Endocrine

Question 1

Describe the pathogenesis of T1DM.

Answer 1

it is an autoimmune disease in which the immune system mediates destruction of beta islet cells; once 90% of these cells are destroyed, T1DM occurs

Question 2

In those with T1DM, what percentage of beta islet cells must be destroyed before the onset of disease?

Answer 2

about 90%

Question 3

Describe the risk factors and pathogenesis of T2DM.

Answer 3

• obesity is the most significant risk factor with genetics and age also contributing
• obesity is associated with increased plasma levels of free fatty acids, which makes muscles more insulin resistant and stimulates hepatic glucose production
• in normal patients, the pancreas secretes more insulin to compensate, but in diabetics, free fatty acids fail to stimulate pancreatic insulin secretion
• overtime, hyperglycemia develops, which eventually desensitizes beta islet cells to glucose

Question 4

Why is age a risk factor for T2DM?

Answer 4

because as one ages, their endogenous insulin production decreases

Question 5

Why do T2DM patients eventually have low levels of insulin production?

Answer 5

because as hyperglycemia develops, beta islet cells eventually become desensitized to glucose

Question 6

Which type of diabetes has a stronger genetic component?

Answer 6

T1DM has a 50% concordance rate between identical twins while T2DM has a 90% concordance rate

Question 7

Describe the Somogyi effect and how it should be managed?

Answer 7

• a finding in some diabetics which can complicate treatment
• patients may experience nocturnal hypoglycemia and counterreulatory systems then contribute to morning hyperglycemia
• diagnosed by obtaining a 3 am glucose level rather than waiting til the morning fasting level
• the treatment is counter intuitive in that it is a decrease in insulin levels rather than an increase

Question 8

Describe the Dawn phenomenon.

Answer 8

• a cause of morning hyperglycemia in some diabetics

- attributed to nocturnal secretion of growth hormone, which antagonizes insulin and contributes to hyperglycemia

Question 9

How is a diagnosis of diabetes made?

Answer 9

if any of the following criteria are met on two separate days

• fasting plasma glucose >126
• random plasma glucose >200 in any patient with symptoms
• 2-hr, 75g glucose tolerance test > 200
• HbA1c > 6.5 percent

Question 10

What screening recommendation is in place for diabetes and what is the preferred method?

Answer 10

• all adults over 45 should be screened every 3 years

- the preferred test is a fasting plasma glucose

Question 11

How should a clinician respond to a screening fasting plasma glucose of 116?

Answer 11

patients with a glucose level between 100-126 should undergo a 2-hr, 75g glucose tolerance test for further screening

Question 12

Describe the symptoms of diabetes.

Answer 12

• polyuria and polydypsia
• fatigue and weight loss
• blurred vision
• fungal infections
• numbness, tingling of the hands and feet

Question 13

What are the general principles for treating outpatient diabetics?

Answer 13

• monitor HbA1c every 3 months with a goal < 7
• monitor daily glycemic levels at home
• check feet and BP at every visit
• screen for microalbuminuria, check BUN and creatinine, assess vision, measure cholesterol levels annually
• prescribe a daily aspirin to all those over 30 years old
• provide the pneumococcal vaccine

Question 14

What is the goal HbA1c in diabetic patients?

Answer 14

less than 7 is associated with a marked reduction in risk for microvascular complications

Question 15

How much insulin do most T1DM patients require?

Answer 15

0.5-1.0 units/kg/day split 50/50 between long-acting forms and regular forms

Question 16

What are the typical blood sugar goals for diabetic patients?

Answer 16

fasting blood glucose less than 130 and peak postprandial glucose less than 180

Question 17

What are the typical blood sugar goals for diabetic patients?

Answer 17

fasting blood glucose less than 130 and peak postprandial glucose less than 180

Question 18

Describe the macrovascular complications of diabetes and the practical consequences of these.

