Browsing by Author "Donegan, Diane"
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Item A novel preoperative score to predict long-term biochemical remission in patients with growth-hormone secreting pituitary adenomas(Elsevier, 2023) Cohen-Cohen, Salomon; Rindler, Rima; Botello Hernandez, Edgar; Donegan, Diane; Erickson, Dana; Meyer, Fredric B.; Atkinson, John L.; Van Gompel, Jamie J.; Medicine, School of MedicineObjective Transsphenoidal surgery (TSS) is considered the treatment of choice in most patients with growth hormone (GH)-secreting pituitary adenomas. Several preoperative factors have been studied to predict postsurgical remission. Our objective was to design a score that could be used in the preoperative setting to identify patients that will achieve long-term biochemical remission after TSS. Methods A retrospective analysis of consecutive patients with GH-secreting pituitary adenomas that underwent TSS in our institution from 2000 to 2015 who fulfilled prespecified criteria were included. Logistic regression methods were used to evaluate independent preoperative variables predicting long-term remission. Beta coefficients were used to create a scoring system for clinical practice. Results Sixty-eight patients were included, with a mean follow-up time of 87 months. Twenty (29%) patients had tumors with a Knosp grade ≥ 3A. Gross-total resection was achieved in 43 (63%) patients. Thirty-three (48%) patients had long-term biochemical remission after TSS. In a multivariate analysis, the following variables were statistically significantly associated with long-term biochemical remission: age, adenoma size (diameter), Knosp grade, GH level, and insulin growth-factor 1index 1 at diagnosis. A score of <3 out of 8 total points was identified as a cutoff associated with long-term remission, with a sensitivity of 91.4% and specificity of 72.7% (AUC 0.867, OR 28.44, 95% CI 6.94–116.47, P = < 0.001). Conclusions A novel, simple, easy-to-use scoring system was created to identify patients with the highest chances of long-term biochemical remission following TSS. This scale should be prospectively validated in a multicenter study before widespread adoption.Item Autologous stem cell transplantation in adults with atypical teratoid rhabdoid tumor: a case report and review(Taylor & Francis, 2024) Griffith-Linsley, Jackson; Bell, William Robert; Cohen-Gadol, Aaron; Donegan, Diane; Richardson, Angela; Robertson, Michael; Shiue, Kevin; Nevel, Kathryn; Pathology and Laboratory Medicine, School of MedicineAim: Atypical teratoid rhabdoid tumor (ATRT) is a rare and highly aggressive primary CNS neoplasm, predominantly observed in children. The use of autologous stem cell transplantation (ASCT) in pediatric ATRT has shown promise; however, its utility in adult ATRT remains unclear. Patients & methods: This study presents the case of an adult patient with ATRT who is in remission after ASCT and reviews the literature on ASCT in adults with ATRT. Four cases of ATRT in adults who underwent ASCT were identified, with pertinent data summarized. Results: All five patients survived longer than the historical average survival rate, four of whom had no clinical or radiographic evidence of disease at the final follow-up. Conclusion: Based on limited data, there may be a role for ASCT in the treatment of adults with ATRT.Item Hyperphosphatemic Tumoral Calcinosis With Pemigatinib Use(Elsevier, 2022-07-16) Puar, Akshan; Donegan, Diane; Helft, Paul; Kuhar, Matthew; Webster, Jonathan; Rao, Megana; Econs, Michael; Medicine, School of MedicineBackground/objective: Pemigatinib, a fibroblast growth factor receptor (FGFR) 1-3 inhibitor, is a novel therapeutic approach for treating cholangiocarcinoma when an FGFR fusion or gene rearrangement is identified. Although the most reported side effect of pemigatinib is hyperphosphatemia, tumoral calcinosis with soft tissue calcifications is not widely recognized as a complication. We report a case of patient with hyperphosphatemic tumoral calcinosis on pemigatinib. Case report: A 59-year-old woman with progressive metastatic cholangiocarcinoma, despite receiving treatment with cisplatin and gemcitabine for 7 months, was found to have an FGFR2-BICC1 fusion in the tumor on next-generation sequencing. Pemigatinib was, therefore, initiated. Four months into the therapy, multiple subcutaneous nodules developed over the lower portion of her back, hips, and legs. Punch biopsies revealed deep dermal and subcutaneous calcifications. Investigations revealed elevated serum phosphorus (7.5 mg/dL), normal serum calcium (8.7 mg/dL), and elevated intact fibroblast growth factor-23 (FGF23, 1216 pg/mL; normal value <59 pg/mL) levels. Serum phosphorus levels improved with a low-phosphorus diet and sevelamer. Calcifications regressed with pemigatinib discontinuation. Discussion: Inhibition or deficiency of FGF-23 results in