Endocrine Test 3 (Adrenal Gland)

Mineralocorticoid Excess: Clinical manifestations

-HTN -Hypokalemia -Metabolic alkalosis (losing H+ in urine) -Na=normal or hypernatremic (depends on volume load:peripheral edema) -symptoms associated with mild hypokalemia (fatigue, muscle weakness, lassitude; delays depolarization and slows everything down) -Severe Hypokalemia (polydipsia, polyuria, paresthesias, paralysis/tetany)

Mineralocorticoid Excess: consider diagnosis in patients with...(4)

-HTN with Hypokalemia -hypertension and low dose diuretic induced hypokalemia -severe resistant HTN -HTN and adrenal incidentaloma (seen when doing tests for something else)

Disorders of the adrenal gland

Excess or Deficiency

other clinical manifestations of addison's disease

-changes in distribution of body hair -GI disturbances -weakness -hypoglycemia -postural hypotension -weight loss -adrenal crisis

Secondary causes of adrenal insufficiency: Pituitary apoplexy

-consequence of infarcted pituitary or transient reduction of blood supply during surgery -Sheehans syndrome- blood loss associated with partuitin

Addison's Disease: Sexual Dysfunction

-decreased axillary and pubic hair -loss of libido -amenorrhea in 25% of women -these features common in women, in whom androgen production primarily occurs in adrenal glands. -features uncommon in men, in whom androgen production occurs primarily in the testes

what is the treatment for the late onset type of congenital adrenal hyperplasia

-dexamethasone 0.5mg QD (glucocorticosteriod to suppress ACTH) -antiandrogen (spironolactone 100-200mg) or flutamide probably equally effective -mineralocorticoid replacement not needed*

Cushing's Syndrome Dx: other lab findings

-elevated Alk Phos (bc bone breakdown) -granulocytosis (increased neutrophils bc bone breakdown) -thrombocytosis -hypercholesterolemia -hypertriglyceridemia -glucose intolerance/DM -severe hypercortisolism (ectopic ACTH) = hypokalemia Other -hypercoaguable state (increased risk of DVT with subsequent PE)

Adrenal Incidentaloma: Evaluation for hormone secretion Presence of functioning mass suggested by..

-history -physical -lab findings

Clinical manifestations in secondary and tertiary adrenal insufficiency are similar to those of primary adrenal insufficiency except:

-hyperpigmentation is not present in secondary/tertiary do to the ACTH secretion not being increased -dehydration is not present, and hypotension is less prominent

what is the medical treatment for Cushings (2nd line): -patients waiting for pituitary radiation or have had and awaiting results -or not surgical candidates

-ketoconazole (anti fungal that inhibits conversion of hydroxylase), metyapone, mifepristone (adrenal blockade that suppresses adrenal gland) -somatostatin (decreases ACTHand may reduce tumor size)

if confirmed secondary adrenal insufficiency

-low ACTH and low cortisol -MRI pituitary gland

Chronic: what is secondary adrenal insufficiency characterized by

-only glucocorticosteriod deficiency is present -adrenal gland itself is intact (still controlled by RAA-mineralocorticosteriod)

Secondary causes of adrenal insufficiency: Hypothalamic-Pituitary dysfunction

-pituitary or hypothalamic tumors -or surgical or irradiation to areas

what makes up the adrenal crisis in addisons

-profound fatigue -dehydration -vascular collapse (decrease in BP) -renal shut down (low Na, high K)

Mineralocorticoid Excess: Dx what is not recommended for all HTN patients

-screening is NOT recommended for all HTN patients

Adrenal Incidentaloma: functional masses

-subclinical Cushings Syndrome -Pheochromocytoma -Aldosteronomas

If confirmed primary adrenal insufficiency...

