3. Overview
“ Secondary” HTN accounts for ~5-10%
of other cases and represents potentially
curable disease
Often overlooked and underscreened
Controversy over screening and
treatment in some cases
4. Overview
Testing for 2ry HTN can be expensive and requires high index of
clinical suspicion.
General principles:
New onset HTN if <30 or >50 years of age
HTN refractory to medical Rx (>3-4 meds)
Specific clinical/lab features typical for dz :
5.
6.
7.
8. Routine Laboratory Tests
1. Urinalysis
2. Complete blood count
3. Blood chemistry (potassium, sodium and
creatinine)
4. Fasting glucose
5. Fasting lipid profile
6. Standard 12-leads ECG
Investigation of all patients with hypertension
9. Renal Parenchymal Disease
Common cause of secondary HTN (2-
5%)
HTN is both cause and consequence of
renal disease
Assessment of creatinine clearance and
GFR are diagnostic.
13. RAS screening/diagnostics
Sens Spec Limitation/Etc
Duplex U/S 90-95% 60-90%
Operator dependent, 10-20%
Captopril
Renography
83-91% 87-93%
Accuracy reduced in pt with renal
insufficiency, lacks anatomical info;
good predictor of BP response
MRA 88-95% 95%
False positive artifact resp, peristalsis,
tortuous vessels; cost
Bruit 39-65% 90-99%
Insensitive, severe stenosis may be
silent
Angiography
Gold
std
Gold
std
Invasive, nephrotoxicity, little value in
predicting BP response
18. Primary Aldosteronism
Primary Aldosteronism, previously felt to be an
unlikely cause of 2ry HTP, now is more
commonly observed depending on the severity of
HTP :
8% Stage 2
13% of Stage 3) and
20% of those with resistant hypertension.
(10th
Annual SMA-ASH Carolinas Georgia Chapter Meeting, 2006)
19. Primary Aldosteronism
Prevalence .5- 2.0% (5-12% in referral centers)
Etiology
Adrenal adenoma
Bilat adrenal hyperplasia, glucocorticoid suppressible hyperaldo,
adrenal carcinoma
Clinical:
May be asymptomatic.
Headache, weakness, paralysis, polyuria
Retinopathy, edema uncommon
Hypokalemia (K normal in 40%), metabolic alkalosis, high-nl Na
20. Screening for Hyperaldosteronism
• Spontaneous hypokalemia (<3.5 mmol/L).
• Profound diuretic-induced hypokalemia (<3.0
mmol/L).
• Hypertension refractory to treatment with 3 or
more drugs.
• Incidental adrenal adenomas.
21.
22. Pheochromocytoma
Catecholamine-producing neuroendocrine
tumor that arises from chromaffin cells
Adrenal Medulla : 80-85% pheochromocytomas
Extra-adrenal paragangliomas
Often in head and neck (glomus jugulare) and
rarely produce catecholamines.
Some can be dopamine producing.
23. Epidemiology
Incidence: 1 in 100,000 each year
Prevalence among pts with HTP
In adults – 0.1-0.6%
In children – 1%
Traditional rule of 10
10% bilateral, 10% familial, 10% extra-adrenal, and
10% malignant.
Recent reports found 12-24% of sporadic
pheochromocytoma with germline mutation.
24. Clinical Presentation
Paroxysmal attacks of Headache, palpitations,
and sweating.
Adults more often have paroxysmal hypertension
(50%) while
Children have sustained hypertension (70-90%)
20% of children will be normotensive at diagnosis.
25. Screening for Pheochromocytoma
• Paroxysmal and/or severe sustained hypertension refractory to usual
antihypertensive therapy;
• Hypertension and symptoms suggestive of catecholamine excess (two or more of
headaches, palpitations, sweating, etc);
• Hypertension triggered by B-blockers, MAO inhibitors, clonidine, micturition, changes
in abdominal pressure or tyramine containing foods.
• Incidentally discovered adrenal mass.
• Multiple endocrine neoplasia (MEN) 2A (medullary carcinomas of thyroid) or 2B
(mucosal neuromas) ; von Recklinghausen’s neurofibromatosis, or von Hippel-Lindau
disease.
26. Pheochromocytoma – Screening.
Best detected during or immediately after
episodes
Sensitivity Specificity
Plasma free
metanephrine
>.66nmol/L
99% 89%
24hr urine
metanephrine
(>3.7nmol/d)
77% (95%) 93% (96%)
24 urine VMA 64% 95%
Lenders, et al. JAMA 2002 Mar 20;287(11):1427-34
27. Pheochromocytoma - Diagnosis
Imaging for localization of tumor
Sens Spec PPV NPV
(MIBG) scintigraphy 78% 100% 100% 87%
CT 98% 70% 69% 98%
MRI 100% 67% 83% 100%
Akpunonu, et al. Dis Month.October 1996, p688
30. Cushings syndrome - diagnosis
Screen:
24 Hr Urine free cortisol
>90ug/day is 100% sens and 98% spec
false + in Polycystic Ovarian Syndrome, depression
Confirm
Low dose dexamethasone suppression test
1mg dexameth. midnight, measure am plasma cortisol
(>100nmol is +)
Other tests include dexa/CRH suppresion test
Imaging
CT/MRI head (pit) chest (ectopic ACTH tumor)
31. Coarctation of Aorta
Congenital defect, male>female
Clinical
Differential systolic BP arms vs legs
(=DBP)
May have differential BP in arms if defect
is prox to L subclavian art
Diminished/absent femoral art pulse
Often asymptomatic
Echo-Doppler, CT angiography,
aortography.
33. Hyperthyroidism
33% of thyrotoxic pt develop HTN
Usually obvious signs of thyrotoxicosis
Dx: TSH, Free T4/3, thyroid RAIU
34. Hypothyroidism
25% hypothyroid pt develop HTN
Mechanism mediated by local control, as
basal metabolism falls so does
accumulation of local metabolites;
relative vasoconstriction ensues
35.
36. Summary
Screening for 2ry HTN can be expensive and requires clinical
suspicion and knowledge of limitations of different tests
General principles:
New onset HTN if <30 or >50 years of age
HTN refractory to medical Rx (>3-4 meds)
Specific clinical/lab features typical for dz :
@ Hypokalemia in the absence of diuretic therapy may indicate a state
of mineralocorticoid excess
@ Excess aldosterone production (Conn’s)
@Excess glucocorticoid production (Cushing’s)
@Excess T3&T4 (hyperthyroidism)
@ Epigastric bruits, differential BP in arms, episodic HTN/flushing/palp.