Osilodrostat improves blood pressure and glycemic control in patients with Cushing's disease: a pooled analysis of LINC 3 and LINC 4 studies.

Purpose: To evaluate the effect of osilodrostat and hypercortisolism control on blood pressure (BP) and glycemic control in patients with Cushing's disease.

Methods: Pooled analysis of two Phase III osilodrostat studies (LINC 3 and LINC 4), both comprising a 48-week core phase and an optional open-label extension. Changes from baseline in systolic and diastolic BP (SBP and DBP), fasting plasma glucose (FPG), and glycated hemoglobin (HbA) were evaluated during osilodrostat treatment in patients with/without hypertension or diabetes at baseline.

Policy for transitioning childhood-onset growth hormone deficiency from pediatric to adult endocrine care in Belgium.

Growth hormone (GH) deficiency (GHD) in children and adolescents can vary in severity and origin, with GH replacement therapy proving effective in achieving genetic target height. Optimal outcomes are seen in those treated early and with higher doses. As patients approach adult height, priorities shift towards optimizing metabolic effects, maintaining body composition, and enhancing bone mass and muscle strength.

Long-term efficacy and safety of subcutaneous pasireotide alone or in combination with cabergoline in Cushing's disease.

Objective: This study evaluated short- and long-term efficacy and safety of the second-generation somatostatin receptor ligand pasireotide alone or in combination with dopamine agonist cabergoline in patients with Cushing's disease (CD).

Study Design: This is an open-label, multicenter, non-comparative, Phase II study comprising 35-week core phase and an optional extension phase. All patients started with pasireotide, and cabergoline was added if cortisol remained elevated.

Long-term efficacy and safety of osilodrostat in patients with Cushing's disease: results from the LINC 4 study extension.

Objective: To evaluate the long-term efficacy and safety of osilodrostat in patients with Cushing's disease.

Methods: The multicenter, 48-week, Phase III LINC 4 clinical trial had an optional extension period that was initially intended to continue to week 96. Patients could continue in the extension until a managed-access program or alternative treatment became available locally, or until a protocol amendment was approved at their site that specified that patients should come for an end-of-treatment visit within 4 weeks or by week 96, whichever occurred first.

[F] MFBG PET imaging: biodistribution, pharmacokinetics, and comparison with [I] MIBG in neural crest tumour patients.

Purpose: Despite its limitations, [I]MIBG scintigraphy has been the standard for human norepinephrine transporter (hNET) imaging for several decades. Recently, [F]MFBG has emerged as a promising PET alternative. This prospective trial aimed to evaluate safety, biodistribution, tumour lesion pharmacokinetics, and lesion targeting of [F]MFBG and perform a head-to-head comparison with [I]MIBG in neural crest tumour patients.

Exploring stem cell biology in pituitary tumors and derived organoids.

Pituitary tumorigenesis is highly prevalent and causes major endocrine disorders. Hardly anything is known on the behavior of the local stem cells in this pathology. Here, we explored the stem cells' biology in mouse and human pituitary tumors using transcriptomic, immunophenotyping and organoid approaches.

Randomized Trial of Osilodrostat for the Treatment of Cushing Disease.

Context: Cushing disease, a chronic hypercortisolism disorder, is associated with considerable morbidity and mortality. Normalizing cortisol production is the primary treatment goal.

Objective: We aimed to evaluate the safety and efficacy of osilodrostat, a potent, orally available 11βhydroxylase inhibitor, compared with placebo in patients with Cushing disease.

Use of thyroid hormones in hypothyroid and euthyroid patients: a THESIS* survey of Belgian specialists *THESIS: treatment of hypothyroidism in Europe by specialists: an international survey.

Background: Hypothyroidism is a topic that continues to provoke debate and controversy with regards to specific indications, type of thyroid hormone substitution and efficacy. We investigated the use of thyroid hormones in clinical practice in Belgium, a country where currently only levothyroxine (LT4) tablet formulations are available.

Method: Members of the Belgian Endocrine Society were invited to respond to an online questionnaire.

Levoketoconazole improves clinical signs and symptoms and patient-reported outcomes in patients with Cushing's syndrome.

Purpose: The efficacy of levoketoconazole in treating hypercortisolism was demonstrated in an open-label phase 3 study (SONICS) of adults with endogenous Cushing's syndrome (CS) and baseline mean urinary free cortisol (mUFC) ≥  1.5× ULN. Clinical signs and symptoms and patient-reported outcomes from the SONICS trial were evaluated in the current manuscript.

Evaluation of the Efficacy and Safety of Switching to Pasireotide in Patients With Acromegaly Inadequately Controlled With First-Generation Somatostatin Analogs.

Acromegaly is a rare, serious endocrine disorder characterized by excess growth hormone (GH) secretion by a pituitary adenoma and overproduction of insulin-like growth factor I (IGF-I). Transsphenoidal surgery is the treatment of choice, although many patients require additional interventions. First-generation somatostatin analogs (SSAs) are the current standard of medical therapy; however, not all patients achieve control of GH and IGF-I.

Efficacy and safety of mitotane in the treatment of adrenocortical carcinoma: A retrospective study in 34 Belgian patients.

Objectives: Evaluation of patient characteristics and mitotane use in the treatment of adrenocortical carcinoma (ACC) over a 4-year period in Belgium.

Material And Methods: This was a multicentre retrospective review of the outcome of 34 patients treated with mitotane for ACC during the period [01/2008-12/2011] (12 diagnosed before and 22 diagnosed during the study period) and evaluated up to 06/2013.

Results: Patient and tumour characteristics were consistent with those generally described for ACC.

Pituitary tumors contain a side population with tumor stem cell-associated characteristics.

