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Flashcards in Adrenal Gland Disorders Deck (31)
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1
Q

Addisons Disease: general characteristics

A
  • Cortisol: major product of fasciculata layer of adrenal cortex, vital for cardiovascular homeostasis
    • Deficiency results in decreased cardiac output and vascular tone
    • Patients often develop hypovolemia –> stimulates ADH –> increased free water absorption & hyponatremia
  • If primary adrenal cortex dysfunction exists: patients also lack aldosterone –> hyperkalemic
  • Divided into primary (adrenal gland) and secondary (pituitary & hypothalamus) dysfunction
2
Q

Primary adrenal insufficiency (adrenal gland dysfunction): causes

A
  • Autoimmune:
    • Addisons Disease (70-80%) most common in developed countries
  • Tuberculosis:
    • 10-20% most common in developing countries
  • Other: 10%
3
Q

Secondary adrenal insufficiency: causes

A
  • Pituitary and hypothalamus
  • Following exogenous glucocorticoid withdrawal
  • Following cure of Cushing’s disease
  • Hypothalamic/pituitary lesions
4
Q

Primary adrenal insufficiency: pathophysiology

A
  • Patients with primary adrenal disease: hyperpigmentation due to increased production of POMC (ACTH precursor in the pituitary)
    • POMC: also precursor of melanocyte stimulating hormone (MSH) –> hyperpigmentation
  • Patients are deficient in cortisol and aldosterone –> develop hyponatremia and hyperkalemia
  • 60% of patients with autoimmune adrenal insufficiency have autoimmune dysfunction of another gland (thyroid)
    • Hypothyroidism (25%)
    • Graves disease (11%)
    • Premature gonadal failure
    • Type 1 diabetes (10%
  • Proposed theory: polyglandular autoimmune syndrome - endocrine cell undergoes normal damage but does not get recognized as self by body (leads to autoimmune attack in susceptible individual - HLA-DR3, -DR4)
5
Q

Secondary adrenal insufficiency: pathophysiology

A
  • Patients have low ACTH levels
  • No hyperpigmentation
  • Preserved aldosterone synthesis –> normokalemic
6
Q

Addisons Disease: clinical manifestations

A
  • S/S divided into acute and chronic
  • Chronic sx:
    • Weakness, fatigue, dizziness, anorexia, nausea, abdominal pain, diarrhea
  • Acute:
    • All of the above + fever, hypotension, confusion
  • Other sx: weakness, fatigue, dizziness, anorexia, weight loss, salt craving
  • Lab abnormalities: hyponatremia, hyperkalemia (primary), hypoglycemia
    • Because cortisol is counter-regulatory hormone
  • Identifiable risk factors for adrenal insufficiency: autoimmune disease, trauma, sepsis, HIV/AIDS, malignancy, glucocorticoid treatment, complicated delivery and head injury (pituitary infarct)
7
Q

Addisons Disease: diagnosis

A
  • Best way = Cortrosyn/Cosyntropin stimulation test
    • Baseline serum cortisol followed by 250ug of synthetic ACTH
    • Blood drawn at 30 & 60 minutes to check for serum cortisol
    • Stimulated level greater than 20ug/dL indicates adequate adrenal cortisol reserves
    • If < 18 ug/dL: adrenal insufficiency present
  • Caveat: in recent (less than 6 month) pituitary or hypothalamic injury - pituitary (adrenal?) may still be able to respond to Cotrosyn test
8
Q

Addisons Disease: imaging considerations

A
  • Two typical abnormal adrenal gland appearances:
    • Small atrophic glands with or without dense calcifications indicate autoimmune, ALD, AMN
    • Enlarged glands with hemorrhage or necrosis
  • CT identifies both
9
Q

Addisons Disease: treatment

A
  • Glucocorticoids replacement: oral glucocorticoids given on chronic basis
    • Hydrocortisone, prednisone, dexamethasone
  • In acute crisis: saline infusion and stress dose steroids given
  • Fludrocortisone to replace aldosterone in primary gland failure
  • Sex steroid replacement necessary in women: give DHEA
10
Q

Pheochromocytoma: general characteristics

A
  • Chromaffin cells: adrenal medulla cells that appear dark due to oxidized catecholamines
  • Chromaffin cell tumors secrete excess epinephrine and norepinephrine
  • Most arise from adrenal medullary cells
  • Pheochromocytomas: rare
    • 2-8 cases/million people
    • Represents the most common adrenal tumor in adults
11
Q

Pheochromocytoma: pathophysiology

A
  • Neuroendocrine cells contain surface receptor (ret) –> binds glial-derived neurotrophic growth factor (GDNF) causing cell signaling –> initiates production of NE and epi
  • Mutation to ret receptor –> increased activation and hormone secretion
  • Germline mutations in ret implicated in Multiple Endocrine Syndrome:
    • MEN 2a: pheochromocytoma, medullary thyroid carcinoma, hyperparathyroidism
    • MEN 2b: pheochromocytoma, medullary thyroid caricinoma, mucosal neuromas
  • Other germline mutations discovered that indicate familial forms of pheochromocytomas - may account for 25-30% of cases
    • VHL, NF1, familial carotid body tumors, familial paragangliomas
12
Q

