scholarly journals Comorbidity and cardiovascular risk factors in adult GH deficiency following treatment for Cushing's disease or non-functioning pituitary adenomas during childhood

2012 ◽  
Vol 166 (4) ◽  
pp. 593-600 ◽  
Author(s):  
Oskar Ragnarsson ◽  
Charlotte Höybye ◽  
Peter J Jönsson ◽  
Ulla Feldt-Rasmussen ◽  
Gudmundur Johannsson ◽  
...  
Keyword(s):  
Cardiovascular Risk ◽  
Cushing’S Disease ◽  
Gh Deficiency ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Pituitary Tumour ◽  
Cushing's Disease ◽  
Pituitary Hormone ◽  
Gh Treatment

ObjectiveCushing's disease (CD) and non-functioning pituitary adenoma (NFPA) are rare in paediatric patients. The aim of this study was to describe long-term consequences in adults with GH deficiency (GHD) treated for CD or NFPA during childhood.Design, patients and methodsThis was a retrospective analysis of data from KIMS (Pfizer International Metabolic Database). Background characteristics, anthropometry and comorbidity were studied in 47 patients diagnosed with childhood-onset (CO)-CD and 62 patients with CO-NFPA. Data from 100 ACTH-sufficient patients with CO-idiopathic hypopituitarism (CO-Idio) were used for comparison. Cardiovascular risk profile was analysed at baseline and at 1 year on GH treatment in a subgroup of patients (17 CO-CD, 24 CO-NFPA and 55 CO-Idio) not receiving GH treatment at study entry.ResultsThe median age at diagnosis of pituitary tumour was 14.0 years (range 10–17) in patients with CO-CD and 13.7 years (range 8–17) in CO-NFPA. In addition to GHD, 41% of patients with CO-CD had three or four other pituitary hormone deficiencies compared with 78% of patients with CO-NFPA (P<0.001). Eighty-nine per cent of patients with CO-CD had height SDS lower than 0 compared with 61% of patients with CO-NFPA (P=0.002). Hypertension was more common in CO-CD compared with CO-Idio (23 vs 9%,P=0.018). At 1 year on GH treatment, total- and low-density lipoprotein-cholesterol decreased significantly in CO-CD but not in CO-NFPA.ConclusionAdult patients with GHD following treatment for paediatric CD and NFPA have long-term adverse consequences. Despite more severe hypopituitarism in CO-NFPA, patients with CO-CD have more frequently compromised final stature.

scholarly journals Clinical features of GH deficiency and effects of 3 years of GH replacement in adults with controlled Cushing's disease

2010 ◽  
Vol 162 (4) ◽  
pp. 677-684 ◽  
Author(s):  
Charlotte Höybye ◽  
Oskar Ragnarsson ◽  
Peter J Jönsson ◽  
Maria Koltowska-Häggström ◽  
Peter Trainer ◽  
...  
Keyword(s):  
Clinical Features ◽  
Cushing’S Disease ◽  
Gh Deficiency ◽  
Low Density Lipoprotein ◽  
Group Versus ◽  
Density Lipoprotein ◽  
Cushing's Disease ◽  
Gh Treatment ◽  
Cross Sectional ◽  
Gh Replacement

ObjectivePatients in remission from Cushing's disease (CD) have many clinical features that are difficult to distinguish from those of concomitant GH deficiency (GHD). In this study, we evaluated the features of GHD in a large cohort of controlled CD patients, and assessed the effect of GH treatment.Design and methodsData were obtained from KIMS, the Pfizer International Metabolic Database. A retrospective cross-sectional comparison of background characteristics in unmatched cohorts of patients with CD (n=684, 74% women) and nonfunctioning pituitary adenoma (NFPA;n=2990, 39% women) was conducted. In addition, a longitudinal evaluation of 3 years of GH replacement in a subset of patients with controlled CD (n=322) and NFPA (n=748) matched for age and gender was performed.ResultsThe cross-sectional study showed a significant delay in GHD diagnosis in the CD group, who had a higher prevalence of hypertension, fractures, and diabetes mellitus. In the longitudinal, matched study, the CD group had a better metabolic profile but a poorer quality of life (QoL) at baseline, which was assessed with the disease-specific questionnaire QoL-assessment of GHD in adults. After 3 years of GH treatment (mean dose at 3 years 0.39 mg/day in CD and 0.37 mg/day in NFPA), total and low-density lipoprotein cholesterol decreased, while glucose and HbAlc increased. Improvement in QoL was observed, which was greater in the CD group (−6 CD group versus −5 NFPA group,P<0.01).ConclusionIn untreated GHD, co-morbidities, including impairment of QoL, were more prevalent in controlled CD. Overall, both the groups responded similarly to GH replacement, suggesting that patients with GHD due to CD benefit from GH to the same extent as those with GHD due to NFPA.

