Ch. 10 Intermittent Episodes of Sweating, Palpitations, and HTN Flashcards
A 34 y/o woman presents with cc of what she calls “rushes,” intermittent episodes of sweating, headaches, and palpitations lasting for a few minutes and occurring sporadically every few days. These episodes can occur at any time of day and have sometimes awakened her from sleep. She notes that exercise may provoke her symptoms. She has no significant PMH. Her physical exam is remarkable only for newly discovered HTN, with a BP of 165/100 mmHg. Her biochemical workup revelas an elevated 24 hr urine metanephrine (1,163 mcg/day; normal <400). A dedicated adrenal-protocol CT scan shows a 4-cm mass in the R adrenal gland with central cystic change.
What is the most likely dx?
Catecholamine surge 2/2 Pheochromocytoma
In a pt with newly discovered HTN coupled with reports of episodes where she experiences sweating, flushing, and palpitations lasting for a few minutes, pheochromocytoma = most likely dx.
This is further supported by her biochemical workup confirming elevated urine metanephrine levels and CT scan showing a mass in her R adrenal gland. Additionally, she has:
orthostatic hypotension (adrenergic receptors exposed to large amounts of catecholamine become desensitized over time.. normal baroreceptor reflex which causes vasoconstriction upon standing from supine position may be compromised)
elevated hematocrit and serum glucose (due primarily to catecholamine stimulation of lipolysis (breakdown of stored fat) leading to high levels of free fatty acids and the subsequent inhibition of glucose uptake by muscle cells)
Pheochromocytoma
Pathophysiology
5 P’s
Genetic association:
Pathophysiology
- Catecholamine-producing tumor that is derived from chromaffin cells in the adrenal medulla or sympathetic ganglia
5 P’s:
- Pressure (HTN) **most common sign**
- Pain (headache)
- Perspiration (episodic)
- Palpitation
- Pallor
Genetic association:
- MEN 2
- NF 1
- VHL
Carcinoid Syndrome
Pathophysiology
Symptoms
Triggers
Pathophysiology
- Excess serotonin release
- Malignant proliferation from neuroendocrine cells
- Most commonly arise from small bowel
- Need liver metastasis or extra-GI tumor for syndrome
Symptoms:
- Bronchospasm
- Diarrhea
- Flushing of skin
- Right-sided heart disease
Triggers
- Alcohol
- Emotional stress
Fibromuscular Dysplasia
Pathophysiology
Presentation
Pathophysiology
Non-atherosclerotic, non-inflammatory disease of the blood vessels that causes abnormal growth within the wall of an artery
Most commonly affects renal & carotid arteries
(Renal artery has “string of beads” appearance due to medial thinning alternating with stenosis)
Presentation:
Severe HTN in young female
Insulinoma
Origin & Association
Malignant or benign?
Whipple’s Triad
Origin & Association:
- Tumor of pancreatic beta cells
- MEN 1
- 90% benign
Whipple’s Triad:
- Hypoglycemia
- Symptoms of hypoglycemia (tremulousness, palpitations, perspiration, and anxiety)
- Improvement after carbohydrate load
Coarctation of the aorta
Presentation:
Association:
Presentation:
- HTN in the arms but not the legs
- Weak femoral and pedal pulses
Association
- Turner syndrome
- Aortic valve pathology
What is the differential dx for surgically correctable HTN?
95% of HTN cases are due to essential HTN
5% due to surgically correctable causes:
- pheochromocytoma,
- adrenal adenomas that produce cortisol or aldosterone
- renal artery fibromuscular dysplasia
- aortic coarctation
Effects of normal and excessive amounts of catecholamine
Receptor: a1, a2, b1, b2
a1
- smooth muscle contraction, gluconeogenesis, glycogenolysis
- HTN, hyperglycemia
a2
- smooth muscle contraction, platelet aggregation
- pallor
b1
- chronotropic, inotropic, sweat glands
- tachycardia, sweating
b2
- smooth muscle relaxation
- hypotension
Pheochromocytoma
Rule of 10’s and is it still true?
- 10% bilateral
- 10% extra-adrenal
- 10% familial
- 10% multifocal
- 10% malignant
Rule of 10’s disproved in 2000 after a series of reports described germline mutations causing pheochromocytoma
MEN 2A (gene mutation: RET) - 50% risk
MEN 2B (gene mutation: RET) - 50% risk
NF1 (gene mutation: NF1, negative regulator of ras oncogene pathway) - 5% risk
VHL (gene mutation: VHL, tumor suppressor) - 20% risk
What are the predominant catecholamines in adrenal and extra-adrenal tumors?
Combination of epinephrine and norepinephrine, with norepinephrine being the predominant catecholamine
About 30% produce only norepinephrine
Dopamine-secreting tumors are rare and usually found in paragangliomas (extra-adrenal).
Do not usually present with HTN –> instead, these pts have watery diarrhea which reflects effects that dopamine has on GI tract –> additionally, these tumors can have co-secretions with VIP which can exacerbate watery diarrhea
Phenylethanolamine N-methyltransferase, the enzyme that converts NE to epi, is primarily present in the adrenal medulla and organ of Zuckerkandl. Therefore, pheochromocytomas outside of these locations produce little or no epi
The adrenal medulla is composed of ___________-derived chromaffin cells.
Neural crest
Why do patients with pheochromocytoma have elevated hematocrit levels? hyperglycemia?
The chronic alpha constriction in patients with pheochromocytoma leads to volume depletion and hemoconcentration.
Additionally, paraneoplastic production of EPO leading to high hematocrit levels may be associated with pheochromocytoma
Catecholamines = potent stimulators of hepatic glucose production (epi) + inhibitors of insulin secretion and action (norepi)
What is the gold standard lab test to help make dx of pheochromocytoma?
24 hr urine testing of catecholamine levels and their metabolites
Catecholamines:
- Epi
- NE
- Dopamine
Metabolites:
- Metanephrine
- Normetanephrine
- Vanillylmandelic acid
High specificity (98%) but lower sensitivity (90%) so generally performed twice
What medications can interfere with urine or plasma testing… causing a false elevation of catecholamines?
- Beta blockers
- Decongestants
- Antidepressants (notably TCAs)
- MAO-I
- Venlafaxine
- Antipsychotics (notably clozapine)
Whenever possible, interfering meds should be discontinued for 2 weeks prior to biochemical testing for pheochromocytoma
Algorithm for dx and tx of pheochromocytoma
Clinical suspicion –> 24 hr urine catecholamines + metanephrines –> if > 2x upper limit of normal –> CT or MRI of abdomen
If imaging (+) –> increase intravascular volume with/ pre-op alpha blockade (phenoxybenzamine) to allow reduction in catecholamine-induced vasoconstriction and resulting volume depletion; followed by possible beta blockade for 2 weeks –> SURGICAL RESECTION
If imaging (-) –> additional imaging: MIBG or (18)F-Dopa-PET
I-MIBG = norepi precursor that is taken up by chromaffin cells, and is highly specific for pheochromocytoma (may be useful in cases of suspected multifocal or extra-adrenal disease)
