Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P61278 (somatostatin)
 22,083 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Pituitary diseases are often unrecognized in the elderly, although if they can be at the basis of several pathological conditions. We report three clinical cases. Patient n. 1: 87 years old woman, in poor general condition. Thyroid function evaluation showed secondary hypothyroidism. Subsequent pituitary function evaluation demonstrated hypopituitarism with empty sella. The diagnosis was "hypopituitarism with secondary hypothyroidism and adrenocortical insufficiency, in empty sella" starting substitutive treatment with glucocorticoids and L-thyroxine, with improvement in her clinical conditions. Patient n. 2: 74 years old woman, with severe congestive heart failure. Her clinical history revealed hypothyroidism. An endocrine evaluation (in absence of therapy) demonstrated panhypopituitarism with secondary hypothyroidism and adrenocortical insufficiency in presence of empty sella. The patients was started on substitutive treatment and her conditions improved. Patient n. 3: 74 years old man with several atrial fibrillation episodes and hyperthyroidism. Thyroid function evaluation suggested secondary hyperthyroidism confirmed by the presence of a pituitary macroadenoma. The patient underwent surgical adenomectomy by trans-sphenoidal route. The clinical conditions of the patient improved, but a slight secondary hyperthyroidism was still present caused by the persistence of residual pathological tissue in the right cavernous sinus region confirmed by octreoscan suggesting the presence of a lesion endowed with somatostatin receptors. The patient was started on long acting octreotide treatment, which is still in progress. In conclusion, pituitary diseases pass often unrecognized in the elderly. Their prompt recognition and treatment can resolve dangerous situations for the patients.
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PMID:[Pituitary pathology in elderly patients admitted in a division of internal medicine. Description of 3 cases]. 1119 82

Pituitary tumours are a common type of intracranial neoplasm and, depending on the cell type of origin, have diverse endocrine and reproductive effects. The developmental biology of the different cell types is understood to result from a sequential activation of a cascade of transcription factors, and mutations in these factors result in various forms of hypopituitarism. Tumours in the pituitary gland arise from activation of dominantly acting oncogenes such as gsp, or from loss of function of a series of tumour suppressor genes such as MEN1. Abnormal patterns of DNA methylation may be implicated in the allelic losses that cause tumour suppressor gene silencing. The different clinically recognized types of pituitary tumour are currently treated by medical therapies such as dopamine and somatostatin agonists, surgery or radiotherapy. However, these treatments are not entirely satisfactory and recent advances in gene therapy may offer valuable new therapeutic opportunities for patients with aggressive tumours that fail to respond to traditional approaches.
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PMID:Pituitary tumours. 1122 62

Acromegaly, a chronic disease of growth hormone (GH) hypersecretion, is most typically caused by a pituitary adenoma. Early diagnosis is critical for prompt intervention to prevent deleterious effects of prolonged exposure to elevated GH and insulin-like growth factor Type I (IGF-I) levels. Current therapy for acromegaly includes several options: surgery, radiotherapy and pharmacotherapy. Transsphenoidal adenomectomy remains a mainstay of therapy for acromegaly. Cure rates are high in microadenomas, but < 50% in macroadenomas. Conventional and stereotactic procedures for radiation therapy are also effective in decreasing GH levels in acromegalic patients, but they need years to normalise GH hypersecretion and carry with them the risk of hypopituitarism. The major classes of drugs currently used to treat acromegaly are dopamine agonists and analogues of somatostatin. Dopamine agonists bind to the D2 receptor and suppress GH hypersecretion in some patients with acromegaly. Their clinical effectiveness is modest, although promising results have been obtained with two novel compounds, quinagolide and cabergoline, that possess long duration of action. Somatostatin analogues have been shown to improve clinical symptoms of acromegaly, decrease hypersecretion of GH and IGF-I and reduce tumour volume in a clinically significant number of patients. Octreotide is administered by s.c. route several times a day, but the recently developed sustained release formulations (octreotide LAR and SR lanreotide) are administered only every 7-28 days by i.m. injections. The complications associated with somatostatin analogues are small, relative to the benefits. Lastly, compounds with a novel mechanism of action, the GH receptor antagonists, are presently under investigation.
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PMID:Current management of acromegaly. 1124 4

