Citations

SummaryPurposeThe distinction between corticotropin (ACTH)‐producing pituitary adenomas and occult ectopic ACTH neoplasms is a challenge and frequently complicated by the detection of nonfunctioning pituitary adenomas on dynamic magnetic resonance imaging (DMRI). Herein, we explored quantitative differences in DMRI measures from ACTH‐producing pituitary adenomas.Materials and methodsFifty‐five patients with pathology confirmed ACTH‐producing and 44 with nonfunctioning pituitary adenomas were analysed in this retrospective pilot study. The intensities of adenomas and of adjacent pituitary tissue were measured by drawing a region of interest. Time–intensity curves were then constructed, and quantitative analysis included: enhancement time, enhancement peak and prepeak slope (PPS). Multivariable logistic analysis and receiver operating characteristic curves (ROC) were used to evaluate the parameters.ResultsQuantitative analysis showed that tumour PPS in ACTH‐producing adenomas was markedly lower than that in nonfunctioning adenomas (P = 0·0042) and that the PPS of the adjacent pituitary gland was not different (P = 0·2441). The PPS was >3·0 in 59·1% of nonfunctioning adenomas and ≤3·0 in 69·1% of ACTH‐producing adenomas (P = 0·0049). Logistic analysis revealed lower tumour PPS levels (P = 0·0123, OR 1·24, 95% CI: 1·05–1·52) were associated with ACTH‐producing adenomas. The optimal PPS cut‐off determined by ROC analysis was 2·89, with a sensitivity of 69% and specificity of 70%. No significant difference was found between the two groups in enhancement time or enhancement peak.ConclusionEnhancement parameters in DMRI can help distinguishing ACTH producing from nonfunctioning pituitary adenomas, which could be useful in the differential diagnosis between ACTH‐producing pituitary adenomas and ectopic ACTH syndrome complicated with nonfunctioning pituitary adenoma.

AbstractBackgroundTo assess the risk of cerebrovascular accidents (CVAs) and second brain tumors (SBTs) in patients with pituitary adenoma after surgery or radiotherapy.MethodsA cohort of 143 people from Olmsted County, who were diagnosed with pituitary adenoma between 1933 and 2000, was studied. Only patients from Olmsted County were included because of the unique nature of medical care in Olmsted County, which allows the ascertainment of virtually all cases of pituitary adenoma for this community's residents and comparisons to the general population in the county. Surgical resection was performed in 76 patients, 29 patients underwent radiotherapy (with 21 undergoing both surgery and radiotherapy), 5 patients were reirradiated, and 59 patients were managed conservatively and observed.ResultsMedian follow-up was 15.5 years. There was no difference in CVA-free survival between treatment groups. On univariate analysis age > 60 years (hazard ratio [HR], 11.93; 95% CI, 6.26–23.03; P < .001); male sex (HR, 3.67; 95% CI, 2.03–6.84; P < .001), and reirradiation (HR, 3.41; 95% CI, 1.05–9.68; P = .04) were associated with worse CVA-free survival. In multivariate analysis, only age > 60 years was associated with worse CVA-free survival. Compared with the general population, there was a 4-fold increase in the rate of CVAs in pituitary adenoma patients (HR, 4.2; 95% CI, 2.8–6.1). Two patients developed SBT (an irradiated patient and a surgically managed patient).ConclusionCVA is a significant risk for patients with pituitary tumors, but treatment does not seem to impact the risk. Even with long-term follow-up, SBTs are a rare event regardless of treatment modality.

Although the autoantigen involved in Graves’ hyperthyroidism is known to be the TSH receptor (TSHr), whether this antigen plays a primary role in the pathogenesis of Graves’ ophthalmopathy (GO) is unclear. We sought to determine whether fibroblasts derived from orbital adipose/connective tissue are capable of differentiating into adipocytes that bear immunoreactive and functional TSHr. In addition, we assessed relative levels of TSHr gene expression in normal and GO orbital adipose/connective tissue specimens.GO and normal orbital preadipocyte fibroblasts, cultured under conditions known to stimulate adipocyte differentiation, showed evidence of adipogenesis and positive immunostaining for TSHr protein. In addition, significantly more cAMP was produced in response to TSH stimulation in the differentiated cultures than in undifferentiated cultures derived from the same individuals’ cells. Other studies demonstrated relatively greater TSHr gene expression in GO than in normal orbital tissue specimens.These results indicate that orbital preadipocyte fibroblasts increase their TSHr expression with differentiation and suggest that these cells play an important role in the pathogenesis of GO. Furthermore, our studies support the concept that TSHr may be an important target antigen in this condition. Factors that stimulate adipocyte differentiation and TSHr expression in the orbit in GO have yet to be defined.

