1 MAGDI AWAD SASI 2013 ADRENAL GLAND DISORDERSADRENAL GLAND Either of two small, dissimilarly shaped endocrine glands, one locatedabove each kidney, consisting of the cortex, which secretes severalsteroid hormones, and the medulla, which secretes epinephrine. The adrenal cortex produces corticosteroids which include glucocorticoids(primarily cortisol), mineralocorticoids (primarily aldosterone), andandrogens (primarily dehydroepiandrosterone and androstenedione). Function is regulated by the neuroendocrine hormones from the pituitary,hypothalamus and renin-angiotensin system.((NOT THE MEDULLA)) Glucocorticoid-- Prominent effects include anti-inflammatory actions andincreased hepatic gluconeogenesis and help body respond to stress. . Mineralocorticoids regulate electrolyte transport across epithelialsurfaces, particularly renal conservation of Na in exchange for K. Glucocorticoid and Mineralocorticoids are essential for life .
2 MAGDI AWAD SASI 2013 ADRENAL GLAND DISORDERS Adrenal androgens--chief physiologic activity occurs after conversion totestosterone. The adrenal medulla is composed of chromaffin cells, which synthesizeand secrete catecholamines (mainly epinephrine and lesser amounts ofnorepinephrine). Chromaffin cells also produce bioactive amines and peptides (eg,histamine, serotonin, chromogranins, neuropeptide hormones Epinephrine and norepinephrine(( the major effector amines of thesympathetic nervous system)), are responsible for the “flight or fight”response (ie, chronotropic and inotropic effects on the heart;bronchodilation; peripheral and splanchnic vasoconstriction with skeletalmuscular vasodilation; metabolic effects including glycogenolysis,lipolysis, and renin release). Hypofunction may be primary (malfunction of the adrenal gland itself, asin Addisons disease) or secondary (due to lack of adrenal stimulation bythe pituitary ((2ry)) or hypothalamus((3ry)). Hyperfunction produces distinct clinical syndromes. Hypersecretion of androgens results in adrenal virilism;of glucocorticoids, Cushings syndrome;And of aldosterone, hyperaldosteronism (aldosteronism). These syndromes frequently have overlapping features. Hyperfunction may be compensatory, as in congenital adrenalhyperplasia, or due to acquired hyperplasia, adenomas, oradenocarcinomas. Excess quantities of epinephrine and norepinephrine are produced inpheochromocytoma .
3 MAGDI AWAD SASI 2013 ADRENAL GLAND DISORDERSFUNCTION OF THE GLAND:Cortex -Stimulated by ACTHHormone precursor: CholestrolSecretes: Cortisol Aldosterone Sex hormones: Androgen ,EstrogenHORMONE FUNCTIONALDOSTERONE Renal : Na & Cl reabsorption; K excretionGI : Na absorptionGLUCO-CORTICOIDS Increase serum glucose by gluconeogenesis &glycogenolysis especially during STRESSBlocks inflammation(IL6,PG,lymphokines)Counteracts effect of histamine-inflammationRequired for ANG2-maintain vasculatureSEX HORMONE Physiologically insignificantBecomes useful during menopause in women
4 MAGDI AWAD SASI 2013 ADRENAL GLAND DISORDERSSYMPTOMATOLOGY:ALDOSTERONE DEFICIENCYDecrease in plasma volume leading to dehydration.Hypotension to shock.Increased K.Metabolic acidosis .CORTISOL DEFICIENCYANOREXIA, N/V, ABDOMINAL PAIN, WT LOSS, LETHARGYHYPOGLYCEMIAHYPOTENSIONHYPERKALEMIA, WEAK PULSEHYPERPIGMENTATIONIMPAIRED STRESS TOLERANCESEX HORMONE DEFICIENCYLOSS OF BODY HAIRLOSS OF LIBIDO OR IMPOTENCEMENSTRUAL & FERTILITY DISORDERADRENAL CORTEX DISORERS ADRENAL INSUFFICIENCY ADRENAL CRISIS CUSHING’S SYNDROME ALDOSTERONISM
5 MAGDI AWAD SASI 2013 ADRENAL GLAND DISORDERSADRENAL INSUFFICIENCYADDISON’S DISEASE Is a hormone deficiency caused by damage to the outer layer of theadrenal gland (adrenal cortex). Addisons disease is a disorder that results in the body producinginsufficient amounts of certain hormones produced by the adrenal glands. Sometimes, Addisons disease also involves insufficient production ofaldosterone, one of the mineralocorticoid hormones. Insufficiency of corticosteroids can be total when the operation of allhormones drops out, and partial fallout of activity of one adrenalhormone. Addisons disease can be life-threatening. Addisons disease can occur at any age, but is most common in peopleages 30 to 50.ETIOLOGY: Autoimmune processes -80% of cases-corticosteroid, aldost,androgen-all Pituitary failure( atrophy, necrosis)-no HYPERKALEMIA/PIGMENTATION TB, Syphilis, coccid mycosis ,Histoplasmosis, CMV(AIDS) Tumor ,Metastases , Amyloidosis, Hemochromatosis Hemorrhage-warfarin, shock, major surgery, antiphospholipid. Drugs that block corticosteroid synthesis (eg, ketoconazole). All groves syndrome-achalasia, alacrima,neurologic disease. Polyglandular atrophy Addisons disease may coexist with diabetes mellitus or hypothyroidism.
