DISORDER OF ADRENAL GLAND Lecture for 5 vintage

DISORDER OF ADRENAL GLAND Lecture for 5. vintage 2. LF UK Prague

Adrenal Gland • • Cortex Medulla

Adrenal gland • Geminate organ - 10 - 15 g in adulthood • Influence over metabolism saccharides, oils, albumins, ions and water • Adaptation gadgetry

Adrenal cortex • Zona glomerulosa - small influence ACTH, secretion aldosterone • Zona fasciculata - cholesterol, below stimulation ACTH, cortisol • Zona reticularis - poor on lipids, secretion adrenal androgens, oestrogens, lower intensity production and readiness issue glucocorticoids and C 19 steroids

Development cortices • Zona juvenilis (DHEA) • Maturing fruit

Secretion of corticoids • ACTH • Changes in ionic economy (on K) • High flow neck

Products of cortices • Glukocorticoids • Mineralocorticoids • Adrenal gonadal hormones androgens and estrogens

Biosynthesis of steroids • Acetylcoenzym A • Esters cholesterol • Cholesterol

Cellulate biosynthesis • Mitochondrie cholesterol pregnenolon • Endoplasmatic reticulum

Endoplasmatic reticulum

Chief products • Glucocorticoid cortisol (10 - 30 mg/day) • DHEA ( 10 - 40 mg/day) • Mineralocorticoid aldosterone ( 0, 05 - 0, 25 mg/day)

Cortisol metabolism • Secretion in diurnal rhythm, maximum morning o'clock • Structure on CBG ( cortisol binding glob. ) ) (oestrogen. and tyroid. ) • alpha 1 fibralbumin- transcortin - 90 - 95 % cortisol • Biologist. half - time - 80 - 150 mine.

Cortisol metabolism II • Cortisol cortisone (11 beta dehyrogenasis) • Mineralocorticoid receptors

Drive secretion • Hypotalamus CRH • Hypophysis - ACTH • Adrenal gland - cortisol • Cortisol - CRH

Drive secretion II • Closed circuit backward structure • Variable setting • Daily rhythm • Stress • Displacement - supresion

Aldosterone • Renin angiotenzin system • On and pressure in afferent arteriols • Rentention Na and vazocontriction rise blood pressure

Aldosterone - drive secretion

Aldosterone • Primary hyperaldosteronism - low renin • Secondary hyperaldosteronism - high renin • ACTH - works less than cortisol

Effects of glucocorticoids • • • Influence over intermediary metabolism Stimulation of glukoneogenesis Increased saving glycogen in liver Decrease utilization glucose on the fringe Increased mobilization lipide

Effects of glukocorticoids II • • • Lowered extrahepatal proteosynthesis Increased evolution amino - acids Increased hepatic proteosynthesis Anti - inflammatory effect Immunosuppressive therapy effect Resorbence waters

Effects of mineralocorticoids • • Retention soda lye ions Excretion potassium ions Retention waters Regulation volume extracellular ( largely intravascular) liquid • Increasing extracellular space

Effects of androgens testosterone • • • Anabolic effect Muscle, vocal cords, bone External genital Growth, hematopoesis, spermatogenesis Sexual behaviour Back regulation

Effects of androgens DHT • • • Facial and bodily feathering Acne Sebum Prostate Back regulation

Hypocortisolism Addison dissease • 1. Primary - increased secretion ACTH acute chronic • 2. Secondary - lowered secretion ACTH

Chronic generalize • Prime atrophy adrenal- illnes of immunity adrenalitis • TBC of adrenal gland • Mycoses and histoplasma, syphilis • Inborn hypoplasis or aplaus od adrenal gland • State after adrenalectomy

Adrenalitis

Chronic generalize II • Recessive hereditary falling - short with cerebral disorder (blocked on X chromosomal) • Destruction tissues - polypuses, base, oil, amyloid • Hemochormatosis

Chronic dissociation function • Block some from enzymes steroidogenesis with hyperplasia of adrenal gland • Wherewith height is block (more closely to cholesterol), by is major

Secondary hypocorticolism • Starvation wages ACTH • Hypotalamo -hypofysis : lesion of hypotalamus or hypophysis • State after therapy with corticoids inhibition of secretion

