Endocrine Flashcards
(99 cards)
1
Q
Describe the pathogenesis of T1DM.
A
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
2
Q
In those with T1DM, what percentage of beta islet cells must be destroyed before the onset of disease?
A
about 90%
3
Q
Describe the risk factors and pathogenesis of T2DM.
A
- 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
4
Q
Why is age a risk factor for T2DM?
A
because as one ages, their endogenous insulin production decreases
5
Q
Why do T2DM patients eventually have low levels of insulin production?
A
because as hyperglycemia develops, beta islet cells eventually become desensitized to glucose
6
Q
Which type of diabetes has a stronger genetic component?
A
T1DM has a 50% concordance rate between identical twins while T2DM has a 90% concordance rate
7
Q
Describe the Somogyi effect and how it should be managed?
A
- 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
8
Q
Describe the Dawn phenomenon.
A
- a cause of morning hyperglycemia in some diabetics
- attributed to nocturnal secretion of growth hormone, which antagonizes insulin and contributes to hyperglycemia
9
Q
How is a diagnosis of diabetes made?
A
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
10
Q
What screening recommendation is in place for diabetes and what is the preferred method?
A
- all adults over 45 should be screened every 3 years
- the preferred test is a fasting plasma glucose
11
Q
How should a clinician respond to a screening fasting plasma glucose of 116?
A
patients with a glucose level between 100-126 should undergo a 2-hr, 75g glucose tolerance test for further screening
12
Q
Describe the symptoms of diabetes.
A
- polyuria and polydypsia
- fatigue and weight loss
- blurred vision
- fungal infections
- numbness, tingling of the hands and feet
13
Q
What are the general principles for treating outpatient diabetics?
A
- 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
14
Q
What is the goal HbA1c in diabetic patients?
A
less than 7 is associated with a marked reduction in risk for microvascular complications
15
Q
How much insulin do most T1DM patients require?
A
0.5-1.0 units/kg/day split 50/50 between long-acting forms and regular forms
16
Q
What are the typical blood sugar goals for diabetic patients?
A
fasting blood glucose less than 130 and peak postprandial glucose less than 180
17
Q
What are the typical blood sugar goals for diabetic patients?
A
fasting blood glucose less than 130 and peak postprandial glucose less than 180
18
Q
Describe the macrovascular complications of diabetes and the practical consequences of these.
A
- 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
19
Q
What is the most common cause of death in diabetic patients?
A
coronary artery disease secondary to accelerated atherosclerosis
20
Q
Describe diabetic nephropathy.
A
- 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
21
Q
Why is the diabetic BP goal lower than in the general population of hypertensives?
A
it is 130/80 because hypertension will accelerate macrovascular atherosclerosis and the progression from diabetic nephropathy to ESRD
22
Q
How should diabetic patients with microalbuminuria be managed?
A
- 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
23
Q
How should diabetic patients who require radiocontrast be prepped?
A
they should be generously hydrated before and their metformin should be held for at least 48 hours after to reduce the risk of AKI
24
Q
Describe the pathogenesis of diabetic nephropathy.
A
- 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
25
Describe non-proliferative diabetic retinopathy
- 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
26
Describe proliferative diabetic retinopathy.
- 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)
27
Describe the peripheral neuropathy found in diabetics.
- 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
28
What cranial nerve complications arise in those with diabetes?
- 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
29
What is mononeuropathy?
- 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
30
Diabetic neuropathy can take what forms?
- 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
31
How does autonomic neuropathy present in diabetics?
- impotence is the most common presentation
- neurogenic bladder
- gastroparesis
- alternating constipation and diarrhea
- postural hypotension
32
What is charcot foot?
a complication of diabetes whereby nerve injury prevents patients from feeling pain, so repetitive injuries go unnoticed and ultimately remain unhealed
33
Why are diabetics more susceptible to infection?
- wound healing is impaired by reduced blood supply and neuropathy
- WBC functioning is also impaired
34
What are the complications of chronic diabetes?
- 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
35
Describe the pathogenesis of DKA.
- insulin deficiency leads to hyperglycemia, which promotes osmotic diuresis and volume depletion
- glucagon excess promotes ketone formation and acidosis
36
DKA
- 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
37
Why would someone in DKA not have ketones in their serum or urine?
- 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
38
What happens to electrolyte levels in those with DKA?
- hyponatremia although total body sodium is normal
- hyperkalemia even though total body potassium is low
- typically, phosphate and magnesium levels are low
39
What is the sodium correction factor in those with diabetes?
serum sodium is 1.6 mEq/L higher for every 100 mg/dL increase in glucose
40
What is the treatment for DKA?
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
41
What is the most severe complication that needs to be avoided during the treatment of DKA?
cerebral edema which can occur if glucose levels decrease too quickly
42
Describe and explain the pathogenesis of hyperosmolar hyperglycemic nonketotic syndrome.
- 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
43
Hyperosmolar Hyperglycemic Nonketotic Syndrome
- 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
44
Describe the treatment for hyperosmolar hyperglycemic nonketotic syndrome.
