Effects of a single dose of pasireotide on glucose metabolism in patients with Cushing's disease and predictors of diabetes mellitus developement during treatment

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.

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Growth hormone deficiency and replacement in hypopituitary patients previously treated for acromegaly or Cushing's disease

Acta Endocrinologica ◽

10.1530/eje.0.1460067 ◽

2002 ◽

pp. 67-74 ◽

Cited By ~ 50

Author(s):

U Feldt-Rasmussen ◽

R Abs ◽

BA Bengtsson ◽

H Bennmarker ◽

M Bramnert ◽

...

Keyword(s):

Quality Of Life ◽

Diabetes Mellitus ◽

Growth Hormone ◽

Cushing’S Disease ◽

Cushing's Disease ◽

Research Database ◽

Serum Concentrations ◽

Gh Replacement ◽

Previously Treated

OBJECTIVE: To compare baseline characteristics in adult patients with growth hormone (GH) deficiency (GHD) who had previously been treated for Cushing's disease or acromegaly with data from patients with GHD of other aetiologies. To study the effects of GH therapy in those patients who had completed at least 6 months of GH replacement. DESIGN: Data from a large outcomes research database (KIMS (Pharmacia International Metabolic Database)). METHODS: 135 patients were identified with previous Cushing's disease, 40 had had acromegaly, and 1392 had GHD of other aetiologies. The number of additional hormone deficiencies, and the mean age of the patients were similar in the three groups. Similar proportions of patients in each group were treated using surgery, but radiotherapy was used more often in patients with acromegaly than those with other diagnoses. RESULTS: At baseline, the prevalence of diabetes mellitus and hypertension were significantly higher in the group treated for Cushing's disease, and the prevalence of stroke was significantly higher in the group treated for acromegaly. The incidence of coronary heart disease and claudication were similar in all three groups. Patients treated for Cushing's disease had lower bone mineral density and suffered fractures more often than other GHD adults. Body mass index, waist-hip ratio, serum concentrations of lipids and standard deviation scores of serum concentrations of insulin-like-growth factor-I were similar in the three groups. The dose of GH administered was comparable in the three groups and the effects of GH replacement on waist circumference, blood pressure and quality of life were also similar across the groups. The numbers and types of adverse events reported were not different between the groups. CONCLUSIONS: These data suggest that the characteristics of patients in these diagnostic groups depend on the primary disease which resulted in GHD, and that the clinical expression of GHD does not differ between the groups. Patients with previous hypercortisolism showed more long-term effects of their disease, such as diabetes mellitus, hypertension and fractures. A benefit from GH replacement was evident in patients previously treated for acromegaly and Cushing's disease particularly in relation to quality of life.

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Hypophysectomy for a Dog with Coexisting Cushing's Disease and Diabetes Mellitus

Journal of Veterinary Medical Science ◽

10.1292/jvms.09-0348 ◽

2010 ◽

Vol 72 (3) ◽

pp. 343-348 ◽

Cited By ~ 1

Author(s):

Hirokazu ISHINO ◽

Yasushi HARA ◽

Takahiro TESHIMA ◽

Shigeki TANAKA ◽

Susumu TAKEKOSHI ◽

...

Keyword(s):

Diabetes Mellitus ◽

Cushing’S Disease ◽

Cushing's Disease

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Mortality and Morbidity in Cushing's Disease over 50 Years in Stoke-on-Trent, UK: Audit and Meta-Analysis of Literature

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jc.2010-1942 ◽

2011 ◽

Vol 96 (3) ◽

pp. 632-642 ◽

Cited By ~ 197

Author(s):

R. N. Clayton ◽

D. Raskauskiene ◽

R. C. Reulen ◽

P. W. Jones

Keyword(s):