6 MAGDI AWAD SASI 2013 ADRENAL GLAND DISORDERSSIGNS AND SYMPTOMS:Signs and symptoms of Addisons disease usually develop slowly, often overseveral months, and may include:Mineralocorticoid deficiency↑ in urinary excretion of Na,↓ in urinary excretion of KInability to concentrate urine,with electrolyte imbalancesevere dehydrationplasma hypertonicity, acidosis,hypotensioncirculatory collapseGlucocorticoiddeficiencyDisturbances incarbohydrate, fat andprotein metabolism,decrease liver glycogenHypoglycaemia andanorexiaDestruction ofadrenal glandMineralocorticoid &glucocorticoid deficiency• Symptoms & Signs usually do not appear until ~90% of adrenal gland hasbeen compromised.A. Manifestation, connected with the falling of mineral corticoids:1) DEHYDRATION develops owing to loss of sodium ions (decreasesrearbsortion) with the loss of water (polyuria).2) HYPOTENSION - by decrease of circulating blood volume.3) HEMOCONCENTRATION is connected with liquid loss, results todisorders of microcirculation and hypoxia.
7 MAGDI AWAD SASI 2013 ADRENAL GLAND DISORDERS4) Decreasing of kidney blood circulation is stipulated by increase ofarterial pressure with disturbances of glomerular filtration anddevelopment of intoxication (nitrogenemia);5) HYPERKALEMIA -- by decrease secretion of potassium ions and theiroutput from the damaged cells.6) Distal canales acidosis. It is connected with disorders of acidogenesis indistal nephron canals.7)HYPEREMESIS- Gastro-intestinal disorders (nausea, vomiting, diarrhea).Loss of sodium (osmotic diarrhea) and intoxication have significantmeaning. This disorders without appropriate correction result to death.Think of Addison’s in all those with unexplained abdominal symptoms.B. Manifestations by disorders of glucocorticoid function of adrenal: Muscle weakness and fast tiredness Decrease of ability to remove water during water load (water poisoning). Weight loss and decreased appetite (HYPOGLYCEMIA) HYPOTENSION -- (permissive reaction on catecholamine’s)90% Darkening of the skin (HYPERPIGMENTATION-- bronzed disease) Diffuse tanning over nonexposed as well as exposed areas over knuckles,elbows, knees, nail beds, palmer creases, and posterior neck. Nipples and areolar darken, new scars pigmented ,skin in pressure areas Depression , emotional changes, mental irritability. Salt craving
8 MAGDI AWAD SASI 2013 ADRENAL GLAND DISORDERS Irritability Fever ,myalgia, arthralgia,vitiligo 10%. Sometimes, however, the signs and symptoms of Addisons disease mayappear suddenly.
