Journal of Endocrinological Investigation

Background/Aims: The use of glycated hemoglobin (HbA1c) measurement in gestational diabetes mellitus (GDM) is controversial. Aim of the present study was to determine HbA1c levels in a series of GDM patients, in order to verify the possible contribution of HbA1c to GDM management. Materials/Subjects and methods: The study included 148 caucasian GDM patients. GDM screening was performed between the 24th and the 28th week of gestation by a two-step procedure, according to the 4th and 5th International Workshop Conference on Gestational Diabetes Mellitus recommendations. Exclusion criteria were: preexisting diabetes, corticosteroid therapy, history of asthma or hypertension, known fetal anomaly, history of previous stillbirth, preterm delivery considered to be likely for either maternal disease or fetal conditions. HBA1c was determined by a standard HPLC technique. Results: At GDM diagnosis, all HbA1c levels were ≤6% and the greatest frequency (71/148; 48.0%) of HbA1c values resulted in the range 5.0–5.3%. This frequency increased to 54% before delivery. A significant correlation between HbA1c values at GDM diagnosis and individual BMI prior to conception was observed. The proportion of pregnancies presenting negative outcomes increased progressively with increasing HbA1c levels, from 6.2% (1/16) for HbA1c levels <5% to 18.3% (13/71) for HbA1c 5.0–5.3%, to 37.8% (17/45) in patients with HBA1c levels 5.4–5.6%, to 56.2% (9/16) for HbA1c levels >5.6%. ROC analysis showed that HbA1c at diagnosis and before delivery resulted a good predictor of adverse pregnancy outcome. Conclusions: The present results indicate that HbA1c levels could be of help in predicting adverse pregnancy events.

The effects of the oral hypoglycemic agent, phenformin, were studied on the binding of 125I-insulin to its receptors in IM-9 human cultured lymphocytes. Three h after the addition of 5 μg/ml of phenformin to these cells there was detectable stimulation of 125l-insulin binding; maximal effects were seen after 18 h. A detectable effect of phenformin was seen at 1 μg/ml and maximal effects were seen at 5 μg/ml. These studies demonstrate therefore that phenformin increases the binding of 125l-insulin to human cultured lymphocytes, and raise the possibility that phenformin could act in vivo to regulate insulin receptors.

The antiarrhythmic agent amiodarone was found to inhibit the stimulatory effects of L-triiodothyronine on [3H ] thymidine incorporation into GH3 rat pituitary tumor cells. This inhibitory effect of amiodarone was detected at concentrations as low as 0.5 μM; at 2 μM greater than 50% of the stimulatory effect of L-triiodothyronine was inhibited. The effect of amiodarone was present at all concentrations of L-triiodothyronine tested (50 pM to 10 nM), suggesting that amiodarone acted as a non-competitive antagonist. These studies raise the possibility, therefore, that the effect of amiodarone on thyroid hormone metabolism may be mediated in part by an inhibition of thyroid hormone action at the cellular level.

Objectives: To assess short-term spontaneous evolution of alterations in thyroid function tests in aged hospitalized patients after discharge. Methods: A group of 146 patients (mean age±SD 85.9±6.2 yr) was studied. Serum concentrations of TSH, free T4 (FT4), and free T3 (FT3) were evaluated in every patient both after admission and 1 month after discharge. Results: At entry, both serum TSH [median (interquartile range), 2.19 mU/l (0.89–2.31)] and FT4 (mean±SD, 16.7±3.4 pmol/l) concentrations were into the normal range, whereas serum FT3 concentrations were low (3.3±0.7 pmol/l). After discharge TSH and FT4 concentrations remained normal and FT3 low. However, both serum TSH [2.53 mU/l (1.24–3.33); p<0.01] and FT3 (3.7±1.0 pmol/l; p*#x003C;0.001) concentrations significantly increased. Most patients (no.=124, 84.9%) showed the euthyroid sick syndrome (ESS). After discharge, ESS diminished to 76 (52.1%) subjects. Patients who normalized thyroid function tests showed significantly lower TSH values at entry compared with those who persisted with altered thyroid function tests [1.27 mU/l (0.69–1.89) vs 1.69 mU/l (0.96–2.91), p<0.05]. Logistic regression analysis showed that serum levels of TSH at admission was the only variable negatively related to normalization of thyroid function [odds ratio 0.730; confidence interval 95%, 0.567–0.940; p=0.01). Conclusions: About 35% of aged patients hospitalized for acute illness spontaneously normalize their thyroid function tests 1 month after discharge, mainly due to the correction of ESS. Serum TSH levels at admission seem to be the only variable negatively related to normalization of thyroid function at this time.

