Persistent severe visual field impairment is associated with obesity and tumour invasiveness, but not with pituitary dysfunction, in patients with craniopharyngioma.

PURPOSE: Craniopharyngiomas (CP) are benign tumours of the sellar region. Hypopituitarism, visual deficits, hypothalamic damage with consequent obesity and related increased cardiovascular risk, are complications due to the tumour itself or secondary to treatment strategy. We retrospectively correlated visual field status with clinical, neuroradiological, histopathological features and management strategy, in a single-centre cohort of patients with CP. METHODS: Thirty-four patients (16 M; median age 27.2 ± 21.8 yrs) with CP were included. We evaluated visual field status, assessed by means of standard automated perimetry and expressed as mean deviation (MD), at last follow-up visit (median 14 ± 11.7 yrs). MD has been correlated with clinical, radiological, histological data and treatment modalities. RESULTS: In univariate analysis worst eye MD was significantly associated with panhypopituitarism (p 0.010). In multivariable linear regression, panhypopituitarism (p 0.008), CP recurrence (p 0.020) and DI (p 0.004) were found to be the main independent predictors of a worse visual field outcome. When stratifying patients according to the degree of visual field impairment (MD < -12 dB Vs MD > -12 dB), the main independent predictors of worse visual field outcome were older age at diagnosis (p 0.010), CP histological subtype (p 0.004), invasiveness (p 0.04), CP recurrence (p 0.035), DI (p 0.002) and weight at last follow-up (p 0.012). CONCLUSION: In CP patients the long-term ophthalmological impairment is frequent, especially at older age, and strictly related to tumour invasiveness and recurrence, and associated to pituitary disfunction and obesity.

AN ITALIAN SURVEY OF COMPLIANCE WITH MAJOR GUIDELINES FOR L-THYROXINE OF PRIMARY HYPOTHYROIDISM.

OBJECTIVE: The adherence by endocrinologists to guideline regarding levothyroxine (LT4) therapy and the compliance of patients may impact the management of hypothyroidism. The aim of this study was to compare the adherence of Italian endocrinologists to the ATA/AACE and ETA guidelines on the management of newly diagnosed primary hypothyroidism and to validate the Italian version of the Morisky-Green Medical Adherence Scale-8 (MMAS-8) questionnaire as applied to the evaluation of the adherence of patients with hypothyroidism to LT4 treatment. METHODS: This was an observational, longitudinal, multicenter, cohort study, involving 12 Italian Units of Endocrinology. RESULTS: The study enrolled 1,039 consecutive outpatients (mean age 48 years; 855 women, 184 men). The concordance of Italian endocrinologists with American Association of Clinical Endocrinologists/American Thyroid Association (AACE/ATA) and European Thyroid Association (ETA) recommendations was comparable (77.1% and 71.7%) and increased (86.7 and 88.6%) after the recommendations on LT4 dose were excluded, considering only the remaining recommendations on diagnosis, therapy, and follow-up. The MMAS-8 was filled out by 293 patients. The mean score was 6.71 with 23.9% low (score <6), 38.6% medium (6 to <8), 37.5% highly (= 8) adherers; the internal validation coefficient was 0.613. Highly adherent patients were not more likely to have good control of hypothyroidism compared with either medium (69% versus 72%, P = .878) or low (69% versus 43%, P = .861) adherers. CONCLUSION: Clinical management of hypothyroidism in Italy demonstrated an observance of international guidelines by Italian endocrinologists. Validation of the Italian version of the MMAS-8 questionnaire provides clinicians with a reliable and simple tool for assessing the adherence of patients to LT4 treatment. ABBREVIATIONS: AACE = American Association of Clinical Endocrinologists; ATA = American Thyroid Association; EDIPO = Endotrial SIE: DIagnosis and clinical management of Primitive hypothyrOidism in Italy; eCRF = electronic case report form; ETA = European Thyroid Association; fT3 = free triiodothyronine; fT4 = free thyroxine; LT4 = levothyroxine; MMAS-8 = Morisky-Green Medical Adherence Scale-8; PH = primary hypothyroidism; T3 = triiodothyronine; T4 = thyroxine; TSH = thyroid-stimulating hormone; US = ultrasonography.

Vitamin D receptor gene polymorphisms/haplotypes and serum 25(OH)D3 levels in Hashimoto's thyroiditis.

