The size of the community rather than its geographical location better defines the risk of iodine deficiency: results of an extensive survey in Southern Italy.

AIM: The objective of this study was to establish the status of iodine nutrition in Southern Italy. MATERIAL AND METHODS: The survey was carried out on 11-14 yr old children attending primary school and living in urban and non urban areas of 8 regions of Southern Italy. Urinary iodine excretion (UIE) was measured in 23,103 urinary samples randomly collected. RESULTS: Median UIE in the whole studied population was 74 µg/l [interquartile range (IR) 34-139 µg/l]. UIE was significantly higher in chief towns compared to non chief towns (81 µg/l, IR 39-145 µg/l vs 73 µg/l, IR 33-138 µg/l, p<0.0001) and in areas with >500 inhabitants per km² (median 87 µg/l, IR 43-154 µg/l) compared to areas with 100-500 per km² (median 66 µg/l, IR 29-126 µg/l, p<0.0001) and with <100 per km² (median 61 µg/l, IR 25-121 µg/l, p<0.0001). Median UIE was significantly lower in inland mountainous/hilly areas (68 µg/l, IR 30-129 µg/l) compared to coastal mountainous/hilly areas (79 µg/l, IR 37-144 µg/l, p<0.0001) and lowland (79 µg/l, IR 37-146 µg/l, p<0.0001). According to a binary logistic regression model, population density was the only independent parameter significantly associated with UIE ≥ 100 µg/l. CONCLUSION: The results of the present survey indicate that: 1) in Southern Italy mild to moderate iodine deficiency is still present; 2) median UIE in non urban areas is lower than in urban areas and is related to the size of the community rather than to its geographical location, being higher in a larger community. This may be due to better diversification of dietary habits and the easier availability of iodized salt and processed food through commercial facilities, more common in larger communities. Future monitoring surveys should take into account these observations.

The effect of voluntary iodine prophylaxis in a small rural community: the Pescopagano survey 15 years later.

CONTEXT: Iodine deficiency disorders are a major public health problem, and programs have been implemented to improve iodine nutrition. OBJECTIVE: The objective of the study was to verify the effects of voluntary iodine prophylaxis in a small rural community (Pescopagano, Italy). DESIGN: The design of the study was the evaluation of the prevalence of thyroid disorders 15 years after a previous survey conducted before iodine prophylaxis. SETTING: The setting for this study was a general community survey. PARTICIPANTS: One thousand one hundred forty-eight residents were examined in 2010 and 1411 in 1995. RESULTS: In 2010, 757 of 1148 subjects (65.9%) routinely used iodized salt, urinary iodine excretion being significantly higher than in 1955 (median 98.0 µg/L, vs 55.0 µg/L, P < .0001). The prevalence of goiter was lower in 2010 than in 1995 (25.8% vs 46.1%, P < .0001), mainly due to the reduction of diffuse goiter (10.3% vs 34.0%, P < .0001). In 2010 vs 1995, thyroid autonomy in subjects younger than 45 years old (3 of 579, 0.5% vs 25 of 1010, 2.5% P = .004) and nonautoimmune hyperthyroidism in subjects older than 45 years old (8 of 569, 1.4% vs 18 of 401, 4.5%, P = .03) were less frequent. The prevalence of hypothyroidism was higher in 2010 vs 1995 (5.0% vs 2.8%, P = .005), mainly because of an increased frequency of subclinical hypothyroidism in subjects younger than 15 years old (7 of 83, 8.4% vs 0 of 419, 0.0%, P < .0001). Accordingly, serum thyroid autoantibodies (19.5% vs 12.6%; P < .0001) and Hashimoto's thyroiditis (14.5% vs 3.5%; P < .0001) were more frequent in 2010 than in 1995. CONCLUSIONS: In the present work, the role of voluntary iodine prophylaxis was assessed in a small rural community relatively segregated, in which genetic and other environmental factors have not substantially changed between the 2 surveys. Iodine intake strongly affected the pattern of thyroid diseases, but the benefits of correcting iodine deficiency (decreased prevalence of goiter and thyroid autonomy in younger subjects and reduced frequency of nonautoimmune hyperthyroidism in older subjects) far outweighs the risk of development of thyroid autoimmunity and mild hypothyroidism in youngsters.

