Focal Seizures in a Patient With Chronic Basal Ganglia Calcifications Secondary to Idiopathic Primary Hypoparathyroidism.

Patients with hypoparathyroidism can present with concurrent basal ganglia calcifications (BGCs). The exact pathogenesis is unknown, although it is thought to relate to calcium-phosphate deposition from chronic hypocalcemia and hyperphosphatemia. We present the case of a 65-year-old man with known idiopathic primary hypoparathyroidism and concurrent extensive BGC. Thirty years after diagnosis, he presented with focal seizures despite a decade of stable intracranial calcifications on imaging. Serum calcium, phosphate, 25-hydroxyvitamin D, and parathyroid hormone levels were well controlled during this period. He was commenced on lifelong levetiracetam with subsequent seizure remission. Given the scarcity of literature surrounding focal seizures and BGC, it is essential to raise awareness in this area.

Variants in ZFX are associated with an X-linked neurodevelopmental disorder with recurrent facial gestalt.

Pathogenic variants in multiple genes on the X chromosome have been implicated in syndromic and non-syndromic intellectual disability disorders. ZFX on Xp22.11 encodes a transcription factor that has been linked to diverse processes including oncogenesis and development, but germline variants have not been characterized in association with disease. Here, we present clinical and molecular characterization of 18 individuals with germline ZFX variants. Exome or genome sequencing revealed 11 variants in 18 subjects (14 males and 4 females) from 16 unrelated families. Four missense variants were identified in 11 subjects, with seven truncation variants in the remaining individuals. Clinical findings included developmental delay/intellectual disability, behavioral abnormalities, hypotonia, and congenital anomalies. Overlapping and recurrent facial features were identified in all subjects, including thickening and medial broadening of eyebrows, variations in the shape of the face, external eye abnormalities, smooth and/or long philtrum, and ear abnormalities. Hyperparathyroidism was found in four families with missense variants, and enrichment of different tumor types was observed. In molecular studies, DNA-binding domain variants elicited differential expression of a small set of target genes relative to wild-type ZFX in cultured cells, suggesting a gain or loss of transcriptional activity. Additionally, a zebrafish model of ZFX loss displayed an altered behavioral phenotype, providing additional evidence for the functional significance of ZFX. Our clinical and experimental data support that variants in ZFX are associated with an X-linked intellectual disability syndrome characterized by a recurrent facial gestalt, neurocognitive and behavioral abnormalities, and an increased risk for congenital anomalies and hyperparathyroidism.

Physician-Authored Feedback in a Type 2 Diabetes Self-management App: Acceptability Study.

BACKGROUND: Type 2 diabetes (T2D) is increasingly prevalent in society, in part because of behavioral issues, with sedentary behavior, reduced exercise, and the consumption of foods with a high glycemic index being major contributors. There is evidence for the efficacy of mobile apps in promoting behavior change and lifestyle improvements in people with T2D. Many mobile phone apps help to monitor the condition of people with T2D and inform them about their health. Some of these digital interventions involve patients using apps on their own or in conjunction with health care professionals. OBJECTIVE: This study aimed to test the acceptability of receiving app-based, daily physician feedback for patients with T2D that is informed by the continuous monitoring of their activity, food choices, and glucose profiles, with the aim of encouraging healthier behavior. The GLOOK! app was designed and developed by an academic research team and pilot-tested at an Australian public hospital. METHODS: A total of 15 patients diagnosed with T2D wore a glucose monitor and an Apple Watch for 12 days. The uploaded data were integrated into the GLOOK! app on the patients' smartphones, which also enabled the recording of activity and consumed food. A physician provided daily feedback to each individual through the app based on their data from each of the 12 days. At the beginning and end of the study, data were collected on vital signs, anthropometry, hemoglobin A1c level, fructosamine level, and fasting lipids level. Participants were also interviewed at the beginning and end of the study to assess the acceptability of the intervention and its potential impact on promoting positive behavior change. RESULTS: Over the 12 days of the study, there was a significant reduction of 0.22% (P=.004) in hemoglobin A1c level. There were favorable changes in fructosamine and lipid fractions; however, none reached significance. There was also a fall of 0.65 kg in body weight and falls in blood pressure and pulse rate that did not reach significance. Patient feedback on the GLOOK! system was positive. Of the 15 participants, 13 (87%) were enthusiastic about continuing to use the app system if some usability and reliability aspects were improved. All participants regarded the personalized physician feedback as supportive and helpful in understanding their own health behavior. Of the 15 participants, 4 (27%) felt that using the system encouraged long-term behavior changes. CONCLUSIONS: A mobile app system that provides people with T2D daily, physician-generated, personalized feedback can produce favorable changes in glycemic and cardiovascular risk parameters-even in the short term-and encourage better self-management of their condition. Study participants found the experience of using the mobile app system acceptable and were motivated to establish longer-term lifestyle improvements through behavior changes.