-test for steroid autoantibodies -marker of autoimmune andrenalitis -if negative, CT scan of adrenal glands (tumor, ETC)

Dx of Chronic Primary adrenal insufficiency

1 hour Cosyntropin Test -ACTH stimulation test -Individual is given 0.25mg of cosyntropin in a IV bolus (best to give in morning) -cortisol concentrations are measured in 0, 30, and 60 min -normal response to cosyntropin is a rise in the serum cortisol concentration after 30-60min to a peak of 18-20 (excludes adrenal insufficiency) -stimulated cortisol concentration level less than 18 suggests adrenal insufficiency

Cushing's Syndrome: Etiology 1. rare disease 2. Majority from what 3. more males or females 4. what is the most common cause

1. -- 2. ACTH producing pituitary adenoma (cushings disease) 3. F>M 4. medical use of corticosteroids for immunosuppression (IATROGENIC)

Adrenal Insufficiency: Tuberculosis 1. what % 2. results from what

1. 10-20% of cases (most common causes worldwide) 2. hematogenous spread from active infection

Pheochromocytoma: Initial tests for Dx (2)

1. 24 hour urinary measurement of fractionated catecholamines, vanillymandelic acid (VMA) and metanephrine levels 2. Fractionated plasma free metanephrine levels

Cushing's Syndrome: Dx if H and P are suggestive (3)

1. 24 hour urine -measure urinary free cortisol (level > 50mcg/24 hr on 3 separate collections = cushings 2. overnight dexamethasone suppression test -give 1mg dexamethasone at 11pm -measure plasma cortisol at 8am -plasma cortisol > 1.8 = hypercortisolism 3. normal cortisol level = diurnal -highest in am, lowest in pm -cushings= blunted diurnal response -elevated night time cortisol > 50% of am via late night salivary=hypercortisolemia *have to have 2 of these)

Adrenal Insufficiency: Autoimmune Disease 1. what % 2. what are the 2 syndromes

1. 70% 2. -Polyglandular Autoimmune Syndrome 1: hypoparathyroidism, adrenal insufficiency, and Candidiasis -Polyglandular Autoimmune Syndrome 2: Adrenal insufficiency, autoimmune thyroid disease, and insulin dependent diabetes Patients with isolated autoimmune adrenal insufficiency are predominately male ( 71% ) in first two decades of life, equally male and female in third decade and predominately female thereafter ( 81% ). Autoimmune adrenal insufficiency as part of the polyglandular syndromes are predominately female ( 70% ). Approximately one half of patients with autoimmune adrenal insufficiency will have one or more autoimmune endocrine disorders.

Adrenal Insufficiency: what are the 7 primary causes of adrenal insufficiency

1. Autoimmune Disease 2. Tuberculosis 3. Fungal Infections 4. HIV 5. Adrenal Hemorrhage 6. Metastatic carcinoma 7. Drugs

what are the 2 phenotypes of 21 alpha hydroxylase deficiency

1. Classic= dx at birth or early childhood (external genitalia gets bigger and looks like a micropenis) 2. Late onset= develops after puberty (oliomenorrhea, hirsutism, can look like POS)

Chronic Primary Adrenal Insufficiency: Treatment during times of stress 1. Minor Illness 2. Surgery

1. Glucocorticoids should be increased 2-3X the usual daily dosage for 3-days 2. Glucocorticoid dosage highly variable depending upon the severity of the surgery *Cortisol secretion normally incrases with the stress of illness or surgery

Mineralocorticoid Excess: Clinical Manifestations 1. What are the 2 major clinical findings 2. what is the clinical hallmark

1. HYPERTENSION -usually recognized on evaluation of HTN and hypokalemia -dependent upon the degree of volume expansion that occurs -hypervolemia leads to increased vascular resistance that perpetuates the hypertension -BP is often substantially elevated -may be resistant to HTN treatment HYPOKALEMIA -hypersecrtion of aldosterone which directly promotes potassium secretion in the cortical collecting tubule contributes to urinary potassium wasting 2. HYPOKALEMIC HYPERTENSION Hypertension: Hypervolemia is responsible for another characteristic finding in primary aldosteronism, marked suppression of renin release, leading to a very low plasma renin activity. This finding is of diagnostic importance in distinguishing primary from secondary forms of hyperaldosteronism.

