Diseases of the Adrenal gland Adrenal insufficiency Cushing

Diseases of the Adrenal gland

• Adrenal insufficiency • Cushing disease vs syndrome • Pheochromocytoma • Hyperaldostronism

What are the layers of the adrenal gland ? ? And what does each layer produce ? ?

What are the layers of the adrenal gland ? ? And what does each layer produce ? ?

Adrenal insufficiency • What is adrenal insufficiency ? • What are the possible underlying causes ? • How many types of adrenal insufficiency exist and how do they differ? • How does it manifest ? • How is it treated ?

Adrenal insufficiency • A disorder caused by the destruction of the adrenal cortices Causes : • The most common cause of adrenal insufficiency in adults is chronic exogenous steroid use ( how ? ? ? ) • Autoimmune destruction accounts for 80% of the primary cases in the U. S • Other causes include congenital enzyme deficiencies • hemorrhage (Waterhouse-Friderichsen) • TB • other infections • May be isolated or be a component of a polyglandular autoimmune syndrome

Presentation • Symptoms • • fatigue worsened by stress weakness weight loss nausea and vomitting • Physical exam • increased skin pigmentation (due to elevated pro-opiomelanocortinin → MSH and ACTH) • hypotension

• Labs : elevated plasma ACTH ( in primary adrenal insufficiency ) • It is diagnosed by demonstrating a low basal serum cortisol level that does not increase appropriately after stimulation with the ACTH analogue cosyntropin. • decreased aldosterone leads to ühyponatremia ühyperkalemia ühypoglycemia üincreased BUN & Cr ümetabolic acidosis üeosinophilia

Treatment of adrenal insufficiency • Pateints with primary adrenal insufficiency require glucocorticoid and mineralocorticoid replacement , but those with central disease require glucocorticoid replacement only , WHY ? ? ? • Administer stress dose steroids at time of stress(surgery)

Cushing disease vs. syndrome • What are they ? • How do they differ ? • How do thy manifest ? • How are they diagnosed ? GOLD STANDARD ? • How are they treated ?

Cushing disease vs syndrome • A condition that refers a constellation of signs and symptoms caused by prolonged exposure to supraphysiologycal levels of glucocorticosteroids. • Iatragenic followed by ACTH secreating pituitary adenoma are most common causes.

Presentation • Symptoms • depression and psychological changes • oligomenorrhea • growth retardation • weakness • acne • excessive hair growth • symptoms of diabetes (polydipsia, polyuria, dysuria) • Physical exam • hypertension • central obesity • muscle wasting • thin skin that easily bruises • purple striae • hirsutism • moon facies • buffalo hump

1 - 24 hour free urinary cortisol (GOLD STANDARD ) 2 -low-dose dexamethasone suppression test (cortisol levels generally not suppressed in Cushing syndrome) 3 -midnight salivary cortisol • Hyperglycemia hypokalemia and hypernatremia could also exist • to localize lesion: Ø ACTH Ø high dose dexamethasone supression test (cortisol levels suppressed if ACTH source is pituitary adenoma, but generally not if ectopic ACTH production) Ø CT and MRI to localize lesions Ø Inferior petrosal sinus sampling

• Resection of source • For non resectable tumors: • • ketoconazole (inhibits P 450) aminoglutethimide (inhibits P 450) metyrapone (blocks adrenal enzyme synthesis) mitotane (adenolytic)

PRIMARY HYPRALDOSTERONISM • Excess production of aldosterone independent of the physiological regulator of its production ( WHICH IS ……. . ? ) • MOST COMMON CAUSE IS ………. . ?

• Symptoms hypertension (secondary to increased plasma volume secondary to increased sodium reabsorption) • Suspect the diagnosis in patients with resistant hypertension who develop severe hypokalemia after initiation of a thiazide diuretic (such as HCTZ) • • headache polyuria (secondary to hypokalemic nephropathy) muscle weakness (secondary to hypokalemia) Physical examtetany (hypokalemia) parestesias peripheral edema in severe cases hypertension

• hypokalemia • hypernatremia • low plasma renin (neg. regulation by high aldsterone) • metabolic alkalosis (dumping H+ for Na+) • HOW IS IT DIAGNOSED ? ?

Treatment • Surgical adrenalectomy for adenoma • bilateral adrenalectomy should not be performed • Spirolactone or eplerenone (aldosterone receptor antagonist) for bilateral adrenal hyperplasia or bilateral adnomas

Pheochromocytoma Composed of which type of cells ? ? What do they secrete ? What are the know familial causes of these tumors ? What are the possible sites for pheos ? Is there a percentage of malignant pheos ? How do they present , what is the classical triad of symptoms they produce ? • How are they diagnosed ? How are tumors localized? • How are they treated ? • What is the antihypertensive medication that is absolutely contraindicated to give on its own in pheos ? • • •

• Q 1 --A patient with lethargy, nausea, and reported muscle weakness is given a series of tests to rule out physical causes. During these tests it is revealed that plasma corticotropin is above normal and cortisol is below normal. Renin is above normal and aldosterone is below normal. Adrenal androgens are below normal. Which of the following clinical conditions would be most likely to produce this set of signs and symptoms?

