Secondary Causes

Table of Contents

Renovascular HTN

Suggest Renovascular HTN:

Suggesting renovascular HTN if: (≥ 2 of:)

1. Sudden onset or worsening HTN at age >55 or < 30yo

2. Abdominal bruit

3. Resistant HTN (≥3 drugs)

4. Increase in creatinine ≥ 30% with initiation of ACEi

5. Atherosclerotic vascular dz in pts who smoke or have dyslipidemia

6. Pulmonary edema with hypertensive surges

Exam:
- Hear epigastric bruits (both atherosclerotic and FMD mechanisms)
Two types:
- Atherosclerosis
  - Vascular risk factors (i.e. smoking, dyslipidemia)
  - Proximal renal arteries
- Fibromuscular Dysplasia
  - Younger patients (women)
  - Distal renal arteries
Mechanism:
- Unilateral --> Elevates BP through renin-mediate mechanism
- Bilateral --> Sodium excess elevate BP
Diagnosis:
- Captopril-enhanced radioisotope renal scan
  - Do not use in CKD (GFR < 60)
- MRI Angiography (gadolinium)
- CT angiography (for those with normal renal function) (Grade B). (Grade D).
- Renal Doppler
  - Recommended if GFR < 30 (cannot use iodinated or gadolinium contrast)
Treatment
- Fibromuscular Dysplasia
  - Percutaneous renal angioplasty --> treatment of choice.
- Atherosclerotic Disease
  - Controversial!!!
  - ASTRAL Trial and STAR Trial do not support angioplasty over medical therapy.
  - Recommendations:
    - Aggressive risk factor modification (BP control, dyslipidemia therapy, smoking cessation).
    - Percutaneous stenting ONLY for those with refractory HTN despite extensive treatment, or progressive loss of renal function.
- Bilateral Renal Artery Disease --> at risk of worsening renal function when treated with RAAS drugs (ACEi or ARBs). Especially in those with aggressive diuretic use. Be careful if serum creatine rises > 25% of baseline.

Suspect when:

Screening for hyperaldosteronism should be considered:

Diagnosis:

A. To estimate:	B. From:	Multiply (B) by:
Plasma renin concentration (ng/L)	Plasma renin activity (ng/mL/hr)	0.192
Plasma renin activity (ng/L/sec)	Plasma renin activity (ng/mL/hr)	0.278
Plasma aldosterone concentration (pmol/L)	Plasma aldosterone concentration (ng/dL)	28

Positive Screening Test: plasma aldo-to-renin activity ratio > 750 pmol/L/ng/ml/hr (or 144 pmol/L/ng/L when renin is measured as renin mass or concentration)

Step #2: If screening test positive, autonomous aldo secretion present: Do Confirmatory test

If adrenal mass present + eligible for surgery --> Adrenal venous sampling (assess for lateralization of secretion)

saline loading tests (perform either):
1. Administer 2L of normal saline IV over 4h with the patient in a recumbent position. Primary hyperaldosteronism is defined as a post-infusion plasma aldosterone >280 pmol/L. If <140 pmol/L, primary hyperaldosteronism is unlikely. Values in between are considered indeterminate;
2. Administer PO sodium, 200 mmol/day x3 days, with primary hyperaldosteronism defined as a 24-hr urinary aldosterone >33 nmol/d (measured from the morning of Day 3 to the morning of Day 4). If <28 nmol/day, primary hyperaldosteronism is unlikely.
a plasma aldosterone to PRA ratio greater than 1400 pmol/L/ng/ml/hr (or 270 pmol/L/ng/L), with a plasma aldosterone greater than 440 pmol/L.
captopril suppression test: Administer 25-50mg captopril orally after the patient has been sitting or standing for 1 hour. While seated, renin and plasma aldosterone levels should be measured at time zero and 1-2 hours after ingestion. Primary hyperaldosteronism is unlikely if plasma aldosterone is suppressed by >30% following captopril ingestion. In primary hyperaldosteronism, plasma aldosterone remains elevated, while renin remains suppressed.

Adrenal CT or MRI to localize lesion
- If lesion found & fit for surgery--> do adrenal venous sampling to see if it is source of hypersecretion
- If imaging normal & fit for surgery
  - Adrenal Venous Sampling --> bilateral or unilateral production? for possible adrenalectomy
If family history of hyperaldosteronism or young stroke ≤40yo OR onset of HTN ≤ 20y and negative imaging --> test for Glucocorticoid Remediable Aldosteronism

Management

Surgery? - find out if candidate (above testing) --> possible unilateral laparoscopic adrenalectomy
Medications:
- Mineralocorticoid Receptor Antagonists (i.e. aldosterone)

Suspect when:

Suspect Pheochromocytoma when:

Paroxysmal and/or severe (BP ≥ 180/110) sustained HTN refractory to anti-HTN therapy
HTN + symptoms suggesting catecholamine excess (headaches, palpitations, sweating, panic attacks, pallor)
HTN triggered by B-blockers, MAO Inhibitors, Micturition, abdominal pressure
HTN + incidentally discovered adrenal mass + MEN2A/2B or von Recklinghausen neurofibromatosis or von Hippel-Lindau disease
Positive biochemical screening tests --> Localize with MRI (preferred), CT if MRI unavailable, or I-131 scintigraphy.

Investigations:
- Screening:
  - 24-hr urine total metanephrines and catecholamines (sn 90-95%)
    OR
    - 24-hr urine fractionated metanephrines (sn 100%) + 24hr urine creatinine (to confirm accurate collection)
  - Plasma metanephrine measurement and free normetanephrines, where available may be considered (sn 99%)
  - Urinary VMA measurements should not be used for screening
- If borderline result, or possible false positive result
  - Repeat testing and/or clonidine suppression test.
- Do biochemical testing BEFORE imaging (to avoid incidentalomas)
- Imaging:
  - MRI (preferred)
  - CT (if MRI unavailable)
  - I-131 metaiodobenzylguanidine scintigraphy (aka MIBG)
Treatment:
- Surgical removal!
  - Peri-operative management:
    - Alpha-blockers started 10-14d pre-op. (can include phenoxybenzamine (long-acting non-selective irreversible alpha-blocker), prazosin, doxazosin
    - Add Dihydropyridine CCB
    - Add other anti-HTN agents
    - Avoid diuretics if possible
    - Encourage volume + salt intake pre-op (volume contraction is common)
  - Post-Op
    - Hold anti-HTN drugs
    - May need aggressive IV fluids
  - Long-Term
    - Follow urinary or plasma metanephrines (screen for recurrence)