10 MAGDI AWAD SASI 2013 ADRENAL GLAND DISORDERS• Examine for hyperpigmentation: Hand: palmar creases Mouth and lips Areas usually covered by clothing: nipple Areas irritated by belts, straps, collars or rings• Look for vitiligo• Look for sparse axillary hair and pubic hair• Examine the abdomen for adrenal scar• Examine blood pressure for postural hypotension• Signs of critical deterioration (Addisonian crisis):– Shock (low BP, tachycardia)– hypothermia
11 MAGDI AWAD SASI 2013 ADRENAL GLAND DISORDERSSCREENING AND DIAGNOSISDoctor will talk first about the medical history and the signs and symptoms.If doctor thinks that patient may have Addisons disease, He may undergo someof the following tests: Blood test. ACTH stimulation test. Insulin-induced hypoglycemia test. Imaging tests.BLOOD TEST: Measuring blood levels of sodium, potassium, cortisol and ACTH gives thedoctor an initial indication of whether adrenal insufficiency may becausing the signs and symptoms. A blood test can also measure antibodies associated with autoimmuneAddisons disease.BUSE• Low Na• High K• Low HCO3• AzotemiaFBC• Elevatedhematocrit• Low WBCcount• Relativelymphocytosis• IncreasedeosinophilsRBS / DXT• Hypoglycemia(< 3 mmol/L)
12 MAGDI AWAD SASI 2013 ADRENAL GLAND DISORDERSBlood chemistry • Low serum Na (< 135 mEq/L)• High serum K (> 5 mEq/L)• Ratio of serum Na:K: < 30:1• Low fasting blood glucose (< 50 mg/dL [< 2.78 mmol/L])• Decreased plasma HCO3 (< 20 mEq/L)• Elevated BUN (> 20 mg/dL [> 7.1 mmol/L])ACTH stimulation test This test involves measuring the level of cortisol in the blood before andafter an injection of synthetic ACTH. Plasma ACTH -INCREASED 1RY , DECREASED 2RYACTH signals – adrenal glands to produce If adrenal glands are damaged, the ACTH stimulation test shows that theoutput of cortisol in response to synthetic ACTH is blunted or nonexistent.Preinjectionplasma cortisollevel (N= 138 –690 nmol/L)IVTetracosactide250 µgPlasma cortisollevel at 30 – 90minutes postinjection (≥ 500nmol/LFailure torespond →adrenalinsufficiency (?Primary /secondary)
13 MAGDI AWAD SASI 2013 ADRENAL GLAND DISORDERSInsulin-induced hypoglycemia test Occasionally, doctors suggest this test if pituitary disease is a possiblecause of adrenal insufficiency (secondary adrenal insufficiency). The test involves checking the blood sugar (blood glucose) and cortisollevels at various intervals after an injection of insulin.In healthy people, glucose levels fall and cortisol levels increase.Imaging testsAbdominal x ray- Calcifications in the adrenal areas - PTBChest x ray----Small heartComputerized tomography (CT) scan of the abdomen to check the sizeof adrenal glands and look for other abnormalities that may giveinsight to the cause of the adrenal insufficiency. And may also suggest a CT scan or magneticresonance imaging (MRI) scan of the pituitarygland if testing indicates the patient havesecondary adrenal insufficiency.NegativeSynacthentestHigh plasmaACTH levelADDISON’SDISEASE
14 MAGDI AWAD SASI 2013 ADRENAL GLAND DISORDERSTREATMENT If patient receive an early diagnosis of Addisons disease, treatment mayinvolve taking prescription corticosteroids. Because the body isnt producing sufficient steroid hormones, doctor mayhave recommend to take one or more hormones to replace thedeficiency. Cortisol is replaced using hydrocortisone (Cortef), prednisone orcortisone. Fludrocortisone (Florinef) replaces aldosterone, which controlsthe bodys sodium and potassium needs and keeps the blood pressurenormal. In addition, doctor may recommend treating androgen deficiency with anandrogen replacement called dehydroepiandrosterone. Some studies indicate that, for women with Addisons disease, androgenreplacement therapy may improve overall sense of well-being, libido andsexual satisfaction. These hormones are given orally in daily doses that mimic the amountbody normally would make, thereby minimizing side effects. If facing a stressful situation, such as an operation, an infection or a minorillness, doctor will suggest a temporary increase in dosage. If ill with vomiting and cant retain oral medications, may needcorticosteroid injections. COPING SKILLS:Carry a medical alert card and bracelet at all times.Stay in contact with doctor.Keep extra medication handy
15 MAGDI AWAD SASI 2013 ADRENAL GLAND DISORDERSAddisonian crisis An addisonian crisis is a life-threatening situation that results inHYPOTENSION, HYPOGLYCEMIA and HYPERKALEMIA. This situation requires immediate medical care. Treatment typically includes intravenous injections of:1. Hydrocortisone2. Saline solution3. Sugar (dextrose)ADRENAL CRISIS IS :Acute episodes from stress that taxesthe adrenal cortical function beyond itscapabilities.Examples of acute insufficiency are:а) State after removal of adrenalsb) Hemorrhage in adrenals which arisesduring sepsis, meningococci infection(syndrome Waterhouse-Friderixan);chronic anticoagulant therapy, DIC.c) Rapid withdrawal of steroids (fromprevious treatment).• Fast falling of the adrenalsfunction causes development ofcollapse and the patients can dieduring the first day.
