Visual acuity in patients with non-functioning pituitary adenoma: Prognostic factors and long-term outcome after surgery.

Background: Visual acuity (VA) and visual field defects (VF) are evaluated in the preoperative management of non-functioning pituitary adenoma (NFPA). The former is less studied than the latter. Research question: To analyze preoperative factors, including adenoma volumetry, associated with reduced VA and postoperative improvement of VA over five years after surgery. Methods: Eighty-seven patients who had primary surgery for NFPA were retrospectively reviewed. Eyes were categorized by best/worse preoperative VA. Ophthalmology review was performed before surgery, at three months, one to two years, and five years post-surgery. Results: Reduced VA in any eye was present in 55%. VA of the worse eye improved in 77% and normalized in 54%. The majority improved within three months. Additional cases with VA improvement were seen at 1-2 years after surgery. No further improvement was seen five years after surgery. Fifty percent of patients with, per definition, normal preoperative VA showed improved VA postoperatively. Tumor height above the sella in the sagittal plane was the best radiological predictor of reduced VA. Volumetry did not add to accuracy. Age, sagittal tumor height and visual field defects were risk factors of preoperative reduced VA. No predictors of postoperative recovery were identified. Conclusion: Half of patients with reduced VA recover fully. All patients, independent of age and degree of VA reduction, may improve. No predictors of recovery were found. Early improvement is common and improvement beyond two years is unlikely. The frequency of reduced VA is underestimated. The present results could be of value in pre- and postoperative counseling.

Increased Mortality Persists after Treatment of Cushing's Disease: A Matched Nationwide Cohort Study.

Context: Whether biochemical remission normalizes life expectancy in Cushing's disease (CD) patients remains unclear. Previous studies evaluating mortality in CD are limited by using the expected number of deaths in the background population instead of the actual number in matched controls. Objective and setting: To study mortality by time-to-event analysis in an unselected nationwide CD patient cohort. Design and participants: Longitudinal data from the Swedish Pituitary Register of 371 patients diagnosed with CD from 1991 to 2018 and information from the Swedish Cause of Death Register were evaluated. Four controls per patient (n = 1484) matched at the diagnosis date by age, sex, and residential area were included. Main outcome measures: Mortality and causes of death. Results: The median diagnosis age was 44 years (interquartile range 32-56), and the median follow-up was 10.6 years (5.7-18.0). At the 1-, 5-, 10-, 15-, and 20-year follow-ups, the remission rates were 80%, 92%, 96%, 91%, and 97%, respectively. Overall mortality was increased in CD patients compared with matched controls [hazard ratio (HR) 2.1 (95% CI 1.5-2.8)]. The HRs were 1.5 (1.02-2.2) for patients in remission at the last follow-up (n = 303), 1.7 (1.03-2.8) for those in remission after a single pituitary surgery (n = 177), and 5.6 (2.7-11.6) for those not in remission (n = 31). Cardiovascular diseases (32/66) and infections (12/66) were overrepresented causes of death. Conclusions: Mortality was increased in CD patients despite biochemical remission compared to matched controls. The study highlights the importance of careful comorbidity monitoring, regardless of remission status.

An early post-operative ACTH suppression test can safely predict short- and long-term remission after surgery of Cushing's disease.

PURPOSE: The present study evaluates the usefulness of an ACTH suppression test shortly after surgery, and to determine optimal cut-off values of included laboratory analyses, in predicting short- and long-term remission after surgery of Cushing's disease. METHODS: A 48 h suppression test with betamethasone 2 mg/day applied after 45 transphenoidal adenomectomies in 28 patients was evaluated. Receiver operating characteristic (ROC)-curves were created for the included assays: plasma cortisol, plasma adrenocorticotropic hormone (ACTH) and urinary free cortisol (UFC). Plasma levels of cortisol and ACTH were measured both at 24 and 48 h. Youden's index was used to determine cut-off with the highest sensitivity and specificity in predicting short- (3 months) and long-term (5 years or longer) remission. The area under curve (AUC) illustrated the clinical accuracy of the different assays. RESULTS: Plasma cortisol after 24 h with betamethasone was most accurate in predicting both short- and long-term remission. 3 months remission with cut-off 107 nmol/L: sensitivity 0.85, specificity 0.94, positive predictive value (PPV) 0.96 and AUC 0.92 (95% CI 0.85-1). 5 years remission with cut-off 49 nmol/L: sensitivity: 0.94, specificity 0.93, PPV 0.88, AUC 0.98 (95% CI 0.95-1). Analyses of ACTH or UFC did not improve diagnostic accuracy. CONCLUSIONS: A 48 h, 2 mg/day betamethasone suppression test after transphenoidal surgery of Cushing's disease could predict short- and long-term remission with a high accuracy. Suppression of plasma cortisol after 24 h with betamethasone to values excluding Cushings disease in the diagnostic setting yielded the highest accuracy in predicting long-term remission.