Diabetes Mellitus ◽

Risk Factors ◽

General Population ◽

Cushing’S Disease ◽

Meta Analysis ◽

Age At Diagnosis ◽

Cushing's Disease ◽

Persistent Disease ◽

Overall Mortality

Context: Pituitary ACTH-dependent Cushing's disease (CD) is uncommon, and there are very limited data on long-term mortality. Objective: The aim was to summarize what is known about mortality in ACTH-dependent CD, to report on our own data, and to provide a meta-analysis of six other reports that addressed mortality of CD. Design and Methods: Vital status of 60 CD patients was recorded as of December 31, 2009, and the standardized mortality ratio (SMR) was calculated and compared with the general population of England and Wales, United Kingdom. A meta-analysis of SMRs from seven studies (including ours) was performed for overall mortality in CD. Where reported (four studies), a similar meta-analysis was performed for those patients whose hypercortisolism was in remission after treatment compared to those patients from the same center with persistent disease. Results: 1. From Stoke-on-Trent, 51 of 60 patients were female, median age at diagnosis was in the range of 36–46 yr, and median follow-up was 15 yr. There were 13 deaths, nine due to cardiovascular disease. Overall SMR for the whole cohort was 4.8 (95% confidence interval, 2.8–8.3) (P < 0001). SMR for vascular disease was 13.8 (7.2–36.5) (P < 0001). For persistent disease (n = 6), SMR was 16 (6.7–38.4) vs. remission (n = 54) SMR of 3.3 (1.7–6.7); after adjustment for age and sex, relative risk of death for persistent disease was 10.7 (2.3–48.6) (P = 0.002). Hypertension and diabetes mellitus were associated with significantly worse survival. 2. Using a random effects model meta-analysis revealed an overall (remission plus persistent disease) SMR of 2.2 (1.45–3.41) (P < 0.001). Pooled SMR was 1.2 (0.45–3.2) (P = not significant) for patients in remission and 5.5 (2.7–11.3) (P = 0.001) for patients with persistent disease. Persistence of disease, older age at diagnosis, and presence of hypertension and diabetes are the main determinants of mortality. Conclusions: Overall mortality in CD is double that of the general population. However, patients with CD in remission fare much better than those with persistence of hypercortisolism, and they appear not to have an increased mortality rate. Hypertension and diabetes mellitus are risk factors for worse outcome. Because diagnosis and treatment of patients are at a young age, much longer follow-up of patients in remission is required before one can be confident that their mortality outcome is no different from that of the general population, especially because cardiovascular risk factors may persist after successful biochemical control of the disease.

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SOM230 in Cushing’s disease complicated by poorly controlled diabetes mellitus

Journal of Endocrinological Investigation ◽

10.1007/bf03345407 ◽

2011 ◽

Vol 34 (9) ◽

pp. 731-732 ◽

Cited By ~ 4

Author(s):

C. Fiorentino ◽

C. Motta ◽

D. T. Wolosinska ◽

S. Monti ◽

F. Mori ◽

...

Keyword(s):

Diabetes Mellitus ◽

Cushing’S Disease ◽

Cushing's Disease

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Voxel-based comparison of brain glucose metabolism between patients with Cushing's disease and healthy subjects

NeuroImage Clinical ◽

10.1016/j.nicl.2017.10.038 ◽

2018 ◽

Vol 17 ◽

pp. 354-358 ◽

Cited By ~ 7

Author(s):

Shuai Liu ◽

Yinyan Wang ◽

Kaibin Xu ◽

Fan Ping ◽

Fang Li ◽

...

Keyword(s):

Glucose Metabolism ◽

Cushing’S Disease ◽

Healthy Subjects ◽

Cushing's Disease ◽

Brain Glucose ◽

Brain Glucose Metabolism

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Molecular-metabolic interaction of pituitary-adrenal axis with adrenocorticotropic and glucocorticoid hormone in Cushing’s disease

10.21203/rs.3.rs-869037/v1 ◽

2021 ◽

Author(s):

Jie Ding ◽

Ming Feng ◽

Marcus Hacker ◽

Li Huo ◽

Xiang Li

Keyword(s):

Glucose Metabolism ◽

Cushing’S Disease ◽

Fdg Pet ◽

Pituitary Adenomas ◽

Cushing's Disease ◽

Molecular Signaling ◽

Adrenal Axis ◽

Pet Ct ◽

Fdg Pet Ct ◽

Pituitary Adrenal Axis

Abstract Purpose This study aimed to investigate C-X-C motif chemokine receptor 4 (CXCR4) molecular signaling pathway and the glucose metabolism of pituitary-adrenal axis in Cushing’s disease (CD) by using 68Ga-pentixafor and 18F-FDG PET/CT. Methods We recruited eleven patients including 4 primary CD, 3 recurrent CD and 4 non-functional pituitary adenoma (NFPA) patients. Both 68Ga-pentixafor PET/CT and 18F-FDG PET/CT were performed. The radio-uptake of pituitary-adrenal axis was correlated with the hormone levels (including serum adrenocorticotropin, serum cortisol and 24-h urine free cortisol). Results The uptake of pituitary adenomas and bilateral adrenals in primary and recurrent CD patients were significantly higher than NFPA patients in 68Ga-pentixafor PET. Besides, hormone level was significantly correlated with the uptake of 68Ga-pentixafor in pituitary adenomas and adrenal tissue but not with glucose metabolism determined by 18F-FDG PET. Conclusions In this pilot study, we found activated CXCR4 molecular signaling rather than glucose metabolism regulation along the pituitary-adrenal axis in CD patients. 68Ga-pentixafor PET/CT might have the potential in detecting ACTH-producing pituitary microadenoma.

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