Pheochromocytoma: clinical manifestations

A
  • Headache, sweating, palpitations (clinical triad)
    • +/- hypertension
  • No flushing - pallor instead because of vasoconstriction
  • Other sx: anxiety, epigastric pain, orthostatic hypotension (hypovolemia), and chest pain
  • Pheochromocytomas (<1%), hyperaldosteronism (5-10%), and Cushing’s (<0.5%) can all cause HTN, should be included in DDX for secondary HTN
    • Primary HTN accounts for 85% of the cases
  • Signs and symptoms
    • Revolve principally around excess catecholamines
      • α1 receptors mediate vasoconstriction and thus activation can lead to HTN
      • β1 receptors mediate positive inotropy, chronotropy, increase sweating
      • β2 receptors mediate muscle bed vasodilation
  • Epinephrine works principally through β receptors to cause tachycardia, sweating, but not significant HTN (mostly due to β2 vasodilation)
  • Norepinephrine works through a & β receptors causing similar set of signs, but with added a1 related hypertension
  • Secretion from tumor can fluctuate - symptoms can be episodic
13
Q

Possible risk of patient with pheochromocytoma being on beta blocker

A
  • Unopposed a1 vasoconstrition and HTN —> dramatic increase in blood pressure
  • Start on a-blocker first
  • Then β-blocker after adequate blockade pre-operatively
14
Q

Pheochromocytoma: differential diagnosis

A
  • Anxiety/panic attacks
  • Alcoholism
  • Drugs (cocaine/PCP)
  • Thyrotoxicosis
  • Menopausal syndrome
  • Hypoglycemia
  • Withdrawal of adrenergic inhibitor
15
Q

Pheochromocytoma: diagnosis

A
  • Can be tough - pheo called “great mimic”
  • Endocrine principle: biochemical diagnosis must be established prior to anatomic localization - 5-10% of people with adrenal mass on CT have non-functioning masses
  • Great deal of variety in what product a tumor creates - standard workup includes 24 hour urine for catecholamines (Epi & NE), metabolites (metanephrine, normetanephrine, VMA, HVA)
  • Plasma metanephrines if high risk patient with family hx and adrenal mass
  • Plasma catecholamine measurement is difficult
  • Certain drugs can interfere with testing, should be avoided for two weeks:
    • TCA, beta-blockers, alpha-blockers, alpha-2-agonists (clonidine), decongestants, benzos, amphetamines, ETOH withdrawal
  • Once diagnosis is made - localization is relatively easy
    • 90% of tumors are in adrenal gland
    • 10% are extra-adrenal in sympathetic chain
    • 98% of tumors in abdomen - CT and MRI are helpful
16
Q

Pheochromocytoma: 10% rule

A
  • 10% extra-adrenal
  • 10% bilateral
  • 10% malignant (dopamine secretion) - most likely extra-adrenal
  • 10% recurrence after removal
  • 10% calcify
  • 10% kids
  • 10% familial (now thought to be more like 20-30%)
17
Q

Pheochromocytomas: imaging considerations

A
  • AKA paraganglioma or ganglioneuroma
  • Usually appear spherical and well-circumscribed on imaging > 4cm in size - easy to see
  • CT: variable
  • MRI: hyperintense on T2WI
    • Heterogeneous enhancement
18
Q

Pheochromocytomas: treatment

A
  • Surgical removal after a-blockade with labetolol or phenoxybenzamine to avoid hypertensive crisis
  • Need a-blockers because they will vasodilate once removed, become very hypotensive
19
Q

Adrenal insufficiency: familial syndromes

A
  • MEN 2A/2B
  • VHL
  • NF1
  • Familial carotid body tumors
  • Familial paragangliomas
  • Can test for all with genetic testing
20
Q

Cushing’s Syndrome: causes

A
  • Most commonly iatrogenic (due to chronic administration of glucocorticoids in tx of autoimmune/inflammatory disorders)
  • Otherwise, ACTH-dependent or ACTH-independent
    • ACTH-independent: caused by excess function of adrenal cortex
  • Most common cause of endogenous Cushing’s: pituitary tumor (80%)
21
Q

Cushing’s Syndrome: clinical signs and symptoms

A
  • Obesity: central adiposity, supraclavicular fat pad, dorsoclavicular fat pad (buffalo hump), facial fat pads
  • Skin changes: facial plethora, easy bruisability, “onion paper skin” (very thin), purplish-red striae
    • Purple striae seldom seen in other diseases
  • Insulin resistance and hyperglycemia
  • Hirsutism
  • Hypertension
  • Gonadal dysfunction: amenorrhea, infertility, decreased libido
  • Proximal muscle weakness
  • Osteoporosis
  • Depression
  • Routine lab findings: hypokalemic alkalosis in syndromes of marked hypersecretion of cortisol - ectopic ACTH or adrenal carcinoma
    • Due to increased cross-reactivity with mineralocorticoid receptor
22
Q