16 MAGDI AWAD SASI 2013 ADRENAL GLAND DISORDERSOccur in :1.Following stress , infection, surgery ,trauma.2. Prolonged fasting in patient with latent insufficiency.3. Sudden with drawl of adrenocortical hormone in pt with insufficiency4. Following bilateral adrenlectomy or removal of functioning adrenal tumorthat has suppressed other adrenal.5. Following sudden destruction of pituitary gland( pituitary necrosis) ORwhen the thyroxine is given to a patient with hypoadrenalism.6. Following injury to both adrenals by:TRAUMA ANTICOAGULANT THERAPYINFECTION HEMORRHAGETHROMBOSIS 2RY CARCINOMAABDOMINAL DISCOMFORTEMOTIONAL UPSET HIGH TEMPERATUREC/F:CNS-headache , confusion ,lassitude , coma.GIT- nausea , vomiting , diarrhea , abdominal painFever with fatigubilty.SIGNS:FLUID LOSS/DEHYDRATIONHYPOTENSIONCYANOSIS
17 MAGDI AWAD SASI 2013 ADRENAL GLAND DISORDERSANY PATIENT WITH GIT SYMPTOMS AND SHOCK IN STEROID WITHDRAWL.Skin hyperpigmentation , meningococcimeia with purpuraLAB:Hyponatremia ,Hyperkalemia, Hypoglycemia ,Hypercalcemia, High eosinophil.Hyperuricemia , lymphocytosis, HyperuremiaIF YOU FIND HYPERPIGMENTATION LOOK FOR OTHER (( H))= CRISISAdrenal hormone assay : hydroxycorticoid &17ketsteroid in 24HR urinedetectedCosyntropin stimulation test :Cosyntropin(ACTH) 0.25mg I/VS.cortisol 30 , 60 minNormally raises to 20 micgm/dlStope hydrocortisone before 8hr of the testPlasma ACTH is markedly elevated in 1ry adrenal disease ((200pg/dl))GOALS OF CARE:TO REVERSE SHOCKREPLENISH NEEDED STEROIDTREATMENT:Dxtose 5% , Normal salineADRENAL CORTICAL HORMONE REPLACEMENT: INJECTABLEHIGH SALT DIETANTIBIOTICS.
18 MAGDI AWAD SASI 2013 ADRENAL GLAND DISORDERSCUSHING’S SYNDROMECAUSE:Sustained over production of glucocorticoids by adrenal gland fromACTH by pituitary tumor.
20 MAGDI AWAD SASI 2013 ADRENAL GLAND DISORDERSTruncal obesityBuffalo humpMoon- faceWeight gainSodium retention with hypertensionThinning of extremities – from loss of muscle tissue due to proteincatabolismPurple striae – from thinning of skinEchymosis from slight traumapoor wound healinghypertension, hyperglycaemiaANDROGENIC EFFECTS:OligomenorrheaHirsutismGynaecomastiaDecreased libidoTREATMENT & NURSING CARE:PSYCHOLOGICAL SUPPORTPREVENT INFECTION – INFLAM & IMMUNE RESPONSE ARE SUPPRESSEDPROMOTE SAFETYSURGERY – SUB/TOTAL ADRENALECTOM
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22 MAGDI AWAD SASI 2013 ADRENAL GLAND DISORDERSAldosterone is a hormone that controls sodium and potassium levels in theblood. Hyperaldosteronism leads to retention of salt and loss of potassium,which then leads to hypertension (high blood pressure).PRIMARY – CONN’S SYNDROME(73%)unilateral adenoma-B/L CORTICAL HYPERPLASIAA.D .,defect allowing ACTH stimulation of Aldosterone production.SECONDARYWho is affected by Hyperaldosteronism? People in their 30’s-50’s (adulthood), with prevalence increasing with age Females are more likely to be affected than males African Americans have a significantly greater risk of fatality from thedisease than other races.CONN’S SYNDROMEPRIMARY ALDOSTERONISMCAUSE:ADRENAL ADENOMAS/SX:HYPOKALEMIAFATIGUEHYPERNATREMIA, HPN, TETANYMANAGEMENT:SURGERYALDACTONE – ALDOSTERONE ANTAGONIST
23 MAGDI AWAD SASI 2013 ADRENAL GLAND DISORDERSConn’s disease Usually caused by a benign tumor of the adrenal gland or bilateral adrenalhyperplasia (enlargement of an organ caused by an increase in thereproduction rate of its cells) .Features:- Hypertension (0.7%HTN PTS) - headacheMalignant HTN RARE, typically moderate, diastolic only w out S&S.- Hypokalemia metabolic alkalosis - tateny ¶sthesia- Fatigue - polyuria and polydipsia- Nocturia escape phenomenon prevents edema- Muscle weakness-Paralysis simulating periodic paralysis.Secondary Hyperaldosteronism is when the excess aldosterone is causedby something outside the adrenal gland and mimics the primarycondition.The problem is outside the adrenal gland:e.g. RENIN – ANGIOTENSIN SYSTEMCauses of Secondary Hyperaldosteronism: Increased renin production, commonly caused by the ingestion of oralcontraceptives and toxemia from pregnancy.Renin - An enzyme secreted by and stored in the kidney area thatstimulates aldosterone and therefore, raises blood pressure
