgen execs. The increased production of androgens in PCOS may be secondary to the hyperinsulinemia that develops in association with obesity.

The high insulin levels stimulate insulin-like growth factor-1(IGF-1)concentration in the ovary and cause increased androgen secretion. PCOS may result from hypothalamic-pituitary abnormalities affecting the cyclic release of gonadotropins. N.B.: These change in gonadotropin secretion may lead to anatomic changes in the ovary and stimulation of ovarian androgen production.

2- Adrenocortical or ovarian tumors: adrenocortical or ovarian tumors can be associated with cortisol and produced with adrenogen execs. * Adrenocortical carcinomas secrete androgens alone or in combination with cortisol and produce either a pure virilizing syndrome or a mixed Cushings virilizing syndrome. * Ovarian tumors: Such as arrhenoblastomas and hilus cell neoplasms, are capable of secreting large amounts of testosterone and producing virilization.

Congenital Adrenal hyperplasia(CAH): Is a condition in which there is an inborn defect in one of the enzyme involved in cortisol biosynthesis. The most common type is a defect in 21- hydroxylase, the adrenal cortex has an impaired capacity to secrete cortisol.

The decrease in cortisol production causes an increase in ACTH secretion in response to the negative feedback activation of pituitary function. ATCH stimulate the adrenal cortex causing precursors of cortisol biosynthesis to be shunted to the biosynthesis of androgen. When the fetus is exposed to increase amounts of androgen, it undergoes change in the development of the external genitalia. This may create difficulties in sexual identification of the new born.

For example; a female fetus with this defect develops an enlargement of the clitoris and fusion of the labia major. The genitalia then resemble male external genitalia. The syndrome of a masculinized genetically female fetus caused by androgen excess in utero is called female pseudohermaphroditism. N.B.; manifestation of androgen excess in patients with congenital adrenal hyperplasia can also develop at puberty or after puberty.

3- Late onset or non classic CAH: Is consequence of a milder form of congenital adrenal hyperplasia with only partial defects in 21-hyrdoxlase, 11-beta- hydroxlase,or 3-beta-ol-dehydrognase, delta 4,5-isomerase.

Androgen Excess Differential Diagnosis I. androgen excess of adrenocortical origin. A) Cortisol excess: Cushings syndrome. B) Androgen excess only. 1. prenatal : congenital adrenal hyperplasia(CAH). 2. postnatal : a. late manifestation of CAH. b. carcinoma. 3. pubertal or postpubertal. a. hyperplasia, with or without polycystic ovaries. b. carcinoma. II. androgen excess of ovarian origin A) NEOPLASMS: arrhenoblastoma,adrenal rest cell neoplasms, hilus cell neoplasm,luteoma. B) Hilus cell or leydig cell hyperplasia. C) Polycystic ovary syndrome.

Continue: Androgen Excess Differential Diagnosis III. simple or idiopathic hirsutism. IV. miscellaneous cause. A. endocrine 1. acromegaly 2. pregnancy 3. hypothyroidism 4. menopause 5.androgen therapy 6. inanition B. Non endocrine 1. immobilization 2. body cast 3. porphria 4. congenital ectodermal dysplasia.

Clinical and laboratory Evaluation of Hirsute Women: It is necessary to determine whether the hirsutism is present by itself or accompanied by manifestation of virilization. It is also important to determine whether the symptoms are those of androgen excess alone or are accompanied by symptoms of cortisol excess. A history of recent onset and rapid progression of excessive hair growth frequently suggests a malignancy as the source of excessive androgen production.

Tests to document excessive androgen production include: Measurement of blood levels of total and free testosterone,DHEA, androstenedione. When PCOS is suspected, measurement of serum LH and glucose and insulin levels is helpful. Patient suspected of non classical CAH should have, in addition, measurement of serum 17 alpha-hydroxyprogesterone and 17 alpha- hydroxypregnenolone before and after stimulation with corticotrophin.

In the presence of an enzyme defect, this stimulation result in an exaggerated rise of these steroid precursors and helps confirm the diagnosis. Patient suspected of an adrenal or ovarian androgen secreting tumor should undergo a pelvic examination abdominal and pelvic CT scan, MRI, or ultrasound.