Cushing’s Syndrome: diagnosis

A
  • Defined by inappropriate elevation of cortisol
  • Examine sequential photographs: look for clinical signs and symptoms
  • If clinical s/s are present & chronic administration of glucocorticoids not thought to be the cause - proceed with 2 diagnostic tests
    • Bedtime salivary cortisol - positive result is elevated
    • Overnight 1mg dexamethasone suppression test (DST)
      • Administer 1mg dexamethasone at 11pm night before
      • Positive test = 8am plasma cortisol > 1.8ug/dL
    • 24-hour urinary free cortisol (UFC)
      • Positive test = > 90-100 ug/day
23
Q

Situations that can cause false-positives in Cushing’s screening DST

A
  • Acute and chronic illness
  • Obesity
  • Sleep apnea
  • PCOS
  • High estrogen states
  • Drugs (dilantin, phenobarbital)
  • Alcoholism
  • Anorexia
  • Renal failure
  • Depression

But most of these situations will have normal 24-hour UFC

24
Q

Cushing’s Syndrome: how to distinguish ACTH-dependent from ACTH-independent

A
  • High/normal ACTH = ACTH dependent
    • = Cushings Disease or ectopic ACTH syndrome
  • Low ACTH = ACTH independent
    • = Cortisol producing adrenal adenoma, cortisol producing adrenal carcinoma, or nodular adrenal hyperplasia
  • Also use 8mg dexamethasone suppression test (DST)
    • Suppression happens = pituitary
    • No suppression = ectopic/adrenal
25
Q

Cushing’s Disease: imaging considerations used to distinguish different types of adrenal hypersecretion of cortisol

A
  • Try to localize it: pituitary MRI, chest CT, abdominal CT, inferior petrosal sinus sampling
    • Tx with pituitary surgery, chest surgery, abdominal surgery, cortisol synthesis inhibitors
  • CT, MRI, ultrasonography, isotope scanning with iodocholesterol - used to define adrenal lesions
    • In ACTH hypersecretion: used to exclude presence of solitary adrenal adenoma/carcinoma & confirm bilateral adrenal hyperplasia/nodular adrenal hyperplasia
    • Effectively localize adrenal tumors (usually > 1.5cm)
    • 10% incidence of silent adrenal nodules - biochemical testing performed in conjunction with localization studies (ensure identified lesion is biologically significant)
26
Q

Cushing’s Disease/primary adrenal disease: treatment

A
  • Surgical removal of:
    • Isolated adenoma OR
    • Adrenal affected with macronodular hyperplasia OR
    • Adrenal gland containing carcinoma
  • Bilateral adrenalectomy
    • May be required to adequately treat macronodular hyperplasia with bilateral involvement
  • Medical therapy
    • Usually adjunctive/temporizing/not curative
    • Involves use of drugs that inhibit adrenal cortisol production
      • Ketoconazole, metyrapone, aminoglutethimide, mitotane
      • Mitotaine: only adrenolytic agent, used palliatively in carcinoma patients
27
Q

Hyperaldosteronism: causes

A
  • Aldosterone-producing adenoma (APA) = 34% of patients
    • Treat with surgery
  • Idiopathic hyperaldosteronism (IHA) = 66% of patients
    • Treat medically
28
Q

Hyperaldosteronism: features suggestive of primary disease (in patient with hypertension)

A
  • High likelihood of APA
  • Young age at onset (< 40 years old)
  • Resistance to multiple antihypertensive medications
  • Stage 2 ( > 160-179 / 100-109) or more severe hypertension
  • Presence of hypertension with adrenal adenoma found incidentally on body imaging
  • Hypertension in patient who has first-degree relative with primary hyperaldosteronism
29
Q

Primary hyperaldosteronism: diagnosis

A
  • Clinical triad: hypertension, hypokalemia, metabolic alkalosis
  • Aldosterone/plasma renin activity (PRA) ratio > 20-30
    • with PRA < 2 ng/mL/hr
  • Biochemical dx confirmed with suppression test prior to anatomic localization
    • Challenged with IV saline load - should suppress aldosterone levels in patient with essential hypertension, has little effect on patient with primary hyperaldosteronism
30
Q

Antihypertensive medications that interfere with diagnosis of primary hyperaldosteronism

A
  • Beta-blockers
  • Diuretics
  • Spironolactone
  • ACE inhibitors

Patient should also be euvolemic and normokalemic (avoid confounding stimuli to renin/aldosterone)

31
Q

Hyperaldosteronism: imaging considerations and treatment

A
  • CT scan of adrenal gland performed
  • Unilateral lesion > 1 cm seen: aldosterone-producing adenoma diagnosed
    • Surgery is therapeutic choice
  • No lesion, bilateral lesions, or very small lesions seen: confirm diagnosis with adrenal vein sampling
    • Unilateral elevation of aldosterone: small adenoma, requires surgery
    • Bilateral elevation of aldosterone: either idiopathic hyperaldosteronism (IHA) or glucocorticoid-remedial hyperaldosteronism (GRA)
      • GRA diagnosed by direct genetic testing, elevated levels of 18-hydroxycortisol; treated with glucocorticoid replacement
      • IHA treated with aldosterone antagonist (spironolactone, eplerenone)