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IGMC SHIMLA
Most common endocrine disorder in pregnancy. 1-2% pregnant women. Pregnancy may modify course of thyroid disease. Pregnancy outcome can depend on optimal management of thyroid disorders.
The Himalayan goiter belt - words largest belt from Kashmir to Naga Hills.
Thyroid; derived from Greek word means shield gland. Highly vascular organ.
TRH
PITUITARY 3,5,3,5 tetra-iodo-L-thyronine (levothyroxine,L-thyroxine,T4)
TSH
THYROID
iodine
reduced in gut
iodide
transported to
Thyroid
MIT
DIT
FT3
pmol/L
3-5.7
2.8-4.2
2.4-4.1
(1)
(2) (3)
peripheral metabolism.
placental type II deiodinase
?
(fetus is dependent on type II conversion)
T4
pl type III deiodinase
T3
rT3
T4
3,3diiodothyronine(T2)
CLINICAL IMPORTANCE Need for T4 production TT3 & TT4 levels Interference with FT4 assay accuracy T3 & T4 metabolism Need for T4 production
Placental de-iodination of T4
organization
Goal TSH(mIU/L)
ACOG oct 2007 USPSTF(United States Preventive Services Task Force) TES(The Endocrine Society) AACE( American Association of Clinical Endocrinologists) BTA(British thyroid association)
Case finding
Recommended
Routine
Recommended
Case finding
0.4-2.0
Recommended
Goiter
h/o hyperthyroid or hypothyroid disease, postpartum thyroiditis or thyroid surgery Previous therapeutic head or neck irradiation Autoimmune disorder Family history of thyroid disease Infertility History of miscarriage or preterm delivery Thyroid antibodies Unexplained anemia or hyponatremia Increased cholesterol level
Events in fetus
Maternal thyroxine in coelomic fluid THR gene expression in human brain Fetal iodine uptake Fetal thyroxine secretion 6 weeks 8 weeks 10-14 weeks 18 weeks
Hyperthyroidism
Postpartum thyroiditis
Incidence: 1 - 3 per 1000 pregnancies. Types: Primary - inadequate thyroid hormone production despite pituitary gland stimulation(including iodine deficiency). Central - insufficient stimulation of the thyroid by the pituitary or hypothalamus.
PRIMARY HYPOTHYROIDISM
SECONDARY HYPOTHYROIDISM
Hashimoto thyroiditis Subacute thyroiditis Endemic iodine deficiency Suppurative thyroiditis Previous thyroidectomy Previous radioablation Medication exposure
Lymphadenoid thyroiditis ; chronic lymphocytic thyroiditis. Most common cause in iodine sufficient population. Incidence: 4 per 1000. female: male : 5:1 Antithyroid antibodies damage the gland. Transient hyperthyroidism destroyed) hypothyroidism(90% gland
Subacute painful thyroiditis Viral infection Sudden onset Fever, myalgia, neck pain
Subacute granulomatous thyroiditis Subacute lymphocytic thyroiditis Transient hyperthyroidism Transient hypothyroidism 90% recover
Lasts 4-6 weeks; may be 9 months Differentiated from Graves disease by lack of radioiodine uptake on thyroid scan Symptomatic treatment.
Leading cause of preventable mental retardation worldwide. Mean IQ loss of 13.5 points. Iodine sufficiency determined through measuring median Urinary Iodine excretion. Insufficient urinary iodine: Pregnancy : <150mcg/L Lactation : <100mcg/L renal clearance Iodine needs increase in pregnancy fetal and placental uptake
Recommended iodine intake (g/d) Pregnant women Lactating women Children 0-5 years 6 to 12 years 250 250 90 120
>12 years
150
180
Iodised salt : 4676 mg/kg Shrimp (85 grams) : 35mcg Egg, boiled : 12mcg Navy beans, cooked cup : 32mcg Potato with peel, baked 1 medium : 60mcg Seaweed (7 grams) dried 4,500mcg (highest). ?
Secondary hypothyroidism Pituitary necrosis from vascular hypoperfusion Spectrum varies from failure of lactation or resume menses to acute panhypopituitarism 90% develop secondary hypothyroidism.
Secondary hypothyroidism Peripartum period Autoimmune disorder Anterior pituitary destruction Panhypopituitarism to single hormone deficiency Imaging: enhancing sella turcica mass Mass effects (headache and visual field changes)
TSH ; N FT4 & FT3 Prevalence in pregnancy- 2-5% 31% +ve for TPO antibodies. More commonly seen with autoimmune diseases
N TSH
FT4
Prevalence: 1-2% of pregnancies. No adverse affects on pregnancy outcome No benefit of levothyroxine treatment.
