Etiology of Acromegaly from the Neuroendocrine Point of View: A Historical Perspective

Reichlin, Seymour

doi:10.1007/978-1-4613-1913-9_2

Cited by 3 publications

(3 citation statements)

References 50 publications

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“…Although various causes of acromegaly have been reported, over 99% of cases were derived from primary pituitary adenoma [10], and the etiology of tumors was likely to be of monoclonal origin [11]. Currently, surgical therapy by the transsphenoidal route and medical therapy with bromocriptine are the two main methods for treating active acromegaly, but in many cases the goal of a "cure" cannot be realized.…”

Section: Discussionmentioning

confidence: 99%

Heterogeneous Responses to the Long-Term Treatment of Active Acromegaly with Octreotide.

Chang

Kuo

Fang³

et al. 1996

Endocr J

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Abstract. To study GH response to the long-acting somatostatin analogue, we treated 11 actively acromegalic patients with octreotide (Sandostatin),100 µg, sc, tid, for six months. Their endocrinological outcomes and clinical improvements varied. The 11-h GH secretory profiles on pretreatment day confirmed the hypersecretion of GH in all patients. Three hours after the first dose of octreotide, serum GH declined rapidly to levels below 5 ng/ml in all but two patients who failed to normalize their serum GH. In spite of the subsequent doses, there was no further suppression in serum GH. Drug resistance with GH rebound developed in some patients after three months of continued treatment.The paradoxical serum GH rises in response to oral glucose or iv TRH detected before the treatment in all patients attenuated or disappeared after the 6-month octreotide therapy; an exceptional case was one of the above-mentioned two patients, whose serum GH was stimulated more than before by glucose and TRH at the end of therapy. Serum insulin-like growth factor I (IGF-I) levels of all patients showed a significant reduction after 6-month treatment, but their mean values remained abnormally high. There were no intolerable adverse side effects; some patients, however, experienced pain at the injection site, passage of loose stool, and incidence of new gall stone or intrahepatic lesions on octreotide therapy. We concluded that octreotide was a useful long-term adjunctive therapeutic agent for patients with active acromegaly, but that a high degree of response heterogeneity including total refractoriness would be expected.

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Section: Discussionmentioning

confidence: 99%

Heterogeneous Responses to the Long-Term Treatment of Active Acromegaly with Octreotide.

Chang

Kuo

Fang³

et al. 1996

Endocr J

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“…The majority of pituitary tumors are extremely sensitive to stimulatory neurohormones (1,2). Although the cellular alterations responsible for this phenomenon are still unclear, pituitary tumors acquire an enhanced susceptibility to stimulatory inputs by both responding to abnormal stimuli and losing the normal mechanisms of desensitization.…”

Section: Increased Action Of Stimulatory Neurohormonesmentioning

confidence: 99%

“…The anterior pituitary consists of several differentiated cell types that are susceptible, with variable frequency, to excessive proliferation result¬ ing in adenoma formation. In the past two decades, several theories have been put forward to elucidate the pathogenetic events involved in pituitary tumor forma¬ tion (1,2). In particular, it has been proposed that pituitary adenomas might arise as a consequence of either abnormal regulation by hypothalamic or periph¬ eral agents or intrinsic cellular alterations (Fig.…”

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confidence: 99%

Cellular alterations in pituitary tumors

Spada

Vallar

Faglia

1994

European Journal of Endocrinology

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In the last few years, molecular studies on pituitary adenomas have yielded evidence supporting a primary pituitary origin of these tumors. Although the existence of genomic alterations in tumoral cells is strongly suggested by the fact that almost all pituitary adenomas are monoclonal in origin, structural genetic abnormalities such as rearrangement, deletion or mutation, which could result in transcriptional activation, have been identified in a minority of tumors. As far as the possible loss of anti-oncogenes in pituitary tumors is concerned, gene alterations have not been found in the p53 nor in the retinoblastoma gene, while loss of chromosome 11q13 sequences, which contain the deduced location of the yet uncloned MEN-1 gene, has been reported in a subset of GH-secreting adenomas. With regard to the activation of dominant oncogenes in the process of tumor formation, activating mutations of either the Gs alpha-subunit or the ras gene have been identified in a large proportion of GH-secreting adenomas and in individual particularly invasive tumours, respectively. Promoting agents such as hypothalamic neurohormones and growth factors may be required for the selective growth of genetically altered cells. In this respect, it is worth noting that receptor/postreceptor alterations occurring in pituitary tumors may cause an increased action of stimulatory neurohormones with growth promoting properties as well as defective action of inhibitory inputs.

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Clonal Origin of Pituitary Adenomas*

Herman

Fagin

Gonsky

et al. 1990

The Journal of Clinical Endocrinology & Metabolism

529

214

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As the pathogenesis of pituitary adenomas remains unclear, the tumor clonal composition of these common neoplasms was studied. Clonality was determined in female patients by analysis of restriction fragment length polymorphisms of the X-chromosome genes hypoxanthine phosphoribosyl transferase and phosphoglycerate kinase in conjunction with their respective methylation patterns. Peripheral lymphocyte DNA was screened from 62 female patients undergoing transsphenoidal surgery for pituitary adenoma. Eleven patients were heterozygous for the BglI site on PGK, 4 for the BamHI site on HPRT, and 1 patient for both sites. Of these 16 patients, 3 had acromegaly, 4 had Cushing's disease, 7 had hyperprolactinemia, and 2 were clinically nonfunctional. After surgery, morphological study, including immunohistochemistry and electron microscopy of the pathological specimens, allowed a direct comparison between clonality and tumor cell type. Control fresh normal pituitary tissue was found to be polyclonal. The following tumors were monoclonal: all 3 somatotroph adenomas, 4 of 4 lactotroph tumors, 3 of 4 corticotroph cell adenomas, a gonadotroph adenoma, and a nonsecretory adenoma. A mixed plurihormonal adenoma was polyclonal, as were 2 tumors consisting of adenomatous lactotrophs interspersed with nontumorous adenohypophyseal pituitary tissue and one corticotroph adenoma mixed with normal pituitary tissue. Functional pituitary adenomas derived from somatotrophs, corticotrophs, or lactotrophs and nonsecretory tumors are monoclonal in nature, suggesting that somatic cell mutations precede clonal expansion of these cells and play a major role in pituitary tumorigenesis.

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Etiology of Acromegaly from the Neuroendocrine Point of View: A Historical Perspective

Cited by 3 publications

References 50 publications

Heterogeneous Responses to the Long-Term Treatment of Active Acromegaly with Octreotide.

Heterogeneous Responses to the Long-Term Treatment of Active Acromegaly with Octreotide.

Cellular alterations in pituitary tumors

Clonal Origin of Pituitary Adenomas*

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