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adrenal glands disorder
The adrenal glands are located above the kidneys and are divided into an outer cortex and inner medulla. The cortex secretes steroid hormones like cortisol and aldosterone which are regulated by the hypothalamus-pituitary-adrenal axis. The medulla secretes catecholamines which are regulated by the sympathetic nervous system. Diseases can result from hypofunction or hyperfunction of the adrenal cortex and include Addison's disease, Cushing's syndrome, Conn's syndrome and pheochromocytoma. Laboratory tests are used to diagnose the underlying cause and guide treatment options such as hormone replacement or surgery.
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adrenal glands disorder
- 1. ADRENAL GLANDS SMS 3023 Dr.MohanaD r. alwan
- 2. Adrenal Glands Suprarenal glandsSuprarenalglands • Paired organ each weight about 4 grams, pyramidal in shape, located on the top of the kidneys, one on each side at the level of the T12 • It enclosed by fibro elastic connective tissue capsule.
- 3. Adrenal glands • Eachgland is divided into tow parts: – CortexCortex – outer part of gland • Part of hypothalamus – pituitary – adrenal axis • Secrete a variety of steroid hormones – MedullaMedulla – inner part of gland, (20% of gland) • Part of sympathetic nervous system • Secrete catecholamines – Both parts are structurally and functionally different
- 4.
- 5. Adrenal cortex • Thelarge cortical cells are arranged into three layers or zones : – The zona glomerulosazona glomerulosa, • The thin outermost layer • Constitute about 15% of cortex – The zona fasciculatazona fasciculata, • The middle and largest portion • Constitute about 75% of cortex. – The zona reticulariszona reticularis, • The innermost zone.
- 6. Histology of adrenalglands
- 7. Adrenal cortex • Zonaglomerulosa:Zona glomerulosa: – Produce meniralocorticods – Mainly aldosteronealdosterone (because it contain enzyme aldosterone synthasealdosterone synthase)) Hormones that help control the balance of minerals (Na+ and K+) and water in the blood
- 8. Adrenal cortex • AldosteronesecretionAldosterone secretion
- 9. Adrenal cortex • Zonafasciculata:Zona fasciculata: – Produce glucocorticods – Mainly cortisolcortisol andand corticosteronecorticosterone – The human adrenal glands produce the equivalent of 35–40 mg of cortisone acetate per day – The secretion of these cells is controled by hypothalamic-pituitary axis via ACTH Hormone that play a major role in glucose metabolism as well as in protein and lipid metabolism
- 10. Adrenal cortex • Zonareticularis:Zona reticularis: – The innermost layer of the adrenal cortex, lying deep to the zona faciculata and superficial to the medulla. – These cells produce androgensandrogens
- 11. Adrenal cortex • Zonareticularis:Zona reticularis: – The androgens produced includes • Dehydroepiandrosterone (DHEA) • Androstenedione – Synthesized from cholesterolSynthesized from cholesterol • DHEA is further converted to DHEA-sulfate via a sulfotransferase
- 12. Adrenal cortex • Zonareticularis:Zona reticularis: – The androgens produced are released into the blood stream and taken up in the testis and ovaries to produce testosterone and the estrogens respectively.
- 13. Regulation of adrenal gland secretionACTH Cortisol Cortisol
- 14. Disorders of adrenalcortex • Patient with adrenal disorders can presentPatient with adrenal disorders can present with features related to:with features related to: • HYPOFUNCTION OF THE GLANDHYPOFUNCTION OF THE GLAND • HYPERFUNCTION OF THE GLANDHYPERFUNCTION OF THE GLAND
- 15. DISORDERS OF ADRENALCORTEX
- 16. Adrenal hypofunction • Outlines –INTRODUCTION – AETIOLOGY AND PATHOGENESIS – CLINICAL FEATURES – INVESTIGATIONS – MANAGEMENTS
- 17. Adrenal Hypofunction • Adrenalinsufficiency leads to a reduction in the output of adrenal hormones – glucocorticoids and/or mineralocorticoids • Two types of adrenal insufficiency • Primary insufficiencyPrimary insufficiency • inability of the adrenal glands to produce enough steroidinability of the adrenal glands to produce enough steroid hormoneshormones • Secondary insufficiencySecondary insufficiency • inadequate pituitary or hypothalamic stimulation of the adrenalinadequate pituitary or hypothalamic stimulation of the adrenal glandsglands
- 18. • CausesCauses – GlucocorticoidtreatmentGlucocorticoid treatment – Autoimmune adrenalitisAutoimmune adrenalitis – TuberculosisTuberculosis – AdrenalectomyAdrenalectomy – Secondary tumor depositsSecondary tumor deposits – AmyloidosisAmyloidosis – HaemochromatosisHaemochromatosis – Histoplasmosis, tuberculosis, CMV, AIDSHistoplasmosis, tuberculosis, CMV, AIDS – adrenal haemorrhageadrenal haemorrhage Adrenal Hypofunction Common
- 19. Adrenal Hypofunction • CausesCauses •Metabolic failure in hormone productionMetabolic failure in hormone production • Congenital adrenal hyperplasia e.g. 21-hydroxylase deficiency, 3-β-hydroxysteroid dehydrogenase deficiency • Enzyme inhibition e.g. ketoconazole • Accelerated hepatic metabolism of cortisol e.g. phenytoin, barbiturates, rifampicin
- 20. Adrenal Hypofunction • Othercauses – ACTH blocking antibodies – Mutation in ACTH receptor gene – Adrenal hypoplasia congenita – Familial adrenal insufficiency
- 21. Addison diseaseAddison disease Autoimmune Isolatedor associated with other autoimmune disease Presents with tiredness, weight loss, skin pigmentation Aldestrone & cortisol low, high ACTH, high renin Low sodium , high potasium ACTH stimulation test Adrenal antibodies Treatment : cortisol + aldestrone .