Answer 18

• they experience accelerated atherosclerosis
• this manifests as coronary artery disease, peripheral vascular disease, and cerebrovascular disease, increasing the risk of MI, CHF, and MI
• this is the reason why diabetics have a lower BP target of 130/80 and a lower LDL target of 100 mg/dL

Question 19

What is the most common cause of death in diabetic patients?

Answer 19

coronary artery disease secondary to accelerated atherosclerosis

Question 20

Describe diabetic nephropathy.

Answer 20

• this is why diabetic patients are screened for microalbuminuria on a yearly basis with the threshold of 30-300mg 24-hour protein or an albumin-creatinine ratio of 0.02-0.2
• microalbuminuria usually takes 1-5 years to progress to diabetic nephropathy
• includes nodular glomerular sclerosis (aka Kimmelstiel-Wilson) syndrome, diffuse glomerular sclerosis, and isolated glomerular basement membrane thickening
• strict glycemic control prevents the progression from microalbuminuria to proteinuria
• initiating ACE inhibitors or ARBs when patients meet criteria for microalbuminuria is also an important preventative step
• avoiding proteinuria is important because combined with hypertension, it leads to a decrease in GFR, renal insufficiency, and then ESRD

Question 21

Why is the diabetic BP goal lower than in the general population of hypertensives?

Answer 21

it is 130/80 because hypertension will accelerate macrovascular atherosclerosis and the progression from diabetic nephropathy to ESRD

Question 22

How should diabetic patients with microalbuminuria be managed?

Answer 22

• the concern is for diabetic nephropathy which could then progress to ESRD
• strict glycemic control and initiation of ACE inhibitors or ARBs when patients meet microalbuminuria criteria decreases the rate of progression to nephropathy
• blood pressure control with ACE inhibitors lowers the risk of progressing from nephropathy to ESRD and a dietary restriction of protein is recommended

Question 23

How should diabetic patients who require radiocontrast be prepped?

Answer 23

they should be generously hydrated before and their metformin should be held for at least 48 hours after to reduce the risk of AKI

Question 24

Describe the pathogenesis of diabetic nephropathy.

Answer 24

• hyperglycemia increases GFR
• increased GFR leads to microalbuminuria and eventually proteinuria
• proteinuria signals the onset of diabetic nephropathy
• hypertension and proteinuria ultimately lower GFR
• low GFR leads to renal insufficiency and ESRD

Question 25

Describe non-proliferative diabetic retinopathy

Answer 25

• retinal damage due to chronic hyperglycemia
• more common than the proliferative type
• characterized by leaking capillaries and macular edema, so fundoycopic exam shows hemorrhages, exudates, microaneurysms, and venous dilatation
• usually asymptomatic until the edema or ischemia involves the central macula
• best treated with blood sugar control

Question 26

Describe proliferative diabetic retinopathy.

Answer 26

• retinal damage due to chronic hyperglycemia
• less common than the non-proliferative type
• characterized by neovascularization in the setting of chronic hypoxia with resultant traction on the retina
• can lead to vitreal hemorrhage or retinal detachment
• best treated with peripheral retinal photocoagulation, surgery, and anti-VEGF (ranibizumab)

Question 27

Describe the peripheral neuropathy found in diabetics.

Answer 27

• a distal, symmetric neuropathy which affects a “stocking/glove” pattern because it affects the longest nerves first
• loss of sensation is followed by ulcer formation, ischemia of pressure point areas, and charcot joints
• can also have painful neuropathy with hypersensitivity to light touch, which elicits a burning pain, particularly at night

Question 28

What cranial nerve complications arise in those with diabetes?

Answer 28

• diabetes leads to nerve infarction, most often affecting CN III, but occasionally IV or VI
• diabetic third nerve palsy presents with eye pain, diplopia, ptosis, and an inability to adduct the eye but spares the pupil

Question 29

What is mononeuropathy?

