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Adrenal

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Adrenal

  1. 1. ADRENAL CORTEX By Khaled Hadhoud A.PROF. of Internal Medicine Endocrinology unit Zagazig University
  2. 2. Physiological considerations : 1. Zona glomerulosa:  secretes aldosterone Na & H2O retention.
  3. 3. 2. Zona fasciculata :  secretes glucocorticoids, mainly cortisol (hydrocortisone ). Metabolic effects of cortisol • On fat (in excess)  mobilization & deposition in abnormal sites. • On proteins  catabolic, (in excess)  muscle wasting & osteoporosis. • On carbohydrates : ↑ gluconeogenesis & ↓ glucose uptake by the muscle cells, (in excess)  hyperglycaemia. • On H2O & electrolytes  Na & H2O retention & K excretion. o On blood (bone marrow) ↑RBCs & ↓ eosinophils & lymphocytes. • Androgenic. • Anti-allergic (tend to – Ag - Ab reaction). • Anti - inflammatory (& in excess - fibrous tissue formation & destroys elastic fibers ).
  4. 4. N.B.: • Zona fasciculata is under the control of ACTH. • ACTH is derived from a large precursor molecule which also gives rise to melanocyte stimulating hormone, lipotropin & endorphins (POMCpro-opio-melano-cortin). 3. Zona reticularis : • Secretes sex hormones, mainly androgens & small amount of oestrogen & progesterone. • The main androgen is dehydro- epiandrosterone which enhances protein anabolism & promotes the development of male 2ry sexual characters "& sexual hair in ♀. • The end products of androgens are 17 ketosteroids ( which are excreted in urine). • It is under the control of A.C.T.H. N.B. • Sources of androgens: • In ♂  (adrenal, testes). • In ♀  (adrenal).
  5. 5. CONN'S SYNDROME (1ry hyperaldosteronism ) Causes: • Adrenal aldosterone producing adenoma (60%). • Hyperplasia of zona glomerulosa (bilateral)(40%). • Aldosterone producing carcinoma (rare).
  6. 6. Clinical picture: 1. Hypertension : may be severe, due to  Na retention. 2. Hypokalaemia : leading to : • Apathy, Paraesthesia. • Arrhythmias as extrasystoles. • Atony of intestine  constipation & even paralytic ileus. • Muscle weakness & even episodic paralysis (& if the respiratory musclesare affected  dyspnea). • Impaired glucose tolerance (in 50%) because K has a direct effect on insulin release from B cells & may influence insulin action.
  7. 7. 3. Alkalosis "metabolic": Due to heavy loss of H+ in urine  tetany. 4. Absence of oedema : due to K diuresis  polyuria. Impaired tubular reabsorption of water (renal concentration defect)  polyuria "due to prolonged Hypokalaemia".
  8. 8. • Investigations: 1. Biochemical changes : • Hypokalaemia (N = 3.5 - 5 mEq / L ). • Hypenatraemia (N = 140 mEq /L ). • Alkalosis ( ↑serum Hco3 mEq/L) (N=22- 30 mEq /L) 2. Urinary changes: • Polyuria. • ↑ K, ↓Na. • ↑ aldosterone excretion ( N = 12 - 50 ug / 24 hs). 3. Measurement of plasma level of: • Renin : ↓ in 1ry hyperaldosteronism ( & remains low on Na restriction ).
  9. 9. N.B. • Plasma renin level is high in cases of 2ry hyperaldosteronism. – You must stop ttt of HPN before measurement of renin • Aldosterone : high despite high Na load (N=3 - 15ng/dl) N.B. • In 2ry hyperaldosteronism, aldosterone level can be ↓by Na load. • 4. U/S& adrenal CT.
  10. 10. Differential diagnosis : a. From hypertensive conditions associated with Hypokalaemia : • Hypertension "malignant or renal" with 2ry hyperaldosteronism. • Diuretics causing Hypokalaemia in hypertensive patient. • Cushing syndrome, CAH & rarely Juxtaglomerular hyperplasia. • Intake of exogenous mineralocorticoids. • K-losing nephropathies causing or associated with HPN e.g. bartter's syndrome, Liddle's syndrome. b. From other causes of Hypokalaemia & familial periodic
  11. 11. Treatment: Surgical removal of the adenoma (after correction of the electrolyte imbalance). Medical ttt: • In bilateral adrenal hyperplasia. • Amiloride (40mg/day) is preferable to spironolactone (which leads to gynaecomastia & impotence on chronic use ).
  12. 12. CUSHING'S SYNDROME Causes: Endogenous Cashing syndrome " rare, yearly incidence of one/million". Pituitary cushing syndrome (cushing disease ). • The most common cause of endogenous Cushing (75 %). • 80 % are caused by pituitary basophil micro-adenoma secreting excessive of ACTH " the remaining cases may be of hypothalamic origin". • it is commoner in ♀ than ♂.
