CME INDIA Case Presentation by Dr Mritunjay Kumar Singh, Nephrologist Physician, Secretary, CCDSI, Gaya.

CME INDIA Case Study

CASE: A 40-year-old male, Headache – 2 months, BP – 200/120mm of Hg

  • Pulse – 80/min .NO R-R/R-F delay
  • Had h/o hypertension for 1 years, on amlodipine(5mg), and atenolol(50mg), poorly controlled HTN
  • No renal bruit/ No Cushingoid features
  • Lab- scr-0.8, BUN- 8, U/R – no albumin, Na- 135
  • k- 2.9meq/L, HCO3- 29

So, we have a case with Hypertension accompanied by Hypokalemia. At this juncture, what comes in your mind?

  1. Because this patient has worsening hypertension, persistent hypokalemia despite potassium supplementation, and resistant hypertension, it is reasonable to evaluate for underlying causes of hypertension.
  2. Think for the most common cause of hypokalemia in a hypertensive patient. Is its diuretic use. (By enhancing urinary flow and sodium delivery through the collecting tubule, both thiazide and loop diuretics promote renal potassium secretion. Potassium secretion is further enhanced in the setting of diuretic-induced intravascular volume depletion and secondary aldosterone stimulation)
  3. Think for gastrointestinal problems, such as diarrhoea or vomiting, though these patients would generally not be hypertensive.
  4. Think for magnesium deficiency due to malabsorption, poor dietary intake, or exposure to medications such as aminoglycosides.
  5. But history rules out these things. Spontaneous hypokalemia, in the absence of diuretic use, deserves further evaluation.

D/D Now appears to be

  1. Essential hypertension with diuretic use-ruled out
  2. Primary Aldosteronism
  3. Chushing Syndrome
  4. Pheochromocytoma
  5. Reno vascular disease
  6. Malignant hypertension

So, what tests you want at this moment?

Plasma Aldosterone Concentration (PAC), Plasma Renin Activity (PRA):  Test is positive if both conditions met:

  1. PAC > 20ng/dl
  2. PAC/PRA > 30
  • Most antihypertensive medications can be continued except MRA (stopped for 6weeks prior to test).
  • Correct potassium to within normal range prior to test

Pearls to remember

  • Relying solely on an elevated PAC: PRA without attention to the level of PAC may yield false positive results because patients with low-renin essential hypertension will be included.
  • Aside from stopping aldosterone-receptor antagonists, such as spironolactone or eplerenone, for six weeks, there is no need initially to stop other antihypertensive medications before obtaining a PAC: PRA.
  • Aldosterone is secreted in bursts, the PAC: PRA could change within minutes. Early morning levels are most representative.
  • The decision about whom to evaluate further for primary aldosteronism should not be dependent on only one determination of PAC: PRA.
  • If repeated determinations demonstrate a PAC:PRA>30 and a PAC >15 ng/dL, confirmatory biochemical testing, such as measuring PAC before and after 2 L of normal saline administration or a 24-hour urinary aldosterone excretion after three days of oral salt loading (six g sodium chloride) with careful blood pressure monitoring is indicated to diagnose primary aldosteronism.
  • Neither oral salt loading nor saline infusion should suppress the autonomously secreted hormone from an adenoma.
  • The clinical response to a trial of aldosterone-receptor antagonists is not in itself diagnostic of primary aldosteronism, because many patients with resistant essential hypertension have a favourable response to these medications

(Perm J. 2009 Winter; 13(1): 73–76 Antoine C Abcar, MD and Dean A Kujubu, MD)

What was done in this case?

  •  In our case, the values were as follows:
  •  PAC 40.1 ng/dl (N: 1-16 ng/dl) and
  •  PRA 0.7 ng/ml/h (N: 0.5-1.9 ng/ml/h).
  •  PAC/PRA ratio was 57.24.

What is now probable diagnosis?

