Thyroid hormone is produced by iodination of tyrosine residues in thyroglobulin to form mono or diiodo tyrosine
Estrogen acts on liver to produce TBGstimulatory effect of hCG on the TSH thyroid receptor identical alpha subunit10,000 IU/L increment in circulating hCG corresponds to a mean T4 increment of 0.1 ng/dl, and in turn to a lowering of TSH of 0.1 mU/L.
Overt: 0.61%s/c: 5.48%
Lithium causes hypothyroidism by inhibiting thyroid hormone releaseAmiodarone: iodine containg drug may also cause hypothyroidism
Four inorganic compounds are used as iodide sources, depending on the producer: potassium iodate, potassium iodide, sodium iodate, and sodium iodide.
Serum TSH is more sensitive than free T4 for detecting hypothyroidism and for following effectiveness of replacement therapy. If the TSH is abnormal, then evaluation of free T4 is recommended. The presence of antithyroid antibodies identify a population of women at particular risk for pregnancy complications(miscarriage), postpartum thyroid dysfunction.Free T4 index:TT4*Resin T3 uptake
Pregnancy is associated with a decrease in antibody titers due to trophoblast secretion of immunosuppressant factors
long-acting thyroid-stimulating antibody (LATS) TSI
In c/o previousthyroidectomy or ra I tt patient may be euthyroid but antibodies may still be present
Lid lag (elicited by having the patient follow your finger as you move it from the top to the bottom of their visual field. Lid lag is present if the upper lid is slow to follow the eye on downward movement and white sclera becomes exposed above the iris)Lid retraction and stare (the white sclera abovethe iris is visible at rest. The orbit appears prominentbut is not actually bulging (proptotic))
Clubbing (individuals without clubbing display a diamond-shaped window at the base of the nailbeds when two fingers from opposite hands areopposed dorsally. The distal angle between thetwo opposed nails should be minimal. In individualswith digital clubbing, the diamond window isobliterated and the distal angle between the nailsincreases with increasing severity of clubbing)
Block and replace therapy not adviced as antithyroid medications cross placenta but levothyroxine does not. Leading to fetal hypothyroidism.
Cesarean to avoid dystocia in extremely large fetal goiter.
Intervention on behalf of fetus should not be undertaken until mother is stabilized as vaginal or c sn may exacerbate thyroid storm
distinguished from postpartum Graves’ disease by an I123 uptake and scan (low or normal uptake in PPT compared to a diffusely increased uptake consistent with Graves’).However, this requires interruption of the woman’s breastfeeding.In Graves’ disease, hyperthyroidism will persist, whereas in PPT the hyperthyroid phase will spontaneously resolve.
Thyroid disease in pregnancy
DR RAJEEV SOODDR RASHMI VOHRADEPT. OF O.B.G. 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 - word’s largest belt from Kashmir to Naga Hills.
Thyroid; derived from Greek word – means shield gland. Highly vascular organ. Brownish red, 2 lobes (4x2cm), one isthmus(2x2cm). 30% have pyramidal lobe. Weight: 15-20g
iodine reduced iodide transported Thyroid in gut to Iodide incorporated into gp thyroglobulin MIT DIT T4 enters circulation by direct glandular secretion. T3 is produced by mono-deiodination of T4 in periphery.
T4 bound to circulating transport proteins – Thyroxine binding globulin (TBG), Thyroxine binding prealbumin or transthyretin, Albumin.
Increased thyroxine requirement in pregnancy:(1) TBG Free thyroid hormones H-P-T axis stimulation(2) hCG stimulates TSH rp(3) peripheral metabolism. ? placental type II deiodinase T4 T3 (fetus is dependent on type II conversion) pl type III deiodinase T4 rT3 3,3’diiodothyronine(T2)
PHYSIOLOGIC CHANGE CLINICAL IMPORTANCEIncreased TBG Need for T4 production TT3 & TT4 levels Interference with FT4 assay accuracyPlacental de-iodination of T4 T3 & T4 metabolism Need for T4 productionIncreased iodine clearance iodine requirement(renal clearance and fetal transfer) Risk of maternal and fetal hypothyroidism and goiterB HCG elevation 1st TM FT4 & TSH Transient mild thyrotoxicosisReduction in TSHRAb during Graves’ disease improvementpregnancyPostpartum increase in thyroid Exacerbation of Graves’ diseaseantibodies Precipitation of postpartum thyroiditis
organization Thyroid screening Goal TSH(mIU/L) Treatment of with TSH subclinical hypothyroidismACOG Case finding Not specified Not recommendedoct 2007USPSTF(United Case finding Not specified Not specifiedStates PreventiveServices Task Force)TES(The Endocrine Case finding 2.5 in Ist TM RecommendedSociety) 3 in IInd &IIIrd TMAACE( American Routine 0.3-3.0 RecommendedAssociation of ClinicalEndocrinologists)BTA(British thyroid Case finding 0.4-2.0 Recommendedassociation)
Sign/symptoms of hypo or hyperthyroidism 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 infetusMaternal thyroxine in coelomic fluid 6 weeksTHR gene expression in human brain 8 weeksFetal iodine uptake 10-14 weeksFetal thyroxine secretion 18 weeks
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. Subclinical – Elevated TSH levels normal FT4 in absence of clinical symptoms. Overt – increased TSH with low thyroxine levels with clinical symptoms.