Addison´s dissease clinical symptoms • • • Asthenia, muscular weakness, fatigue Chromatosis leather Weight - shortage Lack of appetite, vomitus Chromatosis mucous membrane Hypotension 99% 98% 97% 90% 82% 80%

Addison´s dissease clinical symptoms II • • Spontaneous hypoglycemia Lowered acidity gastric juice Mulligrubs Hunger after salts Diarrhoea Block Vitiligo 50% 34% 22% 20% 19% 6%

Clinical symptoms Patofysiology of glucocorticoids • Sugars hypoglycemia, hunger, cereberal disfunction, changes EEG, nausea, sweat • Proteins and oils weight - shortage, astenia, hypochlesterolemia, keto - acidosis • Haemopoiesis normocyt. pancytopenia, hypoleucocytosis • CNS endocrinous psycho - complex • Increased issue MSH (ACTH) - chromatosis

Clinical symptoms Patofysiology of mineralocorticoids • Hyponatremia fatigue, weakness, discomfort, vomitus • Extracellular exsiccation headache, apathy, fuzziness, disturbances sense of • Hypercalemia muscular convulsions, paralytic dementia, arrhytmia, hyperkalemic EKG • Acidosis hyperventilation, disturbances sense

Patofysiology of androgens • Decrease anabolic substances stimulation asthenia, decrease sarcotome • Decrease androgen stimulation impotence, amenorroe, retirement secondary sexual signs

Diagnostics laboratory • • • Fall cortisol below 100 nmol/l Changes in surface ACTH Hyponatremia Hypercalemia Squamous cell blood sugar curve at OGTT • Weak or zero answer in ACTH test

Diagnostics of Addisonism Differential diagnosis • 1. construction sequence cases weakness, decrease yoke, anorexia, hypotension, diarrhoeas (gasteroenteritis, appendicitis, NPBacute abdominal cases, DM, Tx) • 2. construction sequence cases muscular adynamia ( we myasthenia syndromes)

Differential diagnosis II • 3. construction sequence cases with hyperpigmentation (porfyria, chronic liver dissease, hemochromatosis) • 4. construction sequence cases after bunk - up korticoicoids- relative hypocorticolism

Chronic adrenal insuficience Substitute therapy • 10 as far as 35 mg cortisol every day according to materiality p. about. • Hydrocortison digitizer. a 10 mg preservation rhythm • Synthetic korticoids always (Prednison) - mineralocorticoid! 1/4 digitizer. 9 - alpha- fluorokortizol (Florinef)

Reservation surgical achievements • Preoperative dosage 50 mg Hydrocortison and. m. or 100 mg and. v. (in infusion) • During operation 100 mg and. v. a 4 throw • After operation 50 as far as 25 mg and. m. /day until at application p. o.

Secondary adrenal insuficience Therapy • 1. Begin displacement • 2. Ablation causes -e. g. hypotyreosis

Addisons crisis Etiology • Crossing unrecognized or untreated insuficience to the crisis • Low treatment insuficience- stress, stress • Sudden bunk - up glucoortidoid therapy • Sudden destruction adrenal - bleeding,

Addisons crisis Symptoms • Muscular weakness, heavy adynamy as far as paralytic dementia limbs • Vomit, diarrhoea, coeliac colic • Hypotention, hypovolemia, hyponatremia • Circulatory malfunctioning, disturbances of kardiology- arythmia • Irritation and later apathy as far as somnolence

Addisons crisis Therapy • Bolus 100 mg Hydrocortisonu and. v. • Infusion 100 mg Hydrocortisonu and. v. a 1 throw. after 6 throw. • Supply liquid 2 - 4 l/day in infusion ev. inclusive glucose

Addisons crisis Therapy • After stabilization ( circulation, minerals etc. . ) - 50 mg and. m. a 12 h. • Displacement preparation p. about. antibiotics, treatment evocatory causes

Suprarenal overaction • Hypercorticolisms • Hyperaldosteronisms • Overproduction androgens or estrogens

Hypercortisolism Prime (Cushing´s sy. ) • Overproduction glucocorticoids mineralocorticoids, adrenal androgens • adenoma of adrenal gland • carcinoma of adrenal gland • ectopia or deposit of remnants andrenal tissues

Tumor of adrenal cortex Clinical manifestations • • • Cushing's syndrome Androgen hypersecretion (AGS) Hormonal dumb (incidentalom) Estrogenni hypersecretion Androgens and estrogens HCG, hypoglycemia 45% 30% 15% 2, 5% 1, 4%

