Nyenwe - Endocrine HTN Flashcards
What 3 endocrine conditions are associated with hypertension?
- Pheochromocytoma
- Mineralocorticoid excess: 1o aldosteronism
- Glucocorticoid excess: Cushing
- Others: acromegaly, DM, obesity, CAH, estrogen-induced or pregnancy-induced HTN, renin-secreting tumors, hypo/hyperthyroidism, Liddle syndrome
Pheochromocytoma
-
Catecholamine-secreting tumor of chromaffin cells of adrenal medulla (directly innervated by SYM nervous system via Ach nicotinic receptors)
1. Paragangliomas (10%) when they arise from sympathetic ganglia (similar presentation/tx) - HTN
- Uncommon, but: 1) curable, 2) lethal paroxysms, 3) malignant potential (10%), 4) clue to wider problem, i.e., a familial syndrome (so not an “end of the road” diagnosis)
What familial syndroms are associated with pheochromocytomas?
- Usually autosomal dominant: implications for family members
- MEN-2A: medullary thyroid carcinoma + hyperPTH
- MEN-2B: medullary thyroid carcinoma + multiple mucosal neuromas
- Familial pheochromocytoma w/o assoc disorder
- VHL
- Neurofibromatosis
What is the sequence from tyrosine to epinephrine?
- Tyrosine
- Dopa
- Dopamine
- NE
- Epinephrine
Why are catecholamine metabolites measured for pheochromocytoma dx? What are they?
- Metabolites are more stable than the compounds themselves, so they are typically measured to make the diagnosis
- Epi/NE to metanephrine/normetanephrine -> VMA
1. Can measure metanephrine in urine or plasma, but urine tends to have more specificity (fewer false positives) - Dopamine -> HVA
How is pheochromocytoma diagnosed?
- Clinical suspicion: headache, HTN, palpitations, diaphoresis
-
Biochemical confirmation
1. Blood: acute episodes, or high BP
2. Urine: metanephrines, catecholamines (should be twice the normal level in 24-hr sample) -
Anatomical localization (i.e., pheo or paraganglioma) via imaging:
1. CT, MRI
2. 131I-MIBG
What are the clinical and metabolic features of pheochromocytoma?
- Paroxysmal (sudden) symptoms: headache, diaphoresis, palpitations
1. May be precipitated by variety of stimuli: positional changes, emo stress, abdominal pressure on tumor, medications, etc. - Labile or paroxysmal HTN
- Family hx of pheochromocytoma
- Metabolic features:
1. Hypercatabolism: INC metabolic rate, profuse sweating, weight loss
2. Hyperglycemia: catecholamine stimulation of hepatic glucose production and INH of insulin secretion and action
What are the vascular/hematological manifestations of pheo?
- Orthostatic hypotension due to catecholamine-induced vasoconstriction and plasma contraction
- Elevated hematocrit: plasma volume contraction and hemoconcentration
- Very rarely: polycythemia from paraneoplastic production of erythropoietin
What 4 symptoms are key to pheo presentation?
- Headache
- Sweating
- Palpitations
- HTN
What are the symptoms of pheo in paroxysmal attacks?
- Headache, sweating, palpitations
- Pallor, nausea, tremor
- Anxiety, abdominal pain, chest pain
- Weakness, dyspnea, weight loss
- Flushing, visual disturbance
How is pheo treated?
- Pre-op: alpha (+/- beta) blockade (can only use beta-blockers after full alpha blockade), fluids (normal saline, if volume contracted)
- Intra-op: IV agents, fluids, other sites
- Post-op: fluids, pressors
34-y/o man w/episodes of palpitations and severe, pounding headache, usually lasting <30 min. No hx of hypertension or other medical problems. BP is 160/95 and HR 78/min; otherwise exam is normal. Plasma potassium is 4.4 mM.
Disorder? Diagnostic tests? Pathology?
- Catecholamine secretion from a pheo or paraganglioma
- DIAGNOSIS: can measure metanephrines in the urine/plasma (urine more specific; fewer false +’s)
1. 24-hr urine: NE way high, Epi not high -> it is possible for tumor to only make NE - PATHO: tumors -> mostly unilateral, but bilateral in 10% of cases
- Not everyone with HTN should be tested for this bc it is RARE
- Imaging attached
What do mineralocorticoids do?
- Stimulate distal renal tubules to reabsorb Na+ from tubular fluid and excrete K+ and H+
- INC NA+ and K+ channels in luminal membrane of tubular cells, and synthesis of NA+/K+ ATPase that generates gradients that drive ion mvmt
- INC ECF volume by INC amt of Na+ in body, and INC BP due to greater intravascular volume and INC arteriolar resistance
- Lower plasma K+ levels, and INC plasma pH
What happens in mineralocorticoid excess? Counter-regulatory mechs?
- Causes HTN and hypokalemic alkalosis
- Hypernatremia and edema do NOT occur
1. Plasma Na+ only INC slightly (and usually stays normal) bc regulated by ADH and thirst that control water balance -> dilute plasma to prevent hyper-osmolarity
2. ECF expansion stops before edema devo, in part bc ANP levels rise, limiting Na+ retention - Aldosterone secretion regulated by volume of ECF
30-y/o man with T1D found unconscious and diaphoretic in home. What is best course of action?
Give 1mg glucagon subcu, but once they are awake, you will need to feed them because they have used up the glycogen stores in the liver (and you do not want them to get hypoglycemic again)
What would glucose, insulin, and C-peptide look like in a case of sulfonylurea-induced hypoglycemia?