Vitamin D deficiency has been associated with multiple chronic diseases, including metabolic disorders such as insulin resistance and type 2 diabetes (T2D). The aim of the study was to analyze the association between validated predicted serum vitamin D status and the risk of developing T2D in a large prospective cohort based on a Mediterranean population. The SUN project is a prospective and dynamic Spanish cohort that gathers university graduates who have answered lifestyle questionnaires, including a validated Food Frequency Questionnaire. The association between predicted serum vitamin D and the risk of T2D was assessed through Cox regression models according to quartiles (Q) of predicted vitamin D at baseline. The models were adjusted for potential confounders and sensitivity analyses were performed to ensure the robustness of our findings. Our study included a total of 18,594 participants and after a total follow-up of 238,078 person-years (median follow-up of 13.5 years), 209 individuals were diagnosed with incident T2D. We found a significant inverse association between predicted levels of serum vitamin D and the risk of developing T2D, after adjusting for potential confounders and performing different sensitivity analyses (hazard ratio Q4 vs. Q1: 0.48, 95% CI 0.26–0.88; p for trend = 0.032). The outcomes suggest that higher levels of vitamin D at baseline may be associated with a reduced risk of developing T2D.

The effect of exogenous prednisone on serum thyrotropin (TSH), thyroxine (T4), and triiodothyronine (T3) concentrations was investigated in four patients with non-functioning thyroid glands receiving T4 replacement therapy. Orally administered prednisone, in a dose of 20 mg each day for nine days, resulted in a significant decrease in mean serum TSH levels (p < 0.01) without significant changes in levels of serum T4, T3, and thyroxine binding globulin (TBG). These findings suggest an inhibitory action of relatively low pharmacologic doses of prednisone on TSH release without changes in circulating thyroid hormone concentrations or inhibition of the peripheral conversion of T4 to T3.

In order to gain further insight into hypopituitarism, that ensues moderate to severe traumatic brain injury (TBI), a group of experts actively working in the field gathered to exchange recent data and concepts. The objective arising from the meeting was to enhance the awareness of both medical specialists and health care administrators on the problem, whose prevalence is higher than previously thought. Guidelines for the diagnosis and management of TBI-mediated hypopituitarism were produced.

Besides anabolic steroids, the most common performance-enhancing hormones are erythropoietin (EPO), insulin, GH, and gonadotropins, mostly indistinguishable from endogenous hormones and with very short half-life. This makes virtually impossible to demonstrate their use by measuring their concentration in the blood or urine. A possible approach to the problem may lie in indirect demonstration through detection of the biological effects of these substances. The finding of an increased hematocrit level is suspicious but not clearly demonstrative of EPO abuse. Very high levels of circulating EPO could be associated with a strong suspicion of doping, when associated to other abnormal parameters, such as Ht, sTFRr, EPO, RDW. The presence of antibodies against the polysaccharide fraction of lateral chains of EPO has been observed only in patients treated with rhEPO. Owing to the pulsatile pattern of GH, particularly during physical exercise, pathologically high values may be found in normal subjects. Therefore, as in the case of EPO, evidence of GH abuse can be gathered only indirectly by detecting the biological effects of its administration. In training subjects GH treatment increased GH, IGF-I, IGFBP-3 and ALS, and decreased IGBP-2. After cessation of treatment IGF-I, IGFBP-3 and ALS approached basal values between 49 and 96 h. Also the bone parameters PICP ICIP, PIUP and osteocalcin increased significantiy. Four days after cessation of treatment, levels of PIIIP and ICTP were still abnormally elevated. In conclusion, increases in IGF-I, IGFBP-3, ALS, PIIIP and ICTP are all indicative of recent GH abuse or of acromegaly.

