Diagnosis and Management of Multiple Endocrine Neoplasia Type 1 (MEN1)

Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominantly inherited disorder, characterised by the occurrence of tumours of the parathyroid glands, the pancreatic islets, the pituitary gland, the adrenal glands and neuroendocrine carcinoid tumours. Carcinoid tumours of the thymus and pancreatic-duodenal gastrinomas are the most harmful tumour types, since these tumours have malignant potential and curative treatment is difficult to achieve

Factors influencing the acceptability of energy policies:A test of VBN theory

This paper examines factors influencing the acceptability of energy policies aimed to reduce the emission of CO2 by households. More specifically, it is Studied to what extent the value-belief-norm theory of environmentalism (VBN theory; Stern, [(2000). Toward a coherent theory of environmentally significant behavior. Journal of Social Issues, 56(3), 407-424.]) is successful in explaining acceptability judgements. In contrast to previous studies, we test the full VBN theory. A questionnaire Study was conducted among 112 Dutch respondents. Results confirmed the causal order of the variables in VBN theory, moving from relative stable general values to belief's about human-environment relations, which in turn affect behaviour specific beliefs and norms, and acceptability judgements, respectively. As expected, all variables were significantly related to the next variable in the causal chain. Biospheric values were also significantly related to feelings of moral obligation to reduce household energy consumption when intermediate variables were controlled for. Furthermore, as hypothesized, personal norms mediated the relationship between AR and acceptability judgements, AR beliefs mediated the relationship between AC beliefs and personal norms, AC beliefs mediated the relationship between NEP and AR beliefs, and NEP mediated the relationship between values and AC beliefs. (c) 2005 Elsevier Ltd. All rights reserved.</p

Variable clinical expression in patients with a germline MEN1 disease gene mutation: clues to a genotype–phenotype correlation

Multiple endocrine neoplasia type 1 is an inherited endocrine tumor syndrome, predominantly characterized by tumors of the parathyroid glands, gastroenteropancreatic tumors, pituitary adenomas, adrenal adenomas, and neuroendocrine tumors of the thymus, lungs or stomach. Multiple endocrine neoplasia type 1 is caused by germline mutations of the multiple endocrine neoplasia type 1 tumor suppressor gene. The initial germline mutation, loss of the wild-type allele, and modifying genetic and possibly epigenetic and environmental events eventually result in multiple endocrine neoplasia type 1 tumors. Our understanding of the function of the multiple endocrine neoplasia type 1 gene product, menin, has increased significantly over the years. However, to date, no clear genotype–phenotype correlation has been established

Recent results of basic and clinical research in MEN1:opportunities to improve early detection and treatment

Due to the variable expression of multiple endocrine neoplasia type 1 (MEN1), it is difficult to predict the course of the disease. However, knowledge about the normal function of the MEN1 gene product, together with the effects of cellular derangement by subsequent genetic events, has increased considerably. At first, the possible existence of a genotype-phenotype correlation is discussed. Thus, mild-and late-onset phenotypes may be distinguished from more malignant phenotypes depending on the character of the primary MEN1 disease gene mutation. Subsequently, tumor-promoting factors such as gender, additional genetic mutations and ecogenetic factors may contribute to the course of the disease. New developments in management are based on the knowledge and experience of the multidisciplinary teams involved. Finally, the metabolic effects of MEN1 mutations in aged patients are discussed. Early identification of predisposition to the disease, together with knowledge about the natural history of specific mutations, risks of additional mutations and periodic clinical monitoring, allow early treatment and may improve life expectancy and quality of life

Quality of life, daily functioning, and symptoms in hypothyroid patients on thyroid replacement therapy: A Dutch survey

