Somatostatin analogs in the treatment of acromegaly: the choice is now possible

Chanson, Philippe

doi:10.1530/eje.0.1430573

Cited by 7 publications

(6 citation statements)

References 13 publications

(9 reference statements)

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“…The GH-inhibitory activity of cyclic somatostatin analogs, possessing high affinity to sst2, like octreotide, lanreotide and RC-160 has been extensively examined in vitro as well as in animal models [33,39]. Octreotide, RC-160 and lanreotide show potent abrogation of GH release in rat pituitary adenoma cell lines like GH3 and GH4C1 [13,35,106,107]. Hofland et al (1994) have compared the GH-inhibitory profiles of octreotide, RC-160 and lanreotide in human GHsecreting pituitary tumor cells as well as normal rat anterior pituitary cell in vitro.…”

Section: Gh-inhibitory Activity Of Somatostatin Agonistsmentioning

confidence: 99%

“…A number of studies have compared the therapeutic efficacy of octreotide LAR and lanreotide SR. Data from most studies seem to suggest that octreotide-LAR is more efficacious in acromegaly patients than lanreotide SR [106,[165][166][167][168]. Freda et al (2002) have reported that a greater percentage of patients treated with octreotide LAR showed inhibition of GH levels (and concomitant normalization of IGF-1 levels) acromegaly patients receiving lanreotide SR [32,106,[168][169][170].…”

Section: Clinical Efficacy Of Somatostatin Agonists In Acromegalymentioning

confidence: 99%

“…Freda et al (2002) have reported that a greater percentage of patients treated with octreotide LAR showed inhibition of GH levels (and concomitant normalization of IGF-1 levels) acromegaly patients receiving lanreotide SR [32,106,[168][169][170]. Most of the above studies comparing lanreotide SR with octreotide-LAR involved patients who were treated with sc lanreotide before the administration of octreotide-LAR, making critical interpretation of the data difficult.…”

Section: Clinical Efficacy Of Somatostatin Agonists In Acromegalymentioning

confidence: 99%

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GH-Inhibitory Activity of Novel Somatostatin Agonists: Potential Applications in Acromegaly

Dasgupta¹

2005

CMCIEMA

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Acromegaly is a relatively rare debilitating disease caused by hypersecretion of growth hormone (GH). Despite a multimodality approach involving surgery, radiation, dopamine agonists and somatostatin agonists the management of acromegaly in some patients has remained a challenge. Although, octreotide and lanreotide are the mainstay for medical therapy in acromegaly, their relatively short biological half-life, pharmacokinetic profiles and side effects emphasize the need for a new generation of somatostatin analogs with improved therapeutic index. The antisecretory activity of somatostatin is mediated by high affinity somatostatin receptors (which belong to five subtypes) on pituitary adenomas. The suppression of GH secretion by somatostatin is mediated primarily by sst2 and sst5, via inhibition of cAMP and intracellular calcium levels. Additionally, the inhibition of exocytosis and cell proliferation by ssts also contributes to the antisecretory activity of somatostatin. Sst2 and sst5 are expressed in almost all GH-secreting adenomas. The present review summarizes the in vitro and in vivo GH-inhibitory activity of novel somatostatin agonists and their potential applications in the therapy of acromegaly. The signaling networks underlying somatostatin receptor subtypes particularly sst2, sst5 and sst1 in mediating the antisecretory activity of somatostatin agonists have been discussed. A brief summary of the clinical efficacy of currently available somatostatin agonists in acromegaly patients is also presented. Novel somatostatin analogs like PTR3173, ASS-52, SOM230, KE108 and bispecific agonists (analogs targeting more than one cellular receptor) like BIM-23244 and BIM-23A387 represent a new generation of GH-inhibitory agents, which may lead to improved therapeutic strategies in acromegaly.

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Section: Gh-inhibitory Activity Of Somatostatin Agonistsmentioning

confidence: 99%

Section: Clinical Efficacy Of Somatostatin Agonists In Acromegalymentioning

confidence: 99%

Section: Clinical Efficacy Of Somatostatin Agonists In Acromegalymentioning

confidence: 99%

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GH-Inhibitory Activity of Novel Somatostatin Agonists: Potential Applications in Acromegaly

Dasgupta¹

2005

CMCIEMA

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“…[66][67][68] SST analogs significantly reduce GH secretion and IGF-1 levels in patients with acromegaly. 35,36,39,41,42,53,75,[77][78][79][80][81][82][83][84][85][86][87][88]89 Their use is indicated in patients with a macroadenoma who have persistent disease after transsphenoidal surgery, as interim treatment in patients awaiting the full effects of external irradiation, and as preoperative treatment for 2 to 3 months to improve the medical condition of patients with severe disease. It can also be offered as primary therapy in patients who refuse surgery or those with severe medical problems that preclude surgery.…”

