M. D. Finocchiaro

Maternal hypothyroxinaemia during the first half of gestation in an iodine deficient area with endemic cretinism and related disorders

OBJECTIVE Iodine deficiency is well known as the cause of several disorders such as endemic goitre and cretinism, along with a wide spectrum of psychoneurological development disorders including endemic mental deficiency and endemic cognitive deficiency, which are generally correlated to damage to the fetus. Such damage Is, by Inference, deemed a consequence either directly of iodine deficiency or of insufficient availability of thyroxine at the feto‐placental unit level. Early pregnancy represents the crucial period for neurogenesis in the embryo. Several experimental studies have emphasized the direct role of maternal T4 in neurological embryo‐genesis, before the onset of fetal thyroid function and, therefore, Its protective role In fetal thyroid failure. The objective of this study was to evaluate whether Iodine deficiency may Influence thyroid status of pregnant women throughout the first half of pregnancy.

Enhanced iodine concentrating capacity by the mammary gland in iodine deficient lactating women of an endemic goiter region in Sicily

Iodine balance during pregnancy and lactation was investigated by measuring iodine con-centration in the urine of 11 pregnant women, born and living in a moderately iodine deficient endemic goiter area in Northeastern Sicily, collected during the last week of pregnancy, and between the 5th and 7th day after delivery, and in their milk sampled simultaneously with the urine of their newborns. The results were compared with those obtained on similar samples from 16 euthyroid age-matched nongoitrous women and their offspring from an iodine sufficient area. Urinary iodine concentration in pregnant women from the endemic area (1.28 ± 0.13 gMg/dl, mean ± SE) was significantly lower than that of pregnant women from the iodine sufficient area (3.77 ± 0.57 gMg/dl) (t = 3.56, p < 0.005). The longitudinal measurement of iodine concentration in each nursing woman showed a marked increase (≈90%) when compared with the values obtained during pregnancy in both endemic and control groups (2.32 ± 0.36 and 7.76 ± 2.08 gMg/dl; t = 2.13 p < 0.05, respectively). The slight difference in milk iodine concentration between the endemic (3.25 ± 0.77 gMg/dl) and the control (4.33 ± 0.57 gMg/dl) group was not statistically significant (t = 1.14; p < 0.5, NS). Similarly no difference was found in urinary iodine excretion between the endemic and the control newborn groups (3.41 ± 0.76 and 4.30 ± 0.65 gMg/dl, respectively, t = 0.88 p < 0.1, NS). The similarity between milk and urinary iodine content of newborns in the two areas was in contrast with the greatly different daily iodine intake of the mothers (endemic area 45 ± 6 gMgl/24h vs control area 106 ± 23 gMgl/24h, t = 2.14 p < 0.05 estimated in general population). An explanation for this was given by the calculation of milk iodine uptake (% intake) by the mammary gland, which was higher in endemic as compared with the control group (45 ± 6% vs 34 ± 4%). Enhanced iodine uptake by the mammary gland of the lactating mothers from endemic goiter area in the presence of low iodine supply can account for the above findings. This enhanced concentrating capacity, being inversely related to daily iodine intake (r = -0.41 p < 0.05), appears to be a further effort to effectively compensate for iodine deficiency, in order to prevent congenital hypothyroidism and to correct transient hypothyroidism of the infant.

Partial beneficial effects of the so called “silent iodine prophylaxis” on iodine deficiency disorders (IDD) in Northeastern Sicily endemia

The prevalence of goiter among schoolchildren and the daily urinary iodine excretion in the general population were evaluated in 4 municipalities in the endemic goiter area in Northeastern Sicily in two different surveys. The first, carried out in 1977–1978, covered 2,493 (91%) schoolchildren; the second, in 1987–1988, covered 2,167 (92%) schoolchildren. A dramatic decrease in goiter prevalence was apparent in each community as follows: in Castell’ Umberto (3,904 inhabitants, altitude 641/750 m above sea level) goiter prevalence (G) decreased from 79.7% to 44.2% with a percent reduction (%r) of 44.5 and an increase in 24-h urinary iodine excretion (UIE) from 22.3 ± 16.4 μg / 24 h (n = 30) to 48.7 ± 43.4 (n = 50). A similar trend was apparent in Tortorici (10, 194 inhabitants, 475/700 m) where G decreased from 62.2 to 26.5% (% r 57.4) with a UIE increase from 28.4 ± 29.6 (n = 35) to 47.6 ± 59.3 (n = 40); in Sinagra (3,387 inhabitants, 300 m) where G decreased from 61.6 to 32.7% (% r 46.9) and UIE increased from 26.0 ± 21.1 (n = 25) to 66.6 ± 69.6 (n = 102) and in Sant’Angelo di Brolo (5,732 inhabitants, 380 m) where G decreased from 48.7 to 27.5% (% r 43.5) and UIE increased from 26.3 ± 16.7 (n =30) to 47.7 ± 73.8 (n = 34). These events are clearly related and certainly dependent on the changed alimentary habits in the area due to the improved distribution of frozen food and industrially prepared dairy products, eventually enriched by iodine. Despite the increase in iodine intake, goiter is still present in the communities along with endemic cretinism, apparent in 3 children born after 1977. The persistence of endemic goiter and, however, of major iodine deficiency disorders (IDD), suggests the inadequacy of the so called silent iodine prophylaxis in preventing IDD, constitutes a criterion of major severity of the endemia and requires the immediate introduction of iodine prophylaxis.

