Guo, Qinghua

AbstractPituitary stalk interruption syndrome (PSIS) is a rare type of hypopituitarism manifesting various degrees of pituitary hormone deficiency. Although mutations have been identified in some familial cases, the underpinning mechanisms of sporadic patients with PSIS who are in a vast majority remain elusive, necessitating a comprehensive study using systemic approaches. We postulate that other genetic mechanisms may be responsible for the sporadic PSIS. To test this hypothesis, we conducted a study in 24 patients with PSIS of Han Chinese with no family history using whole‐exome sequencing (WES) and bioinformatic analysis. We identified a group of heterozygous mutations in 92% (22 of 24) of the patients, and these genes are mostly associated with Notch, Shh, Wnt signalling pathways. Importantly, 83% (20 of 24) of the patients had more than one mutation in those pathways suggesting synergy of compound mutations underpin the pathogenesis of sporadic PSIS.

Objective The objective of this study was to determine whether dynamic magnetic resonance imaging (dMRI) enhancement parameters could predict dopamine agonist (DA) resistance in prolactinomas. Methods We retrospectively identified patients with prolactinomas who were treated with DA and underwent dMRI from 2001 through 2012 at Mayo Clinic (Rochester, MN). Intensities of the adenoma and pituitary gland were measured by drawing regions of interest on the images. Enhancement ratio, enhancement peak, prepeak slope (PPS), and enhancement time were compared between DA-resistant and DA-responsive groups, between DA-treated and DA-naive groups, and between the first and follow-up dMRIs. Results We identified 49 patients with prolactinomas, with 6 (12.2%) showing DA resistance. Thirty-seven patients (75.5%) underwent dMRI while receiving treatment, 12 (25.5%) underwent dMRI before starting therapy, and 10 (20.4%) had follow-up dMRI after DA therapy. The PPS of the tumor was higher in the treatment-resistant group versus the responsive group (mean [SD], 4.42 [3.19] vs 2.65 [1.59]; P = 0.03), whereas no difference was noted in the pituitary gland (5.79 [2.21] vs 4.06 [2.48]; P = 0.11). Logistic regression analysis indicated that tumor PPS was associated with DA resistance (odds ratio, 1.71; 95% confidence interval, 1.07–3.27; P = 0.02). Conclusions Dynamic MRI with PPS analysis potentially can be used early in the treatment course to evaluate DA resistance in pituitary prolactinomas.

SummaryPurposeThe distinction between corticotropin (ACTH)‐producing pituitary adenomas and occult ectopic ACTH neoplasms is a challenge and frequently complicated by the detection of nonfunctioning pituitary adenomas on dynamic magnetic resonance imaging (DMRI). Herein, we explored quantitative differences in DMRI measures from ACTH‐producing pituitary adenomas.Materials and methodsFifty‐five patients with pathology confirmed ACTH‐producing and 44 with nonfunctioning pituitary adenomas were analysed in this retrospective pilot study. The intensities of adenomas and of adjacent pituitary tissue were measured by drawing a region of interest. Time–intensity curves were then constructed, and quantitative analysis included: enhancement time, enhancement peak and prepeak slope (PPS). Multivariable logistic analysis and receiver operating characteristic curves (ROC) were used to evaluate the parameters.ResultsQuantitative analysis showed that tumour PPS in ACTH‐producing adenomas was markedly lower than that in nonfunctioning adenomas (P = 0·0042) and that the PPS of the adjacent pituitary gland was not different (P = 0·2441). The PPS was >3·0 in 59·1% of nonfunctioning adenomas and ≤3·0 in 69·1% of ACTH‐producing adenomas (P = 0·0049). Logistic analysis revealed lower tumour PPS levels (P = 0·0123, OR 1·24, 95% CI: 1·05–1·52) were associated with ACTH‐producing adenomas. The optimal PPS cut‐off determined by ROC analysis was 2·89, with a sensitivity of 69% and specificity of 70%. No significant difference was found between the two groups in enhancement time or enhancement peak.ConclusionEnhancement parameters in DMRI can help distinguishing ACTH producing from nonfunctioning pituitary adenomas, which could be useful in the differential diagnosis between ACTH‐producing pituitary adenomas and ectopic ACTH syndrome complicated with nonfunctioning pituitary adenoma.