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Purpose: Papillary thyroid carcinoma (PTC), the most common thyroid cancer histotype, has a good prognosis even when spread to the neck lymph node (LN). The prognostic role of LN metastases' location is still controversial. The aim of the present study was to evaluate the clinical relevance of the number and location of LN metastases at presentation in PTCs., Methods: This retrospective study included a consecutive series of 1653 PTC patients followed for a mean period of 5.9 years in a referral thyroid cancer clinic. All patients have undergone thyroidectomy with the dissection of at least six LNs. According to the LN status, patients were subdivided into 569 N0 (34.4%), 644 N1a (39.0%, central compartment) and 440 N1b (26.6%, latero-cervical compartment)., Results: Age at diagnosis was significantly lower in N1b (39.8, IQR 30.7-51.6) and N1a (40.1, IQR 31.3-50.1) than in N0 (44.7, IQR 36.6-55.0 yrs). The male gender was more prevalent in N1b than in N1a and N0 (F/M = 1.9/1, 4.0/1 and 5.5/1, respectively). Persistent/recurrent disease at last control was significantly more frequent in N1b (29.8%) than in N1a (14.3%), and in N1a than in N0 (4.2%) (p < 0.01 for all). Also, distant metastases were significantly (p < 0.001) more frequent in N1b (14.1%) than in N1a (4.3%) and N0 (1.6%). LN metastases' number (>5) was a significant risk factor for persistent/recurrent disease only for N1a patients., Conclusions: These data indicate that persistent/recurrent disease and distant metastases are significantly more frequent in patients with latero-cervical LN (N1b) metastases and that the LN location should be used for a better postsurgical risk stratification.

Purpose: We recently reported that a high BMI and high waist circumference prevalence is present in Sicilian children and that the male gender is associated with a significant risk of obesity. Early-life and parent-related risk factors were investigated 1521 Sicilian children (752 females and 769 males, aged 9.0-14.0 years) to identify biological and environmental factors that can contribute to obesity onset., Methods: Anthropometric measurements of children, their urban vs rural area provenience, birth weight and neonatal feeding were collected. In addition, the BMI and educational level of their parents and the perception of their child weight status were investigated., Results: In the study cohort, the prevalence of overweight and obesity was 27.2 and 14.1 %, respectively, significantly (p < 0.05) higher in males than in females. Breastfeeding emerged as a protective factor (OR 0.64; p < 0.0005), while risk factors for developing childhood obesity were a birth weight ≥4.0 kg (OR 1.83; p < 0.05), an overweight or obese mother (OR 2.33; p < 0.0001) or father (OR 1.68; p < 0.0001) and a mother with a low/medium education level (OR 1.72; p < 0.005)., Conclusion: Understanding risk factors for pediatric obesity is a prerequisite to identify children at highly risk of being obese and to predispose early intervention strategies.

Purpose: Autoimmune polyendocrine syndromes (APS) type III are characterized by the association of autoimmune thyroid disease (ATD) with other autoimmune diseases such as diabetes, alopecia, pernicious anemia, vitiligo and chronic atrophic gastritis. A strong association between ATD and atrophic gastritis (AG) has been demonstrated. Moreover 10 % of patients affected by AG have a predisposition to develop gastric carcinoid and adenocarcinoma as a result of chronic hypergastrinemia caused by achlorhydria and subsequent ELC cells neoplastic transformation., Methods: The aim of the study is to evaluate, in a consecutive series of patients followed for ATD in our outpatients clinic, the prevalence of AG. In the period 2004-2014, 242 patients with ATD underwent a screening performing APCA, Vitamin B12, ferritin, iron, and hemoglobin and red cells count measurements with subsequent gastroscopy in case of APCA positivity., Results: We found 57/242 (23.5 %) patients with APCA positivity. Of these patients 33/57 (57.8 %), 31 F and 2 M, were affected by Graves disease; 24/57 (42.1 %) 21 F and 3 M by Hashimoto thyroiditis; 10/57 (17.5 %) presented with anemia, 14/57 (24.5 %) with vitamin B12 deficiency, 9/57 (15.7 %) with iron deficiency. In 2/57 a gastric carcinoid was found., Conclusions: Our data confirm the high association rate of AG in ATD which frequently is not an isolated disease but configure the picture of APS type III and need to be followed accordingly. An early diagnosis may be useful for diagnosis of gastric carcinoids and to explain and treat a gastric related L-thyroxine malabsorption and presence of chronic unexplained anemia.

