Background: Tyrosine hydroxylase (TH) is the first enzyme in the pathway of catecholamine synthesis catalyzing the conversion of tyrosine to dihydroxyphenylalanine (DOPA). To establish a molecular marker for adrenal pheochromocytomas, we compared the expression in various adrenal tumors in comparison to normal adrenal glands.
Methods: Tissue from 19 pheochromocytomas (PHEO), 20 aldosterone-producing adenomas (APA), 20 cortisol-producing adenomas (CPA), and 20 non-functional adenomas (NFA) was obtained following laparoscopic surgery. Seven normal adrenal glands were obtained during autopsy. The diagnosis was confirmed by various biochemical tests, histological investigation, and clinical follow-up. Extracted RNA underwent Real Time RT-PCR using TH specific primers and probe (detection limit 3.2×102 copies/μg RNA (cp)). mRNA levels were normalized to GAPDH mRNA levels. ROC analysis was performed to established cut-offs with specificity of at least 95%.
Results: PHEO demonstrated higher TH expression with a median of 8.6×106 cp (range 7.2×1044.3×107 cp) than detected in normal adrenal glands with a median of 1.1×106 cp (range 7.4×1031.8×107 cp). In contrast, expression was significantly lower (P<0.001) in APA, CPA, and NFA with 2.8×104 cp (3.5×1021.6×106 cp), 5.3×103 cp (7.5×1022.5×105 cp), and 6.6×103 cp (3.2×1021.5×107 cp), respectively. ROC analysis suggested a threshold of 1.1×106 cp with a sensitivity of 95% and specificity of 95%. No significant correlations were found between TH expression and nor-/metanephrine levels, chromogranin A levels or tumor size.
Conclusion: Characterization of TH expression may serve as a molecular marker to distinguish adrenal pheochromocytomas from other adrenal neoplasms. Such criteria could be used to evaluate biochemical tests for the diagnosis of these tumors.
25 - 29 Apr 2009
European Society of Endocrinology