L'hypophyse et ses traitements : comment peuvent-ils influer sur le comportement ?: The pituitary and its treatments: how can they influence behaviour?

Behaviour may be influenced by pituitary hormones or treatments. Dopamine agonist (DA) indicated in prolactinomas treatment can cause side effects, and especially impulse control disorders. In the context of prolactinomas treatment, impulse control disorders (ICD) have been reported like gambling, compulsive shopping, but mostly hypersexuality. These ICD can occur with low AD doses, and seem to be independent of type of molecule and psychiatric medical history. The main pathophysiologic hypothesis is a dysregulation of dopaminergic pathway involved in reward system. Given the possible devastating social impact of these ICD, they have to be screened in patients treated with DA. Our social behaviour can also be impacted by oxytocin. This hormone secreted on physiologic state at posterior pituitary, but also by others areas of brain and brainstem, has an impact on attachment in pair partners and in parent-child relationship, but also in empathy behaviour. Oxytocin affects as well eating behaviour with an anorexigenic impact. Studies on small populations assessed the relevance of an oxytocin treatment in several endocrine and nutritional pathologies like post-surgery craniopharyngioma, panhypopituitarism and obesity. Despite promising results, several pitfalls prevent yet the oxytocin use in clinical practice.

Case-control study on the use of pituitary-derived hormones from sheep as a potential risk factor for the occurrence of atypical scrapie in Great Britain.

A case-control study was conducted in 2013 to investigate the use of pituitary-derived hormones from sheep as a potential risk factor for the presence of atypical scrapie in Great Britain sheep holdings. One hundred and sixty-five holdings were identified as cases. Two equal sets of controls were selected: no case of scrapie and cases of classical scrapie. A total of 495 holdings were selected for the questionnaire survey, 201 responses were received and 190 (38.3 per cent) were suitable for analysis. The variables 'use-of-heat-synchronisation/superovulation' and 'flock size' were significantly associated with the occurrence of atypical scrapie. Farms with atypical cases were less likely (OR 0.25, 95 per cent CI 0.07 to 0.89) to implement heat synchronisation/superovulation in the flock than the control group. Atypical cases were 3.3 times (95 per cent CI 1.38 to 8.13) more likely to occur in large holdings (>879 sheep) than in small flocks (<164 sheep). If the 'use-of-heat-synchronisation/superovulation' is a proxy for the use of pituitary-derived hormones, the significant negative association between having a case of atypical scrapie and the use of these practices rules out the initial hypothesis that using these drugs is a risk factor for the occurrence of atypical scrapie. Flock size was a significant risk factor for atypical scrapie, consistent with a previous generic case-control study.

Management of hyperglycaemia in Cushing's disease: experts' proposals on the use of pasireotide.

Cushing's disease causes considerable morbidity and mortality, including cardiovascular, metabolic, respiratory and psychiatric complications, bone demineralization and increased susceptibility to infections. Metabolic complications include a high prevalence of impaired glucose tolerance, fasting hyperglycaemia and diabetes. Although pituitary surgery is the gold-standard treatment, other treatment strategies such as radiotherapy and medical therapy to reduce cortisol synthesis may be proposed in the event of recurrence or failure, or when surgery is not an option. Bilateral adrenalectomy can also be considered. One of the medical treatments used in Cushing's disease is the somatostatin analogue pasireotide, which acts on adrenocorticotropic hormone (ACTH) secretion by the pituitary. Its efficacy in reducing urinary free cortisol, plasma cortisol and ACTH, and in improving the clinical signs of the disease has been demonstrated. Its observed adverse effects are similar to the known effects of first-generation somatostatin analogues, although disturbances of carbohydrate metabolism are more frequent and more severe with pasireotide. The aim of the present review was to summarize the epidemiology and pathophysiology of the disturbances of glucose metabolism that arise in Cushing's disease, and to propose recommendations for detecting and monitoring glucose abnormalities and for managing pasireotide-induced hyperglycaemia.

Drugs in the medical treatment of Cushing's syndrome.