Neuroendocrine axes function as an ensemble of regulatory loci which communicate and maintain homeostasis via time-delayed blood-borne signals. The growth hormone (GH)-insulin-like growth factor I (IGF-I) feedback axis sustains a vividly pulsatile mode of interglandular signalling. Pulsatility is driven jointly by hypothalamic GH-releasing hormone (GHRH) and GH-releasing peptide (GHRP), and modulated by somatostatinergic restraint. Paradoxically, intermittent somatostatin inputs also facilitate somatotrope-cell responses to recurrent secretagogue stimuli, thereby amplifying pulsatile GH secretion. A concurrent low basal (8-12% of normal total) rate of GH release is controlled positively by GHRH and GHRP and negatively by somatostatin. Sex-steroid hormones (such as oestradiol and aromatizable androgen) and normal female and male puberty augment GH secretory-burst mass 1.8- to 3.5-fold, whereas ageing, relative obesity, physical inactivity, hypogonadism, and hypopituitarism mute the amplitude/mass of pulsatile GH output. An abrupt rise in circulating GH concentration stimulates rapid internalization of the GH receptor in peripheral target tissues, and evokes second-messenger nuclear signalling via the STAT 5b pathway. Discrete GH peaks stimulate linear (skeletal) growth and drive muscle IGF-I gene expression more effectually than basal (time-invariant) GH exposure. A brief pulse of GH can saturate the plasma GH-binding protein system and achieve prolonged plasma GH concentrations by convolution with peripheral distribution and clearance mechanisms. A single burst of GH secretion also feeds back after a short latency on central nervous system (CNS) regulatory centres via specific brain GH receptors to activate somatostatinergic and reciprocally subdue GHRH outflow. This autoregulatory loop probably contributes to the time-dependent physiologically pulsatile dynamics of the GH axis. More slowly varying systemic IGF-I concentrations may also damp GH secretory pulse amplitude by delayed negative-feedback actions. According to this simplified construct, GH pulsatility emerges due to time-ordered multivalent interfaces among GHRH/GHRP feedforward and somatostatin, GH and IGF-I feedback signals. Resultant GH pulses trigger tissue-specific gene expression, thereby promoting skeletal and muscular growth, metabolic and body compositional adaptations, and CNS reactions that jointly maintain health and homeostasis.
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PMID:Neurophysiological regulation and target-tissue impact of the pulsatile mode of growth hormone secretion in the human. 1152 85

Endocrine inactive pituitary adenomas represent about one quarter of all pituitary tumors. By immunocytochemistry, most of these tumors are positive for intact gonadotropins and/or their subunits. Clinical presentation is usually secondary to mass effect symptoms, such as visual disturbances, headache, and hypopituitarism. Differential diagnosis is usually accomplished by neuroradiologic studies, even though in selected cases positron emission tomography and/or single photon emission tomography may aid to distinguish pituitary adenomas from other endocrine inactive lesions, such as meningiomas and craniopharyngiomas. Surgical management is usually considered the first choice treatment for patients with endocrine inactive pituitary adenomas because it is very effective in ameliorating symptoms of chiasmal compression and headache. Radical removal of the tumor, however, is difficult to obtain because of the frequent invasiveness into the cavernous sinus. Radiation therapy diminishes the likelihood of tumor recurrence, especially in patients with demonstrable tumor remnants after surgery. Medical therapy with dopaminergic drugs, somatostatin analogs, or gonadotropin-releasing hormone agonists or antagonists causes mild reduction of tumor size in few patients and, therefore, seems to be of limited value in the therapeutic management of patients with endocrine inactive pituitary adenomas.
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PMID:Endocrine inactive and gonadotroph adenomas: diagnosis and management. 1176 33

