Circulating endogenous digitalis-like factor(s) (EDLF) in man is derived from the adrenals and its secretion is ACTH-dependent.

Adrenal origin and ACTH-dependent secretion of endogenous digitalis-like factor(s) (EDLF) was investigated. Twelve normal weight normotensive subjects (normal group) and 10 patients with Addison's disease (Addison group) were subjected to prolonged ACTH stimulation with 1 mg tetracosactin-depot im. Blood sampling was at 0 and 240 min. Digitalis-like reactivity was monitored in plasma extracts (combined organic solvent solid phase method) by digoxin and ouabain radioimmunoassay (RIAD and RIAO, respectively). 3H-ouabain concentration on erythrocytes (OBS) was also determined. Na+, K+-ATPase inhibition by normal plasma extract was tested by measuring Vmax and Km of 86Rb+-transport into human erythrocytes. In the normal group basal median plasma concentrations RIAD (0.07 nmol/l) and RIAO (0.89 nmol/l) increased significantly after ACTH administration (median 0.31 and 1.83, respectively; Wilcoxon, p<0.01). In contrast, in the Addison group no plasma RIAD and RIAO reactivity was detected before or after ACTH administration with minor exceptions. The OBS remained unchanged in the Addison group at 0 and 240 min; in the normal group there was a significant decline at 240 min (Wilcoxon, p<0.05) implying increase in circulating EDLF after ACTH stimulation. In the 86Rb+-transport experiments, 2 nmol/l ouabain or 2 nmol/l plasma-extracted ouabain reactivity both significantly impaired substrate affinity equally increasing Km without affecting Vmax. In men, the adrenals may produce and secrete EDLF, whose secretion appears to be ACTH-dependent.

Assessment of the frequency of mutant (hprt-) T lymphocytes from peripheral blood of patients with Hashimoto's thyroiditis.

A salient feature of Hashimoto's thyroiditis (HT) is the T-cell-mediated destruction of the thyroid gland leading to hypothyroidism. In HT, as in other autoimmune diseases, a central premise has been that autoreactive T cells must be dividing in response to autoantigens, accumulating random spontaneous mutations during the activation process. Here, we have examined this hypothesis by using as monitor of somatic cell mutation the hprt gene, encoding the salvage pathway enzyme hypoxanthine-guanine phosphoribosyl transferase. Eleven newly diagnosed patients with HT and 10 patients with chronic disease were selected for the study, whereas 10 healthy individuals were used as controls. Peripheral T cells were cultured under limiting dilution conditions in the presence of 6-thioguanine and the frequency (MF) of surviving mutant hprt(-) T cells was calculated by Poisson statistics. It was observed that the mean MF value of either patient group (6.6 +/- 5.8 per 10(6) cells for the newly diagnosed, and 8.8 +/- 4.0 per 10(6) cells for the patients with chronic disease) was not significantly different (p > 0.05) from that of the control group (6.8 +/- 6.4 per 10(6) cells). These data do not support the concept that patients with HT have an increased number of actively dividing T cells in the circulation compared to healthy controls. Autoreactive T cells may be activated mainly in situ or home readily to the thyroid in the early stages of the disease and reach a nonexpansion stage as the chronic disease is stabilized.

An XY female with Müllerian duct development and persistent Wolffian duct structures.

Disorders of sexual differentiation are usually diagnosed at an early age. We hereby describe a case of a 29-year-old phenotypic woman who during the evaluation of amenorrhea was found to have a 46, XY karyotype. Further evaluation (including laparoscopy) suggested that she presented a variant of gonadal dysgenesis, with the particularity of having well-developed müllerian structures and testicular remnants alongside a steroid-producing gonadoblastoma.

High plasma amylin/islet amyloid polypeptide levels in patients with residual medullary thyroid carcinoma after total thyroidectomy.

