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AbstractAs a result of treatment and diagnosis, adults with primary or metastatic brain tumors experience comorbidities that impacts their health and well-being. The Children’s Oncology Group has guideline recommendations for childhood survivors of brain tumors; however, guidelines for monitoring long-term sequela among adult brain tumor survivors are lacking. The purpose of this review is to present the screening recommendations for the long-term complications after brain tumor treatment from a multidisciplinary panel of healthcare professionals. Chronic complications identified include cognitive dysfunction, vasculopathy, endocrinopathy, ophthalmic, ototoxicity, physical disability, sleep disturbance, mood disorder, unemployment, financial toxicity, and secondary malignancy. We invited specialists across disciplines to perform a literature search and provide expert recommendations for surveillance for long-term complications for adult brain tumor survivors. The Brain Tumor Center Survivorship Committee recommends routine screening using laboratory testing, subjective assessment of symptoms, and objective evaluations to appropriately monitor the complications of brain tumor treatments. Effective monitoring and treatment should involve collaboration with primary care providers and may require referral to other specialties and support services to provide patient-centered care during neuro-oncology survivorship. Further research is necessary to document the incidence and prevalence of medical complications as well as evaluate the efficacy of screening and neuro-oncology survivorship programs.

A 52-year-old African woman was found to have a pelvic mass at the age of 41. Following resection of small bowel tumors at the time, she was diagnosed with GIST and peritoneal metastases were confirmed. Despite treatment with imatinib, her disease progressed and was started on regorafenib. Due to lack of consistent insurance coverage, she took this medication intermittently for several years, and her tumor progressed to develop intra-abdominal peritoneal and pelvic metastases. She underwent debulking surgery, and her disease subsequently remained stable with regorafenib. Unfortunately, she developed hemoptysis which led to discontinuation of regorafenib, and while off treatment, the patient developed altered mentation, extreme lethargy, and poor PO intake. She was found to have a serum calcium of 16 mg/dL and was admitted for treatment of severe hypercalcemia. With intravenous (IV) fluids, calcitonin and zoledronic acid, her calcium improved to 11-12 mg/dL; however, despite additional therapies, including denosumab and repeat zoledronic acid, her calcium did not normalize. Further evaluation revealed: 25-hydroxy-vitamin D3 level 22.2 ng/mL (normal), 1,25-dihydroxy-vitamin D3 107 mcg/mL (elevated), PTH 6. 0 pg/ml (low), and PTHrP 3.3pmol/L (low). She was given a diagnosis of calcitriol-mediated hypercalcemia and started on IV hydrocortisone 100 mg every 12 hours. Her serum calcium started to improve within 48 hours and normalized after eight days to 9.8mg/dL. Her clinical condition improved, and she was discharged with prednisone 20 mg daily. At the time of her post-hospital follow up several days later, her serum calcium remained normal. Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.

INTRO ACTH-secreting pheochromocytoma is rare, posing challenges in diagnosis and management. Here we report two cases with different presentations and pre-operative approaches. CASES Patient 1 A 59 yo female who presented for basal cell carcinoma resection experienced hypertensive crisis intra-op and NSTEMI due to stress cardiomyopathy. The patient reported spells of palpitations, diaphoresis, tremors and pallor since 2015. She had elevated plasma metanephrine (M) 19.4 (0-0.49nmol/L), normetanephrine (NM) 24.7 (0-0.89nmol/L), 24-hour urine M 18711 (30-180mcg) and NM 11897 (128-484mcg). Imaging demonstrated a 5.6 x 5.5 x 5.8cm left adrenal mass. After pre-operative alpha and beta blockade, patient underwent left adrenalectomy. Pre-op 24-hour urine cortisol was checked as part of secondary HTN evaluation and found to be elevated at 219 (3.5-45mcg). She did not have any features of Cushing’s and this was initially felt to be an appropriate stress response. Due to persistent post-op hypotension and a low 10PM random cortisol level of 3.4mcg/dL, which was inappropriate given patient’s clinical status, hydrocortisone was started with subsequent hemodynamic improvement. Our suspicion was that she had an ACTH-secreting pheochromocytoma, which would have resulted in hypercortisolism pre-op, and secondary AI post-op. Pathology report later confirmed ectopic ACTH production with 25% cells positive with immunostaining. Patient 2 A 48 yo female was admitted for hypertensive urgency with symptoms of palpitations, facial and abdominal swelling, easy bruising and proximal muscle weakness. Her labs showed elevated 24-hour urine epinephrine 115 (0-20mcg), norepinephrine 366 (0-135mcg), plasma M 288 (0-62pg/mL) and NM 475 (0-145pg/mL), and an AM cortisol was 47.9mcg/dL. Aldosterone and renin levels were DISCUSSION Within the past 6 months, we have seen 2 cases of ACTH-secreting pheochromocytoma with different clinical symptoms and pre-op courses. Ectopic ACTH secretion may not cause classic Cushingoid features as in patient 1. Failure to recognize ectopic ACTH pre-op can lead to post-op complications such as AI. Patient 2 demonstrates that treatment of the hypercortisolemia may be necessary in order to adequately control BP and glucose levels prior to surgery.