Objective: To explore the nature and extent of possible residual complaints among Dutch hypothyroid patients using thyroid replacement therapy, we initiated a comprehensive study measuring health-related quality of life (QoL), daily functioning, and hypothyroidism-associated symptoms in patients and control persons. Methods: An online survey measuring thyroid-specific QoL (ThyPRO), daily functioning, and hypothyroidism-associated symptoms (ThySHI) was distributed among treated hypothyroid patients and control individuals. The advertising text was formulated in an open-ended manner. Patients also provided their most recent thyroid blood values and their thyroid medication. Results: There was a large-sized impairment of QoL (Cohen's d = 1.04, +93 % ThyPRO score) in hypothyroid patients on thyroid replacement therapy (n = 1195) as compared to controls (n = 236). Daily functioning was significantly reduced i.e., general health (-38 %), problems with vigorous- (+64 %) and moderate activities (+77 %). Almost 80 % of patients reported having complaints despite thyroid medication and in-range thyroid blood values, with 75 % expressing a desire for improved treatment options for hypothyroidism (total n = 1194). Hypothyroid patients experienced 2.8 times more intense hypothyroidism-associated symptoms than controls (n = 865, n = 203 resp). Patients' median reported serum concentrations were: TSH 0.90 mU/L, FT4 17.0 pmol/L, and FT3 2.67 pmol/L, with 52 % having low T3 levels (<3.1 pmol/L). The QoL was not found to be related to age, sex, BMI, menopausal status, stress, serum thyroid parameters, the origin and duration of hypothyroidism, the type of thyroid medication, or the LT4 dose used. Conclusions: Our study revealed major reductions in quality of life and daily functioning, and nearly three times more intense hypothyroidism-associated symptoms in treated hypothyroid patients as compared to controls, despite treatment and largely in-range serum TSH/FT4 concentrations. The QoL was not associated with serum thyroid parameters. We recommend future research into the origin of persisting complaints and the development of improved treatment modalities for hypothyroidism

A comparative study of 3D measuring methods for monitoring breast volume changes

Three-dimensional (3D) imaging techniques are promising new tools for measuring breast volume, for example in gender-affirming therapy. Transgender individuals can be treated with gender-affirming hormone therapy (GAHT). A robust method for monitoring breast volume changes is critical to be able to study the effects of feminizing GAHT. The primary aim of this study was to compare the accuracy of three 3D devices (Vectra XT, Artec LEO and iPhone XR) for measuring modest breast volume differences using a mannequin. The secondary aim of this study was to evaluate these methods in several performance domains. We used reference prostheses of increasing volumes and compared the volumes using GOM-inspect software. For Vectra XT 3D images, manufacturer-provided software was used to calculate volumes as well. The scanning methods were ranked based on their performance in a total of five categories: volume estimations, costs, user-friendliness, test subject- friendliness and technical aspects. The 3D models analyzed with GOM-inspect showed relative mean estimate differences from the actual volumes of 9.1% for the Vectra XT, 7.3% for the Artec LEO and 14% for the iPhone XR. For the Vectra XT models analyzed with the built-in software this was 6.2%. Root mean squared errors (RMSE) calculated based on the GOM-inspect volume analyses showed mean RMSEs of 2.27, 2.54 and 8.93 for the Vectra XT, Artec LEO and iPhone XR, respectively. The Vectra software had a mean RMSE of 3.00. In the combined performance ranking, the Vectra XT had the most favorable ranking, followed by the Artec LEO and the iPhone XR. The Vectra XT and Artec LEO are the preferred scanners to monitor breast development due to the combination of higher accuracy and overall performance. The current study shows that 3D techniques can be used to adequately measure modest breast volume differences and therefore will be useful to study for example breast changes in transgender individuals using feminizing GAHT. These observations may also be relevant in other fields of 3D imaging research.</p

Bilaterality, not multifocality, is an independent risk factor for recurrence in low-risk papillary thyroid cancer