- 22. Addison’s disease: pathogenesis •Progressive destruction of entire adrenal cortex , This is usually autoimmune based. • Most likely the result of cytotoxic T lymphocytes, although 50% of patients have circulating adrenal antibodies. Adrenal Hypofunction Addison’s diseaseAddison’s disease Primary hypoaldosteronismPrimary hypoaldosteronism
- 23. Addison’s disease: Clinicalfeatures Common Less common Tiredness, generalized weakness, lethargy Hypoglycemia Anorexia, nausea, vomiting Depression Hyponatremia Hyperkalemia ,Hypercalcemia Convulsions Dizziness and postural hypotension Pigmentation Loss of body hair (woman)
- 24. Addison’s disease: clinicalfeatures • hyperpigmentationhyperpigmentation
- 25. Addison’s disease: clinicalfeatures • HyperpigmentationHyperpigmentation
- 26. ADRENAL CRISIS • Acuteadrenal insufficiencyAcute adrenal insufficiency • Medical emergency • Acute in onset; can be fatal if not promptly recognized and treated • Clinical features : • Severe hypovolaemia • Dehydration • Shock • Hypoglycaemia • possible mental confusion and loss of consciousness
- 27. ADRENAL CRISIS • Causes: • Precipitated by stress • infection, trauma or surgery in patients with incipient adrenal failure/treated with glucocorticoids if dosage is not increase • Adrenal haemorrhage • due to cx of anticoagulant treatment • Meningococcal septicaemia
- 28. INVESTIGATIONS (HORMONAL) • Plasmacortisol concentration • <50nmol/L at 0900H → effectively diagnostic • >550nmol/L excludes the Dx • ACTH stimulation test / Synacthen test • Measurement of plasma ACTH • Metyrapone test • CRH stimulation test • Plasma renin and aldosterone levels
- 29. PLASMA ACTH MEASUREMENT •To differentiate between primary and secondary adrenal failure • Primary insufficiency - ACTH increased • Secondary insufficiency - ACTH decreased
- 30. INVESTIGATIONS (HORMONAL) • ACTHstimulation test / Synacthen test SHORT TEST LONG TEST Take blood sample at 0900H for measurement of cortisol Inject 250µg ACTH im or iv Take further blood sample after 30 and 60 min for cortisol measurement Day 1 : inject 1 mg depot ACTH IM im Days 2 and 3 : repeat Day 4 : perform short ACTH test
- 31. METYRAPONE TEST • Measuresthe ability of the pituitary gland to release ACTH in response to decreased blood cortisol levels. • Metyrapone inhibits cortisol production by blocking the conversion of 11-deoxycortisol to cortisol by 11-beta-hydroxylase
- 32.
- 33. CRH STIMULATION TEST •To differentiate between secondary adrenal insufficiency dt pituitary or hypothalamic dis. • Results : • Pituitary disease – blunted or nil response • Hypothalamic lesions – positive response
- 34. PLASMA RENIN ANDALDOSTERONE • Give an indication of mineralocorticoid activity. • Adrenal insufficiency – Low aldosterone level with high renin
- 35. Management • Hormone replacementHormonereplacement • Life-long replacement therapy • Hydrocortisone and 9α-fludrocortisone • Secondary adrenocortical insufficiency • Hormone replacement • may also require more definitive treatment e.g. surgical removal of a pituitary tumour.