What are the laboratory findings in Chronic Primary Adrenal insufficiency (Addisons) (2)

1. Hyponatremia -85-95% of patients -salt craving may be present -less common in secondary/tertiary adrenal insufficiency. *Hyponatremia: Reflects both sodium loss and volume depletion caused by mineralocorticoid deficiency ( aldosterone ) and increased vasopressin secretion caused by coritsol deficiency. Hyponatremia is less common in secondary or tertiary due to general preservation of aldosterone release and generally less prominent reduction in cortisol secretion 2. Hyperkalemia -60-65% of patients -not present in secondary/tertiary *Hyperkalemia Entirely due to hypoaldosteronism, since one of the major functions of aldosterone is to promote the urinary excretion of dietary potassium Not present in secondary or tertiary causes secondary to the present of aldosterone

what are the clinical manifestations of Adrenal Crisis (6)

1. Hypotension**** (postural) 2. shock 3. may mimic acute abdomen (abdominal tenderness, n/v, fever) 4. confusion 5. weakness 6. lethargy

What are the secondary causes of Adrenal Insufficiency

1. Hypothalamic-Pituitary dysfunction 2. Exogenous glucocorticoids 3. Rarer causes (Pituitary apoplexy)

Adrenal Crisis may occur in what situations (3)

1. In a previously undiagnosed patient with adrenal insufficiency who has been subjected to serious infection or acute major stress 2. in a patient with known adrenal insufficiency who had failed to take more glucocorticoids during infection or major illness 3. in patients who are abruptly withdrawn from doses of glucocorticoids, leading to secondary adrenal insufficiency

Mineralocorticoid Excess: Dx 1. If HTN with drug resistance, hypokalemia, adrenal mass, or HTN before age 40.. 2. diagnosis suggested of primary aldosteronism when 3. diagnosis suggested of secondary aldosteronism when

1. Measure plasma renin and aldosterone -calculate aldosterone/renin ratio (AAR) -must normalize K prior to testing (around 3.0) -low renin level and high aldosterone level =someting secreting aldosterone 2. when PRA (plasma renin activity) is suppressed and PAC (plasma aldosterone concentration) is elevated=Conns 3. when both PRA and PAC is elevated and the PAC/PRA<10 (not conns)

Mineralocorticoid Excess: 1. what is the treatment for Bilateral Hyperplasia 2. what are the goals of therapy

1. Medical management with mineralocorticoid antagonists -spironolactone -epleronone 2. normalization of potassium; normalization of BP

what are the 3 anatomic zones of the adrenal cortex and their secretions

1. Outer (Zona Glomerulosa): secretes mineralococorticoid (aldosterone) 2. Intermediate (Zona Fasiculata): secretes cortisol 3. Inner (Zona Reticularis): secretes adrenal androgens

Cushing Syndrome:ACTH Dependent (2)

1. Pituitary adenoma: corticotroph releasing too much ACTH and adrenal gland responds to that 2. Ectopic secretion of ACTH from non pituitary tumor: from anywhere, producing ACTH, stimulates adrenal gland to release too much cortisol

Adrenal Gland: Aldosterone 1. controlled by 2. initiated by 3. what does not significantly effect mineralocorticosteriods 4. Assess (Renin levels; Oral or IV Na load)

1. RAA regulatory cycle 2. release of Renin from juxtaglomerular cells -increased Angio 1 to Angio 2= increased aldosterone (high Na retention and K excretion) 3. hypothalamic damage 4. Renin levels: high renin = mineralocorticosteriod deficiency Oral or IV Na load = suppression of aldosterone (absent suppression=mineralocorticosteriod excess )

Adrenal Gland: Cortisol 1. regulated by 2. Hypothalamic Pituitary Adrenal Axis

1. Regulated by feedback loop 2. Hypothalamus = increase CRH in response to stress (exogenous or endogenous) Increased CRH= increased ACTH (pituitary) = increased cortisol

what is the treatment for the classic type of Congenital Adrenal Hyperplasia

1. Replace glucocorticoids and mineralocorticoids -suppress ACTH and androgen overproduction -allows normal growth and sexual maturation in children -hydrocortisone or prednisone (replacement) -fludrocortisone (if hypotension) 2. Prevent virilizaton -Antiandrogens (flutanide-blocks testosterone) + aromatase inhibitors (testolactone)

