A Thyroid Testing Algorithm: Results of a Pilot Study

We conducted a pilot study to evaluate an algorithm for thyroid function testing consisting of initial serum thyrotropin values, measured by a sensitive immunoradiometric assay (TSH-IRMA) followed by a computer-directed decision to order further studies. We divided 216 outpatients according to their serum TSH-IRMA values as follows: suppressed (\u3c 0.1 mU/L, group I); low (0.1 to 0.4 mU/L, group II); normal (0.5 to 5.0 mU/L, group III); and high (\u3e 5.0 mU/L, group IV). Thyroxine (T4), resin uptake (RU). and free thyroxine index (FTI) tests on groups I, Il, and IV revealed that T4 and RU were normal for most patients in all groups and FTI was normal in 80% of group 1, 93.4 % of group ll, and 93.3% of group IV. All patients in group I were designated hyperthyroid from either an exogenous or endogenous source. All patients in group ll were clinically euthyroid except one; 50% were taking either L-thyroxine or propylthiouracil and 50% had no identifiable thyroid disease. Patients in group IV were hypothyroid. Overall, TSH was more effective in detecting both hypothyroidism and hyperthyroidism than either serum T4, RU ratio, or both combined in FTI since results of these measures fell in the normal range for most patients in all groups. We conclude that a computer-directed algorithm with TSH-IRMA as the initial step is useful in the evaluation of suspected thyroid dysfunction, that T4 and RU may be helpful when TSH is abnormal or borderline, and that suppressed TSH-IRMA values (\u3c0.1 mU/L) but not low values (0.1 to 0.4 mU/L) are consistently associated with hyperthyroidism. Results obtained by use of the algorithm may be misleading in patients with hypothalamic pituitary dysfunction, but its use should reduce the number of redundant and unnecessary T4 and RU tests

Prolonged Remission of Cushing\u27s Disease Following Bromocriptine Therapy

A 33-year-old woman developed hypercorticism of fulminant onset following delivery of a full-term, normal child. An ectopic hormone-producing neoplasm was excluded by extensive studies. Pituitary dependent hypercorticism of intermediate lobe origin was suggested on the basis of onset following pregnancy, failure of Cortisol suppression by high-dose dexamethasone, hyperresponsiveness of prolactin to thyrotropin-releasing hormone stimulation, and reduction in adrenocorticotropin titers following oral administration of bromocriptine. Initial remission of disease achieved with bromocriptine was followed by recurrence on discontinuation of the agent. However, complete remission which occurred following a prolonged course of bromocriptine has persisted for a total of 22 months

Disturbances in Lipid Metabolism Associated with Chylothorax and its Management

Changes in circulating lipid status were studied in a 70-year-old woman during management of chylothorax that included chest drainage, pleuroperitoneal shunting, and a successful thoracic duct ligation. Hypolipidemia with a relative decline in high-density lipoprotein (HDL) cholesterol was apparent at presentation. Following recovery, serum HDL cholesterol rose to the upper limit of normal. Apolipoprotein A-l (Apo A-l) was discordantly raised during the period of pleuroperitoneal shunting. We speculate that diversion of chylomicrons to the liver with subsequent hydrolysis accounted for a release of Apo A-l particles into the circulation at a time when the formation of HDL was compromised by a state of starvation

Pregnancy Following Sequential Bromocriptine Therapy in a Hyperprolactinemic Subject

Regular menses were maintained in a 26-year-old woman with a prolactinoma by sequential bromocriptine therapy given for either five or 14 days of the menstrual cycle. She conceived promptly when desired

Season and vitamin D status are independently associated with glucose homeostasis in pregnancy

