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)

Paradigms for managing acromegaly have undergone major changes in the past two decades. This has been brought about by combining surgical, pharmacological and radiotherapeutic approaches that provide tight biochemical control to reduce mortality to that of the general population. The biochemical targets for treatment are a growth hormone of <2.5 ng/mL (approximately 7.5 mU/L) and a normal, age-adjusted insulin-like growth factor-1. Until 20 years ago, dopamine agonists were the only class of pharmaceutical agents available to control acromegaly. They have a limited adjunctive role, even with the development of second-generation selective agonists such as cabergoline. Surgery and radiotherapy were the mainstay of acromegaly management before the advent of the effective pharmacological therapies of the modern era: somatostatin analogues and pegvisomant, a growth hormone receptor antagonist. Somatostatin analogues achieve biochemical control in approximately 60% of patients. Pegvisomant, which is available in the USA and Europe and has just been registered in Australia, normalizes insulin-like growth factor-1 in nearly all patients but has no effect on tumour mass. Surgery is an appropriate first-line therapy for microadenomas as the chance of success is high. For large and/or invasive tumours where the prospect of surgical cure is remote, first-line therapy is somatostatin analogue treatment with debulking surgery having an adjunctive role to achieve tight control or to alleviate compression of the optic chiasm. Although acromegaly remains a challenging disease to manage, the expanding range of therapeutic options is likely to result in a better outcome for patients and offers the potential to tailor therapy based on a patient's individual requirements.
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PMID:Newer options in the management of acromegaly. 1678 Apr 50

Evidence based drug therapy is currently available for the treatment of prolactinomas and growth hormone secreting adenomas (acromegaly). Dopamine agonists such as bromocriptine, quinagolide or cabergoline represent the standard therapy for the treatment of micro- and macro-prolaktinomas. In pregnancy, more differentiated, individual and patient-adapted therapeutic procedures have to be considered. Transsphenoidal adenomectomy is the treatment of choice for patients suffering from acromegaly. If biochemical cure (defined by normalized IGF-1 serum levels or by a GH nadir <1 microg/l during a 3-h oral glucose tolerance test) cannot be achieved, somatostatin analogues such as octreotide and lanreotide are effective. In some cases, dopamine agonists can be added. In therapy-resistant cases, growth hormone receptor antagonists can be used.
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PMID:[Treatment of pituitary gland hyperfunction: from acromegaly to prolactinoma]. 1703 81

The mechanism of action of acetaminophen is currently widely discussed. Direct inhibition of cyclooxygenase isoforms remains the commonly advanced hypothesis. We combined behavioral studies with molecular techniques to investigate the mechanism of action of acetaminophen in a model of tonic pain in rats. We show that acetaminophen indirectly stimulates spinal 5-hydroxytryptamine (5-HT)1A receptors in the formalin test, thereby increasing transcript and protein levels of low-affinity neurotrophin receptor, insulin-like growth factor-1 (IGF-1) receptor alpha subunit, and growth hormone receptor and reducing the amount of somatostatin 3 receptor (sst3R) mRNA. Those cellular events seem to be important for the antinociceptive activity of acetaminophen. Indeed, down-regulation of sst3R mRNA depends on acetaminophen-elicited, 5-HT1A receptor-dependent increase in neuronal extracellular signal-regulated kinase 1/2 (ERK1/2) activities that mediate antinociception. In addition, spinal growth hormone (GH) and IGF-1 receptors would also be involved in the antinociceptive activity of the analgesic at different degrees. Our results show the involvement of specific 5-HT1A receptor-dependent cellular events in acetaminophen-produced antinociception and consequently indicate that inhibition of cyclooxygenase activities is not the exclusive mechanism involved. Furthermore, we propose that the mechanisms of 5-HT1A receptor-elicited antinociception and the role of the spinal ERK1/2 pathway in nociception are more intricate than suspected so far and that the GH/IGF-1 axis is an interesting new player in the regulation of spinal nociception.
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PMID:Acetaminophen recruits spinal p42/p44 MAPKs and GH/IGF-1 receptors to produce analgesia via the serotonergic system. 1708 3