High Probability of APA (Aldosterone producing Adenoma)

Favouring Points:

  • Spontaneous hypokalemia
  • Suppressed PRA
  • High PA (>20ng/dl)
  • Younger age (<50)
  • More severe HTN

CT abdomen done:

CME INDIA Learning Points

  • The presence of mineralocorticoid excess should be suspected in any patient with the triad of hypertension, unexplained hypokalemia, and metabolic alkalosis.
  • Hypokalemia and mineralocorticoid excess have negative effect on cardiovascular system and can lead to increase CV mortality.
  • In hypertensive patients, it is prudent to aim for serum potassium levels 3.5 to 5.0 mEq/L.
  • The mineralocorticoid excess states should receive a mineralocorticoid receptor antagonist.

What was done?

Amlodipine and Atenolol were stopped–Aldactone 25 mg, later increased to 50 mg, later on ACEI was added. Good control of BP achieved.

Quick Take-home Message

  • HTN- often severe, rarely malignant
  • No edema
  • Hypokalemia is inconsistent – 50% in APA, 17% in IHA and normal in most GRA.
  • Metabolic alkalosis
  • Mild hypernatremia

Hormonal profile in PA

  • Increased plasma aldosterone (PA)
  • Increased plasma renin activity (PRA)
  • Increased PA: PRA

Adrenal Surgery

  • Surgery is the treatment of choice for the lateralizable variants of primary aldosteronism, including typical aldosteronomas, renin-responsive adenomas (RRAs), and primary adrenal hyperplasia (PAH). Patients with renin-secreting tumors are typically young females and have severe hypertension and hypokalemia.
  • Contrast enhanced CT appears to be the diagnostic procedure of choice, since false negative results occur with arteriography or renal vein renin sampling.
  • ACEI/ARB should be used with caution to avoid first dose hypotension.
  • Surgical removal of the tumor cures the disease.

How to rule out Cushing’s

  • Another cause of hypertension with hypokalemia is Cushing’s syndrome.
  • Cushing’s syndrome, a result of excess endogenous glucocorticoid secretion, presents with hypertension, central obesity, abdominal striae, glucose intolerance, depression, weakness, and characteristic moon facies. History excludes this possibility.
  • Hypokalemia is most noted in the ectopic adrenocorticotropic hormone syndrome.
  • The initial screening involves collecting a 24-hour urine for free cortisol. Values that are more than three to four times normal are diagnostic for Cushing’s syndrome.
  • Owing to the difficulty in correctly collecting a 24-hour urine sample, however, some physicians prefer performing a low dose dexamethasone-suppression test by obtaining an 8 am cortisol level after the administration of 1 mg of dexamethasone at bedtime (11–12 pm).

How to rule out pheochromocytoma

  • Pheochromocytoma is classically described as presenting with paroxysms of adrenergic symptoms, such as palpitations, headaches, anxiety, and sweating, associated with labile hypertension.
  • Most pheochromocytomas, however, present with persistent hypertension.
  • The clinical manifestations of a pheochromocytoma depend on the predominant catecholamine that the tumour produces and whether the secretory pattern is continuous or paroxysmal. Although pheochromocytomas are rare, autopsy studies suggest that they are present more often than they are diagnosed. These patients tend to have a decreased intravascular volume status, and thus both PRA and PAC levels are elevated
  • Twenty-four-hour urinary fractionated metanephrines and catecholamines may be the preferred diagnostic test, but some advocate the use of plasma-fractionated free metanephrine because of its ease of collection and high sensitivity.

How to rule out Renovascular hypertension

  • Fibromuscular dysplasia is the most common cause of renovascular hypertension in the younger patient, whereas atherosclerotic vascular disease is the most common in the older patient. Both may manifest as resistant hypertension.
  • Acute renal deterioration after administration of ACEI or ARB and recurrent episodes of flash pulmonary edema suggest either bilateral renal vascular disease or disease in a patient with a solitary kidney.
  • The presence of a systolic–diastolic abdominal or flank bruit or a renal sonogram demonstrating marked differences in kidney sizes suggest renal vascular disease.
  • Although renal arteriography remains the diagnostic gold standard for renovascular disease, magnetic resonance angiography techniques and computed tomography (CT) angiography.

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