Metabolic Effects of Growth Hormone Replacement Therapy in Adults - with Special Reference to Insulin Sensitivity

A risk for premature atherosclerosis and increased cardiovascular mortality has been reported in adult patients suffering from growth hormone deficiency (GHD) and receiving conventional hormone substitution without growth hormone (GH) replacement. GHD patients are resistant to insulin, which is a potential risk factor for cardiovascular mortality. Insulin resistance can develop from an unfavourable body composition, which entails increased fat mass and decreased lean body mass due to loss of the stimulating effect of GH on lipolysis and protein synthesis. GH replacement therapy reverses these untoward changes in body composition, but it apparently does not fully restore sensitivity to insulin. The aim of the research underlying this thesis was to examine the role of free fatty acids (FFAs) in GH-induced insulin resistance in adults with GHD. To accomplish that objective, a euglycaemic hyperinsulinaemic clamp and indirect calorimetry techniques were used to study the effect of GH on insulin sensitivity. Impaired insulin-stimulated glucose metabolism was detected after six months of GH therapy, and this negative effect was correlated with enhanced lipolysis and lipid oxidation (paper 1). In two follow-up studies, the GH-induced resistance to insulin could be prevented by using the antilipolytic agent acipimox to inhibit the increase in lipolysis; acipimox was administered during both acute and chronic treatment with GH. Obviously, it was possible that other hormones, such as cortisol could have been involved in the observed effect. However, a confounding influence of cortisol replacement therapy was ruled out by results showing that insulin sensitivity did not differ, regardless of whether cortisol was given before or after the clamp. Our findings supported the theories that stimulation of lipolysis by GH is the main cause of GH-induced insulin resistance, and that co-administration of an antilipolytic agent can block the rise in FFA levels during GH replacement therapy and thereby partially prevents the accompanying deterioration in glucose metabolism

Insulin sensitivity in adults with growth hormone deficiency and effect of growth hormone treatment.

Adult growth hormone deficiency (GHD) is a multifactorial disorder in which pituitary dysfunction associated with pituitary adenomas or their treatment plays a major role. The introduction of recombinant growth hormone (GH) for the treatment of GHD has opened up new treatment avenues but has also raised concerns about possible untoward long-term metabolic effects of GH, such as the potential effect of GH on insulin sensitivity and a deterioration in glucose tolerance. Research has shown that GH induces insulin resistance by the stimulation of lipolysis and a concomitant switch from oxidation of glucose to oxidation of lipids, during both acute and chronic treatment. However, although this is a consistent effect of GH therapy, it does not mean per se that it leads to abnormal glucose tolerance and diabetes mellitus. This article discusses this and other potential long-term metabolic effects of GH, and raises a number of questions to be addressed by future research

Second-line palliative chemotherapy, survival, and prognostic factors in patients with advanced pancreatic cancer

Introduction: Pancreatic cancer is a highly lethal disease with a close association between incidence and mortality. First-line (FL) palliative chemotherapy prolongs survival and alleviates cancer-related symptoms. However, the survival benefit of second-line (SL) treatment is uncertain, as studies fail to consistently show prolonged survival for any given SL treatment, and in the absence of prognostic factors patients will receive a futile treatment. The aim of this study was to examine prognostic factors and survival in patients with pancreatic cancer, with special reference to SL therapy. Material and methods: This retrospective study included all patients with histopathologically verified pancreatic adenocarcinoma who received palliative chemotherapy at Skåne University Hospital and died between 1 Feb 2015 and 31 Dec 2017. Results: During the study period, a total of 170 patients with pancreatic cancer died after receiving palliative chemotherapy. Of these, 72 had received SL treatment after progression on FL treatment. Median overall survival (OS) from the start of SL treatment was 5.0 months (95% CI: 4.0–6.1). Median OS was 2.9 months for patients with performance status 2 at start of SL treatment compared to 5.3 months for patients with performance status 0–1 (p =.03), and 3.5 months (95% CI: 3.0–5.4) in patients with hypoalbuminemia (<36 g/L) at the start of SL therapy compared to 8.0 months (95% CI: 5.3–11.1) for patients with normal albumin levels (p =.009). Weight loss during FL therapy, a doubling of CA 19-9 after FL therapy, and length of progression-free survival during FL treatment were not associated with survival following SL therapy. Conclusion: Poor performance status and hypoalbuminemia are negative prognostic factors for survival on SL palliative treatment in patients with advanced pancreatic cancer. Possible gain in survival should be carefully considered before initiating SL chemotherapy

Palliative sedation via intraosseous vascular access : A safe and feasible way to obtain a vascular access end of life

