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Int J Reprod BioMed Vol. 14. No. 11. pp: 677-686, November 2016 Review article

Thyroid hormone dysfunction during : A review

1 2 2 2 Aynadis AlemuP P M.Sc., Betelihem TerefeP P M.Sc., Molla AbebeP P M.Sc., Belete BiadgoP P M.Sc.

1. Amhara Regional Health Abstract Bureau, Dessie Regional Health Research Laboratory, Dessie, dysfunctions such as , thyrotoxicosis and thyroid nodules Ethiopia may develop during pregnancy leading to , placental abruptions, 2. School of Biomedical and preeclampsia, preterm delivery and reduced intellectual function in the offspring. Laboratory Sciences, College of Epidemiological data have shown the significant role of maternal thyroid hormone Medicine and Health Sciences, University of Gondar, Ethiopia. in fetal neurologic development and maternal health. It has been suggested that the deleterious effects of thyroid dysfunction can also extend beyond pregnancy and delivery to affect neuro-intellectual development in the early life of the child. Pregnancy poses an important challenge to the maternal thyroid gland as hormone

requirements are increased during gestation as a result of an increase in thyroid- binding globulin, the stimulatory effect of HCG on TSH receptors, and increased peripheral thyroid hormone requirements. Maternal thyroid dysfunction is associated with increased risk for early abortion, preterm delivery, neonatal morbidity and other obstetrical complications. Early diagnosis for thyroid dysfunction of pregnant Corresponding Author: Belete Biadgo, School of women and treatment of thyroid dysfunction during pregnancy is important and cost Biomedical and Laboratory effective to avoid both fetal and maternal complications secondary to thyroid Sciences, College of Medicine and dysfunction. Therefore the aim of this review was to assess the thyroid function Health Sciences, University of changes occurring during pregnancy, the different disorders with their maternal and Gondar, Ethiopia. P.O.Box: 196.

Email: [email protected] 61T fetal implications, the laboratory diagnosis and the best ways of management of Tel: (+25) 1918295071 these conditions.

Received: 5 June 2016 Accepted: 22 August 2016 Key words: Thyroid hormone, Pregnancy, Gondar, Ethiopia.

Introduction thyrotoxicosis can affect the mother health as well as the child before and after delivery that regnancy is a natural physiological can result in fetal disease; in humans, this changes that is accompanied with includes a high incidence of mental hormonic and metabolic alterations retardation (2). The fetal thyroid gland begins P concentrating iodine and synthesizing THs caused by a variety of conditions that results in many pathophysiologic processes, some of after months of gestation. Although the which have potentially serious outcomes if left requirement for TH before this time is untreated. Thyroid diseases during pregnancy exclusively supplied by the mother which is are related to maternal and fetal most important to fetal brain development, complications. Therefore in this article, we try significant fetal brain development continues to review the thyroid function aberrations considerably beyond the first trimester (1, 2). occurring during pregnancy, the different Evident maternal thyroid failure during the first disorders with their maternal and fetal half of pregnancy has been associated with implications, the laboratory diagnosis and the several pregnancy complications including best ways of management of these conditions. preeclampsia, premature labor, fetal death and low birth weight and intellectual Physiological changes of thyroid function impairment in the offspring (3). in mother and during pregnancy THs have most profound effects on the Thyroid hormones (TH) are very important terminal stages of fetal brain differentiation for growth and development of brain for the and development, including synaptogenesis, fetus and neonate, in addition for many other dendrites growth and axons myelination and aspects of pregnancy, fetal growth and neuronal migration. TH receptors are broadly development (1). The thyroid gland dispersed in the fetal brain, and existing prior dysfunctions like hypothyroidism and to the time the fetus is able to synthesize TH. Alemu et al