- 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
45
How is BMI calculated?
as weight in kg/height in meters squared
46
If you calculate an individual's BMI and determine that they are obese, what should your next step be?
obtain a waist circumference to asses their abdominal obesity, which is a great risk factor for medical conditions
47
What is the threshold at which waist circumference corresponds to an increased cardio metabolic risk?
circumference over 40 inches in men and 35 in women
48
Describe the mechanism of the following obesity medications:
- orlistat
- lorcaserin
- phentermine and topiramate
- 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
49
What is the most effective treatment for obesity?
bariatric surgery
50
Who is a candidate for bariatric surgery?
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
51
Which organ is most at risk during periods of hypoglycemia?
the brain, which isn't capable of utilizing free fatty acids as an energy source
52
Describe changes in hormone levels that occur as blood glucose drops.
- 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
53
At what point does hypoglycemia become symptomatic?
around 50 mg/dL
54
What are the possible causes of hypoglycemia?
- drug induced (i.e. too much insulin or sulfonylurea)
- insulinoma
- ethanol ingestion
- idiopathic
- adrenal insufficiency, liver failure, critical illness
- disorders of carbohydrate metabolism
55
How does ethanol ingestion contribute to hypoglycemia?
because poor nutrition leads to decreased glycogen and the metabolism of alcohol consumes NAD levels
56
If a patient presents with hypoglycemia of unknown cause, how can you eliminate drug-induced hypoglycemia?
- measure plasma insulin level
- measure C-peptide
- look for anti-insulin antibodies
- measure a plasma and a urine sulfonylurea level
57
What are the clinical features of hypoglycemia?
- 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
58
How does the presentation of hypoglycemia often differ in patients with diabetes and why?
- 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
59
How should hypoglycemia be treated?
- 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
60
What is important to remember in the treatment of ethanol-induced hypoglycemia?
these patients must be given thiamine before administering glucose to avoid Wernicke's encephalopathy
61
Hypoglycemia
- 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
62
Insulinoma
- 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
63
What is whipple's triad?
- 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
64
Zollinger-Ellison Syndrome
- 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
65
What is normal basal gastric acid output and what level is indicative of a gastrinoma?
normal is less than 10 mEq/hr and a level over 15 mEq/hr is consistent with zollinger-ellison syndrome
66
What is the typical presentation of a glucagonoma?
- 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
67
What is the typical presentation of a somatostatinoma?
a classic triad of gallstones, diabetes, and steatorrhea
68
What is the typical presentation of a VIPoma?
- watery diarrhea leading to dehydration, hypokalemia, and acidosis
- achlorhydria
- hyperglycemia
- hypercalcemia
69
Cushing Syndrome
- 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
70
What is the difference between cushing syndrome and cushing disease?
- cushing syndrome is an excess of glucocorticoids due to any cause
- cushing disease is an excess of glucocorticoids from a pituitary adenoma
71
Describe the physiologic effects of cortisol.
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
72
Why does ectopic ACTH production lead to cushing syndrome?
because an ACTH-secreting tumor is outside the normal negative feedback loop
73
What is the most common cause of ectopic ACTH production and cushing syndrome?
small cell carcinomas of the lung
74
Describe the presentation of cushing syndrome.
- 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
75
What causes of cushing syndrome lead to androgen excess?
- 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
76
Describe the ways in which we initial screen for Cushing's syndrome.
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
77
Describe how Cushing syndrome is diagnosed an worked up.
- 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
78
What is a high-dose dexamethasone suppression test?
- 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
79
What is a CRH stimulation test?
- 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
80
How are the various causes of Cushing's syndrome differentiated?
- 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
81
What is the rule of 10s for pheochromocytoma tumors?
- 10% are familial
- 10% occur in children
- 10% are bilateral
- 10% are multiple
- 10% are extra-adrenal
- 10% are malignant
82
What is the most common extra-adrenal site for a pheochromocytoma?
the organ of Zuckerkandl located at the aortic bifurcation
83
Pheochromocytoma
- 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
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?
non-adrenal tumors cannot methylate norepinephrine, so those that present with elevated epinephrine levels must be adrenal in origin
85
Why does treatment of pheochromocytoma involve preparation with an alpha and a beta blocker?
- the alpha blocker is used to control blood pressure
| - the beta blocker is used to decrease tachycardia
86
If a patient presents with hypertension and hypokalemia, what is the presumptive diagnosis?
some cause of hyperaldosteronism
87
Primary Hyperaldosteronism
- 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
88
What is the name given to an aldosterone-producing adrenal adenoma?
Conn syndrome
89
What is a saline infusion test for those with hyperaldosteronism?
- a confirmatory test for primary hyperaldosteronism
| - normal patients will decrease aldosterone levels in response but those with primary aldosteronism will not
90
What is adrenal venous sampling?
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
91
How is secondary hyperaldosteronism distinguished from primary?
- secondary is associated with elevated renin levels while primary is not
- edema is seen in those with secondary but not primary hyperaldosteronism
92
What tumors are associated with MEN type I, MEN type IIA, and MEN type IIB?
- 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
93
Acute Adrenal Insufficiency
- 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
94
Primary Adrenal Insufficiency
- 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
95
What causes secondary adrenal insufficiency
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
96
What form of adrenal insufficiency is accompanied by hypoaldosteronism and why?
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
97
How do those with primary and secondary adrenal insufficiency respond to an ACTH infusion test?
- 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
98
Describe the pathogenesis of primary adrenal insufficiency and it's clinical manifestations.
- 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
99
Congenital Adrenal Hyperplasia
- 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
