Double adenomas of the pituitary reveal distinct lineage markers, copy number alterations, and epigenetic profiles

Purpose Pituitary adenoma (PA) constitutes the third most common intracranial neoplasm. The mostly benign endocrine lesions express no hormone (null cell PA) or the pituitary hormone(s) of the cell lineage of origin. In 0.5–1.5% of surgical specimens and in up to 10% of autopsy cases, two or three seemingly separate PA may coincide. These multiple adenomas may express different hormones, but whether or not expression of lineage-restricted transcription factors and molecular features are distinct within multiple lesions remains unknown. Methods Searching the data bank of the German Pituitary Tumor Registry 12 double pituitary adenomas with diverse lineage were identified among 3654 adenomas and 6 hypophyseal carcinomas diagnosed between 2012 and 2020. The double adenomas were investigated immunohistochemically for expression of hormones and lineage markers. In addition, chromosomal gains and losses as well as global DNA methylation profiles were assessed, whenever sufficient material was available (n = 8 PA). Results In accordance with the literature, combinations of GH/prolactin/TSH–FSH/LH adenoma (4/12), GH/prolactin/TSH–ACTH adenoma (3/12), and ACTH–FSH/LH adenoma (3/12) were observed. Further, two out of 12 cases showed a combination of a GH/prolactin/TSH adenoma with a null-cell adenoma. Different expression pattern of hormones were confirmed by different expression of transcription factors in 11/12 patients. Finally, multiple lesions that were molecularly analysed in 4 patients displayed distinct copy number changes and global methylation pattern. Conclusion Our data confirm and extend the knowledge on multiple PA and suggest that such lesions may origin from distinct cell types.

Two Cases of Double Adenomas in a Surgical Series over 16 Years in a Single Centre

Background: Double pituitary adenomas (DA) are two morphologically and immunohystochemically different tumours in the same gland. They are rare, generally small adenomas and divided in: separated, when clearly recognizable before or during surgery, and contiguous, when diagnosed only in the following histopathological examination. Acromegaly and Cushing’s disease are the main prevalent clinical presentation. Objective: We described two cases of DA in a surgical series over 16 years in a single center. Methods: In September 2018 we diagnosed a DA in a man with acromegaly (case 1). In order to assess the presence of other cases of DA, we performed a retrospective analysis of the endonasal endoscopically operated sellar adenomas from January 2004 to December 2019. Results : 468 pituitary adenomas were found. A DA with a Pit-1 positive small macroadenoma (GH-TSH- PRL positive) and an ACTH microadenoma clinically silent in an acromegalic woman was retrospectively found (case 2). Conclusion : Our analysis confirms that DA are rare (0.4 % of the pituitary adenomas) and often associated with acromegaly. Their pre-operatively diagnosis is difficult but clinician’s awareness of DA can improve the diagnosis. The use of pituitary transcription factors could be useful in detecting DA.

Use of Preoperative Imaging in Primary Hyperparathyroidism

Context Preoperative imaging is performed routinely to guide surgical management in primary hyperparathyroidism, but the optimal imaging modalities are debated. Objective Our objectives were to evaluate which imaging modalities are associated with improved cure rate and higher concordance rates with intraoperative findings. A secondary aim was to determine whether additive imaging is associated with higher cure rate. Design, Setting, and Patients This is a retrospective cohort review of 1485 adult patients during a 14-year period (2004-2017) at an academic tertiary referral center that presented for initial parathyroidectomy for de novo primary hyperparathyroidism. Main Outcome Measures Surgical cure rate, concordance of imaging with operative findings, and imaging performance. Results The overall cure rate was 94.1% (95% confidence interval, 0.93-0.95). Cure rate was significantly improved if sestamibi/single-photon emission computed tomography (SPECT) was concordant with operative findings (95.9% vs. 92.5%, P = 0.010). Adding a third imaging modality did not improve cure rate (1 imaging type 91.8% vs. 2 imaging types 94.4% vs. 3 imaging types 87.2%, P = 0.59). Despite having a low number of cases (n = 28), 4-dimensional (4D) CT scan outperformed (higher sensitivity, specificity, positive predictive value, negative predictive value) all imaging modalities in multiglandular disease and double adenomas, and sestamibi/SPECT in single adenomas. Conclusions Preoperative ultrasound combined with sestamibi/SPECT were associated with the highest cure and concordance rates. If pathology was not found on ultrasound and sestamibi/SPECT, additional imaging did not improve the cure rate or concordance. 4D CT scan outperformed all imaging modalities in multiglandular disease and double adenomas, and sestamibi/SPECT in single adenomas, but these findings were underpowered.

Prospective comparison of high resolution ultrasonography with technetium sestamibi scintigraphy and operative findings in detection of abnormally hyper functioning parathyroid gland/glands in primary hyperparathyroidism

Background:Ultrasonography is cheap, easily available and convenient modality of diagnosis.Methods: We prospectively studied 61 patients with PHPT. Patients preoperatively underwent USG neck and MIBI scan, results were interpreted independently and compaired with intra operative findings.Results:61 patients who underwent parathyroidectomy for PHPT were studied. Ultrasonography neck showed correct side in 46/51 (90%) and correct site in 32/51 (63%) patients with single parathyroid adenomas. MIBI scan showed correct side and site of parathyroid adenoma in 46/50 (92%) and 43/50 (86%) patients respectively. Patients with double adenomas USG neck showed positive results in all 5 patient with 100% sensitivity where as MIBI scan showed positive results in four out of five patients (80%). 1 patient with four gland hyperplasia USG picked three out of four enlarged glands while as MIBI scan not picked any of the enlarged glands. Operative findings revealed that right lower parathyroid gland was the most common gland involved (54%) followed by left lower (29%), right upper (6.6%), left upper (0%) and multiple / bilateral (9.6%).Conclusions:USG is an affordable, conventional and useful tool in detecting enlarged parathyroid glands in most of the patients with PHPT, but operator dependant. However, when USG can’t detect enlarged parathyroid gland 99mTc-MIBI Scan is complimentary to it.