Pheochromocytoma: Pheos mean dusky, Chromo mean color, Cytoma mean tumor refers to color the tumor cells acquire when stained by chromium salts. It is a rare cause of secondary hypertension. It is an adrenal medullary or sympathetic chain (paraganglioma) tumor that releases excessive amounts of catecholamines (epinephrine, norepinephrine and dopamine) in sustained or intermittent manner.

N.B.: Pheochromocytoma affect 0.1% to 0.5% of the hypertensive population and may have fatal outcome if undiagnosed or untreated. Pheochromocytoma occurs equally in men and women and has a peak incidence between age 30 and 50. 90% of these tumors are derived from adrenal medullary chromaffin cells, and 10% are extraadrenal, located in the retropertioneal area (organs of Zuckerkandl), celiac and mesentric ganglia, and urinary bladder. Pheochromocytoma are usually benign (95% of cases), but they may be malignant and present with distant metastases.

Clinical manifestation: Clinical manifestation of these tumors are related to the release of catecholamine. 1. The most prominent feature is hypertension that may be paroxysmal (45% of cases) or sustained. N.B.: Patients with paroxysmal symptom develop acute episodes of sever hypertension (250/140 mm Hg)lasting minutes to hours. The episodes may be triggered by exercise, ingestion of tyrosine-containing foods (red wine, aged cheese, yogurt ), caffeine-containing foods, abdominal palpation, or induction of anesthesia.

2. Patients remain normotensive between episodes. - headaches on the top of their head. - palpitations. - pallor. - diaphoresis. - dysrhythmias. * Patients with sustained hypertension may also show variability in their high-blood pressure readings and complain of headaches and irregular heartbeat.

3.Patients present with symptoms of orthostatic hypotension, especially if the tumor secretes significant amounts of dopamine.

Diagnosis: 1. The biochemical evaluation of patients suspected of a Pheochromocytoma. Consists of measurement of plasma or urinary levels of : epinephrine, norepinephrine, and their metabolites metanephrine and normetanephrine. Because normal adrenal secretion of epinephrine and norepinephrine may vary, distinction between physiologic and pathologic hypersecretory states may be difficult with a single determination of catecholamine levels.

Norepinephrine can increase with a change from the recumbent to the upright position. Catecholamines are also increased with an acute myocardial infarction, volume depletion, hypothyroidism, and other physical or emotional stress. Peripheral vasodilators, cocaine, phenoxybenzamine can increase catecholamine release. Insulin-induced hypoglycemia can evoke major increases in epinephrine and small increases in norepinephrine. Drugs such as clonidine, decrease plasma norepinephrine levels.

2. Basal plasma catecholamine levels should be obtained with the patient resting in the supine position for at least 30 minutes. Normal levels: - epinephrine, range from o to 100 pg/ml. - norepinephrine, 0 to 500 pg/ml. - dopamine, 0 to 100 pg/ml. Markedly increased levels (epinephrine more than 500 pg/ml and norepinephrine greater than 1500 pg/ml) are virtually diagnostic of pheochromocytoma.

3. Basal urinary catecholamines should be collected for 12 hours during the night. Normal levels: - epinephrine, 0 to 20 mg/day. - norepinephrine, 0 to 100 mg/day. - metanephrines, 0 to 300 mg/day. - normetanephrines, 50 to 800 mg/day. - vanillyl mandelic acid (VMA), 0 to 7 mg/day. Patients with pheochromocytoma have high urinary catecholamine levels.

4. In borderline cases, a clonidine suppression test may help differentiate normal subjects from patients with a pheochromocytoma (How?) - 0.3 mg of clonidine, is administered orally after two baseline blood samples for epinephrine and norepinephrine are obtained. - Plasma epinephrine and norepinephrine samples are repeated 3 hours after clonidine administration. Patients with a pheochromocytoma fail to suppress catecholamine secretion, whereas clonidine will restore normal levels of catecholamines in other hyperadrenergic states.

Treatment: 1. Surgical resection of the pheochromocytoma and exploration of the retroperitoneal space for paraganglia-derived tumors. 2. Patients' blood pressure should be stabilized preoperatively by: - alpha adrenergic blocking agents. such as phenoxybenzarnine. - Beta-blockers, such as propranolol, when needed. - Phenoxybenzamine is also used as medical treatment to block catecholamine effects in patients with malignant, unresectable pheochromocytomas.

