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Adrenal Disorders-Kuliah Update
Adrenal Disorders-Kuliah Update
Mardianto Divisi Endokrin dan Metabolik Bagian Penyakit Dalam FK USU RSUP H. Adam Malik Medan
salt sugar
sex
Hypothalamus-Pituitary-Adrenal axis
Circadian regulation Stress: Physical stress + Emotional stress Hypoglycemia Cold exposure Pain CR H
Cortis Cortis ol ol
Adrenal cortex
ticothropin releasing hormone; ACTH=adrenocorticothropin hormone. Kirk LF. Am Fam Physician 2000
Production of catecholamines
Adrenocortical disorders
Cushings Syndrome
Supraphysiologic glucocoticoid exposure (excess cortisol)
Protein catabolic state Liberation of amino acids by muscle AA are transformed into glucose and glycogen and then transformed into fat
F>M (3:1)
Cushings Syndrome
Symptoms and Sign
Weight gain, round facies and truncal obesity Weakness Hypertension Hirsutism (in women) Amenorrhea Cutaneous striae Ecchymoses Osteoporosis Hyperglycemia
Percent of Patients
97 87 82 80 77 67 65 Common Common
Cushing Syndrome
Continue Evaluation
Cushing syndrome doubful PsudoCushings Treat underlying illness Follow clinical examination Repeat evaluation
CRH stimulation test High dose DST Positron emission scanning: occult neuroendocrine and ather ACTH-secreting tumors
Cushings Syndrome
Treatment program :
The resolution of hypercorticolism The parellel treatmet of the complications of CS (e.g. hypertension, osteoporosis, diabetes mellitus, mucle rehabilitation) Management of glucocorticoid withdrawal and hypothalamic pituitary-adrenal (HPA) axis recovery
Treatment: Surgical
Cushings disease
Transphenoidal surgery (TSS)
The treatment choice The longterm surgical cure rate for ACTH secreting microadenomas is 8090%. Transient post-op diabetes insipidus, adrenal insufficiency, CSF rhinorrhea, meningitis
Tansphenoidal irradiation
If TSS is not curative. High success rate in kids (80%) Low success in adults (20%)
Cushings Syndrome
Treatment: Surgical
Cushings disease
Bilateral adrenalectomy
If failed pituitary surgery Life-long steroid replacement
Adrenal lesions/carcinoma
Removal of primary lesion Survival based on underlying disease
Cushings Syndrome
Treatment: Medical Used as prep for surgery or poor operative candidate Metyrapone- inhibits conversion of deoxycortisol to cortisol Aminoglutethimide-inhibits desmolase Cholesterol to pregnenolone Blocks synthesis of all 3 corticosteroids Side effects: N/V, anorexia, lethargy Ketoconazole- an imidazole that blocks cholesterol synthesis Mitotane (O-P-DDD)-inhibits conversion to pregnenolone Inhibits final step in cortisol synthesis Destroys adrenocortical cells (spares glomerulosa cells)
Addisons Disease
Background: Thomas Addison first described the clinical presentation of primary adrenocortical insufficiency (Addison disease) in 1855 in his classic paper, On the Constitutional and Local Effects of Disease of the Supra-Renal Capsules. Pathophysiology:
Addison disease is adrenocortical insufficiency due to the destruction or dysfunction of the entire adrenal cortex. It affects both glucocorticoid and mineralocorticoid function. The onset of disease usually occurs when 90% or more of both adrenal cortices are dysfunctional or destroyed.
