[Familial pituitary adenomas: clinical and genetic aspects].

Pituitary adenomas can occur in a familial context, or they can be isolated cases, sometimes due to a predisposing syndrome. In multiple endocrine neoplasia type 1, they often associate with a mutation of the menin gene, a tumor-suppressing gene. A new germinal mutation predisposing to the development of multiple endocrine neoplasias has recently been identified in MENI-negative subjects on the gene CDKN1B encoding for p27(kip1)protein.

Etiological diagnosis of hyperprolactinemia.

There are numerous etiologies of hyperprolactinemia, a common reason for consultation. Diagnostic measures must be capable of identifying the tumors, the most frequent of which are prolactin adenomas. Hypothalamic-pituitary MRI is the reference morphological examination.

Gs alpha overexpression and loss of Gs alpha imprinting in human somatotroph adenomas: association with tumor size and response to pharmacologic treatment.

Gs alpha, the alpha-subunit of the heterotrimeric GTP-binding protein, is coded from the GNAS gene, which is imprinted in a tissue-specific manner. Gs alpha is paternally silenced in normal pituitary, but Gs alpha imprinting relaxation is found in some tumoral tissue. In addition, Gs alpha mRNA levels are high in some somatotroph adenomas not bearing the active Gs alpha mutant, the gsp oncogene.

Prolactinoma surgery.

Surgery is generally used as second-line treatment in prolactinomas. For microprolactinomas, it may be indicated in cases of resistance or intolerance to dopamine agonists or where patients prefer definitive cure to lifelong drug treatment. In highly trained hands, selective adenomectomy results in normalization of prolactin levels in 75-90% of cases with little morbidity and no mortality.

Mutations in the aryl hydrocarbon receptor interacting protein gene are not highly prevalent among subjects with sporadic pituitary adenomas.

Context: Limited screening suggests that three germline mutations in the aryl hydrocarbon receptor interacting protein (AIP) gene are not involved in sporadic pituitary tumorigenesis. Multiple novel mutations of this gene have since been identified in familial isolated pituitary adenoma cohorts.

Objective: The objective of the study was to undertake full AIP coding sequence screening to assess for the presence of germline and somatic mutations in European Union subjects with sporadic pituitary tumors.

Aryl hydrocarbon receptor-interacting protein gene mutations in familial isolated pituitary adenomas: analysis in 73 families.

Context: An association between germline aryl hydrocarbon receptor-interacting protein (AIP) gene mutations and pituitary adenomas was recently shown.

Objective: The objective of the study was to assess the frequency of AIP gene mutations in a large cohort of patients with familial isolated pituitary adenoma (FIPA).

Design: This was a multicenter, international, collaborative study.

Gamma knife radiosurgery is a successful adjunctive treatment in Cushing's disease.

Objective: Though transsphenoidal surgery remains the first-line treatment of Cushing's disease, recurrence occurs frequently. Conventional radiotherapy and anticortisolic drugs both have adverse effects. Stereotactic radiosurgery needs to be evaluated more precisely.

[KIMS observational study of GH therapy in GH-deficient adults: 12-month follow-up analysis of the French cohort].

KIMS study is an international, observational study initiated in 1994 in which France has been involved since 2003. Its aim is to collect on a widespread basis long-term data from GH-deficient adults treated or not treated with growth hormone in daily practice. Among 330 patients already enrolled by 128 centers in France at the data lock point for this first interim analysis, 122 patients were followed up for at least 12 months and their results are presented herein.

Pituitary deficiency after brain radiation therapy.

Brain radiotherapy is a frequent and overlooked cause of pituitary deficiency in adults which may alter patients' health and quality of life. Hormonal consequences have been better studied in children. The onset of hormonal deficiencies depends on the dose delivered to the pituitary-hypothalamic region while their incidence and severity depends on dose fractionating and follow-up duration.

Identification and functional analysis of the novel S179R POU1F1 mutation associated with combined pituitary hormone deficiency.

Context: The pituitary-specific transcription factor 1 plays a key role in the development and differentiation of three pituitary cell types: somatotrophs, lactotrophs, and thyrotrophs. Several mutations of the human gene (called POU1F1) have been shown to be responsible for a phenotype of combined pituitary hormone deficiency involving GH, prolactin (PRL), and TSH.

Objective: We have identified a novel homozygous C to G mutation in exon 4 of the POU1F1 gene (S179R) in a patient with this rare phenotype.

Guidelines of the Pituitary Society for the diagnosis and management of prolactinomas.

In June 2005, an ad hoc Expert Committee formed by the Pituitary Society convened during the 9th International Pituitary Congress in San Diego, California. Members of this committee consisted of invited international experts in the field, and included endocrinologists and neurosurgeons with recognized expertise in the management of prolactinomas. Discussions were held that included all interested participants to the Congress and resulted in formulation of these guidelines, which represent the current recommendations on the diagnosis and management of prolactinomas based upon comprehensive analysis and synthesis of all available data.