24 MAGDI AWAD SASI 2013 ADRENAL GLAND DISORDERS Conditions like congestive heart failure, liver failure, kidney disease,cirrhosis, and dehydration Certain medicines like diuretics and fludrocortisone.SYMTOMS: Symptoms are similar to those of Primary Hyperaldosteronism Moderate hypertension (high blood pressure) Most individuals have no other specific symptoms. However, some mayhave:◦ Muscle weakness ,Fatigue◦ Temporary paralysis ,Cramping◦ Headaches◦ Low potassium level◦ Tingling◦ Muscle spasms
25 MAGDI AWAD SASI 2013 ADRENAL GLAND DISORDERSDIAGNOSIS: High NA intake and low k Elevated aldosterone levels can be measured in the blood or urine. 24 HR urine collection is assayed for Aldosterone ,Cortisol , Creatinine. Plasma assayed for Aldosterone at 8 AM while PT is supine afterovernight recumbency and again after 4 HR upright.Adrenal Adenoma ---more than 20mg/dl not raiseAdrenal hyperplasia----less than 20mg/dl raise upright Low plasma rennin less than 5mg/dl with 24 hr urine Aldosterone morethan 20mg/dl indicates HYPERALDOSTERONISM. Urine Ald. less 20mg /24hr seen in gonadal/adrenal enzyme defect. Once hyperaldosterone is diagnosed, plasma assayed for 18hydroxy-corticosterone—above 85mg/dl—adrenal neoplasm.◦ In a blood test, PRA (Plasma renin activity), is used to distinguishbetween primary (low PRA) and secondary Hyperaldosteronism(high PRA). Abdominal CT scans can show adrenal masses Electrocardiograms (ECGs) can show abnormalities in heart rhythm thatare often associated with low potassium level. It is likely that many cases of secondary Hyperaldosteronism are neverdetected.Treatments: Secondary Hyperaldosteronism is treated by treating the underlyingcause. Typically, medication and diet (but not surgery) are used Spironolactone is the treatment of choice.
26 MAGDI AWAD SASI 2013 ADRENAL GLAND DISORDERS When untreated, the disease can lead to uncontrolled hypertension(which can become a risk factor for stroke and heart disease). The outlook for the patient depends on the cause of the conditionAdrenocortical Neoplasms• May be responsible for a variety of hyperadrenalismsa) functional adenomas most commonly associated withhyperaldosteronism and Cushing syndrome• A virilizing neoplasm high incidence to be carcinogenic• Functional and non-functional adrenocortical neoplasms cannot bedifferentiated solely on basis of morphologya) Hormone measurementsb) Most adrenocortical adenomas do not cause hyperfunction• Adrenocortical carcinomas are rarea) two rare inherited adrenal cortical carcinomasi) Li-Fraumeni syndrome- autosomal dominant- predisposition to develop other cancers due to mutations in p53ii) Beckwith-Wiedemann syndrome• Generally, adrenal adenomas are small (1-2cm) whereas adrenalcarcinomas are large, invasive lesionsa) adrenal carcinomas metastasize via lymphatics and inferior vena cavai) mean survival is ~2 yrs.
27 MAGDI AWAD SASI 2013 ADRENAL GLAND DISORDERSAdrenal Medulla• Most important diseases of adrenal medulla are the neoplasmsa) neuronali) Neuroblastomaii) Mature ganglionic cell tumorsb) Chromaffin cellsi) pheochromocytoma• Pheochromocytomaa) neoplasm composed of chromaffin cellsi) synthesize and release catecholamine’s.b) familial syndromes (~10%)• i) MEN2A and MEN2Bii) type I neurofibromatosisiii) Von Hippel-Lindau diseaseiv) Sturge-Weber syndromec) Extra-adrenal source (~10%)i) carotid bodyii) organ of Zuckerkandl• d) are bilateral (~10%)i) may be as high as 50% in familial casese) malignant (~10%)i) more common when arise in extra-adrenal sitesHORMONES: EPINEPHRINENOREPINEPHRINEPHEOCHROMOCYTOMA: This is a rare tumor of chromaffin tissue which secretscatecholamine’s & is responsible for less than 0.1% of causes ofH.T.
