Faculty Bibliography

The majority of prolactinomas are treated with dopamine agonists (DA) with excellent response, however DA-resistance occurs in 10% of prolactinomas. Somatostatin (SST) receptors have been increasingly studied in prolactinomas. There are five SST receptor subtypes and a significant number of prolactinomas show expression of SST₅ and SST₁ mRNA. The somatostatin analog (SSA) pasireotide, which has 40-fold greater binding affinity to SST₅ compared to first-generation SSAs, shows promising results in case reports of DA-resistant prolactinomas. This two-center retrospective cohort study investigated the expression patterns of dopamine 2 (D2R), SST₂ and SST₅ receptors in surgical specimen of 34 patients with prolactinomas, 22 of which were DA-resistant. In vitro effects of cabergoline, octreotide and pasireotide on prolactin production was also examined in cultured prolactinoma cells. Receptor expression was scored using the immunoreactivity score (IRS). 31/34(91%) patients used DA preoperatively; 22/34(64.7%) were DA-resistant. Receptor expression in the cases was 97.1% for D2R, 70.6% for SST₅ and 41.2% for SST₂. In the majority of SST₂ positive cases SST₂ expression was very low. In in vitro studies comparing the effects of octreotide, pasireotide, and cabergoline on prolactin secretion, octreotide was the least potent drug and cabergoline was the most potent. SST₅ and D2R expression was highest in prolactinomas showing the highest response to pasireotide and cabergoline in vitro (median D2R IRS 1.0 vs 8.0 for < 50% vs. > 50% inhibition by cabergoline and median SST₅ IRS 3.5 avs. 12.0 for < 50% vs. > 50% inhibition by pasireotide). In a subgroup, pasireotide inhibited prolactin secretion with comparable potency to cabergoline. Targeting SST₅ with pasireotide may be a potential treatment modality for further clinical investigation in the treatment of a subset of DA resistant or intolerant prolactinomas.

INTRODUCTION:The purpose of this study is to examine the effect of admission glucose in patients hospitalized with COVID-19 with and without diabetes mellitus in a largely African American cohort. DESIGN AND METHODS:This study included 708 adults (89% non-Hispanic Black) admitted with COVID-19 to an urban hospital between 1 March and 15 May 2020. Patients with diabetes were compared with those without and were stratified based on admission glucose of 140 and 180 mg/dL. Adjusted ORs were calculated for outcomes of mortality, intubation, intensive care unit (ICU) admission, acute kidney injury (AKI), and length of stay based on admission glucose levels. RESULTS:Patients with diabetes with admission glucose >140 mg/dL (vs <140 g/dL) had 2.4-fold increased odds of intubation (95% CI 1.2 to 4.6) and 2.1-fold increased odds of ICU admission (95% CI 1.0 to 4.3). Patients with diabetes with admission glucose >180 mg/dL (vs <180 g/dL) had a 1.9-fold increased mortality (95% CI 1.2 to 3.1). Patients without diabetes with admission glucose >140 mg/dL had a 2.3-fold increased mortality (95% CI 1.3 to 4.3), 2.7-fold increased odds of ICU admission (95% CI 1.3 to 5.4), 1.9-fold increased odds of intubation (95% CI 1.0 to 3.7) and 2.2-fold odds of AKI (95% CI 1.1 to 3.8). Patients without diabetes with glucose >180 mg/dL had 4.4-fold increased odds of mortality (95% CI 1.9 to 10.4), 2.7-fold increased odds of intubation (95% CI 1.2 to 5.8) and 3-fold increased odds of ICU admission (95% CI 1.3 to 6.6). CONCLUSION:Our results show hyperglycemia portends worse outcomes in patients with COVID-19 with and without diabetes. While our study was limited by its retrospective design, our findings suggest that patients presenting with hyperglycemia require closer observation and more aggressive therapies.