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Autoimmune thyroid diseases (AITDs) can be associated with type 1 diabetes (DM1). The prevalence of serum antibodies against thyroid hormones (THAb) in subjects with autoimmune diseases other than DM1 is increasing. No data are available for DM1.The objectives were evaluate the rate of associated AITD; the rate of positiveness for serum THAb; the panel of THAb based on thyroid hormone interaction and on Ig class; and the association of AITD alone, THAb alone, or AITD plus THAb with diabetes-related complications.This was an observational, prospective study with 6-year (2005-2011) follow-up.The setting was an outpatient diabetes clinic.Fifty-two consecutive subjects (53.8% males; mean age, 37.4 ± 7.4 y; diabetes duration, 19.9 ± 8.2 y) with DM1. All participants completed the study.Main outcome measures were AITD rate; THAb positivity according to hormone interaction and Ig class; association of AITD and THAb with diabetes-related complications.AITD rate increased from baseline (34.6%) to follow-up (38.5%). Subjects with DM1 had a high prevalence of THAb (92.3%). The presence of AITD at baseline was associated with subsequent development of macroangiopathy (0 vs 33% at baseline and follow-up, respectively; P = .029). Some THAb patterns, the majority having T3 binding in common, were associated with the progression and development of diabetes-related complications.THAb synthesis in DM1 might be driven by increased glycosylation of thyroglobulin. Anti T3-THAb may cause a relative "tissue hypothyroidism" by sequestering thyroid hormone, this at least partially contributing to worsening diabetes-related vascular complications. In a clinical setting THAb positivity could identify subjects more likely to develop diabetes complications.

Proton-pump inhibitors (PPIs) impair tablet levothyroxine (LT4) intestinal absorption by increasing the gastric pH and decreasing LT4 dissolution in the stomach.The purpose of this study was to verify whether a liquid formulation of LT4 would correct LT4 malabsorption induced by PPIs.This was a prospective observational cohort study. The study was conducted from 2012 to 2013, and the mean duration of the follow-up was 23.7 ± 11.9 weeks.The study was conducted in a tertiary university hospital outpatients clinic.Upon informed consent, we recruited 24 consecutive adult patients (18 women and 6 men), who took LT4 for replacement (n = 14) or suppressive purposes (n = 10) and who had absorption of tablet LT4 impaired by PPIs.The 24 patients were switched from the tablet to the oral solution LT4 at the same daily dose.Significantly lower mean TSH levels were seen with the oral solution than with the tablet as were significantly greater rates of serum TSH less than or equal to the specified cutoff values (replacement [REP] group) or ≤ 0.10 mU/L (suppressive [SUP] group) with the oral solution than with the tablet.Serum TSH was lower with the oral solution than with the tablet formulation (REP group, 1.7 ± 1.0 mU/L vs 5.4 ± 4.3, P.0001; SUP group, 0.1 ± 0.3 mU/L vs 2.1 ± 2.7, P.0001). In the REP group, the rate of TSH values of ≤ 4.12 or ≤ 2.5 mU/L was 29 of 30 (96.7%) or 24 of 30 (80.0%) postswitch but only 17 of 36 (47.2%) or 9 of 36 (25.0%) preswitch (P.0001). In the SUP group, the rate of serum TSH values of ≤ 0.10 mU/L was 26 of 35 (74.3%) postswitch but 0 of 22 (0%) preswitch (P.0001).These data demonstrate the continued absorption of liquid LT4 despite the increased gastric pH due to PPI therapy.

Context: Coronary atherosclerosis in acromegaly was not extensively investigated in the literature until now. At autopsy, it was demonstrated in about 20% of patients with long-lasting disease, and myocardial infarction was reported as cause of death in a quarter of acromegalics. Objective: The objective of the study was to evaluate coronary atherosclerosis in a cohort of acromegalics with controlled or uncontrolled disease. Design: Coronary risk was evaluated by the Framingham algorithm, according to the Framingham score (FS). Patients were stratified into low (20%) midterm risk. Coronary calcium deposits were detected by multidetector computed tomography and measured by the Agatston algorithm. Coronary artery calcium [Agatston score (AS)] was quantified at the level of left main artery, left anterior descendent artery, left circumflex artery, right coronary artery, and posterior descendent artery. Total AS values in healthy persons are less than 50 (aged < 60 yr) and less than 300 (age ≥ 60 yr). Patients: Thirty-nine patients (12 males and 27 females, aged 53.0 ± 2.1 yr) were evaluated. In each patient, the mean of at least four determinations of serum IGF-I, assayed during the last 2 yr before study, was normalized for the age-matched normal range, and the result was presented as sd value (IGF-I sd). On the basis of serum IGF-I sd, acromegaly was considered controlled (≤1.9 sd; n = 24) or uncontrolled (≥ 2.0 sd; n = 15). Results: The FS was intermediate in 12 and high in two acromegalics. Overall, the FS was not correlated with serum GH values and IGF-I sd. Mean FS was not significantly different between patients with controlled and uncontrolled acromegaly. Total AS was increased in nine patients, most frequently in left anterior descendent, left circumflex, and left main arteries. In these nine patients, mean AS was similar in individuals with controlled and those with uncontrolled acromegaly, and the rate of 17% patients with controlled disease having increased AS was not statistically different from the rate of 33% uncontrolled acromegalics. Total AS was increased in six of 12 males and in three of 27 females (χ2 7.1, P < 0.01). Overall, total AS correlated with FS (r2 = 0.4, P < 0.0002) but not age, body mass index, disease duration, indexed left ventricular mass, serum cholesterol, triglycerides, GH, or IGF-I levels. Increased AS was more frequently observed in acromegalics with diabetes mellitus (χ2 = 5.2, P < 0.05) or hypertension (χ2 = 9.8, P < 0.002) but not in smokers (χ2 = 1.34, P = NS). Seven of nine patients with coronary calcium deposits had a FS greater than 6%. In six of 13 patients with FS greater than 6%, multidetector computed tomography did not demonstrate coronary calcifications. Conclusions: In our study, the integrated evaluation of FS and AS showed that 41% of acromegalics are at risk for coronary atherosclerosis and that coronary calcifications were evident in about half of them despite the fact that myocardial infarction was not more frequent in acromegalic patients than the general population. Moreover, the control of acromegaly did not influence significantly the extent of coronary atherosclerosis.