A pilot clinical study to Evaluate Liraglutide-mediated Anti-platelet activity in patients with type-2 Diabetes (ELAID study).

BACKGROUND: Liraglutide is an effective treatment for the management of type 2 diabetes mellitus (T2DM). In addition to glycemic control and potential cardioprotective effects, recent studies suggest a possible role for liraglutide in the inhibition of platelet reactivity, further attenuating atherothrombotic risk in patients with T2DM. We evaluated the in-vivo antiplatelet effect of liraglutide in T2DM patients without macrovascular disease or concurrent anti-platelet therapy. METHODS: A double-blind, placebo-controlled pilot study of 16 T2DM patients, 51-69 y/o, (mean age 60.4 y/o, 63.0% male) randomised to receive liraglutide (1.8 mg/day) or placebo (saline) for 6 months was conducted. Platelet aggregation studies at baseline and after initiation of the study intervention: days 1, 7, and 14 and months 1, 3 and 6 were performed. RESULTS: Liraglutide (n = 7) and placebo (n = 9) treated patients demonstrated normal platelet aggregation responses although transient and significant attenuation in maximum slope of platelet aggregation in response to collagen (p ≤ 0.05), arachidonic acid (p ≤ 0.05) and ADP (p ≤ 0.02) was observed in liraglutide compared to placebo treated patients in the first week. CONCLUSIONS: In this pilot study of patients with T2DM liraglutide treatment was associated with a significant, early and transient decrease in maximum slope of platelet aggregation. The clinical significance of this effect is currently unknown and may warrant further investigation. CLINICAL TRIAL REGISTRATION NUMBER: UTN 1111-1181-9567.

Evaluation of an alternative skeletal muscle index for skeletal muscle mass assessment in a group of Australian women.

BACKGROUND: Sarcopenia is assessed by several methods, including dual energy X-ray absorptiometry (DEXA), which provide a height-adjusted skeletal muscle index (H-SMI). A SMI 2 standard deviation below the young adult reference [1] combined with low muscle strength or performance is used to identify sarcopenia. As height declines with age, H-SMI may underestimate low skeletal muscle mass in the older population. Our study aims to evaluate an alternative SMI and to examine its relationship to grip strength in a group of Australian women. METHODS: Women from two cohorts were analysed. 2041 women had body composition data (112 had calf circumference, 137 had leg length measurements) without grip strength, and 49 women had grip strength measured (40 had body composition data).The relationship between leg length-adjusted SMI (LL-SMI) to grip strength and anthropometric variables to skeletal muscle mass by DEXA were examined by linear regression analysis. RESULTS: Cohort 1: Older women were compared to younger women. Older women were shorter but leg length did not differ between different age groups. H-SMI was not different between groups (P = 0.528). LL-SMI was lower in older women (P = 0.002). Cohort 2: LL-SMI was significantly associated with grip strength (P = 0.048) after adjustment for age. CONCLUSION: Older women were shorter, while leg length did not differ from the younger group. H-SMI may obscure and may underestimate low muscle mass in older individuals. LL-SMI may be a better measure of skeletal muscle mass in older individuals. These alternate SMI would benefit from further exploration in older individuals.

