Search

Context: Cardiovascular (CV) risk profile might differ between growth hormone-treated patients with craniopharyngioma and non-functioning pituitary adenoma (NFPA), since patients with craniopharyngioma more frequently suffer from hypothalamic metabolic disruption., Objective: The aim of this study is to investigate the CV risk profile in adult patients with craniopharyngioma compared to NFPA before and after treatment with growth hormone (GH) replacement therapy due to severe GH deficiency., Design: A sub-analysis of the Dutch National Registry of Growth Hormone Treatment in Adults was performed, in which we compared 291 patients with craniopharyngioma to 778 patients with NFPA. CV risk profile and morbidity were evaluated at baseline and during long-term follow-up within and between both groups., Results: At baseline, patients with craniopharyngioma demonstrated higher BMI than patients with NFPA, and men with craniopharyngioma showed greater waist circumference and lower HDL compared to men with NFPA. During follow-up, BMI, as well as diastolic blood pressure among patients using antihypertensive drugs, deteriorated in the craniopharyngioma group compared to the NFPA group. Lipid profile improved similarly in both groups over time. No differences were found between groups in the occurrence of diabetes mellitus, cerebrovascular accidents, CV disease, or overall mortality., Conclusion: This study suggests that overall CV risk profile is worse in craniopharyngioma patients with GH deficiency compared to patients with NFPA. During GH replacement therapy, patients with craniopharyngioma demonstrated an increase in BMI over time, where BMI remained stable in patients with NFPA. Also, diastolic blood pressure did not improve with antihypertensive drugs in craniopharyngioma patients as seen in patients with NFPA.

The 2020 COVID-19 crisis has had and will have many implications for healthcare, including pathology. Rising number of infections create staffing shortages and other hospital departments might require pathology employees to fill more urgent positions. Furthermore, lockdown measures and social distancing cause many people to work from home. During this crisis, it became clearer than ever what an asset digital diagnostics is to keep pathologists, residents, molecular biologists and pathology assistants engaged in the diagnostic process, allowing social distancing and a 'need to be there' on-the-premises policy, while working effectively from home. This paper provides an overview of our way of working during the 2020 COVID-19 crisis with emphasis on the virtues of digital pathology., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: The effects of growth hormone (GH) replacement therapy on fracture risk in adult GH deficient (GHD) patients with different etiologies of pituitary GHD are not well known, due to limited data. The aim of this study was to investigate characteristics and fracture occurrence at start of (baseline) and during long-term GH replacement therapy in GHD adults previously treated for Cushing's disease (CD) or acromegaly, compared to patients with previous nonfunctioning pituitary adenoma (NFPA)., Methods: From the Dutch National Registry of Growth Hormone Treatment in Adults, a nationwide surveillance study in severe GHD adults, all patients using ≥30 days of GH replacement therapy with previous NFPA (n = 783), CD (n = 180) and acromegaly (n = 65) were selected. Patient characteristics, fractures and potential influencing factors were investigated., Results: At baseline, patients with previous CD were younger, more often female and had more often a history of osteopenia or osteoporosis, whereas patients with previous acromegaly had more often received cranial radiotherapy and a longer duration between treatment of their pituitary tumor and start of adult GH replacement therapy. During follow-up, a fracture occurred in 3.8 % (n = 39) of all patients. Compared to patients with previous NFPA, only patients with previous acromegaly had an increased fracture risk after 6 years of GH replacement therapy., Conclusions: During GH replacement therapy, an increased fracture risk was observed in severe GHD adult patients previously treated for acromegaly, but not in those previously treated for CD, compared to severe GHD adult patients using GH replacement therapy because of previous NFPA. Further studies are needed to confirm these findings and to elucidate potential underlying mechanisms.