Evidence has confirmed that it is challenging signaling from the TSH receptor on thyroid to identify the molecular targets for TH action epithelial cells. Closure to the end of the first in the developing brain, but some trimester of pregnancy in humans, when HCG improvement has been made (4, 5). levels reaches at peak, a substantial fraction of the thyroid-stimulating activity is from HCG. Mechanisms of physiological changes of During this time, levels of TSH become thyroid function in pregnancy suppressed. The thyroid-stimulating activity of Thyroid stimulation starts as early as the HCG actually causes some women to cause first trimester by β-HCG hormone, which transient (8, 9). shares some structural homology with thyroid- The potential source of TH for the fetus is stimulating hormone (TSH). There is also an its own thyroid and the thyroid of the mother. estrogen-mediated increase in circulating Human acquire the ability to levels of thyroid-binding globulin (TBG) during synthesize TH at approximately the first pregnancy by 2-3 times in serum TBG trimester of gestation. Current evidence from concentrations. TBG which is one of the several species indicates that there is numerous protein that transport TH in the significant transfer of maternal THs across the blood with high affinity for thyroxine (T4) placenta and also the placenta contains increases in serum a few weeks after deiodinases that can convert T4 to T3 (10). conception and ranges a plateau during mid- Pregnant mother and infant protection is a gestational period. The mechanism for this priority in the health because these population increase in TBG involves both increased hepatic groups are mostly exposed to the diseases synthesis of TBG and estrogen mediated and death. Thyroid dysfunction is one of the perpetuation in sialylation of TBG that common complications of pregnancy and it increases the half-life from 15 min to 3 days to contributes significantly to the maternal and fully sialylated TBG (6). fetus morbidity and mortality. There is limited Elevated levels of TBG lead to lowered free attention and information related to thyroid T4 concentrations, which results in increased dysfunction and its complication during TSH secretion by the pituitary and, pregnancy. Therefore, the aim of this review subsequently, enhanced production and TH was to assess the magnitude of maternal and secretion. The net effect of elevated TBG fetal thyroid dysfunction and its complication synthesis is to force a new equilibrium in pregnancy secondary to thyroid between free and bound THs and therefore a dysfunction. substantial increase in total T4 and triiodothyronine (T3) levels. The augmented Thyroid hormone abnormalities during demand for THs is reached by about 20 wk of pregnancy gestation and persists until term (6, 7). Reflecting changes in iodine metabolism, Hyperthyroidism which is an essential requirement for TH Hyperthyroidism typically is the disease synthesis, increased demand for iodine results process in which excessive TH is synthesized from a significant pregnancy-associated and excreted, whereas the term thyrotoxicosis increase in iodide clearance by the kidney and refers to increased amounts of TH in the draw off maternal iodide by the fetus. During circulation (11). It can occur in approximately pregnancy there is an increased iodine 1% of the population and up to 0.4% of the excretion in the urine as a result of increased (12). Previous study by Wang et glomerular filtration and decreased renal al found that the prevalence of thyroid tubular absorption. In addition, maternal iodine dysfunction was 10.2%, hyperthyroidism, is actively transported to the feto-placental hypothyroidism and hypothyroxinemia were unit, which contributes to a state of relative 1.8, 7.5 and 0.9% respectively (13). (8, 9). There are 2 causes of hyperthyroidism, like The other factor is the impact of HCG classic causes which is found in the general secreted by the placenta of humans. Thyroid population, and the other causes are specific stimulation in response to the thyrotropic during pregnancy. True hyperthyroidism is activity of HCG overrides the normal action of differentiated from other forms by elevated the hypothalamic pituitary thyroid feedback radioactive iodine uptake (RAIU). The other system. TSH that can bind and transduce forms are differentiated from true