Fatigue,
Insomnia,
Constipation,
Cold intolerance, Weight gain,
Periorbital oedema,
Myxedema, Prolonged relaxation of DTRs.
Goiter.
deafness, stunted growth , Peripartum hypoxia and increased risk of neonatal mortality
low birthweight,
Stillbirth, PPH.
Goal
Euthyroidism at the time of conception. If on treatment- delay pregnancy until TSH is normal.
do not take levothyroxine and multivitamins at the same time (interference with absorption of thyroxine)
adequate iodine intake (250mcg/d). Dietary goitrogens : cabbage, cauliflower, broccoli and even water purifying agents should be avoided. Boiled water is recommended.
S.TSH
0.08-<3
>/=3
Repeat TSH,FT4, TPO Levothyroxine started TSH>/=3 N FT4, +/- TPO SUBCLINICAL HYPOTHYROIDISM TSH>/=3 Low FT4 +/-TPO
Normal results
HYPOTHYROIDISM
Levothyroxine sodium - most widely prescribed treatment Safe for both mother and fetus. Category A. Available dosages - 25300 mcg.
Bioavailability affected by medications or food: taken empty stomach. Absorption: Carafate, cholestyramine, ferous sulphate & calcium carbonate. Clearance: phenytoin, carbamazepine. Postpartum: Decrease dose by 30% (diagnosed in pregnancy) Prepregnancy dose (hypothyroid before pregnancy) TSH reassessed 6 week postpartum.
ON MOTHER
ON FETUS
Women should be clinically and biochemically euthyroid prior to labor. Obstetric complications including increased risk of stillbirth, preterm delivery, pre-eclampsia and placental abruption should be kept in mind.
Causes:
Thyroid dysgenesis
Thyroid apasia Thyroid hypoplasia
Thyroid ectopy
Drug induced (thioamides ,amiodarone , lithium , potassium iodide) Dyshormogenesis
In utero therapy:
Thyroid antibodies:
directed towards cytoplasmic antigensthyroid peroxidase (TPOAb) and thyroglobulin (TgAb) antibodies.
TPOAB
subtle maternal thyroid dysfunction autoimmune imbalance; rejection of the fetus thyroid antibodies affecting fetal thyroid gland ; fetal loss Associated increased maternal age
antibody titers
postpartum flare up
postpartum thyroiditis.
Incidence: 0.1 to 0.4 % Types: Subclinical hyperthyroidism-suppressed TSH, normal FT4 and FT3 Overt-suppressed TSH and elevated FT4 and/or FT3 Gestational- detected in pregnancy.
Intrinsic thyroid disease Graves disease (most common) Toxic nodule single or multiple Subacute or silent thyroiditis Excessive, exogenous thyroid hormone Factitious Therapeutic(amiodarone) Gestational thyrotoxicosis Hyperemesis Gestational trophoblastic disease Hydatidiform mole Multiple gestations Hydrops Rare TSH producing pituitary tumour Iodine induced Struma ovaii.
Autoimmune disorder.
Incidence: 0.5%
Most common cause of hyperthyroidism in pregnancy
Immunoglobulins, ( IgG subclass). 2 types: Stimulating thyroid stimulating immunoglobulins(TSI); Graves' disease. Blocking thyrotropin binding inhibitory immunoglobulins(TBII); Hashimoto's thyroiditis.
TSI fetal tachycardia, goiter, IUGR, craniosynostosis, premature skeletal maturation, CHF, hydrops. TBII fetal bradycardia, goiter, IUGR.
3rd trimester
Woman requiring antithyroid drugs for Graves disease into third trimester
Nervousness,Agitation,Fatigue Tachycardia/palpitations Heat intolerance Increased appetite, Weight loss Change in bowel habits Skin/hair/nail changes; Skin is soft and moist Onycholysis (separation of the distal nail from its bed)
Lid retraction
Proptotis
Graves' orbitopathy: Chemosis (swelling of the conjunctiva), Proptosis (exophthalmos or bulging orbit), Dysconjugate gaze (double vision on looking to the extremes of the visual field) Pretibial myxedema ( thyroid dermopathy) bilateral, firm, nonpitting, asymmetric plaques or nodules, most often confined to the pretibial area ; may occur anywhere Thyroid bruit Clubbing
ON PREGNANCY
ON FETUS
Spontaneous abortion, Preterm birth, Pre-eclampsia, Abruption, Fetal growth restriction, Perinatal morbidity and mortality, Congestive heart failure, Thyroid storm.
Congenital malformations of heart, kidney or brain. Fetal Graves disease fetal tachycardia, high output cardiac failure, NIHF, craniosynostosis, LBW, fetal goiter, Fetal demise.
