L-thyroxine requirement in patients with autoimmune hypothyroidism and parietal cell antibodies

BACKGROUND: Hypothyroid patients on l-T(4) therapy may require replacement doses exceeding the theoretical needs to normalize serum TSH due to low patient compliance, drugs interference, and malabsorption. OBJECTIVE: We examined whether autoimmune gastritis might cause increased l-T(4) requirement in patients with autoimmune thyroiditis receiving l-T(4) replacement. PATIENTS: We studied 391 patients with clinical or subclinical hypothyroidism from autoimmune thyroiditis who had achieved normal serum TSH concentration (0.3-3.0 microU/ml) under l-T(4) for at least 6 months. Patients were screened for serum parietal cell antibodies (PCA) as a marker of autoimmune gastritis, and the PCA status was correlated with the l-T(4) dose. We also studied a group of 60 patients receiving l-T(4) replacement after total thyroidectomy. RESULTS: PCA-positive (155 of 391) and PCA-negative (236 of 391) patients did not differ for pretherapy serum TSH levels and thyroid volume. The l-T(4) requirement was significantly (P = 0.002) higher in PCA-positive (1.24 +/- 0.40 microg/kg x d) than in PCA-negative patients (1.06 +/- 0.36 microg/kg x d), and a significant positive correlation was found between l-T(4) requirement and serum PCA levels. Among PCA-positive patients, l-T(4) requirement was even higher in those with proven gastritis (1.52 +/- 0.40 microg/kg x d) compared with those without gastric damage (1.15 +/- 0.33 microg/kg x d) (P < 0.0001). The increased l-T(4) requirement was confirmed also in PCA-positive thyroidectomized patients (1.81 +/- 0.27 microg/kg x d) compared with PCA-negative thyroidectomized patients (1.52 +/- 0.24 microg/kg x d). Independent variables affecting l-T(4) requirement were PCA and serum TSH at diagnosis. CONCLUSIONS: Autoimmune gastritis is an additional factor affecting l-T(4) requirement in patients with autoimmune thyroiditis. Serum PCA measurement should be considered in patients with an unexplained high requirement of l-T(4).     

Decreased suppressor T-lymphocytes in autoimmune thyroid diseases detected by monoclonal antibodies

Monoclonal antibodies reacting with cell surface antigens of helper (T4), suppressor (T8) T cells and common T-cell antigen (T3) were used by an immunofluorescence technique to enumerate peripheral T-lymphocytes in 42 patients with Graves' disease and 16 patients with Hashimoto's thyroiditis. The percentages of total T cells (cells which react with anti-T3) and helper/inducer cells (cells which react with anti-T4) among peripheral mononuclear cells in Graves' and Hashimoto's patients were not significantly different from those found in normal controls, except for a decrease in cells which react with anti-T3 in toxic Graves' disease without medication. The most important finding was a decrease in the percentage of cytotoxic/suppressor T cells (cells which react with anti-T8) in toxic Graves' disease and Hashimoto's thyroiditis. In patients with Graves' disease who were hyperthyroid or euthyroid on propylthiouracil treatment and euthyroid after radioactive iodide treatment, the percentage of cells which react with anti-T8 was also decreased, but this did not reach statistical significance. These findings support the hypothesis of defects in suppressor T-lymphocytes in autoimmune thyroid diseases.     

Follow-up of low-risk patients with differentiated thyroid carcinoma: a European perspective

OBJECTIVE: Because differentiated (follicular and papillary) thyroid cancer (DTC) may recur years after initial treatment, the follow-up of patients with DTC is long term. However, this population has changed, with more individuals being discovered at an earlier stage of the disease, so that previous follow-up protocols based mostly on data from high-risk patients no longer apply. We sought to develop an improved protocol for the follow-up of low-risk patients with DTC based on the findings of recent studies. METHODS: We analysed recent literature on the follow-up of DTC. RESULTS: Recent large studies have produced three important findings: (i) in patients with low-risk DTC with no evidence of disease up to the 6- to 12-month follow-up, diagnostic whole-body scan adds no information when serum thyroglobulin (Tg) is undetectable and interference from anti-Tg antibodies is absent; (ii) use of recombinant human thyroid-stimulating hormone to aid Tg measurement is effective and provides greater safety, quality-of-life and work productivity than does levothyroxine withdrawal with its attendant hypothyroidism; and (iii) ultrasonography performed by an experienced operator is the most sensitive means of detecting neck recurrences of DTC. CONCLUSIONS: We present a revised follow-up protocol for low-risk patients taking into account the above findings. This protocol should help clinicians enter a new era of monitoring characterized by greater safety, simplicity, convenience and cost savings.     

Impact of Glucose Tolerance Status,Sex, and Body Size on Glucose Absorption Patterns During OGTTs

OBJECTIVE

We studied whether patterns of glucose absorption during oral glucose tolerance tests (OGTTs) were abnormal in individuals with impaired glucose regulation and whether they were related to sex and body size (height and fat-free mass). We also examined how well differences in insulin sensitivity and β-cell function measured by gold-standard tests were reflected in the corresponding OGTT-derived estimates.

RESEARCH DESIGN AND METHODS

With validated methods, various aspects of glucose absorption were estimated from 12-point, 3-h, 75-g OGTTs in 66 individuals with normal glucose tolerance (NGT), isolated impaired fasting glucose (i-IFG), or isolated impaired glucose tolerance (i-IGT). Insulin sensitivity and β-cell function were measured with the euglycemic-hyperinsulinemic clamp and intravenous glucose tolerance tests, respectively. Surrogate markers of both conditions were calculated from OGTTs.

