Cardiovascular risk profile in growth hormone-treated adults with craniopharyngioma compared to non-functioning pituitary adenoma: a national cohort study.

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.

Digital pathology in the time of corona.

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.

Effect of long-term GH replacement therapy on cardiovascular outcomes in GH-deficient patients previously treated for acromegaly: a sub-analysis from the Dutch National Registry of Growth Hormone Treatment in Adults.

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.

Efficacy and safety of growth hormone treatment in adults with growth hormone deficiency: a systematic review of studies on morbidity.

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.

A long-term follow-up study of eighteen patients with thyrotrophin-secreting pituitary adenomas.

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.

Predictors of endoscopic transsphenoidal surgery outcome in acromegaly: patient and tumor characteristics evaluated by magnetic resonance imaging.

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.