In vivo assessment about the effects of a diet containing iodine-enriched foodstuffs. A pilot study in 30 volunteers.

BACKGROUND: Iodine deficiency (ID) still now represents one of the major worldwide health problems. ID is the result of insufficient dietary iodine intake. Iodine is an essential micronutrient but scarcely present in nature. The main strategy for the correction of ID is the fortification of table salt with iodide/iodine but Italy is far from reaching an iodized salt use higher 90% of population. Also because of the evidence for the risk on blood pressure, it is recommended to decrease the daily salt intake to less than 5 g/d. An opportunity to increase the iodine intake is the possibility to introduce iodine fortification in the industrial processing of foods. AIM: The aim was to evaluate the effectiveness of a diet containing iodized foods enriched during industry processing with protected iodized salt (Presal®). SUBJECTS AND METHODS: The evaluation of increasing of iodine intake was assessed by measuring the urinary iodine excretion (UIE) in 30 healthy volunteers who added to their alimentary habits a basket of iodine-enriched foodstuffs. RESULTS: Median UIE at baseline was 105 µg/l, 156 µg/l during the enriched diet and 90.5 µg/l a week after withdrawal of enriched diet. CONCLUSIONS: Stable iodized salt (Presal®) represents a good way to introduce iodine with the normal diet without increasing the normal consumption of salt for the healthy problems related to the blood pressure. The availability of stable iodized salt (Presal®) allows the preservation of iodine after cooking.

Amiodarone and the thyroid: a 2012 update.

Amiodarone-induced thyroid dysfunction occurs in 15-20% of amiodarone-treated patients. Amiodarone-induced hypothyroidism (AIH) does not pose relevant problems, is easily controlled by L-thyroxine replacement, and does not require amiodarone withdrawal. Most frequently AIH develops in patients with chronic autoimmune thyroiditis. Amiodarone- induced thyrotoxicosis (AIT) is most frequently due to destructive thyroiditis (type 2 AIT) causing discharge of thyroid hormones from the damaged, but otherwise substantially normal gland. Less frequently AIT is a form of hyperthyroidism (type 1 AIT) caused by the iodine load in a diseased gland (nodular goiter, Graves' disease). A clearcut differentiation between the two main forms is not always possible, despite recent diagnostic advances. As a matter of fact, mixed or indefinite forms do exist, contributed to by both thyroid damage and increased thyroid hormone synthesis. Treatment of type 1 (and mixed forms) AIT is based on the use of thionamides, a short course of potassium perchlorate and, if treatment is not rapidly effective, oral glucocorticoids. Glucocorticoids are the first-line treatment for type 2 AIT. Amiodarone should be discontinued, if feasible from a cardiac standpoint. Continuation of amiodarone has recently been associated with a delayed restoration of euthyroidism and a higher chance of recurrence after glucocorticoid withdrawal. Whether amiodarone treatment can be safely reinstituted after restoration of euthyroidism is still unknown. In rare cases of AIT resistance to standard treatments, or when a rapid restoration of euthyroidism is advisable, total thyroidectomy represents a valid alternative. Radioiodine treatment is usually not feasible due to the low thyroidal iodine uptake.

The effect of dietary iodine supplementation in dairy goats on milk production traits and milk iodine content.

Dairy products offer an important source of iodine for humans, particularly infants and children. An adequate iodine content in the diet of lactating animals must guarantee a suitable milk iodine concentration. In this experiment, the effects of iodine supplementation of dairy goat diets on the iodine concentration, milk yield, and milk composition of goat milk were studied. Thirty crossbred dairy goats of the Sarda population were divided into 3 groups supplemented with 0 (control group), 0.45 (group 1), or 0.90 (group 2) mg of KI/d per goat. The dose of KI (76.5% of iodine) was dissolved in water and orally administered with a syringe every day for 10 wk. Mean milk iodine concentrations were 60.1 +/- 50.5, 78.8 +/- 55.4, and 130.2 +/- 62.0 microg/L (mean +/- SD) in the control group, group 1, and group 2, respectively. The extent of iodine enrichment in milk was approximately 31% in group 1 and 117% in group 2 compared with the control group. Milk yield was not influenced by KI supplementation and averaged 1,229, 1,227, and 1,179 g/d in groups 0, 1, and 2, respectively. Milk urea nitrogen concentration was significantly lower in the KI-supplemented groups (32 and 33 mg/dL in groups 1 and 2, respectively) than in the control group (37 mg/dL). Iodine supplementation of dairy goat diets can increase milk iodine content without adverse effects on milk production traits.

