Francesca Sorvillo

Long‐term effects of lanreotide SR and octreotide LAR® on tumour shrinkage and GH hypersecretion in patients with previously untreated acromegaly

background and objective The therapeutic efficacy of lanreotide SR and octreotide LAR® has been studied widely in patients treated previously with neurosurgery and/or radiotherapy. These therapies limit the evaluation of the long‐term effects of somatostatin analogues on tumour shrinkage. Neurosurgical and radiotherapy treatments cause irreversible anatomical changes in pituitary morphology, which can make accurate evaluation of tumour shrinkage difficult. The aim of this study was to investigate the therapeutic efficacy of lanreotide SR and octreotide LAR® in previously untreated patients with acromegaly. We aimed to investigate the long‐term effects of these drugs on tumour shrinkage and growth hormone (GH) hypersecretion without the confounding influences of previous therapy.

Recombinant Human TSH Modulates In Vivo C‐Telopeptides of Type‐1 Collagen and Bone Alkaline Phosphatase, but Not Osteoprotegerin Production in Postmenopausal Women Monitored for Differentiated Thyroid Carcinoma

In women monitored for thyroid carcinoma, short‐term stimulation with rhTSH induced an acute decrease in serum C‐telopeptides of type‐1 collagen and an increase in serum BALP levels without any effect on OPG production. The inhibitory effect of TSH on bone resorption occurred only in postmenopausal women who showed low BMD and a high bone turnover rate as an effect of L‐thyroxine suppressive therapy.

Grey-scale analysis allows a quantitative evaluation of thyroid echogenicity in the patients with Hashimoto's thyroiditis

objective In the present study we have performed a grey‐scale quantitative analysis of thyroid echogenicity in the patients affected by Hashimotos thyroiditis (HT), obtaining a numerical estimate of the degree of hypoecogenicity associated with the appearance of thyroid dysfunction.

Temporal relationship between the appearance of thyroid autoantibodies and development of destructive thyroiditis in patients undergoing treatment with two different type-1 interferons for HCV-related chronic hepatitis: A prospective study

In this prospective study we performed repeated evaluations of thyroid status in patients undergoing treatment with different preparations of recombinant interferons (IFNs), in order to identify early markers of thyroid dysfunction. Moreover, we aimed to investigate whether the development of thyroid dysfunction was related to the appearance of thyroid autoimmunity. Our study included 51 consecutive patients without pre-existing thyroid disease, admitted to our hospital for Hepatitis C virus (HCV)- related chronic hepatitis. Thirty-six patients (Gr. A) were treated with IFN-α 2b plus ribavirin (RIBA), whereas 15 patients (Gr. B) underwent treatment with IFN-αcon-1 (CIFN) plus RIBA. Thyroid autoimmunity and function were prospectively evaluated before, every month during treatment and for 6 months after IFN withdrawal. At study entry, all patients were euthyroid and negative for thyroid autoantibodies. In Gr. A, 10 patients developed thyroid autoimmunity after a median period of 3 months (range: 1–6) treatment with IFN-α+RIBA. At the time of appearance of thyroid autoantibodies, 4 patients developed destructive thyrotoxicosis (overt in one case, subclinical in 3 cases), while other 4 patients showed a high reduction of serum TSH levels (median decrease: − 75.7%, range: −61.9- −84.2), which reached the low values of normal range. After a median period of 2 months (range: 1–3) from these biochemical abnormalities, 6 patients continuing antiviral treatment developed hypothyroidism (overt in 3 cases and subclinical in the other 3). In Gr. B, 5 patients developed thyroid autoimmunity after a median period of 3 months (range: 2–10) of treatment with CIFN+RIBA. Soon after the appearance of thyroid autoantibodies, all patients developed an overt thyrotoxicosis (with hyperthyroidism in 2 cases). Antiviral treatment was discontinued in all 5 cases. Thereafter, thyroid function recovered spontaneously without significant modifications of serum TGAb and TPOAb levels until the end of the study. In conclusion our prospective study demonstrated that: 1) the appearance of thyroid autoantibodies during treatment with IFN was accompanied in most cases by the occurrence of a destructive process in the thyroid gland; 2) The clinical expression of destructive thyroiditis was more evident in patients treated with CIFN than that in patients treated with IFN; 3) The thyroid clinical outcome of these patients was strictly correlated to the continuation of cytokine treatment.

Interferon-related thyroid autoimmunity and long-term clinical outcome of chronic hepatitis C.

