Doubts and Concerns about Isolated Maternal Hypothyroxinemia

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 iodine-deficient and-sufficient areas, and the effectiveness of iodine prophylaxis on maternal thyroid function and neuropsychomotor development in offspring

The changing phenotype of iodine deficiency disorders: a review of thirty-five years of research in north-eastern sicily

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.

Iodine status and supplementation in pregnancy: an overview of the evidence provided by meta-analyses

Iodine supplementation during pregnancy in areas with mild-moderate defciency is still a matter of debate. The present study aimed at systematically reviewing currently available evidences provided by meta-analyses with the aim to further clarify controversial aspects regarding the need of iodine supplementation in pregnancy as well as to provide guidance on clinical decision-making, even in areas with mild-moderate defciency. Medline, Embase and Cochrane search from 1969 to 2022 were performed. For the purpose of this review, only studies containing meta-analytic data were selected. A total of 7 meta-analyses were retrieved. Four meta-analyses evaluated the relationship between iodine status during pregnancy and neonatal and maternal outcomes suggesting the existence of a U-shaped correlation between iodine status and several maternal and neonatal consequences, especially if iodine status is evaluated at the beginning of pregnancy. Three meta-analyses evaluating the results of intervention trials failed to provide straightforward conclusions on the benefts of iodine supplementation in pregnant women in areas with mild-moderate iodine defciency. Although evidence coming from meta-analyses suggests a role of iodine status during pregnancy in determining maternal and child outcomes, results of meta-analyses of intervention trials are still controversial. Several factors including, degree of iodine defciency, and pooling studies conducted in areas with diferent iodine intake, may account for the lack of benefts reported by metaanalyses of intervention trials. More high-quality, randomized, controlled trials including information on timing, dose and regimen of iodine supplementation are needed to further elucidate this issue

Global incidence and prevalence of differentiated thyroid cancer in childhood: systematic review and meta-analysis

ObjectiveDifferentiated thyroid cancer (DTC) is rare in childhood and adolescence although it represents the most frequent endocrine malignancy in this population. DTC includes both papillary thyroid carcinoma (PTC) and follicular thyroid carcinoma (FTC). Most pediatric DTCs are PTCs, while FTCs are rare. To date, no systematic reviews on the global epidemiology of pediatric and adolescent DTC have been published. This systematic review and meta-analysis aims to estimate the overall incidence and prevalence of DTCs in patients aged 0–19 years.MethodsThe systematic research was conducted from January 2000 to December 2021 through MEDLINE via PubMed, Cochrane Library, and Embase databases. Two separate meta-analyses were performed for PTC and FTC.ResultsAfter the selection phase, a total of 15 studies (3,332 screened) met the inclusion criteria and are reported in the present systematic review. Five studies were conducted in Europe, five in North America, two in South America, one in Asia, one reported data for 49 countries and territories across the five continents, and one from both the USA and Africa. Most of the studies (n = 14) reported data obtained from national registries, and only one provided information collected from hospital medical records. Beyond the actual trend over time, our study reported a pooled global incidence rate (IR) of PTC and FTC in the pediatric age of 0.46 (95% CI: 0.33–0.59) and 0.07 (95% CI: 0.02–0.12) per 100,000 person-years, respectively. The highest IRs were recorded among Caucasian girls, and the lowest in black or other races/ethnicities.ConclusionOur data confirm that DTC in the pediatric population is a rare condition. The pooled IRs of the studies included in this meta-analysis are ~0.5 for PTC, which is the most common histological type when both genders and all age groups are considered. The implementation of a prospective international registry on pediatric DTC, as part of the wider European Registries for Rare Endocrine Conditions, has been recently proposed. In addition to providing relevant information on the clinical behavior of this rare disease, standardization of data collection will be pivotal to fill current gaps and allow an accurate estimation of the real incidence and risk factors of DTC

Nutrizione iodica globale nel 2020

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Female Reproductive Factors and Differentiated Thyroid Cancer