Answer 29

• a microvascular complication of diabetes whereby vasculitis leads to axonal ischemia and then infarction
• often affects the median, ulnar, or common perineal nerves
• can present as diabetic lumbrosacral plexopathy; deep pain in the thigh with atrophy and weakness sin the thigh and hip muscles
• can present as diabetic truncal neuropathy with pain in the distribution of one of the intercostal nerves

Question 30

Diabetic neuropathy can take what forms?

Answer 30

• peripheral neuropathy in a stocking/glove pattern
• diabetic third nerve palsy with eye pain, diplopia, ptosis, and an inability to adduct the eye
• mononeuropathies of the median nerve, ulnar nerve, common perineal nerve, one of the intercostal nerves, or the lumbosacral plexus
• autonomic neuropathy with impotence, neurogenic bladder, gastroparesis, alternating constipation/diarrhea, or postural hypotension

Question 31

How does autonomic neuropathy present in diabetics?

Answer 31

• impotence is the most common presentation
• neurogenic bladder
• gastroparesis
• alternating constipation and diarrhea
• postural hypotension

Question 32

What is charcot foot?

Answer 32

a complication of diabetes whereby nerve injury prevents patients from feeling pain, so repetitive injuries go unnoticed and ultimately remain unhealed

Question 33

Why are diabetics more susceptible to infection?

Answer 33

• wound healing is impaired by reduced blood supply and neuropathy
• WBC functioning is also impaired

Question 34

What are the complications of chronic diabetes?

Answer 34

• accelerated atherosclerosis leading to CAD, peripheral vascular disease, and cerebrovascular disease
• microalbuminemia leading to diabetic nephropathy and then renal insufficiency and ESRD
• diabetic retinopathy
• peripheral neuropathy, CN III palsy, mononeuropathies, and autonomic neuropathy
• increased susceptibility to infection

Question 35

Describe the pathogenesis of DKA.

Answer 35

• insulin deficiency leads to hyperglycemia, which promotes osmotic diuresis and volume depletion
• glucagon excess promotes ketone formation and acidosis

Question 36

DKA

Answer 36

• a complication of predominately T1DM, driven by an insulin deficiency and glucagon excess which ultimately drive osmotic diuresis and ketone formation
• presents with n/v, Kussmaul respirations, abdominal pain, fruity breath, signs of volume depletion, polydipsia, polyuria, polyphagia, weakness, and altered consciousness
• labs demonstrate serum glucose between 450-850, a metabolic acidosis with anion gap, ketonemia and ketonuria, hyperosmolarity, hyponatremia, hyperkalemia
• treat with NS, then add D5; start an insulin drip at 0.1 U/kg/hr; add potassium within 2 hours of insulin

Question 37

Why would someone in DKA not have ketones in their serum or urine?

Answer 37

• this can be a false negative in those who are experiencing circulatory collapse
• lactate production in these patients results in less acetoacetate and more B-hydroxybutyrate production, but B-hydroxybutyrate is not measured by normal testing

Question 38

What happens to electrolyte levels in those with DKA?

Answer 38

• hyponatremia although total body sodium is normal
• hyperkalemia even though total body potassium is low
• typically, phosphate and magnesium levels are low

Question 39

What is the sodium correction factor in those with diabetes?

Answer 39

serum sodium is 1.6 mEq/L higher for every 100 mg/dL increase in glucose

Question 40

What is the treatment for DKA?

Answer 40

fluids, insulin, and potassium

• begin with fluid replacement using normal saline, and add D5 once the blood glucose reaches 250 mg/dL to prevent hypoglycemia
• give a priming dose of 0.1 U/kg of regular insulin followed by a 0.1 U/kg/hr infusion there after
• replace potassium within 1-2 hours of starting insulin

Question 41

What is the most severe complication that needs to be avoided during the treatment of DKA?

Answer 41

cerebral edema which can occur if glucose levels decrease too quickly

Question 42

Describe and explain the pathogenesis of hyperosmolar hyperglycemic nonketotic syndrome.

