ENDOCRINE SYSTEM BLOCK

Click to edit Master subtitle style Ronald Chrisbianto Gani 405090223 Faculty of Medicine 2009 Tarumanagara University

CASE 3
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PHYSIOLOGY OF CORTEX ADRENAL

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ADRENAL GLAND

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Sherwoods Human Physiology

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Color Atlas of Physiology

STEROIDOGENIC PATHWAY

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Sherwoods Human Physiology

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Color Atlas of Physiology

CONTROL OF CORTISOL SECRETION

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Sherwoods Human Physiology

CIRCARDIAN RHYTHM

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Color Atlas of Physiology

CUSHINGS SYNDROME
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DEFINITION

A constellation of clinical features that result from chronic exposure to excess glucocorticoids of any etiology

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EPIDEMIOLOGY

1-2 / 100.000 per year Mostly in women, exception in prepubertal cases, men dominates 90% caused by microadenoma (<1cm in size) 5-10% caused by macroadenoma (>1cm in size)
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Harrisons Principle of Medicine

ETIOLOGY
Causes of Cushing Syndrome ACTH-dependent Cushings Cushing's disease (= ACTH-producing pituitary adenoma) Ectopic ACTH syndrome (due to ACTH secretion by bronchial or pancreatic carcinoid tumors, small cell lung cancer, medullary thyroid carcinoma, pheochromocytoma and others) ACTH-Independent Cushing's Adrenocortical adenoma Adrenocortical carcinoma Rare causes: PPNAD, primary pigmented nodular adrenal disease; AIMAH, ACTH-independent AIMAH, ACTHAbbreviations:ACTH, adrenocorticotropic hormone; massive adrenal hyperplasia; McCune-Albright pigmented independent macronodular hyperplasia; PPNAD, primary nodular adrenal disease syndrome 5/21/12 4:1 1:1 F : M ratio % 90 75 15

4:1

10 5 10 1 <1

Harrisons Principle of Medicine

ECTOPIC ACTH SECRETION

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Cecil Medicine

SIGN & SYMPTOMS

Body System Body fat Skin Bone Muscle Cardiovascular Metabolism Reproductive system Signs and Symptoms Weight gain, central obesity, rounded face, fat pad on back of neck ("buffalo hump") Facial plethora, thin and brittle skin, easy bruising, broad and purple stretch marks, acne, hirsutism Osteopenia, osteoporosis (vertebral fractures), decreased linear growth in children Weakness, proximal myopathy (prominent atrophy of gluteal and upper leg muscles) Hypertension, hypokalemia, edema, atherosclerosis Glucose intolerance/diabetes, dyslipidemia Decreased libido, in women amenorrhea (due to cortisolmediated inhibition of gonadotropin release)

Central nervous system Irritability, emotional lability, depression, sometimes cognitive defects, in severe cases, paranoid psychosis Blood & Immune Increased susceptibility to infections, increased white blood cell count, eosinopenia, hypercoagulation with increased risk of deep vein thrombosis and pulmonary embolism Harrisons Principle of Medicine

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SIGNS & SYMPTOMS

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MOON FACE

First time diagnosed 5/21/12

4 month later
Sherwoods Human Physiology

RADIOLOGIC EVALUATION

Abdominal CT Scan For suspected ectopic ACTH production high-resolution CT Hypersecretion of pituitary ACTH MRI with gadolinium contrast May not be able to detect small microadenoma False-positive to cyst and nonsecretory lesion 5/21/12

Harrisons Principle of Medicine

ALGORITHM TO SUSPECTED CUSHINGS SYNDROME

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Test

Diagnostic Tests to Determine the Type of Cushing's SyndromeAdrenal Tumor Pituitary Pituitary Ectopic ACTH or
Macroadenoma Microadenoma CRH Production to <10 N to 95 to <10 <10

Plasma ACTH level Percent who respond to high-dose dexamethasone Percent who respond to CRH

>90

>90

<10

<10

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Harrisons Principle of Medicine

DIFFERENTIAL DIAGNOSIS

Pseudo-Cushing Syndrome

Caused by chronic alcoholism Abdnormalities in steroid output, modestly elevated urine cortisol, blunted circardian rythm of cortisol levels, resistance to supression using the overnight dexamethasone test Discontinuation of alcohol and/or improvement of emotional status, result of steroid testing return to normal
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INCINDENTALOMA

Incidental masses discovered during radiographic testing for another condition Asymptomatic Adrenal Mass Found in ~6 % of adult subjects to autopsy Uncommon in age <30 years
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ADRENAL MASSES