Sarcopenia in women with hip fracture: A comparison of hormonal biomarkers and their relationship to skeletal muscle mass and function.

OBJECTIVES: Sarcopenia is a decline in skeletal muscle mass and function. It is associated with adverse outcomes and increased mortality. Sarcopenia is also reported to be prevalent in the hip fracture population. Our aims in this study are to compare the hormonal profile in women with hip fracture to controls, and to assess the relationship between hormonal biomarkers to skeletal muscle mass and function in these women. METHODS: A cross sectional study was performed enrolling women above age 60 years old with hip fracture as a study group. For comparison healthy women from the community were recruited. Peripheral blood samples were obtained for analysis of hormonal profiles. Measures of skeletal muscle mass and function by muscle area on computed tomography, dual energy X-ray absorptiometry, bioelectrical impedance analysis, and grip strength was performed. RESULTS: A high proportion of sarcopenic individuals were detected in the hip fracture group (60%). Women with hip fracture compared to controls were older (P = 0.073), had lower serum albumin levels (P < 0.001), serum insulin-like growth factor-1 (IGF-1) (P < 0.001), insulin-like growth factor binding protein -3 (IGFBP-3) (P < 0.001), free testosterone levels (P = 0.001), and impaired beta cell function by homeostasis model assessment (HOMA beta) (P = 0.038). CONCLUSIONS: There is a high proportion of sarcopenic individuals in the hip fracture group. Lowered serum levels of IGF-1 and IGFBP-3, HOMA beta cell function, and free testosterone levels were detected in this group and may serve as potential biomarkers of sarcopenia.

Ambulatory Blood Pressure Monitoring in Type 2 Diabetes Mellitus: A Cross-sectional Study.

BACKGROUND: Ambulatory blood pressure (ABP) monitoring in type 2 diabetes (T2DM) is not yet routine in clinical practice. OBJECTIVES: To quantify abnormal ABP patterns and their associations with diabetic complications, and to assess the reliability of office blood pressure (OBP) for assessing BP in T2DM. METHODS: In a cross-sectional study, eligible patients with T2DM underwent OBP and 24- hour ABP measurements under standardized conditions and screening for diabetic complications. RESULTS: 56 patients (mean age 67 ± 10 years, males 50%) completed assessment. 43(73%) had a known history of hypertension. Non-dipping and nocturnal systolic hypertension (SHT) were prevalent in 31(55%) and 32(57%) patients, respectively. 16(29%) demonstrated masked phenomenon, but only three (7%) demonstrated white coat effect. Nocturnal SHT had a significant association with composite microvascular complications independent of daytime systolic BP control (adjusted odds ratio (OR) 1.72(CI 1.41-4.25). There was no association between other abnormal ABP patterns and diabetic complications. The sensitivity and specificity of OBP for diagnosing HT or assessing BP control was 59% and 68% respectively. The positive and negative predictive values were 74% and 52% respectively. CONCLUSION: Non-dipping, reverse dipping, nocturnal SHT and masked phenomenon are highly prevalent in patients with T2DM with or without a known history of hypertension. Compared with non-dipping, nocturnal SHT may be a stronger predictor of end organ damage. The reliability of OBP for assessing BP in T2DM is only modest. Patients with T2DM are likely to benefit from routine ABP monitoring.

Subclinical hypothyroidism during pregnancy: the Melbourne public hospitals consensus.