Adrenal glands consist of 2 distinct regions

1. adrenal cortex 2. adrenal medulla

Mineralocorticoid Excess: Workup (Conns) 1. After dx is established, what is the next step

1. adrenal imaging (CT=method of choice) -helps differentiate adrenal tumor from bilateral adrenal hyperplasia -treatment is different (adrenal tumor can be cut, bilateral adrenal hyperplasia can't be cut)

Cushing's Syndrome: ACTH Independent (adrenal gland's fault) (3)

1. adrenocortical adenoma 2. adrenocortical carcinoma (cancerous inside gland pumping too much cortisol 3. nodular adrenal hyperplasia

Clinical features of pheochromocytoma 1. epidemiology 2. biologic behavior 3. secretion 4. clinical presentation 5. macroscopic features 6. microscopic features

1. adults; both sexes; all ages, especially 30-50 years old 2. 90% benign, 10% malignant 3. high levels of catecholamines; most secrete epinephrine 4. episodic or sustained hypertension, sweating, palpitations, hyperglycemia, glycosuria 5. mass, often hemorrhagic; 10% bilateral; 10% extra-adrenal 6. nests of large cells, vascular stroma

Mineralocorticoid Excess: what are the causes of primary hyperaldosteronism (3)

1. aldosterone producing adenoma (most common) 2. bilateral adrenal hyperplasia (25%) 3. aldosterone secreting carcinoma *coming from adrenal gland

Congenital Adrenal Hyperplasia 1. what is it 2. what does degree of impairment of glucocorticoid and mineralocorticoid based on 3. who does androgen excess present in

1. autosomal recessive disorder of adrenal steroid biosynthesis (results in glucocorticoid and mineralocorticoid deficiency) 2. based on severity of mutations 3. all patients -sever viralization of external genitalia in neonatal girls -young women with non classic CAH (hirsutism and oligomenorrhea resembling PCOS)

PHEOCHROMOCYTOMA 1. what is it 2. occurrence 3. how does it occur and what does it feature 4. what % are malignant

1. catecholamine secreting tumor that arises from the chromatin cells of the adrenal medulla and the sympathetic ganglia 2. very rare (occurs in less than 0.2% of patients with HTN) 3. sporadically or inherited (features of MEN type 2 syndrome) 4. 10% (most benign)

Cushing's Syndrome: PE findings (5)

1. centripetal obesity (wasting of arms and legs) 2. Round of face (moon facies) 3. dorsocervial fat pad (buffalo hump) 4. more specific -facial plethora/redness in cheeks -supraclavicular filling -fragility of skin (thin, easily bruised, broad purplish stria) -proximal muscle weakness (inability to stand from seated position; disability with combing hair) 5. ectopic ACTH=hyperpigmentation of knuckles, skin, scars

What are the clinical manifestations of Chronic Primary Adrenal Insufficiency (Addisons) (11)

1. chronic malaise 2. weakness 3. anorexia 4. weight loss 5. nausea/vomiting 6. Postural Dizziness/Syncope 7. Vague symptoms (often misdiagnosed as depression) 8. Hyperpigmentation 9. sexual dysfunction 10. musculoskeletal symptoms 11. psychiatric manifestations

Clonidine Suppression tests Results 1. in patients with essential HTN, plasma catecholamine/normetanephrine concentrations will 2. in patients with pheochromocytoma, the concentrations of catecholamine/normetanephrine will

1. decrease 2. remain increased

Pheochromocytoma: Clincal manifestations What is the classical Triad

1. episodic headache -mild to severe -variable in duration -occurs in up to 90% of patients 2. Sweating (60-70% of patients) 3. Tachycardia (palpitations) *Presence of all 3 in association with HTN makes dx likely -can be asymptomatic for years

Cushing's Syndrome 1. Chronic exposure to what

1. excess glucocorticosteriods

Adrenal Incidentaloma: Gradual increase in clinical manifestations that parallel hormone levels 1. what is mandatory 2. what requires exclusion

