BackgroundThe ability to preoperatively predict postoperative complication risks is valuable for individual counseling and (post)operative planning, e.g. to select low-risk patients eligible for short stay surgery or those with higher risks requiring special attention. These risks however, are not well established in pituitary surgery.MethodsWe conducted a systematic review of associations between preoperative characteristics and postoperative complications of endoscopic transsphenoidal surgery according to the PRISMA guidelines. Risk of bias was assessed through the QUIPS tool.ResultsIn total 23 articles were included, containing 5491 patients (96% pituitary adenoma). There was a wide variety regarding the nature and number of risk factors, definitions, measurement and statistics employed, and overall quality of mainly retrospective studies was low. Consistent significant associations were older age for complications in general, and intraventricular extension for cerebrospinal fluid (CSF) leaks. Associations identified in some but not all studies were younger age, increased BMI, female gender, and learning curve for CSF leaks; increased tumor size for complications in general; and Rathke’s cleft cysts for diabetes insipidus. Mortality (incidence rate 1%) was not addressed as a risk factor.ConclusionBased on current literature, of low to medium quality, it is not possible to comprehensively quantify risk factors for complications. Nevertheless, older age and intraventricular extension were associated with increased postoperative complications. Future research should aim at prospective data collection, reporting of outcomes, and uniformity of definitions. Only then a proper risk analysis can be performed for endoscopic pituitary surgery.Electronic supplementary materialThe online version of this article (doi:10.1007/s11102-017-0839-1) contains supplementary material, which is available to authorized users.

Purpose Although transient diabetes insipidus (DI) is the most common complication of pituitary surgery, there is no consensus on its definition. Polyuria is the most overt symptoms of DI, but can also reflect several physiological adaptive mechanisms in the postoperative phase. These may be difficult to distinguish from and might coincide with DI. The difficulty to distinguish DI from other causes of postoperative polyuria might explain the high variation in incidence rates. This limits interpretation of outcomes, in particular complication rates between centers, and may lead to unnecessary treatment. Aim of this review is to determine a pathophysiologically sound and practical definition of DI for uniform outcome evaluations and treatment recommendations. Methods This study incorporates actual data and the experience of our center and combines this with a review of literature on pathophysiological mechanisms and definitions used in clinical studies reporting of postoperative DI. Results The occurrence of excessive thirst and/or hyperosmolality or hypernatremia are the best indicators to discriminate between pathophysiological symptoms and signs of DI and other causes. Urine osmolality distinguishes DI from osmotic diuresis. Conclusions To improve reliability and comparability we propose the following definition for postoperative DI: polyuria (urine production > 300 ml/hour for 3 h) accompanied by a urine specific gravity (USG) < 1.005, and at least one of the following symptoms: excessive thirst, serum osmolality > 300 mosmol/kg, or serum sodium > 145 mmol/L. To prevent unnecessary treatment with desmopressin, we present an algorithm for the diagnosis and treatment of postoperative DI.

Context The improved remission and complication rates of current transsphenoidal surgery warrant reappraisal of the position of surgery as a viable alternative to dopamine agonists in the treatment algorithm of prolactinomas. Objective To compare clinical outcomes after dopamine agonist withdrawal and transsphenoidal surgery in prolactinoma patients. Methods Eight databases were searched up to July 13, 2018. Primary outcome was disease remission after drug withdrawal or surgery. Secondary outcomes were biochemical control and side effects during dopamine agonist treatment and postoperative complications. Fixed- or random-effects meta-analysis was performed to estimate pooled proportions. Robustness of results was assessed by sensitivity analyses. Results A total of 1469 articles were screened: 55 (10 low risk of bias) on medical treatment (n = 3564 patients) and 25 (12 low risk of bias) on transsphenoidal surgery (n = 1836 patients). Long-term disease remission after dopamine agonist withdrawal was 34% (95% confidence interval [CI], 26-46) and 67% (95% CI, 60-74) after surgery. Subgroup analysis of microprolactinomas showed 36% (95% CI, 21-52) disease remission after dopamine agonist withdrawal, and 83% (95% CI, 76-90) after surgery. Biochemical control was achieved in 81% (95% CI, 75-87) of patients during dopamine agonists with side effects in 26% (95% CI, 13-41). Transsphenoidal surgery resulted in 0% mortality, 2% (95% CI, 0-5) permanent diabetes insipidus, and 3% (95% CI, 2-5) cerebrospinal fluid leakage. Multiple sensitivity analyses yielded similar results. Conclusions In the majority of prolactinoma patients, disease remission can be achieved through surgery, with low risks of long-term surgical complications, and disease remission is less often achieved with dopamine agonists.