Hypercortisolism Clinical symptoms • • Marigold face Central obesity Hypertension Pletora Amenorroe Hirsutismus (women) Adynamia, weakness 88% 86% 85% 77% 72% 67%

Hypercortisolism Clinical symptoms II • • Reds stria, ecchymosis Fragility capillary Osteoporosis Dropsy subcutis Fat deposition piggyback Acne Mental changes 60% 59% 58% 57% 54% 46%

Hypercortisolism Clinical symptoms III

Hypercortisolisms Patofysiology of glucocorticoids • Sugars - diabetic resp. prediabet. metabolism, hyperglykemia, steroid diabetes, polyuria, polydypsia, nycturia • Proteins - adynamia, decrease sarcotome, osteoporosis • Lipids - lunar face, buffalo hump, centripetal distribution oil, arteriosclerosis, xantelasma

Clinical symptoms Patofysiology of glucocorticoids II • Haemopoiesis - polyglobulia, leucocytosis, eosinopenia, lymfopenia, trombocytosis, fall antithrombin • Mesenchyme. tissues stria, ecchymosis, purples, took immunity response • Mineralocorticoid. receptors- hypertension • CNS endocrinous psycho - complex

Clinical symptoms Patofysiology III • Surplus aldosterone propensity to hypokalemia, alkalosis and hypernatremia • Surplus androgens partial compensation proteinocatabolic effect of glucorticoids, virilization, acne, hirsutismu, amenorroe

Hypercorticolism • Primary Lowered performance ACTH • Secondary 1. increased performance ACTH 2. lowered performance ACTH

Hypercortisolism Primary • Cushing´s sy. contingent adrenal- tumors of adrenal cortex • Cushing´s sy. contingent ectopia adrenal tissue weaving tumours from adrenal the rest in ovarium or testicle, tumours from adrenal the rest

Hypercortisolism Secondary higher ACTH • Cushing´s sy. hypotalamus - hypophysis (Cushing´s dissease) basophilic or chromofobic adenoma hypophysis, malignant tumours or other lesion, disorder issue CRH • Cushing´s sy. parenoplastic influence peptide with effects ACTH from extrahypofysary tumours (pulmonary etc. )

Hypercortisolism Secondary starvation wages ACTH • Iatrogenic Cushing´s sy. after therapy corticoids or ACTH • Cushing´s sy. with relative hypercotisolism - lowered concetration of transcortin or incompatibility between cortisol-transcortin

Hypercortisolism Prime - diagnostics • High cortisol • Starvation wages ACTH • Adrenal steoidogenesis- inadequate responsive to ACTH • Dexametazon test

Hypercortisolism Secondary - diagnostics • High cortisol • High ACTH ( except bunk - up corticoids and sy. of lowered transkortin!) • Sonografy, CT, bllod tests of steroids after katetrisation of adrenal venous orifice, RTG pulmonary and mediastinum (paraneoplast. )

Hypercortisolism CT - diagnostics

Hypercortisolism Diagnostics fluxional • Obesity (often with DM and hypertensive) cortisol in urine higher cortisol/creatinine - normal purview supresion cortisol – Dexametazon • Sy. Stein Levethal (PCO) sonografy of ovary

Hypercortisolism Therapy • First fiddle. Cushing. sy. adrenalectomia + displacement • Cut. Cushing. sy. adrenalectomia thumped. + displacement • Inoperable construction sequence cases - blockers adrenal steroidogenesis

Hypercorticolism Therapy complication St. p. bilateral adrenalectomy near 7% cases happens to growth reactive hypofyseal adenomas (Nelsonuv sy. ) 50% radical neurosurgery solving

Hyperaldosteronism • Prime - Conn´s sy. adenoma more often sinistral less commonly malignant • Secondary metabolic response with adaptation character from extraadrenal dissease, stimulate system renin- angiotenzin

Hyperaldosteronism

Hyperaldosteronism Prime symptoms • HYPOCALEMIA muscular weakness, fatigue, hypocalemic changes on EKG • HYPERNATREMIA benign hypertension, cefalgia, retinopatia, aggramdizement heart, less frequent dropsies

Hyperaldosteronism Prime symptoms II • KIDNEY hypostenuria, isostenuria, proteinuria, nycturia, polydipsia, lower titrating acidity urine, higher content ammonium ions in urine • ALKALOSIS parestezia