Intraosseous (IO) access is normally reserved for emergencies and critical care conditions when venous cannulation is not possible. Nonetheless, we present a case of IO insertion to a 56-year-old man, tetraplegic for many years due to progressive spinal muscular atrophy and with refractory suffering. The IO access was used for palliative sedation with propofol in a home care setting. The patient died after 11 days of palliative care, of which the last 4 days were with palliative sedation using an IO cannula as a vascular access. No complications were noted from this route of administration. We advocate the use of IO access in the palliative care of terminal ill patients when a venous cannulation is not possible

Prescription of pain medication among older cancer patients with and without an intellectual disability : A national register study

Background: The longevity for people with intellectual disability (ID) has significantly increased in developed countries during the past decades. Consequently, the incidence of cancer is expected to increase in this group. The aim of the present study was to investigate the prescription of pain medication in older cancer patients with intellectual disability (ID) compared to older patients in the general population, surviving or living with a cancer diagnosis. Methods: This Swedish national registry-based study, included people with ID aged 55 years or older in 2012, and alive at the end of that year (ID cohort, n = 7936). For comparisons, we used a referent cohort, one-to-one matched with the general population by year of birth and sex (gPop cohort, n = 7936). People with at least one diagnosis of cancer during 2002-2012 were identified using the Swedish National Patient Register, resulting in 555 cancer patients with ID and 877 cancer patients from the general population. These two cohorts of cancer patients were compared with respect to prescription of pain medication for the period 2006-2012. Outcome data were aggregated so that each patient was categorized as either having or not having at least one prescription of each investigated drug group during the study period, and relative risks (RRs) for prescription were estimated for prescription in the ID cohort vs the gPop cohort. Results: Cancer patients with ID were less likely than cancer patients in the gPop cohort to have at least one prescription of COX inhibitors (RR 0.61) and weak opioids (RR 0.63). They were, however, more likely to be prescribed paracetamol (RR 1.16), antidepressants (RR 2.09), anxiolytics (RR 2.84), and "other hypnotics, sedatives, and neuroleptics" (RR 1.39). No statistically significant differences between the two cohorts were found for strong opioids, antiepileptics, tricyclic antidepressants, or hypnotics and sedatives. Conclusion: In the studied cohort of older people surviving or living with cancer, prescriptions for pain-treatment was less common in patients with ID compared to the general population. These results may suggest that pain is not sufficiently treated among cancer patients with ID, a situation that most likely would compromise the quality of life in this group

The introduction and experiences of methadone for treatment of cancer pain at a low-resource governmental cancer center in india

Objectives: This study aimed to describe the clinical experience of the health-care professionals (HCPs) responsible for the introduction of methadone, for the treatment of complex cancer pain, at a low-resource hospital in India in a patient-group, burdened by illiteracy, and low socio-economic status. Materials and Methods: Ten HCPs: Four medical doctors, four nurses, one pharmacist, and one hospital administrator were interviewed. The interviews are examined using a qualitative conventional content analysis. Results: The interviews showed a confidence amongst the HCPs, responsible for the safe introduction of methadone in a stressful and low-resource surrounding, to patients with cancer pain and the different aspects of methadone, as initiation, titration, and maintenance of treatment. Conclusion: Introduction of methadone for cancer pain management is safe and feasible although low resources in a challenging hospital setting and care environment

Treatment adherence and abandonment in acute myeloid leukemia in pediatric patients at a low-resource cancer center in India

Aim: One of the causes for lower cure rates in acute childhood leukemia in low- and middle- income countries (LMIC) compared to high-income countries is abandonment from treatment. The International Society of Pediatric Oncology (SIOP) defines abandonment as failure to begin treatment or an absence of 4 weeks during treatment. The aim of this study was to evaluate the extent of abandonment among patients diagnosed with acute myeloid leukemia (AML) at the pediatric ward at a low-resource cancer center in India. Methods: Medical records of all patients, aged 0-15 years, diagnosed with AML between January 1, 2014, and March 31, 2015, at the hospital were reviewed. Age, sex, date of diagnosis, and survival during the short follow-up time after completed treatment and information regarding abandonment were collected. SIOP definition of abandonment was used. Eight patients were diagnosed with AML at the hospital whereof 65 met the inclusion criteria of this study. Results: Of the included 65 patients, 6 died before treatment could be initiated and 3 were referred to palliative care upfront. Thus, 56 patients were offered curatively intended treatment. Of these patients, six refused treatment at this stage and another five abandoned during therapy. Altogether, 11 children abandoned treatment. Conclusion: In this study, the abandonment rate from treatment of childhood AML was 20%, which is in concordance from other studies conducted in India and other LMIC, stating that abandonment is a problem and hindrance when treating with a curative intent