OBJECTIVE: We have previously reported that amylin/islet amyloid polypeptide (IAPP) mRNA is detected in a substantial subset of medullary carcinomas of the thyroid (MTCs). The aim of this study was to determine if the amylin/IAPP gene is expressed as the IAPP peptide in MTC tissues. DESIGN AND METHODS: In 10 patients with a histological diagnosis of MTC and with persisting or recurrent disease (basal calcitonin levels >250 pg/ml), the fasting serum insulin and plasma glucose, IAPP and calcitonin levels were measured and compared with those of 18 normal control subjects matched for age and body mass index. IAPP expression was studied by immunohistochemistry in MTCs and lymph-node metastasis tissues. RESULTS: Seven of ten MTC patients had abnormally elevated IAPP levels. Plasma IAPP and serum insulin levels were correlated in both patients and controls, but the slope of the regression line was significantly higher for MTC patients. IAPP staining was detected in four out of 12 random MTC samples and in two out of five lymph-node metastases, using immunohistochemistry. CONCLUSIONS: These results indicate that MTC cells express IAPP at the peptide level and that this raises the peripheral plasma levels. Further studies may reveal whether this is a feature of malignant disease.

Sustained remission of metastatic adrenal carcinoma during long-term administration of low-dose mitotane.

We present our experience with two female patients suffering from metastatic, recurrent adrenocortical carcinomas, to whom o,p'-DDD (mitotane) was administered for unusually long duration. The first patient received mitotane as monotherapy after relapse (in doses ranging from 3 to 6 g/day initially and 1 g/day thereafter, for 13 yr). The second patient presented with metastatic disease and underwent radical surgical excision of the adrenal. Mitotane was administered initially at 2.5 g/day, and the dose was gradually lowered over 8 yr to 1 g/day, without interruption. Both patients tolerated the medication well, regardless of the daily dosage, with complaints limited to epigastric pain and nausea, while their disease has been kept under control for 14 and 16 yr, respectively. The blockade of steroid synthesis with mitotane resulted in hypercholesterolemia in both patients and in premature menopause in the second patient; however, these abnormalities were taken care of with the appropriate therapy. The excellent follow-up of these patients suggests that even in hopeless cases with metastatic adrenocortical carcinoma, mitotane should be administered for very long periods of time as it can be well-tolerated and may be beneficial in the long run.

Perception of family support is correlated with glycemic control in Greeks with diabetes mellitus.

We studied 98 native Greek patients with Type 2 diabetes mellitus. Their degree of glycemic control, evaluated with glycated hemoglobin A1c levels, was correlated with perceived family support, assessed with the Family Support Scale. The different social context of Greece--and its corresponding perception of family support--influence glycemic control in a way that is at variance from data of some studies of Anglo-Saxon families. In conclusion, family support should be taken into consideration in the management of native Greek patients with Type 2 diabetes mellitus.

B-cell autoepitopes on the acetylcholinesterase-homologous region of human thyroglobulin: association with Graves' disease and thyroid eye disease.

OBJECTIVE: Thyroglobulin (Tg) is a large autoantigen involved in autoimmune thyroid diseases. Tg epitopes have, so far, been identified within large peptides. In the present study, we used small synthetic peptides to finely map serological epitopes on the highly immunogenic C-terminal region of Tg. Homology of this region to acetylcholinesterase (AChE) has been implicated in the pathogenesis of thyroid eye disease (TED) through cross-reactive antibodies. METHODS: We tested total IgG purified from four pilot Graves' disease (GD) sera reactive with both Tg and AChE and from three healthy controls, for reactivity against overlapping 20mer peptides (pin synthesis) covering the sequence 2171-2748 of human Tg. Antibody-reactive peptides were subsequently synthesized by a solid-phase technique for confirmation with a large number of sera: 99 GD, 32 Hashimoto's thyroiditis (HT) and 45 healthy controls. RESULTS: Peptides TgP15, TgP26 and TgP41 (amino acids 2339-2358, 2471-2490 and 2651-2670 respectively) were found to be targets of autoantibodies on intact Tg, recognized by a statistically significant proportion of GD sera (22.2%, 35.4% and 30.3% respectively), compared with HT (0%, 15.6% and 6.3% respectively) and healthy controls (0%, 4.4% and 4.4% respectively). The majority of GD sera (56.6%) were positive for at least one of the three peptides. In GD, TgP26 reactivity was found to be associated with TED (48.6% with TED versus 25.5% without TED, P<0.05). CONCLUSION: Some epitopes on the C-terminal region of Tg are associated with GD. A subset of Tg-reactive autoantibodies, directed to this region, is associated with TED and may be involved in the development of the disease.