In a classic article published in this journal more than 50 yr ago, Escamilla and Lisser (1) reported that head trauma accounted for hypopituitarism in only 4 of 595 patients (0.7%). In the following 19 yr, Altman and Pruzanski (2) collected 15 additional cases of posthead trauma hypopituitarism (PHTH) from the international literature. In the subsequent 25 yr, Edwards and Clark (3) collected 34 new cases, so that their review concerned a total of 53 cases. No subsequent review on PHTH has appeared thereafter. After our initial observation of the first genuine case of posttraumatic isolated hypogonadotropic hypogonadism (4), namely the posttraumatic selective damage of the gonadotrophs, we became alerted about PHTH. Our experience with this patient (4) proved to be fruitful, because it helped us to diagnose PHTH—rather than “idiopathic” hypopituitarism—in subsequent patients (5). We learned, in fact, that head trauma can be minor and had occurred several years earlier, so that the patient may lose recollection of it. Thus, we learned to help the patient (and his or her relatives) to recollect these traumas. In addition to screening the literature from 1986 through 1998, we also screened the years 1970–1985 to ensure that Edwards and Clark (3) had not missed some cases, as indeed they did (6–13). Thus, we bring the total of PHTH cases to 367, namely 314 more than the 53 cases reviewed by Edwards and Clark (3). The 314 cases (4–26) include our own 15 cases (Refs. 4 and 5 and our unpublished data), but not the 11 cases reported by Cytowic and Smith (27) in a letter to the editor because of the selectivity of their series (all women who had developed amenorrhea) and the lack of hormone measurements. We warn the reader that not all the articles report all the relevant parameters that we will review, so that the resulting prevalences have different denominators. The aim of the present review is to assess the epidemiological, clinical, and endocrinological features of hypopituitarism following head trauma. Generalities

Papillary thyroid cancer (PTC), but neither the follicular nor the anaplastic histotype [follicular thyroid cancer (FTC), anaplastic thyroid cancer (ATC)], overexpresses simultaneously the protooncogene HGF (hepatocyte growth factor) and its receptor HGF-R (or c-met). Because 1) HGF and c-met map to chromosome 7q21 and 7q31, respectively, 2) FTC loses genetic material at multiple loci with a frequency much higher than PTC, and 3) loss of heterozygosity (LOH) on 7q has been previously found in various tumors, we tested the hypothesis that both FTC and ATC, but not PTC, could harbor LOH in segments of 7q encompassing the loci for HGF and c-met. We screened 6 normal thyroids, 10 colloid nodules, 10 follicular hyperplasias, 10 oncocytic adenomas, 10 follicular adenomas (FA), 10 FTC, 6 ATC, 12 PTC using two microsatellite markers for HGF, and two for c-met. LOH for all 4 markers was found in 100% of FTC, 100% of ATC, and (for only 1 or 2 markers) in 10-29% of FA. This is the first demonstration of an LOH that separates both FTC and ATC from PTC, in the best possible manner: 100% vs. 0%. Clearly, each of the two segments we have probed contains at least one tumor suppressor gene, whose inactivation is crucial for the establishment of the FTC (and ATC) phenotype. This loss of genetic material explains why FTC and ATC, but not PTC, fail to express both HGF and c-met. Our findings may also have immediate diagnostic application, in the context of assisting pathologists in the often difficult task of distinguishing FA from FTC.