Context: IGF-1 plays a role in bone metabolism. Although IGF-1 and bone mass both decrease with advancing age, their relationship in older individuals remains to be elucidated., Objective: The objective was to investigate associations of serum IGF-1 cross-sectionally with quantitative ultrasound and bone mineral density (BMD), and longitudinally with 3-year change in BMD and 10-year fracture risk in older individuals., Design, Setting, and Patients: The study included 627 men and 656 women aged ≥ 65 years from the Longitudinal Aging Study Amsterdam, an ongoing, population-based cohort study., Main Outcome Measures: Main outcome measures included baseline serum IGF-1 concentration; baseline quantitative ultrasound of the heel, including broadband ultrasound attenuation and speed of sound; BMD measured at several body sites at baseline and after 3 years; and prospective fracture incidence over 10 years. Associations were adjusted for relevant confounders., Results: Women, but not men, in the lowest quintile of IGF-1 concentration had lower broadband ultrasound attenuation (B = -4.53; P = .03) and a greater 3-year decrease in total hip BMD (B = -0.02; P = .05), than women in the highest quintile of IGF-1. Moreover, compared to women in the highest quintile of IGF-1, women in the combined lowest four quintiles of IGF-1 had an increased 10-year fracture risk (hazard ratio = 1.98; P = .05)., Conclusions: Associations of lower IGF-1 with lower BUA, greater 3-year decrease in BMD, and increased 10-year fracture risk were only observed in women, not in men. These results support previous findings of gender differences in the relationship between IGF-1 and bone in older individuals.

Context: GH replacement therapy (GH-RT) is a widely accepted treatment in GH-deficient adults with nonfunctioning pituitary adenoma (NFPAs). However, some concerns have been raised about the safety of GH-RT because of its potentially stimulating effect on tumor growth., Objective: The aim of this study was to evaluate tumor progression in NFPA patients using GH-RT., Design, Setting, and Patients: From the Dutch National Registry of Growth Hormone Treatment in Adults, a nationwide surveillance study in severely GH-deficient adults (1998-2009), all NFPA patients with ≥ 30 days of GH-RT were selected (n = 783). Data were retrospectively collected from the start of GH-RT in adulthood (baseline)., Main Outcome Measure: Tumor progression, including tumor recurrence after complete remission at baseline and regrowth of residual tumor., Results: Tumor progression developed in 12.1% of the patients after a median (range) time of 2.2 (0.1-14.9) years. Prior radiotherapy decreased tumor progression risk compared to no radiotherapy (hazard ratio = 0.16; 95% confidence interval, 0.09-0.26). Analysis in 577 patients with available baseline imaging data showed that residual tumor at baseline increased tumor progression risk compared to no residual tumor (hazard ratio = 4.5; 95% confidence interval, 2.4-8.2)., Conclusions: The findings in this large study were in line with those reported in literature and provide further evidence that GH-RT does not appear to increase tumor progression risk in NFPA patients. Although only long-term randomized controlled trials will be able to draw firm conclusions, our data support the current view that GH-RT is safe in NFPA patients.