Vitamin D deficiency and/or reduced function, as per certain polymorphisms of the vitamin D receptor (VDR) gene, have been related to several autoimmune disorders. The present study was aimed to investigate the association of Hashimoto's thyroiditis with vitamin D status and functional polymorphisms (SNPs) of the VDR gene. In this case-control study, 200 euthyroid subjects were enrolled: 100 newly diagnosed HT patients (87 F, 13 M; mean age ± SD 42 ± 15 year) and 100 healthy individuals, matched for age, sex, BMI, and month of blood sampling. Serum 25(OH)D3 was measured by HPLC. The VDR SNPs BsmI, ApaI, and TaqI, in strong linkage disequilibrium with each other, were detected by restriction fragment length polymorphism-PCR. The prevalence of vitamin D deficiency in HT patients was significantly higher than that in the control group (70 vs 18.2 %; p < 0.0001), and median serum 25(OH)D3 level was significantly lower in HT patients than controls (median value: 16.2 vs 37.4 ng/ml; p = 0.026). Moreover, there was a significant inverse correlation between serum 25(OH)D3 and TPOAb concentration (r = -0.669; p = 0.034). Contrarily, the genotype distribution of the studied SNPs was not different in the two groups (BsmI p = 0.783; ApaI p = 0.512; TaqI p = 0.471), as was the allelic frequency [f(B) p = 0.776, f(b) p = 0.887; f(A) p = 0.999, f(a) p = 0.999; f(T) p = 0.617; f(t) p = 0.617]. The present study first investigates newly diagnosed untreated HT and suggests that vitamin D deficiency may contribute to HT development and/or progression, acting as an environmental trigger, while the VDR locus does not appear to be involved in conditioning the genetic susceptibility to the disease, at least in Caucasians.

Oxidative Stress and Advanced Glycation End Products in Hashimoto's Thyroiditis.

BACKGROUND: Oxidative stress, which occurs as a result of an imbalance between free-radical production and antioxidant defense mechanisms, has been implicated in the pathogenesis of several autoimmune disorders, including thyroid diseases. Importantly, it has been correlated to thyroid dysfunction. This study investigated the changes in oxidative balance in euthyroid Hashimoto's thyroiditis (HT) by means of specific serum tests, such as derived reactive oxygen metabolites (d-ROMs) and the biological antioxidant potential (BAP) test. In addition, advanced glycation end products (AGEs) and advanced oxidation protein products (AOPPs)--compounds formed by the transformation of proteins--were evaluated as potential new markers of oxidative stress in this disease. METHODS: This study included 134 euthyroid subject: 71 newly diagnosed HT patients (63 females; M age = 38 ± 13 years) and 63 age and sex-matched healthy controls. None of them were on thyroxine therapy. RESULTS: Serum d-ROMs were elevated, and BAP decreased in HT patients compared with controls (p < 0.001), and the two parameters were inversely correlated (r = -0.211; p = 0.027), clearly indicating an enhanced oxidative stress. Furthermore, AGE levels were higher in HT patients (M = 223.18 AU/g prot) than in controls (M = 189.636 AU/g prot; p = 0.020) and inversely correlated with BAP levels (r = -0.196; p = 0.037). In uni- and multivariate analysis, serum antithyroperoxidase antibodies were the main predictors for d-ROMs (p = 0.006), BAP (p < 0.001), and AGEs (p = 0.014), irrespective of thyrotropin and/or free thyroxine values. No differences in AOPPs levels were found between patients and controls (p = 0.923). CONCLUSIONS: Oxidants are increased and antioxidants decreased in euthyroid HT patients. As a result, the oxidative/antioxidative balance is shifted toward the oxidative side. Moreover, this study reports on a possible significant involvement of AGEs in HT, thus contributing to a better definition of the redox homoeostasis dysregulation in HT.

Skin fibrosis correlates with circulating thyrotropin levels in systemic sclerosis: translational association with Hashimoto's thyroiditis.

Systemic sclerosis (SSc) is a connective tissue disease, characterized by cutaneous and multi-organ fibrosis, and vascular abnormalities. Skin thickening is a characteristic feature of SSc and resembles myxedematous skin. Our aim was to correlate the degree of skin involvement in SSc patients with serum TSH levels, since TSH receptors are widely expressed in human tissues, including the skin. In this cross-sectional study, we enrolled 70 SSc patients, all females with a mean age of 47 ± 11 year. Thirty-five age- and sex-matched HT patients were recruited, as controls. Subjects under L-thyroxine therapy and/or with positive anti-TSH receptor antibodies were excluded. In all subjects, we measured serum TSH, FT4, and free tri-iodothyronine (FT3) levels. Skin thickness was evaluated using the modified Rodnan total skin score (mRSS). mRSS averaged 14 ± 9 for SSc and 4 ± 6 for HT patients. TSH levels positively correlated with skin scores in both SSc and HT patients groups. In SSc patients, FT3 and FT4 showed an inverse correlation with mRSS, while in HT only FT4 levels showed this inverse significance. When divided by cutaneous extent, SSc patients with diffuse disease form had higher TSH serum levels compared to those with the limited form; additionally, the correlations between TSH, FT4, and mRSS reached statistical significance. Our preliminary data clearly indicate that serum TSH is higher in SSc patients with more severe skin disease, and significantly correlate with the mRSS. Therefore, TSH could play a role in the development of cutaneous changes in SSc patients.

