scholarly journals GEOFFREY HARRIS AWARD 2019: Translational research in pituitary tumours

2020 ◽  
Vol 182 (1) ◽  
pp. R1-R13 ◽  
Author(s):  
Günter K Stalla ◽  
Christina Dimopoulou ◽  
Caroline Jung-Sievers ◽  
Eduardo Arzt ◽  
Marcelo Paez Pereda ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Cushing’S Disease ◽  
Additional Treatment ◽  
Cushing's Disease ◽  
Considerable Proportion ◽  
Somatostatin Analogue ◽  
Incomplete Resection ◽  
Pituitary Tumours ◽  
Treatment Concepts ◽  
The Impact

Although effective treatment regimens (surgical resection, drug treatment with dopamine agonists or somatostatin analogues, radiotherapy) have been established for the therapy of most pituitary tumours, a considerable proportion of affected patients cannot completely cured due to incomplete resection or drug resistance. Moreover, even if hormone levels have been normalized, patients with hormone-secreting tumours still show persistent pathophysiological alterations in metabolic, cardiovascular or neuropsychiatric parameters and have an impaired quality of life. In this review reasons for the discrepancy between biochemical cure and incomplete recovery from tumour-associated comorbidities are discussed and the clinical management is delineated exemplarily for patients with acromegaly and Cushing’s disease. In view of the development of additional treatment concepts for the treatment of pituitary adenomas we speculate about the relevance of RSUME as a potential target for the development of an anti-angiogenic therapy. Moreover, the role of BMP-4 which stimulates prolactinoma development through the Smad signalling cascade is described and its role as putative drug target for the treatment of prolactinomas is discussed. Regarding the well-known resistance of a part of somatotropinomas to somatostatin analogue treatment, recently identified mechanisms responsible for the drug resistance are summarized and ways to overcome them in future treatment concepts are presented. Concerning novel therapeutic options for patients with Cushing’s disease the impact of retinoic acid, which is currently tested in clinical studies, is shown, and the action and putative therapeutic impact of silibinin to resolve glucocorticoid resistance in these patients is critically discussed.

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 Lipid Abnormalities in Patients With Cushing’s Disease and Its Relationship With Impaired Glucose Metabolism

2021 ◽  
Vol 11 ◽  
Author(s):  
Xiaolin Sun ◽  
Ming Feng ◽  
Lin Lu ◽  
Zixuan Zhao ◽  
Xinjie Bao ◽  
...  
Keyword(s):  
Cardiovascular Risk ◽  
Glucose Metabolism ◽  
Cushing’S Disease ◽  
Cushing's Disease ◽  
Impaired Glucose Metabolism ◽  
Post Surgery ◽  
Morning Cortisol ◽  
Independent Risk Factors ◽  
Lipid Abnormalities ◽  
The Impact

PurposeDyslipidemia has been frequently reported and associated with increased cardiovascular risk in patients with Cushing’s disease (CD). Few studies are available regarding the relationships between lipid abnormalities and other preoperative metabolic comorbidities in CD, and the data on alterations of the lipid profile after surgery is quite variable. We aimed to investigate the associations between hyperlipidemia and other baseline metabolic and hormonal parameters and the impact of surgical remission on lipid metabolism in patients with CD.MethodsThis retrospective study included 104 patients diagnosed with CD. Baseline hormonal and metabolic parameters were compared between the hyperlipidemia (HLP) group and non-hyperlipidemia (NLP) group, and their relationships with hyperlipidemia at diagnosis were evaluated. Alterations in lipid profiles after surgical remission of CD were evaluated in 65 patients with available follow-up data.ResultsUpon baseline, logistic regression analysis showed that impaired glucose metabolism (IGM) (OR=4.68, 95%CI:1.38–15.91) and morning cortisol levels (per 10 μg/dl change) (OR=1.81, 95%CI:1.11–2.95) are both independent risk factors of preoperative occurrence of hyperlipidemia in patients with CD. The baseline triglyceride (TG) level was positively correlated with systolic blood pressure (SBP) (r=0.297, p=0.003). Lipid abnormalities had improvement but may persist after surgical remission, and the persisted hyperlipidemia is associated with higher baseline total cholesterol (TC) levels (r=0.505, p=0.033).ConclusionsPersistence of post-surgery hyperlipidemia is associated with severe baseline lipid abnormalities. Surgical remission with concomitant control of impaired glucose metabolism at diagnosis may have significant implications for controlling hyperlipidemia and reducing cardiovascular risk in CD.

scholarly journals The impact of the Cushing's Disease remission in associated comorbidities

2014 ◽  
Author(s):  
Vera Fernandes ◽  
Maria J Santos ◽  
Rui Almeida ◽  
Olinda Marques
Keyword(s):  
Cushing’S Disease ◽  
Cushing's Disease ◽  
Disease Remission ◽  
The Impact

CUSHING'S DISEASE IN A PATIENT WITH GONADAL DYSGENESIS AND PITUITARY TUMOUR

1965 ◽  
Vol 48 (1) ◽  
pp. 72-80 ◽  
Author(s):  
H. H. Bassøe ◽  
H. Gadeholt ◽  
K. Ronold ◽  
K. F. Støa
Keyword(s):  
Pituitary Gland ◽  
Cushing’S Disease ◽  
Pituitary Tumour ◽  
Cushing's Disease ◽  
Substitution Therapy ◽  
Pituitary Tumours ◽  
Primary Amenorrhoea ◽  
Ovarian Dysgenesis ◽  
Tumour Formation ◽  
Chromophobe Adenoma

ABSTRACT A thirty-nine years old woman with primary amenorrhoea and increased excretion of gonadotrophins, developed a chromophobe adenoma in the pituitary gland. Only a few years before she died, the diagnosis of Cushing's disease was made which progressed despite hypophysectomy. Evidence is given for the conclusion, that the patient suffered from ovarian dysgenesis, which secondarily led to hyperfunction and tumour formation of the pituitary gland and also to development of Cushing's disease. It is concluded that patients with hypogonadism should be observed for pituitary tumour formation, and that adequate substitution therapy may prevent formation of pituitary tumours.

scholarly journals Adrenal Insufficiency after Incomplete Resection of Pituitary Macrocorticotropinoma of Cushing's Disease. Role of High Molecular Weight ACTH.