Advances in immunocytochemistry, electron microscopy, cell culture, and molecular techniques have demonstrated that 80 to 90% of the clinically nonfunctioning pituitary adenomas are gonadotrope-derived and recently recognized as gonadotropinomas, which account for as many as 40 to 50% of all pituitary macroadenomas. Patients usually present with mass effects including visual field loss and headache, hypogonadism, and hypopituitarism. Commonly, the tumor is found incidentally. Recently, a few patients with gonadotropinomas were reported to have hormonal hypersecretion syndromes such as ovarian hyperstimulation, testicular enlargement, and precocious puberty. The tumors can be divided into two broad categories: functioning gonadotropinomas with positive immunostaining for follicle-stimulating hormone, leutinizing hormone, and/or their subunits; and nonfunctioning gonadotropinomas or null cell tumors with negative immunostaining for all pituitary hormones but positive nuclear immunostaining for steroid factor-1 or DAX-1 characteristic of gonadotrope differentiation, with evidence of gonadotropin production or gene expression at the mRNA level. Gonadotropinomas are monoclonal in origin but the pathogenesis of these tumors is unknown and factors that stimulate clonal proliferation not yet determined. A new pituitary oncogene, pituitary tumor transforming gene, has recently been found to be overexpressed in about two thirds of these tumors but it is also detected in all other pituitary tumor subtypes. Alterations of tumor hormone receptors and local growth factors may also play a role in the tumor development and/or progression. Transphenoidal surgery remains the principal therapy for the macroadenomas. Radiosurgery using gamma knife, the linear accelerator, or proton beam therapy showed promising results, especially for controlling the residual or recurrent tumors. Medical therapy with somatostatin analogs, dopamine agonists, and gonadotropin-releasing hormone agonists and antagonists are rarely effective in reducing tumor size. Experimental therapy with intraoperative local chemotherapy or potential gene therapy requires further investigation.
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PMID:Gonadotropinomas. 1253 57

Thyrotropin-releasing pituitary tumors represent 0.9 to 2.8% of all pituitary adenomas. They cause secondary or central hyperthyroidism. The diagnosis of these tumors has been increasing in the past 20 years. It was produced by introduction of the sensitive immunoradio-metric assay of TSH and better radiological imaging (magnetic resonance imaging). TSH--secreting pituitary adenomas are aggressive and invasive neoplasms. Most reports describe a poor outcome after pharmacological therapy, surgery and radiation therapy. Presently the diagnosis of thyrotropin-secreting pituitary tumor is based on the lack of: a. inhibition of TSH levels in the presence of increased free thyroid hormones; b. response of TSH to stimulation with TRH; c. and presence of a abnormal, neoplastic(adenomatous) intrasellar or parasellar mass. Surgical excision (selective adenomectomy) by the transsphenoidal route is the first treatment. Craniotomy should be reserved for parasellar tumors with significant lateral extension. Pharmacological pretreatment with long acting somatostatin analogues is recently a standard before surgery. This medical treatment of the TSH-omas is effective in reducing TSH and free thyroid hormone plasma levels. Administration of the somatostatin analogues causing tumor mass shrinkage and changes consistency. This pretreatment is effective therapy and improves surgical outcome especially in patients harbouring macroadenomas. Radiotherapy is noncurative and produces long term complications (hypopituitarism). Authors present and discuss current cure criteria of TSH-omas with reference to their clinical experience.
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PMID:[Thyrotropin--TSH secreting pituitary tumor]. 1273 80

