Browsing by Subject "Pituitary tumors"

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    Germline loss-of-function PAM variants are enriched in subjects with pituitary hypersecretion
    (Cold Spring Harbor Laboratory, 2023-01-20) Trivellin, Giampaolo; Daly, Adrian F.; Hernández-Ramírez, Laura C.; Araldi, Elisa; Tatsi, Christina; Dale, Ryan K.; Fridell, Gus; Mittal, Arjun; Faucz, Fabio R.; Iben, James R.; Li, Tianwei; Vitali, Eleonora; Stojilkovic, Stanko S.; Kamenicky, Peter; Villa, Chiara; Baussart, Bertrand; Chittiboina, Prashant; Toro, Camilo; Gahl, William A.; Eugster, Erica A.; Naves, Luciana A.; Jaffrain-Rea, Marie-Lise; de Herder, Wouter W.; Neggers, Sebastian Jcmm; Petrossians, Patrick; Beckers, Albert; Lania, Andrea G.; Mains, Richard E.; Eipper, Betty A.; Stratakis, Constantine A.; Pediatrics, School of Medicine
    Pituitary adenomas (PAs) are common, usually benign tumors of the anterior pituitary gland which, for the most part, have no known genetic cause. PAs are associated with major clinical effects due to hormonal dysregulation and tumoral impingement on vital brain structures. Following the identification of a loss-of-function variant (p.Arg703Gln) in the PAM gene in a family with pituitary gigantism, we investigated 299 individuals with sporadic PAs and 17 familial isolated pituitary adenomas kindreds for PAM variants. PAM encodes a multifunctional protein responsible for the essential C-terminal amidation of secreted peptides. Genetic screening was performed by germline and tumor sequencing and germline copy number variation (CNV) analysis. No germline CNVs or somatic single nucleotide variants (SNVs) were identified. We detected seven likely pathogenic heterozygous missense, truncating, and regulatory SNVs. These SNVs were found in sporadic subjects with GH excess (p.Gly552Arg and p.Phe759Ser), pediatric Cushing disease (c.−133T>C and p.His778fs), or with different types of PAs (c.−361G>A, p.Ser539Trp, and p.Asp563Gly). The SNVs were functionally tested in vitro for protein expression and trafficking by Western blotting, for splicing by minigene assays, and for amidation activity in cell lysates and serum samples. These analyses confirmed a deleterious effect on protein expression and/or function. By interrogating 200,000 exomes from the UK Biobank, we confirmed a significant association of the PAM gene and rare PAM SNVs to diagnoses linked to pituitary gland hyperfunction. Identification of PAM as a candidate gene associated with pituitary hypersecretion opens the possibility of developing novel therapeutics based on altering PAM function.
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    The Need for Patient-centered Education Among Patients Newly Diagnosed With a Pituitary Tumor
    (Endocrine Society, 2021-04-07) Donegan, Diane; Gowan, Tayler; Gruber, Rachel; Cottingham, Ann; Flanagan, Mindy; Erickson, Dana; Imperiale, Thomas F.; Medicine, School of Medicine
    Objectives: Brain tumors, including pituitary adenomas (PA), cause anxiety and distress, with a high unmet need for information correlating with increased anxiety. Condition-specific education may alleviate anxiety. We explored patients' experience around the diagnosis of a PA and piloted a patient education intervention to address peridiagnostic anxiety in adults diagnosed with PA. Methods: Anxiety, patient satisfaction, patient knowledge, and need for information were measured prior to, immediately after, and 1 month following the appointment in this multimethods study. A phone interview to explore patient diagnostic and intervention experiences was analyzed using qualitative methods. Results: A total of 17 patients participated in the study; 15 completed the interview. The baseline need for information was high. Disease-specific anxiety decreased, and patient knowledge and satisfaction increased significantly after the initial visit. Interview analysis identified 3 main themes: (1) the importance of communication; (2) the need for information; and (3) the impact of the diagnosis on patient experience. Conclusions: For patients with newly diagnosed PA, the diagnostic experience was associated with high levels of anxiety. Patients expressed a need for information. Information delivery reduced anxiety and had a positive impact on patient satisfaction. Practice implications: The study findings suggest a need for a streamlined diagnostic process with readily accessible information.