α-Amidated peptides derived from pro-opiomelanocortin in human pituitary tumours

1988 ◽  
Vol 118 (2) ◽  
pp. 329-338 ◽  
Author(s):  
M. Fenger ◽  
A. H. Johnsen
Keyword(s):  
Molecular Weight ◽  
Cushing’S Disease ◽  
Cushing's Disease ◽  
Molecular Forms ◽  
Low Molecular Weight ◽  
Gel Chromatography ◽  
Pituitary Tumours ◽  
Nelson’S Syndrome ◽  
Human Pituitary ◽  
Nelson's Syndrome

ABSTRACT Human pituitary tumours, obtained at surgery for Cushing's disease and Nelson's syndrome, were extracted and the content and molecular forms of proopiomelanocortin (POMC)-derived peptides determined by radioimmunoassay, gel chromatography, reversed-phase high-performance liquid chromatography (HPLC) and sequence analysis. In the tumours from patients with Cushing's disease the mean concentrations of amidated peptides relative to the total amount of POMC were as follows: α-MSH, 1·7%; amidated γ-MSH (γ1-MSH), 8·5% and the peptide linking γ-MSH and ACTH in the precursor (hinge peptide or joining peptide) in its amidated form (HP-N), 17·1%. The same relative concentrations in the tumours from patients with Nelson's syndrome were 8·5% (α-MSH), 7·5% (γ1-MSH) and 12·2% (HP-N). More than 95% of the ACTH(1–39) immunoreactivity eluted as synthetic ACTH(1–39) by gel chromatography and HPLC. The remaining ACTH(1–39) immunoreactivity eluted as partly glycosylated high molecular weight forms. All the α-MSH and its glycine-extended precursor ACTH(1–14) were of low molecular weight, mainly non- or mono-acetylated forms, but significant amounts of diacetylated analogues were also present. γ1-MSH and γ2-MSH immunoreactivities eluted as high molecular weight forms and were partly glycosylated. No low molecular weight forms of γ1-MSH or γ2-MSH could be detected in the pituitary tumours. Amidated hinge peptide was mainly of the 30 amino acid form. In conclusion, all the molecular forms of the amidated peptides detected in tumours from patients with Cushing's disease and Nelson's syndrome were similar to the molecular forms found in the normal human pituitary. The main difference between the tumours and the normal pituitary was the greater amount of peptides produced, particularly α-MSH and γ1-MSH. J. Endocr. (1988) 118, 329–338

Peptides related to α-melanocyte-stimulating hormone are commonly produced by human pituitary corticotroph adenomas: no relationship with pars intermedia origin

1989 ◽  
Vol 120 (3) ◽  
pp. 531-NP ◽  
Author(s):  
P. J. Coates ◽  
I. Doniach ◽  
C. Wells ◽  
A. C. Hale ◽  
L. H. Rees ◽  
...  
Keyword(s):  
Cushing’S Disease ◽  
High Performance ◽  
Cushing's Disease ◽  
Pars Intermedia ◽  
Intermediate Lobe ◽  
Nelson’S Syndrome ◽  
Human Pituitary ◽  
Nelson's Syndrome ◽  
Pituitary Glands ◽  
Corticotroph Adenomas

ABSTRACT The presence of immunoreactive (ir)-α-MSH has been investigated by immunocytochemistry in 24 pituitary adenomas and one case of corticotroph hyperplasia causing Cushing's disease, in four adenomas causing Nelson's syndrome, and in ten 'silent' corticotroph adenomas. It was found that a high proportion of these adenomas have a population of cells containing ir-α-MSH in addition to ir-ACTH. In some instances, these adenomas were clearly not associated with the residual intermediate lobe of the pituitary. Radioimmunoassay of plasma from patients with Cushing's disease or Nelson's syndrome showed elevated levels of ir-α-MSH in the majority of cases. Characterization of the ir-α-MSH in adenoma cells by immunocytochemistry, using an antiserum selective for acetylated forms of α-MSH, suggested that only the desacetyl form was present in each case examined. High-performance liquid chromatography of adenoma tissue extracts revealed material co-eluting with acetylated forms of α-MSH in only one of six cases. These results have been compared with corticotroph adenomas in animal pituitary glands, and it is concluded that the presence of α-MSH peptides cannot be used as a marker for intermediate lobe tumours, and that desacetyl α-MSH is commonly produced by corticotroph adenomas. Journal of Endocrinology (1989) 120, 531–536

TISSUE CULTURE STUDIES ON HUMAN PITUITARY TUMOURS: RADIOIMMUNOASSAYABLE ANTERIOR PITUITARY HORMONES IN THE CULTURE MEDIUM

1978 ◽  
Vol 88 (2) ◽  
pp. 239-249 ◽  
Author(s):  
Loren G. Lipson ◽  
Inese Z. Beitins ◽  
Paul D. Kornblith ◽  
Janet W. Mc Arthur ◽  
Henry G. Friesen ◽  
...  
Keyword(s):  
Tissue Culture ◽  
Cushing’S Disease ◽  
Anterior Pituitary ◽  
Pituitary Hormones ◽  
Cushing's Disease ◽  
Hormone Release ◽  
Pituitary Tumours ◽  
Human Pituitary ◽  
Anterior Pituitary Hormones

