Wouter R. van Furth

Predictors of Quality of Life in Acromegaly: No Consensus on Biochemical Parameters

Background Quality of life (QoL) in patients with acromegaly is reduced irrespective of disease state. The contributions of multifactorial determinants of QoL in several disease stages are presently not well known. Objective To systematically review predictors of QoL in acromegalic patients. Methods Main databases were systematically searched using predefined search terms for potentially relevant articles up to January 2017. Inclusion criteria included separate acromegaly cohort, non-hereditary acromegaly, QoL as study parameter with clearly described method of measurement and quantitative results, N ≥ 10 patients, article in English and adult patients only. Data extraction was performed by two independent reviewers; studies were included using the PRISMA flow diagram. Results We identified 1,162 studies; 51 studies met the inclusion criteria: 31 cross-sectional observational studies [mean AcroQoL score 62.7 (range 46.6–87.0, n = 1,597)], 9 had a longitudinal component [mean baseline AcroQoL score 61.4 (range 54.3–69.0, n = 386)], and 15 were intervention studies [mean baseline AcroQoL score 58.6 (range 52.2–75.3, n = 521)]. Disease-activity reflected by biochemical control measures yielded mixed, and therefore inconclusive results with respect to their effect on QoL. Addition of pegvisomant to somatostatin analogs and start of lanreotide autogel resulted in improvement in QoL. Data from intervention studies on other treatment modalities were too limited to draw conclusions on the effects of these modalities on QoL. Interestingly, higher BMI and greater degree of depression showed consistently negative associations with QoL. Hypopituitarism was not significantly correlated with QoL in acromegaly. Conclusion At present, there is insufficient published data to support that biochemical control, or treatment of acromegaly in general, is associated with improved QoL. Studies with somatostatin receptor ligand treatment, i.e., particularly lanreotide autogel and pegvisomant have shown improved QoL, but consensus on the correlation with biochemical control is missing. Longitudinal studies investigating predictors in treatment-naive patients and their follow-up after therapeutic interventions are lacking but are urgently needed. Other factors, i.e., depression and obesity were identified from cross-sectional cohort studies as consistent factors associated with poor QoL. Perhaps treatment strategies of acromegaly patients should not only focus on normalizing biochemical markers but emphasize improvement of QoL by alternative interventions such as psychosocial or weight lowering interventions.

Preoperative risk factors for postoperative complications in endoscopic pituitary surgery: a systematic review

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.

How non-functioning pituitary adenomas can affect health-related quality of life: a conceptual model and literature review

After treatment for a non-functioning pituitary adenoma (NFA) health-related quality of life (HR-QoL) improves considerably. However, the literature about the normalization of HR-QoL after treatment is inconclusive. Some researchers described a persistently decreased HR-QoL compared to reference data, while others did not. Considering this variety in observed HR-QoL outcomes, the aim of the present review was to provide a literature overview of health outcomes in patients with a NFA, using a conceptual HR-QoL model. A concrete conceptualization of the health outcomes of patients with a NFA can be helpful to understand the observed variety in HR-QoL outcomes and to improve clinical care and guidance of these patients. For this conceptualization, the Wilson and Cleary model was used. This model has a biopsychosocial character and has been validated in several patient populations. In the present review, health outcomes of patients with a NFA were described at each stage of the model e.g. biological and physiological variables, symptom status, functional status, general health perceptions and overall HR-QoL. The Wilson–Cleary model elucidates that elements at each stage of the model can contribute to the impairment in HR-QoL of patients with a NFA, which explains the reported variety in the literature. Furthermore, by applying the model, potential interventions targeting these elements can be identified. While optimal biomedical treatment has always been the focus, it is clearly not sufficient for good HR-QoL in patients with a NFA. Further improvement of HR-QoL should be supported by a pituitary specific care trajectory, including psychosocial care (e.g. self-management training), to beneficially affect characteristics of the patient and the (healthcare) environment, with the utmost goal to optimize HR-QoL in patients after treatment.

Review of Techniques to Achieve Optical Surface Cleanliness and Their Potential Application to Surgical Endoscopes

A clear visualization of the operative field is of critical importance in endoscopic surgery. During surgery the endoscope lens can get fouled by body fluids (eg, blood), ground substance, rinsing fluid, bone dust, or smoke plumes, resulting in visual impairment. As a result, surgeons spend part of the procedure on intermittent cleaning of the endoscope lens. Current cleaning methods that rely on manual wiping or a lens irrigation system are still far from ideal, leading to longer procedure times, dirtying of the surgical site, and reduced visual acuity, potentially reducing patient safety. With the goal of finding a solution to these issues, a literature review was conducted to identify and categorize existing techniques capable of achieving optically clean surfaces, and to show which techniques can potentially be implemented in surgical practice. The review found that the most promising method for achieving surface cleanliness consists of a hybrid solution, namely, that of a hydrophilic or hydrophobic coating on the endoscope lens and the use of the existing lens irrigation system.