This study was carried out in order to evaluate clinical usefulness of cross-linked N-telopeptides (NTx) of type I collagen determination, in patients with primary hyperparathyroidism. Twenty-six consecutive patients (6 males and 20 females, aged 56.3±15.0, SD, yrs) with primary hyperparathyroidism were studied in basal conditions and, ten of them, after surgical cure of the disease. Cross-linked collagen peptides were measured by enzyme-linked immunosorbent assay and conventional markers of bone turnover according to standard procedures. Bone densitometry at the lumbar spine and proximal femur was performed using dual-energy X-ray absorptiometry. Bone mineral density was also assessed at the junction of the distal and middle third of the radius and at the ultradistal radius of the non-dominant arm by a dual photon densitometer. Mean urinary NTx values (194.2±121.9 pmoles bone collagen equivalents/pinoles creatinine) were significantly higher (p<0.001) in respect to those found in normal subjects. The mean increase of Z score values of both serum tartrate resistant acid phosphatase activity (1.4±1.8) and the fasting hydroxyproline/creatinine ratio (1.45±2.0) was significantly lower (p<0.02) in respect to that of NTx Z score values (3.3±3.3); the latter values were not significantly different than mean Z score values of serum osteocalcin (4.0±3.9), serum alkaline phosphatase activity (2.6±2.6) and urinary calcium/creatinine ratio (3.2±3.3). We found a significant inverse correlation between NTx values and both lumbar spine (p<0.01) and ultradistal radius bone mineral density (p<0.05); a modest inverse correlation was also observed between serum tartrate resistant acid phosphatase activity and lumbar spine bone mineral density (p<0.04). Following successful adenoma removal, the percentage decrease of both NTx and hydroxyproline was similar in patients with increased bone turnover rate; major discrepancies were observed in patients with normal values of NTx, the telopeptide reduction being greater than that of hydroxyproline. Finally, in a hypercalcemic patient with metastatic parathyroid cancer, telopeptide excretion was shown to be more sensitive in respect to urinary hydroxyproline when evaluating the effects of antiresorptive therapy. Our results seem to indicate that amongst the markers with good sensitivity, NTx is the only one that is inversely related with bone mineral density at two different skeletal sites. This assay should therefore have a place in both the initial screening and medical follow-up of patients with this glandular disorder; in fact, in both situations an increased urinary excretion of this marker should warn about the possibility of hidden bone loss.

Previous studies with hydrochlorothiazide revealed a calcium retaining effect of this substance. The mechanism by what this is done is still matter of controverse discussion. Effects of hydrochlorothiazide on vitamin D metabolism have been reported as well as those on parathyroid function. To further clarify the calcium retaining potency of hydrochlorothiazide (HCTZ) we treated 10 healthy young volunteers for four weeks with × 50 mg HCTZ. In all volunteers we observed a marked decrease in urinary calcium excretion as well as in calcium clearance. Furthermore, we found a slight rise in ionized serum calcium (6.7%) and in intact PTH, as well as a 36% drop in 1,25-(OH)2D3-levels. These effects were reversible after discontinuation of the treatment. No change was observed in urinary cAMP, phosphate excretion, serum anorganic phosphate levels, serum calcitonin and magnesium levels. Data presented here suggest that treatment with HCTZ causes a persistent reduction in calcium excretion through direct tubular effects, inhibits hydroxylation of vitamin D, and does not affect parathyroid function.