Clinical presentation
Thyroid examination
Thyroid function tests Thyroid antibody tests
Graves disease- a diffuse, symmetric, soft goiter, which may have an audible bruit. Nodular thyroid disease- A palpable nodule (usually 3 cm) Subacute thyroiditis- generalized thyroid tenderness.
Goals
Clinical situations:
Hyperthyroidism under treatment Potential side effects of antithyroid drugs on the fetus discussed. wait 6 months after radioablation. euthyroid at the time of conception. Previous ablation treatment for Graves' disease The dose of thyroid replacement therapy needs to be increased soon after conception. In spite of euthyroidism, high maternal titers for TSI may be present; fetus at risk.
Previous treatment for thyroid carcinoma wait 1 year after completion of radioactive treatment before conception. Inadequately treated hyperthyroidism impaired maturation of the fetal hypothalamic-pituitary-thyroid axis - central congenital hypothyroidism in the infant.
PROPYLTHIOURACIL (PTU) Inhibits conversion of T4 to T3 Crosses placenta less readily. Dose- 300-450mg in 3 divided doses of 100-150mg each. Category D ?
Side effects:
Iatrogenic fetal hypothyroidism Transient leukopenia (10%) Agranulocytosis (0.3-0.4%) Hepatotoxicity (0.1-0.2%) Vasculitis
Side effects: Transient leukopenia (10%) Agranulocytosis (0.3-0.4%) Hepatotoxicity (0.1-0.2%) Vasculitis
Dose monitored with 3-4 weekly FT4 or FT4I levels. Improvement seen in 3-4 weeks; full response 8 weeks.
Monitoring:
Cordocentesis.
Routine fetal blood sampling for thyroid indices is recommended if previous I131 ablation, Abnormal TSIs or TBII, FGR, heart failure or goiter, with or without tachycardia.
Beta adrenergic blockers: propranolol. inhibits MOA: T4 T3 20-40mg orally every 8-12 hours
Supportive Care.
fetal thyrotoxicosis suspected in labor aggressive treatment of maternal thyrotoxicosis
Candidates: Fetuses with neck masses large enough to cause airway obstruction ; to manage airway obstruction after fetal surgery.
It involves securing the neonatal airway (usually with endotracheal intubation often guided by laryngoscopy or bronchoscopy) while the umbilical cord and maternal-fetal circulation remain intact in the hopes of avoiding difficult emergency intubations in the delivery room.
Usually perfomed with cesarean deliveries; described with vaginal deliveries too.
Most commonly diagnosed endocrine malignancy. Incidence: 14 / 1,00,000 pregnant women. Histologic types: papillary, follicular, medullary, Hurthle cell, anaplastic
PRECIPITATING FACTORS
Preeclampsia,
Anemia, Sepsis,
surgery.
Nausea/vomiting/diarrhoea/ dehydration,
Agitation/delirium/coma,
LAB VALUES
T4 & T3
TLC Transaminases
Abdominal pain.
hypercalcemia
beta-blockers - control tachycardia (maintain HR<90bpm)- propranolol 1-2 mg i/v over 5 min to total of 6-10mg 6080 mg every 4 hours orally or NG tube.
STEP 2.CORTICOSTEROIDS Dexamethasone 1-2mg PO/IV/IM 6 hourly Or Hydrocortisone 100mg IV 8 hourly Or Prednisone 60mg PO a day
STEP 3.IODINE(after 1-2 hour of thionamide therapy.) SSKI 5 drops orally 8 hourly. Or 500-1000mg sodium iodide i.v. 8 hourly Or Lugols solution 10 drops orally 8 hourly Or Lithium carbonate 300mg PO 6 hourly Or Iodinated radiocontrast agents iopodate and iopanoic acid 0.51.0 g orally daily.
immunosuppression disappears
TSH and free T4 done 6 weeks post partum. T4 levels must be controlled prior to the next pregnancy.
Both PTU and methimazole excreted in breast milk; PTU is largely protein bound; does not seem to pose a significant risk to the breastfed infant. Methimazole safe only at low doses (1020 mg/day). AAP and WHO support compatibility of breatfeeding and all antithyroid medications
The likelihood of developing postpartum thyroidis is related to serum levels of thyroid autoantibodies. Anti-TPO antibodies are present in 90% of women with PPT.
Women with high antibody titers in early pregnancy have 4050% chance of developing PPT.
Women with type 1 diabetes have a significantly higher incidence, ranging from 18% to 25% due to the high prevalence of TPO antibodies.
HYPERTHYROID PHASE
HYPOTHYROID PHASE
loss of
3 - 8 months postpartum (usually at 6 months) lasts much longer (46 months) fatigue, weight gain, loss of concentration, depression
Patients identified with PPT should be screened regularly since 20 50% of women will develop permanent hypothyroidism within 210 years. A TSH level should be done annually and prior to conception.