Research Areas

The pituitary gland, or "master gland," is a small organ at the brain's base regulating growth, metabolism and reproduction through hormone release. Pituitary adenomas are benign tumors affecting hormonal balance. Adult-onset craniopharyngioma can cause hypothalamic dysfunction, leading to obesity, insulin resistance, sleep and behavioral disorders, and reduced life quality after surgery.

While craniopharyngioma is a rare, benign parasellar tumor, it incurs significant mortality and morbidity from cardiovascular and cerebrovascular diseases due to hypothalamic syndrome and its metabolic sequelae. In a retrospective analysis of 35 patients with AoCP who underwent surgery at our institution, most had developed new-onset obesity, with nearly half developing new-onset Type 2 diabetes mellitus. Among those with liver imaging, most had metabolic dysfunction-associated steatotic liver disease (MASLD), with some progressing to metabolic dysfunction-associated steatohepatitis (MASH) and cirrhosis. Prospective study of six patients with AoCP confirmed that these metabolic changes start within the first year after surgery. By three months postop, elevated liver enzymes and steatosis were seen in most patients. By 12 months, all had steatosis and either diabetes or prediabetes (Cooper J Endocr Soc 2024). We then explored whether growth hormone replacement in these patients who manifest panhypopituitarism can mitigate metabolic dysfunction. We analyzed data from the Hypopituitary Control and Complications Study (HypoCCS), a global prospective surveillance study of adult GH replacement. In 592 patients with AoCP, GH replacement did not improve hepatic outcomes but did improve waist-hip ratio and lipid profiles, suggesting the need to further explore novel approaches to mitigating the development of metabolic complications in AoCP (Cooper J Endocr Soc 2025). I collaborated with colleagues around the world to compile a research topic collection highlighting the ongoing challenges in care and gaps in our understanding of AoCP (Cooper Front Endocrinol 2025). I presented our pilot data on proteomic and metabolomic profiling in craniopharyngioma at the 2026 Endocrine Society meeting.

Postoperative hyponatremia occurs in up to 35% of patients following transsphenoidal surgery for pituitary adenomas and other parasellar masses. We conducted a retrospective study and prospective study aimed to clarify the additive effect of incremental strategies to reduce rates of postoperative hyponatremia. Patient education and protocolized postoperative care plans significantly improved adherence to a protocol of 1L per day of fluid restriction on postoperative days 4–7, which was highly effective at decreasing rates of delayed hyponatremia and hospital readmission by 50%. Results of our study emphasized the importance of a standardized fluid restriction protocol and intervention for prevention of postoperative hyponatremia and hospital readmission and confirmed the challenges of using clinical features to predict those at risk for hyponatremia (Cooper J Clin Endocrinol Metab 2023).

In preclinical studies of pituitary-directed molecular targets, we showed that human prolactinomas express nuclear EGFR and membranous ErbB2, ErbB3 and ErbB4, and that expression correlates with tumor invasion. Pituitary tumor cell lines transfected with EGFR and ErbB2 had downstream effects on prolactin (PRL) gene expression and secretion, as well as on cell proliferation, and animal models implanted with these cell lines developed larger tumors and PRL elevations. Treatment with ErbB tyrosine kinase inhibitors (TKIs) led to regression of xenografted tumors and attenuated PRL secretion. Primary culture of human prolactinomas confirmed expression of ErbB receptors and inhibitory effects of TKIs on PRL secretion and cell proliferation (Cooper Endocrine 2014). In an NIH R21-supported Phase IIa clinical trial, we showed that treatment of patients with aggressive prolactinomas with the EGFR TKI lapatinib may be an effective option for these difficult-to-treat patients (Cooper J Clin Endocrinol Metab 2021).

Corticotroph adenomas are immunopositive for adrenocorticotrophic hormone (ACTH) and are associated with features of hypercortisolism in patients with Cushing's disease. Silent corticotroph adenomas (SCAs) do not manifest biochemical or clinical evidence of hypercortisolism and are typically resected because of mass effects. In a retrospective study of 25 SCAs at our institution, we demonstrated that SCAs have a more aggressive course than do nonfunctioning adenomas, both in terms of recurrence and new-onset hypopituitarism. Using translational pathology, we showed that SCAs incorporate both corticotroph and gonadotroph cell markers, suggesting a common pituitary progenitor cell origin that may underlie its more aggressive behavior (Cooper Horm Cancer 2010).