Prochazka IODINE IN EARLY PREGNANCY – IS THERE ENOUGH ?

Aims: To evaluate the iodine status of patients in early pregnancy and its dependence on level of thyroid-stimulating hormone (TSH). Methods: Between June 2005 and December 2006, 168 patients with a confi rmed vital pregnancy (up to 10 week of pregnancy) were included in the study. The entry criteria were no prior thyroid disease, did not take any other medication, had not undergone radio-iodine therapy and did not take multivitamins containing iodine. The iodine status was measured as the amount of iodine in urine over 24 hours. The TSH level was determined from the blood using chemiluminescence. Results: The average ioduria value in patients was found to be 3.04 μmol/24 hr, with the norm 0.6–2.4 μmol/ 24 hr, median 2.9, SD 1.5. None of the patients had a value lower than 0.9 μmol/24 hr. The average TSH value was 1.98 mIU/l, median was 1.31, SD 0.98. The laboratory limits were set to 0.25–3 mIU/l for pregnant women in the fi rst trimester. Three pregnancies ended in miscarriage by week 12, 1 miscarriage occurred in week 22 and the other pregnancies concluded in delivery between weeks 38-41. Fourteen patients had TSH levels above 3 mIU/l with normal levels od free thyroxine (T4) : 10.3–25 pmol/l. Conclusions: The results of this study did not reveal any iodine defi cit in any of the patients. However 14 patients had elevated TSH levels signalling subclinical or incipiently clinical hypothyroidism. These pacients underwent levothyroxine therapy after endocrinologist’s consultations.


INTRODUCTION
A female organism undergoes many anatomical and functional changes during pregnancy.These changes also occur in the thyroid gland, whose function is closely associated with the metabolism of iodine.Iodine is a part of thyroxine (T4) and triiodothyronine (T3) -hormones of the thyroid gland.In the blood, iodine is in the form of an iodine anion.In the thyroid gland, iodine, regulated by thyroid-stimulating hormone (TSH), is actively taken up, oxidized by peroxidase to elementary iodine and then bound to thyroid-binding globulin (TBG) (ref. 1 ).
Only 20 % of the T3 found in serum originates from the thyroid gland (and only in cases of iodine defi cit), the rest is formed by peripheral deiodization of T4.
Thyroid gland activity is regulated by negative feedback.The tripeptide thyroliberin (TRH) is produced in the hypothalamus and stimulates the production of the glycoprotein TSH from the pituitary gland.The level of T4, as well as T3, also regulates the level of TSH.
Under normal conditions, hormones of the thyroid gland exude a metabolic, calorigenic, diff erentiating effect and regulate cell growth, contribute to the development of the CNS, somatic growth, puberty, regulate the synthesis of proteins important for proper liver, heart, nervous system and muscle function and regulate oxygen consumption and saccharide entry into cells 2,3 .
The aim of our work was to determine the iodine status in the period of early pregnancy (up to the 10 th week of pregnancy) while monitoring TSH.The result may determine whether it is benefi cial to routinely test iodine quantity during pregnancy or not 4 .

PATIENTS AND METHODS
Between June 2005 and December 2006, 168 patients with a confi rmed pregnancy (up to 10 th week of pregnancy) and an average age of 23 years (17-41 years of age) were included in this prospective longitudinal study.The patients fulfi lled the following entry criteria: no previous illness or use of medication for thyroid gland function, did not use any other medication (amiodarone, lithium, interferon α, tamoxifen, metoclopramide, phenothiazine, antidepressives, medication containing iron, multivitamins containing iodine, rifampicin, phenytoin), had not undergone radioiodine therapy.
The iodine level in urine is indicative of iodine balance in the organism.A 24-hour urine sample was tested by an in-house methodology using a photometric detector MAX 002 (Diagnostic Products Corporation, Los Angeles, USA), where the physiological range was 0.6-2.4μmol/24 hr (80-300 mg/24 hr).The TSH level in the blood was measured by the Immulite 2000 immunoassay system using chemoluminescent DPC testing on 3.generation TSH (Diagnostic Products Corporation, Los Angeles, USA), where physiological values range from 0.32-5 mIU/l for non pregant women.
The average TSH value was 1.98 mIU/l.The median was 1.31, SD 0.98.Three pregnancies terminated in spontaneous abortion before week 12.There was 1 spontaneous abortion in week 22 of pregnancy.The other pregnancies concluded with delivery within the 38 th -41 st week of pregnancy.Four patients had a TSH level above 3 mIU/l and ten patiens had levels above 5mIU/l.All of them had a free T4 level in normal range 10.3-25 pmol/l, what gives evidence about subclinical hypothyreosis.All fourteen mothers were immediately refered to endocrinologist and they received levothyroxine therapy.

DISCUSSION
Daily iodine intake should be 150-200 μg/day and this requirement is increased to 250 μg/day during breastfeeding.Iodine excretion slightly increases during pregnancy due to increased renal clearance from increased glomerular fi ltration.The ability of the thyroid gland to accumulate iodine is reduced and this results in hypertrophy of the gland.A 24-hour ioduria value informs us of the amount of iodine in the organism and a value of excreted iodine above 150 μg ensures a suffi cient amount of iodine in the body 5 .10 μg of iodine are excreted into the stool daily.The amount of iodine in the organism ranges between 15-20 mg, the majority of which is found in the thyroid gland 6 .
Iodine defi ciency disorders (IDD) include hypothyroidism and structural changes in the thyroid gland-goiter.A goiter develops due to stimulation by increased levels of TSH and may be associated with normal or impaired thyroid gland function.Uncontrolled iodine intake may lead to both hypo-and hyperthyroidism 7 .
In addition, iodine insuffi ciency leads to the impairment of somatic, sexual and psychological development and difficulties during pregnancy and breast-feeding.A euthyroid state of the mother during early pregnancy is very important for proper development and diff erentiation of the fetal brain.Fetal thyroid gland begins to produce thyroidal hormones after the 12 th week of pregnancy 8 .
The thyroid gland has internal regulatory mechanisms, which allow normal function despite excess iodine and this prevents subsequent overproduction of thyroid hormones.Inhibition of iodine organifi cation occurs and this phenomenon is termed the Wolff -Chaikoff eff ect.It is believed that iodopeptides in the thyroid gland temporarily inhibit thyroideal peroxidases and thus also the iodination of thyroglobulin 9 .Another way of self-regulation is by suppressing the sodium-iodide symporter, which results in a decrease in intrathyroid iodine concentration.This may lead to hypothyroidism.During pregnancy, hypothyroidism carries a higher risk of placental abruption, preeclampsia, mental retardation and impaired development of the central nervous system of the fetus or repeated miscarriages [10][11][12] .
Excessive iodine intake may also lead to hyperthyroidism, especially in patients with autonomous nodules in the goiter, or in populations with a prior iodine deficiency.In iodine-defi cient locations, a sudden increase in iodine intake may induce the development of Graves' disease.This phenomenon is known as the Jod-Basedow phenomenon.Hyperthyroidism during pregnancy increases the risk of premature delivery, delivery of a fetus with low birth weight, risk of congenital birth defects and it aff ects the heart activity of the mother and fetus 13 .

CONCLUSIONS
This study did not confi rm a defi cit of iodine in patients in early pregnancy in our region.Overall, the need for routine ioduria examinations for women in early pregnancy was not confi rmed in our sample.The level of TSH is a senzitive marker of functional thyroid disorders which may be the results of a thyroid autoimmune disorder or (rarely) a defi cit of iodine 14 .