Objective: Serum insulin-like growth factor 1 (IGF-1) concentration decreases, while the prevalence of depressive symptoms increases with advancing age. Although basic research indicates a link between low IGF-1 concentration and depression, this has scarcely been investigated in humans. This study investigates whether lower IGF-1 concentrations are associated with prevalent and incident late-life depression over a 3-year period., Methods: The study included 1188 participants, aged ≥ 65 years, from the Longitudinal Aging Study Amsterdam (LASA), an ongoing, population-based cohort study. Depression was assessed at baseline and after three years using the Center for Epidemiological Studies-Depression Scale (CES-D) and the Diagnostic Interview Schedule (DIS), and categorized into minor depression and major depression (MDD). Serum IGF-1 concentration was determined at baseline. Associations were adjusted for relevant confounders., Results: Serum IGF-1 concentrations were within the normal range (mean 13.9 nmol/l, standard deviation 5.3 nmol/l). At baseline, in men, as compared to high concentrations, mid concentrations decreased the probability of prevalent minor depression (odds ratio [OR] = 0.35, 95% confidence interval [CI] = 0.15-0.82). In women, as compared to high concentrations, low concentrations tended to increase the probability of prevalent MDD (OR = 2.66, 95% CI = 0.89-7.89). At three-year follow-up, in men, no significant prospective associations were detected. In women, as compared to high concentrations, mid concentrations decreased the probability of incident minor depression (OR = 0.43, 95% CI = 0.19-0.95)., Conclusions: Several associations, which differed across the genders, were observed between IGF-1 and depression. Cross-sectional findings were not supported by longitudinal findings, which suggest that IGF-1 may not play an important predictive role in the development of depression in older persons over time. However, a more acute role of IGF-1 in current depression, as indicated by the cross-sectional results, may be possible. Further studies are needed to elucidate the complex relation between IGF-1 and late-life depression., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Context: Radiotherapy is frequently administered as adjuvant treatment in patients with clinically nonfunctioning pituitary adenomas (NFPAs). However, concerns have been raised about potential long-term side effects, including cerebrovascular events (CVEs) and secondary intracranial tumors., Objective: The aim of this study was to analyze the risk of CVEs, secondary intracranial tumors, and mortality in irradiated (IRR) NFPA patients, compared with NFPA patients who were not irradiated (non-IRR)., Design, Setting, and Patients: The study cohort included 806 patients with a NFPA from the Dutch National Registry of Growth Hormone Treatment in Adults, a nationwide long-term surveillance study in severe GH-deficient adult patients. IRR patients (n = 456) were compared with non-IRR patients (n = 350)., Main Outcome Measures: CVEs, secondary intracranial tumors, and mortality were measured., Results: Sixty-nine subjects developed a CVE. In men, but not in women, the incidence of a CVE was significantly higher in IRR patients than in non-IRR patients (hazard ratio 2.99, 95% confidence interval 1.31-6.79). A secondary intracranial tumor developed in five IRR patients and two non-IRR patients. After adjustment for age, radiotherapy was not associated with mortality., Conclusions: The incidence of secondary intracranial tumors and mortality did not differ between IRR and non-IRR patients. However, a CVE was found significantly more frequently in IRR men but not in women. Further research into the long-term effects of cranial radiotherapy seems mandatory. The potential risks of radiotherapy have to be taken into account when radiotherapy is considered in NFPA patients, and long-term follow-up is recommended.

Objective: The effect of GH deficiency (GHD) on the metabolic profile of acromegaly patients is unclear in patients previously treated for acromegaly, as are the efficacy and safety of GH treatment in this particular group. The aim of the study is to describe the characteristics of patients with severe GHD who were previously treated for acromegaly, and to investigate the effects of long-term GH treatment on cardiovascular risk factors and morbidity, compared with patients who were treated for a nonfunctioning pituitary adenoma (NFPA)., Design: A nationwide surveillance study., Methods: Sixty-five patients from the Dutch National Registry of Growth Hormone Treatment in Adults with previous acromegaly were compared with 778 patients with previous NFPA. Cardiovascular indices, including body composition, lipid profile, glucose metabolism, blood pressure, and morbidity were investigated., Results: GHD patients with previous acromegaly had an unfavorable metabolic profile comparable with or more than GHD patients with previous NFPA. GH treatment led to improvement of the lipid profile in both groups, also after excluding patients using lipid-lowering medication. In patients with previous acromegaly, HbA1c levels increased more than in patients with previous NFPA (estimate 0.03, 95% CI 0.002-0.06, P=0.04). The risk for developing cardiovascular diseases was not different between the groups., Conclusions: The patients with GHD after previous acromegaly have an unfavorable metabolic profile comparable with patients with GHD after previous NFPA. In both groups, the lipid profile improves during GH treatment. Changes in glucose metabolism should be monitored closely. GH treatment in patients with GHD previously treated for acromegaly had no deleterious effect on cardiovascular morbidity., (© 2014 European Society of Endocrinology.)