Answer 42

• it is a state hyperglycemia, hyperosmolarity, and dehydration
• low insulin levels lead to hyperglycemia causing an osmotic diuresis
• small amounts of insulin, however, blunt counterregulatory hormone release like glucagon and prevents ketogenesis

Question 43

Hyperosmolar Hyperglycemic Nonketotic Syndrome

Answer 43

• a state of hyperglycemia, hyperosmolarity, and dehydration seen predominately in those with T2DM
• low insulin levels allow for hyperglycemia and an osmotic diuresis while the little insulin produced prevents glucagon release and thus ketogenesis and acidosis
• presents with thirst, polyuria, signs of hypovolemia, and CNS findings, particularly seizures
• labs show a serum glucose usually over 900, serum osmolarity over 320, no acidosis, and a prerenal azotemia
• treat with fluid replacement and insulin

Question 44

Describe the treatment for hyperosmolar hyperglycemic nonketotic syndrome.

Answer 44

• fluid replacement with normal saline, including 1 L in the first hour and another liter in the next two hours
• provide a 5-10 U insulin bolus followed by continuous low-dose infusion at 2-4 U/hr
• add D5 when glucose levels reach 250 mg/dL
• switch to half normal saline after the patient stabilizes

Question 45

How is BMI calculated?

Answer 45

as weight in kg/height in meters squared

Question 46

If you calculate an individual’s BMI and determine that they are obese, what should your next step be?

Answer 46

obtain a waist circumference to asses their abdominal obesity, which is a great risk factor for medical conditions

Question 47

What is the threshold at which waist circumference corresponds to an increased cardio metabolic risk?

Answer 47

circumference over 40 inches in men and 35 in women

Question 48

Describe the mechanism of the following obesity medications:

• orlistat
• lorcaserin
• phentermine and topiramate

Answer 48

• orlistat is a pancreatic lipase inhibitor
• lorcaserin is a selective 5-HT2C receptor agonist
• phentermine and topiramate is a combination with unknown mechanism of action

Question 49

What is the most effective treatment for obesity?

Answer 49

bariatric surgery

Question 50

Who is a candidate for bariatric surgery?

Answer 50

patients with a BMI greater than 40 who have failed a sufficient exercise and diet regimen and who present with obesity-related comorbid conditions like hypertension or diabetes

Question 51

Which organ is most at risk during periods of hypoglycemia?

Answer 51

the brain, which isn’t capable of utilizing free fatty acids as an energy source

Question 52

Describe changes in hormone levels that occur as blood glucose drops.

Answer 52

• when glucose levels approach the low 80s, insulin levels decrease
• as levels decline further, glucagon levels increase
• epinephrine is the next hormone to combat hypoglycemia, along with cortisol and other catecholamines
• symptoms then begin around a glucose level in the 50s

Question 53

At what point does hypoglycemia become symptomatic?

Answer 53

around 50 mg/dL

Question 54

What are the possible causes of hypoglycemia?

Answer 54

• drug induced (i.e. too much insulin or sulfonylurea)
• insulinoma
• ethanol ingestion
• idiopathic
• adrenal insufficiency, liver failure, critical illness
• disorders of carbohydrate metabolism

Question 55

How does ethanol ingestion contribute to hypoglycemia?

Answer 55

because poor nutrition leads to decreased glycogen and the metabolism of alcohol consumes NAD levels

Question 56

If a patient presents with hypoglycemia of unknown cause, how can you eliminate drug-induced hypoglycemia?

Answer 56

• measure plasma insulin level
• measure C-peptide
• look for anti-insulin antibodies
• measure a plasma and a urine sulfonylurea level

Question 57

What are the clinical features of hypoglycemia?

Answer 57

• rising epinephrine levels cause sweating, tremors, increased BP, elevated pulse, anxiety, and palpitations
• neuroglycopenic symptoms are those resulting from inadequate glucose for the brain, which manifests as irritability, behavioral changes, weakness, drowsiness, headache, confusion, convulsions, and coma

Question 58

How does the presentation of hypoglycemia often differ in patients with diabetes and why?

