Teriparatide as Treatment for Severe Osteoporosis in Lung Transplant Recipients.

Osteoporosis and osteopenia are common in lung transplant (LTx) recipients, with a significantly increased incidence compared to other non-lung solid organ transplant patients. Despite high fracture rates, including in patients treated with antiresorptive medications, there are limited data on the use of anabolic treatments in LTx recipients. We present clinical, biochemical and bone mineral density data for 3 patients with severe osteoporosis treated with teriparatide 20 micrograms daily for 18 months post-LTx. Prednisone doses ranged between 5 and 10 mg daily throughout the treatment period. All patients had previously received zoledronate (last dose 12-24 months prior to teriparatide). Bone turnover was monitored repeatedly during treatment in one patient. Following completion of teriparatide, all patients received consolidation treatment with 4 mg zoledronate. Bone density was measured prior and within 6 to 12 months after completion of teriparatide. All 3 patients experienced an increase in bone density at the lumbar spine (median +12%; range, 2%-14%) and total proximal femur (median +8%, range, 8%-10%). No adverse effects were observed. Given that severe osteoporosis is highly prevalent in LTx patients, teriparatide should be further studied as a treatment in this clinical setting. Our cases suggest it is safe and effective.

Early post-transplant hyperglycemia and post-transplant diabetes mellitus following heart transplantation.

INTRODUCTION: Heart transplantation is an important treatment for end-stage heart failure. Early post-transplant hyperglycemia (EPTH) and post-transplant diabetes mellitus (PTDM) are common following heart transplantation and are associated with increased morbidity and mortality. AREAS COVERED: This review summarizes the clinical characteristics, diagnosis, and treatment of EPTH and PTDM in cardiac transplant patients, incorporating findings from non-cardiac solid organ transplant studies where relevant due to limited heart-specific research. EXPERT OPINION: EPTH following heart transplantation is common yet understudied and is associated with the later development of PTDM. PTDM is associated with adverse outcomes including infection, renal dysfunction, microvascular disease, and an increased risk of re-transplantation and mortality. Risk factors for EPTH include the post-operative immunosuppression regimen, recipient and donor age, body mass index, infections, and chronic inflammation. Early insulin treatment is recommended for EPTH, whereas PTDM management is varied and includes lifestyle modification, anti-glycemic agents, and insulin. Given the emerging evidence on the transplant benefits associated with effective glucose control, and the cardioprotective potential of newer anti-glycemic agents, further focus on the management of EPTH and PTDM within heart transplant recipients is imperative.

Glucagon-like Peptide-1 Receptor Agonist Treatment With Semaglutide in Type 1 Diabetes.

The efficacy of glucagon-like peptide-1 receptor agonists in type 2 diabetes is well established, but their role in type 1 diabetes (T1DM) is less clear. A 36-year-old woman with a 27-year history of T1DM and undetectable c-peptide presented for review of weight management, with body mass index 29.3 kg/m2. A previous trial of dapagliflozin led to no improvement in weight or glycemic control. Semaglutide was introduced (0.25 mg weekly increased to 0.5 mg weekly) and was well tolerated. After 6 months, weight had decreased by 16 kg and insulin dose by 36%. Despite less insulin, hemoglobin A1c improved, with reduced glycemic variability and no increase in hypoglycemia. Semaglutide may exert significant metabolic benefits in patients with established T1DM, even where c-peptide is no longer detectable. This case supports the need for a dedicated trial examining potential benefits of semaglutide in T1DM.

Safety and tolerability of sodium-glucose cotransporter-2 inhibitors in bridge-to-transplant patients supported with centrifugal-flow left ventricular assist devices.

BACKGROUND: The safety and tolerability of sodium-glucose cotransporter-2 inhibitors (SGLT2i) in patients with end-stage heart failure supported with left-ventricular-assist-devices (LVADs), irrespective of diabetes mellitus, is not known. METHODS: A retrospective analysis of 31 outpatients implanted with LVADs as bridge-to-transplant (BTT) was conducted. Patients with biventricular support, aged under 18 years, who were discharged from the index hospitalisation, or were prescribed SGLT2i prior to their first outpatient clinic were excluded. Patient demographics, laboratory studies, pump haemodynamic and adverse event data was collected. RESULTS: Sixteen (51.6%) of 31 patients were prescribed SGLT2i over median 101.5 days (37.5-190.8). No patients discontinued SGLT2i use or reported attributable adverse symptoms. No significant differences between patients prescribed SGLT2i compared to those SGLT2i-naïve were seen in: [1] renal function; [2] weight; [3] mean arterial pressure. There were numerically lower infection-related (n = 4 vs 7, HR 0.32 (0.08-1.28), p = 0.11) and haemocompatibility-related (n = 3 vs 4, HR 0.52 (0.09-2.83), p = 0.45) adverse events in the SGLT2i group, albeit non-significant. CONCLUSIONS: We found SGLT2i to be safe and well-tolerated in the BTT LVAD cohort with no significant difference in rates of infection or haemocompatibility-related adverse events with SGLT2i use. Larger studies will inform further beneficial effects of SGLT2i prescription in this cohort.

