1. Thyroid & neurological disorders in pregnancy Dr.Roaa H. Gadeer MD

2. Physiology of thyroid function TSH is released from anterior pituitary in 1-2 hrs cycle → thyroxin (T4) & triiodothyronin (T3). TSH is released from anterior pituitary in 1-2 hrs cycle → thyroxin (T4) & triiodothyronin (T3). 75% of T4 & T3 are bound to thyroid-binding globulin (TBG), the rest bound to albumin and transthyretin. 75% of T4 & T3 are bound to thyroid-binding globulin (TBG), the rest bound to albumin and transthyretin. Free T4=0.04% and free T3=0.05%. Free T4=0.04% and free T3=0.05%. Iodine is trapped by the gland and converted to iodide to synthesize thyroglobulin. Each molecule carries 3-4 molecules of T4. Iodine is trapped by the gland and converted to iodide to synthesize thyroglobulin. Each molecule carries 3-4 molecules of T4. T3 is produced by peripheral deiodination of T4 and it is 3 times more potent than T4. T3 is produced by peripheral deiodination of T4 and it is 3 times more potent than T4.

3. Physiology of thyroid function In pregnancy: In pregnancy: - TBG ↑ in first 2 wks to reach a plateau at 20 wks due to ↑ Oestrogen level. - ↑ TBG → ↑ serum T4 & T3 with no change in free T4 & T3. - Iodine deficiency (↑GFR + fetal thyroid uptake) → ↑ thyroid gland uptake & enlargement (goitre). - hCG occupies TSH receptors → ↓TSH but it stimulates the gland → ↑ T4. - Placental conversion of T4 to T3 to prevent excess T4 & even low T4 level in late pregnancy.

4. Fetal thyroid function First trimester: fetus needs maternal T4 for brain development. First trimester: fetus needs maternal T4 for brain development. Small amount of maternal T4 crosses placenta before 12 wks. Small amount of maternal T4 crosses placenta before 12 wks. Maternal T3,T4 & TSH does not cross the placenta after 12 wks. Maternal T3,T4 & TSH does not cross the placenta after 12 wks. Fetal thyroid produces T3 & T4 after 10 wk’s gestation & reaches the adult levels at 36 wks. Fetal thyroid produces T3 & T4 after 10 wk’s gestation & reaches the adult levels at 36 wks. Thyrotropin-releasing hormone (TRH) & iodine cross the placenta Thyrotropin-releasing hormone (TRH) & iodine cross the placenta

5. Thyroid function tests TestNormal pregnancyHyperthyroidism TSHNo changeDecreased TBGIncreasedNo change Total T4levelIncreased Free T4 indexNo changeIncreased Total (T3) levelIncreased Free T3 levelNo changeIncreased T3 resin uptakeDecreasedIncreased Thyroid radioactive iodine uptake Increased Increase

6. Aetiology & management Iodine deficiency : Iodine deficiency : - maternal gland has a greater affinity to iodide than placenta and fetus resulting in cretinism. - maternal gland has a greater affinity to iodide than placenta and fetus resulting in cretinism. - Fetal neocortex and basal ganglia are sensitive to iodine deficiency resulting in mental retardation. - Management: - Preconceptional iodine and up to second trimester. - Iodination of water, salt or flour

7. Hyperthyroidism Occurs in approximately 1 in 500 pregnancies. Occurs in approximately 1 in 500 pregnancies. In pregnancy it is due to Grave’s disease (90% to 95%).. In pregnancy it is due to Grave’s disease (90% to 95%).. Graves' disease is an autoimmune disease results in production of thyroid-stimulating antibody (TSA), which mimics TSH and stimulates thyroid function and size increase. Graves' disease is an autoimmune disease results in production of thyroid-stimulating antibody (TSA), which mimics TSH and stimulates thyroid function and size increase. Less common causes: toxic adenoma, toxic multinodular goiter, subacute thyroiditis, TSH producing pituitary tumor, metastatic follicular cell carcinoma, and painless lymphocytic thyroiditis. Less common causes: toxic adenoma, toxic multinodular goiter, subacute thyroiditis, TSH producing pituitary tumor, metastatic follicular cell carcinoma, and painless lymphocytic thyroiditis. Pregnancy-related causes: hyperemesis gravidarum, gestational trophoblastic disease (GTD), and struma ovarii Pregnancy-related causes: hyperemesis gravidarum, gestational trophoblastic disease (GTD), and struma ovarii

8. Hyperthyroidism signs and symptoms: tachycardia > 100 bpm, exophthalmos, thyromegaly, onycholysis (reflect the disease activity), and poor weight gain with good appetite. signs and symptoms: tachycardia > 100 bpm, exophthalmos, thyromegaly, onycholysis (reflect the disease activity), and poor weight gain with good appetite. Symptoms: fatigue and heat intolerance not useful (common in pregnancy). Symptoms: fatigue and heat intolerance not useful (common in pregnancy). laboratory test results: increase in serum T4 level and increase in the FT4 index laboratory test results: increase in serum T4 level and increase in the FT4 index  Complications: pre-eclampsia, thyroid storm, or CHF for the mother, and preterm labour and delivery, IUGR, and stillbirth pre-eclampsia, thyroid storm, or CHF for the mother, and preterm labour and delivery, IUGR, and stillbirth

9. Hyperthyroidism Treatment Is similar to non-pregnant women. Is similar to non-pregnant women. Radioactive iodine is containdicated. Radioactive iodine is containdicated. Drugs: Drugs: - propylthiouracil (PTU) or carbimazole and beta-blockers. - use the minimum dose as they cross the placenta causeing fetal hypothyroidism and goiter. - Both not teratogenic. Not contraindicate breastfeeding. - Both reduce TSH receptors antibodies titer → inhibition of T4 production. - PTU inhibits incorporation of iodine into tyrocine and peripheral conversion of T4 toT3.

