Adreno Cortex

Ronald Chrisbianto Gani405090223

Faculty of Medicine 2009Tarumanagara University

ENDOCRINE SYSTEM BLOCK

CASE 3

PHYSIOLOGY OF CORTEX ADRENAL

ADRENAL GLAND

Sherwood’s Human Physiology 7th Ed

Color Atlas of Physiology 5th Ed

STEROIDOGENIC PATHWAY

Sherwood’s Human Physiology 7th Ed

Color Atlas of Physiology 5th Ed

CONTROLOF

CORTISOLSECRETION

Sherwood’s Human Physiology 7th Ed

CIRCARDIAN RHYTHM

Color Atlas of Physiology 5th Ed

CUSHING’S SYNDROME

DEFINITION

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

Harrison’s Principle of Medicine 18th Ed

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)

Harrison’s Principle of Medicine 18th Ed

ETIOLOGYCauses of Cushing Syndrome F : M ratio %

ACTH-dependent Cushing’s 90

Cushing's disease (= ACTH-producing pituitary adenoma) 4 : 1 75

Ectopic ACTH syndrome (due to ACTH secretion by bronchial or pancreatic carcinoid tumors, small cell lung cancer, medullary thyroid carcinoma, pheochromocytoma and others)

1 : 1 15

ACTH-Independent Cushing's 4 : 1 10

Adrenocortical adenoma 5 – 10

Adrenocortical carcinoma 1

Rare causes: PPNAD, primary pigmented nodular adrenal disease; AIMAH, ACTH-independent massive adrenal hyperplasia; McCune-Albright syndrome

< 1

Abbreviations: ACTH, adrenocorticotropic hormone; AIMAH, ACTH-independent macronodular hyperplasia; PPNAD, primary pigmented nodular adrenal disease

Harrison’s Principle of Medicine 18th Ed

ECTOPIC ACTH SECRETION

Cecil Medicine 23rd Ed

SIGN & SYMPTOMSBody System Signs and Symptoms

Body fat Weight gain, central obesity, rounded face, fat pad on back of neck ("buffalo hump")

Skin Facial plethora, thin and brittle skin, easy bruising, broad and purple stretch marks, acne, hirsutism

Bone Osteopenia, osteoporosis (vertebral fractures), decreased linear growth in children

Muscle Weakness, proximal myopathy (prominent atrophy of gluteal and upper leg muscles)

Cardiovascular Hypertension, hypokalemia, edema, atherosclerosis

Metabolism Glucose intolerance/diabetes, dyslipidemia

Reproductive system Decreased libido, in women amenorrhea (due to cortisol-mediated 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

Harrison’s Principle of Medicine 18th Ed

SIGNS & SYMPTOMS

Harrison’s Principle of Medicine 17th Ed

Harrison’s Principle of Medicine 18th Ed

MOON FACE

Sherwood’s Human Physiology 7th Ed

First time diagnosed 4 month later

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

Harrison’s Principle of Medicine 18th Ed

ALGORITHMTO

SUSPECTEDCUSHING’SSYNDROME

Harrison’s Principle of Medicine 18th Ed

Diagnostic Tests to Determine the Type of Cushing's Syndrome

Test Pituitary Macroadenoma

Pituitary Microadenoma

Ectopic ACTH or CRH Production

Adrenal Tumor

Plasma ACTH level

↑ to ↑↑ N to ↑ ↑ to ↑↑↑ ↓

Percent who respond to high-dose dexamethasone

<10 95 <10 <10

Percent who respond to CRH

>90 >90 <10 <10

Harrison’s Principle of Medicine 18th Ed

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

Harrison’s Principle of Medicine 18th Ed

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

Harrison’s Principle of Medicine 17th Ed

ADRENAL MASSES

Harrison’s Principle of Medicine 18th Ed

ALGORITHMFOR

INCINDENTALOMA

Harrison’s Principle of Medicine 17th Ed

Harrison’s Principle of Medicine 18th Ed

TREATMENT

• Surgical Therapy – Resection via transsphenoidal approach

• Radiation Therapy– 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

• Medical Therapy (combination with surgery)– Hypercortisolism correction ketoconazole