Pituitary transcription factors: from congenital deficiencies to gene therapy.

Despite the existence of interspecies phenotypic variability, animal models have yielded valuable insights into human pituitary diseases. Studies on Snell and Jackson mice known to have growth hormone, prolactin and thyroid-stimulating hormone deficiencies involving the hypoplastic pituitary gland have led to identifying alterations of the pituitary specific POU homeodomain Pit-1 transcription factor gene. The human phenotype associated with rare mutations in this gene was found to be similar to that of these mice mutants.

Epilepsy related to hypothalamic hamartomas: surgical management with special reference to gamma knife surgery.

Objective: A large spectrum of surgical techniques can be proposed to young patients presenting with hypothalamic hamartomas (HH) associated with severe epilepsy. The aim of this report is to point on some clinical and anatomical parameters supposed to influence the choice of the surgical approach and to emphasize the specific role of radiosurgery.

Materials And Methods: We reviewed both our experience and the recent literature based on a Pubmed search.

Clinical characterization of familial isolated pituitary adenomas.

Context: Familial pituitary adenomas occur rarely in the absence of multiple endocrine neoplasia type 1 (MEN1) and Carney complex (CNC).

Objective: Our objective was to characterize the clinical and genealogical features of non-MEN1/CNC familial isolated pituitary adenomas (FIPA).

Design And Setting: We conducted a retrospective study of clinical and genealogical characteristics of FIPA cases and performed a comparison with a sporadic population at 22 university hospitals in Belgium, Italy, France, and The Netherlands.

Activin inhibits the human Pit-1 gene promoter through the p38 kinase pathway in a Smad-independent manner.

The pituitary transcription factor Pit-1 regulates hormonal production from the anterior pituitary gland. However, the mechanisms by which Pit-1 gene expression is regulated in humans are poorly understood. Activin, a member of the TGFbeta superfamily, acts as a negative regulator of cell growth and prolactin gene expression in lactotrope cells.

Genetic screening of combined pituitary hormone deficiency: experience in 195 patients.

Context: Mutations in transcription factors result in combined pituitary hormone deficiency (CPHD).

Objective: A genetic screening strategy, based on endocrine and neuroradiological phenotype according to published knowledge, was applied to establish the prevalence of gene defects in each category of patients and provide a useful framework for clinicians to determine the genetic etiology and recurrence risks for individuals and families.

Design: One hundred ninety-five CPHD patients from the international GENHYPOPIT network were studied, according to their phenotype, for POU1F1, PROP1, LHX3, LHX4, and HESX1.

The role of CBP/p300 interactions and Pit-1 dimerization in the pathophysiological mechanism of combined pituitary hormone deficiency.

Context: Combined pituitary hormone deficiency (CPHD) in humans is caused by mutations of pituitary-specific transcription factors such as Pit-1. Although many patients with CPHD have an autosomal recessive disorder caused by a Pit-1 DNA-binding mutation, there are a number of reports of mutant Pit-1 molecules that either by prediction or through experimentation bind normally to DNA.

Objective: The objective of this study was to understand the pathophysiological mechanisms of mutant Pit-1 molecules with intact DNA binding.

An uncommon phenotype with familial central hypogonadism caused by a novel PROP1 gene mutant truncated in the transactivation domain.

Context: PROP1 gene mutations are usually associated with childhood onset GH and TSH deficiencies, whereas gonadotroph deficiency is diagnosed at pubertal age.

Objectives: We report a novel PROP1 mutation revealed by familial normosmic hypogonadotropic hypogonadism. We performed in vitro transactivation and DNA binding experiments to study functional consequences of this mutation.

Novel mutations within the POU1F1 gene associated with variable combined pituitary hormone deficiency.

Context: Mutations within the gene encoding the pituitary-specific transcription factor POU1F1 are associated with combined pituitary hormone deficiency (CPHD). Most of the affected individuals manifest GH, prolactin, and TSH deficiency.

Objective: We have now screened 129 individuals with CPHD and isolated GH deficiency for mutations within POU1F1.

Outcome of gamma knife radiosurgery in 82 patients with acromegaly: correlation with initial hypersecretion.

Context: Because surgical and medical therapies of acromegaly all have specific limitations, radiotherapy has been used as an adjunctive strategy. Stereotactic radiosurgery has not yet been widely evaluated.

Objective: The objective was to perform an analysis of long-term hormonal effects and tolerance of gamma knife radiosurgery.

Gamma knife surgery for epilepsy related to hypothalamic hamartomas.

Objective: Drug resistant epilepsy associated with hypothalamic hamartoma (HH) can be cured by microsurgical resection of the lesion. Morbidity and mortality risks of microsurgery in this area are significant. Gamma Knife Surgery's (GKS) reduced invasivity seems to be well adapted.