Three Endocrine Neoplasms: An Unusual Combination of Pheochromocytoma, Pituitary Adenoma, and Papillary Thyroid Carcinoma

Background: Three endocrine neoplasms?bilateral pheochromocytomas, somatotrophic pituitary adenoma inducing acromegaly, and papillary carcinoma of the thyroid?occurred concurrently in a patient. A genetic mutation was hypothesized. Possible previously described genetic mutations were explored. Methods: Clinical assessments, laboratory data, images of tumors, histopathology, and immunohistochemistry of excised tissues documented the three neoplasms. Clinical assessment of the patient, family history, and a review of the literature sought a familial basis for the disorders. Results: The methods confirmed the presence of three endocrine neoplasms. Each neoplasm was surgically excised and histologically verified. Surgical and 131I treatments reduced the papillary carcinoma, but eventually this tumor progressed to a lethal degree. History, including that of nine siblings, uncovered no familial neoplasms. No similar case was found in the literature, but possible associations with germline mutations were considered. Conclusions: The concurrent development of pheochromocytomas, pituitary somatotrophic adenoma, and papillary thyroid carcinoma appears to be unique. Nevertheless, such tumors, particularly bilateral pheochromocytomas, strongly suggest a de novo germline mutation in a gene not previously associated with multiple endocrine neoplasia syndromes.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/98488/1/thy%2E2011%2E0345.pd

Implications of the TCGA Genomic Characterization of Papillary Thyroid Carcinoma for Thyroid Pathology: Does Follicular Variant Papillary Thyroid Carcinoma Exist?

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/140262/1/thy.2014.0540.pd

Review of Alpha-Ketoglutaric Acid (AKGA) Hydrazine and Monomethylhydrazine (MMH) Neutralizing Compound

The Johnson Space Center (JSC) White Sands Test Facility (WSTF) and NASA Engineering and Safety Center (NESC) were requested by NASA Associate Administrator for Space Operations to perform an evaluation of a proposed hydrazine/monomethylhydrazine (MMH) fuel treatment method using alpha-ketoglutaric acid (AKGA). This evaluation request was prompted by preliminary tests at the Kennedy Space Center (KSC), suggesting cost and operational benefits to NASA for the Space Shuttle Program (SSP) and other hardware decontamination and decommissioning, in addition to hydrazine and MMH waste treatment activities. This paper provides the team's position on the current KSC and New Mexico Highlands University (NMHU) efforts toward implementing the AKGA treatment technology with flight hardware, ground support equipment (GSE), hydrazine and MMH spills, and vapor control. This evaluation is current to the last data examined (approximately September 2008)

Discordance between imaging and immunohistochemistry in unilateral primary aldosteronism

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/139975/1/cen13442.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/139975/2/cen13442_am.pd

Notch signaling regulates gastric antral LGR5 stem cell function

The major signaling pathways regulating gastric stem cells are unknown. Here we report that Notch signaling is essential for homeostasis of LGR5+ antral stem cells. Pathway inhibition reduced proliferation of gastric stem and progenitor cells, while activation increased proliferation. Notch dysregulation also altered differentiation, with inhibition inducing mucous and endocrine cell differentiation while activation reduced differentiation. Analysis of gastric organoids demonstrated that Notch signaling was intrinsic to the epithelium and regulated growth. Furthermore, in vivo Notch manipulation affected the efficiency of organoid initiation from glands and single Lgr5‐GFP stem cells, suggesting regulation of stem cell function. Strikingly, constitutive Notch activation in LGR5+ stem cells induced tissue expansion via antral gland fission. Lineage tracing using a multi‐colored reporter demonstrated that Notch‐activated stem cells rapidly generate monoclonal glands, suggesting a competitive advantage over unmanipulated stem cells. Notch activation was associated with increased mTOR signaling, and mTORC1 inhibition normalized NICD‐induced increases in proliferation and gland fission. Chronic Notch activation induced undifferentiated, hyper‐proliferative polyps, suggesting that aberrant activation of Notch in gastric stem cells may contribute to gastric tumorigenesis.SynopsisThe Notch signaling pathway is required to maintain LGR5+ antral stem cells and epithelial cell homeostasis.Gastric antral stem cells display active Notch1 receptor signaling.Global Notch inhibition reduces stem and progenitor cell proliferation and increases differentiation of all lineages.Notch activation in LGR5+ stem cells increases stem and progenitor cell proliferation and inhibits differentiation.Notch activation enhances antral stem cell function, leading to tissue expansion via gland fission and tumor formation.The Notch signaling pathway is required to maintain LGR5+ antral stem cells and epithelial cell homeostasis.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/115949/1/embj201490583-sup-0002-EVFigs.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/115949/2/embj201490583.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/115949/3/embj201490583.reviewer_comments.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/115949/4/embj201490583-sup-0001-Appendix.pd