Cushing's syndrome is a complex endocrine condition with potential serious complications if untreated or inadequately treated. Transsphenoidal surgery with resection of a pituitary adenoma is successful in 75 - 80% of patients, but approximately 20 - 25% show persistence of Cushing's, and a similar proportion may experience recurrence within 2 - 4 years post-op. When surgery fails, medical treatment can temporarily suppress excessive cortisol production and ameliorate its clinical manifestations while more definitive therapy becomes effective. We describe pharmacological approaches to the treatment of Cushing's syndrome. Drugs used to suppress cortisol secretion are mostly inhibitors of steroidogenesis. Ketoconazole, fluconazole aminoglutethimide, metyrapone, mitotane and etomidate are in that category. Ketoconazole is in current use while other drugs, although mostly available in the past, continue to have a potential role either alone or in combination. Drugs that suppress adrenocorticotropic hormone (ACTH) secretion are less popular as standard treatment and include cyproheptadine, valproic acid, cabergoline, somatostatin analogs, PPAR-gamma agonists, vasopressin antagonists. Some of these drugs have been tested in limited clinical trials but there is potential therapeutic benefit in analogs with better specificity for the class of receptors present in ACTH-secreting tumors. A third category of drugs is glucocorticoid receptor antagonists. Mifepristone is currently being tested in clinical trials in patients with persistent or recurrent Cushing's disease and in patients with metastatic adrenal cortical carcinoma or ectopic ACTH syndrome not amenable to surgery. We also review replacement therapy after surgery and non-specific drugs to treat complications in patients with severe hypercortisol. The review provides a complete survey of the drugs used in the medical treatment of Cushing's, and new advances in the development of pituitary-active drugs as well as receptor blockers of glucocorticoid action. It also provides avenues for exploration of new drugs active on somatostatin, dopamine and vasopressin receptors. There are effective pharmacological agents capable of chronically reversing biochemical and clinical manifestations of hypercortisolemia in Cushing's syndrome but new drugs are needed with action at the pituitary level.

[Acquired Creutzfeldt-Jakob disease (CJD)--Kuru, iatrogenic CJD, variant CJD].

Human prion diseases can be classified as sporadic, hereditary or acquired. The acquired forms are known to be caused by the transmission to human from human or animal, via medical appliances, oral intake or parenteral solutions. Usually, peripheral infection such as oral(Kuru) or parenteral (human pituitary hormones) transmission causes cerebellar degenerative form, and central nervous system infection such as neurosurgical treatment, dura mater grafts or corneal grafts transmission causes clinical features similar to sporadic form of Creutzfeldt-Jakob disease (CJD). The variant CJD (vCJD) is considered to be transmitted bovine spongiform encephalopathy(BSE) to human through dietary exposure. The early clinical features of vCJD are dominated by psychiatric symptoms, and minor number of patients have neurological symptoms from the onset. After about 6 months, there are frank neurological signs, including ataxia, cognitive impairment and involuntary movements.

Chronic intracerebroventricular infusion of MCH causes obesity in mice. Melanin-concentrating hormone.

Melanin-concentrating hormone (MCH) is a cyclic amino acid neuropeptide localized in the lateral hypothalamus. Although MCH is thought to be an important regulator of feeding behavior, the involvement of this peptide in body weight control has been unclear. To examine the role of MCH in the development of obesity, we assessed the effect of chronic intracerebroventricular infusion of MCH in C57BL/6J mice that were fed with regular or moderately high-fat (MHF) diets. Intracerebroventricular infusion of MCH (10 microg/day for 14 days) caused a slight but significant increase in body weight in mice maintained on the regular diet. In the MHF diet-fed mice, MCH more clearly increased the body weight accompanied by a sustained hyperphagia and significant increase in fat and liver weights. Plasma glucose, insulin, and leptin levels were also increased in the MCH-treated mice fed the MHF diet. These results suggest that chronic stimulation of the brain MCH system causes obesity in mice and imply that MCH may have a major role in energy homeostasis.

Endocrine therapy of transsexualism and potential complications of long-term treatment.