scholarly journals PC3 - 142 Gamma Knife Radiosurgery in Patients with Persistent Acromegaly or Cushing’s Disease: Long-Term Risk of Hypopituitarism

2016 ◽  
Vol 43 (S4) ◽  
pp. S22-S22
Author(s):  
O. Cohen-Inbar
Keyword(s):  
Gamma Knife ◽  
Cavernous Sinus ◽  
Cushing’S Disease ◽  
Hormone Replacement ◽  
Gamma Knife Radiosurgery ◽  
Common Adverse Effect ◽  
Cushing's Disease ◽  
Pituitary Hormone

For patient with a recurrent or residual acromegaly or Cushing’s disease (CD) after resection, Gamma knife radiosurgery (GKRS) is often used. Hypopituitarism is the most common adverse effect after GKRS treatment. The paucity of studies with long-term follow up has hampered understanding of the latent risks of hypopituitarism in patients with a Acromegaly or CD. We report the long-term risks of hypopituitarism for patients treated with GKRS for Acromegaly or CD. Methods: From a prospectively created, IRB approved database, we identified all patients with a Acromegaly or CD treated with GKRS at the University of Virginia from 1989 to 2008. Only patients with a minimum endocrine follow up of 60 months were included. The median follow-up is 159.5 months (60.1-278). Thorough radiological and endocrine assessments were performed immediately before GKRS and at regular follow-up intervals. New onset of hypopituitarism was defined as pituitary hormone deficits after GKRS requiring corresponding hormone replacement. Results: 60 patients with either Acromegaly or CD were included. Median tumor volume at time of GKRS was 1.3 cm3 (0.3-13.4), median margin dose was 25 Gy (6-30). GKRS induced new pituitary deficiency occurred in 58.3% (n=35) of patients. Growth Hormone deficiency was most common (28.3%, n=17). The actuarial overall rates of hypopituitarism at 3, 5, and 10 years were 10%, 21.7%, and 53.3%, respectively. The median time to hypopituitarism was 61 months after GKRS (range, 12-160). Cavernous sinus invasion of the tumor was found to correlate with the occurrence of a new or progressive hypopituitarism after GKRS (p=0.018). Conclusions: Delayed hypopituitarism increases as a function of time after radiosurgery. Hormone axes appear to vary in terms of radiosensitivity. Patients with adenoma in the cavernous sinus are more prone to develop loss of pituitary function after GKRS.

scholarly journals Increased Serum Lipoprotein(a) Concentrations after Growth Hormone (GH) Treatment in Patients with Isolated GH Deficiency

1996 ◽  
Vol 33 (4) ◽  
pp. 330-334 ◽  
Author(s):  
Domhnall J O'Halloran ◽  
Gilbert Wieringa ◽  
Agathocles Tsatsoulis ◽  
Stephen M Shalet
Keyword(s):  
Growth Hormone ◽  
Gh Deficiency ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Serum Lipoprotein ◽  
Lipoprotein Cholesterol ◽  
Low Density Lipoprotein Cholesterol ◽  
Gh Treatment ◽  
Lipoprotein A ◽  
Lipid Fractions

Fourteen post-pubertal subjects (11 male, 3 female) with isolated growth hormone (GH) deficiency were treated with a low dose (0·125 U/kg for the first 4 weeks and thereafter 0·025 U/kg/week) daily sc GH injection for 1 year. Fasting blood samples were collected at entry into the study and subsequently at 3 monthly intervals for estimation of serum cholesterol, high-density lipoprotein-cholesterol, low-density lipoprotein-cholesterol and lipoprotein(a) [Lp(a)]. Serum Lp(a) increased progressively during the treatment period (by analysis of variance) and was 41% higher at 12 months ( P < 0·02) despite the fact that five patients showed little or no change. There was no significant change in any of the other lipid fractions. These observations are of concern as Lp(a) is an independent risk factor for cardiovascular disease and should introduce a cautionary note into the enthusiastic efforts to offer GH replacement to all GH deficient adults.

scholarly journals Evaluation of lipid profile and its relationship with blood pressure in patients with Cushing’s disease