Currently available therapies for acromegaly are transsphenoidal surgery (TSS), radiotherapy (RT) and medical therapy with the dopamine agonists and somatostatin analogues. The goals of these therapies for acromegaly are to normalize excessive hormone secretion, thus normalizing serum levels of growth hormone (GH) and of insulin-like growth factors (IGF-I), to reduce the clinical signs and symptoms of acromegaly and to reduce tumor size in order to relieve any symptoms due to tumor mass effect. These goals should be accomplished while preserving pituitary function and with as few side effects as possible.TSS, the initial choice of therapy in most patients, is the most effective therapy at reducing the signs and symptoms of mass effect such as visual or neurological compromise. TSS is potentially curative, but the outcome is highly dependent on the tumor size, the degree of tumor invasion and the expertise of the surgeon. TSS can achieve biochemical control with normalization of IGF-I in 80-90% of patients with microadenomas and in 50-60% of those with macroadenomas. RT may be used as adjunctive therapy after unsuccessful surgery. RT can lower GH levels and normalize IGF-I levels, but there is a long lag time before this effect is achieved. Biochemical control is not achieved for 6-10 years after conventional fractionated RT; the time to clinical effect after gamma knife RT seems to be shorter. The most common complication after all forms of RT for acromegaly is the development of new hypopituitarism. Medical therapy has assumed the major role as adjunctive therapy of acromegaly. The dopamine agonists used for the therapy of acromegaly include bromocriptine, quinagolide and cabergoline. Cabergoline seems to be the most efficacious of the dopamine agonists for the treatment of acromegaly, with normalization of IGF-I being achieved in up to 35% of patients treated. Dopamine agonists are generally not effective at reducing the size of pure GH-secreting pituitary tumors. Somatostatin analogues are the most effective medical therapy currently available for acromegaly. The clinically available long-acting somatostatin analogues are long-acting octreotide and slow-release lanreotide. Overall, IGF-I levels normalize in about 66% of patients treated with long-acting octreotide and in 48% of patients treated with lanreotide. About 30% of GH-secreting tumors treated with somatostatin analogues as adjunctive therapy will have some shrinkage, and the amount of shrinkage usually ranges between 20 and 50% of tumor size. Signs and symptoms of the disease improve in about two-thirds of patients treated with long-acting somatostatin analogues. Gastrointestinal side effects are common when initiating somatostatin analogue therapy, but these effects do not typically limit continued use. Multi-modality therapy for acromegaly is often needed to achieve disease control. However, even combinations of currently available therapies cannot achieve all the goals of therapy in many patients with acromegaly.
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PMID:How effective are current therapies for acromegaly? 1291 44

Acromegaly is associated with significant morbidities and a 2- to 3-fold increase in mortality because of the excessive metabolic action of GH and IGF-I, a marker of GH output. Reductions in morbidity correspond with decreases in IGF-I, and mortality is lowered following normalization of IGF-I or GH levels. Therefore, this has become an important end point. Current guidelines for the treatment of acromegaly have not considered recent advances in medical therapy, in particular, the place of pegvisomant, a GH receptor antagonist. Treatment goals include normalizing biochemical markers, controlling tumor mass, preserving pituitary function, and relieving signs and symptoms. Surgery reduces tumor volume and is considered first-line therapy. Radiation reduces tumor volume and GH and IGF-I levels, but the onset of action is slow and hypopituitarism typically develops. Therefore, pharmacotherapy is often used following surgery or as first-line therapy for nonresectable tumors. Dopamine agonists can be considered in patients exhibiting minimal disease or those with GH-prolactin-cosecreting tumors but will not achieve hormone normalization in most patients. Somatostatin analogs effectively suppress GH and IGF-I in most patients, but intolerance (e.g. diarrhea, cramping, gallstones) can occur. Pegvisomant, the newest therapeutic option, blocks GH action at peripheral receptors, normalizes IGF-I levels, reduces signs and symptoms, and corrects metabolic defects. Pegvisomant does not appear to affect tumor size and has few adverse effects. Pegvisomant is the most effective drug treatment for acromegaly in normalizing IGF-I and producing a clinical response; it is the preferred agent in patients resistant to or intolerant of somatostatin analogs.
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PMID:Optimizing control of acromegaly: integrating a growth hormone receptor antagonist into the treatment algorithm. 1455 52

Acromegaly is a rare but disabling condition associated with reduced life expectancy. It is caused almost invariably by a growth hormone-secreting pituitary adenoma. Transsphenoidal surgery and/or radiotherapy are still considered to be the treatment of choice, but despite recent advances in both these forms of treatment, the overall surgical cure rate remains approximately 60%, and radiotherapy is characterised by delayed effect and a high incidence of hypopituitarism. Medical therapy in the form of dopamine agonists and somatostatin analogues has traditionally been used as an adjunct to surgery and/or radiotherapy, but is increasingly being used as first line therapy in the treatment of acromegaly. Recently, a third form of medical therapy, the growth hormone receptor antagonist, pegvisomant, has been licensed for use in acromegaly. This article examines the design, properties, clinical efficacy and safety of pegvisomant.
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PMID:The role of growth hormone-receptor antagonism in relation to acromegaly. 1550 Mar 74


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