Answer 58

• diabetics with severe neuropathy have a blunted autonomic response to hypoglycemia and do not respond to hypoglycemia with epinephrine
• as such they don’t experience the typical sweating, tremors, BP or pulse increase, anxiety, or palpitations
• hypoglycemia may go unnoticed until the neuroglycopenic symptoms occur and they are more likely to have altered mental status at the time of presentation

Question 59

How should hypoglycemia be treated?

Answer 59

• provide sugar-containing foods if the patient can eat
• otherwise, give ½ to 2 ampules of D50W IV and switch to D10W as clinical condition improves and glucose levels reach 100 mg/dL
• importantly, if you suspect ethanol-induced hypoglycemia, give thiamine before administering glucose to avoid Wernicke’s encephalopathy

Question 60

What is important to remember in the treatment of ethanol-induced hypoglycemia?

Answer 60

these patients must be given thiamine before administering glucose to avoid Wernicke’s encephalopathy

Question 61

Hypoglycemia

Answer 61

• an imbalance between insulin driving glucose levels down and glucagon, epinephrine, other catecholamines, and cortisol driving glucose levels up
• can be drug induced by insulin or sulfonylureas, an insulinoma, ethanol ingestion, adrenal insufficiency, liver failure, critical illness, etc.
• presents when glucose levels reach the 50s with sweating, tremors, hypertension, tachycardia, anxiety, and palpitations as epinephrine levels rise
• neuroglycopenic symptoms occur next as the brain receives inadequate glucose, manifesting as irritability, behavioral changes, weakness, drowsiness, headache, confusion, etc.
• treat with sugar if capable of PO; otherwise start with D50 until blood sugars reach about 100 mg/dL and then switch to D10
• provide thiamine before glucose if it is ethanol-induced to avoid wernicke’s encephalopathy

Question 62

Insulinoma

Answer 62

• an insulin-producing tumor arising from beta-cells of the pancreas
• associated with MEN I
• presents with symptoms of hypoglycemia including sympathetic activation and neuroglycopenic symptoms
• diagnosed based on a 72-hour fast in which the patient will become hypoglycemic and insulin levels remain abnormally elevated
• the Whipple triad: hypoglycemic symptoms brought on by fasting, blood glucose less than 50 during symptomatic attack, and relief brought about by glucose administration
• treat with surgical correction

Question 63

What is whipple’s triad?

Answer 63

• hypoglycemia symptoms brought on by fasting, blood glucose less than 50 during symptomatic periods, and relief brought about by glucose administration
• a triad suggestive of insulinoma

Question 64

Zollinger-Ellison Syndrome

Answer 64

• a pancreatic islet cell tumor that secretes gastrin, which promotes gastric acid hyper secretion, resulting in ulcers
• may be complicated by GI hemorrhage, GI perforation, gastric outlet obstruction/stricture, and metastatic disease to the liver
• diagnosed based on a secretin test, which normally inhibits gastrin secretion; fasting gastrin levels are also elevated and basal acid output is increased over 15 mEq/hr
• treat with high-dose PPIs

Question 65

What is normal basal gastric acid output and what level is indicative of a gastrinoma?

Answer 65

normal is less than 10 mEq/hr and a level over 15 mEq/hr is consistent with zollinger-ellison syndrome

Question 66

What is the typical presentation of a glucagonoma?

Answer 66

• the classic manifestation is necrotizing migratory erythema below the waist
• other symptoms include glossitis, stomatitis, mild diabetes mellitus, and hyperglycemia with low amino acid levels and high glucagon levels

Question 67

What is the typical presentation of a somatostatinoma?

Answer 67

a classic triad of gallstones, diabetes, and steatorrhea

Question 68

What is the typical presentation of a VIPoma?