Potassium perchlorate only temporarily restores euthyroidism in patients with amiodarone-induced hypothyroidism who continue amiodarone therapy.

CONTEXT: Amiodarone-induced hypothyroidism (AIH) may occur in patients with or without underlying thyroid disorders. In the latter, restoration of euthyroidism, after amiodarone discontinuation, can be facilitated and accelerated by a short course of potassium perchlorate (KClO4). However, it is unknown whether KClO4 may exert similar effects on thyroid function of AIH patients if amiodarone treatment is continued. OBJECTIVE: To evaluate the effects of KClO4 on thyroid function in AIH patients (without underlying thyroid disease) while continuing amiodarone treatment. DESIGN AND PATIENTS: An open, prospective study of 10 consecutive AIH patients without underlying thyroid abnormalities referred to a tertiary referral center, and treated with KClO4 (600 mg/day) for a period of 26+/-13 days (range, 15-45 days). An additional, historical group of 12 consecutive patients with subclinical AIH left untreated while continuing or after withdrawing amiodarone was retrospectively evaluated as to the outcome of thyroid function. MEASUREMENT: Serum free T4, free T3, and TSH concentrations were measured at booking, during KClO4 treatment and after withdrawing the drug. RESULTS: In the prospective study, KClO4 treatment restored euthyroidism in all patients within 28+/-11 days (range, 15-45 days). After KClO4 withdrawal, however, all patients became hypothyroid again after 45+/-15 days (range, 30-60 days). Two patients developed mild leukopenia (1 case) or a slight increase in serum creatinine levels (1 case), which promptly normalized after KClO4 withdrawal. In the historical group, followed for at least 12 months, euthyroidism was spontaneously and stably achieved after an average of 6 months in 5 patients in whom amiodarone could be discontinued, while subclinical hypothyroidism persisted in 7 patients in whom amiodarone had to be continued. CONCLUSIONS: KClO4 very effectively restores normal thyroid function in AIH patients without underlying thyroid abnormalities, despite the fact that amiodarone therapy is continued. However, euthyroidism does not persist after KClO4 is withdrawn; in addition, spontaneous recovery of euthyroidism does not seem to occur in this subset of AIH patients, unless amiodarone is discontinued. Therefore, also in view of its potential side-effects, KClO4 cannot be recommended as a first-line treatment for AIH if amiodarone needs to be continued, while LT4 replacement is recommended under these circumstances, with periodical reassessment of thyroid function.

Early abnormalities of left ventricular myocardial characteristics associated with subclinical hyperthyroidism.

The aim of the present study was to analyze heart function in subclinical hyperthyroidism (sHT) in otherwise healthy subjects by new methods using intramyocardial ultrasonic techniques. Twenty-four newly diagnosed and untreated sHT patients (20 women, 4 men; mean age: 42+/-4 yr) and 24 sex- and age-matched healthy volunteers were studied. All subjects were submitted to conventional 2D color-Doppler echocardiography, pulsed wave tissue Doppler imaging (PWTDI) for the analysis of diastolic function, color Doppler myocardial imaging (CDMI) for the analysis of regional strain and strain rate (SR) expression of regional myocardial deformability, and to integrated backscatter (IBS) for the evaluation of intrinsic contractility and tissue characterization. Regional myocardial systolic strain findings were significantly higher in sHT patients when compared with controls (p<0.001). Considering diastolic SR, the early phase of diastolic SR was compromised in sHT subjects as compared with controls (p<0.001). Cyclic variation index (CVI), expression of intrinsic contractility, was significantly higher in sHT subjects in comparison with controls (p<0.0001). IBS values were comparable between the 2 study groups. In conclusion, the present study suggests that in patients with sHT early systolic hyperdeformability and hypercontractility are present, together with impairment of both active and passive phases of diastole. On the contrary, no left ventricular hypertrophy or other structural alterations are documented.