Background Hypergonadotropic hypogonadism (HH) is characterized by low sex steroid levels and secondarily elevated gonadotropin levels with either congenital or acquired etiology. Genetic factors leading to HH have yet to be fully elucidated. Methods Here, we report on genome and transcriptome data analyses from a male patient with HH and history of growth delay who has an inherited deletion of chromosome Xq28. Expression analyses were done for this patient and his unaffected family members and compared to normal controls to identify dysregulated genes due to this deletion. Results Our patient’s Xq28 deletion is 44,806 bp and contains only two genes, FUNDC2 and CMC4. Expression of both FUNDC2 and CMC4 are completely abolished in the patient. Gene ontology analyses of differentially expressed genes (DEGs) in the patient in comparison to controls show that significantly up-regulated genes in the patient are enriched in Sertoli cell barrier (SCB) regulation, apoptosis, inflammatory response, and gonadotropin-releasing regulation. Indeed, our patient has an elevated follicle stimulating hormone (FSH) level, which regulates Sertoli cell proliferation and spermatogenesis. In his mother and sister, who are heterozygous for this deletion, X-chromosome inactivation (XCI) is skewed toward the deleted X, suggesting a mechanism to avoid FSH dysregulation. Conclusion Compared to the previously reported men with variable sized Xq28 deletions, our study suggests that loss of function of FUNDC2 and CMC4 results in dysregulation of apoptosis, inflammation, and FSH, and is sufficient to cause Xq28-associated HH.

Objective: We describe a case of co-existing Graves disease and struma carcinoid in a woman with an ovarian mass and history of hyperthyroidism.Methods: Patient history, presentation, diagnostic studies, and treatment are described.Results: A 59-year-old female with an antecedent history of hyperthyroidism was scheduled for resection of a 4.1-cm left ovarian mass. Pre-operative labs demonstrated thyroid-stimulating hormone (TSH)

Head and neck paragangliomas are rare neuroendocrine tumors that arise from paraganglion cells of the parasympathetic nervous system. Paragangliomas arising from the midline skull base have only rarely been reported. Surgery is the mainstay of treatment and adjuvant radiation is often recommended. These tumors can rarely secrete metanephrines and normetanephrines which can complicate operative management. Here we present two cases of clival paragangliomas with unique clinical presentations and review the previous literature on skull base paragangliomas.

Background: The incidence of bilateral macronodular adrenal hyperplasia (BMAH) is unknown, but growing in an era of increased utilization of imaging. Coexistence of BMAH and pheochromocytoma has not previously been reported. Clinical Case: A 63-year man presented with enlarging left chest-wall mass found to have a poorly differentiated sarcoma. Staging PET/CT identified a hypermetabolic 2.0 cm left adrenal nodule with SVU of 16.6 concerning for metastasis. Hormonal evaluation included dexamethasone suppression test with 7AM serum cortisol of 24.7 ug/dL (1cm with bilateral gland enlargement consistent with BMAH. Resection of his left adrenal gland was not pursued due to cormorbidities as well as biochemically-silent nature of his pheochromocytoma. To manage his hypercortisolism, he was recently initiated on osilodrostat after completing radiation therapy for his chest-wall sarcoma. Conclusion: This is the first case demonstrating clinical, biochemical, and imaging results consistent with bilateral macronodular adrenal hyperplasia and hypercortisolism also found to have a clinically and biochemically silent, biopsy proven pheochromocytoma. This is also a unique use of osilodrostat to manage BMAH.

Primary bilateral macronodular adrenocortical hyperplasia (PBMAH) is an uncommon cause of adrenal Cushing syndrome (CS) in which cortisol and occasionally other steroid hormones can be secreted under the influence of aberrantly expressed G-protein coupled receptors (GPCRs) in the adrenal cortex. We describe the unique case of a 64-year-old postmenopausal female with PBMAH whose adrenal lesions expressed luteinizing hormone receptors (LHr). She presented initially with CS and underwent right adrenalectomy; a few years later she presented with macromastia and mastodynia, possibly due to estrogen excess from her remaining left adrenocortical masses. Testing before and after treatment with quarterly leuprolide acetate therapy and immunohistochemistry on tissue and targeted sequencing of the genes of interest were performed. Tissue from the patient’s right adrenal was tested for P450 aromatase (CYP19A1) and LHr expression; both were expressed throughout the hyperplastic cortex, although expression was more intense in the adenomatous areas. Targeted sequencing revealed a pathogenic PDE11A mutation, as well as variants in the ARMC5 and INHA genes. PDE11A expression was decreased in the adenoma but there was no loss of heterozygosity for the PDE11A locus. Because of the clinical presentation and LHr expression, quarterly leuprolide acetate therapy was started. Shortly after initiation of therapy, the patient reported decreased breast size and pain; she remains well controlled to date, after 10 years of treatment. This is the first description of a patient with PBMAH presenting with severe macromastia and mastodynia from what appears to be excess estrogen production from her adrenal tumor. The patient had a long-lasting response to chronic leuprolide acetate treatment, showing that drug therapy exploiting the aberrant receptor expression in PBMAH is possible even in the absence of cortisol overproduction.