Iodized Oil: Its Role in the Management of Iodine Deficiency Disorders

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Article Information:


Group: 2007
Subgroup: Volume 5, Issue 2, Spring
Date: June 2007
Type: Review Article
Start Page: 91
End Page: 98

Authors:

  • F Azizi
  • Endocrine Research Center, Research Institute for Endocrine Sciences, Shaheed Beheshti University of Medical Sciences, Tehran, I.R.Iran

      Correspondence:

      Affiliation: Endocrine Research Center, Research Institute for Endocrine Sciences, Shaheed Beheshti University of Medical Sciences
      City, Province: Tehran,
      Country: I.R.Iran
      Tel:
      Fax:
      E-mail: azizi@erc.ac.ir

Abstract:


Although universal salt iodization has been used as the most effective method of providing iodine sup-plementation, in areas where salt iodization program has failed, or when iodized salt is not widely avail-able, iodized oil can be used for iodine supplemen-tation. Following administration of iodized oil, io-dine is continuously released from the lipid stores over long periods of time. The effect may last for one year after oral and up to 3-7 years after intramuscular administration, helping to prevent endemic goiter, physical and psychomotor retardation, and the un-desirable pre- and postnatal complications of iodine deficiency. Iodized oil administration decreases the size of goiter, reverses hypothyroidism, improves psychomotor performance and corrects auditory dis-turbances caused by iodine deficiency. Derma-tologic complications, iodine induced hyperthyroid-ism and hypothyroidism may occur following its use, but enhancement of thyroid autoimmunity and thyroiditis have rarely been reported. The use of io-dized oil during pregnancy has no deleterious ef-fects on the thyroid function of the offspring.

Keywords: Iodized oil;Iodine deficiency disorders;Endemic goiter;Iodine induced hyperthyroidism

Manuscript Body:


Introduction

Although millions of people with iodine malnutrition suffering from goiter, growth and mental retardation have benefited from iodine supplementation, one third of the world population still live in areas of iodine deficiency.1

Universal salt iodization (USI) has been used as the simplest and most effective means of providing iodine supplementation. It has resulted in sustainable elimination of iodine deficiency disorders (IDD) in many countries of the world.2 In some developing countries with iodine deficiency, iodination of salt, bread or water has failed to eliminate IDD; various socioeconomic, climatic, or geographic factors have made systematic and sustainable iodine supplementation difficult and unsuccessful. In such conditions and at the outset of implementation of an IDD prevention program, administration of large quantities of iodine in the form of slowly absorbable iodized oil has been successful in prevention of IDD and in treatment of goiter and hypothyroidism caused by iodine deficiency.3-8 It is the intention of this paper to review the beneficial and side effects of iodized oil administration in the prevention and control of IDD.

General characteristics: Iodized oil is the product of addition of iodine to double bonds of the unsaturated fatty acids of certain plant oils. Administration of iodized oil preparations owes its success to the slow and continuous release of iodide from the lipid stored over long periods of time from various pools, particularly adipose tissue.9

Intramuscularly iodized oil supplementation causes a longer half-life than the oral form. The half-life of iodide, released from stored iodized oil after intramuscularly injection has been reported to be between 5.1 and 5.6 months;3,4 however, other studies have reported different half-lives. The maximum urinary iodine concentration appears 3 months after intramuscularly injection. The decline in urinary iodine concentration is at least bi-exponential, with an early fast period

of one week required to decrease urinary iodine by 50% (t ½) of approximately one week, and a slower component with a t ½ months or more.10 Intramuscular administration of iodized oil appears to help avoid some of the extremely high early iodide concentrations seen after oral intake of iodized oil.

Diarrheal disease11 goiter, 12 iron deficiency,13 malnutrition,14 selenium deficiency,15 use of manioc or cassava,16 and worm infestation,17 may affect the response to iodized oil administration (Table 1).