28 MAGDI AWAD SASI 2013 ADRENAL GLAND DISORDERSThe tumors are usually benign /10% malignant //in over 90% of casesthe tumor found in the adrenal medulla, while it may arise elsewherein the body in sympathetic ganglia (paragangliomas).There is a useful rule of tens’ in this condition:10% are malignant , 10% in children10% are extraadrenal , 10%extreedrenal are extraabdominal10% are familial , 10% bilateral adrenal tumors10% are non hypertensiveIt is associated with MEN type II.• Occasionally, this tumor produces other biogenic steroids or peptidesassociated with Cushing’s Syndrome.• Extra-medulla tumors – 1-3% in chest and neck (usually malignant)• 20% multiple, 10% malignantSYMPTOMS AND SIGNS:Hypertension, may be paroxysmal or persistent. Due to secretion of oneor more of catecholamine hormones or precursors: norepinephrine,epinephrine, dopamine or dopa.Occasionally the pt. may be hypotensive ( dopamine – secreting tumors).some pt. may present with a complication of the hypertension e.g.:stroke, MI, LVFThere may be abdominal pain with vomiting, constipation, wt. loss,glucose intolerance.90% Presented with Palpitation, Hypertension,Sweating &Anxiety.
29 MAGDI AWAD SASI 2013 ADRENAL GLAND DISORDERSDuring the attack the pt. presents with: pallor (some time flushing),palpitation, sweating, headache, anxiety (feeling of death).Tachycardia, sweating, postural hypotension, tachypnea, flushing, coldand clammy skin, severe headache, angina, palpitation, dyspnoeaParoxysmal attacks may be provoked by exercise, anaesthesia, palpationof tumor, postural changes, urination, beta-blockersHyperglycemiaCardiac arrhythmia and congestive heart failure.DIAGNOSTIC TEST :Urine SampleBlood WorkAbdominal CT ScanMRI of the Abdominal RegionAdrenal Gland BiopsyScreening- Two 24 h urines for catecholamines is the best screening investigation- 24 h urine for VMA (15% false negative) and metanephrine (10% falsenegative) - needs vanilla-free diet before collectionIf the diagnosis is established, or strongly suspectedMIBG scan - meta-iodo-benzylguanidine labeled with 131I- Increased uptake by pheochromocytoma
30 MAGDI AWAD SASI 2013 ADRENAL GLAND DISORDERSCT scan of adrenals - patient should be alpha- and beta-blocked to avoidhypertensive episode after contrast administrationEnd products of catecholamine metabolism.DRUGS & FOOD TO BE WITHHELD 24H B4 THE TEST: COFFEE & TEA BANANA VANILLA CHOCOLATESMANAGEMENT:SURGERYMEDICAL : ADRENERGIC BLOCKING AGENTS: PHENTOLAMINENURSING CARE:MONITOR BP IN SUPINE & STANDINGMONITOR URINE FOR GLUC & ACETONE
31 MAGDI AWAD SASI 2013 ADRENAL GLAND DISORDERSThis requires excision of the tumor or long term TX with α and(usually β) adrenoceptor blockade.Prior to surgery give α –antagonist drug such as phenoxybenzamine 10-20mg orally 3-4 times / day for a minimum of 6 weeks to allow restorationof normal plasma volume if tachycardia is there then β –antagonist as propranolol (10- 20 mg ) 3 times daily should be added orcombined α and β-antagonist(e.g. labetalol)can be added.β-antagonist should not be given before the α-antagonist as it may causea paradoxical rise in blood pressure due to unopposed α-mediatedvasoconstriction.During surgery Na-nitropruside & the short acting α-antagonistphentolamine are very useful in controlling hypertension episodes whichmay occur during anesthesia or mobilization of the tumor.post-operativehypotension may occur and require volume expansion and veryoccasionally noradrenalin infusion.After surgery, it is necessary to continually monitor all vital signs in anintensive care unit. When the tumor cannot be surgically removed,medication is needed to manage it. This usually requires a combination ofmedications to control the effects of the excessive hormones. Radiationtherapy and chemotherapy have not been effective in curing this kind oftumor.a. Pre-op: Sympathetic blocking agents= Minipress (prazosin), Hytrin (terazosin),Cardura (doxazosin) to reduce BP and other symptoms of of catecholamine excess Since change in BP sudden, client may experience orthostatic hypotension Use Beta blocking agents such as Inderal to dec. heart rate, BP and force ofcontraction and calcium channel blocking agents also used.b. General management Diet: high in vitamin, mineral, calorie, no caffeine Sedatives; Monitor BP Eliminate attacks; If attack- complete bedrest and HOB 45 degreesc. Surgery via laparoscopic adrenalectomy or open abdominal incision; completeremoval of the tumor cures hypertension in 10-30% of the cases