Summary Objective We aimed to assess the prevalence of impulse control disorders ( ICD s) in patients with prolactin‐secreting adenomas treated with dopamine agonists ( DA s), to identify associated factors and to compare it with a group of patients with nonfunctioning pituitary adenoma. Subjects, Design and Measurement In a postal survey, 77 patients from Group A (patients with prolactinomas and present or past use of DA s) and 70 patients from Group B (patients with nonfunctioning pituitary adenoma and no history of DA therapy) responded to a questionnaire on compulsive shopping, pathologic gambling, hypersexuality and punding. Associated clinical information was obtained through the survey and review of medical electronic records. Results The total ICD prevalence was 24·68% in Group A and 17·1% in Group B ( P = 0·31). Group A had an increased rate of hypersexuality ( P = 0·03). Subgroup analysis revealed that men in Group A had a significantly increased frequency of total ICD s when compared with men in Group B (27·7 vs 3·7%, P = 0·01). No differences in rates of total ICD s were found between women of Groups A and B (20 vs 25·6%, P = 0·78). No association with type, dose or duration of treatment with DA was noted. Conclusions Males with prolactinomas treated with DA s were 9·9 times more likely to develop an ICD than their counterparts with nonfunctioning pituitary adenomas. Until prospective studies on the relationship of DA use in patients with prolactinoma and ICD s are available, the authors propose that patients with prolactinoma be forewarned of possible ICD development with DA therapy.

ObjectivesTo 1) describe and validate an ultrasound‐guided ischial bursa injection technique in an unembalmed cadaveric model and 2) to compare the distance between the ischial tuberosity and the sciatic nerve in a hip neutral versus 90° flexed hip position in asymptomatic volunteers.DesignThe first part was a single‐blind prospective study. The second part was a prospective cohort study.SettingAn academic institution procedural skills laboratory and outpatient clinic.ParticipantsThe first part of the study involved 1 cadaveric specimen. The second part of the study involved 20 asymptomatic subjects. The mean age of the subjects was 28 years, and the mean (standard deviation) body mass index was 23.2 ± 2.8 kg/m2 (minimum, 18.3 kg/m2; maximum, 29.5 kg/m2).MethodsIn the first part of the study, a single operator completed bilateral ultrasound‐guided ischial bursa injections in an unembalmed cadaveric specimen by using diluted colored latex. In the second part of the study, ultrasound was used in 20 asymptomatic volunteer subjects (10 men and 10 women) to measure the distance from the lateral edge of the ischial tuberosity to the sciatic nerve.Main Outcome MeasurementsThe injections were graded for accuracy as follows: accurate (all injectate contained within the ischial bursa), accurate with overflow (injectate within the ischial bursa but also located in adjacent structures other than the needle track), or inaccurate (injectate not within the ischial bursa). The second part of the study measured the distance from the ischial tuberosity to the sciatic nerve with subjects in 2 different positions (prone and side lying with the tested hip flexed to 90°).ResultsPostinjection cadaveric dissections revealed that both ultrasound‐guided injections accurately placed liquid latex within the ischial bursae. There was no evidence of injury to surrounding neurovascular structures. Among asymptomatic volunteers, the average distance between the ischial tuberosity and the sciatic nerve increased from 28.4 mm (range, 20.5‐38.9 mm) in the neutral position to 41.9 mm (range, 30.9‐66.0 mm) with the hip flexed to 90° (average change, 13.5 mm away from the ischial tuberosity; P = .0001).ConclusionsUltrasound‐guided ischial bursa injections are technically feasible. Flexing the hip to 90° increases the distance between the ischial tuberosity and the sciatic nerve in asymptomatic volunteers, thus potentially resulting in a safer needle trajectory when ischial bursa injections are clinically indicated. Further investigation in clinical settings is warranted to validate these findings.