Changes in both size and cytological features of thyroid nodule after levothyroxine treatment

objective We prospectively evaluated the effects of 12 months thyrotropin suppressive levo‐thyroxine (L‐T4) therapy in terms of changes in both thyroid nodule size and cytological features and considered whether thyroid nodule size changes actually resulted in (or were the result of) cytological changes.

Epidemiology and clinical characteristics of endemic cretinism in Sicily

In this study we report the prevalence of endemic cretinism in the general population of two iodine deficient areas in Northeastern Sicily that were described more than 10 yr ago. In addition, the individual characteristics of endemic cretins are considered in order to define the typical expressions of this major iodine deficiency disorder in Sicily. Forty-three mental defectives were identified: 22 were living in an area with three bordering and closely connected municipalities within the province of Messina and with a population of 17,485 inhabitants (prevalence= 0.13%). Three out of the 22 were school-age children. The other community, in the province of Catania, was constituted by a unique and mostly agricultural hamlet, and showed a prevalence of cretinism that was 0.68% (21/3,100). Among the 43 mental defectives, 16 (37%) presented prominent neuromotor and neurosensorial disorders, including deafmutism and were euthyroid, thus conforming to the neurological type of cretinism; 13 (30%) were hypothyroid and exhibited stunted growth without significant neuromotor and neurosensorial impairment (myxedematous cretins). In the remaining 14 individuals (33%) neurological disorders were associated with stunted growth and clinical or biochemical hypothyroidism. These data indicate that also in Sicily endemic cretinism is a continuum of a variety of forms: among these the pure neurological and pure myxedematous forms represent the two extremes.Our observations also indicate that endemic cretinism still represents a major public health problem in Sicily.The finding of 3 endemic cretins younger than 13 yr suggests the persistence of this disorder even in the presence of improved economic, social and nutritional conditions.

Thyroid follicular oncogenesis in iodine-deficient and iodine-sufficient areas: Search for alterations of the ras, met and bFGF oncogenes and of the Rb anti-oncogene

To gain insights into the role of iodine deficiency in favoring thyroid tumorigenesis (particularly of the follicular histotype), 22 Sicilian patients with thyroid tumors were selected for having lived permanently in either one of two areas of different iodine availability. Eleven patients (age 46.1 ±14.6 years, mean±SD; 10 females and 1 male) were from the iodine-deficient (ID) areas of the provinces of Messina and Catania (mean urinary excretion of iodine=48.1 µg/2A hours). Thyroid tumors were follicular or Hürthle cell adenomas (no.=3), follicular carcinomas (FC, no.=4), papillary carcinomas (PC, no.=2) and anaplastic carcinomas (no.=2). Eleven patients (age 47.1±15.2 years; 10 females and 1 male) were from the metropolitan area of Messina, an area of relative iodine-sufficiency (IS) (urinary excretion of iodine=95.2 µg/24 hours). These 11 patients had serum levels of TSH that were significantly lower than the corresponding values of the 11 patients from the ID area (0.76±0.33 vs 1.80±1.22 mU/l, p=0.01) The tumors of the 11 patients from the IS area were: follicular or Hürthle cell adenomas (no.=6), Hürthle cell carcinoma (no.=1), FC (no.=2), PC (no.=2). Molecular biology studies revealed that both the normal as well as the tumor tissue of all 22 patients did not harbor any of the three classical activating mutations (codons 12, 13 and 61) in any of the three ras oncogenes. Similar negative results were obtained as far as loss of heterozygosity of the retinoblastoma (Rb) anti-oncogene is concerned. Immunohistochemistry studies were performed to investigate expression of c-met and basic fibroblast growth factor (bFGF) proto-oncogenes. Only one Hürthle cell carcinoma and the two PC from the IS group, and one FC and the two PC from the ID group stained for the c-met oncogene. Expression of c-met was greater (3+) in the four PC (concerning 70–80% of the tumor cells) than in the other two cancers (1+; <5% of the tumor cells). In the IS group, positivity for bFGF was detected in 3/6 adenomas, 1/2 FC, the Hürthle cell carcinoma and the two PC. In the ID group, positivity for bFGF was observed in 2/3 adenomas, 2/4 FC, the two PC and the two anaplastic carcinomas. The 8 positive cases from the ID group had a greater level of bFGF expression than the 7 positive cases from the IS group (intensity of staining = 2.0+ vs 1.57+). Interestingly, the greatest expression of bFGF was seen in the cases with peri-tumoral lymphocytic infiltration from either group. In the ID group correlations between (i.) pre-intervention serum TSH and intensity of tumoral staining for bFGF, (ii.) serum TSH and per cent of tumoral cells reactive with anti-bFGF and (iii.) between intensity of staining for bFGF and per cent of tumoral cells bFGF +ve were higher than in the IS group. We conclude that activating mutations of ras, loss of DNA from the Rb locus and over-expression of both c-met and bFGF are of no pathogenetic relevance in driving thyroid tumorigenesis of iodine-deficient areas.

Thyroiditis due to Brucella Melitensis

A case of thyroiditis due to Brucella Melitensis is reported. Brucellosis anticipated by about two months the onset of the characteristic symptoms of acute thyroiditis. Cultures of specimens obtained by fine needle aspiration biopsy and microbiological investigations allowed isolation and identification of the germ. This observation allowed the recognition that thyroid gland might harbored secondary localization of a prolonged brucellosis. A microbiological study (the protocol of which is proposed ) of specimen obtained by fine needle aspiration biopsy should be performed in the presence of symptoms and signs of an inflammatory process associated to an acute swelling of the thyroid gland.