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34 MAGDI AWAD SASI 2013 ADRENAL GLAND DISORDERSMultiple Endrocrine Neoplasia Syndromes (MEN)• Group of inherited diseasesa) hyperplasias, adenomas and carcinomas of multiple endocrineorgansi) Occur at younger age vs. cancersii) Arise in multiple endocrine organsiii) Even in one organ, they are multifocaliv) Tumors preceded by hyperplasiav) More aggressive and recur more frequently vs. sporadictumors• MEN-1(( WEMERS SYNDROME))a) Inherited as autosomal dominantb) Is a tumor suppressor genei) Loss of MEN-1 therefore causes tumor genesis- Parathyroid (95% involved)- Pancreas (>40%)- Pituitary (>30%)I- Parathyroid glandA) Primary hyperparathyroidism arising from hyperplasia is a commonfeature MEN-1 or adenoma of several parathyroid gland.B) Occurs in 90% of cases.C) Presents with hypercalcemia.II-Pancreas-pancreatic islet cell tumorsa) Leading cause of death in MEN-1b) Aggressivec) Often functional tumorsi) Gastrinomas (Zollenger-Ellison syndrome)-MOST COMMONii) Insulinomas and resultant hypoglycemia
35 MAGDI AWAD SASI 2013 ADRENAL GLAND DISORDERSIII- Pituitary adenomaA) most common in MEN-1 is prolactinomaB)May secret prolactin ,Growth hormone , ACTH.C)May cause local pressure effects and hypopituitrism.D)Usually non functional.IV- Adrenal cortical adenomaA)Occur in 70%B)Can be adenoma or hyperplasiaC)Bilateral in about halfD) They are generally benign and nonfunctional• MEN-2b (William syndrome)a) Involve also the thyroidb)Adrenal (medulla)c) Major differences between MEN-2a and MEN-2b isi) Do not develop primary hyperparathyroidism (MEN-2b)ii) Develop at extra endocrine sites- lips- tongue- GI tract• MEN-2 carry RET Protooncogenea) persons are advised to have prophylactic thyroidectomy toprevent carcinoma.•Adrenogenital syndrome results from the hereditary stipulated blockadeof cortisole synthesis and amplified formation of androgens from generalintermediate products.
36 MAGDI AWAD SASI 2013 ADRENAL GLAND DISORDERS• Depending on the level of blockade of cortisole synthesis there are threevariants of adrogenital syndrome.• І. Disorders of early stages of synthesis – deficiency of glucocorticoides,mineralcorticoides and androgens hyperproduction. Manifestations: signsof insufficiency of gluco- and mineralocorticoidal functions of adrenalcortex features of early sexual maturing in males, virilization in women(appearance of mans sexual features).• ІІ. Disorders of intermediate stages – deficiency of glucocorticoides,surplus of androgens, formation of mineralocorticoides is not infringed(classical androgenic syndrome). Manifestations are the same, as in thefirst case, only without signs of insufficiency of mineralocorticoidalfunction.• ІІІ. Disorders at final stages of cortirol synthesis – deficiency ofglucocorticoides, hyperproduction of androgens andmineralocorticoide. Features of hyperaldosteronism are connected withmanifestations of classical androgenital syndrome.Adrenocortical neoplasms Adrenocortical neoplasms associated with symptoms of excess ofandrogen are more likely to be androgen secreting adrenal carcinomasthan adenomas. It is also often assoc with hypercortisolism (mixed syndrome) The tumour secretes androgen thus increasing in circulation andconverted to testosterone at the peripheral tissues. May occur at any age , relatively rare. should be suspected when the onset of androgenic symptoms is sudden(i.e., generally <2 yr) and the pace of symptoms is rapid, and when theylead to virilization and masculinization.