678 International Journal of Reproductive BioMedicine Vol. 14. No. 11. pp: 677-686, November 2016 Thyroid dysfunction hyperthyroidism by decreased RAIU like overstimulation of gland growth. hyperthyroidism caused by factors other than Autoantibodies that react with the orbital thyroid gland over-activity may result from muscle of the eye and fibroblasts of skin are inflammatory , pregnancy- also produced and initiate the extra thyroidal specific associations (like hyperemesis manifestations of GD (22, 23). gravidarum and hydatid form mole) and the Like other autoimmune diseases, the presence of ectopic thyroid tissue or by activity of GD is aggravated during the first exogenous sources of TH (14-17). trimester of gestation and decreased during Tissue effects of hyperthyroidism include the latter half of pregnancy, to be aggravated accelerated metabolism, suppressed serum again in the first few months after delivery or TSH, low serum cholesterol, increased bone late in the (24, 25). Fetal turnover and reduced bone density with an effects of Graves hyperthyroidism are increased risk of osteoporosis and fracture hyperthyroidism, intrauterine growth, (18). A study by Marvisi et al found that retardation, short gestational age, still birth, hyperthyroidism strongly is associated with craniosynostosis and also maternal effects are lower TSH values and increased pulmonary hypertension, preeclampsia, preterm delivery, arterial pressure which leads to severe heart failure, thyroid crisis and placental pulmonary hypertension (19). In the first abruption (26). trimester of gestation, the normal elevation in Trophoblastic disease: It is resulted from total T4 and total T3, due to estrogen-induced the production of thyroid stimulators other increase in TBG concentration and HCG than TSH. It is a general term that includes thyroid stimulation with suppression of serum benign and malignant conditions of TSH, may pause difficulties in the diagnosis of hydatidiform mole with frequency of maternal hyperthyroidism (20). approximately 1 in 1500-2000 pregnancies and choriocarcinomas with frequency of 1 in Characteristics of various types of 40-60000 pregnancies (27, 28). The etiology hyperthyroidism of the hyperthyroidism is thought to be related TSH-induced hyperthyroidism: This type to the increased levels of serum HCG in these of hyperthyroidism is due to dysfunction in patients (15). HCG is secreted by placenta TSH that regulates T3 and T4 production. from early pregnancy that shares a common Increased stimulation by inappropriate TSH alpha subunit with TSH. HCG stimulates the secretion may be caused by TSH-secreting normal maternal thyroid via TSH receptor to pituitary adenomas that influences elevated synthesize and secrete TH (29). TH synthesis and release, and not responsive Hyperthyroidism attributable to to normal hormonal feedback control. trophoblastic disease should be suspected in Diagnosis is confirmed by demonstrating a patients who demonstrate increased free lack of TSH response to thyrotropin releasing thyroxine (FT4) and free triiodothyronine (FT3) hormone (TRH) stimulation and radiologic levels, decreased TSH, and significantly imaging of the pituitary (21). increased HCG (30). Although FT4 and FT3 Pituitary resistance to thyroid hormone: levels can be increased with HCG levels It refers to resistance of the pituitary to TH >50,000 IU/L in patients with trophoblastic feedback control, possibly resulting from tumors, serum HCG may reach >300,000 IU/L receptor modification. Diagnostically these compared to the >50,000 IU/L seen in normal patients display an appropriate increase in pregnancy (30). Thyrotoxic patients also have TSH in response to TRH and suppressed TSH a higher serum T4 to T3 ratio than Graves’s in response to T3 (14). patients (28). Hyperthyroidism from thyroid Gestational thyrotoxicosis: Gestational stimulators other than TSH: Graves’ disease thyrotoxicosis is a transient increase in thyroid (GD) is the most common cause of secretion leading to thyrotoxicosis of varying hyperthyroidism which is an autoimmune degrees of severity that can occur when HCG syndrome resulting from the production of levels are very high and considered as a fairly thyroid stimulating (TSAbs), normal phenomena. As HCG is a thyroid sometimes called TSHR Ab capable of stimulator, a state of hyper stimulation of the stimulating thyroidal TSHRs, resulting in thyroid gland is common in early pregnancy. excessive TH production and release, and This form of hyperthyroidism differs from GD