We tested the effect of co-treatment of acromegaly with a somatostatin analogue (SA) and a growth hormone receptor antagonist (GHA). Eleven patients underwent: 1) conventional treatment with SA, 2) discontinued treatment, 3) 6 weeks treatment with GHA (10 mg), 4) 6 weeks treatment with GHA (15 mg), 5) 3 months combined SA and GHA. Circulating IGF-I was lowered by GHA and more so with combined treatment. Treatment with GHA increased endogenous GH levels, which was partly reversed by combined treatment. Plasma glucose levels were highest during SA treatment and lowest with GHA. Co-treatment of acromegaly with SA and GHA is a promising concept.
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PMID:[Medical co-treatment af acromegaly with a somatostatin analogue and a growth hormone receptor antagonist]. 1604 86

Since the initial use of medical treatment for acromegaly, several advances have been made in the understanding of the pathophysiology of growth hormone producing tumors, resulting in the development of multiple medical options and novel treatments. Currently there are three major classes of medication available for the treatment of acromegaly: somatostatin receptor ligands, growth hormone receptor antagonists, and dopamine agonists. Somatostatin receptor ligands are the treatment of choice for acromegaly due to their effectiveness in controlling growth hormone excess in approximately 60% of patients and their beneficial effects on tumor volume. Clinical trials have demonstrated efficacy of pegvisomant in up to 97% of patients, but long term data and safety have yet to be established. Dopamine agonists are inexpensive, but their use is hampered by their lack of efficacy compared to other medications. Medical therapy has an established role as adjuvant therapy after non-curative surgery, as well as primary therapy for selected patients unsuitable for surgical resection. Medical treatment to control growth hormone hypersecretion is often needed after radiation therapy until the effects are evident. Preliminary data suggest a potential role for medical treatment prior to surgical resection, surgical debulking to improve medical efficacy, and combination therapy with multiple medications from the three classes. More studies are required, however, to validate the utility of these approaches in treating acromegaly. With the available therapies, disease control can be achieved in nearly all patients with acromegaly.
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PMID:Medical therapy: options and uses. 1816 11

Growth-hormone hypersecretion, acromegaly, is associated with reduced life expectancy. First line treatment remains surgery, but remission rates vary between 50% and 90%. In case of lack of surgical remission or recurrence, somatostatin agonists can be proposed. However, about 30% of patients are partially or totally resistant to this treatment. The growth hormone receptor antagonist pegvisomant currently needs more prolonged follow-up studies. Conventional radiotherapy and radiosurgery are two radiation treatment modalities that can be proposed to these resistant patients. Reported rates of remission for conventional radiotherapy range between 50% and 60% in patients with acromegaly, with a time to remission delayed by several years, and adverse effects including high rates of hypopituitarism. This treatment could be proposed to patients with aggressive adenomas, in whom surgery cannot allow biochemical control. In contrast, studies on stereotactic radiosurgery reported lower rates of remission, with faster growth hormone hypersecretion decline, and a lower risk of adverse effects. However, this latter technique requires a well defined target volume, which limits its indications. The high precision of this technique makes it possible to be used as an alternative primary treatment to surgery. We reviewed major advantages and drawbacks of each of these techniques, based on recent studies to try to define their respective indications in the therapeutic algorithm of acromegaly.
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PMID:Radiotherapy and radiosurgery in acromegaly. 1817 23

Acromegaly is caused by growth hormone hypersecretion, mostly from a pituitary adenoma, driving insulin-like growth factor 1 overproduction. Manifestations include skeletal and soft tissue growth and deformities; and cardiac, respiratory, neuromuscular, endocrine, and metabolic complications. Increased morbidity and mortality require early and tight disease control. Surgery is the treatment of choice for microadenomas and well-defined intrasellar macroadenomas. Complete resection of large and invasive macroadenomas rarely is achieved; hence, their low rate of disease remission. Pharmacologic treatments, including long-acting somatostatin analogs, dopamine agonists, and growth hormone receptor antagonists, have assumed more importance in achieving biochemical and symptomatic disease control.
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PMID:Acromegaly. 1822 32

