Endocrine disorders during pregnancy.pptx

pathophysiology

1. Endocrine disorders in pregnancy lecturer : - abdi nuh abdi hassan

2. Topics covered Thyroid disorders in pregnancy Parathyroid disorders in pregnancy

3. Introduction Among endocrinopathies in pregnancy, diabetes mellitus – commonest Thyroid disorders are second Pituitary, adrenal and parathyroid disorders are less common Basic pathology – disordered autoimmunity - hypersecretion Fetal lymphocytes Fetal stem cells Fetal DNA Reside in maternal endocrine organs

4. I. THYROID DISORDERS IN PREGNANCY Physiology Pregnancy has a substantial impact on maternal thyroid physiology Symptoms of thyroid disease during pregnancy may be confused as physiological changes 2-5% pregnancies are complicated with thyroid disease

5. The most important physiological changes are Thyroxine binding globulin (TBG) increases – response to estrogen, also half life increases (15 min to 3 days) Increase in thyroid stimulatory factors of placental origin (e.g.. hCG) Decreased iodine availability – enhanced excretion (increased GFR) BMR increases by 25% in pregnancy TBG peaks at ~ 20 wks T4 peaks at ~ 18wks hCG and TSH

6. Pathophysiology of autoimmunity Autoantibodies have one or more of the following effects Stimulation Inhibition Inflammation & destruction Autoimmune phenomenon - follows a precipitating event Viral infection Radiation exposure Inherent genetic predisposition Pregnancy itself

7. Development of antibodies (Fetal – maternal cell trafficking) Fetal lymphocytes (male fetus>female) enter maternal circulation and act against the thyroid parenchyma Maternal microchimerism – SRY region of the male fetal lymphocytes specifically target thyroid cells More commonly thyroid peroxidase antibodies occur (10-20% pregnancies), 50% of these patients develop autoimmune thyroiditis May ultimately develop thyroid failure.

8. A) Hyperthyroidism Symptomatic thyrotoxicosis occurs in 1/1000 or 1/2000 pregnancies Difficult to differentiate mild disease from normal pregnancy symptoms Elevated T4 with markedly depressed TSH is diagnostic Normal T3 and T4 with depressed TSH indicates subclinical hyperthyroidism

9. Thyrotoxic patients will have high Thyroid stimulating antibodies However, since autoimmune remission occurs due to pregnancy – and symptoms are relieved

10. Propylthiouracil was preferred (trans placental passage) to Methimazole (aplasia cutis & embryopathy - choanal atresia) Propylthiouracil – liver failure in pregnancy Carbimazole – used safely in EU (rarely associated with GI anomalies) Recommendations suggest: Propylthiouracil (100-600mg/day) – 1 st line in 1 st trimester Methimazole (10-40 mg/day) in the 2 nd and 3 rd Both equally efficacious

11. Dosage to be adjusted to maintain total T4 at 1 ½ times upper limit of normal TFT – every 2-4 weeks LFT – every 3-4 weeks (Propylthiouracil) CBC – to assess transient leukopenia/agranulocytosis (Methimazole) Subtotal thyroidectomy Severe adverse reactions to medical therapy Persistent high doses are needed (>450mg PTU or >30 mg MMI) Non-adherence to therapy

12. Fetal considerations of maternal hyperthyroidism Thyroid receptor antibodies freely cross placenta TRAb should be measured by 22 wks of gestation in mothers with Graves’ disease h/o Graves’ with I 131 therapy prior to pregnancy Previous neonate with Graves’ disease Previous documented TRAb If I 131 is given inadvertently Suggest abortion Evaluate fetal hypothyroidism

13. Thyroid storm in pregnancy Rare Thyroxine induced myocardial effects – precipitated by preeclamsia, anemia and sepsis Treatment 1g Propylthiouracil orally/RT, then 200mg Q6H 500mg – 1g Sodium iodide or 8 drops of supersaturated KI Dexamethasone 2mg iv Q6H for 4 doses β blockers for tachyarrythmias

14. B) Hypothyroidism Overt Hypothyroidism – High TSH and low T4 Subclinical – High TSH and normal T4 Hypothyroidism – Adverse outcomes in mother and fetus Treatment is known to improve obstetric outcome, however neurodevelopmental long term effects are not known enough Potential benefits > risks – Replacement therapy is indicated in subclinical hypothyroidism

15. Thyroxine requirement in pregnancy is higher than in non pregnant state. 30% increase in dosage is needed (TBG increased) Hypothyroidism diagnosed during pregnancy, treated with 50-100 μ g/day with TFT at 4-6 week intervals Dose adjustment with 25-50 μ g till TSH maintained around 2.5 mIU/L (1 st trimester) and 3.0 mIU/L (2 nd & 3 rd trimesters) Soon after delivery, dose reduction is required

16. Iodine deficiency may be a cause for hypothyroidism. Daily requirement of 220 - 250 μ g/day has to be met (not >500 μ g/day) Fetal manifestations of maternal hypothyroidism Decreased school performance Impaired reading Reduced IQ Congenital thyroid screening – mandatory in the US and EU, not in India.