Cortisol
Abdominal pain Anorexia Vomiting Diarhea
Fluid intake dehydration Hypotension Hypovolemia Renal perfusion BUN Decreased Body Weight General Weakness
ACTH
Addisons Disease
Primary adrenal insufficiency
Causes Infectious TB most common cause in 3rd world countries HIV, histoplasmosis, blastomycosis, coccidiomycosis Autoimmune disorders anti-adrenal antibodies (most cause common) Medications ketoconazole, aminoglutethamide, etomidate Adrenal hemorrhage Lymphoma, bilateral adrenal metastasis, Kaposis sarcoma Infiltrative amylodosis, sarcoidosis, adrenoleukodystrophy
Addisons Disease
Secondary adrenal insufficiency
Pituitary failure panhypopitutarism, Sheehans syndrome (post-partum pituitary injury)
Percent of Patients
99 98 97 90 88 88 64
Addisons Crisis
Acute adrenal insufficiency
Similar causes
Adrenal hemorrhage Chronic steroid use and trauma/stress/surgery
Hypotension, volume depletion, fever, nausea and vomiting, tachycardia, weakness, hypoglycemia Premed prior to interventions
Addisons Crisis
Treatment acut of adrenal crisis
The five Ss management are salt, sugar, steroid, support, and search for presipitating illness. General and supportive measure
Correct volume depletion, dehydration, and hypoglycemia with IV 0.9% saline with 5% dextrose Evaluate and correct infection and other precipitating factors
Glucocorticoid replacement
Administer hydrocortisone 100 mg every 6 hours for 24 hours When the patient is stable, reduce the dosage to 50 mg every 6 hours Taper to maintenance theraphy by day 4 or 5 and add mineralocorticoid theraphy as required Maintain or increase the dose to 200-400 mg/d if complications persist or occur
Addisons Crisis
Maintenance therapy Glucocorticoid and mineralocorticoid
Oral dose hydrocortisone : 10-20 mg in the morning and 5-10 mg later in day. Fludrocortisone : 0,05-0,2 mg/d orally in the morning.
Response to theraphy
General clinical sign, good appetite and sense of well being. Signs of Cushings syndrome indicate overtreatment
Pheochromocytoma
Pheochromocytoma is a rare catecholamine-secreting tumor derived from chromaffin cells. Tumors that arise outside the adrenal gland are termed extra-adrenal pheochromocytomas or paragangliomas. Because of excessive catecholamine secretion, pheochromocytomas may precipitate life-threatening hypertension or cardiac arrhythmias It is associated with spectacular cardivascular disturbances and, when corectly diagnosed and treated curable. When undiagnosed fatal Prevalence estimates 0.01% to 0.1% of the hypertensive population
Pathophysiology
The clinical manifestations of a pheochromocytoma result from excessive catecholamine secretion by the tumor. Catecholamines typically secreted, either intermittently or continuously, include norepinephrine and epinephrine and rarely dopamine. The biological effects of catecholamines are well known. Most pheochromocytomas contain norepinephrine predominantly, in comparison with the normal adrenal medulla, which is composed of roughly 85% epinephrine. Familial pheochromocytomas are an exception because they secrete large amounts of epinephrine. Thus, the clinical manifestations of a familial pheochromocytoma differ from those of a sporadic pheochromocytoma.
Pheochromocytoma
Symptoms :
Due to the pharmacologic effects excess circulating catecholamines A typical paroxysm (the 5 Ps)
Pressure sudden major increase in blood pressure Pain abrupt onset of throbbing headache ; chest and abdominal pain Perspiration profuse generalized diaphoresis Palpitation Pallor
Clinical sign :
Hypertension,orthostatic hypotension, grade II to III retinopathy, tremor, weight loss, fever, painless hematuria, hyperglycemia, erythrocytosis
Pheochromocytoma
Diagnosis :
Demonstration of excessive amounts catecholamines in plasma or urine or degradation product in urine
Urinary metanephrine, normetanephrine, vanilmandelic acid (VMA), and free catecholamine in 24-hour periode Direct measurement plasma NE and EPI. Levels > 2000 pg/ml are abnormal and suggestive Pheochromocytoma
Pheochromocytoma
Treatment :
Surgical resection is only definitive therapy Preoperative preparation with alpha blockade reduce the incidence intraoperative hypertensive crisis and postoperative hypotension The most commonly used agents are phenoxybenzamine (10-20 mg 2-3 times/d, or prazosin 1mg 3 times/day, advanced to 5 mg 3 times/day (7-28 days before surgery) Other agents labetalol or Ca channel blocker