Association between premature mortality and hypopituitarism

textObjective: Cushing's disease (CD) is a rare endocrine disorder characterized by excess secretion of ACTH due to a pituitary adenoma. Current treatment options are limited and may pose additional risks. A literature review was conducted to assess the holistic burden of CD. Design: Studies published in English were evaluated to address questions regarding the epidemiology of CD, time to diagnosis, health-related quality of life (HRQoL), treatment outcomes, mortality, prevalence of comorbidities at diagnosis, and reversibility of comorbidities following the treatment. Methods: A two-stage literature search was performed in Medline, EMBASE, and Science Citation Index, using keywords related to the epidemiology, treatment, and outcomes of CD: i) articles published from 2000 to 2012 were identified and ii) an additional hand search (all years) was conducted on the basis of bibliography of identified articles. Results: At the time of diagnosis, 58-85% of patients have hypertension, 32-41% are obese, 20-47% have diabetes mellitus, 50-81% have major depression, 31-50% have osteoporosis, and 38-71% have dyslipidemia. Remission rates following transsphenoidal surgery (TSS) are high when performed by expert pituitary surgeons (rates of 65-90%), but the potential for relapse remains (rates of 5-36%). Although some complications can be partially reversed, time to reversal can take years. The HRQoL of patients with CD also remains severely compromised after remission. Conclusions: These findings highlight the significant burden associated with CD. As current treatment options may not fully reverse the burden of chronic hypercortisolism, there is a need for both improved diagnostic tools to reduce the time to diagnosis and effective therapy, particularly a targeted medical therapy.

/pdf/the-burden-of-cushing-s-disease-clinical-and-health-related-1tw9j9vdtt.pdf

The burden of Cushing's disease : clinical and health-related quality of life aspects

New insights into the role of cortisol and the glucocorticoid receptor in severe depression.

Many studies have demonstrated the role of psychosocial and behavioural risk factors in the aetiology and pathogenesis of cardiovascular disorders. Recently, a new personality construct, the type D or 'distressed' personality, has been proposed. Type D behaviour is characterized by the joint tendency to experience negative emotions and to inhibit these emotions while avoiding social contacts with others. The observation that cardiac patients with type D personality are at increased risk for cardiovascular morbidity and mortality underlines the importance of examining both acute (e.g. major depression) and chronic (e.g. certain personality features) factors in patients at risk for coronary events. Both type D dimensions (negative affectivity and social inhibition) are associated with greater cortisol reactivity to stress. Elevated cortisol may be a mediating factor in the association between type D personality and the increased risk for coronary heart disease and, possibly, other medical disorders. Studies of the effect of age on hypothalamic-pituitary-adrenal (HPA) function in healthy humans have produced inconsistent results. This may relate to a different prevalence of type D individuals in study samples (i.e. some type D individuals may have alterations within the HPA axis that are similar to HPA axis changes in depressed patients). Further studies of the psychological and biological features of type D individuals may help develop treatment approaches to improve the psychological and physical health of individuals with type D personality.

/pdf/type-d-personality-the-heart-stress-and-cortisol-2ai7kyqx9w.pdf

Type D personality : the heart, stress, and cortisol

The Hypopituitary Control and Complications Study is an international surveillance study evaluating efficacy and safety of GH therapy of adult GH-deficient patients in clinical practice. The present report examined baseline data from 1,123 adult onset (AO) and 362 childhood onset (CO) patients, as well as efficacy in 242 patients who had completed 3 yr of GH treatment. At study entry, mean height, body mass index, waist to hip ratio, and lean body mass were significantly (P 60 yr) patients; conversely, decreases in the low-density lipoprotein/HDL ratio were small and not significant in the younger patients but greater and significant in the middle and older age groups. During the 3-yr treatment, 114 (7.7%) patients discontinued, including 9 (0.6%) for tumor recurrences, 9 (0.6%) for neoplasia, and 9 (0.6%) for side effects. Therefore, these observational data showed significant long-term efficacy of adult GH replacement therapy on body composition and lipid profiles and indicate that age is an important predictor of response.

Human growth hormone replacement in adult hypopituitary patients: long-term effects on body composition and lipid status--3-year results from the HypoCCS Database.

Summary Recently, epidemiological evidence has suggested that hypopituitarism with untreated growth hormonedeficiency (GHD) is associated with a high incidence of cardiovascular mortality and that women are particularly at risk. In the present study, the incidence of cardiovascular disease and prevalence of cardiovascular risk factors in 33 such women was assessed and compared with matched controls. A significantly higher number of diagnosed circulatory disorders occurred in the women with hypopituitarism compared with controls, and drug consumption for cardiovascular disorders was also significantly higher in this group. Furthermore, patients with hypopituitarism had a significantly higher waist:hip ratio and a higher ratio of low-density lipoprotein to high-density lipoprotein than controls. Electrocardiogram data showed that hypopituitarism was associated with more episodes of bradycardia. In summary, women with hypopituitarism had an increased incidence of cardiovascular disease and a less favourable risk factor profile compared with matched controls. The data add support to previous studies that have shown increased risks of cardiovascular mortality associated with hypopituitarism with untreated GHD. We conclude that adequate cardiovascular surveillance programmes are required for patients with pituitary insufficiency.

High incidence of cardiovascular disease and increased prevalence of cardiovascular risk factors in women with hypopituitarism not receiving growth hormone treatment: preliminary results.

Hitherto four relevant cohort studies have been published on the life expectancy of patients with hypopituitarism, two from the UK and two from Sweden. In all four studies patients with acromegaly or Cushing's disease were excluded, and patients with GH replacement were not included. A crude meta-analysis, not considering differences in validity of the study designs, gives an overall Relative Risk (RR) of 1.47, with a relatively small 95% confidence interval of 1.27-1.70. The aim of this critical review was to assess whether lacking validity in the design of one or several of these studies indicates that the true RR might be higher or lower than indicated by meta-analyses. A high frequency of cranial irradiation in one of the Swedish cohorts may explain part of the very high observed RR for cerebrovascular mortality, but there remained a 40% risk increase for cardiac diseases that cannot be explained by irradiation. Some other validity problems, especially seen in the UK studies, will result in under-estimation of the true RR, but for others the direction of bias is uncertain due to lacking information in the original publications. According to our view, it is more probable that the observed overall 50% risk increase for vascular mortality is an under-estimation than an over-estimation of the true RR. This analysis is of a qualitative nature, and it is not possible to quantify to what extent the lacking validity may have affected the RR.

Is Vascular Mortality Increased in Hypopituitarism

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High incidence of cardiovascular disease and increased prevalence of cardiovascular risk factors in women with hypopituitarism not receiving growth hormone treatment: preliminary results.

Is Vascular Mortality Increased in Hypopituitarism