Table 1. Factors influencing the efficacy of iodized oil administration

Factor  Mechanism Reference No.
Diarrheal disease  Availability of iodine 11
Infestation
(ascaris, entameba)
absorption or retention of iodized oil 17
Iron deficiency Thyropeoxidase activity 13
Long standing goiter   Thyroid reserve 12
Malnutrition  Peripheral availability of iodine 14
  Thyroid function  
Selenium deficiency   1, 5- Iodothyronine denominate activity 15
Use of manioc or cassava

Formation of thyocyanate and

Competitive inhibition of iodide transport

16

 

Fig. 1. Individual values and mean (±1 SEM) level (bars) of serum thyrotropin (TSH), thyroxine (T4),
and Triiodothyronine (T3) in schoolboys with iodine deficient hypothyroidism (aged 7 to 15 years) before
therapy (closed circles) and four months after the administration of iodized oil (open circles). The
shaded areas represent the normal ranges in euthyroid children in Tehran.

 


Prevention and treatment of iodine deficiency disorders: Iodized oil has been highly successful as long-term replacement therapy for IDD. The method is inexpensive, approximately € 0.80 per dose, and can be easily implemented through local health services. The effect may last for 7 years in adults and 3-5 years in children after intramuscular injection and for 1 year after oral administration.10,18

The use of iodized oil in the prevention of endemic goiter was initiated by Clarke et al.19 Shortly thereafter McCullagh20 and Hannessy21 reported the reduction of goiter rate in controlled trials of iodinated oil given intramuscularly to goitrous subjects. Iodized oil reduces goiter size,22,23 improves mental and psychomotor performance in schoolchildren,24,25 and prevents undesirable pre- and postnatal complications of iodine deficiency.26 Iodized oil has failed to reverse hypothyroidism in adolescent and adults with endemic myxedematous cretinism;27 it has however been shown to be effective in restoring normal

thyroid function in children with cretinism up to 4 years of age, being only partially beneficial in older children.28 In a study of schoolchildren with goitrous hypothyroidism due to iodine deficiency, it was shown that T4 and TSH reverted to normal in girls8 and boys.29 Fig. 1 shows changes in serum T4, T3 and TSH before and 4 months after intramuscular injection of 480 mg iodized oil, effects which persisted 1-3 years after iodized oil injection.30 Table 2 shows normalization of serum TSH and T4 concentrations for up to 36 months after intervention. The marked decrease in the prevalence of goiters, in particular the larger ones, was also seen after 3 years of injection.

Iodized oil prophylaxis in mothers, before and during the first trimester of pregnancy, has shown improved pyschomotor and intelligence quotients in offsprings.23-25,31 It has been shown that iodized oil administration in children with severe iodine deficiency improves auditory thresholds, 1 to 3 years after intervention.32

 

Table 2. Serum concentrations of TSH and thyroid hormones before and 1, 2 and 3 years after iodized oil injection in both sexes

        Months after injection  
  Sex Before  injection 12 24 36
Serum TSH (mU/L) F 19.9±20.1   0.9±0.8† 0.8±0.6† 1.8±1.6*†
M 20.6±25.7   1.4±2.3† 0.6±1.8† 2.5±2.3*†
Serum T4 (Ag/dL) F 4.6±2.1   10.8±2.8† 9.8±2.5† 9.5±2.1†
M 5.4±2.0  10.7±3.3† 10.2±2.3† 9.7±1.8†
Serum T3(ng/dL) F 167±47   160±40 185±37 150±23
M 168±40   146±39 158±33 151±27

F: Female n=43, M: male n=42; * P<0.001, Compared to 24 months after injection; † Pbefore injection

 

Studies have shown that oral administration of lipiodol before or during the first trimester of pregnancy normalizes thyroid function in newborn babies and mothers. Iodized oil during the first trimester of pregnancy had no deleterious effects and may prevent hypothyroid or neurological cretinism. A decrease in both prematurity and stillbirth rates and the number of abortions was reported amongst the treated subjects.33, 34
Route of administration: Duration of the effects of iodine supplementation is much longer following intramuscular injection, as compared to that of oral administration of iodized oil. However, injections under field conditions in developing countries have disadvantages, especially the potential risk of communicable diseases and dependence on trained manpower. In this regard, oral administration of single doses of iodized oil capsules is a good alternative, since this requires less technical training, fewer instruments, and less time. Also, certain hazards are avoided, such as infections and improper disposal of needles.