HLA DQA1*0501 and DRB1*0301 antigens do not independently convey susceptibility to Graves' disease.

Genes of, or closely associated to, the HLA complex are assumed to contribute to the genetic predisposition of Graves' disease. The aim of this study was to investigate the presence of the HLA DQA1*0501 and DRB1*0301 antigens in Greek patients with Graves' disease. In addition, we tried to establish if there is any association between these antigens and any of the clinical manifestations of the disease. We examined 117 patients with Graves' disease and 104 healthy controls. DNA was extracted from peripheral lymphocytes and the HLA DQA1*0501 and DRB1*0301 genomic regions were amplified by PCR and characterized by hybridization with sequence specific oligonucleotides (SSO). Two of the patients had a positive family history for Graves' disease and 46 had clinical thyroid eye disease (TED). The frequencies of both DQA1*0501 and DRB1*0301 antigens were significantly increased in patients compared to controls (relative risk [RR] 4.2 and 4.5 for each antigen respectively). Neither of these two antigens was an independent risk factor for Graves' disease. However, the combination of both these HLA antigens resulted in a striking increase in the RR for development of Graves' disease especially in females (RR/F=27, RR/M=8.4). No association was found between these antigens and positive family history or the presence of TED. These data suggest that HLA DQA1*0501 and DRB1*0301 antigens are not independent risk factors for the development of Graves' disease. On the contrary, the presence of both these alleles results in a significant increase in the RR for the development of Graves' disease in the Greek population, particularly in females.

Study of the Trp64Arg polymorphism of the beta3-adrenergic receptor in Greek women with gestational diabetes.

OBJECTIVE: This study assessed whether the Trp(64)Arg polymorphism of the beta3-adrenergic receptor (beta3-AR), which has been associated with obesity, insulin resistance, weight gain, and earlier onset of type 2 diabetes, is more frequent in women who develop gestational diabetes mellitus (GDM) or whether it is associated with weight gain during pregnancy RESEARCH DESIGN AND METHODS: A total of 311 Greek pregnant women (180 with GDM and 131 without GDM [control]) who underwent a 100-g oral glucose tolerance test (OGTT) in the third trimester of pregnancy were genotyped for the beta3-AR Arg(64) polymorphism. Insulin levels were also determined during the OGTT. RESULTS: The frequency of Trp(64)Arg heterozygotes in this population was approximately 7% and was similar in the GDM and control groups (6.7 vs. 6.9%) as well as in the obese (BMI > or =27 kg/m2) and the nonobese (6.3 vs. 6.8%) subgroups. In the GDM group, BMI, fasting insulin resistance index, and diastolic blood pressure were significantly higher in Trp(64)Arg carriers; these differences were no longer observed when obesity was considered. In the 4 subgroups (control Trp(64)Trp and Trp(64)Arg and GDM Trp(64)Trp and Trp(64)Arg), a highly significant trend was evident of an increase in the percentage of subjects with shorter height. CONCLUSIONS: The frequency of the Arg(64) allele in Greek pregnant women is relatively rare compared with other ethnic groups and is probably not related to the development of GDM or obesity The observed tendency for shorter body height in Arg(64) carriers merits further evaluation in larger population samples.

Three mRNA transcripts of the proopiomelanocortin gene in human placenta at term.

