Acromegaly : treatment and follow-up : the Leiden studies

LUMCDiabetes, endocriene pathofysiologie en endocriene tumore

Therapeutic options in the management of acromegaly: focus on lanreotide Autogel®

In acromegaly, expert surgery is curative in only about 60% of patients. Postoperative radiation therapy is associated with a high incidence of hypopituitarism and its effect on growth hormone (GH) production is slow, so that adjuvant medical treatment becomes of importance in the management of many patients. To delineate the role of lanreotide in the treatment of acromegaly. Search of Medline, Embase, and Web of Science databases for clinical studies of lanreotide in acromegaly. Treatment with lanreotide slow release and lanreotide Autogel((R)) normalized GH and insulin-like growth factor-I (IGF-I) concentrations in about 50% of patients. The efficacy of 120 mg lanreotide Autogel((R)) on GH and IGF-I levels was comparable with that of 20 mg octreotide LAR. There were no differences in improvement of cardiac function, decrease in pancreatic beta-cell function, or occurrence of side effects, including cholelithiasis, between octreotide LAR and lanreotide Autogel(R). When postoperative treatment with somatostatin analogs does not result in normalization of serum IGF-I and GH levels after noncurative surgery, pegvisomant alone or in combination with somatostatin analogs can control these levels in a substantial number of patient

Patient-reported outcomes in refractory hormone-producing pituitary adenomas: an unmet need

Purpose: To describe quality and outcomes of patient-reported outcome (PRO) measures (PROMs) used in patients with refractory hormone-producing pituitary adenomas, and to provide an overview of PROs in these challenging pituitary adenomas. Methods: Three databases were searched for studies reporting on refractory pituitary adenomas. For the purpose of this review, refractory adenomas were defined as tumors resistant to primary therapy. General risk of bias was assessed using a component approach and the quality of PROM reporting was assessed using the International Society for Quality of Life Research (ISOQOL) criteria.Results: 20 studies reported on PROMs in refractory pituitary adenomas, using 14 different PROMs, of which 4 were disease specific (median general risk of bias score: 33.5% (range 6-50%) and ISOQOL score: 46% (range 29-62%)). SF-36/RAND-36 and AcroQoL were most frequently used. Health-related quality of life in refractory patients (measured by AcroQoL, SF-36/Rand-36, Tuebingen CD-25, and EQ-5D-5L) varied greatly across studies, and was not always impaired compared to patients in remission. Conclusion: There is a scarcity of data on PROs in the subset of pituitary adenomas that is more difficult to treat, e.g., refractory and these patients are difficult to isolate from the total cohort. The patients' perspective on quality of life, therefore, remains largely unknown in refractory patients. Thus, PROs in refractory pituitary adenomas require adequate analysis using properly reported disease specific PROMs in large cohorts to enable appropriate interpretation for use in clinical practice.Metabolic health: pathophysiological trajectories and therap

Limited effects of growth hormone replacement in patients with GH deficiency during long-term cure of acromegaly

The aim of this study was to assess the effects of replacement with recombinant human growth hormone (rhGH) in patients with GH deficiency (GHD) after treatment of acromegaly. Intervention study. Sixteen patients (8 men, age 56 years), treated for acromegaly by surgery and radiotherapy, with an insufficient GH response to insulin-induced hypoglycaemia, were treated with 1 year of rhGH replacement. Study parameters were assessed at baseline and after 1 year of rhGH replacement. Study parameters were cardiac function, body composition, bone mineral density (BMD), fasting lipids, glucose, bone turnover markers, and Quality of Life (QoL). During rhGH replacement IGF-I concentrations increased from −0.4 ± 0.7 to 1.0 ± 1.5 SD (P = 0.001), with a mean daily dose of 0.2 ± 0.1 mg in men and 0.3 ± 0.2 mg in women. Nonetheless, rhGH replacement did not alter cardiac function, lipid and glucose concentrations, body composition or QoL. Bone turnover markers (PINP and β crosslaps) levels increased (P = 0.005 and P = 0.021, respectively), paralleled by a small, but significant decrease in BMD of the hip. The beneficial effects of rhGH replacement in patients with GHD during cure from acromegaly are limited in this study

Clinical unmet needs in the treatment of adrenal crisis: importance of the patient's perspective