Due to the positive effects demonstrated in randomized clinical trials on cardiovascular surrogate markers and bone metabolism, a positive effect of growth hormone (GH) treatment on clinically relevant end-points seems feasible. In this review, we discuss the long-term efficacy and safety of GH treatment in adult patients with growth hormone deficiency (GHD) with emphasis on morbidity: fatal and nonfatal cardiovascular disease (CVD) and stroke, fractures, fatal and nonfatal malignancies and recurrences, and diabetes mellitus. A positive effect of GH treatment on CVD and fracture risk could be concluded, but study design limitations have to be considered. Stroke and secondary brain tumours remained more prevalent. However, other contributing factors have to be taken into account. Regrowth and recurrences of (peri)pituitary tumours were not increased in patients with GH treatment compared to similar patients without GH treatment. All fatal and nonfatal malignancies were not more prevalent in GH-treated adults compared to the general population. However, follow-up time is still relatively short. The studies on diabetes are difficult to interpret, and more evidence is awaited. In clinical practice, a more individualized assessment seems appropriate, taking into consideration the underlying diagnosis of GHD, other treatment regimens, metabolic profile and the additional beneficial effects of GH set against the possible risks. Large and thoroughly conducted observational studies are needed and seem the only feasible way to inform the ongoing debate on health care costs, drug safety and clinical outcomes., (© 2014 John Wiley & Sons Ltd.)

Objective: TSH-secreting pituitary adenomas (TSH-omas) are a rare cause of thyrotoxicosis. First-line therapy for these tumours is neurosurgery, although medical therapy with somatostatin analogues (SSAs) is increasingly used for this indication., Design and Patients: We retrospectively reviewed the data of patients with a TSH-oma (n = 18, 67% males) followed between 1989 and 2011 (median follow-up 7 years, range 1-21) in three academic medical centres in the Netherlands, focusing on the role of SSA treatment., Measurements: Patient records were reviewed for clinical, biochemical, imaging, pathological and treatment characteristics., Results: At initial evaluation, biochemical hyperthyroidism with non-suppressed TSH concentrations was detected in 94% of the patients. The majority of patients (72%) had a macroadenoma with extrasellar extension. Fourteen patients underwent surgery, resulting in postoperative euthyroidism in six patients (43%). Recurrence of hyperthyroidism developed in three of them after 5, 24 and 32 months, respectively. Adjuvant radiotherapy (n = 2) did not induce remission. Three patients received SSA therapy exclusively, resulting in apparent cure in one of them. During long-term follow-up, 72% of all patients required medical therapy (mostly SSA treatment). Euthyroidism was achieved in all but one patient, who refused all treatments., Conclusions: Our results demonstrate that patients with TSH-omas, who often present with large macroadenomas with extrasellar extension, have an excellent response to SSA therapy. Because the results of surgery and radiotherapy are disappointing, primary medical therapy may be considered in virtually all patients, except in case of optic chiasm compression, especially in those harbouring large adenomas with parasellar extension., (© 2013 John Wiley & Sons Ltd.)

The availability of various first-line treatment modalities for acromegaly and evolving surgical techniques emphasize the need for accurately defined predictors of surgical outcome. We retrospectively analysed the outcome of 30 patients with acromegaly after initial endoscopic transsphenoidal surgery in two university hospitals from 2001 until 2009, and reviewed comparable literature investigating predictive tumor characteristics. Medical records were monitored for patient characteristics. Each pituitary magnetic resonance imaging (MRI) scan was revised independently by two neuroradiologists using a standardised analysis form to record distinctive predefined tumor characteristics. All characteristics were independently analysed as predictors for persistent disease, and a multivariable predictive model was created. Literature from 2000 onwards was searched for studies describing tumor characteristics predictive for surgical outcome. The cohort consisted of 27 macroadenomas with 90 % demonstrating signs of parasellar extension. The surgical cure rate overall was 30 %. Independently, next to male sex and increasing tumor size, infrasellar and parasellar extension based on MRI staging tended to increase the risk of persistent disease. In a multivariable analysis, sex and parasellar extension of the tumor were demonstrated to be the variables allowing for the best fitted predictive model for persistent disease. Earlier studies on preoperative tumor characteristics showed comparable results, although these were based on several different tumor classification systems. This retrospective study demonstrates that accurately defined tumor characteristics based on imaging, especially for cavernous sinus invasion, can be helpful in predicting surgical outcome. Comparative studies on different treatment modalities are essential for clinical practice within the scope of re-evaluation of the role of surgery in GH-secreting adenomas.