Answer 68

• watery diarrhea leading to dehydration, hypokalemia, and acidosis
• achlorhydria
• hyperglycemia
• hypercalcemia

Question 69

Cushing Syndrome

Answer 69

• an excess of cortisol
• causes include exogenous glucocorticoids (most common), an ACTH-secreting pituitary adenoma, ectopic ACTH secretion (small cell carcinoma of the lung), or a primary adrenal adenoma/hyperplasia/carcinoma
• presents with muscle weakness, thin extremities, moon facies, buffalo hump, truncal obesity, abdominal striae, osteoporosis, immune suppression, hypertension, diabetes, and easy bruising
• hypertension with hypokalemia and metabolic alkalosis are also common as cortisol increases the sensitivity of arterioles to sympathetic activity and directly activates aldosterone receptors
• diagnosed based on a 24-hour urine cortisol level, increased late nigh salivary cortisol level, or abnormal response to low-dose dexamethasone suppression test
• further evaluation includes measuring the ACTH level, high-dose dexamethasone suppression test, CRH stimulation test, and CT or MRI of the appropriate area
• treatment usually requires discontinuation of exogenous steroids or surgery to remove a tumor

Question 70

What is the difference between cushing syndrome and cushing disease?

Answer 70

• cushing syndrome is an excess of glucocorticoids due to any cause
• cushing disease is an excess of glucocorticoids from a pituitary adenoma

Question 71

Describe the physiologic effects of cortisol.

Answer 71

BIG FIB (catabolism)

• BP is elevated: up regulates a1 receptors on arterioles and can bind aldosterone receptors at high concentrations; generally enhances catecholamine activity
• Insulin resistance
• Gluconeogenesis, lipolysis, and proteolysis
• Fibroblast activity is diminished
• Inflammatory and Immune responses are low: reduced NF-kB and impaired neutrophil migration
• Bone formation: reduced osteoclast activity

Question 72

Why does ectopic ACTH production lead to cushing syndrome?

Answer 72

because an ACTH-secreting tumor is outside the normal negative feedback loop

Question 73

What is the most common cause of ectopic ACTH production and cushing syndrome?

Answer 73

small cell carcinomas of the lung

Question 74

Describe the presentation of cushing syndrome.

Answer 74

• presents with changes in appearance that include central obesity, moon facies, buffalo hump, purple striae on abdomen, and easy bruising
• hypertension
• diabetes
• hypogonadism with menstrual irregularity and infertility
• hirsutism or masculinization in females if the etiology contributes to androgen excess
• MSK changes like proximal muscle wasting and weakness, osteoporosis, aseptic necrosis of the femoral head
• psychiatric disturbances including depression or mania
• increased incidence of infection

Question 75

What causes of cushing syndrome lead to androgen excess?

Answer 75

• ACTH-dependent forms like pituitary adenoma, ectopic ACTH production
• iatrogenic cushing syndrome and adrenal adenomas trigger negative feedback loops that suppress androgen production by the adrenals

Question 76

Describe the ways in which we initial screen for Cushing’s syndrome.

Answer 76

low-dose dexamethasone suppression test:
- dexamethasone at night and then a serum cortisol level is obtained the next morning
- a normal individual has serum cortisol less than 5 and this finding can exclude Cushing syndrome
the other option is a 24-hour urinary free cortisol level

Question 77

Describe how Cushing syndrome is diagnosed an worked up.

Answer 77

• initial screening uses a low-dose dexamethasone suppression test or a 24-hour urinary free cortisol level
• an ACTH level is then measured to narrow down possible etiologies
• a high-dose dexamethasone suppression test differentiates between ectopic and pituitary ACTH production

Question 78

What is a high-dose dexamethasone suppression test?

Answer 78

• a test used in the evaluation of those with Cushing syndrome
• if cortisol levels decrease following administration, this is suggestive of cushing disease
• if cortisol levels remain elevated and plasma ACTH levels are high, this is indicative of an ectopic ACTH-producing tumor

Question 79

What is a CRH stimulation test?

