Citations

Abstract Objective Adrenal adenomas are commonly encountered in clinical practice. To date, population-based data on their impact on cognition, mental health, and sleep are lacking. We aimed to study possible associations between adrenal adenomas and dementia, psychiatric or sleep disorders. Design Population-based cohort study, Olmsted County, MN, 1995-2017. Methods Patients with adrenal adenoma and absent overt hormone excess were age- and sex-matched 1:1 to a referent person without adrenal adenoma. Outcomes were baseline and incident diagnoses of dementia, psychiatric or sleep disorders, assessed using ICD codes. Results Of 1004 patients with adrenal adenomas, 582 (58%) were women, and median age at diagnosis was 63 years. At baseline, and after adjusting for age, sex, education, BMI, and tobacco use, patients with adenoma had higher odds of depression (adjusted odds ratio, aOR: 1.3, 95% CI, 1.1-1.6), anxiety (aOR: 1.4, 95% CI, 1.1-1.8), and substance abuse (aOR: 2.4, 95% CI, 1.7-3.4) compared to referents. During a median follow-up of 6.8 years, and after adjusting for age, sex, socioeconomic status, BMI, tobacco, and substance abuse, patients demonstrated a higher risk of psychiatric and sleep disorders [adjusted hazard ratio (95% CI)]: depression [1.7 (1.3-2.2)], anxiety [1.4, CI (1.1-1.7)], insomnia [1.4 (1.0-1.9)], sleep-related breathing disorders [1.5 (1.1-1.9)], hypersomnias [2.1 (1.0-4.2)], parasomnias [2.1 (1.0-4.2)], and sleep-related movement disorders [1.5 (1.0-2.1)], but not dementia. Conclusions Patients with adenomas demonstrate a higher incidence of psychiatric and sleep disorders, possibly due to the underlying subtle increase in cortisol secretion.

Abstract Background Patients often turn to online reviews as a source of information to inform their decisions regarding care. Existing literature has analyzed factors associated with positive online patient ratings among hand and wrist surgeons. However, there is limited in-depth analysis of factors associated with low patient satisfaction for hand and wrist surgeons. The focus of this study is to examine and characterize extremely negative reviews of hand and wrist surgeons on Yelp.com. Methods A search was performed using the keywords “hand surgery” on Yelp.com for eight major metropolitan areas including Washington DC, Dallas, New York, Phoenix, Los Angeles, San Francisco, Boston, and Seattle. Only single-star reviews (out of a possible 5 stars) of hand and wrist surgeons were included. The complaints in the 1-star reviews were then categorized into clinical and nonclinical categories. Result A total of 233 single-star reviews were included for analysis, which resulted in 468 total complaints. Of these complaints, 81 (18.8%) were clinically related and 351 (81.3%) were nonclinical in nature. The most common clinical complaints were for complication (24 complaints, 6%), misdiagnosis (16 complaints, 4%), unclear treatment plan (16 complaints, 4%), and uncontrolled pain (15 complaints, 3%). The most common nonclinical complaints were for physician bedside manner (93 complaints, 22%), financially related (80 complaints, 19%), unprofessional nonclinical staff (61 complaints, 14%), and wait time (46 complaints, 11%). The difference in the number of complaints for surgical and nonsurgical patients was statistically significant (p < 0.05) for complication and uncontrolled pain. Clinical Relevance Patient satisfaction is dependent on a multitude of clinical and nonclinical factors. An awareness of online physician ratings is essential for hand and wrist surgeons to maintain and improve patient care and patient satisfaction. We believe the results of our study could be used to further improve the quality of care provided by hand and wrist surgeons.