Metabolic Sequelae of Everolimus Treatment After Cardiac Transplant: A Hypothesis-Generating Study.

BACKGROUND: Although modern immunosuppressants improve survival post-transplant, they are associated with long-term metabolic complications, such as post-transplant diabetes mellitus (PTDM). Calcineurin inhibitor-sparing regimens using everolimus attenuate some complications such as left ventricular hypertrophy. However, the metabolic effects of everolimus following transplant are less clear. METHODS: Post-hoc analysis to compare PTDM and other metabolic outcomes in participants of a randomised open-label clinical trial of low-dose everolimus and tacrolimus versus standard-dose tacrolimus in heart transplant recipients (RADTAC1 study). RESULTS: There were 39 participants in the trial; mean follow-up was 6.4±1.5 years. There was a high rate of pre-existing diabetes (26%) and newly diagnosed PTDM (36%) during follow-up. Half the patients who developed PTDM in the everolimus-tacrolimus group (n=4/8) ceased diabetes medications during follow-up, which was not observed in patients on standard tacrolimus (n=0/6). In the first 12 months there was a higher use of non-insulin treatment for diabetes in the everolimus-tacrolimus group compared to the standard tacrolimus group. CONCLUSIONS: This study suggests that treatment with everolimus may be associated with improved glycaemic control of PTDM relative to treatment with standard doses of calcineurin inhibitor. These findings should be further studied in prospective randomised trials.

Diabetes medication following heart transplantation: a focus on novel cardioprotective therapies-a joint review from endocrinologists and cardiologists.

There is accumulating evidence that novel glucose-lowering agents infer potent cardiovascular and renal benefits. Therefore, it is imperative to reassess the management of post-transplant diabetes mellitus and consider the role of newer agents. With improved transplant-related survival and high prevalence of post-transplant diabetes, management of long-term complications such as diabetes are increasingly important. There are limited guidelines to assist in choice of appropriate agents after solid organ transplantation. Traditional therapies including insulin and sulfonylureas may still have a role; however, other agents should be considered prior. The evidence of novel glucose-lowering agents in post-transplant care is limited, and most studies have focused on kidney transplant recipients. While there are some parallels between renal and cardiac transplant recipients, the potential cardiovascular benefits, particularly on cardiac fibrosis are unique to cardiac transplantation. The treatment of diabetes, with a focus on additional cardiac and renal benefits, needs to be brought to the forefront of post-transplant care with incorporation of recent evidence outside of transplantation. The role for novel glucose-lowering agents in cardiac transplant recipients will be explored, with a summary of available evidence.

Female Representation: Australian Diabetes and Endocrinology Societies.

Background: Endocrinology has one of the highest proportions of female specialists and trainees, however females have traditionally been underrepresented in leadership positions and as speakers at scientific meetings. Hypothesis: Females would represent less than half of invited speakers (plenary, symposium sessions) at endocrinology conferences and in leadership positions of endocrinology societies. Method: An audit of Australian diabetes and endocrinology societies and their respective annual scientific meetings between 2016 - 2020. Analysis of the gender of conference speakers across oral, symposium and plenary sessions, session chairs, program organising committees and society committees. Results: A total of 1638 speakers (females 856, 52.3%) across 550.4 hours (females 273.6, 49.7%) of presentations at the conferences were identified. Among plenary sessions of all 3 societies there were more male (61%) than female speakers. A total of 608 session chairs were identified, with 313 (51.5%) females. The majority of organising committee members (n=116) were female (56%), however the representation across each organising committee varied. There was a low proportion of society female council members (39% female). Conclusion: There was an equal representation of females and males as conference speakers and session chairs. However, there was an underrepresentation of women in more prestigious roles of plenary speakers and society council members. We implore conscious efforts to address this disparity.

Hyperprolactinemia and association with prolactinoma in transwomen receiving gender affirming hormone treatment.

PURPOSE: Approximately 0.6% of the adult population identifies as transgender. Gender affirming hormone treatment (GAHT) is required by many to develop physical and psychological characteristics that align with their gender identity. Once started, GAHT is continued lifelong and at higher doses than conventionally used in the management of cis-gendered women. Hyperprolactinemia and pituitary lactotroph adenomas are a potential consequence of GAHT. METHODS: Case series of three transfeminine women with hyperprolactinemia during gender affirming hormone treatment. RESULTS: We report two new cases of prolactinoma and one new case of marked hyperprolactinemia without pituitary adenoma associated with GAHT in transwomen at different stages of hormonal transition. Novel aspects of our case series include the first report of a prolactinoma in a transwoman associated with spironolactone and the alternate progestin medroxyprogesterone acetate and documentation of the transient changes in prolactin from baseline (prior to feminizing hormones) in two transwomen which demonstrate that marked hyperprolactinemia develops early in the course of GAHT. CONCLUSIONS: Transgender women receiving GAHT may be at increased risk for prolactinoma. As the number of transwomen seeking GAHT continues to increase, hyperprolactinemia and GAHT-associated prolactinoma may become an increasingly important component of endocrine practice. Screening of prolactin levels in transwomen receiving GAHT could potentially prevent morbidity related to hyperprolactinemia and allow for early detection of prolactin secreting pituitary adenomas.