Answer 79

• a method for differentiating pituitary from ectopic ACTH production in those with Cushing syndrome
• after CRH is administered, ACTH levels should increase in those with Cushing disease, but likely won’t change if there is ectopic ACTH secretion or an adrenal tumor which is ACTH-independent

Question 80

How are the various causes of Cushing’s syndrome differentiated?

Answer 80

• exogenous glucocorticoids: low ACTH, no imaging abnormalities, and bilateral adrenal atrophy (secondary to low ACTH)
• ACTH-secreting pituitary adenoma: high ACTH, high-dose dexamethasone suppression, pituitary adenoma may be found on imaging, bilateral adrenal growth
• ectopic-ACTH secretion: high ACTH, no response to high-dose dexamethasone suppression, imaging likely to find a lung cancer, bilateral adrenal growth
• primary adrenal adenoma: low ACTH, atrophy of the contralateral adrenal gland

Question 81

What is the rule of 10s for pheochromocytoma tumors?

Answer 81

• 10% are familial
• 10% occur in children
• 10% are bilateral
• 10% are multiple
• 10% are extra-adrenal
• 10% are malignant

Question 82

What is the most common extra-adrenal site for a pheochromocytoma?

Answer 82

the organ of Zuckerkandl located at the aortic bifurcation

Question 83

Pheochromocytoma

Answer 83

• a tumor derived from chromaffin cells of the adrenal medulla or from sympathetic ganglia when extra-adrenal, which produces catecholamines
• associated with MEN2, VHL, and neurofibromatosis type 1
• presents as episodic release of catecholamines (hypertension, headaches, palpitations, tachycardia, anxiety, and sweating)
• diagnosed by increased metanephrines and VPA (catecholamine metabolites) in urine or by elevated urine or serum epinephrine or norepinephrine levels
• treatment is preparation with an irreversible alpha blocker called phenoxybezamine and then a beta blocker (prevents hypertensive crisis during surgery) before removal
• follow the rule of 10s: 10% bilateral, 10% familial, 10% malignant, 10% located outside the medulla

Question 84

What is the difference between a pheochromocytoma that presents with elevated serum levels of epinephrine versus one that presents with elevated levels of norepinephrine?

Answer 84

non-adrenal tumors cannot methylate norepinephrine, so those that present with elevated epinephrine levels must be adrenal in origin

Question 85

Why does treatment of pheochromocytoma involve preparation with an alpha and a beta blocker?

Answer 85

• the alpha blocker is used to control blood pressure

- the beta blocker is used to decrease tachycardia

Question 86

If a patient presents with hypertension and hypokalemia, what is the presumptive diagnosis?

Answer 86

some cause of hyperaldosteronism

Question 87

Primary Hyperaldosteronism

Answer 87

• an excess of aldosterone production by the adrenals independent of any regulation by the renin-angiotensin system
• can be caused by adrenal adenoma, hyperplasia, or carcinoma
• aldosterone increases the activity of Na/K pumps in the collecting tubules and the secretion of hydrogen ions into the collecting tubules
• presenting with hypertension, headache, fatigue, polydipsia, and nocturnal polyuria as well hypokalemia and a metabolic alkalosis
• screen for based on an aldosterone to renin ratio over thirty; diagnose with a saline infusion or oral sodium loading test
• evaluate with an adrenal venous sampling for aldosterone levels to determine if there is an adrenal adenoma or hyperplasia
• treat with resection of an adrenal adenoma or spironolactone for bilateral hyperplasia

Question 88

What is the name given to an aldosterone-producing adrenal adenoma?

Answer 88

Conn syndrome

Question 89

What is a saline infusion test for those with hyperaldosteronism?

Answer 89

• a confirmatory test for primary hyperaldosteronism

- normal patients will decrease aldosterone levels in response but those with primary aldosteronism will not

Question 90

What is adrenal venous sampling?