BACKGROUNDnA high incidence of thyroid autoantibodies and/or disorders was observed in subjects with hepatitis C virus-related chronic hepatitis during interferon-alpha therapy.nnnAIMnTo evaluate whether thyroid autoimmunity and dysfunction, induced by interferon-alpha therapy, could be viewed as predictors for treatment response and as valid prognostic markers of liver disease progression.nnnPATIENTSnA total of 136 subjects (96 males/40 females; median age 48 years; range 23-64) affected by biopsy-proven chronic hepatitis C (33.1% with compensated liver cirrhosis).nnnMETHODSnAll subjects were treated with interferon-alpha therapy at 6 MU 3 times weekly for 12 months and then followed up for an average period of 60 months (range 12-108). Routine laboratory tests, virological assessment, liver ultrasound, thyroid function tests (serum free-triiodothyronine, free-thyroxine, serum thyrotropin), and autoimmunity were performed for all subjects.nnnRESULTSnPercentage of thyroid autoimmunity and thyroid dysfunction in long-term responders was not significantly different compared to that in non-responders (47.0% and 11.8% vs 35.3% and 5.9%, respectively; non significant). The multivariate model demonstrated that the absence of cirrhosis was the only factor significantly related to successful response to therapy (odds ratio: 14.9; 95% confidence interval: 1.9-115.0 for chronic hepatitis C vs presence of cirrhosis). Moreover, the occurrence of thyroid autoimmunity during interferon therapy was similar both in patients with or without worsening of liver disease (33.3% and 39.8%, respectively; p = not significant). No subject with on-going liver disease developed thyroid dysfunction during treatment, as opposed to the 10/118 (8.4%) with a better course of liver disease; however, this difference was not statistically significant. The multivariate model showed that age was the only covariate significantly associated with unfavourable outcome of liver disease (odds ratio: 18.6; 95% confidence interval: 2.3-151.9, for those over 48 years vs younger patients).nnnCONCLUSIONSnThere is no evidence that the immune mechanism involved in the pathogenesis of thyroid autoimmune phenomena is the same as that regulating the therapeutic clearance of HCV or modulating the unfavourable course of HCV-related chronic hepatitis. However, our study confirmed that liver disease seems to progress more slowly in younger subjects.

Iodized salt improves the effectiveness of l‐thyroxine therapy after surgery for nontoxic goitre: a prospective and randomized study

objective To investigate whether the addition of iodized salt to daily diet in thyroidectomized patients for nontoxic goitre could influence the effectiveness of nonsuppressive l‐thyroxine (L‐T4) therapy on thyroid remnant size, during 12 months’ follow‐up after thyroid surgery.

The influence of parity on multinodular goiter prevalence in areas with moderate iodine deficiency

Despite the observation that parity may increase the risk of thyroid carcinoma, very few studies have investigated the possible repercussion of parity on thyroid benign pathology. Recently, parity has been identified as one of the factors contributing to a larger thyroid size in healthy females. The aim of this work was to investigate a possible role for parity on the prevalence of multinodular goiter in iodine deficient areas. For this purpose, the reproductive histories of 2 cohorts of women, normal (Group I, 235 cases) and non-toxic multinodular goiter (NTMNG) affected (Group II, 274 cases) were compared. All subjects were euthyroid and had no previous history of thyroid function abnormalities. The number of full-term previous pregnancies (2.55±0.11 vs 1.77±0.10) and age (47.7±0.76 vs 42.3±0.83 yr) were found significantly higher (p<0.001) in multinodular goiter (MNG) patients than controls. Parity and age were found to be directly correlated (p<0.001), nevertheless the partial correlation coefficients demonstrated an independent and statistically significant difference for both variables between normal and NTMNG. Therefore, the independent effects of parity and age were further investigated. The effect of age on NTMNG prevalence seems to be weaker, in fact significant differences (p≪0.001) for age between patients and controls were detected only when the effect of parity was absent (nulliparous), while with increasing gestations the effect of age disappeared. Our results indicate that age plays a minor role compared to parity which can therefore be considered as a stronger risk factor. In conclusion, the present study shows that, at least in iodine deficient regions, non-toxic multinodular goiter women show a statistically significant higher parity rate than healthy controls. Age may play a certain role but only when additional stronger risk factors are absent.

Increased serum reverse triiodothyronine levels at diagnosis of hepatocellular carcinoma in patients with compensated HCV‐related liver cirrhosis

objective The aim of this study was to investigate changes in thyroid hormone metabolism in relation to the development of hepatocellular carcinoma (HCC) in patients with HCV‐related liver cirrhosis.