Long-term outcome of thyroid function after amiodarone-induced thyrotoxicosis, as compared to subacute thyroiditis.

BACKGROUND: Two main forms of amiodarone- induced thyrotoxicosis (AIT) exist: type 1 AIT is a condition of true hyperthyroidism developing in patients with pre-existing thyroid disorders, and usually requires thyroid ablative treatment. On the other hand, type 2 AIT is a form of destructive thyroiditis occurring in normal thyroids, the management of which usually consists in glucocorticoid treatment. AIM: To assess the long-term outcome of thyroid function in a prospective study of type 2 AIT patients, as compared to patients with De Quervain's subacute thyroiditis (SAT). PATIENTS AND METHODS: Sixty consecutive patients with type 2 AIT were evaluated during oral glucocorticoid treatment (oral prednisone 30 mg/day, gradually tapered and withdrawn over a 3-month period) and followed for 38+/-4 months (range 6-72) thereafter. Sixty consecutive patients with SAT, referred to our Institutes during the same period and treated with the same therapeutic schedule, served as controls. RESULTS: Type 2 AIT patients were older (p<0.0001) and showed a larger male preponderance (M:F 3.6:1 vs 0.5:1, p<0.0001) than SAT patients. Mean serum free T4 (FT4) and free T3 (FT3) concentrations at diagnosis were increased in both conditions, but higher in type 2 AIT than in SAT (FT4 47.6+/-18.8 and 29.6+/-8.3 pmol/l, respectively, p<0.0001; FT3 15.4+/-7.0 and 11.2+/-3.0 pmol/l, respectively, p<0.001). Correction of thyrotoxicosis was obtained in all patients in both groups, but restoration of euthyroidism occurred earlier in SAT than in type 2 AIT (p=0.006). Ten type 2 AIT patients (17%) and 3 SAT patients (5%, p<0.03) became permanently hypothyroid after glucocorticoid withdrawal and required levothyroxine replacement. CONCLUSIONS: A relevant proportion of type 2 AIT patients develop permanent hypothyroidism after correction of thyrotoxicosis. Thus, periodic surveillance of thyroid status is required after type 2 AIT.

Thyroid color flow doppler sonography and radioiodine uptake in 55 consecutive patients with amiodarone-induced thyrotoxicosis.

Amiodarone-induced thyrotoxicosis (AMT) is a life-threatening condition, the appropriate management of which is achieved by identifying its different subtypes. Type 1 AIT develops in patients with underlying thyroid abnormalities and is believed to be due to increased thyroid hormone synthesis and release; Type 2 AIT occurs in patients with a normal thyroid gland and is an amiodarone-induced destructive process of the thyroid. Management differs in the two forms of AIT, since Type 1 usually responds to combined thionamides and potassium perchlorate therapy, while Type 2 is generally responsive to glucocorticoids. Mixed forms, characterized by coexistence of excess thyroid hormone synthesis and destructive phenomena, may require a combination of the two therapeutic regimens. In this cross-sectional prospective study, 55 consecutive untreated patients, whose AIT was subtyped according to clinical and biochemical criteria, were evaluated to assess the specificity of color flow doppler sonography (CFDS) and thyroidal radioiodine uptake (RAIU) in the differential diagnosis of AIT. Sixteen patients (6 men, 10 women, age 66+/-13 yr), who had diffuse or nodular goiter with or without circulating thyroid autoantibodies, were classified as Type 1 AIT; 39 patients (27 men, 12 women, age 65+/-13 yr) with apparently normal thyroids were classified as Type 2 AIT. All Type 1 patients had normal or increased thyroidal vascularity on CFDS, while Type 2 AIT patients had absent vascularity (p<0.0001). Thirteen Type 1 AIT patients had inappropriately normal or elevated thyroidal 3-h and 24-h RAIU values (range 6-37% and 10-58%, respectively), in spite of elevated values of urinary iodine excretion; the remaining 3 patients (two with nodular goiter, one with a thyroid adenoma) had low 3-h and 24-h RAIU values (range 1.1-3.0% and 0.9-4.0%, respectively). The latter patients, who were unresponsive to the combination of methimazole and potassium perchlorate, became euthyroid after the addition of glucocorticoids. Thirty-eight Type 2 AIT patients had low 3-h and 24-h RAIU values (range 0.4-3.7% and 0.2-3.0%, respectively), but one had inappropriately normal 3-h and 24-h RAIU values (6% and 13%, respectively). In conclusion, CFDS can accurately distinguish between Type 1 and Type 2 AIT, and in general the CFDS pattern is concordant with the thyroid RAIU. However, in 4 out of 55 patients (7%) the thyroid RAIU was discrepant, probably reflecting the coexistence of Type 1 and Type 2 AIT. Thus, assessment of both CFDS and RAIU may provide a more accurate subtyping of AIT and help in selecting the appropriate therapy. Finally, in long standing iodine sufficient areas, such as the United States, where the thyroid RAIU is consistently low irrespective of the etiology of the AIT, CFDS offers a rapid and available method to differentiate between Type 1 and Type 2 AIT.