• A. Cushing’s Disease • B. Ectopic corticotropin-producing tumor • C. Secondary renal insufficiency • D. Congenital adrenal hyperplasia • E. Addison’s Disease

• Q 2 --A 48 YO man with a family history of heart disease has followed a hearthealthy lifestyle for 15 years. However, he has recently experienced unusual fatigue and lightheadedness, especially when rising suddenly. Physical examination demonstrates postural hypotension and a darker-than usual complexion for midwinter in the Midwest (he works and exercises indoors). Lab work reveals that he is hyponatremic, hyperkalemic, and hypocalcemic. Further blood tests are ordered to assay plasma corticotropin-releasing hormone (CRH), corticotropin (ACTH), and cortisol. What combination of hyper and/or hyposecretion for these hormones would be the most likely given this man’s signs and symptoms?

• CRH secretion ACTH secretion Cortisol secretion A- hypersecretion B- hypersecretion hyposecretion C -hypersecretion hyposecretion D- hyposecretion E- hyposecretion hypersecretion

Q 3 --A 47 -year-old male has been feeling fatigued and has gained 20 pounds during the last two months. On exam, you note central obesity with proximal muscle atrophy and weakness. Vital signs are as follows: T 98. 4 F, BP 155/90 mm. Hg, HR 85 bpm, RR 14 rpm. BMP is as follows: Na 140, K 3. 9, Cl 102, CO 2 23, BUN 19, Cr 0. 9, Glu 115. 24 -hour urinary free cortisol level is 165 nmol/day (upper range of normal 110138 nmol/day) and morning serum ACTH is 83 pg/m. L (normal is 9 - 52 pg/m. L). Two days later, he receives a high-dose 2 mg dexamethasone suppression test orally every 6 hours for 48 hours. The following morning at 9 am, his serum cortisol level is 300 nmol/L (normal is 50 -200 nmol/L). At 48 hours it is 250 nmol/L. Which of the following should be the next step?

1 -Bilateral inferior petrosal sampling 2 -Initiate treatment with metyrapone 3 -Initiate treatment with ketoconazole 4 -CT of the thorax and abdomen 5 -Brain MRI

• Q 4 --A 69 -year-old presents with granulomatosis with polyangiitis (formerly Wegener's) diagnosed about 8 months ago. He was treated with rituximab and prednisone for induction remission and has required prednisone since his diagnosis. Her temperature is 37 deg C (98. 6 deg F), pulse is 80/min, blood pressure is 150/90 mm. Hg, respirations are 14/min, and O 2 saturation is 99% on room air. His physical examination is notable for the findings in Figures A and B. What would be the most likely electrolyte abnormality found in this patient?

1 -Hypokalemia and hyponatremia 2 -Hyperkalemia and hypernatremia 3 -Hypokalemia and hypernatremia 4 -Hyperkalemia and hyponatremia 5 -Hypercalcemia and hypernatremia

• Q 6 --A patient with chronic obstructive pulmonary disease is admitted to the hospital with cholecystitis. He undergoes cholecystectomy uneventfully and is transferred to the floor. Suddenly, he becomes weak and severely hypotensive. If the patient's symptoms are due to adrenal insufficiency from chronic steroid use, one would expect which of the following • 1 -Elevated renin • 2 -Elevated cortisol • 3 -Decreased ACTH • 4 -Elevated ACTH • 5 -Elevate aldosterone

Q 7 ----A 37 -year-old female presents to general medical clinic with headache, fatigue, and weakness. She also reports that she has been having to get up at night to urinate. She has no significant past medical history. She denies taking any medications. Her vital signs are stable with the exception of blood pressure of 165/100. Physical examination is unremarkable. She is concerned because she never remembers having high blood pressure. A workup of the patient's hypertension is initiated, and it is found that she has an elevated plasma ratio of aldosterone to renin. Which of the following would also be likely in this patient? 1 -Metabolic acidosis 2 -Hyperkalemia 3 -Hyperglycemia 4 -Metabolic alkalosis 5 -High renin levels

• A 56 -year-old male with a history of difficult-to-control hypertension presents to his physician with progressive fatigue and new onset muscle cramps. He has had no recent changes to his medication regimen, which includes hydrochlorothiazide, lisinopril and amlodipine. His physical exam is notable for a blood pressure of 170/100 but is otherwise within normal limits. A routine basic metabolic panel demonstrates the following lab values: Sodium: 147 m. Eq/L Potassium: 2. 6 m. Eq/L Chloride: 102 m. Eq/L HCO 3: 26 m. Eq/L BUN: 13 g/d. L Creatinie: 0. 7 mg/dl Glucose: 98

• What is the mechanism causing the patient's elevated blood pressure? 1 -Adrenal hemorrhage 2 -Cortisol excess 3 -Stress 4 -Medication toxicity 5 -Excess sodium retention