Thyroid

 Gland  and  Pregnancy  

•  Anatomically,  the  thyroid  gland  undergoes  
moderate  enlargement  during  pregnancy  
caused  by  glandular  hyperplasia  and  increased  
vascularity.    
•  increased  TBG  concentra<ons  result  from  
both  higher  hepa<c  synthesis  rates  and  lower  
metabolism  rates  
–  Increases  total  T4  and  T3  but  not  the  
physiologically  important  FT4  and  FT3    

 
 Thyroid  Gland  and  Pregnancy  
•  TRH  levels  are  not  increased  during  normal  
pregnancy.    
•  TSH  levels  decrease  in  pregnancy  
§  May  lead  to  a  misdiagnosis  of  subclinical  
hyperthyroidism  
 
Autoimmunity  and  Thyroid  Disease  
•  Thyroid-­‐s<mula<ng  autoan<bodies,  also  called  
thyroid-­‐s<mula<ng  immunoglobulins  (TSIs),  bind  
to  the  TSH  receptor  and  ac<vate  it,  causing  
thyroid  hyperfunc<on  and  growth.    
•  Thyroid  peroxidase  (TPO)  is  a  thyroid  gland  
enzyme  that  normally  func<ons  in  the  
produc<on  of  thyroid  hormones.  Thyroid  
peroxidase  an<bodies,  previously  called  thyroid  
microsomal  autoan<bodies,  are  directed  against  
TPO    
 Hyperthyroidism  
•  Clinical:  tachycardia,  thyromegaly,  
exophthalmos,  failure  to  gain  weight  despite  
adequate  food  intake  
•  Labs:  
•  Depressed  TSH  level  
•  Elevated  FT4  
•  T3  toxicosis  –  only  FT3  is  elevated  
HYPERTHYROIDISM  IN  PREGNANCY  
 Grave’s  Disease  
•  Most  common  cause  of  thyrotoxicosis  in  
pregnancy  
•  autoimmune  process  associated  with  
thyroid-­‐s<mula<ng  TSH-­‐receptor  an<bodies    
 Treatment  of  Thyrotoxicosis  in  
Pregnancy  
•  Propylthiouracil  (PTU)  is  preferred  because  it  
par<ally  inhibits  the  conversion  of  T4  to  T3  
and  crosses  the  placenta  less  readily  than  
methimazole.    
 
 
 Side  effects  of  an<thyroid  drugs  
•  Hepatotoxicity  
•  Transient  leukopenia  
•  Agranulocytosis  
•  Development  of  an<neutrophil  cytoplasmic  
an<bodies  (ANCA)  
•  Methimazole  embryopathy    
•  characterized  by  esophageal  or  choanal  atresia  
as  well  as  aplasia  cu<s  
 Treatment  of  Thyrotoxicosis  in  
Pregnancy  
•  PTU:  a  dose  of  50  to  150  mg  orally  three  <mes  
daily  may  be  ini<ated  depending  on  clinical  
severity    
•  Methimazole  be  used  at  an  ini<al  higher  daily  
dose  of  10  to  20  mg  orally  followed  by  a  lower  
maintenance  dose  of  5  to  10  mg.    
•  Serum  free  T4  concentra<ons  are  measured  
every  4  to  6  weeks    
 Treatment  of  Thyrotoxicosis  in  
Pregnancy  
•  Subtotal  thyroidectomy    
§  can  be  performed  a^er  thyrotoxicosis  is  medically  
controlled,  preferably  in  the  2nd  trimester  
§  appropriate  for  the  very  few  women  who  cannot  
adhere  to  medical  treatment  or  in  whom  drug  
therapy  proves  toxic    
§  Drawback:  inadvertent  resec<on  of  parathyroid  
glands  and  injury  to  the  recurrent  laryngeal  nerve    
 Treatment  of  Thyrotoxicosis  in  
Pregnancy  
•  Thyroid  abla<on  with  therapeu<c  radioac<ve  
iodine  is  contraindicated  during  pregnancy  
§   may  also  cause  fetal  thyroid  gland  destruc<on    
 Pregnancy  Outcome  
•  In  untreated  women  or  in  those  who  remain  
hyperthyroid  despite  therapy,  there  is  a  higher  
incidence  of  preeclampsia,  heart  failure,  and  
adverse  perinatal  outcomes    
 Fetal  and  Neonatal  Effects  
•  In  most  cases,  the  perinate  is  euthyroid.    
•  In  some,  however,  hyper-­‐  or  hypothyroidism  
can  develop  with  or  without  a  goiter    
 Fetal  and  Neonatal  Effects  
4  possible  presenta<ons  of  a  neonate  exposed  
to  excessive  maternal  thyroxine:  
 