  13. 13. Adrenal Gushing syndrome : (20 %) • Caused by autonomous cortisol production from adenoma, carcinoma or hyperplasia of adrenals. Ectopic Gushing syndrome : ( autonomous ACTH production ) e.g. • Bronchogenic carcinoma, pulmonary carcinoid. • Thymoma, ovarian or pancreatic carcinoma.
  14. 14. ExogenousExogenous CashingCashing syndromesyndrome "" CushingoidCushingoid syndrome "syndrome " ProducedProduced by prolongedby prolonged use ofuse of corticosteroids.corticosteroids.
  15. 15. Clinical picture: Abnormal deposition of fat in certain sites : • In the face  becomes rounded with bloated cheeks ( Moon face). • In the interscapular region  (Buffalo hump). • In the breasts & abdomen  (Trunkal obesity), but the buttocks are hollow with thin limbs (lemon on match sticks).
  16. 16. Disturbances in protein metabolism : • ↑protein catabolism  muscle wasting & weakness (even proximol myopathy). • Osteoporosis : • Kyphosis, shortening • Pathological fractures. • Bruises & purpura (due to ↓support of blood vessels). • Delayed healing of wounds. • Stria rubra: • Due to rupture of weakened s.c. collagen fibers (together with fat mobilization)  purplish lines in the skin around the
  17. 17. Disturbances in carbohydrate metabolism : • Hyperglycaemia & may end in D.M. (in 15% of cases) which is somewhat insulin resistant (steroid diabetes) Disturbances in fluid & electrolytes balance : • Na retention hypertension. • Hypokalaemia  polyuria, alkalosis.
  18. 18. Sexual manifestations : • In females • Amenorrhea. • Acne. • Hirsutism. • In males ↓sexual desire, Impotence ↑estrogen.
  19. 19. General manifestations • Plethoric face due to polycythaemia. • Psychiatric disturbances: common, usually in the form of depression. • Obesity & stunted growth may be the main presenting feature in childhood.
  20. 20. Features suggesting the aetiology : • Evidence of virilizatation (Is most common in)  adrenal carcinoma. • Hypokalaemic alkalosis, myopathy & hyperpigmentation (occur most often in)  Ectopic Cushing syndrome ( the distinguishing clinical features of hypercortisolism are often absent). • Age & sex : • Children (more common in)  adrenal carcinoma. • Adult ♂  Ectopic Cushing. • ♀ in childbearing age "  pituitary Cushing.
  21. 21. Investigations: Investigations which suggest cushing syndrome : • Hypokalaemic alkalosis, Hypernatraemia. • Blood picture ↑RBCs, ↓lymphocytes & eosinophils. • Impaired glucose tolerance. • X-ray  osteoporosis & unsuspected fractures.
  22. 22. Investigations which confirm cushing syndrome. • Plasma cortisol level :(N=5-20ug/dl) " at 8 AM " The earliest indication of increase cortisol secretion is loss of the diurnal variation (circadian rhythm) " normally, plasma cortisol level at 4 p. m. is < 50% of that at 8 a.m N.B. • Then, there is persistent elevation. • Recently diurnal variation can be detected by salivary cortisol.
  23. 23. • Urinary steroid excretion : Hydroxy corticosteroids (17 oH Cs). Urinary free cortisol excretion (the most reliable index of hypercortisolism). • Overnight dexamethasone suppression test: Dexamethasone 1 mg is given orally at night ( 11 pm ) & plasma is obtained at 8 am the following morning  cortisol level <7ug/<dL exclude hypercortisolism.
  24. 24. Investigations to differentiate between the 3 forms of cushing syndrome: • Plasma ACTH: Very high  in Ectopic Gushing. High  in pituitary Cushing. Low or absent  in adrenal Cushing. • CRH stimulation test: (1ug/kg I.V.) ACTH & cortisol levels  in pituitary Cushing. No effect —> in Ectopic or adrenal.
  25. 25. • High dose dexamethasone suppression test: 2 mg / 6 hours for 2 days is given orally. In pituitary Cushing  50 % ↓of 24 hours excretion of 17 OHCs or the plasma cortisol. In adrenal or Ectopic Cushing  no effect. N.B. BIPSS • Localization procedures : Abdominal U/S & C.T. of adrenals  for adrenal tumours. Sellar X-ray detects 10 - 15 % of pituitary tumours & C.T. detects 85% of microadenomas ( MRI is better ). Chest x-ray -. for bronchial carcinoma.
