Thyroid disease

Question 1

Thyroid physiology

Answer 1

• Thyroid releases 90% T4 and 10% T3
• Hypothalamus produces TRH  tripeptide
• Very small changes in T4 result in very large changes in TSH
• T4: prehormone; half life is 1 week
  o Dose change takes 5-6 weeks to change steady state level
  o 100% of serum T4 is released from thyroid
• T3: active hormone
  o Half life is 1 day
  o 20% from thyroid; 80% from peripheral conversion of T4
  o 10X the affinity of T4 for the nuclear receptor
  o Provides the predominant biologic activity
• Thyroid hormone
  o Molecule of thyroglobulin contains 134 tyrosine residues
  o Release: digestion of thyroglobulin by lysosomal enzymes  endocytosis  exocytosis
  o Protein binding:
   > 99% protein bound (TBG, thyroxine binding prealbumin, albumin)
   Only free fraction is biologically active
   Free fraction remains stable in pregnancy
• hCG shares an alpha subunit with TSH

Question 2

Fetal thyroid physiology

Answer 2

• Maternal T4 crosses the placenta; noted as early as 6 weeks
• Important for brain development
• Minimal transfer in 3rd trimester
• Fetal thyroid gland:
  o Iodine uptake: 10 wks
  o Hormone secretion: 18 weeks
  o Most fetal T4 is converted to RT3 (inactive) by the placenta
  o As in adults, T3 provides the predominant biologic activity

Question 3

Thyroid testing in pregnancy

Answer 3

• Symptomatic women, family history, type I DM (5-8% risk of hypothyroidism); 25% risk of postpartum dysfunction
• Presence of goiter (always considered abnormal)
• Prior newborn with thyroid disease
• Previous history of high dose neck radiation

Question 4

Thyroid testing in pregnancy

Answer 4

• Symptomatic women, family history, type I DM (5-8% risk of hypothyroidism); 25% risk of postpartum dysfunction
• Presence of goiter (always considered abnormal)
• Prior newborn with thyroid disease
• Previous history of high dose neck radiation

Question 5

Risk of untreated hyperthyroidism

Answer 5

• Risk of untreated disease:
  o Maternal: PEC, thyroid storm, congestive heart failure, death
  o Neonatal: thyroid dysfunction, may occur independent of treatment or result from treatment
  o Fetal: SAB, PTD, abruption, IUGR (increased 9 fold), IUFD

Question 6

Causes of hyperthyroidism

Answer 6

o Transient hyperthyroidism of hyperemesis gravidarum
 #1 cause of biochemical hyperthyroidism (2/3 of hyperemesis cases)
 FT4/FT4I increase up to 4-6 X normal; proportional so severity of N/V
 No TFTs or therapy needed (up to 25% persist > 20 weeks)
o Graves: #1 cause of overt hyperthyroidism (2/1000 pregnancies)
o Hyperfunctioning nodule: accounts for < 10% of cases
o Subacute thyroiditis (very rare in pregnancy)
o Gestational trophoblastic disease – hCG stimulates thyroid
o Exogenous ingestion

Question 7

Graves disease, mechanism, course, and therapy

Answer 7

• TSH receptor antibodies (TSHRAb)
  o Stimulating  thyroid stimulating immunoglobulines (TSI)
  o Blocking  thyroid-blocking inhibitor immunoglobulines (TBII)
• Course: exacerbation in 1st and 3rd trimesters
  o Incidence of complications (maternal, fetal) is realted to degree of maternal control
• Therapy:
  o Thioamide  PTU and MM
  o Mechanism: interfere with thyroid hormone synthesis; both are compatible with breastfeeding
  o PTU: increased risk of liver failure; drug of choice is MM (PTU is 2nd line)
  o MM  possible embryopathy; aplasia cutis, esophageal atresia, choanal atresia; association has been refuted
  o 1st trimester  PTU (100mg TID)
  o 2nd/3rd trimester  MM 20mg QD

Question 8

How to monitor Grave’s disease in pregnancy

Answer 8

• Monitoring: Follow FT4I Q 4 weeks; dose changes take 5-6 weeks to reach steady state
  o Target levels:
   FT4I – upper limit of normal range (4.5-12.5); to minimize fetal thyroid suppression
   TSH < 0.5 mIU/L
• Other therapies:
  o Beta blockers: propanolol
   Atenolol – risk of IUGR
  o Thyroidectomy: only if medical therapy fails
  o I 131 contraindicated – half life is 1 week; by 10 weeks, fetal thyroid concentrates iodine
   Wait 6 months to conceive
• Fetal surveillance:
  o TSI peak at 28-30 weeks
  o Best time to evaluate for goiter is > 28 weeks; hyperextension of neck, neck mass

