Hypothyroidism and. pregnancy. hyperthyroidism in. Mafauzy Mohamed Health Campus University Sains Malaysia

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1 Hypothyroidism and hyperthyroidism in pregnancy Mafauzy Mohamed Health Campus University Sains Malaysia

2 Hypothyroidism and hyperthyroidism in pregnancy Mafauzy Mohamed Professor of Medicine/ Senior Consultant Endocrinologist Health Campus, Universiti Sains Malaysia

3 Conflict of interest Mafauzy Mohamed has declared no potential conflicts of interest.

4 Learning objectives To understand thyroid gland physiology during pregnancy To know that hypo- and hyperthyroidism in pregnancy increase the risk of adverse outcomes not only for the fetus but also the mother To understand what causes hypo- and hyperthyroidism To appreciate the importance of diagnosis and early treatment To know the treatment of hypo- and hyperthyroidism in pregnancy

5 Thyroid in pregnancy Thyroid gland increases in size by 10% during pregnancy in iodine-replete countries and by 20 40% in iodinedeficient areas Production of T 4 and T 3 increases by 50% during pregnancy Daily iodine requirement increases by 50% during pregnancy 10 20% of all pregnant women in the 1st trimester of pregnancy are TPO or TgAb +ve and euthyroid TSH, under the impact of hcg, is decreased throughout pregnancy

6 Hypothyroidism in pregnancy 2 3% of apparently healthy, non-pregnant women of childbearing age have elevated serum TSH An estimated % would have overt hypothyroidism An estimated 2 2.5% would have subclinical hypothyroidism Prevalence is higher in areas of iodine insufficiency

7 Causes of hypothyroidism Iodine deficiency Hashimoto's thyroiditis Atrophic autoimmune thyroiditis Post-radioablation Post-thyroidectomy

8 Adverse outcomes associated with hypothyroidism Increased risk of premature birth Increased risk of fetal death Low birth weight Miscarriage Impaired fetal neurocognitive development Gestational hypertension

9 Diagnosis of hypothyroidism TSH >2.5 miu/l with decreased FT 4 concentration TSH >10.0 miu/l, irrespective of FT 4 (Subclinical hypothyroidism TSH between 2.5 and 10 miu/l with a normal FT 4 )

10 Treatment L-thyroxine Aim to normalise TSH values within the trimesterspecific pregnancy reference range (1st trimester, miu/l; 2nd trimester, miu/l; 3rd trimester, miu/l) LT 4 dose requires adjustment due to increased demand as pregnancy progresses

11 Hypothyroid before pregnancy Hypothyroid patients receiving LT 4 who are planning pregnancy should have the dose adjusted in order to optimise serum TSH values to <2.5 miu/l preconception ~25 30% increase of daily LT 4 dose is required

12 Hyperthyroidism in pregnancy Graves' disease, the most common cause of autoimmune hyperthyroidism in pregnancy, occurs in 0.1 1% (0.4% clinical and 0.6% subclinical) of all pregnancies Gestational hyperthyroidism (transient hyperthyroidism) occurs in approximately 1 3% of all pregnancies

13 Causes of hyperthyroidism Graves' disease Gestational hyperthyroidism (transient hyperthyroidism) hcg-induced thyrotoxicosis Toxic multinodular goitre Toxic adenoma Factitious thyrotoxicosis Silent thyroiditis Struma ovarii

14 Diagnosis of hyperthyroidism Suppressed or undetectable serum TSH (<0.1mIU/L) Elevated FT 4

15 Obstetrical and medical complications of hyperthyroidism Miscarriages Pregnancy-induced hypertension Prematurity Low birth weight Intrauterine growth restriction Stillbirth Thyroid storm Maternal congestive heart failure

16 Fetal risks for women with Graves' hyperthyroidism Fetal hyperthyroidism Neonatal hyperthyroidism Fetal hypothyroidism Neonatal hypothyroidism Central hypothyroidism

17 Factors for potential complications Poor control of hyperthyroidism throughout pregnancy may induce transient central hypothyroidism Excessive amounts of ATDs can cause fetal and neonatal hypothyroidism High titres of serum TRAb between 22 and 26 weeks gestation are risk factors for fetal or neonatal hyperthyroidism

18 Thyroid receptor antibody (TRAb) TRAb is present in over 95% of patients with active Graves' hyperthyroidism High titres may remain elevated following ablation therapy Indications for ordering TRAb test in Graves' disease include: - Mother with active hyperthyroidism - Previous history of treatment with radioiodine - Previous history of delivering an infant with hyperthyroidism - Thyroidectomy for treatment of hyperthyroidism in pregnancy

19 Treatment The initial dose of ATDs depends on the severity of the symptoms and the degree of hyperthyroxinaemia Initial doses of ATDs are as follows: MMI 5 15 mg daily/carbimazole mg daily/ptu mg daily in divided doses PTU is the preferred treatment in the 1st trimester Following the 1st trimester, consideration should be given to switching to MMI

20 Monitoring FT 4 and TSH should be monitored approximately every 2 6 weeks The primary goal is a serum FT 4 at or moderately above the normal reference range Discontinuation of all ATD therapy is feasible in 20 30% of patients in the last trimester of gestation In women with high levels of TRAb values, ATD therapy should be continued until delivery

21 Indications and timing for thyroidectomy Allergies/contraindications to ATDs Requiring large doses of ATDs Not adherent to drug therapy 2nd trimester is optimal time Preparation with beta-blocking agents and short course of KI solution are recommended

22 Gestational hyperthyroidism (transient hyperthyroidism) Limited to the first half of pregnancy Characterised by elevated FT 4 and suppressed or undetectable serum TSH, in the absence of serum markers of thyroid autoimmunity May be associated with hyperemesis gravidarum (severe nausea, vomiting in early pregnancy with weight loss, dehydration, ketonuria)

23 Management of gestational hyperthyroidism Treatment of hyperemesis gravidarum ATDs are not indicated, since the serum T 4 returns to normal by weeks gestation There are no studies reported in the literature that compare ATD vs supportive therapy When the diagnosis is uncertain, a short course of ATDs is reasonable if hyperthyroidism returns after discontinuation of ATDs, Graves' hyperthyroidism is the most likely diagnosis and further therapy may be required

24 Conclusions Hypothyroidism and hyperthyroidism are not uncommon during pregnancy Both hypothyroidism and hyperthyroidism are associated with adverse maternal and fetal outcomes Early diagnosis and treatment are important Optimal treatment results in improved outcomes

25 4-5 July 2015, Mumbai, India 2015 Asia Pacific Conference on Cardiometabolic Diseases Management IMPROVING THE PATIENT S LIFE THROUGH MEDICAL EDUCATION