Hyperaldosteronism Prime diagnostics • High surface aldosterone and his metabolites in urine • High surface aldosterone an blood test and after katetrisation of adrenal lived • Low plasmatical surface of renin • Normal surface of 17 - cetosteroids and 17 - hydroxycorticoids

Hyperaldosteronisms Prime diagnostics II • Imaging method sonografy CT scintigrafy 19 -125 I cholesterol

Hyperaldosteronism Prime therapy • Adrenalektomia 2/3 standardization hypertensive (months) 1/5 improvement hypertensive always - ren. insuf. cut - and dry • Conservatively (inoperable construction sequence cases) Spirolakton in high taxs (300 - 400 mg) every day

Hyperaldosteronism Secondary - aetiology • Stimulation system renin- angiotenzin Reno - vascular hypertensive, malignant hypertensive overproduction of renin (haemangiopericytoma renis, Robertsons sy. ) hyperplasy ev. Hypertrophy of juxtaglomerular apparatus

Hyperaldosteronisms Secondary - aetiology II • Tubulopaty of kidney – Bartter´s sy. (isn't backward resorpse on) • Overproduction ACTH

Hyperaldosteronism Secondary • Increased surface of aldosterone • Increased surface of renin • Therapy evocatory causes • Spirolakton

Adrenal hyperandrogenism • Clinical manifestations - Adrenogenital sy. • Tumour or hyperplasia cortices adrenal selective disorder steroidogenesis • Overproduction C 19 steroids adenoma or carcinoma

Adrenal hyperandrogenism • Clinical symptoms of virilization near women with hirsutism, hypertrichosis, hair loss • Imaging method • Single out gonadoblastoma overproduction - tumours • Surgical solving

Adrenal hyperestrogenism • Insulated hypersecretion rare, more often with others steroids • Men - waste virilization signs, gynecomastia, atrophy testicles • Women - disturbances cycle and hypermenorroe

Steroid enzymopaty • Metabolism disturbances steroidogenesis • Dissociation adrenal function • Infliction near initial steps of streoidogenesis – high morbidity and morality

Inborn adrenal hyperplasia with virilization • Inborn Adrenogenital sy. • Block 21 - hydroxylase - light forms 70 % of all hyperplazia, heavy form ( salt disorder) 25% • Block 11 a -hydroxylase 3 % • Next blocks forms c. 1%

Defect 21 - hydroxylase • 17 a- hydroxyprogesteron

Defect 21 - hydroxylase • Light form ACTH, hyperplasia with hypersecretion of mineralocorticoids and cortisol with androgen hyperproduction – virilization of habitus (hypertrophy clitoris) • Heavy form trenchs all corticosteroid drugs - virilization waste salts, manifestations at once post natal - exsiccation, vomit, shock, hypo -Na, hyper- K

Steroid enzymopaty Therapy complex • Glucokorticoids - supresesion adrenal stimulation ACTH and overproduction C 19 steroids, at disorder synthesis mineralocorticoid - Florinef • Poverty of androgens – displacement • Virilization near girls - anti - androgens

ADRENAL MEDULLA

Secretion of catecholamines • 90% adrenal pith • 10% chromium - affine tissue except adrenal medula – paragangliomyschemodektoms • paraganglioms- chromium - affine tissue near likable nerve knot on hand • mediastinum, abdomen and saucepan • Zuckerkandl´s organ – chromium - affine tissue near lower mesenteric artery

Pheochromocytoma • Secretion – epinephrine, noradrenaline and dopamin • gastrin, kacitonin, somatostatin, vaso active intestinal peptide (VAS), adrenokortikotropin and adrenomedulin

Clinical symptoms • • • Hypertension above 98% - everlasting 50 - 60% - paroxytone 50% Orthostatic hypotensive 12% Pallor 30 - 60% Flush 18% Fever as far as 66% Vomit 26 - 43% Convulsions 3 - 5%

Glucosic metabolism • Hyperglykemia 42% • PGT 60 - 80% • Diabetes mellitus 25%

Incidence of symptoms • Seconds and o'clock • Every day and after months • Stereotyped at the time continuation and demonstration

