Papers by Francesco Vermiglio
Journal of Endocrinological Investigation, Oct 1, 1984
The 70-year-old patient 1 photographed in Figure 1 represents the most exceptional instance of mo... more The 70-year-old patient 1 photographed in Figure 1 represents the most exceptional instance of monstrous goiter reported in Europe during the last decades and namely in Sicily (1). He lives in an endemic goiter and cretinism areC). in northeastern Sicily (Tortorici countryside) which has been extensively studied (2, 3). The patient developed a visible goiter when he was between 20 and 30 years of age. The goiter reached the actual size about 15 years ago. Due to weight of the thyroid, this patient cannot manage to sleep lying down but only sitting up. The patient exhibits the clinical picture of neurological endemic cretinism (Fig. 2), i.e. severe mental retardation, deafmutism, marked hyperreflexia, clonus of the rotula and of the foot, as has been described other cases from Sicily in the past (4) and even more recently (3). In addition, leukoma of the left cornea is present,
L'Endocrinologo, Mar 14, 2022
Elsevier eBooks, 2009
Hypothyroxinemia is a condition characterized by normal thyroid-stimulating hormone (TSH) concent... more Hypothyroxinemia is a condition characterized by normal thyroid-stimulating hormone (TSH) concentrations, but maternal free-thyroxine concentrations that are below the normal range for the stage of pregnancy. It occurs in very specific environmental and/or physiological circumstances, namely iodine deficiency and pregnancy. The coexistence of both of these conditions results in the highest risk of gestational hypothyroxinemia in the mothers, because the maternal thyroid gland cannot adapt to the increased hormonal requirements due to inadequate iodine availability. Maternal hypothyroxinemia also occurred in women who had started iodine supplementation at least 2 years prior to becoming pregnant and who were also given iodine-containing multivitamin supplements, though to a lesser degree (16%). A study in progress on more than 100 women studied longitudinally throughout gestation indicate that, in moderately iodine-deficient areas, the prevalence of maternal hypothyroxinemia in women who commenced regular use of iodized salt during the first trimester of gestation and took multivitamin supplements containing iodine is very high (50%). In conclusion, not only screening, but also monitoring of maternal thyroid function should be encouraged in moderately iodine-deficient areas, in order to correct maternal hypothyroxinemia promptly and consequently prevent irreversible neurological damage in progeny.
Journal of Endocrinological Investigation, May 20, 2016
Springer eBooks, 1986
The non-neoplastic inappropriate secretion of thyroid stimulating hormone (ITSHS) classification ... more The non-neoplastic inappropriate secretion of thyroid stimulating hormone (ITSHS) classification (1) includes also defective suppression of TSH secretion by somatostatin, dopamine, and other suppressors. These abnormalities have been postulated but not yet, at least contemporarily, documented in any reported case. The present study demonstrates the defective suppression of TSH secretion by dopamine, dopamine agonists, somatostatin, and corticosteroids, and also reports the measurement of plasma immunoreactive endogenous thyrotropin-releasing hormone (TRH) in a patient with ITSHS and thyroid hormone resistance (2).
PubMed, 1998
Iodine availability for maternal thyroid during pregnancy results from a combination of specific ... more Iodine availability for maternal thyroid during pregnancy results from a combination of specific factors (increased urinary iodine loss, fetal-placental unit competition) and is critically reduced by the nutritional deficiency. Hyperestrogenism is associated with increased circulating thyroxine-binding globulin (TBG) levels and a higher binding capacity for T4 and T3, because of a reduced clearance rate of the protein. Our study carried out in a moderately iodine deficiency area from North-Eastern Sicily in pregnant women showed a inadequate synthesis of T4 not proportional to the increased TBG levels. The progressive decrease T4/TBG molar ratio implies the reduction of serum FT4 and the consequently increase of serum TSH. At delivery, about 70% of women showed a critical and transient biochemical hypothyroidism. Mental impairment and neurosensorial and neuromuscular disorders were observed in children born from those women. Therefore, short-term iodine prophylaxis with iodized salt in pregnant women does not correct nor prevent maternal hypothyroxinemia. L-T4 treatment is thus often required.
PubMed, Dec 22, 2016
Iodine deficiency disorders (IDD) still represent a major public health problem, with almost 30% ... more Iodine deficiency disorders (IDD) still represent a major public health problem, with almost 30% of the world population being exposed to the consequences of nutritional iodine deficiency (ID). In Italy, despite a sustained policy of iodine prophylaxis, more than 10% of people is still affected with goiter, and a presumably higher rate of subjects may suffer from minor cognitive deficits due to inadequate iodine supply during antenatal life. This review of systematic observational studies carried out over thirty-five years (1980-2015) in a sentinel ID area in North-eastern Sicily highlights the changing phenotypes of IDD in this region. Over the years profound improvements in nutritional iodine status in North-eastern Sicily has occurred, due to both silent and active iodine prophylaxis. Endemic cretinism, resulting from severe iodine deficiency, has been progressively replaced by less serious deficits of intellectual and cognitive abilities, which nevertheless deserve proper attention.
