The prevalence and significance of nonuniform thyroid radio-isotope uptake in patients with Graves' disease.

OBJECTIVE: To evaluate the prevalence and clinical significance of nonuniform technetium (99m Tc) uptake among patients with Graves' disease (GD). DESIGN, PATIENTS AND MEASUREMENTS: Patients with GD, referred between July 2005 and March 2018, had Tc99 - uptake scans and TSH-receptor antibody (TRAb) measured before antithyroid drug (ATD) therapy. Risk of relapse after ATD cessation was monitored until June 2021 and compared between GD patients based on uptake patterns. RESULTS: Of the 276 GD patients (mean age, 49.8 years; 84% female), 25 (9.0%) had nonuniform Tc99 uptake. At diagnosis, individuals with nonuniform uptake were older (mean age of 61.8 vs. 48.5 years, p < .001), had lower mean thyroid hormone levels (free thyroxine: 36.3 vs. 45.4 pmol/L, p = .04 and free triiodothyronine: 10.0 vs. 17.8 pmol/L, p < .001) and median TRAb levels (4.2 vs. 6.6 U/L, p = .04) compared with those with a uniform uptake. Older age was a significant predictor for the presence of nonuniform uptake in GD patients; odds ratio (95% confidence intervals) of 1.07 (1.03 - 1.10). The risk of relapse was similar in both groups after a median (IQR) follow-up of 41 (13-74) months after ATD cessation (56.0% vs. 46.3%, respectively); hazard ratio (95% confidence intervals) of 1.74 (0.96-3.15). CONCLUSIONS: Nonuniform radio-isotope uptake is seen in 1 in 11 patients with GD which could be misdiagnosed as toxic multinodular goitre if TRAb levels are not measured. Treatment of GD patients with nonuniform radio-isotope uptake with ATD therapy as first-line appears to be equally effective as compared with those with uniform uptake. TRAb testing should be the main diagnostic test for patients with suspected GD with radio-labelled uptake scans being reserved for those who are TRAb negative.

Age May Influence the Impact of TRAbs on Thyroid Function and Relapse-Risk in Patients With Graves Disease.

CONTEXT: Thyrotropin receptor antibodies (TRAbs) play a crucial role in the pathogenesis of Graves disease (GD). However, factors that influence the association of TRAbs with thyroid hormones and relapse risk in GD remain unclear. OBJECTIVE: We investigated the associations of TRAbs at diagnosis with thyroid hormones and relapse risk and potential factors that can influence these associations in GD. DESIGN AND SETTING: A prospective study in an endocrine center in England. PATIENTS AND MAIN OUTCOME MEASURES: Three hundred eighty-four consecutive patients with GD who had measurements of TRAbs and thyroid hormones at diagnosis. The association of TRAbs with thyroid hormones and relapse risk was assessed through linear regression and Cox proportional hazard models, adjusted for confounders. RESULTS: TRAbs were nonlinearly associated with thyroid hormones, following a curve with an initial positive slope and a subsequent flattening (P < 0.0001). Higher TRAbs were associated with greater relapse risk [hazard ratio (HR), 1.05 (95% CI, 1.02 to 1.08) per 1-U/L increase]. These associations were modified by age, but not by sex, race, smoking, or thyroid peroxidase antibody levels. In younger participants, increasing TRAbs were associated with higher thyroid hormones and greater relapse risk [HR, 1.13 (95% CI, 1.04 to 1.23) per 1-U/L increase]. In older participants, TRAbs were not associated with thyroid hormones or relapse risk [HR, 0.99 (95% CI, 0.93 to 1.05) per 1-U/L increase. CONCLUSIONS: In GD, age can influence the effect of TRAbs on thyroid function and relapse risk. TRAbs at diagnosis have better predictive value in younger patients with GD.

Metformin improves circulating endothelial cells and endothelial progenitor cells in type 1 diabetes: MERIT study.