hyperphosphatemia and can lead to ectopic calcification. Pemigatinib, a potent inhibitor of FGFR-1-3, blocks the effect of FGF-23 leading to hyperphosphatemia and tumoral calcinosis as observed in our case. Treatment is aimed primarily at lowering serum phosphate levels through dietary restriction or phosphate binders; however, the regression of tumoral calcinosis can occur with pemigatinib cessation, as seen in this case. Conclusion: As the use of FGFR 1-3 inhibitors becomes more prevalent, we aim to raise attention to the potential side effects of tumoral calcinosis.Item Incidence of Venous Thromboembolic Events in Patients With Endogenous Cushing Syndrome(Endocrine Society, 2021-05-03) Subbu, Karthik; Tariq, Zunera; Erickson, Dana Z.; Bancos, Irina; Donegan, Diane; Medicine, School of MedicineBackground: Hypercortisolemia is a hypercoagulable state associated with increased risk of venous thromboembolic events (VTE). The reported incidence of VTE in patients with ACTH-dependent or independent Cushing Syndrome (CS) is variable, ranging from 3 to 14%. Our aim was to assess the incidence of clinically significant VTE among patients with endogenous CS and to identify risk factors for the development of VTE. Methods: We conducted a single center retrospective longitudinal study of adult patients diagnosed with endogenous CS between 2010 and 2020. Patients with a known prothrombotic disease (e.g. Factor V Leiden), insufficient data, or non-neoplastic hypercortisolism were excluded. Data collected included patient demographics, presenting symptoms, biochemical and radiological workup, treatment details, and incidence of clinically significant VTE. Results: A total of 114 patients (mean age of 45.55 ± 14.78 years, 79.8% women) followed for mean of 3.26 ± 2.9 years were included. Of the 114 patients, 58 (50.9%) had Cushing disease (CD), 40 (35.1%) had CS due to adrenal adenoma/hyperplasia, 6 (3.5%) had adrenocortical carcinoma (ACC), and 10 (8.8%) had ectopic Cushing syndrome (eCS). The overall incidence of VTE at any time point was 14/114 (12.3%); 11 (79%) VTEs were associated with presence of an additional VTE risk factor (8 surgery and 3 malignancy). Prior to any intervention for CS, 3 of 114 (2.6%) patients had a VTE. Surgery for CS (adrenalectomy, transsphenoidal surgery, tumor resection) was performed in 97 patients (85.1%) whereas 17 were treated medically (n=10), died before treatment (n=1) or observed (n=6). VTE occurred in 2 patients receiving medical therapy for CS. The post-operative incidence of VTE was 9 (9.3%; 4 in CD, 1 in adrenal CS, 3 in ACC, and 1 in eCS). VTE occurred ≤ 3-month post-operative in 4 patients (44.4%). Among the 5 patients in whom VTE occurred >3 months post-operative, 3 had recurrent metastatic ACC with hypercortisolemia and 2 were in remission (1 with CS and 1 with eCS). The median time from surgery to VTE occurrence was 315 days (8-1006). Compared to those who did not develop VTE, those who developed VTE had higher mean 24-hour urine free cortisol (4663.6 vs 558.21 mcg/dL; n = 100, P < 0.0001) and mean 1 mg overnight dexamethasone suppression test (36.3 vs 11.8 mcg/dL; n = 69, P = 0.0003), but similar mean late-night salivary cortisol (0.591 vs 0.790 ng/dL, n = 84, P = 0.71) at diagnosis of CS. Discussion: Among those with CS, the overall incidence of VTE was 12.3% and the majority of VTE were provoked (surgery, malignancy). Moreover, VTE was more likely in those with higher UFC and 1 mg overnight dexamethasone suppression test in our cohort. This suggests that in patients with CS who have an active malignancy, severe CS or those undergoing a surgical procedure may be at increased risk of VTE. Future studies should investigate the optimal type and duration of the VTE prophylaxis.Item MON-266 The Association Between Prolactinomas and Weight Gain(Endocrine Society, 2020-05-08) Tariq, Zunera; Sabie, Farah Al; Donegan, Diane; Medicine, School of MedicineIntroduction: The prevalence of obesity is increasing worldwide and treatment remains challenging. Certain endocrine disorders may contribute to weight gain. These are important to recognize as treatment may have beneficial impact on weight. Studies have reported an increased prevalence of obesity in patients with prolactinomas. While several studies have examined the association between weight gain and prolactinomas, the results are conflicting. Therefore, the aim of this study was to determine if BMI is higher among those with a prolactinoma compared to those without. Methods: We identified all patients ≥18 years of age referred to endocrinology between 2008–2018 with a newly diagnosed prolactinoma (defined as a prolactin levels ≥40 ng/ml on 2 separate occasions and a pituitary adenoma evident on MRI without secondary causes for hyperprolactinemia). We extracted the following variables from the medical record: patient demographics, presenting symptoms, prolactin