•  Goitrous  thyrotoxicosis  
•  Goitrous  hypothyroidism  
•  Non-­‐goitrous  hypothyroidism  
•  Fetal  thyrotoxicosis  
 Goitrous  Thyrotoxicosis  
•  caused  by  placental  transfer  of  thyroid-­‐  
s<mula<ng  immunoglobulins  
•  best  predictor  of  perinatal  thyrotoxicosis  is  
the  presence  of  thyroid-­‐sGmulaGng  TSH-­‐
receptor  anGbodies  in  women  with  Graves  
disease  (>3-­‐fold  higher)  
•  nonimmune  hydrops  and  fetal  demise  may  
occur  
 Goitrous  Hypothyroidism  
•  caused  by  fetal  exposure  to  maternally  
administered  thionamides    
•  if  hypothyroidism  is  iden<fied,  the  fetus  can  
be  treated  by  a  reduced  maternal  an<thyroid  
medica<on  dose  and  injec<on  of  
intraamnionic  thyroxine  if  necessary  
 Non-­‐goitrous  Hypothyroidism  
•  develops  from  transplacental  passage  of  
maternal  TSH-­‐receptor  blocking  an<bodies    

Fetal  Thyrotoxicosis  
•  occurs  a^er  maternal  thyroid  gland  abla<on  with  
RAI  
•  may  result  from  transplacental  thyroid-­‐
s<mula<ng  an<bodies  
 Thyroid  Storm  and  Heart  Failure  
•  acute  and  life-­‐threatening  
•  Thyroid  storm  is  a  hypermetabolic  state  and  is  
rare  in  pregnancy.    
•  In  contrast,  pulmonary  hypertension  and  
heart  failure  from  cardiomyopathy  caused  by  
the  profound  myocardial  effects  of  thyroxine,  
is  common  in  pregnant  women    
 Thyroid  Storm  and  Heart  Failure  
•  clinical  manifesta<ons:  unexplained  fever,  
tachycardia,  neurologic  changes,  arrhythmias,  
heart  failure  
Management  of  thyroid  storm  or  
thyrotoxic  heart  failure  

Iodide  inhibits  thyroidal  

release  of  T3  and  T4  

Dexamethasone  blocks  
peripheral  conversion  
of  T4  to  T3  
 Gesta<onal  transient  thyrotoxicosis  
•  results  from  TSH-­‐receptor  s<mula<on  from  
massive—but  normal  for  pregnancy  -­‐
concentra<ons  of  hCG    
•  Results  to  hyperemesis  gravidarum  
 Thyrotoxicosis  and  Gesta<onal  
Trophoblas<c  Disease  
•  abnormally  high  hCG  levels  lead  to  
overs<mula<on  of  the  TSH  receptor    
•  the  prevalence  of  increased  thyroxine  levels  in  
women  with  molar  pregnancy  is  around  
25-­‐65%  
•  with  defini<ve  treatment,  serum  FT4  levels  
usually  normalize  rapidly  in  parallel  with  the  
decline  in  hCG  concentra<ons    
 Subclinical  Hyperthyroidism  
•  characterized  by  an  abnormally  low  serum  TSH  
concentra<on  in  concert  with  thyroxine  hormone  
levels  within  the  normal  reference  range    
•  treatment  is  unwarranted  in  pregnancy  although  
women  may  benefit  from  periodic  surveillance  
•  Long-­‐term  effects:  
§  osteoporosis,  cardiovascular  morbidity,  progression  to  
overt  thyrotoxicosis  or  thyroid  failure  
HYPOTHYROIDISM  IN  PREGNANCY  
 Hypothyroidism  
•  Clinical:  fa<gue,  cons<pa<on,  cold  
intolerance,  muscle  cramps,  weight  gain,  
edema,  dry  skin,  hair  loss,  and  prolonged  
relaxa<on  phase  of  deep  tendon  reflexes    

§  a  pathologically-­‐enlarged  thyroid  gland  is  seen  in  

women  in  areas  of  endemic  iodine  deficiency  or  
those  with  Hashimoto  thyroidiGs  
 Hypothyroidism  
•  Clinical  or  overt  hypothyroidism  is  confirmed  
when  an  abnormally  high  serum  TSH  level  is  
accompanied  by  an  abnormally  low  thyroxine  
level  
•  Subclinical  hypothyroidism  is  defined  by  an  
elevated  serum  TSH  level  and  normal  serum  
thyroxine  concentra<on    
 Overt  Hypothyroidism  and  Pregnancy  
•  The  most  common  cause  of  hypothyroidism  in  
pregnancy  is  Hashimoto  thyroidiGs  
§  characterized  by  glandular  destruc<on  from  
autoan<bodies,  par<cularly  an<thyroid  
peroxidase  an<bodies  
 Treatment  
•  Levothyroxine,  1  to  2  μg/kg/day  
(approximately  100  μg  daily)  
•  surveillance  is  with  TSH  levels  measured  at  4-­‐  
to  6-­‐week  intervals,  and  the  thyroxine  dose  is  
adjusted  by  25-­‐  to  50-­‐μg  increments  un<l  TSH  
values  become  normal  
Pregnancy  Outcome  
 Subclinical  Hypothyroidism  and  
Pregnancy  
•  Lab:  elevated  TSH,  normal  FT4  
•  associated  with  increased  risk  of  severe  
preeclampsia,  GDM,  s<llbirth  
§  currently  no  evidence  that  iden<fica<on  and  
treatment  of  subclinical  hypothyroidism  during  
pregnancy  improves  these  outcomes    
 TSH  level  screening  in  pregnancy  
•  not  rou<nely  done  
•  screening  during  pregnancy  is  recommended  
only  on  those  who  are  at  increased  risk  
Normal  range  for  TSH  per  trimester  

