Clinical Endocrinology

nền tảng và mục tiêu Viêm tuyến giáp tự miễn là một trong những rối loạn tự miễn phổ biến nhất. Kháng thể tự kháng lại tuyến giáp, trong đó kháng thể peroxidase tuyến giáp (TPO‐Ab) và kháng thể thyroglobulin (Tg‐Ab) là hai loại kháng thể tự miễn thông dụng nhất, thường được phát hiện trong huyết thanh qua các khảo sát dân số. Trong nghiên cứu này, chúng tôi đánh giá xem TPO‐Ab và Tg‐Ab có khả năng phát triển song song hay một trong hai loại này có thể phổ biến hơn trong các phân nhóm dân số.

Objective  The influence of infant feeding method (breast/formula) on growth factor levels could underlie associations of breastfeeding with childhood growth and risk factors for cardiovascular disease. We investigated associations of having been breastfed with serum IGF‐I and IGFBP‐3 in childhood.

Methods  Prospective birth cohort study (subsample of the Avon Longitudinal Study of Parents and Children, UK) based on 871 children born in 1991/1992 who underwent clinical follow‐up and blood tests at age 7–8 years. A total of 488 (56%) children had complete data.

Results  In children with complete data, the age‐ and sex‐standardized IGF‐I levels of those who were partially or exclusively breastfed were 6·1 and 13·8 ng/ml higher, respectively, than those who were never breastfed (increase in IGF‐I levels per category of breastfeeding exclusivity: 7·1 ng/ml; 95% CI: 0·3–13·9; P = 0·04). In models also controlling for birthweight, gestational age, mother's age, and socioeconomic and dietary factors, the breastfeeding–IGF‐I association was attenuated (regression coefficient: 3·3 ng/ml; −4·2–10·7; P = 0·4); further adjustment for IGFBP‐3 made little difference (regression coefficient: 4·1 ng/ml; −2·8–10·9; P = 0·2). There was little evidence for an association between breastfeeding and IGFBP‐3 or the molar ratio IGF‐I/IGFBP‐3.

Conclusions  The positive association between breastfeeding and IGF‐I could be due to residual confounding or to chance. Nevertheless, the magnitude of the fully adjusted effect estimate and the novelty of the association suggest that larger studies should now be conducted to confirm or refute the hypothesis that variations in IGF‐I by infant feeding mode explain associations of breastfeeding with health in later life.

We have previously reported that labetalol infusion increases prolactin (PRL) secretion in hypertensive patients. In an attempt to investigate the site where labetalol stimulates PRL, the drug was infused intravenously (100 mg) into healthy subjects, both under basal conditions and after pretreatment with l‐dopa plus carbidopa (250 mg and 25 mg respectively every 6 h for 1 day), since this regimen has been reported to blunt the PRL responses to centrally acting stimuli. The effects of oral labetalol administration (100 and 200 mg) on PRL was also evaluated. Serum PRL concentration did not change after oral labetalol, whereas it was increased by intravenous drug administration. This effect was completely abolished by pretreatment with l‐dopa plus carbidopa. These findings, though they do not demonstrate the mechanism, suggest that the hyperprolactinaemia induced by labetalol is mediated inside the blood–brain barrier.

Objectives  Adiponectin and ghrelin are associated with adiposity and type 2 diabetes in several studies. We sought to prospectively determine the interaction of adiponectin and ghrelin in the development of adiposity and hyperglycaemia.

Design  Prospective observational study.

Participants  393 community‐dwelling Afro‐Jamaicans (mean age 47 ± 13 years; BMI 27·3 ± 6·3 kg/m²; 63% women) without glucose intolerance at baseline.

Measurements  Anthropometry, fasting plasma glucose, 2‐h plasma glucose, insulin resistance (HOMA‐IR), adiponectin and ghrelin concentrations were measured at baseline and 4·1 ± 0·9 years later. Multivariate analyses were used to explore the associations of HOMA‐IR, adiponectin and ghrelin with weight change and glycaemia.

Results  The mean weight change was 2·6 ± 5·5 kg. There were 114 incident cases of impaired glucose tolerance (IGT) and 35 cases of diabetes mellitus. Adiponectin was positively correlated with age and female sex (P‐values < 0·01). After adjusting for age and sex, adiponectin and ghrelin were significantly correlated with weight at baseline and follow‐up. However, they were not associated with weight change even after further adjustment for baseline weight. Adiponectin, but not ghrelin, was associated with 2‐h glucose concentrations at follow‐up even after adjusting for age, sex, HOMA‐IR and BMI (P = 0·04). In the fully adjusted logistic regression model, adiponectin predicted incident IGT (OR 0·93; 95% CI: 0·87–0·99) and attenuated the effect of BMI on incident IGT.

Conclusions  These longitudinal data show that adiponectin and ghrelin may not be causally involved in the development of obesity. However, adiponectin is independently associated with decreased risk of incident IGT.

background  Ghrelin is a potent GH secretagogue that also plays an important role in appetite and weight regulation. Ghrelin increases hunger and food intake, and its levels decrease after a standard meal or glucose.

objective  To examine the effects of standard oral glucose, lipid and protein loads on ghrelin levels, investigating the possibility that these responses may be modulated by several anthropometric and metabolic factors.

subjects and methods  There were 24 adult nondiabetic subjects (13 men/11 women; mean age 55·3 ± 2·9 years, range 26–74 years). Each participant underwent one or more of the following nutrient loads: (i) a standard oral glucose (75 g) load (n = 18); (ii) an oral lipid load (40 g, with 24 g saturated fat; n = 13); (iii) an oral protein load (40 g; n = 11).