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 hypothyroidism(90% gland destroyed)
Subacute granulomatous thyroiditis Subacute lymphocytic thyroiditis Transient hyperthyroidism Transient hypothyroidism 90% 10% recover persistent goiter 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 Excessive iodine (μg/d) intake (μg/d)Pregnant women 250 500Lactating women 250 500Children 0-5 years 90 1806 to 12 years 120 180>12 years 150 180
Iodised salt : 46–76 mg/kg Shrimp (85 grams) : 35mcg Egg, boiled : 12mcg Navy beans, cooked – ½ cup : 32mcg Potato with peel, baked – 1 medium : 60mcg Seaweed (7 grams) dried – 4,500mcg (highest).Iodine should be added after cooking of food. ?
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 Associated with gestational hypertension, preterm delivery, stillbirths, abruption.
N TSH FT4 Prevalence: 1-2% of pregnancies. No adverse affects on pregnancy outcome No benefit of levothyroxine treatment.
Goal To return thyroid hormone levels to within the reference range. ?
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.
>/=1 risk Euthyroid:no factor for S.TSH 0.08-<3 further work thyroid ds up Repeat TSH,FT4, TPO >/=3 Levothyroxine started TSH>/=3 Normal TSH>/=3 Low FT4 results N FT4, +/-TPO +/- TPO SUBCLINICAL HYPOTHYROIDISM HYPOTHYROIDISM EUTHYROID: Stop levothyroxine
Levothyroxine sodium - most widely prescribed treatment Safe for both mother and fetus. Category A. Available dosages - 25–300 mcg. Dose : 30% increase from non pregnant value, if already hypothyroid. If newly diagnosed in pregnancy : 1.0–2.0 mcg/kg/day or approximately 100 – 150 mcg of levothyroxine daily. TSH measured 4-6 weeks following dose change with TSH goal between 0.5-2.5mIU/L Once stable, TSH checked every 8 weeks.
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 Related to Overtreatment smaller head circumference and LBW. hyperthyroidism. transient hair loss. BMD
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.
In utero therapy:Fetus effectively absorbs T4 from amniotic fluid.3rd trimester fetal T4 requirement : 6 ug / kg /day.Intraamniotic administration of 250 – 500 ug of thyroxine done at 7 – 10 days interval.In term infants :Requirement : 10 – 15 ug /kg /day.TSH levels kept below 5 mU /l and T4 levels at 10-16 ug /dl.Tab thyroxine crushed and fed directly to the infant.
Thyroid antibodies: directed towards cytoplasmic antigens- thyroid peroxidase (TPOAb) and thyroglobulin (TgAb) antibodies. directed to the TSH receptor- TSH receptor antibody (TSHRAb). TPOAB present in 10-15% normal population.
Cause: cross reactivity between hcg and TSH at thyroid receptor Nausea and vomiting leading to dehydration, electrolyte imbalance and weight loss. Spontaneous resolution by 18 weeks. Antithyroid medications avoided.
Autoimmune disorder. Incidence: 0.5% Most common cause of hyperthyroidism in pregnancy Symptoms antecedent pregnancy Physiology: antibodies stimulate thyroid receptors; thyroid hypertrophy and hyperfunction. Antibodies: TPO Thyroglobulin Microsomal Thyroid receptor antibodies.
