Evidence for the Presence of Tumor Peptides with Corticotropin-Releasing-Factor-like Activity in the Ectopic ACTH Syndrome

Gv, Upton; Tt, Amatruda

doi:10.1056/nejm197108192850801

Cited by 166 publications

(33 citation statements)

References 22 publications

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“…First, the present results provide a basis for defining an "ecotopic GHRF syndrome" analogous to the ectopic ACTH syndrome (6,7) and indicate that consideration should be given to the possible presence of an extrapituitary tumor in every patient with acromegaly. Second, they provide an explanation for the presence of GH-secreting pituitary tumors in the multiple endocrine neoplasia syndrome, type I (pancreatic islet tumors, pituitary tumors, carcinoid tumors, parathyroid hyperplasia or tumors), and suggest the possibility that other relationships of this type will be uncovered with time.…”

Section: Discussionmentioning

confidence: 75%

“…The data extend the list of ectopic hormones that can be secreted by tumors derived from amine precursor uptake and decarboxylation-containing cells (38). From an evolutionary standpoint, it may be more than just coincidence that ectopic tumors that secrete hormones do so in clusters of interrelated peptides, i.e., ACTH and corticotropinreleasing factor (6), and GH-releasing activity, somatostatin, and GH (present report, 15,19). The possibility is suggested that the genomes for a pituitary hormone and its hypothalamic releasing/inhibiting hormones may be closely related and that there may have been some evolutionary advantage to having the codons for controlling factors in close proximity to those for their target hormone.…”

Section: Discussionmentioning

confidence: 81%

“…The tumors involved have most frequently, though not exclusively, been bronchial adenomas of the carcinoid type, thymomas, pancreatic islet tumors, and small cell lung carcinomas (2)(3)(4)(5). The hormones secreted are peptide and/or protein in nature and resemble the natural secretory products of the hypothalamus, pituitary, parathyroid glands, and pancreatic islets (6)(7)(8)(9)(10)(11).…”

Section: Introductionmentioning

confidence: 99%

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Partial purification and characterization of a peptide with growth hormone-releasing activity from extrapituitary tumors in patients with acromegaly.

Frohman¹,

Szabó²,

Berelowitz³

et al. 1980

J. Clin. Invest.

165

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A B S T R A C T Growth hormone (GH)-releasing activity has been detected in extracts of carcinoid and pancreatic islet tumors from three patients with GHsecreting pituitary tumors and acromegaly. Bioactivity was demonstrated in 2 N acetic acid extracts of the tumors using dispersed rat adenohypophyseal cells in primary monolayer culture and a rat anterior pituitary perifusion system. The GH-releasing effect was dose responsive and the greatest activity was present in the pancreatic islet tumor. Small amounts of activity were also found in two other tumors (carcinoid and small cell carcinoma of lung) unassociated with GH hypersecretion.Each of the tumors contained somatostatin-like immunoreactivity but the levels did not correlate with the net biologic expression of the tumor. Sephadex G-75 gel filtration indicated the GH-releasing activity to have an apparent molecular size of slightly greater than 6,000 daltons. The GH-releasing activity was adsorbed onto DEAE-cellulose at neutral pH and low ionic strength, from which it could be eluted by increasing ionic strength. The GH-releasing activity was further purified by high pressure liquid chromatography using an acetonitrile gradient on a cyanopropyl column to yield a preparation that was active at 40 ng protein/ml. Partially purified GH-releasing activity, from which most of the bioactive somatostatin had been removed, increased GH release by pituitary monolayer cultures to five times base line. Enzymatic hydrolysis studies revealed that the GH-releasing activity was resistant to carboxypeptidase, leucineaminopeptidase, and pyroglutamate-amino-peptidase but was destroyed by trypsin and chymotrypsin, inAddress reprint requests to Dr. Frohman.

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Section: Discussionmentioning

confidence: 75%

Section: Discussionmentioning

confidence: 81%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Partial purification and characterization of a peptide with growth hormone-releasing activity from extrapituitary tumors in patients with acromegaly.

Frohman¹,

Szabó²,

Berelowitz³

et al. 1980

J. Clin. Invest.

165

View full text Add to dashboard Cite

show abstract

“…However, hypocortisolism was not observed postpartum. Fifth, recently several cases of Cushing's syndrome that resolved on excision of ectopic CRH (but not ACTH)-producing tumor have been reported (20,21). Such cases are rare, but they explain the possibility that ectopic CRH production in both extrahypothalamic tumors and placenta may elicit hypersecretion of cortisol despite the presence of CRH binding protein in peripheral plasma.…”

Section: Discussionmentioning

confidence: 99%

Placental corticotropin-releasing hormone may be a stimulator of maternal pituitary adrenocorticotropic hormone secretion in humans.