International Journal of Reproductive BioMedicine Vol. 14. No. 11. pp: 677-686, November 2016 679 Alemu et al in that occurs in women without a past history similar to GD without infiltrative ocular of GD and in the absence of detectable manifestations or (14, 38). TSHR-Ab (29, 31). This disorder occurs in Thyrotoxicosis associated with 0.2% of pregnancies. Mostly patients with inflammatory thyroid disease: Subacute , as many as 60% also called de Quervain’s thyroiditis, exhibit hyperthyroidism (32, 33). Interestingly, is a painful condition of the thyroid gland that more severe vomiting is associated with a appears to be due to viral invasion of the greater degree of thyroid stimulation and thyroid parenchyma and begins much more higher level of HCG. On laboratory suddenly than Hashimoto's thyroiditis. examination, the serum FT4 is more Postpartum thyroiditis may be subclinical or frequently increased compared with the serum produce only fragile clinical manifestations. If FT3 level (34). it is still present, thyroid function testing will The clinical importance of gestational show elevated TH levels and a suppressed transient thyrotoxicosis (GTT) has probably TSH level. After the thyrotoxicosis decreases, been overlooked. From recent studies, it is the patient will be euthyroid for a few weeks. now thought that the prevalence of GTT may Then, because the thyroid has tired its store of be as high as 2-3% of all pregnancies that is hormone, hypothyroidism will develop. In 10-fold more frequent than hyperthyroidism response, the TSH level begins to rise in due to GD (35). The syndrome GTT is about one month, normal thyroid function is important to differentiate from GD because the usually restored, rarely, the hypothyroid phase course of both conditions, the associated fetal may be prolonged by 3-5 months, but rarely it risks, and the management and follow-up are is permanent (39, 40). entirely different (36, 37). Thyrotoxicosis caused by postpartum Hyperthyroidism from thyroid gland thyroiditis may be clinically identical to GD, autonomy: Toxic adenoma, as an which subsides during pregnancy and autonomous , is a discrete worsens immediately afterwards. The thyroid mass whose function is independent or distinguishing feature is that in patients with normal pituitary control. These nodules may GD, the thyroid actively produces hormone be toxic adenomas or hot nodules based on and so takes up radioiodine at 3-5 times the their uptake on radioiodine and appearance normal rate. On the contrary, the thyroid gland on a radioiodine thyroid scan. Toxic or hot releases hormone into the serum in patients nodules secrete THs independent of the with postpartum thyroiditis (40). pituitary because this tissue contains mutated TSHRs. Thyroxine levels typically are Ectopic thyroid tissue elevated in these patients sometimes only T3 Struma ovarii and follicle cancer: A levels are increased (38). Consequently if T4 teratoid tumor of the ovary that is capable of concentrations are normal in such patients T3 producing TH is strauma ovarii. This is an levels should be determined to rule out T3 extremely rare form of thyrotoxicosis and is toxicosis. evident by hyperthyroidism without thyroid In toxic multinodular goiter, the thyroid gland enlargement and suppressed RAIU. gland normally enlarges in reaction to an The disease can be detected by whole body increased demand for THs that occurs in scanning with RAI. Both surgery and pregnancy, iodine deficiency and radioiodine therapy is required since the immunologic, genetic disorders. During these tissue is potentially malignant. TH with phenomenon, there is increased TSH sufficient preserved function can be secreted secretion and a compensatory increase in to cause thyrotoxicosis in case of metastatic thyroid follicles and TH synthesis. When the follicular carcinoma. In most of these cases situation for excessive production of TH there was a previous diagnosis of thyroid subsides, TSH secretion decreases and the malignancy (21). thyroid gland returns to normal size. However, Risks of hyperthyroidism on fetal and permanent changes may have arisen in some maternal well-being: Elevated levels of TH follicle cells that can function autonomously complicating pregnancy is not common, but relative to TSH. These autonomous follicles potentially severe condition occurs in about 2 may produce excessive TH unregulated by out of 1000 pregnancies (41). Uncontrolled TSH, resulting in thyrotoxicosis symptoms hyperthyroidism during pregnancy can