level and tumor size at diagnosis. Comparative data was obtained from the National Health and Nutrition Examination Survey (NHANES) 2015–2016, from which we included only those ≥18 years of age who had BMI data. Results: In total 34 patients with a newly diagnosed prolactinoma (female: 27 /34, 79%, mean age at diagnosis: 35.4 ± 10.7 years) met inclusion criteria. The majority of patients (23/34, 68 %) had microadenomas defined as <1cm. The median prolactin level at diagnosis was 103.3 (IQR 51.3- 249.25). Although the most common presenting symptoms were those consistent with hypogonadism (27/34, 79%) and galactorrhea (16/34, 47%), 1/3 patients also described weight gain. In comparison, 5662 individuals from NHANES (48 ± 18 years, female: 2955/5662, 52%) reported their BMIs. BMI was significantly increased among those with a prolactinoma compared to survey population [median BMI 30.9 kg/m2 (IQR, 24.9- 39) vs 28.3 kg/m2 (24.3- 33), P= 0.02]. This difference persisted even when adjusted for age and sex (P= 0.0002). In addition the prevalence of class II obesity (BMI ≥35 kg/m2) was higher in those with a prolactinoma compared to survey population (38% vs 18%, P=0.005). Among prolactinoma patients, there was a correlation between BMI and log-transformed prolactin levels (R2= 0.24, P=0.003). Conclusion: Weight gain is a presenting symptom for many patients with a newly diagnosed prolactinoma. When compared to a large cohort of adults in the US, those with a prolactinoma have higher BMI and an increased prevalence of class II obesity. Based on the correlation between BMI and log-transformed prolactin levels, we hypothesize that this weight difference may be related to hyperprolactinemia. These findings suggest that, in the appropriate context, hyperprolactinemia should be considered when a patient presents with weight gain.Item 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 MedicineObjectives: 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.Item Not a Grave Finding: Thymic Hyperplasia in the Setting of Graves’ Disease(Elsevier, 2020) Voss, Michael; Saeed, Zeb Ijaz; Donegan, Diane; Medicine, School of MedicineA 30-year-old Caucasian male with no previous medical history presented to the emergency department with sudden onset chest pain brought on by exertion at work. He had never experienced similar episodes before, and chest pain was described as severe, mid-sternal, non-radiating, and was associated with palpitations, dyspnea, and near-syncope. Patient also reported unintentional weight loss of 40 pounds over the 3 months leading up to presentation. Review of systems was positive for diaphoresis, increased anxiety, heat intolerance, and a mild hand tremor for several weeks. He denied cough, changes in vision or voice, nausea, vomiting, diarrhea, constipation, or abdominal pain. He reported no history of tobacco or illicit drug use and no family history of thyroid disease or autoimmune conditions.Item Outcomes of Initial Management Strategies in Patients With Autoimmune Lymphocytic Hypophysitis: A Systematic Review and Meta-analysis(Oxford University Press, 2022) Donegan, Diane; Saeed, Zeb; Delivanis, Danae A.; Murad, Mohammad Hassan; Honegger, Juergen; Amereller, Felix; Oguz, Seda Hanife; Erickson, Dana; Bancps, Irina; Medicine, School of MedicineContext: Lymphocytic hypophysitis (LyHy) is characterized by inflammation of the pituitary and or neuroinfundibulum and is uncommon. Treatment options include observation, high-dose glucocorticoids (HD-GCs) or surgery. Optimal first-line management strategy, however, remains unknown. Objective: This work aimed to assess response to first-line treatment options (observation, HD-GCs, or surgery) of clinically relevant outcomes (symptomatic, hormonal, and radiographic improvement) among patients with LyHy. Methods: A systematic review was conducted in 6 databases through 2020. Meta-analysis was conducted when feasible using a random-effects model. Results: We included 33 studies reporting on 591 patients (423 women, 72%) with LyHy. Improvement/resolution of anterior pituitary dysfunction was highest when HD-GCs was first-line treatment. Surgery was associated with the greatest proportion of patients who had regression on imaging. Subgroup analysis comparing HD-GCs to observation showed the odds of anterior pituitary hormone recovery (OR 3.41; 95% CI, 1.68-6.94) or radiographic regression (OR 3.13; 95% CI, 1.54-6.36) were higher with HD-GCs, but so was the need for additional forms of treatment (OR 4.37; 95% CI, 1.70-11.22). No statistically significant difference was seen in recovery of diabetes insipidus (OR 0.9; 95% CI, 0.26-3.10). Certainty in these estimates was very low. Conclusion: Observation and use of HD-GCs both are successful first-line management strategies in LyHy. Although use of HD-GCs was associated with increased recovery of anterior pituitary hormone deficit, it