ADRENOCORTICAL CARCINOMA PRESENTING AS PRIMARY ALDOSTERONISM IN A YOUNG MAN
A. G. FRASER Medical Registrar, Auckland Hospital, New Zealand
M. S. CROXSON Endocrinologist, Auckland Hospital, New Zealand
E. A. ESPINER
Professor in Medicine, Department of Endocrinology, Princess Margaret Hospital, Christchurch, New Zealand
B. SYNEK Pathologist, Department of Pathology, Medical School, Auckland Hospital, New Zealand
Abstract:
A young Polynesian man presented with severe hypertension complicated by an intracerebral hemorrhage. The hypertension was found to be secondary to hyperaldosteronism from a well differentiated adrenocortical carcinoma. Surgical removal of the tumour has resulted in a near normal blood pressure with no evidence of tumour recurrence or hyperaldosteronism after one year. (Aust NZ J Med 1987; 17: 60-62.)
Key words: Aldosteronism, adrenocortical carcinoma.
Aldosterone-producing adrenocortical carcinoma is a rare tumour.1-3 It usually occurs in older subjects who may have metastatic disease at diagnosis as well as clinical or biochemical evidence of excessive glucocorticoid and androgen production.1 We describe a young man with the unusual presentation of severe hypertension complicated by intracerebral hemorrhage. An initial diagnosis of pheochromocytoma was suggested by the finding of a 5 cm calcified adrenal mass on computerised tomographic (CT) scan. Surprisingly he was found to have isolated hyperaldosteronism due to a well differentiated adrenocortical carcinoma.
CASE REPORT
A 27 year old Cook Island man was admitted following sudden onset of left hemiplegia. He had no significant past history and no recent symptoms on enquiry. On examination he was lean, with no clinical features of Cushing’s syndrome, and no evidence of gynecomastia or testicular atrophy. His blood pressure varied from 220/130 to 250/150 mmHg and renal function was normal. Review of his intravenous urogram showed flecks of calcium in the (L) suprarenal area. A CT scan of the upper abdomen showed a calcified suprarenal mass, 5 cm in diameter. There was no evidence of metastatic tumour (see Fig. 1). CT brain scan showed an intracerebral hemorrhage as the cause of his left hemiplegia.
Investigations included normal urinary and plasma catecholamines and normal suppression of plasma catecholamines with clonidine. Baseline biochemical results included a low serum potassium level (3.0-3.3 mmol/l) with mild alkalosis (CO2 content = 35 mmol/l) and inappropriately normal urinary potassium (54-62 mmol/24 hours). Blood glucose level
was 4.6 mmol/l fasting and 7.0 mmol/l post-prandial. Other investigations, pre-and post-operative, are summarised in Table 1. Plasma aldosterone was measured by a direct radio- immunoassay4 using an antibody raised to aldosterone-3-bovine serum albumin. Urine aldosterone excretion was measured as the acid labile metabolite, modified according to the method of Jowett et al.5 and using an antiserum raised against aldosterone 18, 21-disuccinate. From Table 1, it can be seen that he had suppressed plasma renin activity, and increased urinary aldosterone excretion while plasma aldosterone levels, initially within the stated normal range, were not suppressed after administration of fludrocortisone (0.6 mg/day) for three days (normal <200 pmol/l). Plasma 11-deoxycortisol, dehydroepi- androsterone (DHEA), 24 hour urine cortisol, and a urine steroid profile were all normal. The urine steroid profile was measured by an in-house method using dichloromethane extraction and gas liquid chromatography. The concentration of steroid metabolites in umol/24 hours, with the normal range and inter- assay precision for each sub-group shown in parentheses were: androsterone and etiocholanolone 12 (8-17; 9.7%), 11-deoxysteroids including pregnanetriol and tetrahydro-11-deoxycortisol 6 (3-7; 10.7%), 11-oxy-17-oxo- steroids 8 (4-14; 16.6%) and cortisol derivatives including tetra- hydrocortisone and tetrahydrocortisol 35 (20-45; 11.5%).
Before the diagnosis of primary aldosteronism was made, treatment with captopril (150 mg three times a day) was given with no fall in his blood pressure. Preoperative control was achieved with frusemfde (40 mg), atenolol (100 mg), and hydral- lazine (75 mg three times a day). At operation a 5 cm diameter tumour occupying most of the left adrenal was removed. Histology showed a well differentiated adrenocortical carcinoma characterised by marked nuclear pleomorphism including giant cells, but low rate of mitosis. Evidence of invasion was confined to capsular infiltration with tumour in a capsular vein (Fig. 2)
5
and a separate clump of tumour cells in a small vessel in extracapsular connective tissue. Transmission electron microscopy findings were compatible with tumour of steroid- secreting type. After surgery he developed biochemical evidence of hypoaldosteronism which has persisted for 18 months, although his plasma renin activity was responsive to upright posture at six months. After 18 months he remains well, but with low plasma and urine aldosterone and a plasma renin activity unresponsive to posture. These findings may result from his liberal dietary salt intake. His urine cortisol is unchanged from the preoperative level. Computed tomography of the abdomen shows no evidence of tumour recurrence.