1. exclusion of catecholamine excess from a pheochromocytoma (24 hour urine) 2. autonomous cortisol and aldosterone secretion (Cushings and Conns)

what are the 3 classes of corticosteroid hormones that the adrenal gland produces

1. glucocorticosteriods (cortisol) 2. mineralocorticosteriods (aldosterone) 3. adrenal androgen precursors (DHEA)

Cushing's Syndrome: Clinical Manifestations 1. what affects almost all cells of the body 2. what are the 3 most prominent features 3. what does excess glucocorticosteriod secretion also affect

1. glucocorticosteroids 2. increased gluconeogenesis*, lipolysis, protein catabolism (proximal muscle wasting and weakening) 3. kidneys ability to inactivate cortisol (cortisol takes on mineralocorticosteriod effect on distal tubule -diastolic HTN -Hypokalemia -edema (opposite of addisons)

Pheochromocytoma: Catecholamine Crisis 1. what does this lead to (4) 2. During episodes of hormone release, the patient is...

1. heart failure, pulmonary edema, arrhythmias, intracranial hemorrhage (from vasoconstriction in the increase of BP) 2. -pale and anxious -tachycardic with palpitations -paroxysms generally last less than an hour -precipitated by surgery, position changes, exercise, stress, pregnancy, meds *Abnormalities in carbohydrate metabolism that occur are directly related to the increase in catecholamine production.

hyperplasia drawing: 1. 21 hydroxy 2. 17 alpha hydroxy 3. 11 Beta hydroxy

1. high testosterone 2. high aldosterone 3. high aldosterone and testosterone

Adrenal Incidentaloma 1. the possible presence of a functioning mass is often suggesting by what 2. the absence of the findings reduces but doesn't eliminate the likelihood of finding a pheochromocytoma, cortisol-secreting tumor, or aldosteronoma

1. history (palpitations, sweating, or headache) Physical exam -features of Cushing's syndrome (HTN, central obesity, stria, etc.) -routine lab findings (hyperNa, hypoK) 2. --

Pheochromocytoma: when to suspect diagnosis (5)

1. hyperadrenergic spells -limited episodes of non exertional palpitations, diaphoresis, headache, or tremor 2. family hx of pheochromocytoma 3. incidental discovered adrenal mass (CT abdomen) 4. onset of HTN at young age < 20 5. pressor response during anesthesia, surgery, or angiography (tachycardia, HTN during surgery)

Adrenal Insufficiency: 1. what is the most frequent cause 2. what is the 2nd most frequent cause

1. hypothalamic-pituitary origin 2. Primary adrenal insufficiency (usually acquired): autoimmune destruction of the adrenal glands; or genetic

Adrenal Medulla: 1. where does it lie 2. what does it secrete 3. functionally related to what system

1. in the center of the adrenal gland 2. catecholamines epinephrine and norepinephrine 3. sympathy nervous system

ACTH level responses after dexamethasone suppression test 1. normal response with high cortisol 2. high cortisol with high ACTH= 3. low ACTH and high Cortisol=

1. low ACTH 2. secondary (pituitary tumor elsewhere other than adrenal gland) 3. adrenal gland problem (primary)

Addison's Disease: Psychiatric manifestations (3)

1. memory impairment 2. depression (20-40%) 3. psychosis (20-40%) Pyschosis: Manifested by social withdrawal, irritability, poor judgement, agitation, hallucinations or paranoid delusions. The psychiatric symptoms may begin early in the disease process and predate other symptoms, making diagnosis of there cause difficult.

Congenital Adrenal Hyperplasia: CYP 21 (late onset) 1. enzymatic defect 2. high frequency in who 3. develops when 4. signs of

1. mild enzymatic defect 2. high frequency in Ashkenazi Jews 3. Develops after puberty 4. signs of virilization (hirsutism and acne, amenorrhea or oligomenorrhea) -consider in women: hirsuitism and menstrual irregularities or infertility *will look like POS but ultrasound will show no cysts

Addison's Disease: Hyperpigmentation 1. evident in who 2. what is it caused by 3. where does it occur

