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NBME 21 Answers

nbme21/Block 2/Question#14

A 30-year-old woman comes to the office because she ...

Abnormal brain development

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 +11  upvote downvote
submitted by taway(16),

This question is phrased strangely, but it's essentially asking "what would happen if this woman's hypothyroidism became uncontrolled over the course of her pregnancy?"

currently her TSH is good --> well-controlled hypothryoidism HYPOTHETICAL high TSH --> her hypothyroidism must NOT be well-controlled (due to disruption of the T3/T4/TRH/TSH endocrine axis)

So, now that we understand that the question is asking "what would happen if her hypothyroidism was uncontrolled?"

Answer: cretinism

I think that this question is phrased atrociously, but far be it from me to criticize the USMLE licensing board...

yotsubato  I think that this question is phrased atrociously, Just like the rest of the NBME +3  
b1ackcoffee  exactly how does maternal hashimoto can cause cretinism? +  

 +7  upvote downvote
submitted by direwolf(7),

This has to do with understanding two things, that maternal hypothyroidism is linked to Cretinism/neural development of the fetus, and normal pregnancy physiology. In pregnancy, increased hormones stimulate liver production of various proteins like Sex Hormone Binding Globulin (SHBG),Thyroxine Binding Globulin (TBG), etc. More TBG produced = more T3/T4 is bound. Less T3/T4 causes more TRH release, more TSH release, and more T3/T4 production until free T3/T4 levels are back to normal. In a normal pregnancy, this happens no problem. In someone with pre-existing hypothyroidism though, already has impaired T3/T4 production, and won't be able to keep up with increased demand. Their T3 will rise, but this won't result in increased T3/T4. Typically, women with Hashimoto's desiring to get pregnant will need to increase their levothyroxine dose in anticipation of this pregnancy change.

Autoimmune thyroiditis (aka Hashimoto) + pregnant--> Think about possibility of fetal hypothyroidism due to antibody mediated maternal hypothyroidism. Leads to Cretinism. Findings in infant are the 6'P (Pot belly, Pale, Puffy face, Protruding umbilicus, Protuberant tongue, and Poor Brain development.

neonem  I don't understand the last part of this question stem though... if the mother's TSH *increases* during pregnancy? Wouldn't this further increase her (and/or the fetus's) production of T4 and thus counteract the hypothyroidism? +  
poojaym  @neonem no. Autoimmune hypothyroidism is a destruction of the thyroid gland, and a decrease in production of T3/T4. An increase in TSH means that there is not enough T3/T4 to inhibit TRH, and so TSH is being released to stimulate the thyroid gland. +6  
arezpr  TSH, T3, T4 and thyroglobulin cannot cross the placental barrier. +  
chamaleo  @arezpr although those hormones can't cross, the autoantibodies from Hashimoto's can +  
yotsubato  The baby has its own TSH though +  
sbryant6  TSH comes from the pituitary, and act on the thyroid. Autoantibodies attack the thyroid, so TSH doesn't work. +  
kimcharito  no goiter then? +  

 +3  upvote downvote
submitted by thotaak(4),

Normally maternal T3/4 are required for fetal brain development before fetal thyroid gland is formed. And after fetal thyroid gland is formed, fetal T3/4 helps in brain development. So increase TSH means decreased maternal T3/4 and thus have abn brain development. And yes T3/4 crosses placenta.

thotaak  According to Robbins pathology +1  

I think this gets at a concept related to thyroid levels and pregnancy/estrogen.

Estrogen increases the level of thyroxine-binding globulin, which temporarily decreases free T4 and T3, and increases TSH until the additional TBG becomes saturated, and normal levels are restored.

Since this patient has autoimmune thyroiditis, and requires thyroxine, when her free T4 decreases, and her TSH goes up, she wont make extra T4. So unless she increases her thyroxine dose, she will be hypothyroid --> cretinism in the fetus

exactly how does maternal hashimoto can cause cretinism?

 +0  upvote downvote
submitted by seagull(724),


This article fails to mention poor brain development in HYPERthyroidism. The author must have meant HYPOthyroidism.

This question upsets me to no end.

aesalmon  I agree, the article you linked states "signs of fetal hyperthyroidism such as tachycardia, intrauterine growth retardation, cardiac failure, and the development of fetal goitre" I chose answer E during the exam - "Thyroid gland enlargement" Still trying to understand how they linked cretinism to a case where the mother's hypothyroidism was well controlled, and then asked for the sequelae if her TSH increased. Maybe increased TSH is supposed to indicate worsening hypothyroid - low T3/T4 needing to be stimulated by TSH? +  

My thought process was if the mother has increased TSH, she'd be using more iodine to produce T3/4. Meaning less would be able to get to the baby for brain development.

The mother has autoimmune thyroiditis and treatment is given for hypothyroidism only. why does it matter if the mother's TSH is high or low? Autoantibodies would still be present and they would always cause cretinism irrespective of mother hormones level. Isn't it?

 +0  upvote downvote
submitted by hayayah(603),

Cretinism (congenital hypothyroidism) is the most common cause of treatable mental disability. Causes poor brain development.