Trimester   TSH  
1st     0.1–2.5  mIU/L  
2nd     0.2–3.0  mIU/L  
3rd     0.3–3.0  mIU/L  

Non-­‐pregnant   0.5–4.5  mIU/L  

Stagnaro-Green, et al. Guidelines of the American Thyroid Association for the Diagnosis and Management of Thyroid
Disease During Pregnancy and Postpartum. The American Thyroid Association Taskforce on Thyroid Disease During
Pregnancy and Postpartum. THYROID. 21:10. 2011
 Iodine  deficiency  
•  Dietary  iodine  requirements  are  increased  
during  pregnancy  due  to  increased  thyroid  
hormone  produc<on,  increased  renal  losses,  
and  fetal  iodine  requirements.    
•  Adequate  iodine  is  requisite  for  fetal  
neurological  development    
 Iodine  deficiency  
•  MILD  
§  causes  intellectual  impairment  although  
supplementa<on  does  prevent  fetal  goiter  
•  MODERATE  
§  has  intermediate  and  variable  effects  
•  SEVERE  
§  associated  with  endemic  cre<nism  
 Iodine  deficiency  
•  recommended  daily  iodine  intake  during  
pregnancy  is  220  μg/day,  and  290  μg/day  for  
lacta<ng  women  (Ins<tute  of  Medicine)  
•  250  μg  during  pregnancy  and  breast  feeding  
(Endocrine  Society)  
POSTPARTUM  THYROIDITIS  
 Postpartum  Thyroidi<s  
•  Transient  autoimmune  thyroidi<s  is  consistently  
found  in  approximately  5-­‐10%  of  women  during  
the  first  year  a^er  childbirth  
•  Postpartum  thyroid  dysfunc<on  with  an  onset  
within  12  months  includes  hyperthyroidism,  
hypothyroidism,  or  both  
•  directly  related  to  increasing  serum  levels  of  
thyroid  autoan<bodies  
§  46%  of  those  iden<fied  with  overt  postpartum  
thyroidi<s  had  TPO  an<bodies  (TPOAbs)  in  the  first  
trimester  
 Postpartum  Thyroidi<s  
§  2  phases:  
1.  destruc<on-­‐induced  thyrotoxicosis  with  
symptoms  from  excessive  release  of  
hormone  from  glandular  disrup<on    
§ onset  is  abrupt,  and  a  small,  painless  goiter  is  
commonly  found;  fa<gue,  palpita<ons  are  
present  
§ Thionamides  are  ineffec<ve,  and  if  symptoms  
are  severe,  a  β-­‐blocker  agent  may  be  given    
 Postpartum  Thyroidi<s  
§  2  phases:  
2.  clinical  hypothyroidism  from  thyroidi<s  
§ occurs  between  4  and  8  months  postpartum  
§ Thyromegaly  and  other  symptoms  are  common  
and  more  prominent    
§ Thyroxine  replacement  with  25  to  75  μg/day  is  
typically  given  for  6  to  12  months.    
 Postpartum  Thyroidi<s  
§  women  with  history  of  postpartum  thyroidi<s  should  
be  monitored  annually  for  hypothyroidism  and  
treated  accordingly  
NODULAR  THYROID  DISEASE  
 Nodular  thyroid  disease  
•  Management  of  a  palpable  thyroid  nodule  
during  pregnancy  depends  on  gesta<onal  age  
and  mass  size  
•  Evalua<on  of  thyroid  nodules  during  
pregnancy  should  be  similar  to  that  for  non-­‐
pregnant  pa<ents  
 Nodular  thyroid  disease  
•  Sonographic  examina<on  reliably  detects  
nodules  larger  than  0.5  cm,  and  their  solid  or  
cys<c  structure  also  is  determined  
§  sonographic  characteris<cs  associated  with  
malignancy  include  hypoechogenic  pamern,  
irregular  margins,  and  microcalcifica<ons    
§  Fine-­‐needle  aspira<on  (FNA)  is  an  excellent  
assessment  method,  and  histological  tumor  
markers  and  immunostaining  are  reliable  to  
evaluate  for  malignancy    
 Thyroid  CA  in  pregnancy  
•  When  thyroid  malignancy  is  diagnosed  during  
the  first  or  second  trimester,  thyroidectomy  
may  be  performed  before  the  third  trimester    
•  In  women  without  evidence  of  an  aggressive  
thyroid  cancer,  or  in  those  diagnosed  in  the  
third  trimester,  surgical  treatment  can  be  
deferred  to  the  immediate  postpartum  period