The proopiomelanocortin (POMC) gene whose normal pituitary specific mRNA product is 1200 bases (b) is also expressed in placenta and its peptide derivatives such as ACTH and beta-endorphin may play an important role in the initiation of labor. So far, two mRNA transcripts, one small (800b) and one large (1380b) have been reported in placenta by Northern blot analysis, similar to other endocrine tissues and various extrapituitary tumors; however, it is questionable whether both of these transcripts are effectively translated to a functional protein. We examined by Northern blot analysis the size and the differential expression of placental POMC gene transcripts in pregnant women with different modes of delivery. Placental tissues were collected from two groups of pregnant women, six with vaginal delivery (VD) and five with cesarean section (CS). In both groups of placentae three POMC gene transcripts were detected of 800, 1200 and 1380 bases; the 1200b pituitary specific species often predominated and was always present. The 800b transcript was also always present, while the large transcript (1380b) was expressed in 3/6 VD and 2/5 CS placental tissues. No differences in the relative levels of any of these mRNA species showing effect of the mode of delivery were observed. We conclude that POMC gene transcription in placental tissue at term gives rise to three mRNA transcripts, thus resembling extrapituitary tumors. The reported changes in the levels of the derivative peptides according to the mode of delivery do not reflect changes in POMC mRNA levels and could be attributed to a post-translational effect.

Hormonal parameters in gestational diabetes mellitus during the third trimester: high glucagon levels.

Hormonal parameters during the last trimester of pregnancy contribute to a natural increase of insulin resistance. It is not known whether any of these are further involved in the manifestation of gestational diabetes mellitus (GDM) in affected individuals. Basal levels of adrenocorticotropic hormone, cortisol, growth hormone, insulin-like growth factor-I, prolactin, glucagon, estradiol, progesterone, human placental lactogen and human chorionic gonadotropin were investigated in 15 nonobese women with GDM and 26 matched normal pregnant women (N). A linear discriminant analysis was performed to further compare the predictive value of the basal hormone levels. Plasma glucagon levels were significantly higher in the GDM group (p = 0.014); this difference was even higher (p = 0.007) when the number of women was increased (GDM = 33, N = 62). No significant differences were found in the levels of any of the other hormones. It is not clear whether elevated glucagon levels have any involvement in the pathogenesis of GDM or simply reflect the relative insulin deficiency of these women.

Impaired endothelium-dependent vasodilatation in women with previous gestational diabetes.

OBJECTIVE: To assess whether otherwise healthy women with a history of gestational diabetes mellitus (GDM) may have abnormalities in endothelial function at a very early stage, before glucose intolerance occurs. RESEARCH DESIGN AND METHODS: A total of 33 women with previous GDM (17 nonobese [BMI < 27] and 16 obese [BMI > or = 27]) and 19 healthy nonobese women were examined. A 75-g oral glucose tolerance test was performed, and insulin levels and biochemical parameters were also measured. Using high-resolution ultrasound, we measured vasodilatory responses of the brachial artery during reactive hyperemia (endothelium-dependent vasodilatation), and after nitroglycerin administration, an endothelium-independent vasodilator. RESULTS: Flow-mediated dilatation (FMD) was significantly and equally decreased in both groups of women with previous GDM, compared with control subjects (1.6 +/- 3.7% in the nonobese GDM group and 1.6 +/- 2.5% in the obese GDM group vs. 10.3 +/- 4.4% in control subjects, P < 0.001). FMD correlated inversely with serum uric acid levels, BMI, serum total cholesterol, and basal insulin resistance (homeostasis model assessment). Nitrate-induced dilatation was significantly decreased only in the obese GDM group compared with control subjects, (21.4 +/- 5.1 vs. 27.9 +/- 9.5, P < 0.05). CONCLUSIONS: Endothelial dysfunction, which is considered as a very early index of atherogenesis, is already present in both obese and nonobese women with a history of GDM, even when they have normal glucose tolerance.

Decreased stature in gestational diabetes mellitus.

