Kumar, Aditi

Abstract While adrenal androgen production is primarily regulated by ACTH, some data suggest a less common association between hyperprolactinemia and elevated dehydroepiandrosterone sulfate (DHEA-S). We describe 2 patients with this underrecognized connection. Patient 1, a 60-year-old male, was incidentally found to have bilateral adrenal masses on computed tomography during evaluation of gastrointestinal complaints. Further workup revealed elevated levels of DHEA-S and prolactin, with pituitary macroadenoma identified as the cause, given normalization of both prolactin and DHEA-S on cabergoline therapy. Patient 2, a 38-year-old male, presented with visual field defects, and subsequent pituitary magnetic resonance imaging confirmed a macroadenoma. He also had markedly elevated levels of DHEA-S and prolactin. Both patients were treated with cabergoline, leading to rapid normalization of both prolactin and DHEA-S levels. These cases demonstrate an association between hyperprolactinemia and elevated DHEA-S, supported by the normalization of levels with medical treatment of prolactinoma. Although hyperprolactinemia in the context of a prolactinoma is an uncommon cause of elevated DHEA-S, it should be considered once other etiologies have been excluded.

Abstract Background The overall survival of patients with advanced thyroid cancers that have progressed following targeted therapies is limited, indicating a strong need for salvage treatments. Methods We retrospectively analyzed patients with refractory advanced thyroid cancer treated with pemetrexed‐carboplatin (PC) at Mayo Clinic since 2019. Results Eleven patients, three with anaplastic thyroid cancer (ATC), seven with differentiated or poorly differentiated thyroid cancer (DTC), and one with oncocytic carcinoma of the thyroid, were treated with novel salvage PC. Patients with DTC ( n = 7) had durable responses with a median progression‐free survival of 29 months. One responder included a patient with ATC whose disease progressed following pembrolizumab/axitinib, lenvatinib, and dabrafenib/trametinib. On this fourth line treatment, the patient remains on therapy to date, over 12 months after initial response. Conclusions This case series reinforces prior published phase I clinical trial data and shows that pemetrexed can have potent efficacy in the treatment of the most advanced thyroid cancers.

Introduction: Multikinase inhibitors have clinical activity in radioactive iodine refractory (RAIR) differentiated thyroid cancers (DTCs) but are not curative; optimal management and salvage therapies remain unclear. This study assessed clinical effects of pazopanib therapy in RAIR-DTC patients with progressive disease, examining in parallel biomarker that might forecast/precede therapeutic response. Methods: Assessment of responses and toxicities and of any association between thyroglobulin (Tg) changes cycle 1 and RECIST (response evaluation criteria in solid tumors) response to pazopanib therapy were prospectively undertaken in Tg antibody negative RAIR-DTC patients. RECIST progressive metastatic disease <6 months preceding enrollment was required. With a sample size of 68 (assuming 23 attaining partial response [PR]), there would be 90% chance of detecting a difference of >30% when the proportion of patients attaining PR whose Tg values decrease by >50% is >50% cycle 1 (one-sided α = 0.10, two sample test of proportions). Mean corpuscular volume (MCV) change or mutational status or pretreatment were also explored as early correlates of eventual RECIST response. Results: From 2009 to 2011, 60 individuals were treated and evaluated; (one additional patient withdrew; another was found ineligible before therapy initiation); 91.7% had previous systemic therapy beyond RAI. Adverse events included one death (thromboembolic) deemed possibly pazopanib associated. Twenty-two confirmed RECIST PRs resulted (36.7%, confidence interval; CI [24.6–50.1]); mean administered 4-week cycles was 10. Among 44 fully accessible patients, the Tg nadir was greater among the 20 attaining PR (median: −86.8%; interquartile range [IQR]: −90.7% to −70.9%) compared with the 28 who did not (median: −69.0%; IQR: −78.1% to −27.7%, Wilcoxon rank-sum test: p = 0.002). However, the difference in the proportion of PRs among those whose Tg fell ≥50% after cycle 1 versus those that did not were not significantly correlated (−23.5% [CI: −55.3 to 8.3]; Fisher's exact test p -value = 0.27). RECIST response was also not correlated with/predicted by early MCV change, receipt of prior therapy, or tumor mutational status. Conclusions: This trial prospectively confirmed pazopanib to have clinical activity and manageable toxicities in patients with progressive RAIR-DTC. Response to pazopanib, however, was not robustly forecast by early associated changes in Tg or MCV, by prior therapy, or by tumor mutational status. ClinicalTrials.gov NCT00625846.