Sasaki¹,

Shinkawa²,

Yoshinaga³

1989

J. Clin. Invest.

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To clarify the physiological role of placental corticotropin-releasing hormone (CRH), we measured plasma CRH, ACTH, and cortisol throughout pregnancy. Cerebrospinal fluid (CSF) CRH levels and ACTH responsiveness to synthetic CRH were also quantified in pregnant and nonpregnant women. Maternal plasma CRH levels, which increased progressively during pregnancy, correlated well with both ACTH and cortisol in early labor, delivery, and postpartum samples, and also with cortisol levels in samples before labor. CSF CRH levels in term pregnant women did not differ from those of nonpregnant women. CRH infusion that attained similar plasma CRH levels to those found in late pregnancy elicited significant ACTH release in vivo and regular CRH test provoked normal ACTH response during early pregnancy but no response during late pregnancy. We concluded that: (a) maternal pituitary-adrenal axis correlates well with plasma CRH levels, which are high enough to provoke ACTH release from maternal pituitary; (b) hypothalamic CRH secretion in term pregnant women is not exaggerated; and (c) maternal pituitary is responsive to synthetic CRH in early but not late pregnancy, suggesting that maternal pituitary-adrenal axis is already activated by high circulating CRH. Placental CRH may be an important stimulator of the maternal pituitary-adrenal axis during pregnancy.

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“…Rarely, CS may result from CRH production from SCLCs, MTCs, carcinoids, PETs, chromaffin cell tumours or hypothalamic tumours (Upton & Amatruda 1971, Oldfield et al 1991, Muller & von Werder 1992 Endocrine-Related Cancer (2010) 17 R173-R193…”

Section: Humoral Pnss In Net Cushing's Syndromementioning

confidence: 99%

Paraneoplastic syndromes secondary to neuroendocrine tumours

Kaltsas

Androulakis²,

Herder³

et al. 2010

Endocrine-Related Cancer

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Neuroendocrine tumours may be either benign or malignant tumours, and have the ability to synthesise and secrete biologically active substances characteristic of the cell of origin that can cause distinct clinical syndromes. The term 'paraneoplastic syndromes' (PNSs) is used to denote syndromes secondary to substances secreted from tumours not related to their specific organ or tissue of origin and/or production of autoantibodies against tumour cells; such syndromes are mainly associated with hormonal and neurological symptoms. Appreciation of the presence of such syndromes is important as clinical presentation, if not identified, may delay the diagnosis of the underlying neoplasia. Conversely, early recognition can allow for more rapid diagnosis, particularly as the coexistence of a neoplasm with a clinical or biochemical marker offers an additional determinant of tumour status/progression. PNSs can complicate the patient's clinical course, response to treatment, impact prognosis and even be confused as metastatic spread. Their diagnosis involves a multidisciplinary approach, and detailed endocrinological, neurological, radiological and histological studies are required. Correct diagnosis is essential as the treatment of choice will be different for each disorder, particularly in the case of malignant tumours; it is therefore important to develop appropriate means to correctly identify and localise these tumours. Clinical awareness and the incorporation into clinical practise of 111 In-octreotide scintigraphy, chromogranin A and other evolving biochemical marker measurement techniques have substantially contributed to the identification of patients harbouring such syndromes. Diseasespecific medical therapies are mandatory in order to prevent recurrence and/or further tumour growth. Owing to their rarity, central registration of these syndromes is very helpful in order to be able to provide evidence-based diagnostic and therapeutic approaches.

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Evidence for the Presence of Tumor Peptides with Corticotropin-Releasing-Factor-like Activity in the Ectopic ACTH Syndrome

Cited by 166 publications

References 22 publications

Partial purification and characterization of a peptide with growth hormone-releasing activity from extrapituitary tumors in patients with acromegaly.

Partial purification and characterization of a peptide with growth hormone-releasing activity from extrapituitary tumors in patients with acromegaly.

Placental corticotropin-releasing hormone may be a stimulator of maternal pituitary adrenocorticotropic hormone secretion in humans.

Paraneoplastic syndromes secondary to neuroendocrine tumours

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