Serum interleukin-22 (IL-22) is increased in the early stage of Hashimoto's thyroiditis compared to non-autoimmune thyroid disease and healthy controls.

OBJECTIVE: Hashimoto's thyroiditis (HT) is considered to be a Th1-related autoimmune disease (AID). Recent studies revealed that Th17 lymphocytes (producing mostly IL-17, IL-21 and IL-22) play a major role in numerous AIDs commonly thought to be Th1 diseases. More recently, another subset of Th cells, which produce IL-22 and thus so-called Th-22, have been identified. Few data are available in the literature on the role of IL-22, the main soluble mediator of both Th17 and Th22 cells, in HT. DESIGN: Using IL-22 Quantikine ELISA Kit (lower limit of detection 0.7 pg/ml), we assayed serum levels of IL-22 in three groups of subjects: newly diagnosed HT patients (n=55, 5 males and 50 females, age 38±17 years), non-HT patients with nodular goiter (n=30, 4 males and 26 females, age 43±14 years) and an age- and sex-matched group of healthy individuals. HT patients were euthyroid and were not receiving any treatment. RESULTS: HT patients showed significantly higher levels of serum IL-22 (group A, 42±34 pg/ml) as compared to non-HT-goitrous patients (18±15 pg/ml; P<0.001) and healthy controls (20±13 pg/ml; P=0.014). Serum IL-22 levels did not differ between non-HT-goitrous patients and healthy controls (p=0.496). No significant correlation was found between serum levels of IL-22 and Tg-Ab, TPO-Ab or TSH in the HT patients. CONCLUSIONS: Serum IL-22 is increased in newly diagnosed, untreated HT patients, as compared to thyroid autoimmune disease-free individuals. Our data suggest that IL-22 could play some role in the development of HT.

An uncommon case of Marine-Lenhart syndrome.

The term Marine-Lenhart syndrome describes the association between Graves' disease and autonomously functioning thyroid nodules (AFTN), such as toxic adenoma or toxic multinodular goiter. The two diseases may coexist or may be present at different moments in the same patient. In the literature, there are many reports on the development of Graves' disease after radioiodine treatment for AFTN, but very little information may be found on the occurrence of AFTN after radioiodine therapy for Graves' disease. We describe here the case of a female patient with Graves' disease who was successfully treated with radioiodine for Graves' disease, returning to normal thyroid function. Three years later, biochemical analysis and ultrasound examination identified a thyroid nodule that progressively increased in size. The 99mTc-pertechnetate scintigraphy showed avid uptake in the right lobule, which corresponded to a nodular lesion consistent with AFTN.

An uncommon case of Marine-Lenhart syndrome / Um caso incomum de síndrome de Marine-Lenhart

The term Marine-Lenhart syndrome describes the association between Graves’ disease and autonomously functioning thyroid nodules (AFTN), such as toxic adenoma or toxic multinodular goiter. The two diseases may coexist or may be present at different moments in the same patient. In the literature, there are many reports on the development of Graves’ disease after radioiodine treatment for AFTN, but very little information may be found on the occurrence of AFTN after radioiodine therapy for Graves’ disease. We describe here the case of a female patient with Graves’ disease who was successfully treated with radioiodine for Graves’ disease, returning to normal thyroid function. Three years later, biochemical analysis and ultrasound examination identified a thyroid nodule that progressively increased in size. The 99mTc-pertechnetate scintigraphy showed avid uptake in the right lobule, which corresponded to a nodular lesion consistent with AFTN.

O termo “síndrome de Marine-Lenhart” descreve a associação da doença de Graves e nódulos tireoidianos de funcionamento autônomo (AFTN), como no adenoma tóxico ou bócio multinodular tóxico. As duas doenças podem coexistir ou podem estar presentes em diferentes momentos no mesmo paciente. Na literatura, existem muitos relatos sobre o desenvolvimento da doença de Graves após radioiodoterapia para AFTN, mas muito poucos dados podem ser encontrados em relação ao aparecimento de AFTN após radioiodoterapia para doença de Graves. Descrevemos o caso de uma paciente do sexo feminino com doença de Graves que realizou com sucesso o tratamento com iodo radioativo, com a normalização da função da tireoide. Três anos depois, uma análise bioquímica e um exame de ultrassonografia identificaram o aparecimento de um nódulo na tireoide que progressivamente aumentou de tamanho. A cintilografia com 99mTc-pertecnetato revelou uma captação ávida no lóbulo direito, correspondente à lesão nodular, consistente com uma AFTN.

Lack of association between autonomously functioning thyroid nodules and germline polymorphisms of the thyrotropin receptor and Gαs genes in a mild to moderate iodine-deficient Caucasian population.