results  Fasting ghrelin levels were negatively related to body mass index (BMI; r =−0·47; P = 0·02), waist circumference (r = −0·58; P = 0·0028), waist/hip ratio (r = −0·56; P = 0·0046), fasting insulin (r = −0·44, P = 0·03), and homeostasis model assessment insulin resistance index (HOMA‐R; r = −0·43, P = 0·034). Glucose load induced a decrease in ghrelin levels (P < 0·0001), and this response was modulated by sex (P < 0·0001), in that levels were significantly higher in females. The presence of obesity affected ghrelin response to glucose (< 0·0217), in that log‐transformed ghrelin levels started to increase back to baseline after its initial decline earlier in obese than in lean subjects. Ghrelin levels after a glucose load were lower over time in subjects with more pronounced insulin resistance (P < 0·0001). Similarly, ghrelin levels decreased significantly following the lipid meal (P = 0·035), and were modulated by HOMA‐R (P = 0·027) and gender (P = 0·029). Protein did not affect ghrelin levels.

conclusions  This study demonstrates that ghrelin levels respond in a different manner to glucose, lipid and protein loads, and are subject to modulation according to gender, obesity and insulin sensitivity.

Today, primary hyperparathyroidism (PHPT) in the developed countries is typically a disease with few or no obvious clinical symptoms. However, even in the asymptomatic cases the endogenous excess of PTH increases bone turnover leading to an insidious reversible loss of cortical and trabecular bone because of an expansion of the remodelling space and an irreversible loss of cortical bone due to increased endocortical resorption. In contrast trabecular bone structure and integrity to a large extent is maintained and there may be a slight periosteal expansion. Most studies have reported decreased bone mineral density (BMD) in PHPT mainly located at cortical sites, whereas sites rich in trabecular bone only show a modest reduction or even a slight increase in BMD. The frequent occurrence of vitamin D insufficiency and deficiency in PHPT and increased plasma FGF23 levels may also contribute to the decrease in BMD. The effect of smoking is unsolved. Epidemiological studies have shown that the relative risk of spine and nonspine fractures is increased in untreated PHPT starting up to 10 years before the diagnosis is made. Successful surgery for PHPT normalizes bone turnover, increases BMD and decreases fracture risk based on larger epidemiological studies. However, 10 years after surgery fracture risk appears to increase again due to an increase in forearm fractures.

There are no randomized controlled studies (RCTs) demonstrating a protective effect of medical treatment on fracture risk in PHPT. Less conclusive studies suggest that vitamin D supplementation may have a beneficial effect on plasma PTH and BMD in vitamin D deficient PHPT patients. Hormone replacement therapy (HRT) and maybe SERM appear to reduce bone turnover and increase BMD. However, their nonskeletal side‐effects preclude their use for this purpose. Bisphosphonates reduce bone turnover and increase BMD in PHPT as in osteoporosis and may be a therapeutical option in selected patients with low BMD. Obviously, there is a need for larger RCTs with fractures as end‐points that appraise this possibility. Calcimimetics reduce plasma calcium and PTH in PHPT but has no beneficial effect on bone turnover or BMD. In symptomatic hypercalcaemic PHPT with low BMD where curative surgery is impossible or contraindicated a combination of a calcimimetic and a bisphosphonate may be an undocumented therapeutical option that needs further evaluation.

Using a recently validated radioimmunoassay, changes in circulating somatostatin have been measured in normal subjects after food (a standard breakfast), and oral and intravenous glucose. After the standard breakfast, a clear and sustained rise in plasma somatostatin was seen in all subjects from a mean value (± 1 SE) of 28 ± 7 pg/ml to a mean peak value, at 60 min of 57 ± 11 pg/ml. When glucose was taken by mouth a significant but smaller rise was seen, but intravenous glucose caused no significant change in plasma somatostatin. A rise in circulating somatostatin after feeding has not previously been demonstrated in normal man and it is suggested that somatostatin may have an important endocrine role in the gut.

In both men and women the pulsatile secretory pattern of LH has been extensively characterized. In the present study we used the algorithm for computation of instantaneous secretory rate (ISR) incorporated into the DETECT program to evaluate the secretory activity of gonadotrophs in vivo. We studied the pulsatile release of LH in four healthy women during four phases of the same menstrual cycle (early and late follicular and luteal phases) and in five healthy men. Computation of ISR permitted us to estimate the frequency and the duration of the secretory events from the gonadotrophs. Samples were collected every 10 min for 6 h. The apparent LH pulsatile frequency during the menstrual cycle varied from 5.0±0.8 (mean±SD) during the early follicular phase (EFP) to 5.3±1.2 peaks/6h during the late follicular phase (LFP), to 3.3±1.0 during early luteal phase (ELP) and to 5.3±0.4 peaks/6h during the late luteal phase (LLP). The mean pulse duration also changed throughout the phases of the cycle (EFP 47.4±13‐2 min; LFP 55‐4±21.6 min; ELP 100±50.4 min; LLP 48.1±11 min). In healthy men the LH pulse frequency was 3.8±1.6 peaks/6h and the duration was 71‐5±35.7 min. When time series were analysed for ISR determination no significant changes were observed between the LH pulse frequency detected on ISR and that observed on plasma concentrations. Conversely, a significant reduction of the duration of the pulses was found when using ISR instead of plasma concentration. The mean pulse duration in ISR does not show any significant difference between men (22±10.3 min) and women in the four different phases of the cycle investigated (EFP = 25.2±12 min; LFP = 28±12 min; ELP = 21.6±11 min; LLP = 20±13 min). In conclusion these data suggest that the duration of the LH secretion by the gonadotrophs is not different in men and in women and implied that LH mass and the rate, but not the duration, of the secretory bursts are regulated by GnRH and that steroids affect LH pulsatile secretion by influencing the frequency and/or amplitude of the pulses.