Visual outcomes after endoscopic endonasal pituitary adenoma resection: a systematic review and meta-analysis

PurposePatients with pituitary adenomas often present with visual deficits. While the aim of endoscopic endonasal transsphenoidal surgery (EETS) is to improve these deficits, permanent worsening is a possible outcome. The aim of this meta-analysis was to evaluate the effect of EETS for pituitary adenomas on visual outcomes.MethodsA meta-analysis was conducted according to the PRISMA guidelines. Pooled prevalence was calculated for complete recovery, improvement, and deterioration of visual field deficits, visual acuity and unspecified visual function in fixed- and random-effect models, including assessment of heterogeneity (I2) and publication bias (Begg’s test).ResultsOut of 2636 articles, 35 case series were included in the meta-analysis. Results are described for fixed-effect models. For patients with impaired visual acuity, only one study reported complete recovery (27.2%). Pooled prevalence for improvement was 67.5% (95% CI = 59.1–75.0%), but with considerable heterogeneity (I2: 86.0%), and 4.50% (95% CI = 1.80–10.8%) for patients experiencing deterioration. For patients with visual field deficits, the prevalence was 40.4% (95% CI = 34.8–46.3%) for complete recovery, 80.8% (95% CI = 77.7–83.6%) for improvement, and 2.3% (95% CI = 1.1–4.7%) for deterioration. For the unspecified visual outcomes, pooled prevalence of complete recovery was 32.9% (95% CI: 28.5–37.7%), but with considerable heterogeneity (I2 = 84.2%). The prevalence was 80.9% (95% CI = 77.9–83.6) for improvement and 2.00% (95% CI = 1.10–3.40%) for deterioration. Random-effect models yielded similar results. Publication bias was non-significant for all the outcomes.ConclusionWhile visual deficits improved after EETS in the majority of patients, complete recovery was only achieved in less than half of the patients and some patients even suffered from visual deterioration.

Pituitary Adenoma Apoplexy in an Adolescent: A Case Report and Review of the Literature

We present a 13-year-old boy who was admitted with complaints of a state of progressive sleepiness and a sudden headache with vomiting and fever. Laboratory testing showed hypoglycemia, multiple pituitary hormonal deficiencies, and an elevated C-reactive protein level. A cranial magnetic resonance imaging (MRI) showed an opaque sphenoid sinus and an intrasellar mass suggesting hemorrhage, so that we suspected pituitary apoplexy (PA) originating from a non-functioning adenoma, although a pituitary abscess could not completely be excluded. The boy was treated with antibiotics, hydrocortisone, and levothyroxine. Due to his rapid clinical improvement, no surgery was performed and we considered the diagnosis of PA as confirmed. At follow-up, the MRI scan showed a small residual lesion. Pituitary deficiencies of growth hormone, adrenocorticotropic hormone (ACTH), thyroid-stimulating hormone, and vasopressin persisted. A literature search of all well-documented cases of PA in children or adolescents (n=30, 13 boys and 17 girls) indicated that this condition is rare below 20 years of age but must be considered when a patient experiences headache with or without visual disturbances, even in the presence of clinical and laboratory signals suggestive of pituitary abscess. MRI neuroimaging is helpful in the differential diagnosis. In both conditions, the possibility of ACTH deficiency should always be considered, investigated, and treated. In cases without severe neuro-ophthalmological deficits and/or with a rapid and positive response to acute medical management, one can abstain from surgical treatment.

Intraoperative Identification of a Normal Pituitary Gland and an Adenoma Using Near-Infrared Fluorescence Imaging and Low-Dose Indocyanine Green

BACKGROUND: The intraoperative distinction between normal and abnormal pituitary tissue is crucial during pituitary adenoma surgery to obtain a complete tumor resection while preserving endocrine function. Near-infrared (NIR) fluorescence imaging is a technique to intraoperatively visualize tumors by using indocyanine green (ICG), a contrast agent allowing visualization of differences in tissue vascularization. Although NIR fluorescence imaging has been described in pituitary surgery, it has, in contrast to other surgical areas, never become widely used. OBJECTIVE: To evaluate NIR fluorescence imaging in pituitary surgery, both qualitatively and quantitatively, and to assess the additional value of resecting adenoma tissue under NIR fluorescence guidance. METHODS: We included 10 patients planned to undergo transnasal transsphenoidal selective adenomectomy. Patients received multiple intravenous administrations of 5 mg ICG, up to a maximum of 15 mg per patient. Endoscopic NIR fluorescence imaging was performed at multiple points in time. The NIR fluorescent signal in both the adenoma and pituitary gland was obtained, and the fluorescence contrast ratio was assessed. RESULTS: Four patients had Cushing disease, 1 had acromegaly, and 1 had a prolactinoma. Four patients had a nonfunctioning macroadenoma. In 9 of 10 patients with a histologically proven pituitary adenoma, the normal pituitary gland showed a stronger fluorescent signal than the adenoma. A fluorescence contrast ratio of normal pituitary gland to adenoma of 1.5 ± 0.2 was obtained. In 2 patients; adenoma resection was actually performed under NIR fluorescence guidance instead of under white light. CONCLUSION: NIR fluorescence imaging can easily and safely be implemented in pituitary surgery. The timing of ICG administration is important for optimal results and warrants further study. It appears that injection of ICG can best be postponed until some part of the normal pituitary gland is identified. Subsequent repeated low-dose ICG administrations improved the distinction between adenoma and gland. ABBREVIATIONS: DI, diabetes insipidus FCR, fluorescence contrast ratio ICG, indocyanine green NIR, near-infrared