Reduced and more appropriate referrals of patients with type 2 diabetes using liver stiffness measurement compared to FIB-4.

BACKGROUND: Fatty liver disease and fibrosis are common in patients with type 2 diabetes mellitus (T2DM). Recently published European Association for the Study of the Liver guidelines have suggested screening such patients using liver stiffness measurement (LSM) or fibrosis-4 index (FIB-4) to exclude advanced fibrosis. AIMS: We initiated a screening programme at the diabetes out-patient clinic to assess the reliability of the suggested approaches and resulting referrals. METHODS: In this prospective study, consecutive patients attending for T2DM review at an Irish level 3 (district general) hospital between September and November 2021 were screened for liver fibrosis using LSM and had their FIB-4 calculated. The first 100 patients with valid LSM measurements were included in the analysis. RESULTS: Referral rates to the hepatology clinic varied by modality used. If FIB-4 ≥ 1.3 criterion was used, the referral rate to the hepatology clinic was 45%; using LSM < 8 kPa to rule out advanced fibrosis resulted in 34% referral rate; using LSM ≥ 10 kPa to suggest probable compensated advanced chronic liver disease reduced referral rates to 15%. Combining FIB-4 with LSM in a two-step algorithm led to missed potentially significant liver disease in large numbers. 47% patients with LSM ≥ 8 kPa and 33% with LSM ≥ 10 kPa had FIB-4 < 1.3. CONCLUSIONS: Screening of patients with T2DM using LSM alone rather than FIB-4 leads to reduced numbers of, and more appropriate, referrals to the hepatology clinic. Shifting from an exclusion (LSM < 8 kPa) to an inclusion based (LSM ≥ 10 kPa) approach may lessen the potential of screening to overwhelm hepatology services.

Retrospective national cohort study of pregnancy outcomes for women with type 1 and type 2 diabetes mellitus in Republic of Ireland.

AIM: Report the outcomes of pregnant women with type 1 and type 2 diabetes and to identify modifiable and non-modifiable factors associated with poor outcomes. METHODS: Retrospective analysis of pregnancy preparedness, pregnancy care and outcomes in the Republic of Ireland from 2015 to 2020 and subsequent multivariate analysis. RESULTS: In total 1104 pregnancies were included. Less than one third attended pre-pregnancy care (PPC), mean first trimester haemoglobin A1c was 7.2 ± 3.6% (55.5 ± 15.7 mmol/mol) and 52% received pre-conceptual folic acid. Poor preparation translated into poorer pregnancy outcomes. Livebirth rates (80%) were comparable to the background population however stillbirth rates were 8.7/1000 (four times the national rate). Congenital anomalies occurred in 42.5/1000 births (1.5 times the background rate). More than half of infants were large for gestational age and 47% were admitted to critical care. Multivariate analyses showed strong associations between non-attendance at PPC, poor glycaemic control and critical care admission (adjusted odds ratio of 1.68 (1.48-1.96) and 1.61 (1.43-1.86), p < 0.05 respectively) for women with type 1 diabetes. Smoking and teratogenic medications were also associated with critical care admission and hypertensive disorders of pregnancy. CONCLUSION: Pregnancy outcomes in women with diabetes are suboptimal. Significant effort is needed to optimize the modifiable factors identified in this study.

Subacute thyroiditis post-Pfizer-BioNTech mRNA vaccination for COVID-19.

SUMMARY: There is emerging evidence of an association between COVID-19 vaccination and subacute thyroiditis. We present the case of a 42-year-old female healthcare worker who was diagnosed with subacute thyroiditis 4 days after receiving her second dose of Pfizer-BioNTech vaccine. Her clinical course followed the classical pattern for thyroiditis with spontaneous return to euthyroidism at 6 months post-presentation. The autoimmune/inflammatory syndrome induced by adjuvants has been implicated as a cause of autoimmune conditions post-vaccination and is a potential mechanism for subacute thyroiditis in our case. LEARNING POINTS: Subacute thyroiditis should be considered in all patients who receive any kind of vaccine for COVID-19 and subsequently develop symptoms or signs of hyperthyroidism or neck pain. Subacute thyroiditis is a self-limiting condition, and recognising it is important as no specific thyroid treatment (antithyroid drugs or thyroid hormone replacement) is necessary for most patients. The autoimmune/inflammatory syndrome induced by adjuvants may be an under-recognised cause of endocrinopathies and should particularly be considered post-vaccination.