Background: Fine needle cytology aspirates (FNA) classified as THY4 are a heterogeneous group suspicious for malignancy [papillary thyroid cancer (PTC)], which is confirmed in 50-80% of cases after surgery., Aim: To better stratify THY4 FNA specimens for the relative risk of malignancy., Methods: We retrospectively analyzed 78 thyroid nodules classified as THY4 because of the presence of atypical cells, hypercellular trabeculae and/or intranuclear inclusions (ICI), in the absence of papillae. Two subgroups were identified: group 1 (38 nodules), showing ICI with (no.=17) or without (no.=21) trabeculae and cellular atypia, and group 2 (40 nodules), showing trabeculae and atypia but without ICI., Results: PTC was detected at histology in 56/78 of the patients (71.8%). Malignancy occurred in 36/38 (94.7%) of the patients in group 1 and in 20/40 (50.0%) of the patients in group 2. Therefore, the positive predictive value (PPV) for PTC was 97.3% in the ICI+ specimens (group 1), with a sensitivity of 64.3% and specificity of 95.2%. When only ICI was present, without atypia and trabeculae, the PPV and specificity were similar (95.0 and 95.2%, respectively), but the sensitivity was decreased (48.7%). In specimens without ICI (group 2), the PPV was only 50.0%; however, combined with young age (<40 yr) and male gender, it reached a value similar to that of group1., Conclusions: In ICI+ specimens compared to ICI-, the risk of PTC is nearly doubled, since PPV increases from 50.0% to 97.3%. This observation suggests that surgery should be considered mandatory in all lesions classified THY4 at FNA, although the relevant difference in terms of cancer risk between ICI- vs ICI+ nodules might be an useful information for both the clinician and the patient.

Necrobiosis lipoidica (NL) is a degenerative disease of dermal connective tissue of unknown etiology characterized by erythematous plaques preferentially localized to distal extremities. Skin lesions show a chronic relapsing nature. NL is often associated with diabetes mellitus and satisfactory treatment options are lacking. We describe the spontaneous healing of NL lesions after pancreas and kidney transplantation in a Type 1 diabetic patient with chronic NL recalcitrant to a variety of standard treatments. The 31-yr-old male patient had experienced NL lesions for more than 15 yr; despite various systemic and topical treatments, the skin lesions had pregressively enlarged. Because of end-stage renal disease, a simultaneous pancreas and kidney transplantation was performed and immunosuppressive therapy with tacrolimus (TAC), mycophenolate mofetil (MMF), and prednisone was started. Pancreatic transplantation maintained satisfactory metabolic control with no need of exogenous insulin. After transplantation, skin lesions slowly healed without any specific treatment, leaving residual areas of fibrotic scars. A skin biopsy confirmed the absence of typical NL lymphocytic and histiocytic inflammatory response. Clinical remission of NL lesions may probably be explained by the concomitant effect of multiple-drug regimen for immunosuppression (TAC, MMF, and prednisone) and improved skin microcirculation secondary to the good metabolic control provided by pancreas transplantation.

Diabetic mastopathy, although reported since 1984, is a poorly recognized diabetes complication. It more frequently affects pre-menopausal women with Type 1 diabetes mellitus and microvascular complications. The pathogenesis of this condition is believed to involve mammary tissue autoimmune reaction to the accumulation of abnormal matrix proteins, caused by hyperglycemia. The lesion often simulates breast cancer; its recognition, therefore, is important to avoid unnecessary diagnostic procedures and surgical treatments. We now report a case of diabetic mastopathy which clinically simulated breast cancer in a young pre-menopausal diabetic woman who, after sonography and mammography, was suggested surgery under suspicion of breast cancer. Histopathological examination by core-biopsy ruled out malignancy.

Metastatic cancer to the thyroid is uncommon. Although the thyroid is richly supplied with blood, there are a few reports of metastatic cancer spreading to this gland. The overall incidence in autopsy series has been quite varied, with rates from 1.2 to 24% of malignant tumors. Most of this metastases are not detected in clinical practice. The majority of these patients had widespread metastases and, as a result, had very short survival times. Although detection of metastases to the thyroid gland often indicates poor prognosis, aggressive surgical and medical treatment may be effective, especially for renal carcinoma. In this report, we present a case of renal carcinoma with thyroid metastases and a review of the literature.