BACKGROUND: The impact of multifocality and bilaterality on recurrence in patients with low-risk papillary thyroid cancer (PTC) is relevant when considering patients for a de-escalated treatment strategy: hemithyroidectomy instead of total thyroidectomy followed with or without radioactive iodine. This study aims to analyze contralateral tumor probability in patients treated for low-risk PTC and assess multifocality and bilaterality as possible predictors for recurrence. METHODS: Patients with low-risk PTC treated with total thyroidectomy followed with or without radioactive iodine in the Netherlands between 2005 and 2015 were included in this study. Patients were identified from the Netherlands Comprehensive Cancer Organization (IKNL) and linked with the nationwide network and registry of Pathology in the Netherlands (PALGA). Contralateral tumor probability and recurrence were assessed. RESULTS: Of 791 included patients, 41.8% (331 of 791) had multifocal disease, with 68.9% (228 of 331) of those patients having bilateral disease. The contralateral tumor probability after hemithyroidectomy was 24.6% (150 of 610) for patients with unifocal disease and 43.1% (78 of 181) for patients with multifocal disease. We found a higher trend of recurrence in patients with bilateral disease, regardless of multifocality: in patients with contralateral disease after precompletion diagnosed unifocal disease 7.3% (11 of 150) had recurrent disease, and patients without contralateral disease after precompletion diagnosed multifocal disease 1.9% (2 per 103) had recurrence. Cox regression analysis showed that bilaterality (hazard ratio = 3.621, 95% confidence interval = 1.548 to 8.471) was the sole statistically significant risk factor for recurrence. CONCLUSION: Low recurrence rates are found in patients with either multifocal or bilateral disease with low-risk PTC. Bilaterality should be taken into account when considering these patients for de-escalated treatment strategy.</p

Health-related quality of life in adrenocortical carcinoma:Development of the disease-specific questionnaire ACC-QOL and results from the PROFILES registry

We aimed to develop a disease-specific adrenocortical carcinoma (ACC) health-related quality of life (HRQoL) questionnaire (ACC-QOL) and assess HRQoL in a population-based cohort of patients with ACC. Development was in line with European Organization for Research and Treatment of Cancer (EORTC) guidelines, though not an EORTC product. In phase I and II, we identified 90 potential HRQoL issues using literature and focus groups, which were reduced to 39 by healthcare professionals. Pilot testing resulted in 28 questions, to be used alongside the EORTC QLQ-C30. In Phase III, 100 patients with ACC were asked to complete the questionnaires twice in the PROFILES registry (3-month interval, respondents: first 67, second 51). Confirmatory factor analysis demonstrated the structural validity of 26 questions with their scale structure (mitotane side-effects, hypercortisolism/hydrocortisone effects, emotional effects). Internal consistency and reliability were good (Cronbach's alpha 0.897, Interclass correlation coefficient 0.860). Responsiveness analysis showed good discriminative ability (AUC 0.788). Patients diagnosed more than 5 years ago reported a good HRQoL compared with the Dutch reference population, but experienced residual fatigue and emotional problems. Patients who underwent recent treatment reported a lower HRQoL and problems in several domains. In conclusion, we developed an ACC-specific HRQoL questionnaire with good psychometric properties

Clear cell chondrosarcoma in Von Hippel-Lindau disease

A diagnosis of clear cell chondrosarcoma of the ulna was made in a patient with Von Hippel-Lindau disease (VHL). After surgery, genetic analysis of the tumor tissue showed loss of heterozygosity at the VHL gene locus. Immunohistochemical analysis confirmed loss of expression of the VHL protein in the tumor cells. In addition, abundant Cyclin D1 expression in the tumor was observed. Chondrosarcoma has been described before in a VHL patient and VHL protein expression has been correlated to tumor grade in a series of sporadic chondrosarcomas. In this report, we show that clear cell chondrosarcoma may be a rare but canonical VHL manifestation through a cell-autonomous mechanism involving somatic loss-of-heterozygosity of the VHL tumor suppressor gene. We discuss the relevance of this observation with regard to the pathogenesis of clear cell chondrosarcoma in the context of VHL