BACKGROUND: Interest in potential adverse outcomes associated with maternal subclinical hypothyroidism (normal free T4, elevated thyroid-stimulating hormone (TSH)) has increased significantly over recent years. In turn, the frequency of maternal thyroid function testing has risen, despite universal thyroid function screening not being recommended, leading to a marked increase in referrals to obstetric endocrinology clinics. In 2017 the American Thyroid Association revised their diagnostic and management guidelines. Although welcome, these new guidelines contain recommendations that may cause confusion in clinical practice. AIM: To ensure uniform practice in the diagnosis and management of subclinical hypothyroidism in pregnancy across all Melbourne public hospitals. METHODS: Endocrinology and obstetric representatives from all Melbourne public hospital networks reviewed the 2017 American Thyroid Association guidelines and other relevant literature to develop a consensus for diagnosing and treating subclinical hypothyroidism during pregnancy in Melbourne. The consensus guidelines were then referred to the Endocrine Society of Australia for comment and endorsement. RESULTS: Consensus was achieved and the guidelines were endorsed by the Council of the Endocrine Society of Australia. Trimester and assay-specific TSH reference intervals derived from healthy local populations should be used, where available. When unavailable, a TSH cut-off of 4 mU/L (replacing the previously recommended 2.5 mU/L) should be used to initiate treatment, irrespective of thyroid auto-antibody status. The recommended starting dose of levothyroxine is 50 µg daily, with a therapeutic TSH target of 0.1-2.5 mU/L. Levothyroxine should generally be ceased after delivery, with some exceptions. Hospitals will ensure smooth transfer of care back to the woman's general practitioner with clear documentation of pregnancy thyroid management and a recommended plan for follow-up. CONCLUSION: Fewer women will be classified as having subclinical hypothyroidism during pregnancy, which is likely to lead to reductions in emotional stress, hospital visits, repeated blood tests and financial costs. Uniform clinical practice will occur across Melbourne.

Mitochondrial disease: an uncommon but important cause of diabetes mellitus

Mitochondrial diseases are rare, heterogeneous conditions affecting organs dependent on high aerobic metabolism. Presenting symptoms and signs vary depending on the mutation and mutant protein load. Diabetes mellitus is the most common endocrinopathy, and recognition of these patients is important due to its impact on management and screening of family members. In particular, glycemic management differs in these patients: the use of metformin is avoided because of the risk of lactic acidosis. We describe a patient who presented with gradual weight loss and an acute presentation of hyperglycemia complicated by the superior mesenteric artery syndrome. His maternal history of diabetes and deafness and a personal history of hearing impairment led to the diagnosis of a mitochondrial disorder. Learning points: •• The constellation of diabetes, multi-organ involvement and maternal inheritance should prompt consideration of a mitochondrial disorder. •• Mitochondrial encephalomyopathy, lactic acidosis, stroke-like episodes (MELAS) and maternally inherited diabetes and deafness (MIDD) are the most common mitochondrial diabetes disorders caused by a mutation in m.3243A>G in 80% of cases. •• Metformin should be avoided due to the risk of lactic acidosis. •• There is more rapid progression to insulin therapy and higher prevalence of diabetic complications compared to type 2 diabetes. •• Diagnosis of a mitochondrial disorder leads to family screening, education and surveillance for future complications. •• Superior mesenteric artery syndrome, an uncommon but important cause of intestinal pseudo-obstruction in cases of significant weight loss, has been reported in MELAS patients.

Efficacy and safety of methionine aminopeptidase 2 inhibition in type 2 diabetes: a randomised, placebo-controlled clinical trial.