Iodine supplementation restores fertility of sheep exposed to iodine deficiency.

The aims of the study were to monitor sheep iodine intake in different sheep breeding farms in Abruzzo and to evaluate the effects of iodine supplementation on ovine fertility. The urinary iodine concentrations (UIC) in animals of 8 out of the 11 breeding farms analyzed were borderline (UIC 100-150 microg/l) or very low (UIC < or = 50 microg/l). Only animals bred in 3 farms showed an adequate iodine intake with a mean UIC > or = 300 microg/l. Animals with very low iodine intake had lower T4 and T3 (p < 0.01) serum levels, compared to those with adequate iodine intake. To investigate the effects of iodine supplementation on ovine fertility, 32 ewes and 20 rams, characterized by low UIC, were randomly divided into 2 groups. One group (16 ewes and 10 rams) received a sc injection of 1 ml of Lipiodol, containing 480 mg of iodine, while the remaining animals were employed as control. This treatment was able to maintain UIC above 300 microg/l for 3 months and to increase T4 and T3 serum levels (p < 0.01). After 9 months, the fertility of control and treated animals was assessed by monitoring the rate of successful matings by ultrasonography. The results showed that 100% of treated ewes mated with treated rams were pregnant vs 37% of the control ewes mated with control rams (p = 0.007). The iodine content was 4-fold higher in milk from treated ewes (2393 +/- 453 microg/l), compared to controls (675 +/- 154 microg/l). The results demonstrated that iodine supplementation restores fertility of sheep living in iodine deficient areas and may represent a means to achieve a silent iodine prophylaxis of local populations.

Iopanoic acid rapidly controls type I amiodarone-induced thyrotoxicosis prior to thyroidectomy.

Amiodarone-induced thyrotoxicosis (AIT) may develop either in apparently normal thyroid glands (Type II AIT) or in the presence of sub-clinical thyroid abnormalities (either autonomous goiter or latent Graves' disease; Type I AIT). Mixed forms also occur. While Type I AIT is due to iodine-induced excess thyroid hormone synthesis, Type II AIT is a form of amiodarone (possibly iodine) -induced destructive thyroiditis. Type I AIT is usually treated by combined thionamide and potassium perchlorate therapy, but may be resistant to therapy. On the other hand, Type II AIT often responds favorably to glucocorticoids and may not require further therapy once euthyroidism has been restored. Not infrequently, however, AIT (especially Type I) is resistant to conventional treatment, and several weeks or months may elapse before euthyroidism is restored. Thyroidectomy has been carried out in Type I AIT patients, but thyroid surgery in thyrotoxic patients, especially those with underlying cardiac problems, carries a high surgical risk. In this study we describe 3 patients with Type I AIT, who were successfully treated with a short course of iopanoic acid (IOP), an oral cholecystographic agent, which is rich in iodine and is a potent inhibitor of 5'-deiodinase, resulting in a marked decrease in the peripheral tissue conversion of T4 to T3, in preparation for thyroid surgery. Euthyroidism was rapidly restored in 7-12 days, allowing a subsequent safe and uneventful thyroidectomy in all cases. These patients were then treated with L-T4 for their hypothyroidism and amiodarone was safely re-instituted. We suggest that IOP is the drug of choice in the rapid restoration of euthyroidism prior to definitive thyroidectomy in patients with drug resistant Type I AIT.