Abstract Objective Frailty, characterized by multi-system decline, increases vulnerability to adverse health outcomes and can be measured using Frailty Index (FI). We aimed to assess the prevalence of frailty in patients with adrenal disorders (based on hormonal sub-type) and examine association between FI and performance-based measures of physical function. Design Multi-centre, cross-sectional study (March 2019-August 2022). Methods Adult patients with adrenal disorders (non-functioning adrenal adenomas [NFA], mild autonomous cortisol secretion [MACS], Cushing syndrome [CS], primary aldosteronism [PA]) and referent subjects without adrenal disorders completed a questionnaire encompassing 47 health variables (comorbidities, symptoms, daily living activities). FI was calculated as the average score of all variables and frailty defined as FI ≥ 0.25. Physical function was assessed with hand grip, timed up-and-go test, chair rising test, 6-minute walk test, and gait speed. Results Compared to referent subjects (n = 89), patients with adrenal disorders (n = 520) showed increased age, sex, and body mass index-adjusted prevalence of frailty (CS [odds ratio—OR 19.2, 95% confidence interval—CI 6.7-70], MACS [OR 12.5, 95% CI 4.8-42.9], PA [OR 8.4, 95% CI 2.9-30.4], NFA [OR 4.5, 95% CI 1.7-15.9]). Prevalence of frailty was similar to referent subjects when post-dexamethasone cortisol was &lt;28 nmol/L and was higher when post-dexamethasone cortisol was 28-50 nmol/L (OR 4.6, 95% CI 1.7-16.5). FI correlated with all measures of physical function (P &lt; .001). Conclusions Whilst frailty prevalence was highest in patients with adrenocortical hormone excess, even patients with NFA demonstrated an increased prevalence compared to the referent population. Future longitudinal studies are needed to evaluate the impact of various management strategies on frailty.

OBJECTIVE Inferior petrosal sinus (IPS) sampling (IPSS) is a diagnostic procedure used to guide diagnostic localization of imaging-negative adrenocorticotropic hormone (ACTH)–secreting pituitary microadenomas. However, the efficacy of IPSS has been suboptimal at accurately lateralizing the adenoma, reducing surgical cure rates and leading to unintended pituitary dysfunction due to the added exploration. One rationale for the occasional imprecision is the existence of additional petrosal sinus collateral channels that connect the IPS bilaterally, which may lead to false localization results during sampling. The aim of this study was to explore a potential connection between normal anatomical variation in the angioarchitecture of the IPSs and the ACTH results obtained in subsequent IPSS tests. METHODS A retrospective review was performed on all cases between 1998 and 2013 involving patients at a single institution who underwent IPSS for radiographically equivocal pituitary microadenomas. Cases were reviewed for tumor laterality noted on either operative or pathology reports, as well as the presence of angiographic evidence of cross-filling between the sinuses. In addition, ACTH levels from the right and left IPSs were documented at baseline and at 2, 5, and 10 minutes after corticotropin-releasing hormone (CRH) administration. A ratio of the change in ACTH levels measured at the time of maximal response (10 minutes) versus the levels measured at the initial response (2 minutes) was computed for each patient and compared between patients by their angiographic cross-filling status. RESULTS There were 41 patients with a histopathologically confirmed right- or left-sided ACTH-secreting pituitary microadenoma who underwent preoperative IPSS. Among these patients, 28 (68%) showed angiographic evidence of cross-filling between the IPSs, and 13 showed no cross-filling. On average, ACTH levels increased by a factor of 3.91 ± 0.77 in the contralateral IPS in patients with angiographic cross-filling, compared with a factor increase of only 1.80 ± 0.27 in patients without cross-filling (p = 0.014). In comparison, ACTH levels increased by a factor of 2.01 ± 0.57 in the ipsilateral IPS in patients with cross-filling, and by 8.78 ± 7.30 in those without cross-filling (p = 0.373). CONCLUSIONS The presence of angiographic cross-filling, suggestive of a greater degree of vascular channel networking between the right and left IPS, is a significant factor influencing the measured rates of change of ACTH in IPSS and may impact the specificity of this test to accurately determine microadenoma laterality in the preoperative setting.

