AiDAPT: automated insulin delivery amongst pregnant women with type 1 diabetes: a multicentre randomized controlled trial - study protocol.

Background: Pregnant women with type 1 diabetes strive for tight glucose targets (3.5-7.8 mmol/L) to minimise the risks of obstetric and neonatal complications.

Successful treatment of residual pituitary adenoma in persistent acromegaly following localisation by 11C-methionine PET co-registered with MRI.

Objective: To determine if functional imaging using C-methionine positron emission tomography co-registered with 3D gradient echo MRI (Met-PET/MRI), can identify sites of residual active tumour in treated acromegaly, and discriminate these from post-treatment change, to allow further targeted treatment.

Design/methods: Twenty-six patients with persistent acromegaly after previous treatment, in whom MRI appearances were considered indeterminate, were referred to our centre for further evaluation over a 4.5-year period.

Heterogeneous genetic background of the association of pheochromocytoma/paraganglioma and pituitary adenoma: results from a large patient cohort.

Context: Pituitary adenomas and pheochromocytomas/paragangliomas (pheo/PGL) can occur in the same patient or in the same family. Coexistence of the two diseases could be due to either a common pathogenic mechanism or a coincidence.

Objective: The objective of the investigation was to study the possible coexistence of pituitary adenoma and pheo/PGL.

Cyclins and their related proteins in pituitary tumourigenesis.

Pituitary tumours are benign neoplasms that may cause major endocrine dysfunction. Transgenic disruption of the cell cycle machinery frequently leads to pituitary adenoma formation in animal models. The molecular analysis of human pituitary tumours has found various alterations in the expression of cell cycle regulators: cyclins, cyclin-dependent kinases and their inhibitors.

Differential gene expression in pituitary adenomas by oligonucleotide array analysis.

Objectives: Microarray technology allows for the expression profile of many thousands of genes to be quantified at the same time, and has resulted in novel discoveries about the tumour biology of a number of cancers. We sought to do this in pituitary adenomas, the most common intracranial neoplasm.

Methods: Affymetrix GeneChip HG-U133A oligonucleotide arrays covering 14 500 well-characterised genes from the human genome were used to study pooled RNA for each of the four major pituitary adenoma subtypes.

Role of regulatory factors in pituitary tumour formation.

The molecular basis of pituitary tumorigenesis remains controversial, but there are two major theories which have been subject to most investigation: hormonal (usually hypothalamic factors) and/or growth factor overstimulation, or a molecular defect within the pituitary itself. It has been shown, for example, that excessive regulatory hormone stimulation can lead to an increased number of cells in the pituitary in various physiological or pathological states such as pregnancy (lactotrophs), untreated primary hypothyroidism (thyrotrophs and lactotrophs),primary hypoadrenalism (corticotrophs) and ectopic GHRH-secreting tumours (somatotrophs). Animal models also provide data that in the presence of excessive hypothalamic hormone stimulation, adenoma formation can occur.

Identification of adrenocorticotropin receptor messenger ribonucleic acid in the human pituitary and its loss of expression in pituitary adenomas.

The ACTH receptor (ACTH-R) is the second member of the melanocortin (MC-2) receptor family that includes five seven-transmembrane G protein-coupled receptors and has been shown to be predominantly expressed in the adrenal cortex. It has been postulated that ACTH may regulate its own secretion through ultra-short-loop feedback within the pituitary. ACTH-secreting adenomas are characterized by resistance to glucocorticoid feedback, and they may have dysregulated ACTH feedback.

Discriminatory value of the low-dose dexamethasone suppression test in establishing the diagnosis and differential diagnosis of Cushing's syndrome.

Cushing's syndrome requires a screening test of high sensitivity, followed by biochemical evaluation of the source of the tumor when the cause is ACTH dependent. The high-dose dexamethasone suppression test is still in common use as an aid in differential diagnosis, although its value has been queried. We have routinely used the low-dose dexamethasone suppression test for many years in the diagnosis of Cushing's syndrome but noticed that patients with pituitary-dependent Cushing's syndrome or Cushing's disease, usually showed some degree of suppression of their serum cortisol, compared to those with the ectopic ACTH syndrome.

The expression of the F-box protein Skp2 is negatively associated with p27 expression in human pituitary tumors.

The CDK inhibitor p27 plays a pivotal role in controlling cell proliferation during development, and has been implicated in tumorigenesis. Previous studies have demonstrated changes in p27 protein expression, but not in mRNA levels, in human pituitary tumors. It seems probable that the fall in p27 is due to increased degradation through the ubiquitin-proteasome pathway.

Reduced expression of the growth hormone and type 1 insulin-like growth factor receptors in human somatotroph tumours and an analysis of possible mutations of the growth hormone receptor.

Objective: Clinical acromegaly is characterized by elevated GH secretion in the presence of high circulating IGF-I levels. We hypothesized that the physiological IGF-I/GH negative feedback loop may be reset in somatotroph adenomas, specifically in terms of the level of expression of these receptors or mutations of the GH receptor (GH-R) in such tumours.

Methods: We therefore investigated the full coding sequence of the GH-R in a series of somatotroph and other pituitary adenomas.

The medical management of Cushing's syndrome.

Cushing's syndrome results from prolonged exposure to excessive circulating glucocorticosteroids, and is associated with significant morbidity and mortality. While the treatment of choice in most patients is surgical, the metabolic consequences of the syndrome, including increased tissue fragility, poor wound healing, hypertension, and diabetes mellitus, increase the risks of such surgery. The hypercortisolemia and its sequelae can be efficiently reversed using medical therapy, either as a temporary measure prior to definitive treatment, or longer term in more difficult cases.

Sequence analysis of the PRKAR1A gene in sporadic somatotroph and other pituitary tumours.

Objective: Carney complex (CNC) is an autosomal dominant multiple neoplasia syndrome featuring cardiac, endocrine, cutaneous and neural tumours, as well as a variety of pigmented lesions of the skin and mucosa. Pituitary GH-secreting tumours are found in approximately 10% of patients with CNC. One of the genes responsible for CNC, the PRKAR1A gene located on human chromosome 17q22-24, has recently been cloned.

The tissue distribution of the mRNA of ghrelin and subtypes of its receptor, GHS-R, in humans.

Ghrelin is a novel growth hormone-releasing peptide, originally identified in the rat stomach as the endogenous ligand for the growth hormone secretagogue-receptor (GHS-R1a). Ghrelin is involved in the regulation of GH release, but it has recently been suggested that ghrelin may have other actions, including effects on appetite, carbohydrate metabolism, heart, kidney, pancreas, gonads, and cell proliferation. The distribution of ghrelin, its functional receptor (type 1a) and the unspliced, non-functional GHS-R type 1b mRNA expression was investigated in various human tissues using classical and real-time reverse transcription and polymerase chain reaction.