Constitutively activating germline mutations of the TSH receptor (TSH-R) are considered the cause of hereditary non-autoimmune hyperthyroidism. In this study, 10 members (8 affected and 2 unaffected) of an Italian family with hereditary non-autoimmune hyperthyroidism were investigated for the presence of mutations in the TSH-R gene. The clinical features of the disease were also analyzed. PCR-amplified fragments of the TSH-R gene were obtained from genomic DNA extracted from peripheral blood leukocytes of each family member and analyzed by direct nucleotide sequencing and restriction analysis. An identical germline TSH-R mutation was detected in all the patients with hyperthyroidism but in none of the unaffected family members. The mutation was heterozygotic and determined the substitution of valine for methionine (codon 463; ATG-->GTG) in the second transmembrane domain of the TSH-R. When expressed in chinese hamster ovary (CHO) cells, the Val463 mutant TSH-R induced constitutive activation of the TSH receptor. Analysis of the clinical features of our family and those of other families with hereditary non-autoimmune hyperthyroidism, including one with the same Val463 mutation, revealed wide variability in the phenotypical expression of the disease. Our findings indicate that an activating germline mutation in the TSH-R gene plays a key role in hereditary non-autoimmune hyperthyroidism although the onset of clinical manifestations and the evolution of the disease seem to depend heavily on other factors, thus far unidentified. The absence of a clear correlation between mutant genotypes and phenotypic expression of the disease currently limits the prognostic value of genetic testing in families with hereditary non-autoimmune hyperthyroidism.

The aim of this report was to evaluate the incidence of Type 1 diabetes mellitus (T1DM) in the district of Catania (eastern Sicily) in children under 15 yr of age over a ten-yr period (01/01/1989 - 31/12/1998) in relation to age, sex, monthly-seasonal variability, calendar yr and spatial clustering. The estimated completeness of our register was 99.2%. The overall incidence rate was 12.38 per 100,000 during the period of the study. Twenty-four percent of cases were 0-4 yr at diagnosis, 42% were 5-9 yr and 34% were 10-14 yr. More males (no. 148) than females (no. 125) were newly diagnosed with a male/female ratio similar to the base population ratio in the range 0-14 yr and within age groups. The study revealed a non-random spatial distribution of T1DM incidence in children not accounted for by known demographic factors. A significant seasonal pattern and temporal trend of incidence were also detected.

A longitudinal study was carried out in an area of endemic goiter of north-eastern Sicily. Three different surveys (in 1977, 1983 and 1994) evaluated the epidemiological prevalence of goiter in schoolchildren of the endemic area (towns of Bronte, Troina and Maniaci) in comparison to an iodine sufficient control area (Catania). Biochemical studies were also performed on urinary iodine and thiocyanate (SCN) excretion and 131I thyroid uptake. In the town of Troina an experimental program of active iodine prophylaxis was carried out from 1979 to 1987 by iodinating the municipal water supply. The aim of this study was to evaluate the effect of an active iodine prophylaxis program in comparison to the "silent iodoprophylaxis" due to improved economic conditions and widespread introduction of industrially produced food. In the 1977-94 period a significant decrease of goiter prevalence in schoolchildren was observed in all areas where no active iodoprophylaxis had been introduced. An abnormal prevalence of goiter, however, was still present in Bronte (12.1%) and Maniaci (25.9%) schoolchildren in respect to Catania (0.7%). In Troina, goiter prevalence decreased from 52.2 to 6.1% after only five years of active iodine prophylaxis (1983). It increased to 8.4% seven years after the program was discontinued (1994). In all areas studied average urinary iodine excretion increased by 70-100 micrograms/day except in the more rural area at Maniaci. During the same period urinary SCN values decreased by 30-40% and were lower in Troina (non volcanic soil) than in other towns studied. The balance between iodine and SCN intake appears a relevant factor in the etiology of endemic goiter in these areas and the iodine/SCN ratio inversely correlated with goiter prevalence. The persistence of endemic goiter in spite of the important changes in life style and socio-economic conditions if compared to the dramatic amelioration obtained by an active iodine prophylaxis program, confirms the inadequacy of the silent iodine prophylaxis, and further supports the need of an immediate introduction of active iodine prophylaxis in the areas of endemic goiter in Sicily.