37 MAGDI AWAD SASI 2013 ADRENAL GLAND DISORDERS may be associated with other systemic symptoms including weight loss,anorexia, a feeling of abdominal bloating, back pain. CAH Depends on the nature and severity of the enzymytic defect.Onset of clinical symptoms can occur in thePerinatal periodLater childhoodAdulthood (less common)Anterior pituitaryACTHCholesterolPregnolone17- hydroxypregnenolone17- hydroxyprogesterone2111– deoxycortisolCortisolGlucocorticoidsProgesterone21AldosteroneCorticosterone11- deoxycortisoneMineralocorticoidsTestosteroneAndrostenedioneDehydroxypiandrosteroneSex steroidsAdrenal cortex (bilateral hyperplasia)Congenitaladrenal hyperplasiaAutosomal recessive deficiency of an enzyme in the cortisol syntheticpathways.
38 MAGDI AWAD SASI 2013 ADRENAL GLAND DISORDERS◦ Cortisol secretion is reduced and feedback leads to increased ACTHsecretion to maintain adequate cortisol leading to adrenalhyperplasia.◦ Diversion of the steroid precursors into the androgenic steroidpathways occurs. Thus, 17-hydroxyprogesterone, androstenedioneand testosterone levels are increased, leading to virilization.Virilism==(excessive androgens may cause masculinization).Male excessive estrogen cause feminisation—breast enlargement. Androgens have important functions in women◦ Essential in the production of E2 (in ovary & adipose tissue)◦ Responsible for delivery. & maint. of axillary & pubic hair◦ Important for libido. Virilization: The development of exaggeratedmasculine characteristics, usuallyin women, often as a result ofoverproduction of androgens So, if hyperandrogenism becomesextreme, virilization occurs Symptoms of virilization include1. Excess facial and body hair(hirsutism),2. Baldness3. Acne4. Deepening of the voice5. Increased muscularity
39 MAGDI AWAD SASI 2013 ADRENAL GLAND DISORDERS6. An increased sex drive. In women,1. The uterus shrinks2. The clitoris enlarges (clitoromegaly)3. The breasts become smaller4. normal menstruation stops (amenorrhea)Clinical Manifestation:• Cortisol deficiency – hypoglycemia, inability to withstand stress,vasomotor collapse, hyperpigmentation, apneic spells, muscle weakness& fatigue.• Aldosterone deficiency – hyponatremia, hyperkalemia, vomiting, urinarysodium wasting, salt craving, acidosis, failure to thrive, volume depletion,hypotension, dehydration, shock, diarrhea.• Androgen excess – ambiguous genitalia, virilization of external genitalia ,hirsutism, early appearance of pubic hair, penile enlargement , excessiveheight gain and skeletal advance.*Late onset CAH – normal genitalia, have acne, hirsutism, irregularmenses/amenorrhea.ANDROGEN Testosterone, dehydroepiandrosterone sulfate (DHEAS),dehydroepiandrosterone (DHEA), androstenedione, and androstenediol The ovaries produce 50% of circulating testosterone, 50% of theandrostenedione and 20% of DHEA. The adrenal glands produce all the DHEAS and 80% of the DHEA. Theadrenals also secrete 50% of androstenedione and 25% of testosterone.
40 MAGDI AWAD SASI 2013 ADRENAL GLAND DISORDERS Adrenal androgens increase in response to ACTH stimulation LH stimulates theca cells of the ovaries to secrete androgensHyperandrogenism Excess of androgens may be caused by:◦ primary gonadal disorders◦ primary adrenal disorders◦ iatrogenic In practice though, the causes are restricted to a few conditions:
41 MAGDI AWAD SASI 2013 ADRENAL GLAND DISORDERS◦ PCOS◦ Cushing’s syndrome◦ CAH◦ TumoursLab Testosterone and Dehydroepiandrosterone sulphate (DHEAS)◦ DHEAS hyperandrogenemia of adrenal origin Serum prolactin thyroid stimulating hormone (TSH) Serum 17 hydroxyprogesterone (17-OHP) test –if suspect CAH LH and FSH ( suggestive of PCOS if ratio >2) Lipid profile OGTT◦ Relying on a fasting glucose level alone is inadequate as it is a poorpredictor of impaired glucose tolerance or diabetesEffect of androgens Fat deposition (small breast)◦ Androgens inhibit the ability of some fat cells to store lipids Muscle mass (heavy mascular mass)◦ Androgens promote the enlargement of skeletal muscle cells Brain◦ Enhanced libido.