Based on the knowledge that diagnostic fine needle biopsy of the thyroid (FNAB) results in a prompt increase in circulating thyroglobulin (Tg), we evaluated whether Tg is indeed the postulated antigen for circulating antibodies against thyroid hormones (THAb). Preliminarily, we verified that FNAB causes the release into the bloodstream of iodinated, heterologous, and thus potentially immunogenic, molecules of Tg. Of the initially enrolled 400 patients, 214 had a number of blood drawings sufficient to evaluate over time (before FNAB and 1–3 h, 3 days, 15 days, 30 days, 3 months, 6 months, and 12 months after FNAB) the following parameters: THAb of both IgM and IgG classes, Tg antibodies (TgAb; by a sensitive immunoradiometric assay), and Tg (in the 156 patients who were TgAb negative). We found the following. 1) Serum Tg most often peaks 1–3 h after FNAB (61 ± 45% of the baseline level; mean ± sd). 2) Only 7% of the initially TgAb-negative patients converted to positive, and only 12% of those initially pos...

Three novel point mutations at nucleotides 1249, 1282, and 1614 (exons 9 and 10) of the human thyroid hormone receptor-beta gene were observed in six individuals affected by the syndrome of resistance to thyroid hormone. All three mutations occurred in a heterozygous pattern and caused the following changes in the mature form of the receptor protein: Asp322 to Asn, Glu333 to Gln, and Lys443 to Asn, respectively. The first and third point mutations arose in two unrelated families from eastern Sicily, whereas the second concerned an individual from southern Calabria, apparently presenting a sporadic form of the resistance syndrome. The clinical and biochemical features of resistance to thyroid hormone, both before and after the administration of thyroid hormones, highlight the striking intrafamilial heterogeneity in the phenotypical presentation of the syndrome.

Visual perceptual integrative motor ability was investigated in 719 6- to 12-yr-old, presumably normal, primary schoolchildren living in 2 iodine-deficient endemic goiter areas in Sicily, identified on the basis of the presence (area A) or absence (area B) of endemic cretinism, by administrating the Bender Gestalt test. All of these clinically euthyroid schoolchildren were also examined neurologically by an investigator unaware of the result of the Bender test. Ninety-nine (13.76%) schoolchildren were found to be defective by the Bender test; this prevalence was significantly higher than that (3.0%) found in an iodine-sufficient goiter-free control area (area C) lying at sea level (chi 2 = 36.25; P less than 0.000001). No difference in the prevalence of Bender abnormalities was apparent if the children were divided according to the area of provenience (area A, 14.4%; area B, 13.1%). A high percentage of children falling in the lower range of normality was found in both area A (15.5%) and area B (19.0%); this was significantly higher than that in area C (3.8%; chi 2 = 77.55; P less than 0.000001). Neuromuscular and neurosensorial abnormalities, including increased tendon reflexes, clonus of the foot, Babinski sign, minor disturbances in balance, and gait, and minor defects in hearing and speech, were apparent in 19.3% (area A) and 18.5% (area B) of the children. These disorders were significantly more frequent in defective children identified by the Bender test (33.3%) than in normal children (15.3%; (chi 2 = 17.29; P less than 0.00005). The general intellectual aptitude in Bender deficient subjects was evaluated by the Terman Merrill test and was found to be impaired in 95%, thus confirming the existence of an endemic cognitive deficiency (ECD), distinct from the endemic mental deficiency previously found in other endemic goiter, iodine-deficient areas. ECD seems to be epidemiologically independent of the existence of endemic cretinism. Further clinical auxological and biochemical studies in a selected group of ECD children suggested the epidemiological and, possibly, pathogenic association of cognitive impairment with iodine deficiency.

We studied binding of T4 to the lipid-complexed apolipoproteins (apo) of high density lipoproteins (HDL), the major lipoprotein carrier of thyroid hormones in human plasma, and to lipid-free apoA-I. HDL isolated from fresh normal plasma by ultracentrifugation (density, 1.063-1.210 g/mL) was photoaffinity labeled with [3,5-(125)I]T4 and analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Two bands corresponding to apoA-I (28.3K) and apoC-II or apoC-III (8.6-9.2K) were seen, and their radioactivity decreased by 50-60% when labeled in the presence of 1 mumol/L T4. Photoaffinity labeling of isolated apoA-I also was demonstrated and was decreased 74% by 1 mumol/L T4, suggesting a higher affinity of the lipid-free protein for T4. T4 binding of isolated apoA-I was optimal at pH 7-8, reached a maximum after 1 h at 23 C, and decreased after incubation at 37 C. Scatchard analysis revealed a single T4-binding site with a Ka of 7.5 x 10(7) L/mol at 23 C, pH 8.2. The potency of T4 analogs as inhibitors of T4 binding to isolated apoA-I was L-T4 = D-T4 = triiodothyroacetic acid = L-rT3 much greater than L-T3 much greater than L-thyronine. The binding of T4 to apoA-I was reduced by known inhibitors of T4 binding to serum proteins (diclofenac = mefenamic acid = furosemide = 8-anilinonaphthalene sulfonic acid much greater than dilantin greater than heparin greater than barbital) and by lipids (unsaturated fatty acids greater than cholesterol = cholesterol esters = phospholipids greater than saturated fatty acids = diglycerides = triglycerides). We conclude that the binding of T4 to HDL is mediated by a specific interaction of the hormone with apoA-I and with apoC-II and/or apoC-III. Since the lipid constituents of HDL inhibit T4 binding to apoA-I, the HDL subfraction in plasma that carries most of the HDL-bound T4 should be one with a low lipid content.