Short stature has been associated with various degrees of abnormal glucose tolerance in middle-aged people, where the effects of age and metabolic control would be difficult to exclude. We chose to examine body stature in women with gestational diabetes mellitus (GDM), a prediabetic state affecting a young group of people. A sample of 2772 Greek pregnant women, referred for GDM screening was examined. After a 100-g oral glucose tolerance test, 1787 women were classified as normal (N), 300 women were found with one abnormal glucose value (OAV) and 685 women with GDM. Basal insulin resistance was calculated in 640 women by homeostasis model assessment. In addition, 51 pregnant women with pre-existing Type II (non-insulin-dependent) diabetes mellitus and 109 with pre-existing Type I (insulin-dependent) diabetes mellitus were included in the study. There was a gradual decrease in mean height (cm) as glucose intolerance became more severe: N: 161.0 +/- 6.2, OAV:160.2 +/- 6.1, GDM:158.7 +/- 6.3, Type II diabetes 158.2 +/- 7.0 (p < 0.001, analysis of variance]. Height in Type I diabetes (160.1 +/- 5.9) did not differ from the normal group. The difference in height between the normal and GDM groups remained (p < 0.001) when body weight, age, birth before or after 1960 and educational status were also taken into account. An independent correlation was also found between height and insulin resistance (n = 640) adjusted for the above mentioned variables. In conclusion, short stature appears to be associated with glucose intolerance as an independent variable, even when this intolerance is both mild and temporary. The previously unrecognised independent association of stature with basal insulin resistance merits further investigation.

Genetic screening for RET mutations in families with multiple endocrine neoplasia 2 syndromes.

Mutations in the RET proto-oncogene have recently been recognized to be responsible for the inherited multiple endocrine neoplasia type 2 syndrome. As expected, Greek patients with MEN2 and FMTC carry RET mutations similar to those of other ethnic groups. In those regions of the gene that were analyzed, mutations were detected in six out of six families with classical MEN2A, three out of five of the families with familial MTC, and one case with MEN2B. Presymptomatic screening using DNA analysis has now replaced calcitonin stimulation tests in the offspring of families where the mutation has been characterized. The use of these methods will improve the prognosis in MEN2 patients and will also reduce the psychological burden of risk for a potentially lethal disease on family members.

Endothelial dysfunction of conduit arteries in insulin-dependent diabetes mellitus without microalbuminuria.

OBJECTIVE: Previous studies have shown that endothelial dysfunction, an early sign of atherosclerosis, occurs in animal models of diabetes mellitus and in resistance vessels of patients with insulin-dependent diabetes. In the present study we examined whether young patients with insulin-dependent diabetes without microalbuminuria present abnormal endothelial function of large peripheral arteries. METHODS: Twenty-six patients with insulin-dependent diabetes without microalbuminuria were compared with 26 normal controls and 5 patients with insulin-dependent diabetes with microalbuminuria. Brachial artery diameter was measured at rest, during reactive hyperaemic flow (endothelium-dependent dilatation) and after sublingual isosorbide dinitrate (endothelium-independent dilatation). RESULTS: Baseline artery diameter and flow as well as the degree of reactive hyperaemia were similar in all groups compared to controls. Flow-mediated dilatation was lower in patients with diabetes without microalbuminuria (5.8 +/- 7 vs 11 +/- 7%. P = 0.01) as well as in patients with diabetes without microalbuminuria (0.75 +/- 2.5 vs 11 +/- 7%, P = 0.003); nitrate-induced dilatation was normal in patients without microalbuminuria and attenuated in patients with microalbuminuria. In the group of diabetes patients without microalbuminuria, those with disease duration > 10 years and HbAlc > 6% had the worse endothelial function. CONCLUSIONS: Our results demonstrate that endothelial dysfunction of conduit arteries can be detected in patients with insulin-dependent diabetes mellitus without microalbuminuria, probably contributing to the high prevalence of atherosclerosis in these patients.

Anterior, posterior, or laparoscopic approach for the management of adrenal diseases?