1. nearly all patients with primary adrenal insufficiency 2. increased melanin content in the skin 3. more generalized but is most conspicuous in areas exposed to light (face, neck, and back of hands); also prominent in palmar creases and inner surface of he lips and buccal mucosa)

Cushing's Syndrome: Work up 1. after diagnosis has been made.. 2. Initial

1. need to find cause 2. ACTH level (normal to elevated: cushings disease/ectopic ACTH tumor) -high dose 8mg dexamethasone suppression test to separate -pituitary tumor = suppressed cortisol on 2nd day -ectopic ACTH=no cortisol suppression -or inferior petrol sinus sampling (IPSS) Suppressed (primary adrenal cushings): get CT of abdomen or MRI (adrenal mass) Pituitary adenoma suspected: get MRI

Cushing's Syndrome: Clinical Signs (nonspecific) (8)

1. obesity 2. diabetes 3. diastolic HTN 4. hirsutism 5. psychologic abnormalities (depression, insomnia, hyperarousal, mood swings) 6. cognitive dysfunction 7. menstrual irregularities 8. loss of libido/ED *fat people don't have addisons and skinny people don't have cushings

Adrenal Incidentaloma: evaluation for malignancy 1. what is rare 2. other cancers metastasize to the adrenals 3. what may help determine whether the tumor is benign or malignant

1. primary adrenal carcinoma 2. lung 3. size and imaging characteristics of mass

Adrenal Insufficiency 1. Primary 2. Secondary 3. Tertiary

1. results from the destruction or dysfunction of the adrenal cortex 1. results from ACTH hypo secretion by the pituitary 3. results from interference of corticotropin releasing hormone (CRH) secretion by the hypothalamus

Adrenal Incidentaloma: Tumor characteristics 1. Benign lesions 2. malignant lesions

1. rounded and homogenous 2. lobulated and inhomogeneous

Adrenal Incidentaloma: Differentiating Benign from Malignant 1. imaging = 2. procedure of choice for imagine adrenal gland 3. what increases risk of adrenocortical carcinoma, pheochromocytoma, benign adrenal myelolipoma 4. what is a poor predictor of malignancy 5. what adds additional diagnostic value 6. lipid rich (low attenuation) 7. high attenuation

1. sensitive, suboptimal specificity 2. CT 3. increased mass of tumor 4. size alone 5. tumor density 6. adrenocortical adenomas 7. pheochromocytomas

Adrenal Crisis Labs: Critically ill patients with hypovolemia (4)

1. serum cortisol - less than 10 mcg -or change of cortisol <9 mcg after 0.25 ACTH 2. serum renin 3. serum ACTH 4. electrolytes

Pheochromocytoma: Treatment 1. what is the ultimate therapeutic goal 2. what is essential

1. surgery: complete removal of tumor 2. Preoperative preparation (alpha-adrenergic blockade: vasodilation) -usually given 7-10 days prior to surgery to help control BP -Phenoxybenzamine is preferred drug (need liberal salt intake and hydration to prevent orthostasis; before surgery, BP should be below 160/90 consistently)

Pheochromocytoma: Conclusion 1. doe does not always lead to long term cure of the pheochromocytoma or HTN 2. what is indicated in all patients

1. surgical removal 2. long term monitoring

Pheochromocytoma: other clinical manifestations

1. sustained or paroxysmal hypertension (most common sign) 2. palpitations 3. anxiety 4. generalized weakness 5. orthostatic hypotension 6. weight loss *Patients with symptoms related to paraxysamal elevations in blood pressure HTN, Tachycardia, or Arrythmia during diagnostic procedures such as colonoscopy, induction of anesthesia, surgery or with certain foods containing tyramine should undergo formal evaluation for pheochromocytoma. Symptoms of pheochromocytomas are caused by tumoral secretion of norepinephrine, epinephrine, and dopamine

How do you diagnose Congenital Adrenal Hyperplasia

17 hydroxyprogesterone level -high > 200= consistent with dx -late onset type (elevated 17 hydroxyprogesterone > 1500, 30 min after 0.25 mg synthetic ACTH (cosyntropin test)

Pheochromocytoma: Treatment -After adequate alpha blockade has been achieved, beta blockade is initiated, which occurs when -increased as needed for what