AIMS/HYPOTHESIS: This multicentre randomised double-blind placebo-controlled clinical trial assessed the efficacy and safety of a methionine aminopeptidase 2 (MetAP2) inhibitor, beloranib, in individuals with obesity (BMI ≥30 kg/m2) and type 2 diabetes (HbA1c 53-97 mmol/mol [7-11%] and fasting glucose <15.6 mmol/l). METHODS: Participants were randomised (via a centralised interactive web response system) to placebo, 1.2 or 1.8 mg beloranib s.c. twice weekly for 26 weeks. Participants, investigators and the sponsor were blinded to group assignment. The primary endpoint was the change in weight from baseline to week 26. The trial was terminated early when beloranib development was stopped because of an imbalance of venous thromboembolism events in beloranib-treated individuals vs placebo that became evident during late-stage development of the drug. RESULTS: In total, 153 participants were randomised, 51 to placebo, 52 to 1.2 mg beloranib and 50 to 1.8 mg beloranib. In participants who completed week 26, the least squares mean ± SE weight change (baseline 111 kg) was -3.1 ± 1.2% with placebo (n = 22) vs -13.5 ± 1.1% and -12.7 ± 1.3% with 1.2 and 1.8 mg beloranib, respectively (n = 25; n = 19; p < 0.0001). The change in HbA1c (baseline 67 mmol/mol [8.3%]) was -6.6 ± 2.2 mmol/mol (-0.6 ± 0.2%) with placebo vs -21.9 ± 2.2 mmol/mol (-2.0 ± 0.2%) or -21.9 ± 3.3 mmol/mol (-2.0 ± 0.3%) with 1.2 or 1.8 mg beloranib (p < 0.0001), respectively. The most common beloranib adverse events were sleep related. One beloranib-treated participant experienced a non-fatal pulmonary embolism. CONCLUSIONS/INTERPRETATION: MetAP2 inhibitors represent a novel mechanism for producing meaningful weight loss and improvement in HbA1c. TRIAL REGISTRATION: ClinicalTrials.gov NCT02324491 FUNDING: The study was funded by Zafgen, Inc.

Leukocyte Telomere Length in the Neonatal Offspring of Mothers with Gestational and Pre-Gestational Diabetes.

AIMS: Telomeres undergo shortening with cell division, accelerated by increased oxidative stress. We aimed to demonstrate shortened telomeres in the offspring of mothers who have diabetes as a consequence of exposure to increased oxidative stress during intrauterine development. METHODS: We examined the level of glycaemia (glucose, HbA1c, fructosamine), oxidative stress (lipid peroxidation) and the levels of antioxidant enzymes (Superoxide dismutase (SOD) and Selenium dependent glutathione peroxidase) and correlate these findings with mean telomere length (TL) in maternal and foetal blood in groups of pregnant women with pre-gestational diabetes (PGD), gestational diabetes (GD) and a euglycaemic control group. RESULTS: Foetal and maternal glucose, maternal HbA1c, and foetal insulin and C-peptide were higher in the PGD group with the GD group being intermediate. Markers of oxidative stress did not vary between groups with the exception of foetal SOD activity that was highest in the GD group. There were no detectable differences in maternal or foetal TL between study groups. An exploratory analysis looking at correlations between glycaemic and oxidative stress parameters and TL revealed a negative correlation between maternal and foetal glucose and TL across the whole study population. This relationship held for the short-term marker of glycaemic control, fructosamine. CONCLUSIONS: We were unable to show significant telomere shortening in the offspring of mothers with PGD or GD. Exploratory analysis revealed a relationship between foetal TL and short-term glycaemia particularly in PGD. It is possible that increased telomerase activity can compensate for long-term increased oxidative stress but not for short-term dysglycaemia.

Building the evidence for integrated care for type 2 diabetes: a pilot study.

Integrated care models have the potential to reduce fragmentation in the health system and improve outcomes for people with type 2 diabetes. A pilot evaluation of an integrated care model for people with type 2 diabetes in Melbourne, Australia, is reported on. Two studies were conducted: (1) a 6-month pilot randomised controlled trial (n=56) evaluating the impact of the integrated care model relative to hospital outpatient clinics; and (2) a cross-sectional study (n=92) of patients attending the two services. The primary outcome was diabetes-specific distress; secondary outcomes were perceived quality of diabetes care, diabetes-specific self-efficacy and glycated haemoglobin (HbA1c). There was no effect of service setting on diabetes-specific distress. Participants from the integrated care setting perceived the quality of diabetes care to be higher than did participants from the hospital clinics. Significant HbA1c improvements were observed over time, but with no effect of service setting. The model holds promise for people with type 2 diabetes who need more specialist/multidisciplinary care than can be provided in primary care. Patients' evaluations of the quality of diabetes care received at the integrated care service are very positive, which is likely to be one of the key strengths of the integrated model.

Somatic Mutations of FOXE1 in Papillary Thyroid Cancer.