ABSTRACT A tissue culture study was undertaken to determine if human non-functioning pituitary tumours secrete polypeptide anterior pituitary hormones in vitro and to study the spectrum of hormone release by functioning pituitary neoplasms. Fragments from 48 human pituitary tumours (from patients - 2 with Cushing's disease, 1 with Nelson's syndrome, 5 with amenorrhoea-galactorrhoea, 10 with acromegaly and 30 with non-functioning pituitary tumours) and three normal human anterior pituitary glands (controls) were placed in tissue culture immediately after surgery. The in vitro release of human growth hormone (HGH), prolactin (Prl), thyrotrophin (TSH), adrenocorticotrophin (ACTH), luteinizing hormone (LH) and follicle stimulating hormone (FSH) were measured by radioimmunoassays at the end of one week in culture. Clinical and pathological data were compared to hormone release patterns. In the culture media from control pituitaries the concentrations of the six hormones tested were 100 to 10 000 times greater than in peripheral blood. The medium surrounding the fragments from functioning pituitary tumours contained the following: a) Acromegaly - high levels of HGH and variable concentrations of the other hormones. b) Cushing's disease - ACTH and Prl predominantly. c) Amenorrhcea-galactorrhoea syndrome - prolactin in 4 out of 5 patients, all six polypeptides in one patient. In the media from the 30 patients diagnosed as having non-functioning pituitary tumours, 60 % of the samples contained at least one hormone at a concentration similar to that of the controls and 100 % of the samples contained detectable quantities of at least one hormone.

scholarly journals Nelson's Syndrome

2007 ◽  
Vol 51 (8) ◽  
pp. 1392-1396 ◽  
Author(s):  
Alia Munir ◽  
John Newell-Price
Keyword(s):  
Cushing’S Disease ◽  
Pituitary Tumour ◽  
Bilateral Adrenalectomy ◽  
Cushing's Disease ◽  
Treatment Modalities ◽  
Pituitary Mass ◽  
Nelson’S Syndrome ◽  
Nelson's Syndrome ◽  
Great Heterogeneity ◽  
The One

Nelson's syndrome is a potentially severe complication of bilateral adrenalectomy performed in the treatment of Cushing's disease, and its management remains difficult. Of all of the features of Nelson's syndrome, the one that causes most concern is the development of a locally aggressive pituitary tumour, which, unusually for pituitary disease, may occasionally cause death from the tumour itself. This feature is especially pertinent given the increasing use in Cushing's disease of laparoscopic bilateral adrenal surgery as a highly effective treatment modality to control cortisol-excess. Despite numerous studies and reports, there is no formal consensus of what defines Nelson's syndrome. Thus, some will define Nelson's syndrome according to the classical description with an evolving pituitary mass after bilateral adrenalectomy, whereas others will rely on increasing plasma ACTH levels, even in the absence of a clear pituitary mass lesion on MRI. These factors need to be borne in mind when considering the reports of Nelson's syndrome, as there is great heterogeneity, and it is likely that overall the modern 'Nelson's syndrome' represents a different disease entity from that of the last century. In the present paper, clinical and epidemiological features of Nelson's syndrome, as well as its treatment modalities, are reviewed.

Demonstration of pro-opiomelanocortin mRNA in pituitary adenomas and para-adenomatous gland in cushing's disease and Nelson's syndrome

1993 ◽  
Vol 169 (3) ◽  
pp. 335-339 ◽  
Author(s):  
Marita Fehn ◽  
Maura A. Farquharson ◽  
Doris Sautner ◽  
Wolfgang Saeger ◽  
Dieter K. Lüdecke ◽  
...  
Keyword(s):  
Cushing’S Disease ◽  
Pituitary Adenomas ◽  
Cushing's Disease ◽  
Nelson’S Syndrome ◽  
Nelson's Syndrome

scholarly journals Nelson's syndrome

2010 ◽  
Vol 163 (4) ◽  
pp. 495-507 ◽  
Author(s):  
T M Barber ◽  
E Adams ◽  
O Ansorge ◽  
J V Byrne ◽  
N Karavitaki ◽  
...  
Keyword(s):  
Predictive Factors ◽  
Cushing’S Disease ◽  
Pituitary Tumour ◽  
Cushing's Disease ◽  
Current Evidence ◽  
Pituitary Mass ◽  
Nelson’S Syndrome ◽  
Nelson's Syndrome ◽  
Tertiary Centre ◽  
Threatening Condition

Nelson's syndrome is a potentially life-threatening condition that does not infrequently develop following total bilateral adrenalectomy (TBA) for the treatment of Cushing's disease. In this review article, we discuss some controversial aspects of Nelson's syndrome including diagnosis, predictive factors, aetiology, pathology and management based on data from the existing literature and the experience of our own tertiary centre.Definitive diagnostic criteria for Nelson's syndrome are lacking. We argue in favour of a new set of criteria. We propose that Nelson's syndrome should be diagnosed in any patient with prior TBA for the treatment of Cushing's disease and with at least one of the following criteria: i) an expanding pituitary mass lesion compared with pre-TBA images; ii) an elevated 0800 h plasma level of ACTH (>500 ng/l) in addition to progressive elevations of ACTH (a rise of >30%) on at least three consecutive occasions. Regarding predictive factors for the development of Nelson's syndrome post TBA, current evidence favours the presence of residual pituitary tumour on magnetic resonance imaging (MRI) post transsphenoidal surgery (TSS); an aggressive subtype of corticotrophinoma (based on MRI growth rapidity and histology of TSS samples); lack of prophylactic neoadjuvant pituitary radiotherapy at the time of TBA and a rapid rise of ACTH levels in year 1 post TBA. Finally, more studies are needed to assess the efficacy of therapeutic strategies in Nelson's syndrome, including the alkylating agent, temozolomide, which holds promise as a novel and effective therapeutic agent in the treatment of associated aggressive corticotroph tumours. It is timely to review these controversies and to suggest guidelines for future audit.

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