mayo
Case Report
Primary Aldosteronism in a Patient With Familial Adenomatous Polyposis
GLENN L. ALEXANDER, MD; GEOFFREY B. THOMPSON, MD; AND DAVID A. SCHWARTZ, MD
Patients with familial adenomatous polyposis (FAP) fre- quently have extracolonic manifestations of their disease. Prior reports have indicated an increased prevalence of adrenal lesions in patients with FAP. Although most of the adrenal lesions represent nonfunctioning adenomas, some patients have had hypercortisolism due to adrenocortical carcinoma or bilateral nodular hyperplasia. We present a
F amilial adenomatous polyposis (FAP) is an autosomal dominant disorder caused by a mutation in the ade- nomatous polyposis (APC) gene on chromosome 5q21 and characterized by hundreds of adenomatous colonic pol- yps.12 Many extracolonic manifestations of FAP have been described, including an increased prevalence of adrenal masses.3 The vast majority of these adrenal lesions are nonfunctioning adenomas, but a few patients have had hypercortisolism due to adrenocortical carcinoma3-5 or bi- lateral nodular hyperplasia.6 To our knowledge, no patient with FAP has previously been described who also had primary mineralocorticoid excess. We describe a case of primary aldosteronism (PA) in a patient with FAP.
REPORT OF A CASE
A 58-year-old man with a history of FAP presented for an evaluation of dysplastic changes within his rectal remnant. When he was 22 years old, FAP had been diagnosed during an evaluation for a change in bowel habit; diffuse carpeting of his colon with adenomatous polyps was detected. He underwent a subtotal colectomy with ileosigmoidostomy. Subsequent annual flexible sigmoidoscopies had been re- markable only for occasional diminutive polyps, which had been fulgurated. Six months before presentation, he was found to have low-grade dysplasia within his rectum but no gross polyposis. His medical history was remarkable for a 3-year history of hypertension that was difficult to control; treatment consisted of hydrochlorothiazide, 25 mg/d, minoxidil, 5 mg twice a day, and atenolol, 50 mg/d. Potas- sium chloride, 20 mEq daily, was also necessary. There
case of a patient with FAP who had mineralocorticoid excess due to an aldosterone-producing adrenocortical adenoma.
Mayo Clin Proc. 2000;75:636-637
CT = computed tomography; FAP = familial adenomatous polyposis; PA = primary aldosteronism
was no family history of FAP, but both of his children were subsequently diagnosed with classic FAP.
The patient’s blood pressure was 148/80 mm Hg. Find- ings on the rest of his examination were normal; specifi- cally, he had no skin abnormalities, pigmented retinal le- sions, osteomas, thyroid nodules, or edema. Findings on flexible sigmoidoscopy were grossly normal, but biopsy specimens of the rectal mucosa revealed high-grade dys- plasia. A side-viewing duodenoscopy showed periampul- lary polyps, biopsies of which revealed tubulovillous ade- nomas with low-grade dysplasia.
The patient’s serum potassium level was 3.3 mEq/L (reference ranges shown parenthetically) (3.6-4.8 mEq/L), plasma aldosterone level was elevated at 25 ng/dL (1-21 ng/dL), and plasma renin was suppressed at less than 0.6 ng/ml per hour (2.9-24.0 ng/ml per hour), yielding a plasma aldosterone to plasma renin activity ratio of greater than 41. The urinary aldosterone level after 48-hour oral sodium loading was elevated at 19 µg/24 h (2-16 µg/24 h), with a urinary sodium level of 229 mEq/specimen (40-217 mEq/specimen). Computed tomography (CT) of the abdo- men revealed 2 solid masses (1.0 and 3.0 cm) within the right adrenal gland. The patient underwent a proctectomy, ileostomy, and ileal pouch-anal anastomosis along with a right adrenalectomy. Pathologic study showed 2 adrenal adenomas (Figure 1).
Postoperatively, the patient’s urinary aldosterone level normalized to 14 µg/24 h. When he returned in 3 months for takedown of his ileostomy, he was normotensive and was taking no antihypertensive medications; his serum po- tassium level was 4.8 mEq/L without supplementation.
From the Division of Gastroenterology and Hepatology and Internal Medicine (G.L.A., D.A.S.) and Department of Surgery (G.B.T.), Mayo Clinic, Rochester, Minn.
Address reprint requests and correspondence to Glenn L. Alexander, MD, Division of Gastroenterology and Hepatology, Mayo Clinic, 200 First St SW, Rochester, MN 55905.
DISCUSSION
To our knowledge, this case report is the first to describe PA in a patient with FAP. Since the initial report by Devic and Bussy7 in 1912, several investigators have described individual cases or small series of adrenal lesions in pa-
c 2000 Mayo Foundation for Medical Education and Research
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tients with FAP. Although the true prevalence of adrenal neoplasms in FAP is unknown, Marchesa et al3 reported that 7.4% of patients with FAP at the Cleveland Clinic who underwent surgical exploration or abdominal CT had adrenal lesions compared with 2.9% in an aggregate of studies of non-FAP patients undergoing abdominal CT for any reason. The vast majority of the reported adrenal lesions were asymptomatic nonfunctioning adrenal adenomas; however, 3 patients have been described with adrenocortical carci- noma,4-6 and 1 has been described with hypercortisolism due to adrenal bilateral nodular hyperplasia.3
Even though PA has not been previously described in FAP, it is a common cause of secondary hypertension in the general population, occurring in up to 12% of hypertensive patients.8 Screening for PA has been recommended in pa- tients with hypertension and hypokalemia (regardless of diuretic therapy) and in patients with treatment-resistant hypertension. A plasma aldosterone/plasma renin activity
ratio of greater than 20 suggests PA and should lead to further confirmatory and localization studies.9
Although the cause of the relationship between FAP and adrenal lesions is unknown, Seki et al6 described a loss of heterozygosity in the region of the APC gene in an adreno- cortical carcinoma in a patient with FAP. Wakatsuki et al10 also noted a loss of the normal APC allele in a patient with FAP who had a benign adrenal tumor. Moreover, they genetically investigated 10 adrenal tumors in non-FAP pa- tients and found no APC mutations in the non-FAP group. These findings suggest a “second hit” causing a functional loss of tumor-suppressor activity of the APC gene, which may promote growth of mutated adrenal tissue, predispos- ing patients with FAP to adrenal neoplasms.
The potential etiologic association of FAP and PA is intriguing; however, we cannot rule out the possibility of an unrelated chance occurrence of the 2 conditions in our patient. This potential association could be further assessed by prospectively screening consecutive hypertensive pa- tients with FAP for PA to determine whether the preva- lence of PA in such patients is greater than the prevalence of PA in hypertensive patients without FAP.
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