RESULTS

More rapid glucose absorption (P ≤ 0.036) and reduced late glucose absorption (P ≤ 0.039) were observed in the i-IFG group relative to NGT and i-IGT groups. Women with i-IGT had a lower early glucose absorption than did men with i-IGT (P = 0.041); however, this difference did not persist when differences in body size were taken into account (P > 0.28). Faster glucose absorption was related to higher fasting (P = 0.001) and lower 2-h (P = 0.001) glucose levels and to greater height and fat-free mass (P < 0.001). All OGTT-derived measures of insulin sensitivity, but only one of three measures of β-cell function, reflected the differences for these parameters between those with normal and impaired glucose regulation as measured by gold-standard tests.

CONCLUSIONS

Glucose absorption patterns during an OGTT are significantly related to plasma glucose levels and body size, which should be taken into account when estimating β-cell function from OGTTs in epidemiological studies.Individuals with the prediabetic conditions of impaired fasting glycemia (IFG) and impaired glucose tolerance (IGT) have a higher risk of developing type 2 diabetes than do individuals with normal glucose tolerance (NGT) (1,2). Several studies have shown that men in general have higher fasting plasma glucose (FPG) levels and a higher prevalence of isolated IFG (i-IFG) than do women (3–6). In contrast, women often exhibit higher glucose levels after a standard 75-g oral glucose tolerance test (OGTT) and consequently have a higher prevalence of isolated IGT (i-IGT) (3,4,6) than do men. We and others have previously suggested that the difference in post-OGTT glucose concentration is a consequence of the relatively higher dose of glucose given to women compared with men when seen in relation to their body size (3,4,7). Specifically, it has been shown that there are no sex differences in post-OGTT 2-h plasma glucose (2hPG) levels after adjustment for body height (3,4,7). It has also been suggested, however, that the higher 2hPG levels in women may be attributed to differences in glucose absorption patterns between men and women (8). Healthy women with NGT seem to have lower glucose absorption from the gut during the first hour of an OGTT than do their male counterparts, whereas glucose absorption is higher in women than in men during the last hour of a 3-h OGTT (8). Whether such sex differences in glucose absorption patterns can be explained by differences in body size has not been previously determined.Several factors influence blood glucose concentrations after a meal or an OGTT. In addition to gastric emptying and small intestine digestion and absorption, peripheral insulin sensitivity and the amount of insulin secreted in response to glucose and incretin hormones are major determinants of postprandial or post-OGTT glucose concentration (9–11). The relative contributions of these various factors remains uncertain and controversial (10). More than 20 years ago it was shown that the amount of glucose absorbed in response to varying glucose loads is diminished in individuals with type 2 diabetes (12). Furthermore, a recent study showed that pregnant women with gestational diabetes mellitus had markedly lower glucose absorption than pregnant women with NGT (13). The mechanisms underlying these associations are not well understood. Moreover, it is unclear whether defects in glucose absorption are already present in individuals with slightly elevated blood glucose levels, those with IFG or IGT.Through the use of OGTTs, many methods for estimating β-cell function and insulin sensitivity have been suggested (14–16). These estimates reflect discrete aspects of β-cell function (first phase, second phase, static, dynamic) and more or less specific sites of insulin sensitivity (liver, periphery, whole body), but none of them take into account potential differences in glucose absorption patterns among the tested persons. In this study, we examined whether patterns of glucose absorption during OGTTs differed between individuals with normal and impaired glucose regulation and whether they were related to sex and body size. In addition, we examined how well the differences in insulin sensitivity and β-cell function between normal and impaired glucose regulation as estimated by gold-standard tests were reflected in the corresponding OGTT-derived estimates.     

Follow-up of breast carcinoma

The rationalization of the follow-up schedule for patients treated for breast cancer appears essential due to the high incidence of this disease. The authors retrospectively analyze their series (3,596 patients, from 1971 to 1990) to assess the patterns of both early loco-regional recurrences and distant metastases. Patterns and outcome of local and regional recurrences are reported according to site. The international literature on the subject is reviewed, and the schedule currently employed in the follow-up of breast cancer patients at the Radiotherapy Unit of Florence is reported. Due to the patterns of relapse a more intensive clinical follow-up schedule is suggested during the first 5 years. Less intensive follow-up continues over the whole patients' life span, since failures can occur even after 5 years. Mammography should be repeated every year in the same period to detect eventual homolateral and/or contralateral relapses. Other diagnostic tools should be employed only when symptoms set in. On the ground of the current literature on the subject, no negative impact on survival should be expected from this follow-up schedule.     

Early detection of local recurrences in the follow-up of primary breast cancer

The results of physical examination (PE) in the detection of local recurrences (LR) from breast cancer are reviewed in the follow-up experience of 1139 breast cancer patients. A minimum follow-up time of 5 years was considered. LR accounted for 40% of total first relapses and isolated (without distant metastases) LR represented about 1/3 of total relapses. The chest wall was the most frequent site of LR. The extent of LR was correlated with the probability of associated distant metastases detectable at the time of LR diagnosis, whereas no correlations were found with the presence or absence of subjective symptoms at diagnosis. The mean free interval from primary surgery was 3 months shorter for LR detected in asymptomatic phase than in the symptomatic phase. This difference increased to 5 months for recurrences detected in the first 2 years, when PE controls were repeated every 6 months whereas a smaller difference of 2 months was observed over 2 years with yearly controls. The mean and 5-year actuarial survival was better (75.5 vs. 64.9 months and 54% vs. 40%) for cases detected in the asymptomatic phase than in the symptomatic phase; however, the difference was not statistically significant for the small sample considered and could be even partially due to length biased sampling. On the basis of the reported results, PE should still be recommended as a follow-up test, although further studies are needed to assess its real impact on prognosis.