Postoperative differentiation between unilateral adrenal adenoma and bilateral adrenal hyperplasia in primary aldosteronism by mRNA expression of the gene CYP11B2.
OBJECTIVE
Primary aldosteronism (PA) is characterized by hypertension, hypokalemia and suppressed renin-angiotensin system caused by autonomous aldosterone production. The aim of this study was to localize mRNA expression of the genes coding for steroidogenic enzymes in adrenals from a group of patients with PA and relate this to clinical work-up, histopathology and outcome of adrenalectomy.


METHODS
This was a retrospective study of 27 patients subjected to adrenalectomy for PA.


METHODS
Clinical data were collected and follow-up of all patients was performed. Paraffin-embedded specimens were analyzed by the in situ hybridization technique, with oligonucleotide probes coding for the steroidogenic enzyme genes.


RESULTS
The resected adrenals had the histopathologic diagnosis of adenoma (11), adenoma and/or hyperplasia (15) or hyperplasia (1). CYP11B2 expression (indicating aldosterone production) was found in a dominant adrenal nodule from 22 patients. Fourteen of these had additional CYP11B2 expression in the zona glomerulosa. All 22 patients were cured of PA by adrenalectomy. One of these patients, who had additional high expression of CYP11B2 in the zona glomerulosa, was initially cured, but the condition had recurred at follow-up. Two patients had a mass shown on computed tomography without CYP11B2 but with CYP11B1 and CYP17 expression (indicating cortisol production). Instead their adrenals contained small nodules with CYP11B2 expression. These patients were not cured.


CONCLUSIONS
Clinical data, endocrinologic evaluation and histopathology in combination with mRNA in situ hybridization of steroidogenic enzyme genes provide improved opportunities for correct subclassification postoperatively of patients with primary aldosteronism. At present, the in situ hybridization method is of special value for analysis of cases not cured by adrenalectomy.
Enberg
Ulla
U
Department of Surgical Sciences, Section of Surgery, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden. ulla.enberg@kirurgi.ki.se
Volpe
Cristina
C
Höög
Anders
A
Wedell
Anna
A
Farnebo
Lars-Ove
LO
Thorén
Marja
M
Hamberger
Bertil
B
D000236:Adenoma / Q000473:pathology* / Q000503:physiopathology / Q000601:surgery; D000293:Adolescent; D000310:Adrenal Gland Neoplasms / Q000473:pathology* / Q000503:physiopathology / Q000601:surgery; D000315:Adrenalectomy; D000328:Adult; D000368:Aged; D019405:Cytochrome P-450 CYP11B2 / Q000235:genetics*; D003937:Diagnosis, Differential; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D006929:Hyperaldosteronism / Q000473:pathology* / Q000503:physiopathology / Q000601:surgery; D006965:Hyperplasia; D017403:In Situ Hybridization; D008297:Male; D008875:Middle Aged; D011184:Postoperative Period; D012333:RNA, Messenger / Q000032:analysis; D012189:Retrospective Studies; D013252:Steroid 11-beta-Hydroxylase / Q000235:genetics; D013254:Steroid 17-alpha-Hydroxylase / Q000235:genetics; D016896:Treatment Outcome
D012333:RNA, Messenger; D013254:Steroid 17-alpha-Hydroxylase; D019405:Cytochrome P-450 CYP11B2; D013252:Steroid 11-beta-Hydroxylase