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Adrenal Dr Sohail Inam FRCP(Ed), FRCP Consultant Endocrinologist Prince Sultan Military Medical City Riyadh, Saudi Arabia.

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Presentation on theme: "Adrenal Dr Sohail Inam FRCP(Ed), FRCP Consultant Endocrinologist Prince Sultan Military Medical City Riyadh, Saudi Arabia."— Presentation transcript:

1 Adrenal Dr Sohail Inam FRCP(Ed), FRCP Consultant Endocrinologist Prince Sultan Military Medical City Riyadh, Saudi Arabia

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3 Kidney ACTH CortisolAldosterone Renin Angiotensin II Renin substrate Angiotensin I Androgens CRH AVP

4 Cortisol Energy metabolism – Increases glucose – Increases fat breakdown – Protein breakdown Maintain circulation – Increasing blood volume – Increase in vascular tone Control of inflammation

5 Aldosterone Mineralocorticoid Increase blood volume Kidney & GIT – Na reabsorption – K excretion Vascular endothelium Cardiac

6 Adrenal Andogrens DHEAS, Androstenedione Axillary & pubic hair Libido Muscle strength Immune modulation Bone health

7 Kidney ACTH CortisolAldosterone Renin Angiotensin II Renin substrate Angiotensin I Androgens CRH AVP X

8 Kidney ACTH CortisolAldosterone ↑Renin Angiotensin II Renin substrate Angiotensin I Androgens CRH AVP X

9 Primary Adrenal Insufficiency Damage to adrenal gland All 3 hormones are affected Increase compensation due to lack of feed back – High ACTH levels – High Renin levels

10 Kidney ↓ ACTH ↓CortisolAldosterone Renin Angiotensin II Renin substrate Angiotensin I ↓Androgens CRH AVP X

11 Central Adrenal Insufficiency Damage to pituitary/hypothalamus ACTH levels are low Only cortisol & androgens are affected

12 Causes Primary Adrenal Insufficiency Autoimmune Infection – TB, CMV, HIV, Fungal Hemorrhage or infarction Malignancy Infiltrative – Sarcoidosis, hemochromatosis, amyloidosis Adrenal leukodystrophy Drugs

13 Causes Central Adrenal Insufficiency Exogenous steroid (commonest) Pituitary tumors Infection Inflammation Hemorrhage & infarction Infiltrative Trauma Radiation

14 CLINICAL PRESENTATION Adrenal Insufficiency

15 Chronic Presentation Asthenia Weight loss GIT – Anorexia – Nausea, vomiting and abdominal pain – Diarrhea Postural dizziness Pigmentation (primary)

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17 Chronic Presentation Become very unwell with stress Low BP with postural drop and tachycardia Electrolyte disturbances Hypoglycemia

18 Acute Adrenal Insufficiency Presentation Adrenal crisis (Non-specific) Hypotension – Postural – Recumbent Abdominal pain Electrolyte disturbances Hypoglycemia

19 PrimaryCentral NaLow KHigh or high normalNormal or low normal UreaHighNormal or high CreatinineNormal or highLow normal CalciumNormal or high Electrolyte Abnormalities Adrenal Insufficiency

20 Acute Adrenal Insufficiency Precipitating factors Omission of corticosteroids Increased requirements – Infection – Physical stress – Drugs

21 Diagnosis Measurement of adrenal hormones Cortisol, DHEAS, Aldosterone Primary versus central ACTH, Renin Determine cause

22 Diagnosis Cortisol Random – 8-9 am level – Level during stress Stimulated

23 ACTH Stimulation Test Standard (250 mcg) Can be performed any time though preferably 8-9 am. 0, 30, 60 minute Any value  550 nmol/l excludes adrenal insufficiency in non-critically ill patients Test is abnormal in almost all patients with primary adrenal insufficiency & 90% individuals with central adrenal insufficiency

24 Pituitary Stimulation Tests Insulin tolerance test (ITT) – Gold standard for central disease – Risk from hypoglycemia CRH Metyrapone Other

25 Determine Cause Careful history of previous steroid use Radiology – Adrenal CT (Primary) – Pituitary MRI (Central) Autoantibody Tests specific for suspected etiology

26 Acute AI Management Fluids – Resuscitate – 0.9% NaCl – Glucose Glucocorticoids Treat underlying cause – Precipitation event – Etiology

27 Steroid Therapy Acute crisis – IV Hydrocortisone drug of choice Natural compound & mineralocorticoid activity – 50 mg 6-8 hourly – Taper dose early – No additional benefit of mineralocorticoids Chronic – Maintenance glucocorticoid ± mineralocorticoid Stress dose adjustment

28 CUSHING'S SYNDROME

29 Cushing’s Syndrome Chronic tissue exposure to excess cortisol Exogenous Endogenous

30 Clinical features Weight gain – Central fat distribution Skin changes – Thinning – Striae – Easy bruising Proximal muscle weakness Osteoporosis

31 Cushing’s Syndrome Clinical features Hypertension Glucose intolerance Psychiatric disturbance Hypogonadism Infections

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34 Cushing’s Syndrome Cause ACTH dependent 75-80% – Pituitary adenoma (Cushing’s disease) 60-70% – Ectopic 10-15% ACTH independent – Exogenous steroids – Adrenal adenoma & carcinoma (18-20%) – Bilateral adrenal hyperplasia

35 Ectopic ACTH Secretion Lung – Carcinoid – Small cell carcinoma Pancreas – Neuroendocrine tumors Thymus Other carcinomas

36 Diagnosis Clinical suspicion – Symptoms & signs Documenting hypercortisolism Determining the cause

37 Diagnosis of Cushing’s Syndrome Documenting Excess Cortisol Exclude exogenous steroid use Excess cortisol – 24 Hour urine for free cortisol (>3 x Normal) Loss of diurnal variation – Midnight or late night cortisol (3 samples) Abnormal regulation – Dexamethasone suppression test At least 2 out of 3 should be abnormal

38 Diagnosis of Cushing’s Syndrome Falsely Abnormal Tests Patients who are physically stressed – Sick patients Patients with severe obesity Malnutrition, Anorexia nervosa, Severe exercise Patients with psychological stress – Severe major depressive disorder Chronic alcoholism Drugs

39 Determining the cause ACTH ACTH suppressed (Independent) – Adrenal tumors – Exogenous steroids ACTH normal or elevated (Dependent) – Cushing’s disease – Ectopic Cushing’s

40 Determining the Cause ACTH Dependent MRI pituitary Inferior petrosal venous sampling CT chest and abdomen High dose dexamethasone suppression test Functional nuclear scans

41 Treatment Adrenal tumors – Surgical resection Cushing’s disease – Surgery – Medical therapy – Radiotherapy – Bilateral adrenalectomy

42 Treatment Ectopic ACTH secretion – Treat the underlying tumor (surgical resection) – Medical therapy Somatostatin analogues Adrenal blocking drugs – Bilateral adrenalectomy

43 Treatment Medical Therapy Inhibit ACTH release – Somatostatin receptor analogues – D2 receptor analogues (cabergoline) Block cortisol synthesis – Ketaconozole, Metyrapone, Mitotane Block the cortisol receptor – Mifepristone

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