2018 ◽  
Vol 7 (5) ◽  
pp. 637-644 ◽  
Author(s):  
Lang Qin ◽  
Xiaoming Zhu ◽  
Xiaoxia Liu ◽  
Meifang Zeng ◽  
Ran Tao ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Lipid Profile ◽  
Cushing’S Disease ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Cushing's Disease ◽  
Independent Association ◽  
Lipids Profile ◽  
Restricted Cubic Splines

Introduction The purpose of the study was to describe lipid profile and explore pathogenetic role of LDL-c on hypertension in patients with Cushing’s disease (CD). Hypertension is a common feature in patients with CD. Previous study found low-density lipoprotein cholesterol (LDL-c) uptake in vascular cells might be involved in vascular remodeling in patients with CD. Therefore, we evaluated the relationship between lipid profile and the blood pressure in patients with CD. Methods This retrospective study included 84 patients referred to Huashan Hospital for the evaluation and diagnosis of CD from January 2012 to December 2013. All subjects had detailed clinical evaluation by the same group of endocrinology specialists to avoid subjective influences. Results We found that high LDL-c patients had significant higher body mass index (BMI), systolic blood pressure (SBP), cholesterol (CHO), triglyceride (TG), and apolipoproteinB (apoB) (P < 0.05). An association was detected between SBP values and lipids profile including CHO, TG, LDL-c, apolipoproteinA (apoA), apoB and lipoprotein(a) (LP(a)). After adjustment for all covariates, the LDL-c remained positively associated with SBP. In patients with or without taking statins, patients with LDL-c ≥3.37 mmol/L had higher SBP than patients with LDL-c <3.37 mmol/L. Then, LDL-c was coded using restricted cubic splines (RCS) function with three knots located at the 5th, 50th and 95th percentiles of the distribution of LDL-c. Compared to individuals with 3.215 mmol/L of LDL-c, individuals with 4.0, 4.5 and 5.0 mmol/L of LDL-c had differences of 3.86, 8.53 and 14.11 mmHg in SBP, respectively. Conclusions An independent association between LDL-c and SBP was found in patients with CD. We speculate that LDL-c may be a pathogenic factor for hypertension in those patients.

scholarly journals Significant GH deficiency after long-term cure by surgery in adult patients with Cushing’s disease

2007 ◽  
Vol 156 (2) ◽  
pp. 233-239 ◽  
Author(s):  
Francesca Pecori Giraldi ◽  
Massimiliano Andrioli ◽  
Laura De Marinis ◽  
Antonio Bianchi ◽  
Antonella Giampietro ◽  
...  
Keyword(s):  
Replacement Therapy ◽  
Cushing’S Disease ◽  
Gh Deficiency ◽  
Pituitary Surgery ◽  
Male Gender ◽  
Cushing's Disease ◽  
Gh Secretion ◽  
Wide Variability ◽  
Acth Secreting

Objective: Impaired GH secretion usually accompanies Cushing’s syndrome and a variable proportion of patients reportedly fail to recover normal GH secretion after successful treatment. This wide variability is most probably due to differences in the treatment (i.e. surgery and/or radiotherapy), timing of patient re-evaluation after surgery and dynamic tests employed to challenge GH secretion, and hinders a precise assessment of risk of GH deficiency after cure. The aim of the present study is to evaluate GH secretory status after long-term cure of Cushing’s disease achieved by surgery alone. Design and methods: We studied 34 patients (27 females and 7 males, age range 21–68 years) formerly affected by Cushing’s disease. Patients were studied 2–20 years (median 3.3 years) following remission of hypercortisolism; all patients underwent transsphenoidal surgery with the removal of an ACTH-secreting adenoma; repeat pituitary surgery for relapse was performed in two patients while bilateral adrenalectomy was necessary in two patients. In all subjects, the GH response to GHRH+arginine stimulation was evaluated. At the time of testing, 13 patients were still on steroid replacement therapy. Results: In long-term surgical remission, 22 patients (65.0%) presented subnormal GH secretion; partial GH deficiency (GH peak <16.5 μg/l) was found in 11 patients and severe GH deficiency (GH peak <9 μg/l) in another 11. Male gender and length of hypercortisolism were risk factors for postsurgical GH deficiency. Conclusions: This study demonstrates the presence of GH deficiency in a high percentage of patients with Cushing’s disease after long-term remission of hypercortisolism obtained by surgery alone. Male gender and length of hypercortisolism are the most significant predictors of postsurgical GH deficiency. This finding is significant as it highlights that even the most favourable therapeutical course, i.e. remission achieved by surgery alone, is accompanied by impaired GH secretion. Assessment of GH secretion is therefore recommended for all patients cured from Cushing’s disease, even if not submitted to radiotherapy. Studies on the clinical impact of GH deficiency and the use of GH replacement therapy seem warranted in patients cured from Cushing’s disease.