PurposeSystematic review and meta-analysis comparing endoscopic and microscopic transsphenoidal surgery for Cushing’s disease regarding surgical outcomes (remission, recurrence, and mortality) and complication rates. To stratify the results by tumor size.MethodsNine electronic databases were searched in February 2017 to identify potentially relevant articles. Cohort studies assessing surgical outcomes or complication rates after endoscopic or microscopic transsphenoidal surgery for Cushing’s disease were eligible. Pooled proportions were reported including 95% confidence intervals.ResultsWe included 97 articles with 6695 patients in total (5711 microscopically and 984 endoscopically operated). Overall, remission was achieved in 5177 patients (80%), with no clear difference between both techniques. Recurrence was around 10% and short term mortality < 0.5% for both techniques. Cerebrospinal fluid leak occurred more often in endoscopic surgery (12.9 vs. 4.0%), whereas transient diabetes insipidus occurred less often (11.3 vs. 21.7%). For microadenomas, results were comparable between both techniques. For macroadenomas, the percentage of patients in remission was higher after endoscopic surgery (76.3 vs. 59.9%), and the percentage recurrence lower after endoscopic surgery (1.5 vs. 17.0%).ConclusionsEndoscopic surgery for patients with Cushing’s disease reaches comparable results for microadenomas, and probably better results for macroadenomas than microscopic surgery. This is present despite the presumed learning curve of the newer endoscopic technique, although confounding cannot be excluded. Based on this study, endoscopic surgery may thus be considered the current standard of care. Microscopic surgery can be used based on neurosurgeon’s preference. Endocrinologists and neurosurgeons in pituitary centers performing the microscopic technique should at least consider referring Cushing’s disease patients with a macroadenoma.Electronic supplementary materialThe online version of this article (10.1007/s11102-018-0893-3) contains supplementary material, which is available to authorized users.

Psychiatric and neurocognitive symptoms due to hypercortisolism were already described by Harvey Cushing in his original paper on patients with Cushing's syndrome (CS). Nowadays, it is well known that psychiatric and cognitive complaints are two of the most common, and most distressing, symptoms in patients with CS. Psychiatric symptoms are indeed a major clinical manifestation of CS. The most commonly observed psychiatric conditions are depression and anxiety, whilst mania and psychosis are less common. Several domains of cognitive function are impaired at diagnosis, including episodic and working memory, executive function and attention. Following treatment, onefourth of the patients still experience depressed mood, and the cognitive impairments are only partially restored. Consequently, quality of life in patients with CS is severely and persistently affected. Neuroimaging studies have also illustrated the deleterious effects of hypercortisolism on the brain by demonstrating reduced grey matter volumes and cortical thickness, altered restingstate functional responses and during cognitive tasks, as well as widespread reduced white matter integrity, especially in structures important for cognitive function and emotional processing, both before and after successful abrogation of hypercortisolism. In this paper, we summarize the current knowledge on the psychiatric and neurocognitive consequences of hypercortisolism in patients with CS, both before, and after successful treatment. In addition, we review the structural and functional brain abnormalities associated with hypercortisolism and discuss the influence of these factors on quality of life.

Objective Although widely advocated, applying Value Based Health Care (VBHC) in clinical practice is challenging. This study describes VBHC-based perioperative outcomes for patients with pituitary tumors up to 6 months postoperatively. Methods A total of 103 adult patients undergoing surgery were prospectively followed. Outcomes categorized according to the framework of VHBC included survival, degree of resection, endocrine remission, visual outcome (including self-perceived functioning), recovery of pituitary function, disease burden and health-related quality of life (HRQoL) at 6 months (Tier 1); time to recovery of disease burden, HRQoL, visual function (Tier 2); permanent hypopituitarism and accompanying hormone replacement (Tier 3). Generalized estimating equations (GEEs) analysis was performed to describe outcomes over time. Results Regarding Tier 1, there was no mortality, 72 patients (70%) had a complete resection, 31 of 45 patients (69%) with functioning tumors were in remission, 7 (12%, with preoperative deficits) had recovery of pituitary function and 45 of 47 (96%) had visual improvement. Disease burden and HRQoL improved in 36–45% at 6 months; however, there were significant differences between tumor types. Regarding Tier 2: disease burden, HRQoL and visual functioning improved within 6 weeks after surgery; however, recovery varied widely among tumor types (fastest in prolactinoma and non-functioning adenoma patients). Regarding Tier 3, 52 patients (50%) had persisting (tumor and treatment-induced) hypopituitarism. Conclusions Though challenging, outcomes of a surgical intervention for patients with pituitary tumors can be reflected through a VBHC-based comprehensive outcome set that can distinguish outcomes among different patient groups with respect to tumor type.

Context The increased use of opioids has resulted in an unprecedented opioid epidemic. Chronic opioid use causes hypogonadism, but its frequency, as well as the effects of opioids on other hypothalamo–pituitary–end organ hormone axes, remains unclear. Objective The aim of this systematic review and meta-analysis was to assess the effects of opioid use on pituitary function. Methods Eight electronic databases were searched for articles published up to May 8, 2018. Fixed or random effects meta-analysis was performed to estimate pooled proportions with 95% confidence intervals (CI). This study is reported following the PRISMA and MOOSE guidelines. Data synthesis 52 studies (22 low risk of bias) were included describing 18 428 subjects, consisting of patients with chronic pain (n = 21 studies) or on maintenance treatment for opioid addiction (n = 9) and healthy volunteers (n = 4). The most frequently used opioid was methadone (n = 13 studies), followed by morphine (n = 12). Prevalence of hypogonadism was 63% (95% CI: 55%–70%, 15 studies, 3250 patients, 99.5% males). Prevalence of hypocortisolism relying on dynamic and nondynamic testing was 15% (95% CI: 6%–28%, 5 studies, 205 patients, 57.5% males) and including only studies using the insulin tolerance tests 24% (95% CI 16%–33%, 2 studies, n = 97 patients). In 5 out of 7 studies, hyperprolactinemia was present. No clear effects on the somatotropic and hypothalamo–pituitary–thyroid axes were described. Conclusions Hypogonadism occurs in more than half of male opioid users, and hypocortisolism in approximately one-fifth of all patients. Periodical evaluation of at least the gonadal and adrenal axes is therefore advisable.

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