BACKGROUND: Population-based studies have demonstrated an association of single nucleotide polymorphisms close to the thyroid transcription factor forkhead box E1 (FOXE1) gene with thyroid cancer. The dysregulation of forkhead proteins is increasingly recognized to play a role in the development and progression of cancer. The objective of the study was to seek to identify novel mutations in FOXE1 in papillary thyroid cancer (PTC) and to assess the effect of these mutations on protein expression and transcriptional function on FOXE1 responsive promoters. METHODS: The study was conducted at two tertiary referral hospitals. The coding region of FOXE1 was sequenced in tissue-derived DNA or RNA from 120 patients with PTC and 110 patients with multinodular goiter (MNG). In vitro studies were performed to examine the protein expression and transcriptional function of FOXE1 mutants. A molecular model of the forkhead domain (FHD) of FOXE1 was generated using the SWISS-MODEL online server with the three-dimensional structure of FOXD3 as a template. RESULTS: Three somatic missense mutations were detected in PTC resulting in the amino acid substitutions P54Q, K95Q, and L112F. One additional mutation was detected in a MNG (G140R). In vitro studies demonstrated marked impairment in transcriptional activation by all four FOXE1 mutants, which was not explained by differences in protein expression. Molecular modeling localized three of the mutations to highly conserved regions of the FHD. CONCLUSIONS: We have identified novel somatic mutations of FOXE1 in PTC. Mutational inactivation of FOXE1 is an uncommon event in thyroid tumors but may contribute to thyroid carcinogenesis and dedifferentiation in concert with other oncogenic drivers.

Improving Self-Monitoring of Blood Glucose among Adults with Type 1 Diabetes: Results of the Mobile™ Study.

INTRODUCTION: The objective of this study was to determine whether people with type 1 diabetes are more likely to self-monitor their blood glucose (SMBG) as recommended by their diabetes health care professional using the Accu-Chek Mobile™ (F. Hoffmann-La Roche AG, Basel, Switzerland) monitoring system compared to the Freestyle Optium™ (Abbott, North Chicago, IL, USA). METHODS: Thirty-five participants with type 1 diabetes participating in a randomized cross-over study were assigned to monitor their blood glucose levels for a 3-month period using the Accu-Chek Mobile or the Freestyle Optium monitoring system and then to cross-over to the alternative device. After completion of the 6-month cross-over period, participants were invited to select their meter of choice and were followed for a further 3 months. RESULTS: SMBG frequency increased in both groups but participants monitored significantly more often using the Accu-Chek Mobile meter (frequency SMBG/week median: 19 vs. 10, P = 0.04). After 3 months using each meter, 77% of participants indicated a preference for the Accu-Chek Mobile meter. Monitoring frequency in this group remained higher than baseline during the 3-month post-cross-over follow-up period. CONCLUSION: Our results indicate that the Accu-Chek Mobile meter improves SMBG frequency. After experience of both systems, Accu-Chek Mobile was the meter of choice for the majority of participants in this study. FUNDING: Roche Diabetes Care Unconditional Education Grant.

Nuclear receptor expression in human differentiated thyroid tumors.