OBJECTIVE The aim of this study was to report the treatment course of histologically confirmed metastases to the pituitary gland (pituitary metastasis). METHODS The Mayo data explorer was used to find patients with pituitary metastasis. Twenty-one patients were identified between the years 2001 and 2021, and their data were retrospectively collected. RESULTS The most common primary cancer origin was lung in men (45%) and breast in women (33%). The median age was 66 years (IQR 56–68 years). Patients presented with headache (67% [14/21]), vision problems (86% [18/21]), anterior hypopituitarism (71% [15/21]), and arginine vasopressin deficiency (38% [8/21]). Pituitary metastases were found before the diagnosis of the primary cancer in 5 patients (24%). The mean ± SD tumor size was 2.0 ± 0.7 cm, and 90% (19/21) presented as a solitary pituitary mass with no other intracranial metastatic lesions. Common radiological features were pituitary stalk thickening (90% [19/21]), cavernous sinus involvement (71% [15/21]), and constriction at the diaphragma sellae (52% [11/21]). Transsphenoidal surgery was performed in 20 patients, and subtotal resection was most frequently attained (76% [16/21]). Fourteen patients (67%) had adjuvant radiation therapy, and 15 patients (71%) were treated with systemic therapy. The median time from surgery to the initiation of radiation therapy was 16 days (IQR 11–21 days), and that from surgery to the initiation of systemic therapy was 5.0 months (IQR 1.5–14 months). During management, headaches improved in 57% (8/14) and vision problems improved in 61% (11/18) of cases; new hypopituitarism occurred in 5 patients. Six patients developed recurrence, and the median progression-free survival was 24 months (95% CI 5.4–43 months). After recurrence, 1 patient with adenoid cystic carcinoma was treated with rescue radiotherapy twice, and 4 patients responded well to systemic therapy. The median overall survival (OS) was 25 months (95% CI 7.1–43 months). The mean OS was better in patients with neuroendocrine lung tumor (261 months) and papillary thyroid carcinoma (80 months) and worse in patients with small cell lung cancer (4 months) and unknown origin (5 months). CONCLUSIONS Surgery with or without adjuvant radiotherapy is effective for mass reduction, rapid symptomatic improvement of vision and headaches, and definitive diagnosis. Even after local tumor control failure, some patients still benefit from radiation and/or systemic therapy.

Abstract Background Facial angiofibromas (FAs) are a major feature of tuberous sclerosis complex (TSC). Topical rapamycin can successfully treat FAs. A new stabilized cream formulation that protects rapamycin from oxidation has been developed in 0.5% and 1% concentrations. Objectives To assess the efficacy and safety of a novel, stabilized topical rapamycin cream formulation. Methods This multicentre double-blind randomized placebo-controlled dose–response phase II/III study with a parallel design included participants aged 6–65 years with FAs of mild or moderate severity according to the Investigator’s Global Assessment (IGA) scale. Participants were randomized to one of three treatment arms: topical rapamycin 0.5%, topical rapamycin 1% or placebo. Treatment was applied once daily for 26 weeks. Safety and efficacy measures were assessed at days 14, 56, 98, 140 and 182. The primary endpoint was the percentage of participants achieving IGA scores of ‘clear’ or ‘almost clear’ after 26 weeks of treatment. Secondary measures included Facial Angiofibroma Severity Index (FASI) and participant- and clinician-reported percentage-based improvement. Safety measures included the incidence of treatment-emergent adverse events and blood rapamycin concentration changes over time. Results Participants (n = 107) were randomized to receive either rapamycin 1% (n = 33), rapamycin 0.5% (n = 36) or placebo (n = 38). All treated participants were included in the final analysis. The percentage of participants with a two-grade IGA improvement was greater in the rapamycin 0.5% treatment group (11%) and rapamycin 1% group (9%) than in the placebo group (5%). However, this was not statistically significant [rapamycin 0.5%: odds ratio (OR) 1.71, 95% confidence interval (CI) 0.36–8.18 (P = 0.50); rapamycin 1%: OR 1.68, 95% CI 0.33–8.40 (P = 0.53)]. There was a statistically significant difference in the proportion of participants treated with rapamycin cream that achieved at least a one-grade improvement in IGA [rapamycin 0.5%: 56% (OR 4.73, 95% CI 1.59–14.10; P = 0.005); rapamycin 1%: 61% (OR 5.14, 95% CI 1.70–15.57; P = 0.004); placebo: 24%]. Skin adverse reactions were more common in patients following rapamycin application (64%) vs. placebo (29%). Conclusions Both rapamycin cream formulations (0.5% and 1%) were well tolerated, and either strength could lead to clinical benefit in the treatment of FA.