Section: Medical Managementmentioning

confidence: 99%

Management of Growth Hormone-Secreting Adenomas: An Update

Oyesiku¹

2002

Seminars in Neurosurgery

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Acromegaly is a chronic, debilitating condition caused by excessive secretion of growth hormone (GH). The average incidence of acromegaly is approximately 3.3 per million each year with a prevalence of approximately 60 per million. 1,2 GH-secreting adenomas account for 20% of functional adenomas; 75% of GH adenomas are macroadenomas. In the majority of cases, the condition results from benign pituitary adenomas or, rarely, from ectopic production of GH-releasing hormone (GHRH). Ectopic production of GHRH may be from carcinoid, islet cell, and other tumors and may be identified histologically by hyperplasia of somatotrophs or biochemically by elevated circulating levels of GHRH. Excessive GH results in phenotypic changes including acral enlargement, soft tissue swelling, and facial coarsening. Other features include sweating, menstrual irregularity, headache, arthritis, carpal tunnel syndrome, diabetes, hypertension, cardiac dysfunction, loss of libido, galactorrhea, visual field defects, obstructive sleep apnea, and colonic neoplasia. 1,3-7 The mortality for acromegalic patients is two to three times higher than that of the general population, but with appropriate reduction of GH hypersecretion, it tends to shift into the normal range. 8 Treatment is directed to normalizing GH secretion, eradicating or stabilizing the pituitary tumor, preserving normal pituitary function, and managing any associated complications of GH hypersecretion. The treatment modalities available include transsphenoidal surgery, pharmacotherapy, and radiation or combination therapy. This article provides an update of the pathophysiology of GH hypersecretion in acromegaly, the newly defined diagnostic criteria and the end point for a cure for acromegaly, and new developments in pharmacotherapy and radiotherapy.Objectives: Upon completion of this article, the reader will have been updated on the pathophysiology of growth hormone hypersecretion in acromegaly, the newly defined diagnostic criteria and the end point for a cure for acromegaly, and new developments in pharmacotherapy and radiotherapy.hypothalamus to the anterior pituitary gland where they bind and activate specific G protein coupled membrane receptors. Under the influence of GHRH and SST, GH is released from pituitary somatotrophs in a pulsatile manner and acts on the liver and other peripheral targets to stimulate the production of insulin-like growth GROWTH HORMONE PHYSIOLOGY Normal secretion of growth hormone (GH) is regulated by a complex interaction of stimulatory and inhibitory hypothalamic influences, mediated by GH-releasing hormone (GHRH) and somatostatin (SST), respectively. 9-15 These two hormones are transported from the

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“…Moreover, the SRLs have been shown to be effective as secondary or adjunctive therapy for acromegaly in patients that have already been treated with surgery and/or radiation [9,10]. Two long-acting forms of SRLs, octreotide LAR (long-acting release) and lanreotide PR (prolonged release) are at present available [11]. SRLs induce GH and IGF-I suppression, relief of soft tissue symptoms and control of tumor growth [4].…”

mentioning

confidence: 99%

Sustained Clinical Inactivity and Stabilization of GH/IGF-1 Levels in an Acromegalic Patient after Discontinuation of Somatostatin Analogue Treatment

Avramidis¹,

Polyzos²,

Efstathiadou³

et al. 2008

Endocr J

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Abstract. Background: A 38-year-old woman first presented complaining of foot enlargement, finger numbness, arthralgia, fatigue, galactorrhoea and oligomenorrhea. Her symptoms in conjunction with her coarsened facial features and prognathism led to the suspicion of acromegaly. Basic procedures: Oral glucose tolerance tests (OGTT) were performed at initial presentation and almost yearly thereafter for a period of 14 years. Pituitary computerized tomographies (CT) were performed annually for the first six years and magnetic resonance imaging every two years thereafter. Main findings: The diagnosis of acromegaly was confirmed by OGTT at presentation. A pituitary CT revealed a large invasive pituitary macroadenoma. She remained acromegalic after adenomectomy (evidently partial tumor resection), but was controlled with subsequent long-term somatostatin analogue (SRL) administration. After eight years of SRL administration, she had acceptable stabilization of acromegaly and at that point SRL administration was discontinued. The patient maintained the same control for the following six years up to the present time without further SRL administration. Principal conclusion: This is the first case with stabilization of growth hormone (GH) and insulinlike growth factor-1 (IGF-1) to nearly normal levels and clinical inactivity of acromegaly after withdrawal of long-term treatment with SRLs.

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Somatostatin analogs in the treatment of acromegaly: the choice is now possible

Cited by 7 publications

References 13 publications

GH-Inhibitory Activity of Novel Somatostatin Agonists: Potential Applications in Acromegaly

GH-Inhibitory Activity of Novel Somatostatin Agonists: Potential Applications in Acromegaly

Management of Growth Hormone-Secreting Adenomas: An Update

Sustained Clinical Inactivity and Stabilization of GH/IGF-1 Levels in an Acromegalic Patient after Discontinuation of Somatostatin Analogue Treatment

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