BACKGROUND: Nuclear receptors (NRs) play a key role in endocrine signaling and metabolism and are important therapeutic targets in a number of hormone-dependent malignancies. Studies on the role of NRs in thyroid cancer are limited. OBJECTIVE: The objective of the study was to examine systematically the expression of the 48 human NRs in a series of benign and malignant thyroid tissues. Within the papillary carcinoma cohort, we sought to determine if NR expression differed significantly by BRAF mutation status. PATIENTS AND METHODS: RNA was isolated from multinodular goiter (MNG; n=6), papillary carcinoma (PTC, n=14), follicular carcinoma (FC; n=5), and Hürthle cell carcinoma (HCC; n=7). The 48 human NRs were profiled in this panel by quantitative real time polymerase chain reaction. Protein expression for selected NRs (Rev-erbα and LXR-ß) was examined by immunohistochemistry (IHC) on tissue microarrays comprising benign and malignant thyroid tissues. RESULTS: Across all groups of benign and malignant thyroid tissue, there was prominent expression of LXR-ß and ROR-γ. Key findings in PTC were marked overexpression of RXR-γ and Rev-erbα compared to MNG. Within the PTC cohort, when BRAF(V600E) tumors were compared with wild type BRAF, there was relative upregulation of RXR-γ and Rev-erbα and downregulation of AR, ERR-γ, and ROR-γ. In FC, EAR-2 was overexpressed, while PPAR-α and PPAR-δ were underexpressed compared to MNG. The NR expression profile of HCC was distinct, characterized by significant downregulation of a wide range of NRs. IHC for Rev-erbα and LXR-ß localized protein expression to the tumor cells. Moderate to strong Rev-erbα immunostaining was seen in 22 out of 23 PTC, and, overall, staining was stronger than in the benign group. CONCLUSIONS: These results represent the first systematic examination of NR expression in thyroid cancer. Our finding of tumor-specific patterns of NR expression, as well as significant differences in NR expression between BRAF(V600E) and wild type BRAF PTC, provides a basis for further mechanistic studies and highlights potential novel therapeutic targets for this malignancy.

Bone and metabolic health in patients with non-metastatic prostate cancer who are receiving androgen deprivation therapy.

Androgen deprivation therapy (ADT) in men with prostate cancer increases the risk of osteoporotic fractures, type 2 diabetes and, possibly, cardiovascular events. There is considerable uncertainty about the risk-benefit ratio of ADT in non-palliative treatment; the benefits of ADT in treating non-metastatic prostate cancer need to be carefully weighed against the risks of ADT-induced adverse events. Baseline assessment of bone health at the initiation of ADT should include measurement of bone mineral density (BMD) by dual energy x-ray absorptiometry and, in men with osteopaenia, a thoracolumbar spine x-ray. General measures to prevent bone loss, including regular physical activity, as well as ensuring calcium and vitamin D sufficiency, should be instituted routinely. All men with a previous minimal trauma fracture should receive pharmacological therapy unless contraindicated; for those who have not sustained a minimal trauma fracture, treatment is advised if the BMD T score is ≤ - 2.0, or if the 10-year risk of a major osteoporotic fracture exceeds 20%. Men with prostate cancer who are receiving ADT should be closely monitored for weight gain and diabetes; intensive lifestyle intervention is recommended to prevent ADT-induced weight gain and insulin resistance. Management of the metabolic sequelae of ADT includes optimal reduction of cardiovascular risk factors, with particular attention to weight, blood pressure, lipid profile, smoking cessation, and glycaemic control.

Review of the genetics of thyroid tumours: diagnostic and prognostic implications.

BACKGROUND: Thyroid nodules are common, but only a small proportion harbour malignancy. Despite this, the frequency of thyroid cancer is on the increase and thyroid malignancy is the most common endocrine malignancy. Preoperative diagnosis is based on ultrasound and radionucleotide imaging as well as the fine-needle aspiration biopsy (FNAB). These biopsies yield a large proportion of indeterminate results due to inadequate material for cytological diagnosis, or due to the cytological similarity of FAs and follicular carcinomas. Recent advances in the understanding of the molecular pathogenesis of thyroid malignancy have led to the detection of characteristic genetic alterations in FNABs. This technology has the potential to increase the specificity of this test, combining cytological with genetic testing to reduce the number of indeterminate results, thereby reducing the number of thyroidectomies performed for benign disease. METHODS: This review examines the evidence for the presence of the common genetic alterations in thyroid cancer and outlines the pathological and clinical correlations of these mutations. The practicality and utility of measuring these genetic alterations in FNAB specimens is also outlined as well as the potential for these tests to alter primary management and follow-up of patients with nodular thyroid disease. CONCLUSION: It is likely that a combination of molecular testing and cytological examination of FNAB specimens will prove to be the most efficient and specific method of diagnosing thyroid cancer preoperatively.