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Last posting we discussed taking B/P’s and making a diagnosis of “HTN.” Today we’ll address when & how to identify that rare person with Secondary HTN, i.e. due to a specific illness (in contrast to plain old “Essential HTN”).
Tests to Diagnose Specific Causes of Secondary Hypertension** Hypo- / Hyperthyroidism → TSH ** Renal Disease → Creatinine; Proteinuria; Renal Ultrasound ** 1° Aldosteronism → Ratio of plasma Aldosterone-to-Renin Activity ** Medications → History ** Hyperparathyroidism → Serum calcium (and albumin); serum PTH ** Pheochromocytoma → 24 hr. Urine for Catecholamines, Metanephrines ** Cushing’s Syndrome → 24 hr. Urine for Cortisol ** Obstructive Sleep Apnea → Polysomnogram ** Renal Artery Stenosis → Duplex Ultrasound; MR / CT Angiogram ** Aortic Insufficiency → Cardiac auscultation; Echocardiogram ** Coarctation of Aorta → Echocardiogram; MR / CT Angiogram
The above list is a panorama, not a directive for shotgun testing. Once we diagnose “HTN,” we screen patients with simple tests for the above conditions. If we find a clue suggesting a secondary cause, then we do the specific work-up as noted above.
Tests to Perform on Everyone with Hypertension1. History, inquiring specifically about:
- Dx of HTN <30 y.o. → r/o 1° Aldosteronism, Coarctation of Aorta, Renal Disease
- Paroxysms of severe H/A + palpitations + diaphoresis → r/o Pheochromocytoma
- Excessive daytime drowsiness → r/o Sleep Apnea (if also snores)
- Meds (chronic): esp. Estrogens, NSAIDs, Anti-depressants, Decongestants, Stimulants
- Cushingoid Features → r/o Cushing’s
- Diastolic murmur at L sternal border → r/o Aortic Insufficiency
- Abdominal Bruit: systolic + diastolic → Renal Artery Stenosis
- Pulses (palpate brachial & femoral pulses simultaneously): Delayed femoral → r/o Coarctation of Aorta
- Optic Fundoscopy → abnormalities suggest severe HTN (r/o lots of causes)
- ↑ Creatinine suggests Renal Disease
- ↑ Calcium suggests Hyperparathyroidism
- ↓ Potassium → r/o 1° Aldosteronism
- ↑ Glucose → r/o Cushing’s if stigmata on PE (otherwise, just Dx diabetes)
4. TSH: ↑ = Hypothyroidism, ↓ = Hyperthyroidism5. Urinalysis:
- Proteinuria suggests underlying Renal Disease
- Proteinuria + Hematuria → Glomerulonephritis
- Red cell casts → Gomerulonephritis
A Few Words About Some of the Above Tests:
** Palpating Pulses — Coarctation of the Aorta sometimes presents in adulthood (untreated, 75% of persons die by 45 y.o.). As part of initial PE, with patient supine, palpate the right radial artery & femoral artery simultaneously. Pulses should occur simultaneously, and feel equal. If the femoral pulse is either delayed or of decreased amplitude, work up Coarctation with a Chest MR Angiogram (get an Echo too, but it’s not sensitive as in young children; get a CT angio if there’s a contraindication to an MRI).
** Excessive Daytime Drowsiness — Ask patients if they nod off frequently in the day (not simple sleepiness or desire to nap, but frank nodding-off). If a patient endorses this, inquire about snoring, which is the sine qua non for Obstructive Sleep Apnea (OSA) (lit. “without which not”). Half the world snores, but if someone doesn’t, they can’t have OSA.
Don’t ask about frequent awakenings or insomnia. OSA patients may perceive having slept well through the night; conversely, anyone who sleeps well may recall physiologic awakenings of REM cycles. However, bed partners of people with OSA will describe the patient’s apnea episodes & flailing while asleep.
Anybody with excessive daytime drowsiness deserves a sleep study (polysomnogram). The typical patient is obese, but not necessarily.
** Abdominal Bruit — Lots of people have systolic bruits, which are incidental & very non-specific. However, a pt. with HTN who has both systolic and diastolic bruits undoubtedly has Renal Artery Stenosis. See below for work-up.
** Proteinuria — Large (4+) proteinuria on dipstick, with negative leukocyte esterase & nitrites (i.e. not due to infection), warrants a 24-hr.-Urine for Protein and also a Renal Ultrasound. Certainly repeat the basic U/A first. Give your own specific instructions on 24-hr. collection, since errors abound (clink link for ad nauseum discussion of 24-hr. Urine Collections).
Proteinuria of 2+ or 3+ probably also warrant a 24-hr urine collection, and referral to nephrology if results are >1 gram and collection seems valid. Some nephrologists might pursue a renal biopsy for results of 2-3 grams (everyone does for results >4 g). This is of course a little bit of chicken-and-egg: does proteinuria imply renal disease as a cause of HTN, or does it mean the HTN is causing renal problems? Nephrology should help sort it out.