DISCUSSION
The finding of a large calcified adrenal tumour in a young man with severe hypertension strongly suggested the diagnosis of pheochromocytoma. In the absence of any clinical or biochemical evidence of glucocorticoid or adrenal androgen or estrogen excess, the final diagnosis of isolated hyperaldosteronism due to an adrenocortical carcinoma was quite unexpected. Earlier reports of mineralocorticoid-secreting adrenal carcinoma have emphasised the severity of the hypokalemic alkalosis, associated elevation of glucocorticoids and androgens where clinical features may be absent, and the frequency of metastatic disease at diagnosis.1 Our patient lacked clinical features of excess glucocorticoid or estrogen production and had no change of body habitus after surgery. Patients with feminising adrenal tumours usually have hypogonadism and gynecomastia. Although we did not measure plasma or urine estrogens, estrogen-secretion
| TABLE 1 Clinical Investigations | |||||||
|---|---|---|---|---|---|---|---|
| Before surgery | After 3 days fludrocortisone | 2 weeks after surgery | 5 weeks after surgery | 6 months after surgery | 18 months after surgery | Normal values | |
| Serum potassium (mmoi) Plasma renin activity (ng/ml/h) | 3.0, 3.5 | 3.4* | 4.8 | 5.0 | 4.3 | 4.4 | 3.5-4.8 mmol/l |
| 0800 Supine | 0.2 | 0.3 | 1.7 | 1.2 | 1.0 | 1.05 ±0.53 (SD) ng/ml/h | |
| 1200 Upright | 0.2 | 0.4 | 7.7 | 1.2 | 2.75 ±0.89 (SD)) | ||
| Plasma aldosterone (pmol/l) | |||||||
| 0800 Supine | 353 | 286 | 59 | 170 | <40 | <40 | 80-350 pmol/l |
| 1200 Upright | 373 | 386 | 60 | <40 | <40 | 140-550 | |
| Plasma | |||||||
| 11-deoxycortisol (nmol/l) | 6 | 3.9 | 5.2 | <30 nmol/l | |||
| Dehydroepiandrosterone | |||||||
| (nmol/I) | 18 | 13 | 14 | 14 | 7-30 nmol/l | ||
| 24 hour urines | |||||||
| Na | 181 | 121 | 148 | 202 | 177 | ||
| K | 80 | 96 | 45 | 65 | 54 | ||
| Aldosterone | 165 | 8.6, 11.0 | 8.0 | 5.0 | 10-60 nmol/24 hour | ||
| Cortisol | 144 | 146 | 35-150 nmol/24 hour | ||||
| Blood pressure (mmHg) | 240/140 | 240/130 | 140/90 | 132/98 | 148/100 | 150/90 | |
| Treatment | Nil | Nil | Aldactone (100 mg twice daily) | Nil | Nil | Nil | |
*Patient receiving supplemental potassium, 72 mmol/day.
ADRENOCORTICAL CARCINOMA AND ALDOSTERONISM
by the tumour seems unlikely. Urine cortisol was normal before and 18 months after operation. Urine 17-oxo- steroid derivatives and plasma DHEA were also normal before surgery. These results exclude excessive cortisol or androgen production by the tumour.
Presentation with symptoms of hypokalemia has been almost universal with aldosterone-secreting adrenocortical carcinoma, and plasma potassium has usually been less than 2.5 mmol/1. In this respect our patient and the case described by Grim6 are exceptions. Our patient’s disorder showed the cardinal features of primary hyperal- dosteronism, i.e. hypokalemia, inappropriately normal urine potassium excretion, suppressed renin, and evidence of autonomous and excessive aldosterone secretion. These abnormalities were corrected by removal of the tumour which was also associated with a striking improvement in blood pressure. It is possible that other mineralocor- ticoids in addition to aldosterone contributed to our patient’s disorder. Raised concentrations of plasma deoxycorticosterone (DOC),2.7 18-hydroxycorticosterone (18-OH-B), and 18-hydroxydeoxycorticosterone (18-OH- DOC)2 have been described, the levels overlapping with those from patients with aldosterone-producing adenomas. We did not measure plasma 18-OH-B or 18-OH-DOC and it is possible that these or similar miner- alocorticoids contributed to the aldosterone immunoreactivity measured in urine which was propor- tionately much higher than plasma aldosterone levels. Previous reports of pure mineralocorticoid excess associated with adrenocortical carcinoma are few3,8-11 and in most cases the blood pressure elevation has been mild. Our patient appears to be unique in presenting with an intracerebral hemorrhage secondary to severe hypertension.
The histological result in our patient supports the view of Brooks et al.12 that surgical treatment of apparent aldosterone-producing adenomas is preferred to spironolactone treatment, especially in younger patients. Slee3 describes a case where delayed diagnosis because of medical treatment with spironolactone for three years resulted in metastatic disease being present at operation. Most adrenocortical carcinomas are larger than 6 cm in diameter. However our case, and those of other
authors,7.9 would suggest the need for caution when inter- preting tumour size and isolated hyperaldosteronism as markers of benign tumour. The finding of post-operative hypoaldosteronism supports the view that our patient does not have functioning metastases. Hypersecretion of several unregulated corticosteroids appears to be charac- teristic of the late stages of this disease. It is hoped that the well differentiated pathology and the production of mineralocorticoid alone suggests a less aggressive course than is usual for adrenocortical carcinoma.
Accepted for publication: 22 September 1986.
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