Hypofunction of the adrenal gland

Addisons Disease: Definition: It results from primary or secondary causes. - Primary adrenocortical insufficiency (Addison's disease): Result from destruction of the adrenal cortex. * Tuberculosis used to be the most frequent cause of Addison's disease - Secondary adrenocortical insufficiency: Due to deficient pituitary ACTH secretion causing atrophy of the adrenal cortex.

Etiology: Approximately 80% of primary adrenocortical insufficiency is now idiopathic. The remaining 20% of Addison's disease occurs as a complication of Tuberculosis or in rare situation, is due to: - cancer infections ( bacterial or fungal ). - trauma. - hemorrhagic disorders. - congenital adrenal hypoplasia (autoimmune destruction of the adrenal gland).

Adrenal insufficiency in patients with acquired immune deficiency syndrome (AIDS) occur rarely and is thought to be due to: - disseminated infection. - Neoplasm. - autoimmune process. - changes associated with chronic disease. - malnutrition. The common cause of secondary adrenocortical insufficiency is steroid withdrawal in a patient with adrenal atrophy due to exogenous glucocorticoid therapy.

Pathogenesis: In addition to primary or secondary causes, adrenocortical insufficiency can also be acute or chronic A) chronic adrenocortical insufficiency: - When Addison's disease occurs as a result of gradual destruction of the adrenal gland, chronic adrenal insufficiency is manifested. - Patients of this disease have normal basal cortisol secretion but may have difficulty in increasing cortisol secretion with stress.

N.B.: Over time, even basal cortisol secretion becomes inadequate, and clinical manifestations of adrenocortical insufficiency become evident. However, without an acute stressful event, chronic adrenal insufficiency will usually go unnoticed because of the vaguse symptoms of the disease.

B) Acute adrenocortical insufficiency : - When adrenal need, generated by stress of surgery, trauma, or infection, exceeds the glands capacity for cortisol production. - When 90% or more of the adrenal cortex is nonfunctioning and is usually accompanied by elevated ACTH levels.

Clinical Manifestation : Adrenocortical insufficiency is not manifested until more than 90% of both adrenal cortices are lost. Hyperpigmentation of the skin and mucous membranes is usually the hallmark characteristic that prompts the physician to test for adrenal insufficiency. - It is most pronounced in sunexpsed areas of the body and at pressure point but also occurs on palmer creases, nail beds, the tongue, the nipples, the navel, and the perivaginal and perianal mucosa.

- Present in 92% of patients. - Is caused by increased melanocyte-stimulating hormone and B-lipotropin serum levels, which accompany increased ACTH levels. -Vitiligo also occur but at a much lower incidence of approximately 4 to 17 %. gastrointestinal symptoms such as nausea, abdominal discomphort, diarrhea, vomiting are warning signs that may signal progressive adrenal insufficiency and impending crisis.

Addisonian Crisis : Acute addisonian crisis (apoplexy) results when a patient with undiagnosed Addison's disease becomes stresses or is exposed to a stressful event such as trauma, infection, surgery, or hemorrhage.

Signs and Symptoms : - Anorexia develops and is accompanied by nausea and vomiting.This leads to severe dehydration and hemodynamic instability. - Fever, with or without a concurrent infection. - Abdominal pain and tenderness may confuse the diagnosis as one of acute abdominal event. - Weakness, fatigue. - Confusion. - Coma and shock.

Diagnosis : * The diagnosis of adrenal insufficiency is made by specific laboratory tests. * Patients with primary adrenal insufficiency have decreased cortisol and aldosterone but high ACTH and rennin levels. * The intravenous infusion of synthetic ACTH fails to elicit a rise in cortisol level.

* Because of aldosterone deficiency, electrolyte levels show: -Hyponatremia. -Hyperkalemia. -Metabolic acidosis. -Esinophilia. -Lymphocytosis. -Hypoglycemia. -Increase blood urea nitrogen levels. * Patient with adrenal insufficiency secondary to ACTH deficiency have low levels of both cortisol and ACTH.

References: Phathophysiology, ch.61 Text book of Therapeutic, ch.16 Pharmacotherapy, ch. 74 www.e-medicin.com

Adrenal Disorders Supervised by: Dr.Azza Azzo Dr. Rania Aljezani Presented by: Deema Alangari Fatima...

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