Background— Implantable cardioverter-defibrillator (ICD) therapy in children and congenital heart disease patients is hampered by poor long-term lead survival. Lead extraction is technically difficult and carries substantial morbidity. We sought to determine the outcomes of ICD leads in pediatric and congenital heart disease patients. Methods and Results— The Pediatric Lead Extractability and Survival Evaluation (PLEASE) is a 24-center international registry. Pediatric and congenital heart disease patients with ICD lead implantations from 2005 to 2010 were eligible. Study subjects comprised 878 ICD patients (44% congenital heart disease). Mean±SD age at implantation was 18.6±9.8 years. Of the 965 total leads, 54% were thin (≤7F), of which 57% were Fidelis, and 23% were coated with expanded polytetrafluoroethylene. There were 139 ICD lead failures (14%) in 132 patients (15%) at a mean lead age of 2.0±1.4 years, causing shocks in 53 patients (40%). Independent predictors of lead failure included younger implantation age and Fidelis leads. Actuarial analysis showed an incremental risk of lead failure with younger age at implantation: <8 years compared with >18 years ( P =0.015). The actuarial yearly failure rate was 2.3% for non-Fidelis and 9.1% for Fidelis leads. Extraction was performed on 143 leads (80% thin, 7% expanded polytetrafluoroethylene coated), with lead age as the only independent predictor for advanced extraction techniques. There were 6 major extraction complications (4%) but no procedural mortality. Conclusions— This study demonstrates that ICD leads in children and congenital heart disease patients have an age-related suboptimal performance, further compounded by a high failure rate of Fidelis leads. Advanced extraction techniques were common and correlated with older lead age. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT00335036.

SummaryMyelofibrosis (MF) patients can present with a wide spectrum of disease characteristics. We analysed the consistency of ruxolitinib efficacy across patient subgroups in the COntrolled MyeloFibrosis Study With ORal JAK Inhibitor Treatment (COMFORT‐I,) a double‐blind trial, where patients with intermediate‐2 or high‐risk MF were randomized to twice‐daily oral ruxolitinib (n = 155) or placebo (n = 154). Subgroups analysed included MF subtype (primary, post‐polycythaemia vera, post‐essential thrombocythaemia), age (≤65, > 65 years), International Prognostic Scoring System risk group, baseline Eastern Cooperative Oncology Group performance status (0, 1, ≥2), JAK2 V617F mutation (positive, negative), baseline haemoglobin level (≥100, <100 g/l), baseline platelet count (100–200 × 109/l, >200 × 109/l), baseline palpable spleen size (≤10, >10 cm), and baseline quartile of spleen volume and Total Symptom Score (TSS; Q1 = lowest, Q4 = highest). Mean percentage change from baseline to week 24 in spleen volume and TSS were calculated for ruxolitinib and placebo in each subgroup. Overall survival was estimated by Kaplan–Meier method according to original randomization group. In ruxolitinib‐treated patients, reductions in spleen volume and TSS and evidence of improved survival relative to placebo across subgroups were consistent with those seen in the COMFORT‐I population, confirming that ruxolitinib is an effective therapy for the spectrum of MF patients studied in COMFORT‐I.

Purpose To assess the effects of ruxolitinib on symptom burden and quality of life (QoL) and to evaluate the ability of the modified Myelofibrosis Symptom Assessment Form (MFSAF) v2.0 to measure meaningful changes in myelofibrosis-related symptoms in patients with myelofibrosis. Patients and Methods COMFORT-I (Controlled Myelofibrosis Study With Oral JAK Inhibitor Treatment–I) is a double-blind, placebo-controlled phase III study evaluating ruxolitinib in patients with intermediate-2 or high-risk myelofibrosis. Exploratory analyses were conducted on the following patient-reported outcomes (PROs) assessments: modified MFSAF v2.0 (individual symptoms and Total Symptom Score [TSS]), European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30), Patient Reported Outcomes Measurement Information System (PROMIS) Fatigue Scale, and Patient Global Impression of Change (PGIC). Results Patients receiving ruxolitinib experienced improvements in individual myelofibrosis-related symptoms, although patients receiving placebo experienced worsening (P < .001). The majority (91%) of ruxolitinib-treated patients designated as ≥ 50% TSS responders (≥ 50% TSS improvement) self-reported their condition as either “Much improved” or “Very much improved” on the PGIC. These patients achieved significant improvements in the EORTC QLQ-C30 functional domains and Global Health Status/QoL versus patients receiving placebo, who experienced worsening on these measures (P ≤ .0135). Ruxolitinib-treated patients with a lesser degree of symptom improvement (< 50% TSS responders) also achieved improvements over placebo on these measures. The degree of spleen volume reduction with ruxolitinib correlated with improvements in TSS, PGIC, PROMIS Fatigue Scale, and EORTC Global Health Status/QoL. Ruxolitinib-treated patients who achieved a ≥ 35% reduction in spleen volume experienced the greatest improvements in these PROs. Conclusion Ruxolitinib-treated patients achieved clinically meaningful improvements in myelofibrosis-related symptoms and QoL, but patients receiving placebo reported worsening of symptoms and other PROs.