Italian Journal of Pediatrics, Jan 17, 2018
Background: The available studies concerning the influence of age on the phenotypical expression ... more Background: The available studies concerning the influence of age on the phenotypical expression of differentiated thyroid carcinoma (DTC) have hitherto compared DTC presentation either between pre-pubertal and pubertal children or between pediatric patients and aged adults; aim of this study was to ascertain for the first time whether presentation of DTC may significantly vary according to age, even within a peculiar study population covering only young patients aged less than 30 years. Methods: The main clinical, biochemical and pathologic data at DTC diagnosis were retrospectively recorded in 2 selected cohorts including, respectively, 18 children and adolescents aged less than 18 years (Group A) or 45 young adults aged between 20 and 29.8 years (Group B). Results: The statistical distribution of DTC cases in the different age ranges was found to progressively increase with increasing age; furthermore, the patients of Group A exhibited at diagnosis a more severe clinical involvement and a higher rate of extra-regional metastases; finally, also the association with both autoimmune thyroid diseases (AITDs) and a biochemical hypothyroid pattern was more common in Group A patients. Conclusions: In a study population younger than 30 years: a) the risk of developing DTC increases with age, achieving its zenith during the 3rd decade of life; b) clinical presentation is more severe in children and adolescents younger than 18 years than in the patients aged between 20 and 30; c) in the cohort of children and adolescents DTC is more often associated with AITDs, which might play some role in conditioning the more aggressive phenotypical presentation of DTC in this patient group.
Journal of Endocrinological Investigation, Apr 1, 2005
Journal of clinical & translational endocrinology, Jun 1, 2019
Hyperthyroidism during pregnancy is uncommon. Nonetheless, prompt identification and adequate man... more Hyperthyroidism during pregnancy is uncommon. Nonetheless, prompt identification and adequate management of hyperthyroidism in a pregnant woman is essential, because uncontrolled thyrotoxicosis significantly increases the risk of maternal and fetal complications. Also, fetal prognosis may be affected by the transplacental passage of maternal thyroid stimulating antibodies or thyrostatic agents, both of which may disrupt fetal thyroid function. Birth defects have been reported in association with the use of antithyroid drugs during early pregnancy. Although rarely, offspring of mothers with Graves' disease may develop fetal/neonatal hyperthyroidism, the management of which requires a close collaboration between endocrinologists, obstetricians, and neonatologists. Because of the above considerations, the management of pregnant and lactating women with hyperthyroidism requires special care, bearing in mind that both maternal thyroid excess per se and related treatments may adversely affect the newborn's health. In this review we discuss the diagnosis and management of hyperthyroidism in pregnancy, along with the impact of thyrotoxicosis and medications on fetal outcome. Methods The terms hyperthyroidism or thyrotoxicosis were used in conjunction with the terms reproduction, pregnancy, anti-thyroid drugs, methimazole, carbimazole, propylthiouracil, obstetric outcomes, birth defects, to search MEDLINE for articles published in English in the last 20 years (1998-2018). Additional papers were searched by scrutinizing the reference lists of previously published reviews and meta-analyses. Hyperthyroidism in pregnant women Causes of hyperthyroidism during pregnancy The two most common causes of hyperthyroidism in pregnant women are Graves' disease (GD), due to thyroid stimulation by TRAbs, and gestational transient thyrotoxicosis (GTT) [1]. The latter results
Journal of Endocrinological Investigation, Feb 27, 2015
Springerlink.com drug (ATD) treatment [5], or to occur or worsen after a period of uncontrolled h... more Springerlink.com drug (ATD) treatment [5], or to occur or worsen after a period of uncontrolled hypothyroidism [6]. Accordingly, the European Group on Graves' Orbitopathy (EUGOGO) Consensus Statement few years ago recommended that restoration and maintenance of euthyroidism are priorities in Graves' disease patients with GO [7]. How to treat hyperthyroidism when GO is present is, however, a challenging dilemma [8]. Are current modalities for hyperthyroidism [ATDs, radioiodine (RAI), thyroidectomy] per se capable to affect the course of GO? If orbital disease is present, is it preferable to control hyperthyroidism with ATDs or may thyroid ablation (RAI, thyroidectomy, alone or in association) be advantageous by removing factors (thyroid autoreactive lymphocytes, thyroid antigens) that may promote the occurrence and/or progression of GO? To address these questions, the Italian Society of Endocrinology established a task force of experts with the aim of reviewing the available literature and drawing conclusions based on evidence summary of recommendations is presented in Table 1. Methods Literature search The major source of data acquisition included PubMed search strategies. Papers published in the last 35 years were screened. In addition, the bibliographies of relevant citations and chapters of major textbooks were evaluated for any additional appropriate citation.
