Longitudinal population-based study of progression rates for borderline thyroid-stimulating hormone abnormalities.

BACKGROUND: Current guidelines recommend thyroid-stimulating hormone (TSH) for initial biochemical evaluation of thyroid function, with borderline TSH abnormalities a common finding. The likelihood of a borderline TSH progressing to overt abnormality is not well characterised at the population level. AIMS: To determine risk factors and likelihood for progression of borderline TSH to overt abnormality. METHODS: Population-based retrospective longitudinal data-linkage study for TSH tests performed in Tasmania (1996-2013). Kaplan-Meier methodology was used to summarise conversion time for overt TSH elevation (≥10 mU/L) and overt suppression (≤0.1 mU/L) in patients whose initial TSH was borderline elevated (BeTSH; 4.0-9.99 mU/L) and borderline suppressed (BsTSH; 0.10-0.39 mU/L) respectively. Main outcome measures are the progression from borderline to overt TSH abnormality. RESULTS: A total of 1 296 060 TSH tests was performed on 367 917 patients. Of these, 14 507 (3.9%) patients had BeTSH on initial assessment; mean age 51.4 ± 21.8 years and median TSH of 5.0 mU/L (interquartile range (IQR) 4.4, 5.2). Patients aged ≥80 years were most likely to progress (hazard ratio (HR) = 2.09 compared with age <20 years reference group (95% confidence interval (CI): 1.64, 2.68)). Patients aged 20-39 years had the second-highest rate of progression (HR = 1.49 (95% CI: 1.18, 1.88)). Seven thousand, eight hundred and eighty-three (2.14%) patients had BsTSH; mean age 50.7 ± 22.1 years and median TSH 0.30 mU/L (IQR 0.22, 0.35). Patients aged 60-79 years had the highest rate of progression to overt TSH suppression (HR = 2.47 compared with age <20 years reference group (95% CI: 1.88, 3.22)). CONCLUSIONS: Follow-up intervals for patients with borderline TSH abnormalities should take into account patient age as a progression risk factor.

Case Report: High-concentration Insulin Glargine Overdose Complicated by Hepatic Steatosis.

The use of high-concentration formulations of insulin is becoming more prevalent in the management of patients with diabetes mellitus. Situations of intentional overdose utilizing these agents pose particular challenges because of the altered pharmacology at large doses and the potential complications arising thereof. A patient with type 1 diabetes mellitus self-administered 4050 units of high-concentration (300 units/mL) insulin glargine, in addition to coingestants. The patient subsequently required 7 days of high-dose dextrose infusion in order to avoid hypoglycemia, with no further insulin needed during this period. The patient also developed reversible hepatic steatosis secondary to the prolonged use of high-dose dextrose. Owing to the altered pharmacology of high-concentration insulin glargine when administered at large doses in cases of intentional overdose, patients are likely to require a much longer period of supplemental dextrose support than may otherwise be expected when these agents are used at therapeutic doses. The complication of hepatic injury in the form of steatosis also needs to be considered in these patients, and should prompt the use of adaptive prescriptions of intravenous dextrose where possible.

The Relationship of Gastrinoma in MEN 1 to Helicobacter pylori infection.

CONTEXT: Helicobacter pylori and Multiple Endocrine Neoplasia Type 1 (MEN 1) are risk factors for hypergastrinemia. Gastrin-secreting neoplasms of the foregut mucosa are both a source of, and potentially stimulated by, hypergastrinemia. OBJECTIVE: To determine the relationship between H pylori exposure and the prevalence and severity of hypergastrinemia in patients with MEN 1. DESIGN, SETTING & PATIENTS: Cross-sectional analysis of patients with a common MEN1 gene mutation managed at a tertiary referral hospital that underwent fasting serum gastrin and H pylori serum IgG measurement. INTERVENTION: H pylori IgG and serum gastrin concentration, determined via immunoassay. MAIN OUTCOME MEASURES: The prevalence and severity of hypergastrinemia and its relationship to past H pylori exposure. RESULTS: Thirty-four of 95 (36%) patients were H pylori IgG seropositive. H pylori seropositive patients were significantly more likely to exhibit hypergastrinemia compared with seronegative patients (relative risk [RR] 1.72, P = .023). H pylori exposure also predicted severe hypergastrinemia (RR 3.52, P = .026 and RR 9.37, P = .031 for patients with gastrin ≥ ×4 and ≥ ×8 the upper limit of normal [ULN], respectively). Gastrin concentrations ≥ ×10 ULN occurred exclusively in H pylori seropositive patients (0/61 vs 6/34, P = .001). Serum gastrin and alpha subunit were positively associated in H pylori-exposed (ß = 0.69, P = .001), but not in H pylori-unexposed patients. CONCLUSION: Past H pylori exposure was associated with increased prevalence and severity of hypergastrinemia in MEN 1 patients. Past H pylori-related hypergastrinemia may contribute to the pathogenesis of ongoing gastrin hypersecretion by susceptible foregut neuroendocrine tissues.