Low glucose, high insulin, high C-peptide
What cross-reactivity is possible with the mineralocorticoid receptor?
- Activated by cortisol AND aldosterone, but 11-beta hydroxysteroid dehydrogenase enzyme w/receptor in renal tubule: cortisol -> inactive cortisone
1. Hereditary defects/drug INH of this enzyme produces syndrome of apparent mineralocorticoid excess due to receptor activation by normal levels of cortisol
2. Licorice (candy, tobacco) metabolite (glycyrrhetinic acid) INH this enzyme, yielding mineralocorticoid excess - Severe cortisol excess (e.g., in Cushing) can cause HTN and hypokalemia (mineralocorticoid effects)
- 11-deoxycorticosterone, an aldosterone precursor, is also a mineralocorticoid (remember - 11-beta deficiency in CAH still has HTN)
Where is renin made?
Macula densa cells of the JG apparatus in the kidney
Describe the pathway from prorenin to Angiotensin II. What are the final results?
- INC aldosterone synthesis and secretion
- INC constriction of vascular smooth muscle
- INC release of Epi and NE from adrenal medulla
- INC central SYM outflow and NE release
- INC release of vasopressin (ADH)
Appreciate this.
Good job!
47-y/o woman referred bc of poorly controlled HTN. She has leg cramps and polyuria, but no episodes of headache, sweating or palpitations. There is no family history of hypertension.
She is not obese. HR is 78/min and BP 160/98; the exam is otherwise normal. Plasma potassium: 2.5.
Which endocrine cause of HTN is most likely in this pt? Tests? Major causes of this syndrome?
- Hyperaldo due to low K; also expect alkalosis
- Diagnosis can be made via comparison of plasma aldo/renin and saline test; in this pt:
1. Plasma aldo 25 ng/dL, plasma renin <0.5 ng/ml/hr
2. Pt supine, 2L normal saline infused IV over 4 hrs -> plasma aldo at end of infusion 20 ng/dL - Major causes of this syndrome:
1. Aldosterone-producing adenoma
2. Bilateral adrenal hyperplasia
a. Can distinguish b/t these first 2 via AVS (adrenal veinous sampling) or imaging (abdominal CT shows 2cm mass in L adrenal)
3. Glucocorticoid-suppressible aldosteronism
4. Adrenal carcinoma
How dangerous is insulin anyways?
- According to this study, it is one of the 4 meds implicated in 70% of hospitalizations for adverse drug events in older US adults
What has CBG shown us about the dangers of hypoglycemia?
-
Alarming rate of asymptomatic hypoglycemia measured by continuous glucose monitoring
1. Capillary BG < 50 mg/dl occurs ~10% of time
2. 2 symptomatic hypoglycemia episodes/wk during intensive Rx
3. Body “gets used to” hypoglycemia, no longer manifesting the clinical signs and symptoms (>50% of diabetics in one trial) - Severe hypoglycemia is associated with a 2.5-fold increased risk of 5-year mortality
1. Accounts for 5-10% diabetes deaths, making it more dangerous than hyperglycemia
What are the progressive body changes and symptoms of hypoglycemia as BG DEC?
-
Neurogenic: sweating, palpitations, hunger, nervousness, tremulousness
1. Some ppl may not be able to mount the “protective” neurogenic symptoms that are “food-seeking,” and may present with coma or death -> lower your glucose goes, the more likelihood of neuroglycopenic symptoms - Neuroglycopenic: impaired concentration, tingling, dizziness/faintness, blurred vision
- Severe neuroglycopenic: seizure, coma, death
- Attached image is why 70 is the threshold
What are the conventional risk factors for hypoglycemia in T1D?
- Inadequate caloric consumption: skipped or delayed meals, malnutrition, intercurrent illness
- INC insulin sensitivity: weight loss, exercise, medications (i.e., altered insulin dose), improved fitness
- Impaired glucose production: alcohol intake (can INH gluconeogenesis), liver disease, renal failure
- Other risk factors in attached image
At what BG are people at INC risk of mortality?
- Both HIGH and LOW: both hypo- and hyperglycemia are dangerous
- This graph is for mean glucose and in-hospital mortality in patients with AMI
Why is this chart important?
- OR for 5-year mortality highest in diabetic patients with hypoglycemia
- Male sex and HbA1C also risk factors here
How can hypoglycemia cause an acquired long QT syndrome?
- INC sympathetic activity reduces serum K+, and promotes Ca2+ influx
- Insulin lowers serum K+, reduces K+ efflux, and prolongs cardiac repolarization
- Hypoglycemia reduces HERG channel conduction, which mediates K+ efflux
- REMEMBER: in cardiac action potential, Na+ in (depolarization), K+/Cl- out (slight repolarization), Ca2+ in/K+ out (plateau), then K+ out (repolarization)
What does this graph show you?
- Lower the A1C (greater control of diabetes), the more risk of hypoglycemia
- Another representative graph is attached here, so this must be a thing
What is the syndrome of hypoglycemia associated autonomic failure (HAAF)?
- Recurrent hypoglycemia: results in down-grading of response -> if you have 1, more likely to have more bc body’s ability to respond diminished
- Hypoglycemia unawareness: autonomic warning signs become impaired
- Defective counterregulation
How does a prior episode of hypoglycemia affect the body’s response in subsequent episodes?
- One prior episode of hypoglycemia blunts the epinephrine response in a subsequent episode
- Also blunts the neurogenic and neuroglycopenic symptoms (by as much as 50%, in some cases)
- Insulin levels on the bottom left
How do you treat hypoglycemia in patients with diabetes (image)?
Appreciate this.
Good job!