Causes episodic secretion catecholamines • Physical activity, shock • Direct stimulation tumour /tumour urine. bladder/ • Pharmaceuticals – histamine, tyramine, guanethidin, metoklopramid, methyldopa, ethanol, fenothiazin, tricyclic antidepressant drug • Estrogens and STH

Malignant feochromocytoma • 10% feochromocytoms • Lower incident • - extradarenal localization /higher aggressiveness/ - child's tumours • Histopatologiy resolution unreliable • Invazivity tumour or base - static scatter

Genetics of feochromocytoma • Genes of cancerogenesis • Active oncogens- mutation genes with norm. cellulate function (protoonkogeny) • Tuberculous suppressor genes – mutation linked waste function • Genes prohibitive replication errors in DNA • Identification genes – pharmacology, therapy, screening

Familiarity of feochromocytoma • MEN 2 • von Hippel- Lindu illness (VHL) • Neurofibromatosis type I

Synthesis of catecholamines • L tyrosin - hydroxylase /TH/ • L Dihydroxyfenylalalnin - dekarboxylase aromatic amino - acids • Dopamin - beta- hydroxylase dopaminu • Noradrenaline - fenolethanolamin- Nmethlytransferase /PNMT/ • Adrenalin

Synthesis near feochromocytoma • Higher gene expression for TH • Low activity PNMT – superiority secretion noradrenaline • Adrenal tumours - stimulation PNMT by glucocorticoids- more epinephrine

Laboratory diagnostics of feochromocytoma • Free catecholamines - metabolites above all noradrenaline • Dopamin – starvation wages surface, vyjimecne higher – inactivation betahydroxylase • 3 - methoxy- 4 - hydroxymandlova acid (vanilmandlova, VMA) Low sensibility

Stimulative test - Glukagon • Application 1, 0 mg and. v. • Prompt reply – 1 - 3 - minutes • Evaluation – increasing 3 x, more than 2000 pg/mls. katecholaminu • Hazard hypertensive crisis- Regitin

Supresion test - Klonidin • Alfa 2 adrenoreceptor´s agonist inhibits vacation noradrenaline • Feochromocytoma - without response • Application 0, 3 mg p. o. Absence fall noradrenaline below 500 pg/ml, behind 2 - 3 o'clock, different kriteria • Hazard bradycardia and hypotension

Evaluation tests • Glukagony specificity 100% sensibility 81% • Klonidin specificity 67% sensibility 97% • Combination 80% handhold disorder • Farmakolog. interference – tricyclic antidepressant drug

Imagine of tumor • CT 85 - 95% • MRI – better record, largely extra - adrenal localization • MIBG – 123 I and 131 I /metajodbenzylguanidin/ • 111 I octreotid – malignant feochromocytom • Positron emissive tomography /PET/ - (18 F) -fluorodeoxyglukoza - (11 C) -hydroxyefedrin

Incidentalom • Dispenzarisation – repeated taking • Above 3 cm – surgical solving

Therapy of Feochromocytoma Pre - operative • Stationary bllood pressure 2 - 4 for weeks before operation • Alpha adrenergic blockers

Alpha adrenergic blockers • • Fenoxybeznamin /Dibenylin cps. / • Prazosin /Deprazolin 1 mg, 2 mg digitizer. , , Adversuten 1 mg, 5 mg digitizer. stainless steel. /

Pre - operative options • TK no transcendent 160/90 mm Hg • Orthostatic hypotensixe below 80/45 mm. Hg • Max. 1 cellular extra - systole behind 5 mine. , , EKG without elevace or depression ST and inversion Tvlny

Surgical therapy • Preference laparoscopy achievements • Prevention hypovolemie and hypoglykemie • Selection anaesthetic – halotan increases sensibility myocardium on catecholamines

Postoperative care • Surgical verification laboratory max. behind 2 for weeks • Dispensarisation – lab. verification 1 x yearly after 5 years

Inoperable construction sequence cases • Fenoxybenzamin – Dibenylin • Metyrosin Demser

Cytostatic treatment malignity • Cyklofosfamid, Vinkristin, Dacarbazin • adjustment clinic near 57% • laboratory answer 79%

Other options therapy • Octerotid or alpha interferon • • 50% without progression tumour 2/3 improvement pac. with diarrhoeas, gob and brochoconstriction

Next therapy • Bone implantation – external radiating • MIBG – high doses

Forecast after operation Benign – quinquennial survival 95% Malignant – quinquennial survival 35 60%