** Hypercalcemia — Don’t diagnose this without checking a simultaneous serum albumin. Consider the average albumin as 4.0 g/dL. For every 1.0 change in albumin, the calcium will artifactually change 0.8 mg/dL in same direction. For example, a patient’s calcium is 11.5, while normal is <10.8 (lab normals vary a lot). The Ca++ sounds high; but if the albumin is 5.0, subtract 0.8 from the Ca++ and you’re back down to 10.7 (normal).
Of course, if you Dx “Hypercalcemia,” you have to find the cause:
- Order a Parathyroid Hormone (PTH) for Hyperparathyroidism (cause of HTN)
- Consider a “PTH-related peptide” (PTH-rp) that’s secreted ectopically by neoplasms.
- A high Alkaline Phosphatase + Hypercalcemia mandates a bone scan for pathologic fracture (assuming the Alk Phos isn’t due to liver disease; see last section of posting on Chronic Hepatitis).
- HyperCa++ plus Anemia (normocytic) plus ↑ Creatinine strongly suggests Multiple Myeloma (order a Serum Protein Electrophoresis [SPEP]).
- Other causes of HyperCa++ include Sarcoidosis, Hyperthyroidism, & Lithium therapy.
** Fundoscopic Exam — Examine the optic fundi when you first diagnose HTN, to get an idea of how long / severe blood pressure has been elevated. Most of the time they’ll be normal. But if you see any abnormalities, even just Narrow Arterioles or some A-V Nicking, be impressed. If the patient is older, expect other co-morbidities of long-standing atherosclerosis like coronary artery disease, left ventricular dysfunction, aortic aneurysms. If they’re youngish, work-up the obscure secondary causes of HTN.
I saw a new 39-y.o. patient who’d gone to an ER the day before for headache; her paperwork noted a B/P of >200. I rechecked, only 130/80. So I examined her fundi, & found florid hypertensive retinopathy, everything short of papilledema [only time in my life I’ve ever seen “copper wiring;” looked just like the pictures]. I was sure she had a Pheo — nothing else would give intermittent HTN so severe so young. Never got to find out; her insurance kicked in & she transferred care the next week.
Extra Work-Up for Suspected Secondary Hypertension
The tests listed above are simple and basic: History, brief targeted Physical Exam, Chemistry Panel, TSH, and U/A. But we do need to work up the obscure etiologies on occasion. Certainly, if any clues to secondary causes emerge from our initial inquiry, order specific diagnostics as per our Table above.
The following persons with HTN deserve more extensive testing even in the absence of clues:
- HTN initially diagnosed <30 y.o.
- Recalcitrant HTN (uncontrolled on 4 meds)
- Abnormal Optic Fundi (unless long-term uncontrolled HTN)
Order the following in addition to standard tests:
1. Renal Ultrasound:
- For various intrinsic renal diseases (Polycystic Kidneys, Atrophic Kidneys, etc.)
2. Aldosterone : Renin Activity (ratio)
- For 1° Aldosteronism
- Order single test, i.e. Ratio (lab will give normal ranges)
- Don’t order Aldosterone & Renin separately
- 50% of pts with 1° Aldosteronism have low K+ (so 50% don’t)
3. 24-hr. Urine for Catecholamines & Metanephrines
- For Pheochromocytoma
- Minimally-elevated abnormal aren’t significant
- Give exact instructions on collection (see 24-hr. Urine Collections)
- Discontinue meds that interfere with results x2 weeks prior to collection: Tricyclics, Amphetamines, Alcohol, Acetaminophen, Decongestants, Levodopa, Buspirone
- For Cushing’s Syndrome
- Give exact instructions on collection (see 24-hr. Urine Collections)
Possible Renal Artery Stenosis (RAS)
Renal Artery Stenosis (also called “renovascular hypertension”) is a not-uncommon cause of refractory HTN. It frequently accompanies other end-organ damage from generalized atherosclerosis. Also suspect RAS if any of the following:
- > 50 y.o. and loss of previously-controlled mild HTN
- Creatinine ↑ 50% at 3-5 days after beginning ACE-Inhibitor (or increasing dose)
- Paroxysmal episodes of pulmonary edema
Order a “Duplex Ultrasound of Abdomen for RAS.” This is only useful if the operator is experienced, and the center ideally performs high-volume testing. Better tests, such as CT- or MR-Angiograms, can’t be done if renal function is abnormal.
Then there’s another problem: it’s unclear if surgical correction improves major outcomes, in comparison to risk of operative complications (not insignificant!). Renal artery stents seem definitively out; no help, nothing but complications. On the other hand, intensive medical therapy may 1) not be adequate, and 2) exacerbate renal dysfunction. Bilateral RAS usually warrants surgery more than unilateral.
If in doubt, let Nephrology determine the work-up.
The vast, vast, vast majority of hypertensive patients have “Essential HTN.” Still, perform a number of simple screening exams at time of diagnosis. Order extra work-up if a) initial tests generated specific clues (see Table above); or b) in special circumstances (Table below).
Summary Work-Up for Hypertension
For Everyone w/ HTN
For These Patients
Suspect RAS If:
That’s it for Hypertension. In light of the holidays, next posting may be delayed 3-4 more weeks. Wishing you all a diagnostic coup of whatever sort for the New Year.