Complications of iodized oil administration: Iodine excess, including the over correction of previous states of iodine deficiency, can impair thyroid function. Although a euthyroid individual can tolerate up to 1000 µg iodine per day without side effects,35 smaller doses below 500 µg daily intake may cause adverse effects in a population previously exposed to iodine deficiency.

Dermatological complications: In a study of 3420 patients with simple goiter, skin complications were observed in 29 patients (0.8%), the highest incidence rate being observed in the 20-29, 30-39 and 40-49 year age groups.36 The distribution of the patients with regard to the timing of dermatologic complications is illustrated in Fig. 2. Most of the complications were observed during the first 8-14 days after injection. Among the 29 patients with dermatologic problems, 4 had diffused, generalized lesions and 35 revealed only localized lesion at the site of injection.

Iodine Induced Hyperthyroidism (IIH): A rise in the occurrence of thyrotoxicosis has been reported in several endemics37-40, following reports of occurrence of IIH in two African countries.41,42 Many prophylactic programs with salt iodization at various levels and with iodized oil in varying amounts have failed to demonstrate any increase in incidence of thyrotoxicosis.43-46

 

 

Fig. 2. Time of occurrence of dermatologic side-effects following iodized oil injection. More than half of the cases occurred within 8 to 14 days following injection

 

It has been suggested that IIH is rare in a well-executed IDD control program and the innumerable benefits that correction of iodine deficiency has in preventing brain damage, ensuring child survival and improving the learning abilities may be worth the risk of the rare occurrence of IIH.47

Table 2 shows the rare occurrence of proven IIH, both clinical and laboratory based diagnosis, reported in various studies. Many of the cases reported were transient and subclinical (laboratory increased T4 and/ or T3 only). In the majority of studies the prevalence of IIH was 0.6-1.7%. However, there are many studies in which no IIH was reported. Time of occurrence of IIH is shown in Fig. 3. Following injection of 480 mg iodized oil to 3420 patients with simple goiter, 0.6% developed IIH; 12 of 20 patients were clinically hyperthyroid and 8 patients had to be treated with antithyroids.36

Thyroiditis: Some studies have suggested that excess iodine intake may trigger thyroid autoimmune reactivity by increasing the immunogenicity of thyroglobulin or by inducing damage to the thyroid cells by free radicals.48,49 Cross-sectional studies of populations in Great Britain,50 Italy51 and Denmark

 


Fig. 3. Time of occurrence of hyperthyroidism following iodized oil injection. Twelve out of 20 cases were detected within 3 to 9 months after intervention.

Fig. 4. Time of occurrence of hypothyroidism following iodized oil injection. Fourteen out of 20 cases occurred during first 6 months following injection, only 3 cases were detected after 9 months

coastal areas of Japan and China and may accompany hypothyroidsm.59,60

Sialadenitis: Mammary tissue, salivary glands, gastric mucus and choroids plexus, all of which have the same or a very similar symporter, concentrate iodide by a mechanism similar to that of the thyroid gland. Excess iodine may affect the salivary gland and cause iodine-induced sialadenitis or iodine mumps; 3.5-24% of those receiving iodized oil may develop transient sialadenitis.54,62
Iodized oil in pregnancy: Iodized oil has successfully been used for prophylaxis of iodine deficiency during pregnancy. There are no hard data to show that concentration of circulating iodine reaches the minimum inhibitory level for thyroid function. In a large study of 277 cord blood samples and 1026 blood samples of neonates and infants in Iran, whose mothers had received iodized oil injection during pregnancy, no case of hypothyroidism was detected.63
The use of iodized oil is recommended in remote areas of iodine deficiency, in the beginning of IDD control programs when iodized salt is not widely available and in areas where universal salt iodization has failed. The benefits of iodine supplementation outweigh its risks. When compared to the number
the number of doses given, the side effects occurring from the use of iodized oil for iodine deficiency are too rare to pose any significant obstacle to its continued use. Studies have shown that the use of iodized oil during pregnancy is safe for the mother, the fetus and the neonate.

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