Aldosterone-Producing Adrenocortical Carcinoma without Hypertension
Min Soo Song, Sung Woo Seo, Sang Byung Bae, Yeo Joo Kim, and Sang Jin Kim
Department of Internal Medicine, Soonchunhyang University College of Medicine, Cheonan, Korea
Although adrenocortical tumors are common, adrenocortical carcinomas are rare. Moreover, aldosterone-producing adrenocortical carcinomas without hypertension are exceedingly rare, with only two previously reported cases.
Keywords: Aldosterone; Carcinoma; Hypertension; Hyperaldosteronism
INTRODUCTION
Primary aldosteronism is a syndrome characterized by hypertension and hypokalemia [1]. Aldosterone- producing adenomas (APAs) and bilateral idiopathic hyperaldosteronism (IHA) are the most common causes of primary aldosteronism, with APA accounting for ap- proximately 35% of the cases, and IHA accounting for 60% [2]. Aldosterone-producing adrenocortical carci- nomas (APACs) are a very rare cause of primary aldo- steronism [3]. As a cause of primary aldosteronism, an APAC is characterized by hypertension and hypokale- mia [3]; however, very few APACs have features of nor- motensive primary aldosteronism [4,5]. Here, we report a case of APAC without hypertension.
CASE REPORT
A 32-year-old woman was referred to our hospital for evaluation of a left adrenal mass. She had undergone an appendectomy 2 weeks earlier, and the mass was
diagnosed incidentally on postoperative abdominal ul- trasonography. On admission, her blood pressure was 110/70 mmHg, and her pulse was 80 beats/min. Serial blood pressures during her hospital stay ranged from 110/70 to 130/80 mmHg. The patient had hypokale- mia (2.5 mmol/L) and was started on spironolactone (100 mg twice daily) and oral potassium chloride. The plasma aldosterone level was 389.53 pg/mL (normal range, 10.0 to 105) in the supine position and 716.87 pg/mL in the upright position (normal range, 34.0 to 273.0). Plasma rennin activity was 0.1 nmol/L/hr. Com- puted tomography showed a solid, homogenous adrenal mass with a maximum diameter of 42 mm (Fig. 1). An adrenalectomy with lymphadenectomy was performed. The tumor was an ill-defined, gray-tan solid mass mea- suring 42 × 33 × 22 mm (Fig. 2). Histopathologically, it consisted of a solid nest of bland to anaplastic cells with frequent mitoses and necrosis (Fig. 2). Her potassium level normalized on postoperative day 7 without potas- sium supplements or spironolactone.
Received : June 26, 2008
Revised : August 29, 2008
Accepted: August 31, 2008
Correspondence to Yeo Joo Kim, M.D.
Department of Internal Medicine, Soonchunhyang University Cheonan Hospital, 31 Suncheonhyang 6-gil, Dongnam-gu, Cheonan 330-930, Korea Tel: 82-41-570-3672, Fax: 82-41-574-5762, E-mail: yeojoo@schch.co.kr
DISCUSSION
In approximately 60% of cases, an adrenocortical carcinoma presents with evidence of adrenal steroid hormone excess [6], while APACs are exceedingly rare. To our knowledge, only 59 cases have been reported, in- cluding our case [3]. An APAC is usually associated with hypokalemia, renal potassium leakage, and arterial hypertension due to excessive aldosterone secretion. A few specific symptoms such as muscle weakness and cramping, headache, palpitations, polydipsia, polyuria, and nocturia, or a combination of these symptoms, may be present in cases of marked hypokalemia [7]. Patients with suspected primary aldosteronism can be screened by measuring the morning ambulatory paired random plasma aldosterone concentration and plasma renin activity [2]. However, several studies have shown that most patients with primary aldosteronism have base- line blood potassium levels in the normal range [8,9]. Consequently, hypokalemia is not used to establish the diagnosis of primary aldosteronism, and an increased ratio of plasma aldosterone concentration to plasma re- nin activity is not diagnostic in itself [2]. Primary aldo- steronism can be confirmed by an oral sodium loading test, an intravenous saline infusion test, or a fludrocor- tisone suppression test [2].