scholarly journals Decrease in Carotid Intima-Media Thickness after One Year Growth Hormone (GH) Treatment in Adults with GH Deficiency1

1999 ◽  
Vol 84 (4) ◽  
pp. 1329-1333 ◽  
Author(s):  
Françoise Borson-Chazot ◽  
André Serusclat ◽  
Yadh Kalfallah ◽  
Xavier Ducottet ◽  
Geneviève Sassolas ◽  
...  
Keyword(s):  
Risk Factors ◽  
Cardiovascular Risk ◽  
Cardiovascular Risk Factors ◽  
Gh Deficiency ◽  
Density Lipoprotein ◽  
Intima Media Thickness ◽  
Carotid Intima Media Thickness ◽  
Gh Treatment ◽  
Gh Replacement ◽  
Media Thickness

An increased carotid arterial intima-media thickness (IMT) has been reported in hypopituitary adults untreated for GH deficiency. In the present study, the effect of GH replacement on IMT and cardiovascular risk factors was prospectively investigated, in GH deficiency patients treated at a mean dose of 1 UI/day during 1 yr (n = 22) and 2 yr (n = 11). The IMT measurements were performed by the same experienced physician, and the coefficient of variation (calculated in two control groups) was below 6.5%. IMT at baseline was related to conventional risk factors. After 1 yr GH treatment, IMT decreased from 0.78 ± 0.03 mm to 0.70 ± 0.03 mm (P &lt; 0.001). The decrement was observed in 21 of 22 patients. After 2 yr GH treatment, IMT had stabilized at 0.70 ± 0.04 mm and remained significantly different from baseline values (P &lt; 0.003). GH treatment resulted in a moderate decrease in waist circumference and body fat mass and an increase in VO2 max. Conventional cardiovascular risk factors were unmodified except for a transient 10% decrease in low-density lipoprotein cholesterol at 6 months. The contrast between the limited metabolic effect of treatment and the importance and precocity of the changes in IMT suggests that the decrease in IMT was not exclusively attributable to a reversal in the atherosclerotic process. A direct parietal effect of GH replacement on the arterial wall might also be involved. The consequences, in terms of cardiovascular risk, should be established by randomized prospective trials.

scholarly journals Cardiovascular risk in patients with Cushing’s disease – an interdisciplinary problem

2021 ◽  
Vol 17 (3) ◽  
pp. 197-202
Author(s):  
Agnieszka Jurek ◽  
◽  
Paweł Krzesiński ◽  
Grzegorz Gielerak ◽  
Beata Uziębło-Życzkowska ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Cardiovascular Risk ◽  
Cushing’S Disease ◽  
Treatment Options ◽  
Pituitary Tumour ◽  
Cushing's Disease ◽  
Entire Body ◽  
Systemic Complications ◽  
Cardiovascular Assessment

Cushing’s disease is a chronic endogenous hypercortisolaemia associated with overproduction of adrenocorticotropic hormone by a pituitary adenoma, leading to multiple systemic complications that significantly increase morbidity and mortality, as well as reduce the quality of life as a result of prolonged tissue exposure to excess cortisol. Hypercortisolaemia in Cushing’s disease is associated with significant functional and constitutional disorders of the entire body. The consequences of chronic hypercortisolaemia include haemodynamic disorders associated with excessive vascular contraction and increased blood pressure, obesity, carbohydrate metabolism disorders, dyslipidaemia, and coagulopathies, which may contribute to significant cardiovascular remodelling. Cardiovascular disorders have a particular impact on long-term prognosis and quality of life in Cushing’s disease. If left untreated, Cushing’s disease significantly increases the cardiovascular risk and limits the treatment options for secondary organ complications. Cardiovascular mortality (myocardial infarction, heart failure, stroke) is several times higher in patients with Cushing’s disease than in the general population. Early diagnosis of the corticotropic pituitary tumour, as well as a thorough morphological and functional cardiovascular assessment seem essential in risk stratification. Normalisation of cortisol levels after combined neurosurgical and/or pharmacological treatment reduces mortality and the risk of cardiovascular and respiratory complications. The aim of this study is to present the complexity of clinical problems in patients with Cushing’s disease, who are in a particular need of interdisciplinary care.