  26. 26. Differential diagnosis:• Exogenous obesity, essential HPN & D.M. occurring separately or combined :In such cases : • Obesity is generalized. • Plasma cortisol & urinary end products  normal. • Other causes of obesity : e.g. Myxoedema, Frohlich's syndrome, ..etc • Other causes of Hirsutism. • Other causes of osteoporosis.
  27. 27. • Women on oral oestrogen - containing C.C.P.s may become overweight & may have higher levels of plasma cortisol (due to↑cortisol binding globulin). • Patients suffering from LCF may develop Cashing - like manifestations due to impaired cortisol metabolism. In such cases, plasma cortisol level is raised but, manifestations of LCF are prominent.
  28. 28. N.B. • Pseudo - Cushing syndrome : Chronic alcoholism, acute severe illness, obesity & depression may be associated with mild ↑in cortisol levels & absent diurnal variation.
  29. 29. Treatment: Pituitary Cushing : Surgery : • Trans-sphenoidal hypophysectomy. • Remission (85%). • Complications... Irradiation : e.g. Proton beams, alpha particles. After ttt Cortisone for life. Medical: • Drugs that inhibit ACTH release e.g CYPROHEPTADINE,VALPROATE; BROMOCRIPTINE . • Drugs that inhibit steroidogenesis e.g KETOCNAZOL.
  30. 30. Adrenal Cushing : Adrenal adenoma:  removal. N.B. • Post-operative glucocorticoids replacement is necessary for several months until function returns in contralateral previously suppressed gland. Adrenal carcinoma  removal. • Preoperative ttt.: with enzyme inhibitor " Metyrapone" 11 deoxycortisol cortisol • Post-operative : Give mitotane " for residual disease.
  31. 31. Ectopic Cushing : • Surgical removal of the tumour. Or • Metyrapone ± Mitotane.
  32. 32. ADDISON'S DISEASE Chronic adrenal failure = adrencortrical insufficiency = adrenal hypocorticism Causes : • 1. Auto-immune adrenalitis : ( most common cause, 70%) N.B. This may occur alone or in combination with other auto- immune endocrine insufficiency including IDDM, hypothyroidism (& sometimes hypogonadism, Hypoparathyroidism or pernicious anaemia ) " Schmidt syndrome " . • 2. T.B. of the adrenal glands (10-20%). • 3. Following bilateral adrenalectomy & congenital enzymatic defects. • 4. Sarcoidosis, secondaries, amyloidosis or haemochromatosis (rare causes ).
  33. 33. Clinical picture: Onset is usually insidious, mostly in the adult life & the course is slowly progressive. • Asthenia : Weakness of muscles; Weight loss. Due to : * Lack of cortisol. * Hyperkalaemia. * Hypoglycaemia. + muscles cramps due to hyponatraemia.
  34. 34. • Hypotension Systolic blood pressure > 110 mmHg excludes Addison's disease. Postural hypotension  common due to hypovalaemia & dehydration. • Hypoglycaemia: leading to: Drowsiness, hunger pain & even coma.
  35. 35. • Hyperpigmentation: of skin & m.m. Sites : • Face, neck, groins, axillae, nipples, friction areas, scars as umbilicus, areas exposed to sunlight. • m.m. of mouth, tongue, rectum (state coloured patches). Causes : • Hypocorticism  ACTH ↑melanocyte stimulating hormone (& lipotropin) ↑ pigmentation. • Destruction of the adrenal medulla :  diversion of tyrosine to form melanin instead of adrenaline & noradrenaline.
  36. 36. N.B. • Leucoderma may occur as a part of autoimmune disturbance. • Hyperpigmentation isn't a feature of Simmond's , disease.
  37. 37. • Loss of adrenal androgen : • ↓axillary & pubic hair in ♀(but in ♂, testicular androgen is preserved). • Infertility & amenorrhea in females. • GIT disturbances : • Nausia, vomiting, diarrhea (& even steatorrhea). • Polyuria : due to Na diuresis . • There may be tenderness in the renal angle in T.B. of adrenals. N.B. The patients may present with Addisonian crisis ( see later ).
  38. 38. Investigations: • ↓plasma cortisol level. • ↓24 hour urinary cortisol, 17 oHCs or 17 Ks ( ketosteroids ). • ACTH stimulation test " synacthen test" ( 0.25 mgI.M. or I.V.) • Normal response  plasma cortisol ↑by 6 ug / dl above the basal value. • In 1ry adrenal insufficiency  no response. • In 2ry adrenal insufficiency  normal response
  39. 39. • Biochemical changes : • ↓serum Na, Cl • ↑ serum K, acidosis. • ↑serum Ca. • ↓ serum glucose. • Urine: • ↑volume. • ↑Na & Cl & ↓K excretion. • Blood picture: • Normochromic anaemia. Haemoconcentration ,Eosinophilia & lymphocytosis.