Physiological principles of the interrelationship of sex hormones and their regulation are the foundation of understanding appropriate treatment of the transsexual patient. While both genetic males and females have estrogens and androgens, the quantitative sex hormone production is genetically predetermined by sex hormone production both in the gonads and via peripheral conversion of hormone precursors to sex steroids. Sex hormones exert a negative feedback on the hypothalamus and pituitary gland whereby gonadotropin-releasing hormone (GnRH), pituitary luteinizing hormone (LH), and follicle-stimulating hormone (FSH) are regulated or suppressed by the endogenous levels of these hormones. Sex hormonal therapy induces attenuated GnRH stimulation of LH and FSH causing a reduction of serum sex hormone levels. It is clear that estrogen as well as androgen therapy have a dual role: (i) induction of feminization or virilization and (ii) suppression of the hypothalamic-pituitary-gonadal axis leading to a reduction of endogenous estradiol or testosterone secretion. Cross-sex hormonal treatment may have substantial medical side effects. The smallest dosage of hormonal therapy compatible with the above clinical aims should be used.

[Epidemiology of human diseases caused by unconventional transmissible agents]. / Epidémiologie des maladies humaines à agents transmissibles non conventionnels.

Human unconventional viruses infections are scarcely found with a worldwide occurrence below 1/million inhabitants. The disease would be induced by an interaction between the patient's genetic characteristics and environmental factors. No link has been found between the occurrence of the disease in man and the presence of the animal form of the disease, i.e. scrapie. The professional risk has been pointed out for people working with animals or in the medical sector. Most iatrogenic cases are subsequent to a growth hormone treatment. The other cases are associated with different medical and surgical acts. But the transmission by blood transfusion remains questionable and must be clearly demonstrated.

Cuantificación de hormonas tiroideas y tirotropina en niños críticamente enfermos con septisemia / Quantification of the thyroid hormones and thyrotropine in critically-ill septicemic children

Estudiamos la función hipotálamo, hipofisiaria, tiroidea en 23 niños críticamente enfermos con septicemia y 15 controles sin patología que afectara dicho eje. La comparación de los resultados de las cuantificaciones de 3,3'5-triiodotironina (T3), 3,3'-5'-triiodotironina evidenció franca disminución de T3 y T4 y elevación de T3r y TSH en los septicémicos, con diferencia estadísticamente significativa (P<0.001). Estas alteraciones bioquímicas que traducen un mecanismo del organismo para mantener la homeostasis y evitar el cataolismo, mediante la conservación de energía, mostraron su normalización espontánea en 18 sobrevivientes de los niños septicémicos al recuperarse

A girl treated with growth hormone presenting with neuromyopathy as first sign of acute lymphoblastic leukemia.

An 11-year-old girl being treated with DNA-recombinant growth hormone therapy presented with proximal limb weakness. Laboratory studies were negative. A few months later she presented with acute lymphoblastic leukemia (ALL). A diagnosis of carcinomatous neuromyopathy was made. After successful treatment of the leukemia the symptoms subsided and did not recur.

Role of programmed cell death in the aging process: an unexplored possibility.

The possibility of cell death being a programmed event under neuroendocrine control during aging is discussed. Physiological cell death is currently regarded as a built-in cellular mechanism which can be triggered by extracellular signals. The term 'programmed cell death' is employed when these signals are involved in developmental or adaptive processes. Programmed cell death has a wide incidence throughout the animal kingdom, both during development and reproduction. Consequently, the involvement of such a basic cellular process in aging appears as a plausible possibility. The neuroendocrine system best qualifies as the potential regulator of cell death during aging. First, it is the major regulator of homeostasis and developmental processes in higher organisms. Second, in many instances physiological cell death has been shown to be under control of the neuroendocrine system during development and reproduction. Finally, this system is implied in the decline of several physiological functions during aging. The above considerations point to this unexplored topic as a promising avenue of gerontological research.

[Use and misuse of hormones in female reproductive disorders]. / Die gebruik en misbruik van hormone in geslagskundige gevalle.

The correct use of hormones in genesiological cases is discussed with indications for their use, dosage levels and duration of treatment under the following groups, viz. hypothalamic hormones, hypophyseal hormones, other gonadotrophins, steroids, combinations of the foregoing and prostaglandins. The more important dangers associated with hormone therapy are then briefly discussed with a few examples of the more common and hazardous abuses.