Background: Vitamin D status and season are intrinsically linked, and both have been proposed to be associated with glucose homeostasis in pregnancy, with conflicting results. We aimed to determine if exposure to winter and low maternal 25 hydroxyvitamin D (25OHD) in early pregnancy were associated with maternal glucose metabolism.Methods: This is a secondary data analysis of 334 pregnant women enrolled in the ROLO study, Dublin. Serum 25OHD, fasting glucose, insulin and insulin resistance (HOMA-IR) were measured in early (12 weeks' gestation) and late pregnancy (28 weeks' gestation). Season of first antenatal visit was categorised as extended winter (November–April) or extended summer (May–October). Multiple linear regression models, adjusted for confounders, were used for analysis.Results: Those who attended their first antenatal visit in extended winter had lower 25OHD compared to extended summer (32.9 nmol/L vs. 44.1 nmol/L, P < 0.001). Compared to those who attended their first antenatal visit during extended summer, extended winter was associated with increased HOMA-IR in early-pregnancy (46.7%) and late pregnancy (53.7%), independent of 25OHD <30 nmol/L and confounders. Early pregnancy 25OHD <30 nmol/L and extended winter were independently associated with significantly higher fasting glucose in late pregnancy (B = 0.15 and 0.13, respectively).Conclusions: Women who attended their first antenatal visit during the months of extended winter were more likely to have raised insulin resistance in early pregnancy, which had a lasting association to 28 weeks, and was independent of 25OHD. Our novel findings imply that seasonal variation in insulin resistance may not be fully explained by differences in vitamin D status. This could reflect circannual rhythm or seasonal lifestyle behaviours, and requires further exploration.Trial registration: ISRCTN registry, ISRCTN54392969, date of registration: 22/04/2009, retrospectively registered

Nutrition policy: developing scientific recommendations for food-based dietary guidelines for older adults living independently in Ireland

Older adults (≥65 years) are the fastest growing population group. Thus, ensuring nutritional well-being of the ‘over-65s’ to optimise health is critically important. Older adults represent a diverse population – some are fit and healthy, others are frail and many live with chronic conditions. Up to 78% of older Irish adults living independently are overweight or obese. The present paper describes how these issues were accommodated into the development of food-based dietary guidelines for older adults living independently in Ireland. Food-based dietary guidelines previously established for the general adult population served as the basis for developing more specific recommendations appropriate for older adults. Published international reports were used to update nutrient intake goals for older adults, and available Irish data on dietary intakes and nutritional status biomarkers were explored from a population-based study (the National Adult Nutrition Survey; NANS) and two longitudinal cohorts: the Trinity-Ulster and Department of Agriculture (TUDA) and the Irish Longitudinal Study on Ageing (TILDA) studies. Nutrients of public health concern were identified for further examination. While most nutrient intake goals were similar to those for the general adult population, other aspects were identified where nutritional concerns of ageing require more specific food-based dietary guidelines. These include, a more protein-dense diet using high-quality protein foods to preserve muscle mass; weight maintenance in overweight or obese older adults with no health issues and, where weight-loss is required, that lean tissue is preserved; the promotion of fortified foods, particularly as a bioavailable source of B vitamins and the need for vitamin D supplementation

Adaptor protein-2 sigma subunit mutations causing familial hypocalciuric hypercalcaemia type 3 (FHH3) demonstrate genotype-phenotype correlations, codon bias and dominant-negative effects

The adaptor protein-2 sigma subunit (AP2σ2) is pivotal for clathrin-mediated endocytosis of plasma membrane constituents such as the calcium-sensing receptor (CaSR). Mutations of the AP2σ2 Arg15 residue result in familial hypocalciuric hypercalcaemia type 3 (FHH3), a disorder of extracellular calcium (Ca(2+) o) homeostasis. To elucidate the role of AP2σ2 in Ca(2+) o regulation, we investigated 65 FHH probands, without other FHH-associated mutations, for AP2σ2 mutations, characterized their functional consequences and investigated the genetic mechanisms leading to FHH3. AP2σ2 mutations were identified in 17 probands, comprising 5 Arg15Cys, 4 Arg15His and 8 Arg15Leu mutations. A genotype-phenotype correlation was observed with the Arg15Leu mutation leading to marked hypercalcaemia. FHH3 probands harboured additional phenotypes such as cognitive dysfunction. All three FHH3-causing AP2σ2 mutations impaired CaSR signal transduction in a dominant-negative manner. Mutational bias was observed at the AP2σ2 Arg15 residue as other predicted missense substitutions (Arg15Gly, Arg15Pro and Arg15Ser), which also caused CaSR loss-of-function, were not detected in FHH probands, and these mutations were found to reduce the numbers of CaSR-expressing cells. FHH3 probands had significantly greater serum calcium (sCa) and magnesium (sMg) concentrations with reduced urinary calcium to creatinine clearance ratios (CCCR) in comparison with FHH1 probands with CaSR mutations, and a calculated index of sCa × sMg/100 × CCCR, which was ≥ 5.0, had a diagnostic sensitivity and specificity of 83 and 86%, respectively, for FHH3. Thus, our studies demonstrate AP2σ2 mutations to result in a more severe FHH phenotype with genotype-phenotype correlations, and a dominant-negative mechanism of action with mutational bias at the Arg15 residue