680 International Journal of Reproductive BioMedicine Vol. 14. No. 11. pp: 677-686, November 2016 Thyroid dysfunction promote to congestive heart failure, factitia, iodine ingestion and post-partum preeclampsia, rise in blood pressure in late thyroiditis (21, 49). pregnancy, thyroid storma, , Treatment of hyperthyroidism during premature birth and low birth weight (42). pregnancy: Maternal and fetal outcome is Hyperthyroidism in a newborn can result in directly associated to control of rapid heart rate, which may lead to heart fail- hyperthyroidism. During pregnancy, mild ure; early closure of the soft spot in the skull; hyperthyroidism, in which TSH is low but FT4 poor weight gain; irritability; and sometimes an is normal, does not need treatment. More enlarged thyroid that can press against the severe elevated TH concentration is treated windpipe and interfere with breathing (29). with anti-thyroid medications. The medications Autonomous production of TH and cross the placenta in small amounts and can inadequately treated maternal hyperthyroidism decrease fetal TH production, so the lowest may result in fetal and neonatal possible dose should be used to avoid hyperthyroidism due to the trans-placental hypothyroidism in the baby. The medications transfer of stimulatory TSHRAb (43, 44). can cause adverse effects in some people, Clinical neonatal hyperthyroidism occurs in like allergic reactions, patients with about 1% of infants born to mothers with GD. leucopenia, which can lower a person’s Not often neonatal hypothyroidism may also resistance to infection, liver failure, in rare be observed in the infants of mothers with cases (50, 51). Molar disease should also be Graves’ disease, this may result from trans considered and can potentially lead to placental transfer of circulating maternal anti- fulminant hyperthyroidism, particularly in thyroid drugs, pituitary-thyroid axis women with a pre-existing autonomous suppression from transfer of maternal T4 (45). nodular goiter. However, uncomplicated the most severe manifestation hydatidiform mole is now easily diagnosed in of hyperthyroidism results from untreated the early stages of gestation and therefore, hyperthyroidism and may be precipitated by will rarely lead to severe hyperthyroidism, infection trauma, a surgical procedure and because it lasts only for a few weeks or diabetic ketoacidosis (42, 46). Thyrotoxic months and is rapidly cured by the removal of periodic paralysis is another uncommon the pathological trophoblast (51). problem of hyperthyroidism. It is a reversible disorder characterized by acute muscle Hypothyroidism weakness and hypokalemia. The attacks of periodic paralysis are precipitated by It is the most common pathological hypokalemia that is caused by a transcellular deficiency of TH that accounts approximately shift rather than total body depletion of 2% of women and 0.1-0.2% of men (52). It is potassium (46). common in pregnancy with a predictable Diagnosis of hyperthyroidism: prevalence of 2-3% and 0.3-0.5% for Measurement of the TSH level is the only subclinical and overt hypothyroidism initial test necessary in a patient with a respectively (53). Endemic iodine (I-) possible diagnosis of hyperthyroidism without deficiency accounts for most hypothyroidism evidence of pituitary disease. If the TSH level in pregnant women worldwide while is low, then FT4 should be measured to Hashimoto’s disease is the supreme cause of evaluate for thyrotoxicosis. Measurement of hypothyroidism in I- adequate parts of the FT3 is helpful in the clinical diagnosis of world (54). thyrotoxicosis when the FT4 values are Manifestations of hypothyroidism can range unexpectedly normal (47). Thyroid-stimulating from asymptomatic subclinical detection to levels can be used to monitor the overt myxedema, which is rarely seen due to effects of treatment with anti-thyroid drugs in widespread screening for thyroid disease (55). patients with GD (48). High iodine uptake is A cross sectional study conducted by Alkafajei seen in disease that cause increased T4 et al found that the prevalence of sub clinical synthesis, including GD, toxic multinodular hypothyroidism was 4.3% and 20.8% goiter, toxic adenoma and . according to the general laboratory and Low iodine uptake is seen disease that internationally adopted criteria respectively causes inflammation and release of T4 (56). Effects of hypothyroidism on the fetus including , thyrotoxicosis like impaired brain development, intrauterine

