Lidia Sava

The frequency of cold thyroid nodules and thyroid malignancies in patients from an iodine-deficient area

An analysis of thyroid cancer morbidity was carried out in two adjacent areas of Sicily differing in iodine intake. A consecutive series of 911 patients with “cold” nodules from an iodine‐deficient area (IDA) and 2537 from a control area (CA) were examined by fine needle aspiration and selected for surgery and pathologic examination. Malignancies were found in 27 of the patients (2.96%) from the IDA and in 139 patients (5.48%) from the CA. Based on a population survey indicating that “cold” thyroid nodules were 2.5 times more frequent in the IDA with respect to the CA, we calculated a prevalence of 127 thyroid cancers per 105 inhabitants in the IDA versus 93 in the CA (P < 0.001). Moreover, follicular and anaplastic carcinomas were three times more frequent in the IDA than in the CA (75 versus 24 cases per 105 inhabitants, respectively). These studies indicate that iodine deficiency may be one factor in the development of certain thyroid malignancies in man.

Genetics of Specific Phenotypes of Congenital Hypothyroidism: A Population-Based Approach

Congenital hypothyroidism (CH) may cause severe and irreversible neurologic and developmental abnormalities when not recognized early. Many millions of newborns have now been screened and many thousands of patients with CH have been identified. Approximately 80%-85% have defects of thyroid gland development, while 15%-20% have congenital errors of thyroid hormone biosynthesis. An entire population screened for CH over a long period of time, was studied in the present report, using a population-based approach. In particular, two CH phenotypes, both presenting with in situ thyroid gland (patients with either goiter or with thyroid gland volume ranging from normal to hypoplasic) were analyzed. Mutations were searched in some of the most likely candidate genes: thyroperoxidase (TPO) in patients with CH goiter, Pax8 and thyrotropin receptor (TSHR) in the other group. In the former group (n = 8), four TPO gene mutations were identified in three patients. One patient was a compound heterozygous. In two cases an already described mutation (1277(insGGCC)) was present; in two other cases mutations not previously described (1996(G-->T) and 2295(G-->A)), which induced aminoacid variations with a Glu --> Stop and Val --> Ile changes, respectively, were identified. In all patients mutations were inherited from one of the parents. In the case of the compound heterozygous patient, one mutation was inherited from the mother (1277(insGGCC)) and the other from the father (1996(G-->T), Glu --> Stop). In the latter group (n = 8), a patient with a 16-base pair C(T)(13)CC deletion in TSHR gene intron 8, 42-bp distal to exon/intron 8 splice junction, was identified. No mutation was identified in Pax8 gene.

Ultrasound scanning assessment of L-Thyroxine treatment effectiveness in a group of children with diffuse goiter

Ultrasound scanning is an accurate and objective method to assess thyroid volume; therefore it is useful to evaluate the effectiveness of L-thyroxine treatment in reducing goiter size, especially in children where clinical evaluation is inaccurate. In this prospectic study we evaluated the effectiveness of one-year L-thyroxine treatment in a group of children with nontoxic diffuse goiter coming from an area with low iodine intake. We examined 11 children (7 females, 4 males), age range 9–14 years. At clinical examination, 6 patients had a goiter classified la (according to WHO criteria), 4 had a class lb and only 1 had a class II goiter. In order to achieve an accurate goiter evaluation, the thyroid volume was determined by ultrasonic scanning with a 5 MHz linear probe before and after treatment. Patients were given a dose of L-thyroxine (1.5–2.0 µg/kg/die) in order to significantly reduce serum TSH levels (from 1.8 ± 0.6 to 0.8 ± 0.5 mU/l, mean ± SD). Patients were reexamined at 12 months of therapy and again at 10 months after therapy withdrawal. A significant reduction of the goiter volume (> 20%) was obtained in 6/11 (54%) patients, although serum TSH levels were fully suppressed only in one. The mean goiter size reduction in “responders” was −31.2 ± 9.3 % (m ± SE). After therapy withdrawal goiter size increased in the majority of cases (in 4/11, > 20%). Our study demonstrates that L-thyroxine treatment is effective in reducing goiter size in the majority of children with a diffuse goiter. Full TSH suppression is not necessary to obtain goiter volume reduction because a decrease of TSH levels to low values can already mediate a good therapeutical response. Since the majority of patients shows an increase of thyroid volume after therapy withdrawal, L-thyroxine administration should be a long term therapy.

Cytogenetic analysis in congenital hypothyroidism

In order to evaluate the possible role of genetic factors in the pathogenesis of congenital hypothyroidism (CH), we investigated the occurrence of chromosome aberrations in a consecutive series of 47 patients with CH and 208 matched healthy controls. No abnormal karyotype was found in CH patients. In 5 CH patients and in 3 healthy controls a number of heterochromatin variants was detected. Although chromosomal variants are devoid of phenotypic effects, the frequency of these variants was higher in CH patients than in the control group (10.6% vs 1.4%, p < 0.005). These findings suggest that the association of congenital hypothyroidism with chromosomal variants may reflect more than chance concurrence.

Comment on: Yang et al. (2010) Associations of Hyperglycemia and Insulin Usage With the Risk of Cancer in Type 2 Diabetes: The Hong Kong Diabetes Registry. Diabetes;59:1254–1260

By analyzing data from the Hong Kong Diabetes Registry, Yang et al. (1) conclude that insulin use is associated with a reduced cancer risk in type 2 diabetes. The authors hypothesize that insulin treatment, by causing tighter glycemic control, less oxidative stress, and less inflammation, reduces the risk of cancer. We believe that the study presents serious methodological problems regarding patient matching as well as follow-up and that the conclusions are unrealistic. From the original cohort of 4,623 diabetic patients, including 169 patients who developed cancer among insulin nonusers (4.6 vs. 3.3% among insulin …