Question 9

Role of TSI in pregnancy

Answer 9

• Controversy: role for measuring maternal TSI
  o Pro (endocrine): peak at 28-30 weeks; fetal thyrotoxicosis more likely if TSI > 300% of control levels
  o Cons (ACOG): no practical use; limited value (1% fetal risk of thyrotoxicosis)
  o Possible indications: history of fetal hyperthyroidism, fetal findings, women with h/o Graves not on meds

Question 10

Role of TSI in pregnancy

Answer 10

• Controversy: role for measuring maternal TSI
  o Pro (endocrine): peak at 28-30 weeks; fetal thyrotoxicosis more likely if TSI > 300% of control levels
  o Cons (ACOG): no practical use; limited value (1% fetal risk of thyrotoxicosis)
  o Possible indications: history of fetal hyperthyroidism, fetal findings, women with h/o Graves not on meds

Question 11

Thyroid storm

Answer 11

• Thyroid Storm: life threatening
  o May follow infection, surgery, PEC, delivery
  o Thyroid hormone excess  catecholamine release
  o Diagnosis is CLINICAL: T4 level not helpful in diagnosis
   Fever (>103F)
   Tachycardia
   Agitation (delirium, coma)
   N/V, diarrhea  dehydration
   Congestive heart failure

Question 12

Risks of untreated hypothyroidism

Answer 12

o Childhood intellectual impairment
 Severe iodine deficiency  severe MR (cretinism)
 Milder disease  impaired infant and childhool neurodevelopment
* Serum screening study: IQ decreased 7 points at age 7-9 vs controls

Question 13

Causes of hypothyroidism

Answer 13

• Causes:
  o Chronic autoimmune thyroiditis (Hashimoto)
   #1 cause (present in 8-10% reproductive age women)
   Painless goiter, thyroid peroxidase antibodies, thyroglobulin antibodies
  o Result of therapy
   I 131 ablation (frequency increases with time after therapy); thyroidectomy, medications
  o Iodine deficiency (developing world); iron and antacids decrease iodine absorption
  o Secondary hypothyroidism (rare) – hypothalamic/pituitary failure

Question 14

Treatment of hypothyroidism

Answer 14

• Treatment:
  o Synthroid 100-150 micro QD (increase by 25-50 increments)
  o Goal: TSH < 2.5 mU/L (lower end of therapeautic range)
  o Monitor TSH Q 6-8 weeks, then q trimester
  o L thyroxine requirements increase in pregnancy
   Return to prepregnancy dose postpartum
   Do NOT take PNV at time of synthroid; iron limits uptake of thyroid hormone

Question 15

Postpartum thyroiditis: incidence, symptoms, pathology

Answer 15

Postpartum Thyroiditis:
- Incidence: 10% of pp women (30% with Type I DM)
- Symptoms: depression, carelessness, memoray impairment
- Pathology: destructive lymphocytic thyroiditis
o Transient thyrotoxicosis (for 1-4 months; treat with MM/PTU), then hypothyroidism (4-8 mo pp; treat with l-thyroxine)
o 2/3 resolve by 12 months
- When TPO antibodies are found at 16 weeks; 50% will develop pp thyroiditis; 25% will develop permanent overt hypothyroidsm within 1 year

Question 16

Solitary thyroid nodule

Answer 16

• Noted in 10% of pregnant women
  o If malignant: (long term prognosis is good)
   Papillary 75-80%
   Follicular 15-20%
• Work up: check TSH: if decreased, hormonally active nd NOT malignant
  o If TSH normal, order US of thyroid  could be malignant
• Solid or semicystic  FNA
  o Benign: observe and aspirate if enlarges
  o Suspecte papillary cancer
   1st or 2nd trimester  oerpate 2nd trimester (<24 wk)
   3rd trimester  operate pp
  o Suspect follicular cancer
   Any GA  operate pp
• Generally, surgery avoided in 1st trimester and > 24 weeks
• Lesions are slow growing and delay to pp does not affect outcome

Question 17

Placental transfer of thyroid hormones and antibodies

Answer 17

Question 18

Placental transfer of thyroid hormones and antibodies

Answer 18

Question 19

Differential for goiter

Answer 19

• Iodine deficiency, graves, autoimmune (Hashimoto), excessive iodine intake, thyroid cancer, lymphoma, lithium or thioamide therapy