Clinical Endocrinology, May 6, 2011
We examined the effect of different conditions of nutritional iodine intake on maternal thyroid f... more We examined the effect of different conditions of nutritional iodine intake on maternal thyroid function throughout gestation in a cohort of healthy, anti-thyroid antibody-negative women from a mild-moderately iodine-deficient (ID) area. Observational cohort study. The study included 168 women receiving prenatal preparations containing 150 μg of iodine from early pregnancy (150-I group); 105 women who had regularly used (>2 years) iodized salt prior to becoming pregnant (I-salt group); 160 women neither taking iodine supplements nor using iodized salt (no-I group). Maternal TSH, FT3 and FT4 were determined throughout gestation. Mean TSH concentrations were higher among the 150-I women than in the remaining two groups, and in a high proportion of them, TSH values were found to exceed the upper limit for gestational age. Conversely, the prevalence of low free-thyroxine levels in the 150-I women was similar to that observed in the I-salt women and markedly lower than that recorded for the no-I group. The regular use of iodine-containing supplements proved effective in reducing the risk of inappropriately low FT4 levels during pregnancy. The observed TSH increase in 150-I women may be because of a transient stunning effect on the thyroid gland, occurring as a result of the abrupt increase in daily iodine intake. Whilst the importance of gestational iodine supplementation is undisputed, we believe that in mild-moderately ID areas, women considering conception should be advised to take iodine supplementation for several months prior to pregnancy.
The Journal of Clinical Endocrinology and Metabolism, Jul 1, 2008
Mild to moderate iodine deficiency during pregnancy can cause transient maternal hypothyroidism a... more Mild to moderate iodine deficiency during pregnancy can cause transient maternal hypothyroidism and impaired mental development of the progeny. These unfavorable effects are preventable by iodine supplementation. In Europe, however, less than 50% pregnant women receive iodine-containing supplements, thus representing dietary iodized salt the only carrier of iodine for most women in this life stage. Objective/Design: This longitudinal study is aimed to investigate the effects of long-term iodized salt consumption on maternal thyroid function during gestation. Participants/Outcome Measures: We prospectively evaluated thyroid function in 100 consecutive thyroperoxidase antibody-negative pregnant women from a mildly iodine-deficient area. Sixtytwo women who had regularly used iodized salt for at least 2 yr prior to becoming pregnant and 38 who commenced iodized salt consumption upon becoming pregnant were classified as longterm (LT) and short-term (ST) iodine supplemented, respectively. Results: Long-term iodized salt consumption resulted in a very low prevalence of maternal thyroid failure (MTF) in LT women. Conversely, short-term iodine prophylaxis does not seem to protect against the risk of MTF, the prevalence of which was almost 6-fold higher in ST than LT women (36.8% vs. 6.4%; 2 14.7, P Ͻ 0.0005; relative risk 5.7, 95% confidence interval 2.03-16.08, P Ͻ 0.001). The relative risk reduction amounted to 82.5%, this measure indicating the extent to which long-term iodine prophylaxis using iodized salt would reduce the risk of MTF in ST women. Conclusions: Prolonged iodized salt significantly improves maternal thyroid economy and reduces the risk of maternal thyroid insufficiency during gestation, probably because of a nearly restoring intrathyroidal iodine stores.
Journal of Steroid Biochemistry, Jun 1, 1984
Pediatric Research, Jun 1, 1985
Journal of Endocrinological Investigation, Apr 1, 1995
A case of thyroiditis due to Brucella Melitensis is reported. Brucellosis anticipated by about tw... more 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
Journal of Endocrinological Investigation, Nov 1, 1998
To gain insights into the role of iodine deficiency in favoring thyroid tumorigenesis (particular... more 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 micrograms/24 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 micrograms/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.
Journal of Thyroid Research, 2011
There is evidence that isolated maternal hypothyroxinemia may have detrimental effects on both mo... more There is evidence that isolated maternal hypothyroxinemia may have detrimental effects on both mother and foetus. Nonetheless, this condition is still far from being universally accepted as a separate thyroid disease, and a standard definition of this state of mild thyroid underfunction is still lacking. We will review the biochemical criteria used to define isolated maternal hypothyroxinemia, together with current methodological issues related to FT4 assays. We will also discuss its epidemiological impact in both iodinedeficient and-sufficient areas, and the effectiveness of iodine prophylaxis on maternal thyroid function and neuropsychomotor development in offspring.
Journal of Endocrinological Investigation, Feb 1, 1992
lodine balance during pregnancy and lactation was investigated by measuring iodine concentration ... more lodine balance during pregnancy and lactation was investigated by measuring iodine concentration in the urine of 11 pregnant women, born and living in a moderately iodine deficient endemie 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 sampies from 16 euthyroid age-matched nongoitraus women and their offspring from an iodine sufficient area. Urinary iodine concentration in pregnant women from the endemie area (1.28 ± 0.13)J.g/dl, mean ± SE) was significantly lower than that of pregnant women from the iodine sufficient area (3.77 ± 0.57)J.g/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 endemie and control groups (2.32 ± 0.36 and 7.76 ± 2.08)J.g/dl; t = 2.13 P < 0.05, respectively). The slight difference in milk iodine concentration between the endemie (3.25 ± 0.77)J.g/dl) and the control
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Papers by Francesco Vermiglio