Differentiated thyroid cancer (DTC) is markedly more common in women than men, the highest female-to-male ratio being recorded during the reproductive period. This evidence has led to the suggestion that female hormonal and reproductive factors may account for the observed DTC gender disparity. This review focuses on current evidence on the risk of DTC in conjunction with major female reproductive factors, including the impact of pregnancy on DTC occurrence and progression/recurrence. Overall, studies exploring the link between the risk of DTC and menstrual and menopausal factors, oral contraceptives and/or hormone replacement therapy, showed these associations, if any, to be generally weak. Nonetheless, there is some evidence that higher levels of exposure to estrogens during reproductive years may confer an increased risk of DTC. As far as pregnancy is concerned, it is unclear whether a potential association between parity and risk of DTC actually exists, and whether it is enhanced in the short-term following delivery. A possible role for pregnancy-related factors in DTC progression has been recently suggested by some reports, the results of which are consistent with a worse outcome in the short-term of women diagnosed with DTC during gestation compared to non-pregnant control patients. Also, some progression of disease has been described in women with structural evidence of disease prior to pregnancy. However, there seems to be no impact from pregnancy in DTC-related death or overall survival. Several in vitro and animal studies have evaluated the influence of estrogens (E) and estrogen receptors (ERs) on thyroid cell proliferation. Presently available data are indicative of a role of E and ERs in thyroid cancer growth, although considerable discrepancies in respect to ER expression patterns in thyroid cancer tissues actually exist. Further studies providing more direct evidence on the possible role of E and of placental hormones and growth factors on thyroid growth may expand our knowledge on the mechanisms beyond the gender disparity of proliferative thyroid diseases

Acute liver damage following intravenous glucocorticoid treatment for Graves’ ophthalmopathy

Purpose: Over the last years, there have been several reports on the occurrence of acute liver damage (ALD) in patients affected with Graves’ ophthalmopathy (GO) receiving intravenous glucocorticoids (ivGCs). This article is aimed at reviewing the literature on this specific topic and reporting two new cases of ALD occurring in GO patients while on ivGCs. Methods: The terms “glucocorticoid therapy” and “Graves’ Ophthalmopathy”/“Graves’ Orbitopathy”/”Thyroid eye disease” were used both separately and in conjunction with the terms “liver disease,” “liver damage,” “hepatotoxicity,” “liver failure,” to search MEDLINE for articles published since the first report of ALD in 2000 and up to 2015. Results: ALD [defined as an increase in alanine aminotransferase (ALT) >300 U/L] during or after completion of ivGCs has been so far reported in 17 fully documented cases. Overall, one-half of those patients were diagnosed as having autoimmune hepatitis (AIH) and in the vast majority of the remaining cases a diagnosis of methylprednisolone(MP)-induced hepatotoxicity was suspected. The clinical course of liver injury varied from asymptomatic hypertransaminasemia in the vast majority of patients to fatal hepatic failure in four patients receiving higher (>8 g) cumulative doses of MP. Conclusions: The overall risk of ALD is relatively low (~1 %), and seems higher using a single dose >0.5 g and a cumulative dose >8.5 g MP. Whenever ivGC treatment is required, serum liver enzymes, viral hepatitis markers, and autoantibodies related to AIH should be obtained prior to ivGC administration. Liver function should be monitored during ivGC and up to 6 months after the end of treatment. Prolonging observation after 6 months is likely unnecessary, since all cases of ALD so far reported always occurred well within this term

The iodine nutritional status in the Italian population: data from the Italian National Observatory for Monitoring Iodine Prophylaxis (OSNAMI) (period 2015\u20132019)