This work reports the presence of endemic cretinism in a small district located inside an endemic goiter area in north-eastern Sicily, personally described. The study covers 19 mental defectives (11 females and 8 males, mean age 35.8 +/- 15.5 yr) selected on the basis of severe mental retardation recognized by the local doctors. No systematic survey for cretinism was carried out in the total population. Marked mental retardation was evident in all subjects. Nine of them exhibited clinical and biochemical signs of hypothyroidism (myxedematous cretins). The 10 others were clinically euthyroid and had deaf-mutism and/or pyramidal tract dysfunction (neurological cretinism). Familial aggregation of cretinism was also observed. In both myxedematous and neurological cretins and urinary iodine excretion was very low, but not significantly different from that recorded in the euthyroid controls of the same area. The data available do not clarify the pathogenesis of endemic cretinism in Sicily. However, the marked height retardation, the observation of delayed bone maturation and the severity of mental deficiency suggest that thyroid failure was present in early life. The presence of endemic cretinism today in Sicily constitutes a strong argument in favour of the immediate introduction of adequate iodine prophylaxis.

The reproductive hormone function was investigated in three subjects, two brothers and one unrelated patient, with a Robertsonian translocation, who had come to us because of infertility. Basal levels of LH, FSH, testosterone, 17-beta-estradiol and prolactin were repeatedly measured by radioimmunoassays. In addition, clomiphene citrate, synthetic LH-RH, hCG and TRH tests were carried out. Karyotypes complemented by G-banding and C-banding, repeated semen analyses, and testicular biopsies were also obtained. The karyotype of all three subjects was 45, XY-13, -14, +t(13; 14) (p11; q11). Semen analyses showed oligozoospermia, and reduced or reduced/normal sperm motility. In addition, a high percentage of atypical forms was present in all three subjects. Reproductive hormone measurements in our three patients were substantially normal. Only one of the two brothers exhibited slightly low LH and testosterone levels. Both brothers also had elevated estradiol levels. Gonadotropin and testosterone responses to respective provocative stimuli, as well as prolactin elevation following TRH, were normal. In conclusion, the semen abnormalities observed in these three subjects with Robertsonian translocation appear to be responsible for their impaired fertility. However, the reason why some carriers of the same translocation are fertile and some others are subfertile or infertile remains unclear. It might be speculated that an individual genetic variability is responsible for different degrees of spermatogenic failure, accompanied, in more severe cases, also by reproductive hormone disorders.

We have characterized the GH clinical preparation available in Italy (Grorm, Serono) by gel chromatography and immunoreactivity. Only 50-60% of this preparation can be identified with the active GH monomeric form. Both higher and lower molecular weight compounds are present as well. Then, using a radioimmunoassay technique, we looked for anti-GH antibodies in 21 subjects under Grorm treatment and found them in 6 paitents (28.6%). Two subjects having anti-GH antibodies with high affinity had a lower growth rate. These data suggest that anti-GH antibodies measurement is clinically useful in patients treated with this GH preparation. A more purified preparation should be used when a slowing down of the growth rate is observed in the presence of anti-GH antibodies.

A simple system for simultaneous recording of eye position and spike activity during on-line experimentation is described. The system is based on a relatively inexpensive and widely distributed personal computer. While the hardware is configured from commercially available products, the software has been developed in our laboratory. Data acquisition is controlled by a few routines whose logic is outline, together with the main limitations and the possible improvements of the system itself.

In this work the fate of A14-125 I-insulin inside human cells has been investigated by the complementary use of gel permeation and reversed-phase high performance liquid chromatography to obtain a better resolution of the cell processed radioactive material resulting from the internalization of labeled insulin. Mononuclear leukocytes from 12 normals were incubated with pure A14-125 I insulin at 37 C and internalized radioactivity was characterized after 2, 15 and 60 min. Nearly 14% of intracellular radioactivity was associated to materials with a molecular weight of approximately 300,000. The remaining 86% had a molecular weight lower than 20,000. High molecular weight material showed an elution profile very similar to that obtained from purified human placental insulin receptor and was partially precipitable with antireceptor antibody. The reversed phase high performance liquid chromatography analysis of the low molecular weight material showed two main peaks corresponding to 125 I and A14-125 I-insulin and three intermediate peaks, a, b, c, accounting for about 8% of the recovered radioactivity. By increasing the incubation time of A14-125 I-insulin with monocytes a decrease of insulin peak (2 min: 38 +/- 18%; 15 min: 25 +/- 11%; 60 min: 6 +/- 4%) and a corresponding increase of iodide peak was observed. Immunoprecipitability with anti-insulin antibody was 0% for iodide and a peaks, 60% for peak b, 78% for peak c and 90% for A14-insulin peak. Our results show that intracellular insulin degradation procedes rapidly and in a time-dependent manner and that this process produces insulin derivatives which partially retain the immunological properties of intact A14-125 I insulin.(ABSTRACT TRUNCATED AT 250 WORDS)