2-3 days preoperatively tachycardia

What is the action of aldosterone

Acts primarily in the distal nephron to increase the reabsorption of sodium and chloride and the secretion of potassium and hydrogen *increases Na, decreases K, metabolic alkalosis

What is chronic primary adrenal insufficiency

Addison's Disease

Cushing's Syndrome: Iatrogenic

Administration of exogenous glucocorticosteriods (commonly too much prednisone)

what is a mass lesion greater than 1cm in diameter serendipitously discovered by radiologic evaluation

Adrenal Incidentaloma 2 questions 1. is it malignant 2. is it functioning

Adrenal Insufficiency: What is the fungal infection that can cause adrenal insufficiency

Histoplasmosis

Dx of chronic primary adrenal insufficiency

Basal morning serum cortisol measurement -level less than 3 = adrenal insufficiency -level less than 10 = suggest diagnosis *Serum cortisol concentrations are higher in the early morning range from 10 - 20 ug/dL. Basal morning serum cortisol measurements Not a reliable predictor of deficient adrenal function when used alone

Pheochromocytoma: Radiology

CT with contrast or MRI of abdomen -5% of adrenal incidentalomas = pheochromocytomas

Pheochromocytoma: what is the confirmatory Dx test

Clonidine suppression test (confirms dx) -clonidine normal suppresses the release of catecholamines from neurons but does not effect the catecholamine secretion from pheochromocytoma -Clonidine 0.3mg is administered orally, and plasma catecholamines or fractionated metanephirnes are measured before and three hours after the dose -if levels are still elevated=pheochromocytoma

Once adrenal insufficiency is confirmed, what is the next step

Determine if primary or secondary -ACTH high is primary -ACTH low is secondary

What is the drug that can cause adrenal insufficiency and what does it do

Ketoconazole (inhibits cortisol biosynthesis)

what is the treatment for ectopic ACTH in cushings

Localize the tumor with appropriate scans and surgical removal

1st step after finding high ACTH and high Cortisol

MRI pituitary

Chronic Primary Adrenal Insufficiency: Treatment with 1.Mineralocorticoid replacement 2. Adrenal Androgen Replacement

Mineralocorticoid Replacement 1. Fludrocortisone 100-150mcg day -adequate dose based on orthostatic hypotension -measure Na, K, renin regularly -increase dose during hot or tropical weather conditions 2. -option is patients who lack energy despite optimized glucocorticosteriod/mineralocorticosteriod replacement -women with loss of libido and other features of androgen deficiency -DHEA 25-50 mg QD

Congenital Adrenal Hyperplasia: 21 alpha Hydroxylase deficiency

Most common (95%) Failure of 21 hydroxylation of 17 hydroxyprogesterone (everything is shifted to right side of chart; adrenal gland gets larger) -cortisol and aldosterone defeciency -low cortisol leads to high ACTH= adrenal hyperplasia (overproduction of 17 hydroxyprogesterone and progesterone; high ACTH also = high aldosterone and DHEA-converted to testosterone)

what is the pathophysiology of pheochromocytoma

Pheochromocytomas and paraganglions -synthesize and store catecholamines (norepinephrine, epinephrine, and dopamine: fluctuation of secretion) -hormonal activity of the tumor fluctuates (considerable variation in serial catecholamines)

Chronic Primary Adrenal Insufficiency: Treatment (glucocorticoids)

Replacement therapy with glucocorticoids and mineralocorticoids 1. Glucocorticoid Replacement: Hydrocortisone 15-25mg BID or TID (all patients half dose AM, monitor based on H and P) 2. Stress related does adjustment: double dose in illness with fever; IV hydrocortisone 100mg= prolonged vomiting, surgery, trauma

what is the treatment for an Adrenal Crisis (5)

Requires immediate treatment 1. IV fluids (normal saline) -avoid hypotonic solutions (may worsen hyponatremia) 2. Glucocorticoid replacement (V -hydrocortisone 100mg IV bolus (initiated immediately after labs) 3. Mineralocorticoid replacement not useful* (takes several days for Na retaining effects 4. Search for and treat precipitating causes 5. All patients should wear medical alert bracelet