Dear Editor: In the April 2019 issue of the Journal, Campanozzi et al. (1) reported results of a study aimed at assessing dietary iodine intake in a national sample of Italian schoolchildren and adolescents (aged 6–18 y) using 24-h urine collections [24-h urinary iodine excretion (UIE)]. The study was conducted in the framework of the program MINISAL-GIRSCI (2). The authors conclude that the nutritional iodine intake is still inadequate in the Italian population 14 y after the approval of law n.55/2005, which introduced a nationwide program of iodine prophylaxis on a voluntary basis in our country (3). Their results and conclusion do not reflect the current iodine nutritional status of the Italian population, which appears to be adequate as ascertained by the second survey (period 2015–2019) conducted by the Italian National Observatory forMonitoring Iodine Prophylaxis (OSNAMI) (4; De Angelis et al. 2019, communication at the 40th National Meeting of the Italian Society of Endocrinology). Specifically, it should be considered that the young population the authors studied was recruited in 2009 when the program MINISAL-GIRSCI was implemented (2). In the same period, consistently, the first survey conducted by OSNAMI (2007–2012) on 7455 schoolchildren (age 11–14 y) residing in 9 Italian regions showed that most of the regions were iodine deficient at that time [median spot urinary iodine concentration (UIC) <100 μg/L]; only the Liguria, Tuscany, and Sicily regions showed iodine sufficiency [median UIC ranging from 100 to 160 μg/L). In addition, only 43% of salt sold in Italy was iodized at that time, and the prevalence of goiter in schoolchildren (range: 6%–9%) was slightly higher than the threshold value of 5% in all the examined regions (5). After this time, the General Direction of Food Safety and Nutrition at the Ministry of Health together with the panel of OSNAMI experts at the National Institute of Health decided to intensify nationwide informative campaigns on the use of iodized salt promoting the slogan “less salt but iodized,” in agreement with the nationwide strategy of reducing sodium intake in the population. These efforts have led to the achievement of iodine sufficiency in our country, as demonstrated by the preliminary results of the second OSNAMI survey conducted on 2523 schoolchildren (age 11–13 y) residing in rural (42%) and urban areas (58%) of 7 Italian regions (Liguria, Toscana, Emilia Romagna,Marche, Umbria, Lazio, Sicilia). Analysis of data regarding 3 further regions (Veneto, Lombardia, Calabria) is still ongoing. These preliminary results showed the use of iodized salt in 75% of the Italian school canteens, a median UIC of 118 μg/L (rural areas: 119 μg/L; urban areas: 117 μg/L), and a prevalence of goiter <5% in 6 of the 7 regions (range 1%–4.7%). Only Umbria showed a borderline goiter prevalence value (5.4%). In regard to this, it is important to underline that the assessment of goiter in schoolchildren by ultrasound is an indicator of long-lasting adequate iodine intake in a population. In fact, it has been demonstrated that iodine prophylaxis is able to prevent the development of goiter in children born after the implementation of iodized salt and to further control thyroid enlargement in older children, although it is less effective in reducing goiter size in children exposed to iodine deficiency in the first years of life (6). In their study Campanozzi et al. (1) also suggest to continue monitoring the iodine intake in the Italian population by using 24-h UIE measured in children to properly document changes in iodine intake over the years. They support this conclusion on the basis of the observation that significant discrepancies between 24-h UIE and UIC were found in the first (<7.8 y) and second (7.8–10 y) quartiles of age, where the average 24-h urinary volume was <1 L, but not in the third (>10–12.5 y) and fourth (>12.5–18 y) quartiles of age of the young population they recruited. In particular, they underline that the measurement of UIC in spot samples could lead to an underestimation of iodine deficiency in younger subjects because of the age-related smaller urine volumes producing spuriously higher iodine concentrations. Actually, we believe that the collection of 24-h UIE in a large number of schoolchildren to monitor the iodine nutritional status in the population is not necessary. UIC from spot samples is the recommended indicator for population assessment and monitoring of iodine interventions globally (7, 8). According to the WHO classification, adequate iodine status is indicated by a population median UIC ≥100 μg/L with no more than 20% of samples <50 μg/L; where the median value is <100 μg/L the iodine intake is considered inadequate. If a large number of samples are collected, variations in hydration among individuals (9) and day-today variation in iodine intake (10) generally even out, so that the median UIC in spot samples correlates well with the median from 24-h samples (8). Therefore, if the daily volume of urine produced by a group approximates 1 L/d, as Campanozzi et al. (1) demonstrated to occur in schoolchildren aged>10 y, then the UIC (in micrograms per liter) is interchangeable with the 24-h UIE. Because both OSNAMI surveys were conducted in schoolchildren at such an age that their urine volume can be assumed to be ∼1 L, we are confident that the results so far obtained by OSNAMI are reliable. Furthermore, considering that spot urine samples are far simpler to obtain than 24-h urine collections, in the future the UIC assessment will allow monitoring of iodine nutritional status in the Italian population more frequently than would be possible if 24-h urine collections were undertaken. Consequently, this higher frequency will provide the advantage of a more accurate evaluation of the sustainability of iodine sufficiency just achieved in our country