scholarly journals Circulating IGF-I levels in monitoring and predicting efficacy during long-term GH treatment of GH-deficient adults

2003 ◽  
pp. 499-509 ◽  
Author(s):  
S Ezzat ◽  
S Fear ◽  
RC Gaillard ◽  
C Gayle ◽  
S Marcovitz ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Body Composition ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Long Term Effects ◽  
Gh Treatment ◽  
Igf I ◽  
Total Fat

OBJECTIVE: To investigate the effects of long-term GH in GH-deficient adults, as predicted by IGF-I levels. METHODS: Patients received GH, 5 microg/kg per day for 1 Month and 10 microg/kg per day for another 12-30 Months. Changes in body composition, cardiac structure/function, serum lipids and quality of life were measured. RESULTS: There was a significant increase in lean body mass (LBM) (2.21 kg; P<0.0001) after 6 Months, which was sustained throughout treatment. A larger increase occurred in males than females (2.97 vs 1.19 kg; P<0.0001). Total fat mass was reduced (2.56 kg; P<0.0001 (3.26 kg males, 1.63 kg females)). Responsiveness to GH varied greatly, but LBM changes correlated with IGF-I changes (P<0.004). Furthermore, thinner patients experienced greater and progressive LBM increases. There was an increase in ejection fraction (3.85+/-9.95%; P=0.0002) after 6 Months, sustained to 18 Months. These cardiac effects were equal for males and females, and did not correlate with IGF-I levels. Serum low-density lipoprotein/high-density lipoprotein ratios decreased within 6 Months, and were sustained thereafter. Quality of life improved significantly after 6 Months, an effect that was sustained/enhanced as treatment continued. No major adverse events were identified. CONCLUSIONS: Improved body composition is both reflected by IGF-I changes and predicted inversely by baseline adiposity. Other effects of GH replacement on cardiac function, dyslipidaemia and quality of life, however, do not correlate with circulating IGF-I concentrations. Our findings validate the importance of sustained GH therapy, but caution on the interpretation of IGF-I levels in monitoring the long-term effects of GH treatment.

scholarly journals Effect of long-term GH replacement therapy on cardiovascular outcomes in isolated GH deficiency compared with multiple pituitary hormone deficiencies: a sub-analysis from the Dutch National Registry of Growth Hormone Treatment in Adults

2014 ◽  
Vol 171 (2) ◽  
pp. 151-160 ◽  
Author(s):  
Christa C van Bunderen ◽  
Carline J van den Dries ◽  
Martijn W Heymans ◽  
Anton A M Franken ◽  
Hans P F Koppeschaar ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Replacement Therapy ◽  
Clinical Presentation ◽  
Gh Deficiency ◽  
National Registry ◽  
Pituitary Hormone ◽  
Gh Treatment ◽  
Gh Replacement

ObjectiveIsolated GH deficiency (IGHD) could provide a model to investigate the influence of GH deficiency per se and the effect of GH replacement therapy without the influence from other pituitary hormone deficiencies or their treatment. The aim of this study is to address the questions about differences between IGHD and multiple pituitary hormone deficiencies (MPHDs) in clinical presentation and in responsiveness to GH treatment.DesignA nationwide surveillance study was carried out to describe the difference in the clinical presentation and responsiveness to GH treatment of patients with IGHD and MPHDs.MethodsThe Dutch National Registry of GH Treatment in Adults was founded in 1998 to gain more insight into long-term efficacy and safety of GH therapy. Out of 2891 enrolled patients, 266 patients with IGHD at the start of GH treatment were identified and compared with 310 patients with MPHDs. Cardiovascular indices will be investigated at baseline and during long-term follow-up, including body composition, lipid profile, glucose metabolism, blood pressure, and morbidity.ResultsPatients with IGHD and MPHDs were demonstrated to be different entities at clinical presentation. Metabolically, patients with MPHDs had a larger waist circumference, lower HDL cholesterol level, and higher triglyceride level. The effect of GH treatment was comparable between patient groups. GH seems to protect against rising lipid levels and blood pressure, even after excluding patients using corresponding concomitant medication. The risk for cardiovascular disease or diabetes mellitus during follow-up was not different between patients with IGHD and MPHDs.ConclusionsPatients with IGHD had a less impaired metabolic profile than patients with MPHDs at baseline. Influence of other pituitary hormone replacement therapies on the effect of GH treatment is not demonstrated.

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