A Rare Presentation of Adrenocortical Carcinoma.

An adrenal incidentaloma is a mass found incidentally on radiological imaging performed for other reasons. The prevalence of these incidentalomas increases with age, and they all must be evaluated to determine if they are benign or malignant and if they are functioning or non-functioning. A 71-year-old female presented with sub-acute bilateral lower limb pitting edema and dyspnoea. Imaging showed an 8 cm smoothly defined heterogeneous right adrenal mass and a number of low attenuation lesions throughout the liver. This case report describes a rare presentation of adrenocortical carcinoma due to an adrenal incidentaloma identified on imaging in a patient presenting with bilateral lower limb edema. The laboratory and imaging evaluation of these incidentalomas are also discussed.

PYY is a negative regulator of bone mass and strength.

OBJECTIVE: Bone loss in anorexia nervosa and following bariatric surgery is associated with an elevated circulating concentration of the gastrointestinal, anorexigenic hormone, peptide YY (PYY). Selective deletion of the PYY receptor Y1R in osteoblasts or Y2R in the hypothalamus results in high bone mass, but deletion of PYY in mice has resulted in conflicting skeletal phenotypes leading to uncertainty regarding its role in the regulation of bone mass. As PYY analogs are under development for treatment of obesity, we aimed to clarify the relationship between PYY and bone mass. METHODS: The skeletal phenotype of Pyy knockout (KO) mice was investigated during growth (postnatal day P14) and adulthood (P70 and P186) using X-ray microradiography, micro-CT, back-scattered electron scanning electron microscopy (BSE-SEM), histomorphometry and biomechanical testing. RESULTS: Bones from juvenile and Pyy KO mice were longer (P < 0.001), with decreased bone mineral content (P < 0.001). Whereas, bones from adult Pyy KO mice had increased bone mineral content (P < 0.05) with increased mineralisation of both cortical (P < 0.001) and trabecular (P < 0.001) compartments. Long bones from adult Pyy KO mice were stronger (maximum load P < 0.001), with increased stiffness (P < 0.01) and toughness (P < 0.05) compared to wild-type (WT) control mice despite increased cortical vascularity and porosity (P < 0.001). The increased bone mass and strength in Pyy KO mice resulted from increases in trabecular (P < 0.01) and cortical bone formation (P < 0.05). CONCLUSIONS: These findings demonstrate that PYY acts as a negative regulator of osteoblastic bone formation, implicating increased PYY levels in the pathogenesis of bone loss during anorexia or following bariatric surgery.

The skeletal consequences of thyrotoxicosis.

Euthyroid status is essential for normal skeletal development and the maintenance of adult bone structure and strength. Established thyrotoxicosis has long been recognised as a cause of high bone turnover osteoporosis and fracture but more recent studies have suggested that subclinical hyperthyroidism and long-term suppressive doses of thyroxine (T4) may also result in decreased bone mineral density (BMD) and an increased risk of fragility fracture, particularly in postmenopausal women. Furthermore, large population studies of euthyroid individuals have demonstrated that a hypothalamic-pituitary-thyroid axis set point at the upper end of the normal reference range is associated with reduced BMD and increased fracture susceptibility. Despite these findings, the cellular and molecular mechanisms of thyroid hormone action in bone remain controversial and incompletely understood. In this review, we discuss the role of thyroid hormones in bone and the skeletal consequences of hyperthyroidism.