- 36. Management • Adrenal crisis: • Adequate resuscitation e.g. IV fluids, IV glucose. • IV hydrocortisone 100mg which should be continued four times daily afterwards until the patient can take oral medication.
- 37. Disorders of adrenalcortexDisorders of adrenal cortex
- 38. Adrenal Dysfunction Increase function •Cushing syndrome High Cortisol • Hyperaldosteronism High aldestrone • Pheochromocytoma High catecholamine .
- 39. Hyperaldosteronism • A medicalcondition where too much aldosterone is produced by the adrenal glands, which can lead to sodium retention and potassium loss. • Types: – Primary hyperaldosteronism – Secondary hyperaldosteronism
- 40. Primary hyperaldosteronismPrimary hyperaldosteronism (hyporeninemichyperaldosteronism)(hyporeninemic hyperaldosteronism) Conn’s syndromeConn’s syndrome
- 41. Primary aldosteronismPrimary aldosteronism CONN’SSYNDROME • Characterized by autonomous excessive production of aldosterone by adrenal glands • Presents with HPT, hypokalaemic alkalosis and renal K+ wasting
- 42. Conn’s Syndrome • Causes: –Adrenal adenoma – Bilateral hypertrophy of zona glomerulosa cells – Adrenal carcinoma • Rare cause
- 43. Secondary aldosteronism • Isincreased adrenal production ofIs increased adrenal production of aldosterone in response to non-pituitary,aldosterone in response to non-pituitary, extra-adrenal stimuliextra-adrenal stimuli • Increase renin secretion – (hyperreninemic hyperaldosteronism) • Commoner than primary aldosteronism
- 44. Secondary aldosteronism • Common –CCF – Liver cirrhosis with ascites – Nephrotic Syndrome • Less common – Renal artery stenosis – Sodium – losing nephritis – Renin-secreting tumours
- 45. Conn’s syndrome • Clinicalfeatures: – HypertensionHypertension : aldosterone induced Na retention with increase in ECF volume – Muscle weaknessMuscle weakness: Due to decrease K+ – Muscle paralysis:Muscle paralysis: severe hypokalaemia – Latent tetanytetany and paraesthesiaeparaesthesiae – PolydipsiaPolydipsia, polyuriapolyuria and nocturianocturia: due to hypokalaemic nephropathy
- 46. INVESTIGATION • Electrolyte &blood gasses:Electrolyte & blood gasses: – Hypernatraemia – Hypokalaemica – Alkalosis – Urinary potassium loss, level > 30 mmol daily during hypokalaemia
- 47. INVESTIGATION • Plasma aldosterone: renin activity ratioPlasma aldosterone : renin activity ratio – Sensitive screening test – No need to standardize posture Ratio Interpretation Action <800 Diagnosis excluded Seek other cause >1000,<2000 Diagnosis possible Confirmatory test >2000 Diagnosis very likely Establish cause
- 48. Diagnosis • Perform salineinfusion test (sodium loading)Perform saline infusion test (sodium loading) – Method : infusion of 1.25L of 0.9%saline over 2 hrs – Result: plasma aldosterone remains >240 pmol/l confirm Conn’s syndrome
- 49. Establish cause • PlasmaAldosterone level • Method: – Morning blood sample (pt stayed recumbent since waking) – Second sample after 4 hrs stayed ambulant **Standing renal blood flow stim renin sec aldosterone level
- 50. • Imaging techniques –CT scan – MRI – Can differentiate adenoma from hyperplasia Establish cause
- 51. Treatment • Tumour – Removesurgically • Bilateral adrenal hyperplasia – Spironolactone
- 52. Disorders of adrenalcortexDisorders of adrenal cortex
- 53. CUSHING’S SYNDROME • Definition •Clinical features • Investigations – Screening for Cushing’s syndrome – Elucidation of the cause of Cushing’s syndrome • Management
- 54. CUSHING’S SYNDROME Adrenal cortexhyperfunction • Any condition resulting from overproduction of primarily glucocorticoid (cortisol) • Mineralocorticoid and androgen may also be excessive
- 55. Pseudo-Cushing’s syndrome • Appearcushingoid and have some biochemical abnormalities of true Cushing’s disease • Causes – Severe depression – Alcoholism – Obesity – Polycystic ovarian syndrome
- 56. Etiology • Excessive cortisol(ACTH dependent)~~75% – Pituitary disease • Adenoma (90%) • Hyperplasia (10 %) – Ectopic ACTH syndrome • Malignancy - ( bronchus, thymus, pancreas, ovary ) – Ectopic CRH syndrome – Exogenous ACTH administration
- 57.