Answer 90

a test in which the venous concentration of aldosterone is measured bilaterally in those with confirmed primary hyperaldosteronism; high levels of aldosterone on one side indicates an adenoma and high levels on both sides indicates bilateral hyperplasia

Question 91

How is secondary hyperaldosteronism distinguished from primary?

Answer 91

• secondary is associated with elevated renin levels while primary is not
• edema is seen in those with secondary but not primary hyperaldosteronism

Question 92

What tumors are associated with MEN type I, MEN type IIA, and MEN type IIB?

Answer 92

• MEN I: parathyroid hyperplasia, pancreatic islet cell tumors, pituitary tumors
• MEN IIA: medullary thyroid carcinoma, pheochromocytoma, hyperparathyroidism
• MEN IIB: mucosal neuromas, medullary thyroid carcinoma, marfanoid body habits, pheochromocytoma

Question 93

Acute Adrenal Insufficiency

Answer 93

• a sudden cortisol deficiency
• most often caused by abrupt withdrawal of glucocorticoids, treatment of Cushing syndrome, or Waterhouse-Friderichsen syndrome
• presents with weakness and shock

Question 94

Primary Adrenal Insufficiency

Answer 94

• a chronic lack of cortisol
• most commonly idiopathic in the industrialized world and secondary to TB in the developing world; other causes include adrenalectomy
• lack of cortisol leads to anorexia, n/v, vague abdominal pain, weight loss, hypoglycemia, hyperpigmentation driven by elevated ACTH
• lack of aldosterone leads to hyponatremia, hypovolemia, and hyperkalemia; presenting as hypotension, weakness, and syncope
• diagnosed based on a decreased plasma cortisol level and elevated ACTH level
• treat with daily oral glucocorticoid and daily fludrocortisone for mineralocorticoid replacement

Question 95

What causes secondary adrenal insufficiency

Answer 95

adrenal insufficiency due to long-term steroid therapy; when these patients develop a serious illness or undergo trauma, they cannot release an appropriate amount of cortisol because of chronic CRH and ACTH suppression

Question 96

What form of adrenal insufficiency is accompanied by hypoaldosteronism and why?

Answer 96

primary adrenal insufficiency only because aldosterone production is driven by the renin-angiotensin system and independent of ACTH, so secondary adrenal insufficiency doesn’t impact aldosterone production but adrenal disease will

Question 97

How do those with primary and secondary adrenal insufficiency respond to an ACTH infusion test?

Answer 97

• those with primary adrenal insufficiency show no increase in cortisol levels
• those with secondary insufficiency show no increase in cortisol levels on the first attempt because production is chronically suppressed, but when repeated 4-5 days later, the adrenals respond with increased production

Question 98

Describe the pathogenesis of primary adrenal insufficiency and it’s clinical manifestations.

Answer 98

• adrenal pathology (idiopathic or TB-induced) leads to low cortisol production
• the pituitary responds by increasing ACTH levels but this fails to elicit a response
• ACTH, however, drives MSH production and hyperpigmentation
• additionally, the adrenal failure results in low levels of aldosterone synthesis which contributes to hyponatremia, hypovolemia, and hyperkalemia

Question 99

Congenital Adrenal Hyperplasia

Answer 99

• an autosomal recessive disease
• most commonly caused by a 21-hydroxylase deficiency
• presents with low levels of cortisol and aldosterone production with a secondary increase in ACTH that drives adrenal hyperplasia
• symptoms include ambiguous genitalia or virilization in females plus signs of adrenal insufficiency including hypoglycemia
• the salt wasting form is accompanied by emesis, dehydration, hypotension, shock, hyponatremia and hyperkalemia
• diagnosed based on elevated levels of 17-hydroxyprogesterone
• treat with cortisol and mineralocorticoid replacement in addition to surgical correction of genitalia