10. Hypothyroidism hypothyroidism is uncommon (1%), because it is associated with infertility. hypothyroidism is uncommon (1%), because it is associated with infertility. Causes: autoimmune Hashimoto’s thyroiditis (usaully), idiopathic myoedema, treatment of hyperthyroidism, type 1 diabetes is associated with an increased incidence of subclinical hypothyroidism during pregnancy. Causes: autoimmune Hashimoto’s thyroiditis (usaully), idiopathic myoedema, treatment of hyperthyroidism, type 1 diabetes is associated with an increased incidence of subclinical hypothyroidism during pregnancy. Signs and Symptoms: Asymptomatic, weight gain, lethargy, weakness, cold sensitivity, hair loss, myxedematous changes, and dry skin. TSH level is increased; serum T4 level is low; and the FT4 index is decreased. Signs and Symptoms: Asymptomatic, weight gain, lethargy, weakness, cold sensitivity, hair loss, myxedematous changes, and dry skin. TSH level is increased; serum T4 level is low; and the FT4 index is decreased.

11. Hypothyroidism Treatment: Treatment: - L-thyroxin, starting at 0.05 to 0.10 mg daily. - The dosage should be increased over several weeks the goal is normal laboratory values and resolve of the patient's symptoms. - A maximum dosage of 0.2 mg/d of L-thyroxin should not be exceeded. - TSH level alone can be followed to determine optimal dosing.  Complications : pre-eclampsia, IUGR, abruptio placentae, anaemia, postpartum haemorrhage, stillbirth, and cardiac dysfunction.  Fetal thyroid: not affected..

12. Nodular thyroid disease Evaluation: Ultrasound, and fine-needle aspiration or tissue biopsy Evaluation: Ultrasound, and fine-needle aspiration or tissue biopsy If thyroid carcinoma is found, surgical excision is the primary treatment and should not be postponed because of pregnancy If thyroid carcinoma is found, surgical excision is the primary treatment and should not be postponed because of pregnancy

13. Epilepsy Incidence : 6/1000 pregnancy. Incidence : 6/1000 pregnancy. Seizure frequency may increase, decrease or no change (37%, 13% and 50% respectively). Seizure frequency may increase, decrease or no change (37%, 13% and 50% respectively). Fetal anomalies ↑ in epileptic mother. Fetal anomalies ↑ in epileptic mother. Anti-epileptic drugs (AED) responsible of most of fetal anomalies. Anti-epileptic drugs (AED) responsible of most of fetal anomalies. Control of seizures outweigh the risks Control of seizures outweigh the risks Polytherapy with (AED) caries more risks than monotherapy. Polytherapy with (AED) caries more risks than monotherapy. High doses of folic acid reduces fetal anomalies. High doses of folic acid reduces fetal anomalies. Lower doses of AED carry lower risk of fetal anomalies. Lower doses of AED carry lower risk of fetal anomalies. Patients not taking drugs or having regular seizures carry ↑ risk. Patients not taking drugs or having regular seizures carry ↑ risk.

14. Causes of epilepsy Idiopathic epilepsy. Idiopathic epilepsy. Intracranial infections: meningitis/encephalitis/brain abscess… Intracranial infections: meningitis/encephalitis/brain abscess… Vascular disease :cerebral infarction/eclampsia/sub-arachnoid haemorrhage. Vascular disease :cerebral infarction/eclampsia/sub-arachnoid haemorrhage. Metabolic: liver & renal failure/hponat.glyc.calceamia….. Metabolic: liver & renal failure/hponat.glyc.calceamia….. Drug toxicity: tricyclic antidepressant/local anesthesia (lignocain) Drug toxicity: tricyclic antidepressant/local anesthesia (lignocain) Secondary to specific cause: trauma/intracranial mass/Aps… Secondary to specific cause: trauma/intracranial mass/Aps…

15. Drugs used in epilepsy Enzyme-inducing AED: Enzyme-inducing AED: - Phenobarbitone - Phenytoin. - carbamazepine Non-enzyme-inducing AED: Non-enzyme-inducing AED: - valproate. - Gabapentin. - Lamotrigine. - clonazepam

16. Management of epilepsy Pre-pregnancy counseling: Pre-pregnancy counseling: - Stop AED in patients having no seizure for 2 years. - Use single AED with low dose. - Folic acid 5 mg/day (sp. Carbamazepine & valproate). Antenatal management: Antenatal management: - Screening for fetal anomalies. - Oral vitamin K 10 mg/day from 36 wks onwards to prevent hemorrhage. - Women adviced to take shower rather than bath. - If storoid is given for obstetric indication it should be within 48 hrs (24 mg dexamethazone 24 hrs apart)

17. Management of epilepsy Intrapartum care: Intrapartum care: - Vaginal delivery is advised. - Seizures ↑: sleep disturbance, ↓ drug intake and absorption & hyperventilation (make sure that the drugs has been took). - Seizures during labour are best controlled with IV benzodiazepines (diazepam/clonazepam) Postpartum care: Postpartum care: - Encourage breastfeeding (rare neonatal effects). - A single 1 mg of vitamin K to the neonate is advisable. - Contraception: enzyme-inducing AED reduce the efficacy so 50 ug oestrogen, reduce the free interval to 5-6 days, depo- provera is used every 10 wks & mirena is ideal (progesterone not affected enzyme-inducing AED ).