Mineralocorticoid Excess: what is the general treatment approach for 1. unilateral disease 2. bilateral adrenal hyperplasia

Surgery is only effective for unilateral disease -discrete adenoma in one adrenal with other being normal -unilateral adrenalectomy 2. treat symptoms with K sparing diuretics (spironolactone or eplerenone)- too much aldosterone, blocks effect, so Na and H2O can't be reabsorbed

Mineralocorticoid Excess: what is the treatment for unilateral adenoma or hyperplasia

Unilateral adrenalectomy -induces a marked reduction in aldosterone secretion and correction of hypokalemia in almost all patients -HTN is improved and crew in 35-65% of patients

Adrenal gland disorder: Excess

Usually Neoplasm -increased ACTH (pituitary or ectopic) -adrenal nodules (increase glucocorticosteriods or mineralocosteriods)

What is the Tx for adrenal incidentaloma

adrenal masses associated with confirmed hormone excess or suspects malignancy= surgery (adrenalectom) -functional masses

Once primary or secondary adrenal insufficiency is confirmed what is the next step

assess for mineralocorticosteriod deficiency -measure renin -Primary: high ACTH and high Renin

Pheochromocytomas are tumors of the adrenal medulla, or ___

autonomous nervous system

the adrenal medulla secretes ____ the adrenal cortex secretes ___

catecholamines steroid hormones

what do pheochromocytomas produce and what can that lead to

catecholamines can lead to -racing heart beat -headaches -pallor -sweating -high BP

Secondary causes of adrenal insufficiency: Exogenous glucocorticoids

decrease the secretions of CRH from the hypothalamus which results in decrease ACTH secretion form the pituitary. This leads to decreased cortisol production from the adrenal gland

Addison's Disease: Musculoskeletal Symptoms

diffuse myalgia and arthralgia

Chronic: what is adrenal androgen secretion characterized by

disrupted in both primary and secondary

Addison's Disease: you can get postural dizziness/syncope secondary to what

hypotension from volume depletion

Chronic: what is Addison's disease characterized by

loss of both glucocorticosteriod and mineralocorticosteriod secretion

Acute Adrenal Insufficency: Adrenal Crisis

medical emergency -treatment should not be delayed pending lab results

while most adrenal incidentalomas are ___, as many as 15% secrete excess amounts of hormones

non functional

Cushing's disease is caused by

pituitary corticotroph adenoma

Renin high, aldosterone high= secondary= HTN = ...

renal artery stenosis coarctation of aorta renin-secreting tumor diuretic use

Adrenal glands lie at the ________ of each kidney

superior pole

what is the preferred treatment for all causes of cushings

surgical

what is the treatment for cortisol secreting carcinoma

surgical removal poor prognosis (20% die at 1 year after dx)

Diagnosis of adrenal insufficiency of any cause depends entirely upon what

the demonstration of inappropriately low cortisol production

what happens if you give prednisone to a diabetic

their sugar skies

Hypokalemia can be exacerbated by what

thiazide diuretics -increases Na delivery to collecting duct -drives potassium excretion

what its he treatment for cortisol secreting adrenal adenoma

unilateral adrenalectomy

Cushing's type syndrome

way too much cortisol, but it's coming because there's a pituitary gland tumor/adenoma secreting too much ACTH to adrenal gland

Adrenal crisis may also occur in this situation

After bilateral adrenal infaction or bilateral adrenal hemorrhage

What is an aldosterone producing adrenal adenoma

Conn's Syndrome -causes mineralocorticosteriod excess -5-12% of HTN patients (especially those with hypokalemia -has nothing to do w/ pituitary -usually tumor in adrenal gland that causes secretion of aldosterone and leads to mineralocorticoid excess -too much aldosterone=hypertensive, hyperNa, hypoK -has nothing to do w/ sugar -no muscle wasting or osteoporosis

Adrenal Incidentaloma: FNA of Pheochromocytomas

Contraindicated** -can cause life threatening hypertensive crisis

Primary mineralocorticoid Excess

Primary mineralocorticoid excess