Functional and diagnostic aspects on adrenocortical adenoma

Abstract: Adrenocortical tumours are frequently detected due to increased use of imaging techniques like computed tomography, magnetic resonance imaging or ultrasound. The majority of the patients have tumours that do not have any overproduction of hormone. The functional adrenocortical adenomas are characterized by overproduction of one of the corticosteroids aldosterone, cortisol or androgen. The most common are aldosteronoma and cortisol producing adenoma. It is not possible to differentiate aldosterone and cortisol producing adenoma by histopathological examination. Thus, the clinical data and determination of steroid hormones in blood and urine form the basis to conclude if the extirpated tumour has been functional. The aim of the study was to increase our knowledge of the pathophysiology of adrenocortical lesions. Paper I. An in situ-hybridisation method was developed to use radioactively labelled oligonucleotide probes on paraffin embedded tissue material to demonstrate the gene expression of the steroid synthesizing enzymes and thereby identify the steroid production of adrenocortical adenoma. In vitro release of aldosterone and cortisol from thin slices was compared to the mRNA expression of CYP11B2, CYP11B1 and CYP17, which are coding for the specific enzymes needed for the aldosterone and cortisol synthesis. The results indicate that CYP11B2 expression reflects aldosterone production in the tumour, while CYP17 and CYP11B1 reflects cortisol production. Paper II. The most common forms of primary aldosteronism are unilateral adenoma and bilateral hyperplasia. To attain an optimal treatment there is a demand for thorough functional characterization since adrenalectomy often cures patients with adenoma while patients with hyperplasia are treated medically. To improve the subclassification of primary aldosteronism 27 operated patients were evaluated. CYP11B2 expression was found in an adenoma from 22 patients. Fourteen of these had additional CYP11B2 expression in zona glomerulosa. All these 22 patients were cured from hyperaldosteronism. Three patients, who were not cured, had probably bilateral disease. Two adrenal adenoma had no CYP11B2 expression, but the patients were cured. These results contribute to entirely new possibilities to, postoperatively, determine a correct subclassification of patients with primary aldosteronism. Paper III. The value of adrenal scintigraphy in lateralisation of aldosterone producing adrenocortical adenoma was investigated in 33 patients, who were evaluated according to cure and compared to the scintigraphic pattern. Twenty-seven patients had scintigraphic images showing a unilateral uptake or a bilateral asymmetric uptake indicating unilateral aldosterone overproduction. Twenty-two of these patients were cured, 3 patients were improved, and 2 patients were not cured. Six patients had no uptake at scintigraphy. Adrenal scintigraphy at primary aldosteronism may be a useful complement at the preoperative lateralisation. Paper IV. The majority of adrenocortical incidentaloma are non-hyperfunctioning adrenal adenoma. Some of them may have autonomous cortisol production not fully restrained by the hypothalamus-pituitary-adrenal-axis. The median ratio of CYP17 to CYP11B1 expression for tumours from patients with Cushing´s syndrome was significantly higher than the median ratio for the non-hyperfunctioning tumours. In patients with subclinical Cushing´s syndrome the tumours have a similar high ratio indicating that these patients may be identified with this method.