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Hypertension, hypokalemia and a slightly enlarged left adrenal gland
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A 35-year-old obese black woman with hypertension resistant to triple antihypertensive therapy including lisinopril 40 mg daily, atenolol 100 mg twice daily and hydrochlorothiazide 25 mg daily was referred to the endocrine clinic for the evaluation of an endocrine cause of hypertension.
Physical exam revealed a morbidly obese woman with a blood pressure of 166/98 mm HG and a pulse of 68 bem. She was not orthostatic by pulse or BP. She did not have moon facies, abdominal striae, ecchymoses or hyperpigmentation.
Laboratory studies were significant for a potassium of 3.1 mEql/L that rose to 3.9 mEq/L after a daily supplementation with 40 mEq of potassium. Her serum aldosterone was 11 ng/dL, plasma renin activity of 0.1 ng/mL/h with an aldosterone/plasma renin activity ratio of 110. The potassium supplementation was briefly stopped and a 24 hour urine collection was performed. The volume was 1600 cc and contained creatinine 1.46 gm, aldosterone 30.7 mcg (normal 2.3 to 21), sodium 252 mEq, potassium 90 mEq and free cortisol 35.1 mcg (normal <50). Her renal function was normal with a serum creatinine of 0.6 mg/dL.
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The biochemical testing was suggestive of primary aldosteronism with an aldosterone/plasma renin activity ratio >100, a low serum potassium with renal potassium wasting. A salt loading maneuver was not performed as her 24 hour urine demonstrated she was not hypovolumic nor sodium depleted.
The next step in the evaluation is to determine whether the etiology is a unilateral aldosterone-producing adenoma or bilateral adrenal hyperplasia (idiopathic hyperaldosteronism). Her adrenal imaging proved to be challenging. She had an abdominal/pelvic MRI without and with contrast for the evaluation of fibroids performed three months before that demonstrated a diffuse thickening of the left adrenal gland without focal nodule and a normal appearance of the right adrenal gland. A CT scan with an adrenal protocol was performed (see Figure 1) that showed a slight 8 mm diffuse nodular thickening of the left adrenal gland, which demonstrated more than 60% washout in the delayed images. The right adrenal gland was normal in appearance. The findings of the study were not diagnostic of an adrenal adenoma or hyperplasia.
It is common that adrenal adenomas secreting aldosterone may be small in size (<1 cm) making it difficult to discern a mass on either MRI or CT scans. In addition, because of incidental non-secreting adrenal nodules, biochemical lateralization prior to surgery is necessary even when a mass is seen on imaging studies. Functional nuclear scintigraphy with 131-I-iodocholesterol that accumulates in adrenal cortical adenomas is not widely available in the United States and is not routinely performed. Localization of the excess aldosterone secretion is usually done by bilateral adrenal vein sampling. This technique should be performed by an experienced radiologist who must simultaneously cannulate the right and left adrenal veins. Blood is sampled from the vena cava and the right and left adrenal veins before and after initiation of an infusion of an ACTH analogue (cosyntropin; 50 mcg/h). The blood samples are measured for aldosterone, cortisol and aldosterone/cortisol. Unilateral disease is associated with a larger than four-fold increase in the ratio of aldosterone/cortisol ratio on the side of the tumor compared to the contralateral side. Adrenal hyperplasia will show an equal, bilateral increase in aldosterone/cortisol after stimulation with cosyntropin.
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The adrenal vein sampling in this patient (see Table 1) showed that the cortisol levels were approximately the same in both adrenal veins but after cosyntropin stimulation, aldosterone secretion and aldosterone/cortisol ratio increased more than fourfold on the right compared to the samples from the left adrenal vein. This result is highly suggestive of a unilateral left aldosterone secreting adenoma and not hyperplasia.
Despite the discrepancy between the imaging studies that suggested an enlargement of the left adrenal gland, the patient had an uncomplicated right adrenalectomy based on the data from the adrenal vein sampling. Pathology showed a 12 gm right adrenal gland with a 1.4 cm adrenocortical adenoma and multinodular adrenocortical hyperplasia. After surgery, the patient’s BP was well-controlled with a single antihypertensive agent, hydrochlorothiazide 25 mg daily. Repeat studies performed six months after her surgery showed a normal serum aldosterone level 2 ng/dL, plasma renin activity 1.7 ng/mL/h and aldosterone/renin ratio 1.2. A 1 mg overnight dexamethasone suppression test was normal with a morning cortisol level of 1.2 mcg/dL.
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The evaluation of small aldosterone-secreting adrenal adenomas can be challenging because of the small size of these tumors and the relatively high prevalence of non-hormone secreting adrenal incidentalomas. In addition, only 30% to 60% of primary aldosteronism is caused by a single adenoma with the remaining of the cases caused by bilateral adrenal hyperplasia. More uncommon causes of hyperaldosteronism include unilateral zona glomerulosa hyperplasia, familial hyperaldosteronism type I (glucocorticoid-remediable aldosteronism) and type II (familial aldosterone-producing adenoma and/or bilateral idiopathic hyperplasia), aldosterone-producing adrenocortical carcinomas, and ectopic aldosterone-secreting tumors.
It is important to distinguish between these subcategories of hyperaldosteronism because the single aldosterone secreting adenoma is treated by unilateral adrenalectomy, but bilateral adrenal hyperplasia is managed medically with aldosterone receptor blockers (spironolactone, eplerenone) or with potassium-sparing diuretics that block the aldosterone-sensitive sodium channel in the collecting tubules (amiloride, triamterene).
This patient demonstrated the typical characteristics of an adrenal adenoma in which the patient is generally younger (<50 years), lower potassium levels and higher levels of urinary aldosterone (>30 ug/24 hr) but would have had the wrong adrenal gland removed based on her imaging studies. The adenoma was correctly identified only after adrenal vein catherization. It is possible this patient has a uncommon condition of unilateral hyperplasia but the pathology shows a well encapsulated adenoma in addition to the multiple small cortical nodules. Currently, her adrenal hormone profile is normal. She will be followed carefully because of the diffuse nodular enlargement of her left adrenal gland for the development of adrenal hormone abnormalities. It is not usually recommended to perform a bilateral adrenalectomy at this time based on the increased morbidity and reduction in life expectancy seen in patients after bilateral adrenalectomy.
Stephanie L. Lee, MD, PhD, is an Associate Chief in the Section of Endocrinology, Diabetes and Nutrition and an Associate Professor of Medicine at Boston Medical Center.
For more information:
- Funder JW, Carey RM, Fardella C, et al. Case detection, diagnosis, and treatment of patients with primary aldosteronism: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2008;93:3266.
- Welbourn RB. Survival and causes of death after adreanlectomy for Cushing’s disease. Surgery. 1985;97:16.
- White ML, Gauger PG, Doherty GM, et al. The role of radiologic studies in the evaluation and management of primary hyperaldosteronism. Surgery. 2009;144:926.
- Young WF, Hogan MJ, Renin-independent hypermineralocorticoidism. Tends Endocrinol Metab. 1994;5:97.
- Young WF, Stanson AW, Thompson GB, et al. Role for adrenal venous sampling in primary aldosteronism. Surgery. 2004;136:1227.