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ALGORITHM FOR INCINDENTALOM A

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TREATMENT

Surgical Therapy

Resection via transsphenoidal approach to pituitary gland for patient who cannot undergo surgery, length of time to get full response is very long (up to 10 years), possibility of hypopituitarism

Radiation Therapy

Medical Therapy (combination with surgery)

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Hypercortisolism correction

Cecil Medicine

TREATMENT FOR ADRENAL ADENOMA

laparoscopic, treated with glucocorticoid and mineralocorticoid pre and post operative Despite operative intervention, most patient die within 3 years, metastases most often occur in liver and lung, drugs for corticoadrenal carcinoma mitotane Metastase to bones refrater to 5/21/12 drugs, need radiotherapy Harrisons Principle of Medicine

TREATMENT FOR BILATERAL HYPERPLASIA

Surgical exploration of the pituitary via a transsphenoidal approach finding microadenoma. Total adrenalectomy cure rate almost 100%, need for lifelong mineralocorticoid and glucocorticoid replacement and a 1020% probability of a pituitary tumor developing over the next 10 years (Nelson's syndrome) 5/21/12

Harrisons Principle of Medicine

TREATMENT FOR CUSHING

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Harrisons Principle of Medicine

MINERALOCORTICOID EXCESS / hyperaldosteronism

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HYPERALDOSTERONISM

Twice in women than men Occurs in age of 30 50 ~1% of unselected hypertension patient Classified to

Primary hyperaldosteronism

With adrenal tumor (Conns syndrome)

Without adrenal tumor (bilateral cortical nodular hyperplasia, idiopathic hyperaldosteronism, and/or nodular hyperplasia) unknown cause, no hypokalemia, less evidence of radiologic pahology, lower aldosterone level 5/21/12

Harrisons Principle of Medicine

ETIOLOGY

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Cecil Medicine

ETIOLOGY

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Cecil Medicine

PRIMARY VS SECONDARY

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SIGNS & SYMPTOMS

Hypokalemia Very severe diastolic hypertension Headaches Potassium depletion weakness & fatigue Impairment of urinary concentrating ability polyuria polydipsia Left ventricular hypertrophy secondary to hypertension, but 5/21/12 disproportionate to essential Principle of Medicine Harrisons

DIAGNOSIS

Ditegakkan dengan kadar aldosteron yang tinggi dan renin yang rendah Kalium plasma merupakan petunjuk diagnostik Kriteria diagnosis hiperaldosteronisme primer

Hipertensi diastolik tanpa edema Hiposekresi renin yg tidak merespon thd penurunan volume plasma

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ALGORITH M FOR SUSPECTE D MINERALOCORTICOID EXCESS

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ANTIHYPERTENSIVE DRUGS

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TREATMENT

Primary Hyperaldosteronism

Adenoma :

laparoscopic surgical excision Sodium restriction and spironolactone Medical intervention may be used fro chronic therapy but usually limited to side effects in men

Bilateral Hyperplasia

Surgery only when significant Symptomatic hypokalemia Harrisons Principle of Medicine cannot be

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ADRENAL ANDROGEN EXCESS

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ADRENAL ANDROGEN EXCESS

Excess DHEA & androstenedione converted to testosterone in extraglandular tissue virilization

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Harrisons Principle of Medicine

ADRENAL INSUFFICIENCY
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CLASSIFICATIO N OF ADRENAL INSUFFICIENCY

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PRIMARY ADRENAL INSUFFICIENCY (ADDISONS DISEASE)

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SECONDARY ADRENAL INSUFFICIENCY

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SIGNS & SYMPTO MS

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SIGN & SYMPTOMS

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Harrisons Principle of Medicine

(Hyperpigmentation)

SIGNS & SYMPTOMS

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ALGORITH M FOR ADRENAL INSUFFICIE NCY

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Harrisons Principle of Medicine

TREATMENT

Glucocorticoid replacement

Hydrocortisone 1525 mg Fludrocortisone 100150 g DHEA 2550 mg

Mineralocorticoid replacement

Adrenal androgen replacement

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TREATMENT

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REFERENCES

Fauci AS, Kasper DL, Longo DL, Jameson JL, et al, editors. Harrisons Principle of Internal Medicine. 18th ed. USA : McGraw Hill Medical, 2011 Fauci AS, Braunwald E, Kasper DL, Longo DL, Jameson JL, et al, editors. Harrisons Principle of Internal Medicine. 17th ed. USA : McGraw Hill Medical, 2008 Sudoyo AW, Setiyohadi B, Alwi I,

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