Adrenal crisis is the most severe manifestation of adrenal insufficiency (AI), but AI can present with variable signs and symptoms of gradual severity. Despite current hormone replacement strategies, adrenal crisis is still one of the leading causes of mortality in AI patients. Although underlying factors explaining differences in interindividual susceptibility are not completely understood, several subgroups are particularly vulnerable to adrenal crises, such as patients with primary AI, and patients treated for Cushing's syndrome. Currently, the health care professional faces several challenges in the care for AI patients, including the lack of reliable biomarkers measuring tissue cortisol concentrations, absence of a universally used definition for adrenal crisis, and lack of clinical tools to identify individual patients at increased risk. Also from the patient's perspective, there are a number of steps to be taken in order to increase and evaluate self-management skills and, finally, improve health-related quality of life (HR-QoL). In this respect, the fact that inadequate handling of AI patients during stressful situations is a direct consequence of not remembering how to act due to severe weakness and cognitive dysfunction in the context of the adrenal crisis is quite underexposed. In this narrative review, we give an overview of different clinical aspects of adrenal crisis, and discuss challenges and unmet needs in the management of AI and the adrenal crisis from both the doctor's and patient's perspective. For the latter, we use original focus group data. Integration of doctor's and patient's perspectives is key for successful improvement of HR-QoL in patients with AI.Diabetes mellitus: pathophysiological changes and therap

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.Diabetes mellitus: pathophysiological changes and therap

An overview of clinical activities in Endo-ERN: the need for alignment of future network criteria

Objective Given that volumes of patients and interventions are important criteria to qualify as a reference centre (RC) for the European Reference Network on Rare Endocrine Conditions (Endo-ERN), the present study aimed to evaluate the data that were reported in the original application against subsequent assessments of activity and review the criteria that may define RCs using two main thematic groups (MTGs): Pituitary and Thyroid, as examples. Methods Review of content in application forms and continuous monitoring data and of a survey distributed to RCs. A list of ‘key procedures’ for the assessment of performance of RCs was composed with the help of the Pituitary and Thyroid MTG chairs. Results In the original application, the number of undefined procedures ranged from 20 to 5500/year (Pituitary) and from 10 to 2700/year (phyroid) between applicants. In the survey, the number of key procedures per centre ranged from 18 to 150/year (Pituitary) and from 20 to 1376/year (Thyroid). The median numbers of new patients reported in the continuous monitoring program were comparable with the application and survey; however, some centres reported large variations. Conclusions Monitoring of clinical activity in an ERN requires clear definitions that are optimally aligned with clinical practice, diagnosis registration, and hospital IT systems. This is a particular challenge in the rare disease field where the centre may also provide expert input in collaboration with local hospitals. Application of uniform definitions, in addition to condition-specific clinical benchmarks, which can include patient-reported- as well as clinician-reported outcome measures, is urgently needed to allow benchmarking of care across Endo-ERN

Consensus on criteria for acromegaly diagnosis and remission

Purpose: The 14th Acromegaly Consensus Conference was convened to consider biochemical criteria for acromegaly diagnosis and evaluation of therapeutic efficacy. Methods: Fifty-six acromegaly experts from 16 countries reviewed and discussed current evidence focused on biochemical assays; criteria for diagnosis and the role of imaging, pathology, and clinical assessments; consequences of diagnostic delay; criteria for remission and recommendations for follow up; and the value of assessment and monitoring in defining disease progression, selecting appropriate treatments, and maximizing patient outcomes. Results: In a patient with typical acromegaly features, insulin-like growth factor (IGF)-I &gt; 1.3 times the upper limit of normal for age confirms the diagnosis. Random growth hormone (GH) measured after overnight fasting may be useful for informing prognosis, but is not required for diagnosis. For patients with equivocal results, IGF-I measurements using the same validated assay can be repeated, and oral glucose tolerance testing might also be useful. Although biochemical remission is the primary assessment of treatment outcome, biochemical findings should be interpreted within the clinical context of acromegaly. Follow up assessments should consider biochemical evaluation of treatment effectiveness, imaging studies evaluating residual/recurrent adenoma mass, and clinical signs and symptoms of acromegaly, its complications, and comorbidities. Referral to a multidisciplinary pituitary center should be considered for patients with equivocal biochemical, pathology, or imaging findings at diagnosis, and for patients insufficiently responsive to standard treatment approaches. Conclusion: Consensus recommendations highlight new understandings of disordered GH and IGF-I in patients with acromegaly and the importance of expert management for this rare disease.</p