BACKGROUND: At the advent of laparoscopic adrenalectomy it seemed timely to us to assess the advantages and the overall results of the different techniques that are currently used in an approach to adrenalectomy. PATIENTS AND METHODS: Between 1984 and 1995, 165 patients underwent adrenalectomy. Eighty-six patients (37 men and 49 women with a mean age of 46.4 years) underwent adrenalectomy via the anterior approach, 61 patients (18 men and 43 women with a mean age of 43.8 years) underwent posterior extraperitoneal adrenalectomy, and 18 patients (8 men and 10 women with a mean age of 48.7 years) underwent anterior laparoscopic adrenalectomy. For statistical analysis of the different comparisons between the groups we used the t test for independent samples, the Wilcoxon test, chi-square, and one way analysis of variance. RESULTS: There was no operative mortality. The morbidity was 13.9% in the anterior approach, 9.8% in the posterior approach, and 0% in the laparoscopic approach. The mean operating time for unilateral adrenalectomy was 155.3 min (range 75 to 315) for the anterior approach, 108.6 min (range 60 to 195) for the posterior approach and 116.1 min (range 75 to 180) for the laparoscopic approach. For bilateral adrenalectomy the mean operating time was 165 min for the anterior and 178 min for the posterior approach. The average diameter of tumors resected anteriorly was 8.07 cm (range 2.5 to 20), posteriorly was 5.25 cm (range 0.5 to 14), and laparoscopically was 4.03 cm (range 2 to 6.5). The mean length of postoperative hospitalization for patients undergoing unilateral adrenalectomy was 8 days (range 2 to 25) for the anterior approach, 4.5 days (range 1 to 11) for the posterior approach, and 2.2 days (range 1 to 5) for the laparoscopic approach. Patient controlled analgesia lasted 3.4 days for those operated anteriorly, 2.3 days for those operated posteriorly, and 1.08 days for those that underwent laparoscopic adrenalectomy. CONCLUSIONS: The laparoscopic approach to the adrenal promises the safest and least painful operation with shorter in-hospital stay and the best cosmetic and long-term results. The posterior approach is the fastest of all and a better overall operation than the anterior approach that should only be reserved for removing very large adrenal tumors and when concomitant intra-abdominal procedures, that can't be handled laparoscopically, are anticipated.

Islet amyloid polypeptide (amylin) does not seem to be directly involved in the development of gestational diabetes mellitus.

In order to define the islet amyloid polypeptide (IAPP) levels in gestational diabetes mellitus (GDM) and their interrelationship with the insulin levels, we studied (1) the placental RNA from 10 women (5 with GDM and 5 normals) for IAPP expression by Northern blotting and (2) 10 women with GDM during a 100-gram oral glucose tolerance test and compared these with 11 normal women matched for obesity and age. Plasma levels of glucose, IAPP, insulin, and C peptide were determined. No IAPP expression was detected in any of the placentae after a long exposure. We could not demonstrate any differences in plasma IAPP levels (basal or stimulated) between the two groups of pregnant women. However, in women with GDM we found a lower IAPP/insulin ratio (p < 0.05) and a lower maximal IAPP/maximal insulin response ratio during the oral glucose tolerance test (p < 0.05) than in normal women. Therefore, IAPP does not appear to be directly involved in the development of GDM. The peripheral levels of IAPP relative to insulin are lower in GDM, a finding similar to that described in type 2 diabetes mellitus (non-insulin-dependent diabetes mellitus). This observation further confirms that GDM resembles the early stages of type 2 diabetes mellitus.

Renal, metabolic, and hormonal responses to proteins of different origin in normotensive, nonproteinuric type I diabetic patients.