BACKGROUND: Type 1 diabetes is associated with increased cardiovascular disease (CVD). Decreased endothelial progenitor cells (EPCs) number plays a pivotal role in reduced endothelial repair and development of CVD. We aimed to determine if cardioprotective effect of metformin is mediated by increasing circulating endothelial progenitor cells (cEPCs), pro-angiogenic cells (PACs) and decreasing circulating endothelial cells (cECs) count whilst maintaining unchanged glycemic control. METHODS: This study was an open label and parallel standard treatment study. Twenty-three type 1 diabetes patients without overt CVD were treated with metformin for 8 weeks (treatment group-TG). They were matched with nine type 1 diabetes patients on standard treatment (SG) and 23 age- and sex-matched healthy volunteers (HC). Insulin dose was adjusted to keep unchanged glycaemic control. cEPCs and cECs counts were determined by flow cytometry using surface markers CD45(dim)CD34(+)VEGFR-2(+) and CD45(dim)CD133(-)CD34(+)CD144(+) respectively. Peripheral blood mononuclear cells were cultured to assess changes in PACs number, function and colony forming units (CFU-Hill's colonies). RESULTS: At baseline TG had lower cEPCs, PACs, CFU-Hills' colonies and PACs adhesion versus HC (p < 0.001-all variables) and higher cECs versus HC (p = 0.03). Metformin improved cEPCs, PACs, CFU-Hill's colonies number, cECs and PACs adhesion (p < 0.05-all variables) to levels seen in HC whilst HbA1c (one-way ANOVA p = 0.78) and glucose variability (average glucose, blood glucose standard deviation, mean amplitude of glycaemic excursion, continuous overall net glycaemic action and area under curve) remained unchanged. No changes were seen in any variables in SG. There was an inverse correlation between CFU-Hill's colonies with cECs. CONCLUSIONS: Metformin has potential cardio-protective effect through improving cEPCs, CFU-Hill's colonies, cECs, PACs count and function independently of hypoglycaemic effect. This finding needs to be confirmed by long term cardiovascular outcome studies in type 1 diabetes. Trial registration ISRCTN26092132.

Upper limb musculoskeletal abnormalities and poor metabolic control in diabetes.

INTRODUCTION: An increased prevalence of musculoskeletal disease is recognised in diabetes and is a common source of disability. It is known to predominantly affect the upper limbs especially the hand and shoulder. The relationship with other complications of diabetes and glycaemic control is uncertain. We designed this study to clarify these relationships, and to assess differences between types 1 and 2 diabetes. METHODS: We identified a group of 96 people with established diabetes and examined them for the presence of locomotor disease focussing on the upper limbs. We recorded the mean HbA1c and the presence of diabetic complications, together with the health assessment questionnaire (HAQ) score. We explored correlations between locomotor disease and these variables using logistic regression. We compared data between type 1 and type 2 diabetics and contrasted the amalgamated data with that of a matched control population of medical out patients using Students t tests. RESULTS: Locomotor disease was present in 75% of diabetics with the upper limb the commonest site for abnormalities. This prevalence was significantly higher than that seen in the controls (53%) [p=0.02]. Shoulder capsulitis (25%), carpal tunnel syndrome (20%), tenosynovitis (29%), limited joint mobility (28%) and Dupuytrens contracture (13%) were the most frequent findings and were much commoner than in controls. Capsulitis usually coexisted with other upper limb abnormalities and best predicted the presence of retinopathy and/or neuropathy. The mean HbA1c was significantly higher in patients with combined shoulder and hand problems (9.1%) than in those with no upper limb problems (8.0%) [p=0.018]. The pattern of results was similar in type 1 and type 2 diabetes, although the prevalence of abnormalities and mean HAQ were significantly greater in type 2 patients, which may be in part a function of their greater mean age. CONCLUSION: Upper limb locomotor abnormalities are very common in diabetes and are associated with worse glycaemic control and more diabetic complications. Assessment of upper limb locomotor disease in diabetes should include an estimate of glycaemic control and a search for other complications.

Common ground: the overlap between Endocrinology and Rheumatology.

A number of medical specialities have witnessed a dramatic change in the provision of in patient care over the last decade. Work has moved into outpatient and Day Unit settings and, more recently, into the community. This has led to the amalgamation of speciality based beds with the perceived threat of loss of independence and potential reduction in training opportunities. In reality, our experience of a combined inpatient ward for Rheumatology and Endocrinology patients has been positive, with increased awareness of the coexistence of certain disorders and a resulting enhanced approach to the delivery of patient care, junior doctor education and clinical research. We would like to share our experience by describing some of the overlapping clinical conditions between these specialities that physicians might wish to consider.