1st and 2nd trimester Previous radio-active iodine or thyroidectormy for Graves’ disease New-onset thyrotoxicosis to differentiate Graves’ disease from gestational thyrotoxicosis Previous pregnancy complicated by fetal or neonatal hyperthyroidism3rd trimester Woman requiring antithyroid drugs for Graves’ disease into third trimester
Nervousness,Agitation,Fatigue Eye signs (distinct from Graves’ ophthalmopathy) Tachycardia/palpitations Heat intolerance Lid lag Increased appetite, Weight loss Lid retraction Change in bowel habits Proptotis Skin/hair/nail changes; Skin is soft and moist Onycholysis (separation of the distal nail from its bed) Hair soft, fine and thin
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
Hyperthyroidism can be diagnosed on the basis of 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 To normalize thyroid hormone levels(keeping FT4 in upper normal range <0.85-1.9ng/dl), To treat bothersome adrenergic symptoms of hyperthyroidism.
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. Improvement seen in 3-4 Dose- 300-450mg in 3 divided weeks; full response 8 weeks. doses of 100-150mg each. Category D ? Tapered as pregnancy progresses. Side effects: Iatrogenic fetal hypothyroidism Transient leukopenia (10%) Agranulocytosis (0.3-0.4%) Hepatotoxicity (0.1-0.2%) Vasculitis
METHIMAZOLE Side effects: Dose- 5–20 mg b.i.d Crosses placenta more readily. Transient leukopenia (10%) Category D Agranulocytosis (0.3-0.4%) Methimazole embryopathy – Hepatotoxicity (0.1-0.2%) Esophageal atresia Vasculitis Choanal atresia Cutis aplasia. Dose monitored with 3-4 weekly FT4 or FT4I levels. Improvement seen in 3-4 weeks; full response 8 weeks. Tapered as pregnancy progresses.
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.
Other drugs in hyperthyroidism Beta adrenergic blockers: propranolol. inhibits MOA: T4 T3 20-40mg orally every 8-12 hours
Management Antithyroid medications, beta-blockers and Supportive Care. fetal thyrotoxicosis suspected in labor aggressive treatment of maternal thyrotoxicosis fetus with a large goiter consideration of the best route of delivery Elective cesarean to avoid dystocia management of the fetal airway.
ex utero intrapartum treatment (EXIT) procedure 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 Papillary thyroid cancer : most common type in pregnancy. Excellent long term prognosis Surgey delayed postpartum; depending upon histology. S.thyroglobulin : predictive of recurrent disease. Postsurgical I131 whole body scintigraphy and radioiodine remnant ablation : contraindicated in pregnancy & lactation.
STEP 1. START THIONAMIDES & CONTROL HEART RATE beta-blockers - control tachycardia (maintainTHIONAMIDES- 1 g PTU (orally or through HR<90bpm)- propranolol 1-2 mg i/v over 5 min to total NG tube) 200 mg every 6 hours of 6-10mg 60–80 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 Lugol’s solution 10 drops orally 8 hourly Or Lithium carbonate 300mg PO 6 hourly Or Iodinated radiocontrast agents iopodate and iopanoic acid 0.5–1.0 g orally daily.
immunosuppression postpartum relapse(70%) disappears (within first 3 months) TSH and free T4 done 6 weeks post partum. T4 levels must be controlled prior to the next pregnancy.Drugs in lactating mother: 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 (10–20 mg/day). AAP and WHO support compatibility of breatfeeding and all antithyroid medications
Postpartum Rebound in thyroid autoimmunity lymphocytic infiltration of the thyroid gland 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 40–50% 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 Autoimmune destruction of the immune destruction loss of gland - release of stored hormone functioning thyrocytes 1 - 4 months postpartum 3 - 8 months postpartum (usually at 6 months) self-limiting (1–2 months). lasts much longer (4–6 months) Abrupt onset fatigue, palpitations, sleep fatigue, weight gain, loss of deprivation, nervousness / irritability. concentration, depression small, painless goiter may be present. Antithyroid medications not beneficial.
Patients identified with PPT should be screened regularly since 20– 50% of women will develop permanent hypothyroidism within 2–10 years. A TSH level should be done annually and prior to conception.
EVALUATION OF THYROID NODULE IN PREGNANCY Abnormal TSH Work up N & treat Solid lesion>2cm USG Cystic lesion>4cm Solid lesion<2cm Cystic lesion<4cm <24weeks >24 weeksFNAC Postpartum Levothyroxine follow up Nonmalignant malignant surgery