Symptoms at presentation in conservatively managed patients with non-functioning pituitary adenomas.

PURPOSE: Hypopituitarism and tumor growth are rare in patients with non-functioning pituitary microadenomas (NFPmA). However, patients often present with non-specific symptoms. The aim of this brief report is to examine presenting symptomatology in patients with NFPmA compared to patients with non-functioning pituitary macroadenomas (NFPMA). METHODS: We performed a retrospective review of 400 patients (347 NFPmA and 53 NFPMA) who were conservatively managed; no patients had indications for urgent surgical intervention. RESULTS: Average tumor size was 4.5 ± 1.9 and 15.5 ± 5.5 mm for NFPmA and NFPMA, respectively (p < 0.001). At least one pituitary deficiency was present in 7.5% of patients with NFPmA and 25% of patients with NFPMA. Patients with NFPmA were younger (41.6 ± 15.3 vs. 54.4 ± 22.3 years, p < 0.001) and more commonly female (64.6 vs. 49.1%, p = 0.028). There was no significant difference reported for similarly high rates of fatigue (78.4% and 73.6%), headache (70% and 67.9%), and blurry vision (46.7% and 39.6%). There were no significant differences in comorbidities. CONCLUSION: Despite smaller size and lower rate of hypopituitarism, patients with NFPmA presented with a high prevalence of headache, fatigue, and visual symptoms. This was not significantly different from patients with NFPMA who were conservatively managed. We conclude that symptoms of NFPmA cannot fully be attributed to pituitary dysfunction or mass effect.

Nonfunctioning Pituitary Microadenomas: Should Imaging Interval be Extended? A Large Single-center Cohort Study.

CONTEXT: Characterization of the clinical features and natural history of nonfunctioning pituitary microadenomas (NFPmAs) is limited by heterogeneous and small-scale studies. OBJECTIVE: To characterize the clinical presentation and natural history of NFPmAs and evaluate if imaging follow-up interval can be extended. METHODS: Retrospective single-center cohort study (years 2006-2021) of conservatively managed patients with NFPmAs. Initial symptoms, pituitary function, and tumor size were assessed. A change in NFPmA size ≥2 mm, as determined by pituitary or brain magnetic resonance imaging (MRI), was considered significant. RESULTS: There were 347 patients in the study cohort. Headache (78.4%) and fatigue (70.0%) were commonly reported despite no evidence of mass effect or significant pituitary hypofunction. Pituitary deficiencies at baseline were rare, with hypogonadism being most common (5.1%). During a median imaging follow-up period of 29 months (range 3-154), 8.1% of NFPmAs grew. Growth incidence was 2.1 per 100 person-years with a mean and median time to growth of 38.1 (SD ± 36.4) and 24.5 (interquartile range 12.0-70.8) months, respectively. Tumor growth was mild and not associated with new pituitary deficiencies or visual deficits. CONCLUSION: These data indicate that the natural history of NFPmAs is overall benign. Consequently, we propose that the initial MRI follow-up timeline for NFPmAs can be extended up to 3 years unless a lesion is close to the optic chiasm, there are worrisome mass effect symptoms, or new pituitary deficiencies.

Updates in adrenal steroidogenesis inhibitors for Cushing's syndrome - A practical guide.

Medical therapy is essential in the management of patients with Cushing's syndrome (CS) when curative surgery has failed, surgery is not feasible, when awaiting radiation effect, and in recurrent cases of CS. Steroidogenesis inhibitors have a rapid onset of action and are effective in reducing hypercortisolism, however, adverse effects, including adrenal insufficiency require very close patient monitoring. Osilodrostat is the only steroidogenesis inhibitor to have been assessed in prospective randomized controlled trials and approved for Cushing's disease (CD) by the US Food and Drug Administration and for CS by the European Medical Agency (EMA). Osilodrostat has been shown to be highly effective at maintaining normal urinary free cortisol in patients with CD. Drugs such as metyrapone, ketoconazole (both EMA approved), and etomidate lack prospective evaluation(s). There is, however, considerable clinical experience and retrospective data that show a very wide efficacy range in treating patients with CS. In the absence of head-to-head comparative clinical trials, therapy choice is determined by the specific clinical setting, risk of adverse events, cost, availability, and other factors. In this review practical points to help clinicians who are managing patients with CS being treated with steroidogenesis inhibitors are presented.

Increase in Free and Total Plasma TGF-ß1 Following Physical Activity.

OBJECTIVE: To evaluate effects of physical activity and food consumption on plasma concentrations of free and total transforming growth factor beta-1 (TGF-ß1), beta-2 (TGF-ß2), and beta-3 (TGF-ß3) in individuals with knee osteoarthritis (OA). METHODS: Participants (n = 40 in 2 cohorts of 20; mean age 70 years) with radiographic knee OA were admitted overnight for serial blood sampling. Cohorts 1 and 2 assessed the impacts of food intake and activity, respectively, on TGF-ß concentrations. Cohort 1 blood draws included 2 hours postprandial the evening of day 1 (T3), fasting before rising on day 2 (T0), nonfasting 1 hour after rising (T1B), and 4 hours after rising (T2). Cohort 2 blood draws included T3, T0, fasting 1 hour after rising and performing activities of daily living (T1A), and nonfasting 2 hours after rising (T1B). By sandwich ELISAs, we quantified plasma free and total TGF-ß1 concentrations in all samples, and plasma total TGF-ß2 and TGF-ß3 in cohort 2. RESULTS: Free TGF-ß1 represented a small fraction of the total systemic concentration (mean 0.026%). In cohort 2, free and total TGF-ß1 and total TGF-ß2 concentration significantly increased in fasting samples collected after an hour (T1A) of activities of daily living (free TGF-ß1: P = 0.006; total TGF-ß1: P < 0.001; total TGF-ß2: P = 0.001). Total TGF-ß3 increased nonsignificantly following activity (P = 0.590) and decreased (P = 0.035) after food consumption while resting (T1B). CONCLUSIONS: Increased plasma concentrations of TGF-ß with physical activity suggests activity should be standardized prior to TGF-ß1 analyses.