Abstract Objective Glucocorticoid withdrawal syndrome (GWS) is a scarcely studied phenomenon that complicates the recovery following surgical remission of hypercortisolism. We aimed to characterize the presence and trajectory of glucocorticoid withdrawal symptoms in the postoperative period and to determine presurgical predictors of GWS severity. Design Longitudinal observational study. Methods Glucocorticoid withdrawal symptoms were prospectively evaluated weekly for the first 12 weeks following surgical remission of hypercortisolism. Quality of life (CushingQoL and Short-Form-36) and muscle function (hand grip strength and sit-to-stand test) were assessed at the baseline and at 12 weeks after surgery. Results Prevalent symptoms were myalgias and arthralgias (50%), fatigue (45%), weakness (34%), sleep disturbance (29%), and mood changes (19%). Most symptoms persisted, while myalgias, arthralgias, and weakness worsened during weeks 5-12 postoperatively. At 12 weeks after surgery, normative hand grip strength was weaker than at baseline (mean Z-score delta −0.37, P = .009), while normative sit-to-stand test performance improved (mean Z-score delta 0.50, P = .013). Short-Form-36 Physical Component Summary score worsened (mean delta −2.6, P = .015), but CushingQoL score improved (mean delta 7.8, P &lt; .001) at 12 weeks compared to baseline. Cushing syndrome (CS) clinical severity was predictive of postoperative GWS symptomology. Conclusion Glucocorticoid withdrawal symptoms are prevalent and persistent following surgical remission of hypercortisolism with baseline CS clinical severity predictive of postoperative GWS symptom burden. Differential changes observed in muscle function and quality of life in the early postoperative period may reflect the competing influences of GWS and recovery from hypercortisolism.

Abstract Objective Prospective data on determinants of muscle strength impairment and quality of life in patients with various subtypes and severity of endogenous hypercortisolism are lacking. Design Single-center cross-sectional study, 2019 to 2022. Methods Patients with Cushing syndrome (CS) and mild autonomous cortisol secretion (MACS) were assessed with clinical and biochemical severity scores, muscle function (nondominant hand grip strength and sit-to-stand test), and quality of life (Short Form-36 [SF36] and CushingQoL). Referent subjects were recruited from the local population undergoing abdominal imaging for reasons other than suspected adrenal disorder. Results Of 164 patients, 81 (49%) had MACS, 14 (9%) had adrenal CS, 60 (37%) had pituitary CS, and 9 (5%) had ectopic CS. Median age was 53 years (interquartile range: 42-63 years), and 126 (77%) were women. The SF36 mental component score was similarly low in patients with MACS vs CS, but physical component score was lower in CS when compared to MACS (mean of 34.0 vs 40.5, P = .001). Compared to MACS, patients with CS had lower scores on the standardized CushingQoL (mean of 47.1 vs 34.2, P &lt; .001). Compared to referent subjects, patients with MACS demonstrated reduced muscle strength, similar to patients with CS (mean sit to stand Z-score of −0.47 vs −0.54, P = .822). Clinical severity (r = −0.22, P = .004) but not biochemical severity was associated with sit-to-stand test performance. Conclusions Both patients with overt CS and MACS demonstrate reduced muscle strength and low quality of life. The clinical severity score utilized is associated with both physical and psychosocial components of CushingQoL and with the physical component of SF36.