Pituitary adenomas cause significant endocrine and mass-related morbidity. Little is known about the mechanisms that underlie pituitary tumor pathogenesis. In the present study, we searched for a side population (SP) in pituitary tumors representing cells with high efflux capacity and potentially enriched for tumor stem cells (TSCs).

Giant prolactinomas in women.

Objective: To characterise distinctive clinical features of giant prolactinomas in women.

Design: A multicentre, retrospective case series and literature review.

Methods: We collected data from 15 female patients with a pituitary tumour larger than 4 cm and prolactin levels above 1000 μg/l and identified 19 similar cases from the literature; a gender-based comparison of the frequency and age distribution was obtained from a literature review.

Prevalence and risk factors of impaired glucose tolerance and diabetes mellitus at diagnosis of acromegaly: a study in 148 patients.

Acromegaly is frequently associated with alterations of glucose metabolism but factors predisposing these patients to exhibit impaired glucose tolerance or overt diabetes at diagnosis are poorly understood. This study included 148 patients with newly diagnosed acromegaly (80 men; mean age: 45 ± 20 year). All patients underwent an oral glucose tolerance test (OGTT), unless already treated for diabetes.

Active acromegaly is associated with decreased hs-CRP and NT-proBNP serum levels: insights from the Belgian registry of acromegaly.

Objective: Patients with active acromegaly have an increased prevalence of cardiomyopathy and heart failure but a less than expected risk of coronary artery disease, considering the frequent association of diabetes mellitus and hypertension. We examined whether changes in high-sensitive C-reactive protein (hs-CRP) and N-terminal pro-brain natriuretic peptide (NT-proBNP) might contribute to this phenomenon.

Design And Methods: Two hundred patients of the Belgian acromegaly registry (AcroBel) were divided in two groups: active disease (IGF1 Z-score >2; n=95) and controlled disease (IGF1 Z-score ≤2; n=105).

Spectrum and prevalence of FP/TMEM127 gene mutations in pheochromocytomas and paragangliomas.

Context: Pheochromocytomas and paragangliomas are genetically heterogeneous neural crest-derived neoplasms. We recently identified germline mutations of the novel transmembrane-encoding gene FP/TMEM127 in familial and sporadic pheochromocytomas consistent with a tumor suppressor effect.

Objectives: To examine the prevalence and spectrum of FP/TMEM127 mutations in pheochromocytomas and paragangliomas and to test the effect of mutations in vitro.

A homozygous inactivating calcium-sensing receptor mutation, Pro339Thr, is associated with isolated primary hyperparathyroidism: correlation between location of mutations and severity of hypercalcaemia.

Background: Inactivating mutations of the calcium-sensing receptor (CaSR), a G-protein-coupled receptor with extracellular (ECD), transmembrane (TMD) and intracellular (ICD) domains, cause familial hypocalciuric hypercalcaemia, neonatal severe primary hyperparathyroidism and occasionally primary hyperparathyroidism in adults.

Objective: To investigate a patient with typical symptomatic primary hyperparathyroidism for CaSR abnormalities. PATIENT AND DESIGN: A 51-year-old woman with primary hyperparathyroidism was investigated for CaSR abnormalities as her severe hypercalcaemia (3·75 mm) persisted after the removal of two large parathyroid adenomas and she was the daughter of normocalcaemic consanguineous parents.

GNAS defects identified by stimulatory G protein alpha-subunit signalling studies in platelets.

Context: GNAS is an imprinted region that gives rise to several transcripts, antisense transcripts, and noncoding RNAs, including transcription of RNA encoding the alpha-subunit of the stimulatory G protein (Gsalpha). The complexity of the GNAS cluster results in ubiquitous genomic imprints, tissue-specific Gsalpha expression, and multiple genotype-phenotype relationships. Phenotypes resulting from genetic and epigenetic abnormalities of the GNAS region include Albright's hereditary osteodystrophy, pseudohypoparathyroidism types Ia (PHPIa) and Ib (PHPIb), and pseudopseudohypoparathyroidism (PPHP).

Divergence between growth hormone and insulin-like growth factor-i concentrations in the follow-up of acromegaly.

Context: Divergence between GH and IGF-I values is regularly observed in treated acromegalic patients, and its significance is unclear.

Objectives: The objective of the study was to explore the frequency and identify potential determinants of discordant serum GH and IGF-I concentrations in noncured acromegalic patients.

Patients: Two hundred twenty-nine noncured acromegalic patients of the Belgian acromegaly registry (AcroBel) were grouped according to their mean GH level (< or = or > 2 microg/liter) and IGF-I z-score (< or = 2 or > 2).

Health-related quality of life in acromegalic subjects: data from AcroBel, the Belgian registry on acromegaly.

Objective: To assess the impairment of quality of life (QoL), evaluated by the acromegaly QoL (AcroQoL) questionnaire, in patients with controlled and uncontrolled acromegaly.

Design: Cross-sectional evaluation of AcroBel, a national observational registry of acromegalic patients newly diagnosed or in follow-up.

Methods: Disease perception by the patients was evaluated by the disease-specific signs and symptoms score (SSS) and QoL was assessed by the AcroQoL questionnaire.

AcroBel--the Belgian registry on acromegaly: a survey of the 'real-life' outcome in 418 acromegalic subjects.

Objectives: To constitute a registry on acromegaly, AcroBel, to evaluate the epidemiology and quality of care of acromegaly in Belgium and Luxembourg.

Design: A nationwide survey from June 2003 till September 2004 aiming to collect data from all patients with acromegaly who had visited the participating endocrine clinics after 1 January 2000.

Methods: Retrospective data collection coupled to a visit within the survey period, allowing sampling of metabolic parameters and centralised determination of GH and IGF-I.