  40. 40. • Investigation to find the cause : • Adrenal antibodies - in  autoimmune Addison. • X-ray: - adrenal calcification in T.B. cases. - evidence of pulmonary T.B.
  41. 41. Differential diagnosis: • D.D. from 2ry hypo – adrenalism • Other causes of pigmentation e.g. racial, haemochromatosis, porphyria & ancanthosis nigricans, neurofibromatosis. • Asthenia & pigmentation may occur also in : e.g. pellagra, CML (especially, in patients on busulfan therapy), CRF, chronic arsenic poisoning, thyrotoxicosis, advanced malignancy, Malabsorption syndrome.
  42. 42. Treatment: Replacement therapy : • Glucocorticoids prednisolone 5 mg in the morning & 2.5 mg in the evening. • Mineralocorticoids  fludrocortisone 0.1 mg every other day. N.B. • Active T.B. cases should receive anti-T.B. therapy.
  43. 43. Acute Adrenal Failure Addisonian Crisis• Causes : •In addison's disease : • Previously undiagnosed patients may present in crisis either spontaneously or ppted by intercurrent illness. • Patients already on ttt, on facing severe intercurrent illness without increasing the replacement dose. •In sheehan syndrome  if ttt is initiated with thyroxin alone without cortisone. • After bilateral adrenalectomy ( or pituitary surgery ).
  44. 44. • After sudden corticosteroid withdrawal. • Acute meningococcal septicaemia (waterhouse friderichsen syndrome). Hge may occur in the adrenal gland acute adrenal failure. • Medical ttt for adrenal carcinoma ( e.g. with metyrapone, mitotane ). • Massive thrombosis of adrenal veins ( during pregnancy, puerperium & burns).
  45. 45. Clinical Picture: • Sudden onset of severe weakness, mental confusion, abdominal pain, anorexia; nausia, vomiting, diarrhea. • Dehydration  shock. • If not treated  coma & death within 24 hours.
  46. 46. Investigations: • ↓ serum Na. • ↑ serum K. • ↓serum cortisol.
  47. 47. Treatment of addisonian crisis : • Correction of volume depletion & electrolyte status by I.V. saline & glucose" 10 %". • Hydrocortisone ( Solucortif)  100 mg I.V. then 100 mg as I.V. infusion / 8 hours (in 5 % glucose)  then gradual tapering ( until the maintenance dose is reached within 5 days ). • Fludrocortisone:  0.1mg/day (added- when the daily dose of hydrocortisone has reached 100 mg/day). • Proper ttt of infections & precipitating factor.
  48. 48.  Plasma 17- hydroxyprogeste rone is elevated in 21(OH)ase ; &11- desoxycortisol is elevated in 11(OH)ase
  49. 49. CONGENITAL ADRENAL HYPERPLASIA " Adrenogenital Syndrome " • Definition : Group of condition caused by inherited enzymatic defects in the enzymes necessary for the synthesis of cortisol ↓cortisol ↑ ACTH adrenal hyperplasia & ↑synthesis of the hormone proximal to the block. • Causes :
  50. 50. Enzyme ↓ Hormonal changes Clinical features 17 oH ase ↓" extremely rare" ↓ glucocorticoids & sex hormones. ↑mineralocorticoids. HPN & Hypokalaemia. In females  sexual infantilism. In males  ♂pseudohermaphroditism 21 oH ase ↓, " it is the commonest form " ↓ glucocorticoids & mineralocorticoi ds. ↑sex steroids Salt losing syndrome : Due to aldosterone ↓: Hypotension. Hyperkalaemia - ♀ pseudohermaphroditism -♂ precocious puberty 11 B oH ase ↓"accounts for ↑11deoxycorticosterone, deoxycortisol & androgens. ↓cortisol Hypertension. Virilization  ♀ pseudohermaphroditism ♂
  51. 51. N.B. • Pseudohermaphroditism :  (phenotypic sex disturbance ). • True hermaphroditism :  (chromosomal sex disturbance). [Differentiated by doing sex chromatin pattern].
  52. 52. Treatment: 1. Replacement therapy : • Prednisolone ( 7.5 mg / day ). • To replace the deficient cortisol in glucocorticoids deficient forms. • --ACTH: ↓blood pressure in hypertensive forms. ↓androgen in virilizing forms. • Fludrocortisone (0.1mg/day) in mineralocorticoid deficient forms.
  53. 53. Surgical correction : • For ♀pseudohermaphroditism . N.B. In ♂ pseudohermaphroditism  male functioning is impossible & so female sex assignment is advisable  surgical correction of genitalia & gonadectomy are required plus oestrogen administration  relatively normal but infertile ♀.

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