Metabolomics – a Promising Approach to Pituitary Adenomas

Introduction

Difficulty in establishing the diagnosis of Cushing's disease is well known, given the impossibility of performing a biopsy of the ACTH-secretory pituitary adenomas due to their extremely small size. This impediment can be overcome if we observe the results obtained by Oklu et al. (2013) in their metabolomics study. In this study, eight patients with suspected Cushing's disease, who presented clinical manifestations suggestive of hypercorticism (e.g., hypertension, osteoporosis, easy bruising, weight gain, fatigue, diabetes mellitus, hirsutism, moon face, etc.), but with indeterminate imaging, were evaluated. To confirm the diagnosis, these patients underwent bilateral inferior petrosal sinus sampling with dosage of central blood samples at 0’, 3’, 5’, 10’, and 15’ after intravenous injection of CRH. ACTH-secretory pituitary adenomas were confirmed in seven patients, while in one patient, the diagnosis was excluded. Plasma obtained after centrifugation of central blood samples from the ipsilateral inferior petrosal sinus to ACTH-secreting adenomas (seven samples) was compared to contralateral plasma samples and two samples from the patient to whom the ACTH secretion had not been documented (nine samples).

Metabolomics – A Promising Approach to Pituitary Adenomas

Postoperative follow-up showed an improvement in symptomatology in four patients and a remission of symptoms in the remaining three patients. Using three LC-MS methods (hydrophilic interaction liquid chromatography method for analyses of polar metabolites in the positive and negative ion modes respectively, and a reversed-phase method to profile lipids in the positive ion mode), initially identified 12 significantly different metabolites in ACTH-pituitary adenomas compared to the control group (p

First Metabolomics Study on Pituitary Adenomas

The first metabolomics study on pituitary adenomas was conducted by Oklu et al. (2013). They evaluated the metabolomic profile in seven patients with ACTH-secreting pituitary adenomas using plasma from the inferior petrosal sinus in comparison with nine contralateral plasma samples. The results showed that metabolites such as deoxycholic acid, 3-methyladipate, and pyridoxate were significantly altered. The pathways affected included alanine, aspartate, and glutamate metabolism, vitamin B metabolism, lysine biosynthesis, purine metabolism, amino sugar and nucleotide sugar metabolism, glycolysis or gluconeogenesis, and starch and sucrose metabolism.

Recent Studies on Metabolomics

In 2017, Ijare et al. used NMR spectrometry to assess the metabolomic profile in FSH/LH and PRL-secreting adenomas in postoperative pituitary tissue. They observed that both types of pituitary adenomas contain central nervous system metabolites such as phosphoethanolamine, glutamate, glutamine, N-acetyl aspartate, aspartate, and myo-inositol. Additionally, comparing these two types of pituitary adenomas, it was found that phosphoethanolamine, N-acetyl aspartate, and myo-inositol are downregulated in PRL-secreting pituitary adenomas, while aspartate, glutamate, and glutamine are upregulated. Ijare’s study is currently underway, and a larger number of patients could provide additional insights into the evaluation of the metabolomic fingerprint in the FSH/LH and PRL-pituitary adenomas. This ongoing research could lead to more precise diagnostic tools and therapeutic targets for these adenomas.

Conclusion

The metabolomics approach offers promising insights into the diagnosis and understanding of pituitary adenomas. The pioneering work by Oklu et al. (2013) and subsequent studies have laid the groundwork for future research. Continued advancements in metabolomics could potentially revolutionize the diagnostic and therapeutic landscape for pituitary adenomas, providing more personalized and effective treatment options.

References

Oklu, R., et al. (2013). Metabolomics study on ACTH-secreting pituitary adenomas. Journal of Clinical Endocrinology & Metabolism.

Ijare, O., et al. (2017). Metabolomic profiling of pituitary adenomas using NMR spectrometry. Endocrine Pathology.