Thyroid Carcinoma Metastasis to Skull with Infringement of Brain: Treatment with Radioiodine

Background: Infringement by differentiated thyroid carcinoma on the brain is rare but, when suspected, the patient deserves special attention. A patient with an enlarging metastasis of thyroid carcinoma to the skull that was impinging on the brain illustrates diagnostic and therapeutic strategies applicable to the treatment of metastatic carcinoma. Methods: A case study was performed. Computed tomography (CT) and magnetic resonance imaging (MRI) were done, serum thyroglobulin was measured, and tumor responses to thyroxine and 131I treatments were monitored. Tumor dosimetry, enabled by scintigraphy with 131I employing single photon emission tomography fused with CT (SPECT-CT), was performed. Results: The metastasis was from a follicular variant of papillary thyroid carcinoma. During thyrotropin stimulation the tumor enlarged. The tumor decreased in volume after each of two 131I therapies. Dosimetry indicated delivery of 1970 and 2870cGy to the tumor and 35 and 42cGy to the brain, respectively, in the two treatments. The patient has survived for more than 11 years since diagnosis. Conclusions: A metastasis from a follicular variant of papillary carcinoma increased in volume during hypothyroidism producing more infringement on the brain. Beyond the effects of thyroxine therapy, 131I treatments induced recession of tumor volume. In patients with metastases that concentrate 131I, dosimetry with SPECT-CT can predict absorbed doses of radiation to the tumor and to the adjacent organs and thus lay a basis for data-based decisions on 131I therapies. Therapy may induce prolonged survival in patients with metastases infringing on the brain.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/78102/1/thy.2008.0426.pd

HIV testing implementation in two urban cities: Practice, policy and perceived barriers

Background Although funding has supported the scale up of routine, opt-out HIV testing in the US, variance in implementation mechanisms and barriers in high-burden jurisdictions remains unknown. Methods We conducted a survey of health care organizations in Washington, DC and Houston/Harris County to determine number of HIV tests completed in 2011, policy and practices associated with HIV testing, funding mechanisms, and reported barriers to testing in each jurisdiction and to compare results between jurisdictions. Results In 2012, 43 Houston and 35 DC HIV-testing organizations participated in the survey. Participants represented 85% of Department of Health-supported testers in DC and 90% of Department of Health-supported testers in Houston. The median number of tests per organization was 568 in DC and 1045 in Houston. Approximately 50% of organizations in both DC and Houston exclusively used opt-in consent and most conducted both pre- and post-test counseling with HIV testing (80% of organizations in DC, 70% in Houston). While the most frequent source of funding in DC was the Department of Health, Houston organizations primarily billed the patient or third-party payers. Barriers to testing most often reported were lack of funding, followed by patient discomfort/refusal with more barriers reported in DC. Conclusions Given unique policies, resources and programmatic contexts, DC and Houston have taken different approaches to support routine testing. Many organizations in both cities reported opt-in consent approaches and pre-test counseling, suggesting 2006 national HIV testing recommendations are not being followed consistently. Addressing the barriers to testing identified in each jurisdiction may improve expansion of testing