Is the IFN-alpha-related thyroid autoimmunity an immunologically heterogeneous disease?

Dear Sir, Over the last years, many studies have aimed to investigate the relationship between the appearance of autoimmune phenomena in the course of interferon-alpha (IFN-a) treatment and the therapeutic response of the underlying viral or neoplastic disease [1–5]. We read with great interest the paper by Dalgrad et al. which demonstrated that, in patients treated with IFN-a plus ribavirin for HCV-related chronic hepatitis, the response to the antiviral treatment was not correlated to the appearance of thyroid dysfunction [5]. This result was in accordance with previous studies [1, 2, 4], but in disagreement with others demonstrating that the IFN-induced thyroid disease occurred more frequently in patients with a sustained response to the cytokine treatment [3]. The authors considered the different duration of the cytokine treatment as a possible factor explaining this discrepancy. We think that immunological and genetic aspects should also be considered in this context. The type 1 immune response plays a critical role in the resolution of viral infection, as well as in the development of many autoimmune diseases [6–8]. In thyroid autoimmune disease, however, the T helper (Th)1 and Th2 responses coexist in the same patients, although with different reciprocal intensity in relationship with the clinical expression of the disease process [9]. The type 1 response seems to be dominant in the course of hypothyroidism occurring in patients with Hashimoto’s thyroiditis and in the course of silent thyroiditis, whereas the type 2 response has been correlated mainly with the appearance of hyperthyroidism in the cases affected by Graves’ disease [10–13]. In particular, the thyroid-destructive process in Hashimoto’s thyroiditis seems to be induced mainly by cell-mediated immunity, as demonstrated by the increase of serum Th1 cytokines in this condition [13]. However, Graves’ thyrotoxicosis is induced by the thyroidstimulating autoantibodies to thyrotropin receptor, the production of which is likely to depend on Th2 cell function [12]. The same mechanisms should be considered for the IFN-related thyroid autoimmunity. In this view, the patients who develop Graves’type thyrotoxicosis in the course of treatment with IFN-a should be considered immunologically different to those showing hypothyroidism or transient thyrotoxicosis by a destructive process in the thyroid gland [14, 15]. The fact that in the various studies the different clinical pictures of the IFN-related thyroid autoimmunity were not considered separately could explain the controversial data of literature about the correlation between the response to the antiviral treatment and the appearance of thyroid disease. Unfortunately, such differentiation is not always possible because different expressions of the thyroid disease can occur in the same patient, suggesting a possible evolution of the immunological process throughout the IFN treatment [16]. However, a probable correlation between the remission of chronic hepatitis and the appearance of thyroid disease should be considered only for those patients with a Th1-mediated destructive process in the thyroid gland, mainly when the antiviral treatment is performed with IFN-a plus ribavirin [17]. Nevertheless, it does not mean that the two events are constantly correlated. In fact, most of the patients with sustained response to antiviral treatment show neither thyroid autoimmunity nor thyroid dysfunction [17]. This apparent paradox is easily explained by the fact that whilst the response to the antiviral treatment is related to both host and viral factors [18, 19], the genetic background seems to play a predominant role in determining the occurrence of the IFN-related thyroid autoimmunity [20]. In this view, the IFN-a plus ribavirin treatment can trigger a Th1-mediated cytotoxic process in the thyroid gland Journal of Internal Medicine 2002; 252: 377–378

Diabetes insipidus and increased serum levels of leptin and lactate-dehydrogenase (LDH) in an adolescent boy with a primary intracranial germinoma. Case Report and an endocrinological revaluation of literature

A 16-year-old boy presented with a four-month history of polyuria-polydipsia and a diplopia which had reverted after treatment. The neuroimaging studies performed had been strongly suggestive of an optic nerve glioma, while en-docrinological investigation (β-hCG 420 IU/L) has lead to the correct diagnosis later confirmed at the immunohystochemical analysis performed at biopsy. The high serum level of hCG was unaffected by bromocriptine nor octreotide, while the PRL level (80.0 μg/L) was reduced only by bromocriptine. Among the several tumor markers which may be secreted by such lesions, ours is the first reported case of an elevation of serum LDH for a primary intracranial germinoma. Moreover, the elevated value of serum leptin reported by us might be due to the insensitivity of the hypothalamic structures to endogenous leptin.