1. ‫الرحمن‬ ‫ا‬ ‫بسم‬
‫الرحيم‬

2. Secondary
Hypertension
Work-up
By
Tamer Moustafa Abe Elghany
MD, FESC

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 :

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.

10. Renovascular HTN
 Incidence 1-30%
 Etiology
 Atherosclerosis 75-90%
 Fibromuscular dysplasia 10-25%
 Other
 Aortic/renal dissection
 Takayasu’s arteritis
 Thrombotic/cholesterol emboli
 CVD
 Post transplantation stenosis
 Post radiation

11. Renovascular HTN - Clinical
 History
 Onset HTN age <30 or >55
 Negative FH of HTN
 Sudden onset uncontrolled HTN in previously well controlled pt
 Accelerated/malignant HTN
 Intermittent pulm edema with nl LV fxn
 Clinical exam. /Lab. findings
 Epigastric bruit, particulary systolic/diastolic
 Advanced fundal changes, grade III/IV retinopathy
 Azotemia induced by ACEI, ARBs or diuretics
 Paradoxical worsening of HTN with diuretics
 2ry aldosteronism : ↑ plasma renin & ↓ s. Na&K
 Unilateral small kidney, difference >1.5cm, on sonography

12. Renovascular HTN - diagnosis
 Physical findings (bruit)
 Duplex U/S
 Captopril renography
 Magnetic Resonance Angiography
 Renal Angiography

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

14. Screening Strategy (Index of suspicion & need intervention)

15. Fibromuscular dysplasia
 10-25% of all RAS
 Young female, age 15-40
 Medial disease 90%, often involves
distal RA

16. Atherosclerotic RAS
 75-90% of RAS
 Usually men, age>55, other atherosclerotic dz

17. Fibromuscular Dysplasia, before
and after PTRA
Atherosclerotic RAS before and after stent
Safian & Textor. NEJM 344:6;

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.

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

28. Cushing’s syndrome/
hypercortisolism
 Rare cause of secondary HTN (.1-.6%)
 Etiology:
pituitary microadenoma,
iatrogenic (steroid use),
ectopic ACTH,
adrenal adenoma
 Clinical
 Sudden weight gain, truncal obesity, moon facies,
abdominal striae, DM/glucose intolerance, HTN,
prox muscle weakness, skin atrophy,
hirsutism/acne

29. Cushings syndrome

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.

32. Coarctation of Aorta
Brickner, et al. NEJM 2000;342:256-263

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

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.

37. Summary

38. Tamer
MD, FESC