- 58. ACTH dependent causes *Hypersecretionof ACTH and Cortisol is greater in ectopic ACTH syndrome than Cushing Disease
- 59. Etiology • Excessive cortisol(ACTH independent) ~25%~25% – Adrenal tumour • Adenoma • carcinoma – Nodular hyperplasia – Exogenous glucocorticoid administration
- 60.
- 61. Etiology • Excess cortisolbinding globulinExcess cortisol binding globulin – Estrogen therapy : Osteoporosis, OCP – Pregnancy
- 62. Clinical features • Truncalobesity with deposition of adipose tissue in characteristic site (moon face, buffalo hump)– exact mechanism unknown • Thinning of skin – catabolic response • Purple striae – catabolic response • Excessive bruising – catabolic response
- 63. Cont.. • Hirsutism (esp adrenal carcinoma ) - ↑ adrenal androgen • Menstrual irregularities - ↑ adrenal androgen • Skin pigmentation ( ACTH ↑ ) – melanocyte stimulating activity
- 64. Cont.. • Hypertension –mineralocorticoid effect → sodium retention – Potassium wasting → hypokalamic alkalosis • Glucose intolerance - ↑ hepatic gluconeogenesis and insulin resistance • Muscle weakness and wasting – catabolic response in peripheral supportive tissue
- 65. Cont.. • Back pain( osteoporosis and vertebral collapse) – inhibit bone formation • Psychiatric disturbances – euphoria, mania, depression
- 67. Laboratory investigations Thereare two diagnostic steps in the investigation of patient suspected of having Cushing's syndrome Screening test for identification of Cushing's syndrome. the demonstration of high plasma cortisol level Identification of cause
- 68. 1. Demonstration ofincreased cortisol Assessment of circadian rhythm in cortisol secretion 24-Hour urinary free cortisol excretion Overnight / low dose dexamethasone suppression test
- 69. Laboratory investigations 1. Assessmentof circadian rhythm in cortisol secretion. Measure 8 am and 11 pm serum cortisol level Normal : Serum value @ midnight is 50% less than value @ 8 am Cushing’s syndrome : rhythum is loss Pseudo-Cushing : normal circadian.
- 70. Laboratory investigations 2. Measuring24-hour urinary free cortisol Level (umol/ 24 h )Level (umol/ 24 h ) InterpretationInterpretation < 300< 300 NormalNormal 300 - 700300 - 700 Severe depressionSevere depression StressStress > 700> 700 Diagnostic ofDiagnostic of Cushing's syndromeCushing's syndrome
- 71. Laboratory investigations 3. Lowdose Dexamethasone suppression test : 0.5 mg Dexametason (oral) given 6 hourly for 2 days blood for plasma cortisol collected 6 hour after last dose urine for UFC is collected before & on the 2nd day of Dexa Result: UFC suppress by 50% ( < 70nmol/24h) normal plasma cortisol suppress < 140 nmol/L pseudo- Cushing no suppression of UFC & Pl. cortisol Cushing's synd
- 72. Elucidation of thecause • High dose Dexamethasone suppression test • Normal individuals suppress plasma cortisol to < 50 nmol/L. • Patients with Cushing's syndrome fail to show complete suppression of plasma cortisol levels. This test is highly sensitive (> 97%).
- 73. 2. Elucidation ofthe cause • Plasma ACTH – Normal < 50 ng/L – Low – adrenal causes – Elevated • Slight – pituitary dependent Cushing’s • Gross – ectopic secretion of ACTH
- 74. Elucidation of thecause • CRH Test – Differentiate ectopic ACTH secretion and Cushing’s disease. – Cushing’s disease – plasma ACTH increases 50% over baseline and cortisol increase by 20% – Ectopic ACTH or adrenal tumour – no response
- 75. Elucidation of thecause • Imaging – CT scan of adrenal gland: TRO adrenal tumor – MRI of pituitary gland: majority microadenoma ( < 10mm). MRI reveal lesion in 50 - 60% of cases – CT scan/MRI of thorax & abdomen: ectopic ACTH producing tumor
- 76. Treatment • Depend ofCushing's syndrome depends on the etiology: – Adrenal adenoma – Adrenal Carcinoma – resection – Cushing’s disease - transphenoidal hyposectomy – Drug ( block cortisol synthesis ) - metyrapone