2001 ◽  
Vol 48 (1) ◽  
pp. 43-51 ◽  
Author(s):  
NORIYOSHI YAMAKITA ◽  
TOSHIHIRO MURAI ◽  
YUTAKA OKI ◽  
TAKASHI MATSUHISA ◽  
TOSHIFUMI HIRATA ◽  
...  
Keyword(s):  
Molecular Weight ◽  
Adrenal Insufficiency ◽  
High Molecular Weight ◽  
Cushing’S Disease ◽  
Cushing's Disease ◽  
Incomplete Resection

scholarly journals Doubled mortality rate in irradiated patients reoperated for regrowth of a macroadenoma of the pituitary gland

2004 ◽  
pp. 497-502 ◽  
Author(s):  
EM Erfurth ◽  
B Bulow ◽  
CH Nordstrom ◽  
Z Mikoczy ◽  
L Hagmar ◽  
...  
Keyword(s):  
Mortality Rate ◽  
Life Expectancy ◽  
Cushing’S Disease ◽  
Pituitary Adenomas ◽  
Cox Regression ◽  
Cushing's Disease ◽  
Calendar Time ◽  
Cox Regression Analysis ◽  
Risk Increase ◽  
The Impact

BACKGROUND: Reduced life expectancy has been shown in patients with hypopituitarism, mainly caused by cardiovascular diseases. A major cause of hypopituitarism is pituitary adenomas, and radiotherapy may be employed as a treatment modality to reduce the post-operative regrowth rate of these tumours. Recently, we showed that in patients with craniopharyngiomas, tumour regrowth foreshadowed a fourfold risk increase for death. For patients with pituitary adenomas, the impact of regrowth on life expectancy is, however, not known. OBJECTIVE: To assess the impact of a reoperation due to a regrowth of a pituitary macroadenoma on mortality, taking into account other candidate prognostic factors. DESIGN AND PATIENTS: In 281 patients with operated and irradiated macroadenomas, excluding acromegaly and Cushing's disease, 35 patients had a regrowth (median follow-up 16.6 years). Possible risk factors for tumour regrowth were investigated by Cox regression models. RESULTS: For tumour regrowth, age, calendar time at primary surgery, gender and extension of tumour growth had no statistically significant impact. For younger patients, the proportion of regrowths was higher, but after age-stratified Cox regression analysis only regrowth was shown to have a significant impact on mortality, with a more than doubled mortality risk for patients with tumour regrowth as compared with the non-regrowing tumour patients (hazard ratio=2.24, P<0.001). This finding was corroborated by cohort analyses using the general population as an external comparison group. CONCLUSION: Among patients with irradiated pituitary macroadenomas, excluding acromegaly and Cushing's disease, a doubled mortality rate was observed for those reoperated for tumour regrowth as compared with patients with non-regrowing tumours.

scholarly journals ACTH Dependent Cushing’s Syndrome: A 72-Hour Trial of Octreotide will Identify Patients with Pituitary Dependent and Ectopic ACTH Overproduction

2020 ◽  
pp. 65-70
Author(s):  
Omayma Elshafie ◽  
Nicholas Woodhouse
Keyword(s):  
Cushing’S Syndrome ◽  
Cushing’S Disease ◽  
Somatostatin Receptors ◽  
Serum Cortisol ◽  
Cushing's Syndrome ◽  
Cushing's Disease ◽  
Pituitary Tumours ◽  
Ectopic Acth ◽  
Suppression Test ◽  
Cortisol Levels

Aims: To determine whether the use of an octreotide suppression test will reliably distinguish pituitary from ectopic ACTH overproduction.  Somatostatin receptors are expressed in NETs, but are downgraded in the pituitary as the result of hypercortisolaemia. Octreotide should therefore lower ACTH and cortisol levels in patients with NETs but not in patients with Cushing’s disease and pituitary tumors. Methodology: A cross sectional study was performed in 13 patents with ACTH dependent Cushing’s (8 women, 5 men) with ages ranging between 21 to 40 years were studied. Serum cortisol concentrations were measured at 0800 hrs before and during the administration of. Octreotide at a dosage of 100 mcg subcutaneously every 8 hours for 72 hours. Results: The serum cortisol concentrations returned to normal in 4 patients who were later documented to have ectopic disease, two with typical bronchial carcinoids and two with pancreatic NETs and metastatic disease. The other 9 patients had no suppression in serum cortisol concentrations and were documented later to have pituitary tumours. Conclusion: These results indicate that a short trial of octreotide will identify patients with ectopic disease as evidenced by a fall in serum cortisol levels whereas in those with Cushing’s disease and pituitary tumours serum cortisol levels remains unchanged.  Recommendation: We recommend all patients with ACTH dependent Cushing’s syndrome have an octreotide suppression test, even if the MRI shows an adenoma, so as to exclude the possibility of a pituitary incidentaloma in a patient with ectopic disease, or false localization from IPSS to the pituitary gland due to ectopic CRH secretion.

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