International Journal of Reproductive BioMedicine Vol. 14. No. 11. pp: 677-686, November 2016 681 Alemu et al death, low birth weight, neonatal respiratory disease states results from inflammation distress, increased and preterm secondary to infiltration of the gland by birth are commonly observed (57, 58). A lymphocyte and leucocytes. Women have study also reported by Renée et al and Negro transient hyperthyroidism or hypothyroidism et al showed that infants born to thyroid occurring 3-6 months after delivery that is peroxidase (TPO) antibody positive mother associated with the development of a small, and euthyroid pregnant women had painless goiter. More than 90% of patients significantly smaller head circumference, with thyroiditis recover wholly but the condition reduced brain weight and lower brain-to- body may relapse during second pregnancy. It ratio than those born to TPO antibody should be noted that patients with postpartum negative mothers which is associated with an hypothyroidism may present with postpartum increased risk of miscarriage and premature depression. As much as 30% of cases after 3 delivers (57, 59). years, and in 50% at 7-10 years develop permanent hypothyroidism. Nearly all the Characteristics of various types of women with postpartum thyroiditis have TPO hypothyroidism antibody. This marker can be a useful Hashimoto’s disease (Chronic screening test in early pregnancy as 50% of ): It is the most women with antibodies will develop thyroid common type of thyroiditis and the most dysfunction postpartum (64). common cause of primary hypothyroidism. In Iatrogenic hypothyroidism: Iatrogenic which the attacks the thyroid, hypothyroidism is resulted from thyroid causing inflammation and interfering with its surgery, exposure of the thyroid to external capacity to produce THs (25). Hashimoto's radiation for neck carcinomas or from RAI to thyroiditis patients may develop a goiter or treat GD. Typically hypothyroidism occurs have thyroid atrophy. Patients with goiter may within 1 month following total thyroidectomy have antibodies that stimulate thyroid growth, and within 1 year after RAI therapy for GD whereas patients with an atrophic thyroid have (14). antibodies that inhibit the trophic effects of Iodine deficiency, thyroid enzyme TSH on the gland. Early Hashimoto’s defects, thyroid hypoplasia and thyroiditis is associated with a firm goiter, but goitrogens: Iodine deficiency or excess, and later in the disease process a shrunken the ingestion of goitrogens may cause fibrotic hypo functioning thyroid gland hypothyroidism on rare occasions by develops (60, 61). Chronic autoimmune decreasing TH synthesis or release. Iodine thyroiditis is the most important cause of deficiency, thyroid enzyme defects, thyroid hypothyroidism in up to 90% of pregnant hypoplasia and goitrogens may cause TH women with hypothyroidism during pregnancy deficiency in a developing fetus, resulting in test positive for thyroid antibodies (53). cretinism (14, 65). A study by Mezosi et al The disease is characterized by the reported that the mean thyroid volume of presence of high affinity and concentrations of women with severe iodine deficiency was serum thyroid antibody. The most frequently significantly larger than that in the group with detected antibodies are TPO antibody and adequate iodine intake and the frequency of antibody (TGAb). In its initial goiter was increased in all groups with iodine phase, Hashimoto’s thyroiditis can cause deficiency (66). hyperthyroidism that presents as a painless Congenital hypothyroidism (CH): goiter caused by lymphocytic infiltration of the Congenital hypothyroidism (cretinism) is a TH thyroid gland. Positive TPO antibody and/or deficiency at birth that occurs in 1/3000 TGAb test results are found in approximately newborns, as a result of the absence of 5% of euthyroid pregnant women. However, a thyroid tissue (thyroid dysgenesis) and thyroid autoantibody prevalence of up to 15% hereditary defects in TH biosynthesis. Thyroid has been found in pregnant women (62). dysgenesis occurs more commonly in female Postpartum thyroiditis: It is an infants and permanent abnormalities occur in inflammation of the thyroid gland that affects 1 of every 4000 infants. It is one of the most about 5-18% of healthy pregnant women in common preventable causes of mental different populations during the first year after retardation. Most infants with CH do not show delivery (63). The hypothyroidism of these an obvious clinical manifestation of