OBJECTIVE: Whether the differences in renal function found in vegetarian compared with omnivorous subjects are related to quantity or quality of the protein is unknown. We have studied the renal function of nine normotensive, nonproteinuric type I diabetic patients who were fed in random order for 4 weeks either an animal protein diet (APD) (protein intake 1.1 g . kg-1 . day-1) or a vegetable protein diet VPD (protein intake 0.95 g . kg-1 . day-1). The two diets were isocaloric. RESEARCH DESIGN AND METHODS: In a crossover study, we measured glomerular filtration rate (GFR) (inulin clearance), renal plasma flow (RPF) (p-aminohippurate clearance), plasma amino acids, growth hormone, glucagon, insulin-like growth factor I-(IGF-I), and microalbuminuria. RESULTS: GFR and RPF were lower with the VPD than with the APD (89.9 +/- 4.1 vs. 105.6 +/- 5.1 ml . min-1 . 1.73 m-2, P < 0.05, and 425.7 +/- 22.2 vs. 477.8 +/- 32.2 ml . min-1 1.73m-2, P < 0.05, respectively). Renal vascular resistance (RVR) was higher with the VPD than with the APD (101 +/- 25 vs. 91 +/- 10 mmHg . min-1 . ml-1, P < 0.05). Filtration fraction (FF) remained unchanged after either diet. Fractional clearance of albumin fell with the VPD to 2.0 +/- 0.65 from 3.4 +/- 1.15 x 10-6 (P < 0.05). At the end of the APD and VPD, the plasma levels of growth hormone and glucagon did not differ significantly. Plasma levels of IGF-I were higher with the APD than with the VPD (1.1 +/- 0.6 vs. 0.9 +/- 0.13 U/ml, P < 0.05). Plasma concentrations of valine and lysine were significantly higher with the APD than with the VPD (234.6 +/- 30.3 vs. 164.5 +/- 25.4 mm1/1, P < 0.05, and 565 +/- 45.1 vs. 430 +/- 56.1 mmol/l, P < 0.05, respectively), whereas plasma valine was strongly correlated to the GFR (r = 0.832, P < 0.01). No differences were found in other amino acids. CONCLUSIONS: A VPD has significantly different renal effects from an APD equal in protein intake in normotensive type I diabetic patients. This could be explained partly by differences in plasma concentrations of amino acids and IGF-I.

Antibodies to acetylcholinesterase cross-reacting with thyroglobulin in myasthenia gravis and Graves's disease.

In the present study we analysed by ELISA the ability of sera from 50 patients with myasthenia gravis (MG), 20 with Hashimoto's thyroiditis (HT), 53 with Graves' disease (GD) and 36 healthy controls (CR) to react with acetylcholinesterase (AChE) from Electrophorus electricus and human thyroglobulin (Tg). Significantly increased anti-AChE activity was exhibited by a high proportion of MG (IgG 36%) and GD (IgG 21%) sera, while increased anti-Tg activity was detected in all three patient groups (MG, IgG 26% and IgA 26%; HT, IgG 85% and IgA 40%; and GD, IgG 51%). Interestingly, a significant proportion of MG and GD sera exhibited both IgG anti-AChE and anti-Tg activities (MG, 18%; P < 0.001; and GD, 15%; P < 0.001, versus CR, 0%). This bi-reactivity was exhibited by anti-AChE antibodies cross-reacting with Tg (anti-AChE/Tg activity); (i) serum anti-AChE activity was effectively inhibited by soluble Tg, and (ii) affinity-purified anti-Tg antibodies cross-reacted with AChE. Cross-reactivity seems to be a property of pathological (auto)antibodies; induced (rabbit) antibodies to AChE or Tg were highly monospecific. Analysis of clinical data showed that increased IgG anti-AChE/Tg activity was well associated with: (i) overlapping GD in MG (P < 0.02), and (ii) ophthalmopathy in GD (P < 0.01). In contrast, no correlation was noted in MG between anti-AChE activity units and anti-Tg activity units or acetylcholine receptor antibody titres. The clinical significance of anti-AChE/Tg antibodies remains to be elucidated.

Increased incidence of medullary carcinoma of the thyroid in rural regions in Greece.

A role of environmental factors for the development of Medullary Carcinoma of the Thyroid (MTC) has been shown for animals, but has only been speculated for humans. In the present study we analyzed our registry of 58 sporadic MTCs for the place of origin and place of residence and compared these with 408 other thyroid carcinomas of different histology who are attending the same Endocrine Clinics in the Athens area. Clustering of sporadic MTCs was observed in the Ionian islands, where an increased incidence of familial cases has previously been observed. Patients with sporadic MTCs originated more frequently from rural areas (p = 0.0006), where the main occupation is agriculture. No important differences were observed concerning the place of residence. We speculate that exposure to sunshine, which is greater in rural areas, may be one factor which, through vitamin D, could be involved in the development of C-cell tumors in predisposed individuals.