BACKGROUND: Mutations of the thyrotropin receptor (TSHR) and/or Gαs gene have been found in a number of, but not all, autonomously functioning thyroid nodules (AFTNs). Recently, in a 15-year-old girl with a hyperfunctioning papillary thyroid carcinoma, we found two somatic and germline single nucleotide polymorphisms (SNPs): a SNP of the TSHR gene (exon 7, codon 187) and a SNP of Gαs gene (exon 8, codon 185). The same silent SNP of the TSHR gene had been reported in patients with AFTN or familial non-autoimmune hyperthyroidism. No further data about the prevalence of the two SNPs in AFTNs as well as in the general population are available in the literature. AIM: To clarify the possible role of these SNPs in predisposing to AFTN. METHODS: Germline DNA was extracted from blood leukocytes of 115 patients with AFTNs (43 males and 72 females, aged 31-85 years, mean ± SD = 64 ± 13) and 100 sex-matched healthy individuals from the same geographic area, which is marginally iodine deficient. The genotype distribution of the two SNPs was investigated by restriction fragment length polymorphism-polymerase chain reaction. RESULTS: The prevalence of the two SNPs in our study population was low and not different to that found in healthy individuals: 8 % of patients vs. 9 % of controls were heterozygous for the TSHR SNP and 4 % patients vs. 6 % controls were heterozygous for the Gαs SNP. One patient harbored both SNPs. CONCLUSIONS: These results suggest that these two SNPs do not confer susceptibility for the development of AFTN.

The unusual association of Graves' disease, chronic spontaneous urticaria, and premature ovarian failure: report of a case and HLA haplotype characterization / A associação incomum entre doença de Graves, urticária crônica idiopática e insuficiência ovariana prematura: relato de caso clínico e tipagem HLA

Chronic spontaneous urticaria (CSU), defined as the occurrence of spontaneous wheals for more than six weeks, has been associated with autoimmune diseases. Herein, we report the unusual association of CSU, Graves' disease, and premature ovarian failure. Human leukocyte antigen (HLA) studies were performed. A 36-year-old woman presented symptoms and signs of hyperthyroidism for three months. In the same period, the patient complained of widespread urticarial wheals, intensely itchy, and poorly responsive to therapy with antihistaminic agents. Hyperthyroidism was confirmed biochemically, and treatment with methimazole was started. As hyperthyroidism improved, a marked improvement in her urticaria was also observed. However, the patient continued to complain of amenorrhea. Endocrine evaluation, at the age 38, was consistent with premature ovarian failure. This is the first report of coexistence of GD, CSU, and POF. The genetic background of such unusual association is a specific combination of HLA.

A urticária crônica idiopática, caracterizada pelo aparecimento de pápulas espontâneas e persistentes por pelo menos seis semanas, tem sido associada a doenças autoimunes. Apresentamos aqui o caso da associação incomum entre urticária crônica idiopática, doença de Graves e falência ovariana prematura. Foram conduzidos estudos de tipagem HLA. Uma mulher de 36 anos apresentou sinais e sintomas de hipertireoidismo por três meses. No mesmo período, a paciente queixou-se do aparecimento de pápulas urticariformes generalizadas que coçavam intensamente e não eram responsivas ao tratamento com anti-histamínicos. O hipertireoidismo foi confirmado bioquimicamente, e o tratamento com metimazol foi iniciado. Assim que os valores hormonais se normalizaram, observou-se uma melhoria significativa do quadro de urticária. No entanto, a paciente continuou a apresentar amenorreia. A avaliação endocrinológica, com a idade de 38 anos, mostrou falência ovariana prematura. Este é o primeiro caso de associação entre doença de Graves, urticária idiopática crônica e falência ovariana prematura. A base genética dessa associação incomum é representada por combinações específicas de haplótipos HLA.

The unusual association of Graves' disease, chronic spontaneous urticaria, and premature ovarian failure: report of a case and HLA haplotype characterization.

Chronic spontaneous urticaria (CSU), defined as the occurrence of spontaneous wheals for more than six weeks, has been associated with autoimmune diseases. Herein, we report the unusual association of CSU, Graves' disease, and premature ovarian failure. Human leukocyte antigen (HLA) studies were performed. A 36-year-old woman presented symptoms and signs of hyperthyroidism for three months. In the same period, the patient complained of widespread urticarial wheals, intensely itchy, and poorly responsive to therapy with antihistaminic agents. Hyperthyroidism was confirmed biochemically, and treatment with methimazole was started. As hyperthyroidism improved, a marked improvement in her urticaria was also observed. However, the patient continued to complain of amenorrhea. Endocrine evaluation, at the age 38, was consistent with premature ovarian failure. This is the first report of coexistence of GD, CSU, and POF. The genetic background of such unusual association is a specific combination of HLA.