also was associated with greater likelihood of additional treatment after withdrawal. Optimal dosing and duration of HD-GCs remains unknown.Item Revisiting Pituitary Apoplexy(Oxford University Press, 2022-07-26) Donegan, Diane; Erickson, Dana; Medicine, School of MedicinePituitary apoplexy (PA) is a rare clinical syndrome due to pituitary hemorrhage or infarction. It is characterized by the sudden onset of one or more of the following: severe headache, visual disturbance, nausea/vomiting, and or altered mental status. Most commonly, PA occurs in an underlying pituitary adenoma. The pathophysiology is not fully understood, but it is thought to involve elements of increased metabolic demand and/or compromise to the vasculature of the pituitary or pituitary tumor. Several risk factors have been described. Stabilization of the patient on presentation, replacement of hormonal deficiencies, and reversal of electrolyte abnormalities are the recommended initial steps in the management of patients with PA. Surgical decompression of the mass effect had been the recommended treatment for patients with PA; however, retrospective studies of patients with PA have demonstrated similar outcomes when a conservative approach is applied. This suggests that in highly selected clinical scenarios (mild visual deficit and improving symptoms), conservative management is possible. Further studies, however, are necessary to better stratify patients but are limited by the rarity of the condition and the acuity.Item THU035 Impact Of Surgery Or Medical Treatment With The Selective Glucocorticoid Receptor Modulator Relacorilant On Hypercoagulopathy In Patients With Cushing Syndrome(The Endocrine Society, 2023-10-05) Simeoli, Chiara; Di Paola, Nicola; Stigliano, Antonio; Lardo, Pina; Kearney, Tara; Mezosi, Emese; Ghigo, Ezio; Giordano, Roberta; Mariash, Cary N.; Donegan, Diane; Feelders, Richard A.; Hand, Austin L.; Moraitis, Andreas G.; Pivonello, Rosario; Medicine, School of MedicineIn patients with Cushing syndrome (CS), hypercoagulability represents a significant concern, leading to an elevated risk for thrombotic events. Hypercoagulability persists for several months (mos) after curative surgery, and current CS treatment guidelines recommend anticoagulation therapy for up to 3 mos after surgery. In patients with Cushing disease, hemostatic parameters may even worsen after surgery, independent of surgical outcome, with improvements beginning about 3 mos after successful surgery (Casonato et al. Blood Coagul Fibrinolysis 1999). This transient worsening may be due to increased inflammation as cortisol levels, and hence cortisol’s anti-inflammatory effects, are reduced after successful surgery, leading to increased activity in the coagulation cascade, which normalizes over time. Here, we evaluate the impact of surgery or treatment with the selective glucocorticoid receptor modulator relacorilant (RELA) on the coagulation state in patients with CS, reporting findings from a retrospective, longitudinal, monocentric, surgical cohort study and an open-label phase 2 study of RELA (NCT02804750). In the surgical study, coagulation markers were assessed in 30 patients before curative surgery and in remission. In the RELA study, patients received either RELA 100-200 mg for 12 weeks or RELA 250-400 mg for 16 weeks; coagulation markers were assessed in 34 patients throughout the study. In the surgical study, baseline (BL) mean 24-h urinary free cortisol (UFC) was 615.6 mcg/day (by immunoassay; 2.1x upper limit of normal [ULN]); mean and median time to hemostasis assessment after remission were 6.2 and 6 mos, respectively. Significant mean changes from BL were observed in activated partial thromboplastin time (aPTT; +2.0 sec, P=0.031), factor VIII (fVIII; -24.2%, P=0.044), and von Willebrand factor (vWF; -20.6%, P=0.018), whereas platelet count was unchanged. In the RELA study, BL mean UFC was 211.9 mcg/day (by tandem mass spectrometry; 4.2x ULN). Similar to the surgical study, significant mean changes from BL to last observed visit were reported in aPTT (+1.5 sec, P=0.046), fVIII (-18.9%, P=0.022), and platelet count (-68.8*109/L, P<0.0001), while vWF was unchanged. Significant improvements in other coagulation factors, eg, fIX and fX, were seen in patients with abnormal values at BL. These studies showed that coagulation markers in patients with CS improve 6 mos after curative surgery, and that treatment with RELA may have similar effects after 3-4 mos. The previously observed transient increase in fVIII immediately after surgery was absent with RELA, where negative mean changes from BL were seen throughout the study. This is presumably due to the less abrupt reduction of cortisol activity with RELA compared to surgery. RELA’s effects on hypercoagulopathy support further investigation of preoperative use and in patients with CS who are not eligible for surgery.