Quality of Life and Work Capacity Are Unrelated to Approach or Complications After Pituitary Surgery.

OBJECTIVE: Endoscopic pituitary surgery has shown favorable clinical outcomes. Less is known about the impact of surgical approaches on health-related quality of life (HRQoL) and work capacity. The present study was undertaken to compare transsphenoidal microscope-assisted surgery with endoscopic transsphenoidal surgery regarding preoperative and surgical factors for the final outcome of HRQoL and work capacity. METHODS: In a retrospective study of patients operated on for pituitary adenoma, outcome was compared between those operated on before and after transition with endoscopic surgery at our department. Data were gathered via patient questionnaires and patients' files. RESULTS: After exclusions, 235 patients were included (99 microsurgical and 136 endoscopic). Frequency of complications was similar but tumor size was significantly larger in the endoscopic group. Complications did not affect HRQoL or work capacity. HRQoL was not affected by surgical technique but showed an overall trend toward lower values compared with the general population. Sick leave, return to work frequency, and permanent sick leave were not affected by surgical technique. Female gender was a factor for lower ratings in all outcome variables. CONCLUSIONS: Surgical technique does not influence HRQoL or work capacity in this long-term follow-up although both are decreased compared with the general population. We conclude that fully endoscopic pituitary surgery, despite including larger tumors, bears the same risk for complications as microsurgery. In addition, females have a greater risk for decrease in HRQoL and work ability. This factor should be taken into account when informing patients and appreciating expectations of treatment.

Reduced Quality of Life in Patients with Pituitary Dysfunction After Aneurysmal Subarachnoid Hemorrhage: A Prospective Longitudinal Study.

OBJECTIVE: Pituitary dysfunction (PD) after aneurysmal subarachnoid hemorrhage (SAH) has been demonstrated in several studies. Given the similarities between psychological symptoms and reduced quality of life (QoL) in patients with PD and fatigue commonly seen in patients after SAH, we investigated the relationship between QoL and PD after SAH. METHODS: There were 51 patients with aneurysmal SAH prospectively recruited and evaluated for health-related QoL using the Psychological General Well-Being Index. Evaluations were conducted 3-6 months (n = 45), 6-12 months (n = 44), and 12-24 months (n = 44) after SAH, with concomitant assessment of endocrine function. The study protocol also included a magnetic resonance imaging examination 3 months after SAH. RESULTS: Mean general well-being scores showed a positive trend from 97.3 at 3-6 months to 104.3 at 12-24 months for all patients. Multiple regression analysis identified age, sex, Hunt and Hess grade, and PD as independent predictors for general well-being. Patients with PD had significantly lower scores compared with patients with normal pituitary function at 3-6 months (85.4 vs. 101.7) and 6-12 months (90.4 vs. 105.3). This result was due to central hypoadrenalism (score 81.6 at 3-6 months and score 82.2 at 6-12 months) but not other types of PD. The extent of magnetic resonance imaging lesions had a significant negative correlation to Glasgow Outcome Scale score at all follow-up evaluations. All patients with hypothalamic magnetic resonance imaging lesions had evidence of PD at some point during the follow-up period. CONCLUSIONS: The results support PD, and central hypoadrenalism in particular, as a contributing factor for impaired health-related QoL in patients after SAH.

High prevalence of pituitary dysfunction after aneurysmal subarachnoid hemorrhage: a long-term prospective study using dynamic endocrine testing.

OBJECTIVE: Impaired systemic hormonal activity caused by hypothalamic and pituitary injury may contribute to neuropsychologic disturbances and poor quality of life after aneurysmal subarachnoid hemorrhage (SAH). This prospective study was designed to longitudinally evaluate long-term clinical outcome and pituitary function after SAH using dynamic tests for adrencorticotropic and somatotropic secretory capacity. METHODS: Endocrine function was assessed by basal hormonal concentrations at 6-12 months and 12-24 months after SAH. At the 12-24 months follow-up, dynamic provocative evaluation of adrenocorticotropic hormone (ACTH) and growth hormone (GH) was performed using the insulin tolerance test (ITT). In patients where ITT was contraindicated, an ACTH stimulation test was used to assess ACTH capacity, and a growth hormone releasing hormone (GHRH)-arginine stimulation test was used to assess GH capacity. RESULTS: Of 60 patients with SAH screened, 51 were included in the study, and 44 remained to be tested at the two follow-up visits. As assessed by basal hormone concentrations alone, the prevalence of pituitary dysfunction was 34% at 6-12 months and 41% at 12-24 months. When using dynamic tests (12-24 months), impaired pituitary function was detected in 43%. The ITT detected more cases of central hypoadrenalism and GH deficiency compared with the ACTH- and GHRH-arginine-stimulation tests, respectively. CONCLUSIONS: Application of dynamic endocrine tests revealed a high frequency of long-term hypothalamic-pituitary dysfunction after aneurysmal SAH. The role of pituitary dysfunction in the recovery after SAH merits further evaluation.