This paper presents an overview of the evolution of pituitary surgery for acromegaly. It begins with the first case, attempted in 1893, through the initial transsphenoidal successes in 1907-1910, to the development of effective craniotomy approaches, and ultimately to the resurrection of the transsphenoidal approach in the 1970s and thereafter. Today, the minimally endoscopic transnasal endoscopic approach is fast becoming the norm. Indications for surgery include active acromegaly, visual loss and other forms of mass effect, pituitary tumor apoplexy, and failure of other therapies (medical, radiation). Contraindications include advanced age, debility or other medical conditions increasing the risk of general anaesthesia or surgery. Surgery for acromegaly has the advantage of immediate lowering of the growth hormone excess, with endocrine remission rates of 70% for microadenomas and 50% for macroadenomas. When surgery fails to obtain remission, a program of therapy is designed for the patient to include adjunctive medical therapy (dopamine agonists, somatostatin analogs, and growth hormone receptor antagonists), radiation therapy or radiosurgery (Gamma knife, Cyberknife, etc.).
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PMID:Surgery for acromegaly: evolution of the techniques and outcomes. 1822 47

Pituitary adenomas are the most common intrasellar tumors. With the exception of prolactinomas, first-line treatment is almost always surgical. Prolactinomas are usually treated with dopamine agonists such as cabergoline or bromocriptine. Somatostatin analogues, such as octreotide and lanreotide, can be adjunctive to surgical therapy in acromegaly, although they can be used as primary therapy in selected cases. Pegvisomant, a growth hormone receptor antagonist, is reserved for acromegalic patients who are resistant to treatment with somatostatin analogues. No effective medical therapy is available for adenomas that secrete adrenocorticotropic hormone, and occasionally bilateral adrenalectomy is required to resolve severe hypercortisolemia. Radiation therapy (fractionated or radiosurgery) can be used for residual or recurrent pituitary tumors. Asymptomatic, nonfunctioning pituitary adenomas may be followed without any intervention, but surgery is typically indicated if there are symptoms of mass effect on the optic chiasm or endocrine dysfunction. In the hands of an experienced pituitary neurosurgeon, the prognosis for endocrinologic recovery and visual improvement is good.
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PMID:Pituitary tumors. 1952 54

The introduction of effective pharmacological treatments has changed the management of acromegaly. However, chronic, life-long treatment with somatostatin analogues and/or growth hormone receptor antagonists is very expensive. We estimated the costs of treatment algorithms to control acromegaly from a Dutch perspective. We used the following assumptions: after the diagnosis of acromegaly there is a mean remaining lifespan of approximately 33 years; the success rates of surgery and somatostatin analogues in controlling the disease are approximately 60%; and the lifelong costs of different algorithms to control acromegaly in 100 patients ranged from 43 million euros (primary surgery and secondary somatostatin analogues) to 57 million euros (primary somatostatin analogues and secondary surgery) and even reached 95 million euros (medical treatment only). In algorithms that include trans-sphenoidal surgery, the lifetime treatment costs are almost 46-59% cheaper per 100 patients than in algorithms with medical treatment but without trans-sphenoidal surgery. Algorithms with primary surgery and secondary somatostatin analogs are 30% cheaper per 100 patients than algorithms with primary somatostatin analogues and secondary surgery. Per 100 patients, algorithms including lanreotide Autogel are 14-34% more expensive than algorithms including octreotide long-acting release. These life-long costs should be taken into consideration when making choices between treatment algorithms.
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PMID:Cost-effectiveness of lanreotide Autogel in treatment algorithms of acromegaly. 1952 94


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