682 International Journal of Reproductive BioMedicine Vol. 14. No. 11. pp: 677-686, November 2016 Thyroid dysfunction hypothyroidism at birth. This may result from Dietary Supplements like iodine is an remaining neonatal thyroid function, because important mineral for a mother in pregnancy, of an over expression of deiodinases by because the thyroid uses iodine to make TH. compensatory mechanisms in target organs, During pregnancy, the baby gets iodine from or in the TH received from breast milk (67). the mother’s diet. A woman requires more Risk of hypothyroidism on fetal and iodine when they are pregnant (74). Choosing - maternal well-being: Some similar problems iodized salt supplemented with I P P over plain - caused by hyperthyroidism can occur with salt and prenatal vitamins containing IP P will hypothyroidism. Uncontrolled hypothyroidism ensure dietary supplement. A prospective during pregnancy can lead to preeclampsia, study conducted by Murcia et al found that anemia, abruption, miscarriage, low birth women took mean dose of 100-149 ug/day weight, and rarely congestive heart during pregnancy, and their children showed a failure (58). A study by Casey et al found that two point decreased in PDI compared with the the three-fold risk of and a children of mother taking <100 ug/day. This two-fold risk of preterm delivery were reported difference was greater when mother took in mother with sub-clinical hypothyroidism >150 ug/day with a decreased of 5.5 points (68). Because of THs are crucial to fetal brain (75). and development, uncontrolled hypothyroidism especially during Conclusion the first trimester can affect the baby’s growth and brain development (58, 68). Different studies have showed that thyroid Previous study conducted by Haddow et al dysfunction is common in pregnancy. The reported that untreated hypothyroidism during major causes for this dysfunction is hormonal pregnancy can cause a significant decreased and metabolic changes during pregnancy in the intelligence quotient of children (69). leading to profound alterations of the Two prospective studies showed that biochemical parameters of the thyroid persistent hypothyroxinemia at 12 wk of function. Understanding the normal gestation was associated with an 8-10 point physiological adaptation of the pituitary- deficit in mental and motor function scores in thyroidal axis in pregnancy enables us to infant offspring compared to children of manage cases of thyroid dysfunction. mothers with normal thyroid function and the Uncorrected thyroid function in pregnancy has first trimester maternal FT4 was a significant adverse effects on fetal61T 61T and maternal well- predictor of orientation scores. But the being. Thyroid disease usually affects females developmental scores were not influenced by of the reproductive age group and caring for further declines in maternal FT4 at 24 and 32 these women during pregnancy requires wk gestation (70, 71). careful monitoring of both the mother and the Management of hypothyroidism in fetus. Appropriate diagnosis, care and pregnancy: Hypothyroidism is treated with management of thyroid dysfunction in the pre- synthetic TH called thyroxine (LT4) which is pregnancy, pregnancy and post-pregnancy identical to the natural T4. Pregnant women periods are important to minimize the risk of with pre-existing hypothyroidism will need to complications, long-term effects of the mother increase their pre-pregnancy dose of T4 to and fetus. keep normal thyroid gland function. Thyroid gland function should be monitored every 6 to Recommendation 8 weeks during pregnancy. Synthetic T4 is Clinical evaluation of the patient’s safe and necessary for the well-being of the symptoms as well as laboratory testing should fetus if the mother has hypothyroidism (72). be done carefully to assess thyroid function Asymptomatic pregnant women should be during pregnancy. It is recommended that all routinely screened for hypothyroidism and pregnant mothers should be given thyroid patients with subclinical hypothyroidism function test and those who have thyroid should be treated to ensure a healthy dysfunction should be provided appropriate pregnancy (73). A prospective intervention treatment and follow up until there will have trial study found that treatment of normal thyroid function. Developmental follow- hypothyroidism by LT4 reduces the risk of up of the babies of thyroid dysfunction adverse maternal and fetal outcomes (60). mothers is also recommended in order to

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