First-trimester glycaemic markers as predictors of gestational diabetes and its associated adverse outcomes: A prospective cohort study.

OBJECTIVE: Gestational diabetes mellitus (GDM) is associated with excessive fetal growth in later gestation. Recent data suggest accelerated growth may begin before 28 weeks' gestation when GDM is typically diagnosed. The identification of pregnancies at risk of early fetal growth would enable early intervention. We assessed the use of early pregnancy HbA1c in predicting excessive fetal growth. RESEARCH DESIGN AND METHODS: Women were recruited at antenatal booking from a major maternity unit in the UK. HbA1c was measured at <14 weeks gestation in 1243 women at risk of GDM as defined by UK NICE risk factors of whom 1115 underwent OGTT. Women with previous GDM were excluded. Comprehensive fetal ultrasound was performed at 28 weeks' gestation alongside 75 g OGTT in 976 of these women. GDM was defined using WHO criteria. Pregnancy outcomes were extracted from the regional maternity care database. RESULTS: Two hundred and thirty-six women screened positive for GDM. At diagnosis, GDM pregnancies demonstrated higher adjusted fetal weight percentile than non-GDM pregnancies: (51.8 vs. 46.3, p = 0.008). This was driven by increases in the fetal abdominal circumference percentile in GDM compared with non-GDM pregnancies (55.3 vs. 46.2, p = <0.001). Early pregnancy HbA1c was higher in the GDM versus non-GDM group: (35.7 mmol/mol vs. 32.9 mmol/mol p = <0.01). A threshold for predicting excessive fetal growth was not identified in this cohort. CONCLUSIONS: Accelerated fetal growth is evident prior to the diagnosis of GDM. There remains a need for suitable methods of early identification of pregnancies at high risk for early accelerated fetal growth due to GDM. First-trimester HbA1c was not useful in identifying these pregnancies. NOVELTY STATEMENT: WHAT IS ALREADY KNOWN?: Recent research suggests excessive growth associated with GDM may begin prior to 28 weeks' gestation, when GDM is typically tested for WHAT THIS STUDY HAS FOUND?: Pregnancies affected by GDM are already subject to accelerated fetal growth in comparison to non-GDM pregnancies by way of higher estimated fetal weight and fetal abdominal circumference Neither first-trimester HbA1c nor plasma glucose was useful predictors of these outcomes WHAT ARE THE IMPLICATIONS OF THIS STUDY?: Highlights the emergence of excessive growth prior to detection of GDM Reinforces need for suitable methods of identifying such pregnancies in earlier gestation.

A Case of macro-TSH masquerading as subclinical hypothyroidism.

A 47-year-old man was commenced on levothyroxine following a diagnosis of subclinical hypothyroidism with nonspecific symptoms. Despite increasing doses of levothyroxine, his thyroid-stimulating hormone (TSH) remained elevated and he was referred for further assessment as he was unable to tolerate further titration. On assessment, his thyroid function demonstrated an elevated TSH and elevated free-T4. The initial impression was of iatrogenic thyrotoxicosis, with possible underlying thyroid hormone resistance, TSHoma or assay interference. After discontinuation of levothyroxine, free-T4 normalised but TSH remained elevated. There was a normal response to thyrotropin-releasing hormone (TRH) testing. T3 suppression testing demonstrated free-T4 reduction but persistently high TSH. THRß sequencing was normal. TSH measurement by alternative assays revealed discrepant results. Gel filtration chromatography revealed the presence of high-molecular weight TSH variant alongside normal TSH. Macro-TSH is a rare phenomenon with spuriously elevated TSH and which may mimic subclinical hypothyroidism. Recognition of macro-TSH avoids misdiagnosis and prevents inappropriate treatment.

Twenty-four-hour growth hormone profiling in the assessment of acromegaly.

OBJECTIVES AND BACKGROUND: Recent guidelines recommend insulin-like growth factor (IGF-1), random growth hormone (GH) and nadir GH on an oral glucose tolerance test (OGTT) for assessment of acromegaly. At this Regional Centre, the 24-hour GH profile has also been used. DESIGN PATIENTS AND MEASUREMENTS: We evaluated 57 GH profiles from 34 patients from 2008 to 2012. Samples were drawn every 2 hour and matched with 0800 GH, nadir GH after OGTT and IGF-1. RESULTS: Correlations between the mean 13-point profiles and mean 5-point profile, OGTT nadir and 0800 GH were as follows: r = .99, .99 and .90, respectively (P < .01 for all). The correlation between the mean 13-point profiles and IGF-1 was r = .32 P = .02.Of 5 patients with very high 0800 GH preoperatively (≥20 µg/L), mean 13-point GH reduced by 88%-99% postoperatively. IGF-1 did not normalize in these patients, and all required extra treatment. Preoperatively, all patients had concordant 0800 GH and IGF-1. Postoperatively, 6 patients had 0800 GH <1 µg/L and high IGF-1; only 2 of these had a 13-point mean >1 µg/L, but 5 required further treatment. CONCLUSIONS: Growth hormone profiling is not necessary for assessing the majority of patients with acromegaly if there is confidence in the local IGF-1 assay. When undertaken, a 5-point profile is adequate. In patients with very high 0800 GH, 24-hour profiling was useful in demonstrating partial therapeutic success but did not alter management. Further work is needed to explore the possible role of GH profiling in stratifying patients with discordant IGF-1 and GH results.