17. C) Gestational Thyrotoxicosis Also called Transient hyperthyroidism Associated with hyperemesis gravidarum High serum thyroxine and low TSH levels High βhCG levels – structural similarity to TSH Gestational trophoblastic disease can also present with hyperthyroidism

18. Patients with hyperemesis should be evaluated for T4, TSH and TRAb Anti thyroid drugs – not indicated β blockers for peripheral manifestations Anti thyroid drugs are to be given only if Graves’ disease is diagnosed Free T4 > 1 ½ times > upper limit of normal TSH <0.01 μ IU/ml

19. D) Post partum thyroiditis Transient autoimmune thyroiditis 5-10% of women within a year of childbirth Women with TRAb and anti-TPO antibodies before pregnancy are more prone to develop this condition Likelihood of developing post partum thyroiditis is high in Type 1 diabetics and patients with chronic viral hepatitis

20. Clinical features 30% chance of eventual permanent hypothyroidism Post partum depression is associated with it, although not very conclusively

21. Recommended patient profiles for targeted thyroid disease case finding in women seeking pregnancy, or newly pregnant

22. E) Nodular Thyroid disease Small thyroid nodules – normal in pregnancy Some studies suggest these nodules turning malignant Diagnosis is mainly by sonography & FNAC FNAC – if nodules > 1cm 5mm to 1cm with suspicious/high risk history

23. If nodules are detected early Surgery within 26 wks – after that, surgery can stimulate preterm labour

24. If nodules are detected in the 3 rd trimester, surgery – after delivery. Papillary and follicular carcinomas are relatively slow growing & surgery can wait Radio-iodine therapy at least 4 weeks after cessation of breastfeeding and the lady asked not to conceive for 6 months to a year

25. II. PARATHYROID DISORDERS Fetal Calcium needs – 300 mg/day Pregnancy – increased renal loss Increased intestinal absorption Serum albumin low, Corrected Ca – normal

26. Pregnancy has no significant effect on PTH levels Vitamin D levels higher – especially 3 rd trimester Not due to PTH Due to PTHrP, estradiol, prolactin & placental lactogen all stimulate 1 α hydroxylase (renal)

27. A) Hyperparathyroidism As in non pregnant state – commonest parathyroid adenoma Hyperemesis Renal calculi Psychiatric disorders Generalized weakness Pregnancy blunts the effects due to higher calcium requirement by the fetus Soon after delivery, postpartum hypercalcemic crisis can occur Still births and preterm deliveries higher.

28. Management Elective neck exploration well tolerated even in 3 rd trimester Asymptomatic women to be given 1 – 1.5g phosphate orally/day in divided doses Patient in hypercalcemic crisis… Furosemide to maintain urine output >150ml/hr Mithramycin at 25 μ g/kg once and 24 hrs later Calcitonin 100U every 6 hrs/8 hrs (sc or im)

29. B) Hypoparathyroidism Commonest cause – post thyroid/parathyroid surgery Facial muscle spasms, muscle cramps, paraesthesia of lips, tongue, fingers, feet. Chronic hypocalcemia – multiple bone fractures in the neonate Treatment Calcitriol is the treatment of choice Vitamin D – 50,000 – 150,000 U/day to increase levels of calcitriol Calcium gluconate 3-5 g/day Low phosphate diet

30. C) Pregnancy associated osteoporosis Increased calcium demand and poor oral intake during pregnancy – reduced bone mineral density Incidence is 4/million pregnancies Back pain Hip pain Difficulty in weight bearing Treatment is with calcium and Vitamin D supplements

31. E) Lymphocytic hypophysitis Autoimmune infiltration of pituitary parenchyma by lymphocytes & plasma cells Associated with hypopituitarism and mass effects Imaging cannot distinguish it from pituitary adenoma Hormone replacement therapy – usually only option Spontaneous regression possible – most develop panhypopituitarism Surgery only indicated to debulk and reduce mass symptoms

32. Take home messages Physiology of pregnancy alters the course of most endocrine disorders Index of suspicion must be high in pregnancy mainly due to overlapping normal symptoms of pregnancy Thyroid screening in pregnancy is important, especially to prevent fetal hypothyroidism

33. Thank you