Iodine deficiency disorders in Europe.

Iodine deficiency disorders (IDD) are related to the degree of iodine deficiency. In European countries, characterized by mild to moderate iodine deficiency, neurological deficits or minor neuropsychological impairments have been described. Urinary iodine excretion (UIE) ranged from 30 to 170 mcg/L, 141 millions of people were at risk of IDD, 97 millions were affected by goiter and 0.9 millions had an impaired mental development. Iodine prophylaxis is devoid of adverse reactions with the exception of sporadic cases of transitory hyperthyroidism, associated to the severity of iodine deficiency before the prophylaxis. The International Council for Control of IDD recommends an universal iodine prophylaxis, instituted gradually in severe iodine deficient countries. The total cost of universal iodine prophylaxis is very cheap compared to the social cost of goiter and cretinism. In conclusion, most European countries are still characterized by mild to moderate iodine deficiency. Iodine prophylaxis programs are already operating, its cost is irrelevant with respect to the undebatable beneficial impact on the health. Adverse effects are not observed except in severe iodine deficient areas where iodine intake was abruptly increased.

Non-palpable thyroid nodules in a borderline iodine-sufficient area: detection by ultrasonography and follow-up.

Thyroid ultrasonography was performed in 482 subjects, free of known thyroid disease and living in a borderline iodine-sufficient urban area, to assess the prevalence of non-palpable thyroid nodules and evaluation their evolute during a 3-yr follow-up. The mean (+/-SD) thyroid volume in the whole study group was 10.9+/-3.7 ml and was higher in males (12.9+/-3.6 ml) than in females (9.2+/-2.9 ml) (p<0.0001). Thyroid volume was correlated with body surface, height and weight, while no correlation was present with lean and fat body mass. Goiter was found in 5/256 females and in 13/226 males. Thyroid nodules were found in 27/482 subjects (18 females, 9 males). Single nodules were found in 17/464 subjects (3.66%) with a thyroid gland of normal volume and in 4/18 subjects (22.2%) with goiter (chi2=10.21; p=0.001). Multiple nodules were found in 3/464 subjects (0.6%) with a thyroid of normal volume and in 3/18 (16.6%) subjects with goiter (chi2=24.31; p<0.0001). The prevalence of thyroid nodules was significantly higher in females >35 yr than in those <34 yr (chi2=7.47; p=0.0062). A significant increase (>30%) of nodular volume was found in 5 subjects, while an increased number of nodules was found in 8. In conclusion, thyroid ultrasonography reveals the presence of thyroid nodules in a significant proportion of apparently thyroid disease-free subjects living in a borderline iodine-sufficient urban area. Incidentally discovered thyroid nodules are associated with goiter and are likely to progress in volume and number.

The spectrum of thyroid disorders in an iodine-deficient community: the Pescopagano survey.

We carefully assessed thyroid status and goiter by ultrasound in 1411 subjects virtually representing the entire resident population of Pescopagano, an iodine-deficient village of Southern Italy. Median urinary iodine excretion was 55 microg/L. The prevalence of goiter was 16.0% in children and 59.8% in adults. Thyroid nodularity was 0.5% in children and progressively increased with age to 28.5% in the 56- to 65-yr-old group. The prevalence of present or past hyperthyroidism was 2.9%, including 9 cases with toxic diffuse goiter and 20 with toxic nodular goiter. Functional autonomy was rare in children, progressively increased with age up to 15.4% in the elderly, and was related to nodular goiter. The prevalences of overt and subclinical hypothyroidism in the adults were 0.2% and 3.8%, respectively. Serum autoantibodies to thyroglobulin and thyroperoxidase were detected in 12.6% of the entire population. The prevalence of diffuse autoimmune thyroiditis was 3.5%, being very low in children. Thyroid cancer was found in only 1 case. In conclusion, in the present survey of an iodine-deficient community, a progressive increase with age of goiter prevalence, thyroid nodularity, and functional autonomy was observed. Hyperthyroidism was twice as high as that reported in iodine-sufficient areas, mainly due to an increased frequency of toxic nodular goiter. Although low titer serum thyroid antibodies were relatively frequent, the prevalences of both overt and subclinical autoimmune hypothyroidism were not different from those observed in iodine-sufficient areas.