An APAC is a rare cause of primary aldosteronism. Typically, a patient with an APAC has features of prima- ry aldosteronism, including hypertension and hypokale- mia. Nevertheless, two of the 58 reported APAC patients
| Characteristic | Muthusethupathi et al. [4] | Yamazaki et al. [5] | Current case |
|---|---|---|---|
| Age, yr | 40 | 25 | 32 |
| Gender | Male | Male | Female |
| Race | No data | Japanese | Korean |
| Blood pressure, mmHg | 90/70-120/80 | 120/80 | 110/70-130/80 |
| Potassium, mmol/L | 2.3 | 2.1 | 2.5 |
| Aldosterone, pg/mL | 1,170-1,290 (50-200) | > 4,000 (7-12) | 389-716 (10-273) |
| Plasma renin activity, nmol/L/hr | 0.7 | 0.3 | 0.1 |
| Tumor size, mm | 56 × 60 | ND | 42 × 33 |
| Site | Right | Left | Left |
| Lymph node metastasis | Positive | ND | Positive |
| Other adrenal hormones | Not increased | Not increased | Not increased |
| Postoperative stay, day | 15 | ND | 7 |
ND, not descriptive.
had normal blood pressure [3]. The two cases of APAC without hypertension were reported by Muthusethu- pathi et al. [4] and Yamazaki et al. [5] Information on these two published cases and our case is summarized in Table 1.
Vantyghem et al. [7] presented two cases of APA with- out hypertension; including these two cases, 18 cases of normotensive primary hyperaldosteronism have been reported. Only 10 of these cases have been published in the English literature, and about 75% of cases have been reported in Eurasians. Of the three cases listed in Table 1, one patient was Japanese, and another patient was Korean; no information was available regarding the third.
The normal blood pressure in these rare cases of pri- mary aldosteronism is not fully understood, and various explanations have been offered, including an absence of volume expansion, a low-salt diet, abnormal atrial natriuretic peptide activity, and the use of glucocor- ticoids [7]. The patients might have been hypotensive before the onset of the disease, might have experienced a blunted response to pressor agents, or might have ex- hibited associated hypopituitarism [4]. The exact cause of this disease in our patient remains unknown.
Conflict of interest
No potential conflict of interest relevant to this article was reported.
REFERENCES
1. Ganguly A. Primary aldosteronism. N Engl J Med 1998;339:1828- 1834.
2. Young WF. Primary aldosteronism: renaissance of a syn- drome. Clin Endocrinol (Oxf) 2007;66:607-618.
3. Seccia TM, Fassina A, Nussdorfer GG, Pessina AC, Rossi GP. Aldosterone-producing adrenocortical carcinoma: an unusual cause of Conn’s syndrome with an ominous clinical course. Endocr Relat Cancer 2005;12:149-159.
4. Muthusethupathi MA, Vimala A, Jayakumar M, Rajendran S. Normotensive primary aldosteronism due to adrenocortical carcinoma. Nephron 1998;79:247-248.
5. Yamazaki H, Abe Y, Katoh Y, et al. Establishment of an adre- nocortical carcinoma xenograft with normotensive hyperal- dosteronism in vivo. APMIS 1998;106:1056-1060.
6. Allolio B, Fassnacht M. Clinical review: Adrenocorti- cal carcinoma: clinical update. J Clin Endocrinol Metab 2006;91:2027-2037.
7. Vantyghem MC, Ronci N, Provost F, et al. Aldosterone-pro- ducing adenoma without hypertension: a report of two cases. Eur J Endocrinol 1999;141:279-285.
8. Schwartz GL, Turner ST. Screening for primary aldosteron- ism in essential hypertension: diagnostic accuracy of the ratio of plasma aldosterone concentration to plasma renin activity. Clin Chem 2005;51:386-394.
9. Williams JS, Williams GH, Raji A, et al. Prevalence of pri- mary hyperaldosteronism in mild to moderate hypertension without hypokalaemia. J Hum Hypertens 2006;20:129-136.