(1600mg) and metyrapone (2g)

Cecil Medicine 23rd Ed

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 drugs, need radiotherapy

Harrison’s Principle of Medicine 18th Ed

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 10–20% probability of a pituitary tumor developing over the next 10 years (Nelson's syndrome)

Harrison’s Principle of Medicine 18th Ed

TREATMENT FOR CUSHING

Harrison’s Principle of Medicine 18th Ed

MINERALOCORTICOID EXCESS / HYPERALDOSTERONISM

HYPERALDOSTERONISM• Twice in women than men• Occurs in age of 30 – 50• ~1% of unselected hypertension patient• Classified to– Primary hyperaldosteronism

• With adrenal tumor (Conn’s 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

– Secondary Hyperaldosteronism• Response to activation of RAA system or at Bartter syndrome

Harrison’s Principle of Medicine 18th Ed

ETIOLOGY

Cecil Medicine 23rd Ed

ETIOLOGY

Cecil Medicine 23rd Ed

PRIMARY VS SECONDARY

Harrison’s Principle of Medicine 17th Ed

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 disproportionate to essential hypertension• Proteinuria • Renal failure• Hypertension complication structural damage of cerebral

circulation, retinal vasculature, kidneyHarrison’s Principle of Medicine 18th Ed

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– Hipersekresi aldosteron yg tidak berkurang setelah

volume expansion

ALGORITHMFOR

SUSPECTEDMINERALO-CORTICOID

EXCESS

Harrison’s Principle of Medicine 18th Ed

ANTIHYPERTENSIVE DRUGS

Harrison’s Principle of Medicine 17th Ed

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 cannot be controlled by

medical intervention

Harrison’s Principle of Medicine 18th Ed

ADRENAL ANDROGEN EXCESS

ADRENAL ANDROGEN EXCESS

• Excess DHEA & androstenedione converted to testosterone in extraglandular tissue virilization

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ADRENAL INSUFFICIENCY

CLASSIFICATIONOF

ADRENALINSUFFICIENCY

Harrison’s Principle of Medicine 18th Ed

PRIMARY ADRENAL INSUFFICIENCY (ADDISON’S DISEASE)

SECONDARY ADRENAL INSUFFICIENCY

SIGNS&

SYMPTOMS

SIGN & SYMPTOMS

Harrison’s Principle of Medicine 17th Ed

SIGNS&

SYMPTOMS(Hyperpigmentation)

ALGORITHMFOR

ADRENALINSUFFICIENCY

Harrison’s Principle of Medicine 18th Ed

TREATMENT

• Glucocorticoid replacement– Hydrocortisone 15–25 mg

• Mineralocorticoid replacement– Fludrocortisone 100–150 μg

• Adrenal androgen replacement– DHEA 25–50 mg

Harrison’s Principle of Medicine 18th Ed

TREATMENT

Harrison’s Principle of Medicine 18th Ed

REFERENCES• Fauci AS, Kasper DL, Longo DL, Jameson JL, et al, editors.

Harrison’s Principle of Internal Medicine. 18th ed. USA : McGraw Hill Medical, 2011

• Fauci AS, Braunwald E, Kasper DL, Longo DL, Jameson JL, et al, editors. Harrison’s Principle of Internal Medicine. 17th ed. USA : McGraw Hill Medical, 2008

• Sudoyo AW, Setiyohadi B, Alwi I, Simadibrata M, Setiadi S, et al, editors. Buku Ajar Ilmu Penyakit Dalam 5th ed. Jakarta : Pusat Penerbitan Ilmu Penyakit Dalam FKUI, 2006

• Arrend WP, Armitage JO, Clemmons JR, Drazzen JM, Griggs J, et al. Goldman’s Cecil Medicine. Philadelphia : Elsevier Saunders 2008

• Sherwood L. Human Physiology from Cells to System. 7th Ed. USA : Brooks / Cale Cengage Learning 2010