Pituitary dysfunction after aneurysmal subarachnoid hemorrhage is associated with impaired early outcome.

OBJECTIVE: Poor outcome and neuropsychological sequelae after aneurysmal subarachnoid hemorrhage (SAH) is a persistent problem. Pituitary dysfunction has been proposed as a contributing factor. Clinical studies have given variable and conflicting results on its importance and incidence after SAH. The aim of this study was to prospectively examine SAH patients with assessment of endocrine function in the acute stage and at early follow-up and to compare clinical SAH features to endocrine abnormalities indicating pituitary dysfunction. METHODS: Endocrine function was assessed by basal hormonal concentrations at 5 to 10 days and 3 to 6 months after SAH. Growth hormone deficiency also was evaluated by the growth hormone releasing hormone-arginine stimulation test at follow-up. Clinical outcome was assessed and scored according to the Glasgow Outcome Scale. RESULTS: Fifty-one SAH patients were included and assessed in the acute stage after the bleed. Six were lost to follow-up. The overall prevalence of pituitary dysfunction was 37% and 27% in the acute stage and at follow-up, respectively. Patients with evidence of pituitary dysfunction had significantly worse outcome according to Glasgow Outcome Scale at both occasions. The ruptured aneurysm was more commonly located in the circle of Willis among patients with pituitary dysfunction in the acute stage. CONCLUSIONS: The present results support earlier findings that hormonal abnormalities are not infrequent after SAH. Furthermore, our data suggest that pituitary dysfunction is associated with worse clinical outcome and is more common among patients with bleeding sites close to the hypothalamus.

Subclinical hypercortisolism and CT appearance in adrenal incidentalomas: a multicenter study from Southern Sweden.

Evaluation of subclinical hypercortisolism (SH) in patients with adrenal incidentaloma (AI) including its correlation to size, attenuation at unenhanced computed tomography (CT) and unilateral or bilateral adrenal disease. Nine hospitals in Southern Sweden investigated during 2005-2007 consecutively patients with AI with hormonal and CT examinations according a regional protocol. Two hundred and twenty-eight patients with AI with median size 2.0 cm were included. One mg overnight dexamethasone suppression test (DST) was performed in 223 patients and basal P-ACTH measured in 146 patients. SH was defined as cortisol ≥ 50 nmol/l at DST in combination with basal ACTH <2 pmol/l. In patients with unilateral AI 42% (76/180) had inadequate suppression at DST and 23% (27/115) had SH. The probability for SH and inadequate suppression at DST correlated positively to size and inversely to attenuation at CT. Bilateral AI were found in 43 patients and of these 70% (30/43) had inadequate suppression at DST and 42% (13/31) SH. The patients with SH or inadequate suppression at DST had increased frequency of hypertension which increased further in patients with post-DST cortisol ≥ 140 nmol/l. The applied criterion for SH is useful for initial evaluation of patients with AI. SH is common in patients with AI, particular in bilateral disease. In patients with unilateral AI the probability for SH correlated positively to size and inversely to attenuation at CT. Furthermore, SH and the post-DST cortisol concentration was associated with hypertension.

Classification of pituitary growth hormone producing adenomas according to SIPAP: application in clinical practice.

BACKGROUND: In 1997, the SIPAP classification was introduced, a guide designed for MRI, to characterize pituitary adenomas with emphasis on extrasellar extensions and impact on adjacent structures. To our knowledge no previous evaluation of the inter-observer agreement of the SIPAP classification has been performed. PURPOSE: To evaluate the inter-observer agreement of the SIPAP classification. MATERIAL AND METHODS: Sixty patients operated on for growth hormone producing pituitary adenomas at Lund University Hospital 1991-2007 had an assessable preoperative MRI scan. Forty-five of them also had an assessable postoperative MRI scan. The mean time between surgery and postoperative MRI scans was 11 months. Two observers evaluated all the MRI scans independently. The outcome of the evaluation is presented as the percentage of concordance in each of the evaluated directions and the degree of discrepancy for each of the directions evaluated. RESULTS: In 284 (79%) of 360 preoperative gradings both observers agreed completely. In 17 of the 60 preoperative MRI scans, both observers made identical assessments according to the SIPAP classification in all the six different directions of tumor extension. In 76 gradings the results differed between the observers. The difference was 1 grade (or less) in 69 cases. In 230 (85%) of 270 postoperative gradings the results were identical for both observers. In 18 of the 45 postoperative MRI scans, both observers made the same assessments according to the SIPAP classification in all the six different directions of tumor extension. In 40 gradings the results differed between the observers. The difference was 1 grade (or less) in all 40 cases. CONCLUSION: We found a relatively high inter-observer agreement both pre- and postoperatively, supporting the usefulness and easy applicability of the SIPAP system for grading of pituitary adenomas pre- as well as postoperatively.