4/7/06njm

**Q. Is my first trimester patient always hyperthyroid if her labs are
abnormal?**

A. No, not necessarily. If she is clinically stable, then wait till
18-20 weeks to decide. See details

**More about the question**

A patient presents in the first trimester with hyperemesis. One of your
colleagues obtains a complete thyroid function panel. The thyroid
stimulating hormone (TSH) is significantly decreased. The patient
follows up with you and wants to know how soon she should start her
hyperthyroid medication.

**Quick answer**

If clinically stable, then wait till 18-20 weeks to decide if the
patient is truly hyperthyroid

Now, let's explore this issue a little more closely.

**Here is a common scenario from the Perinatology Corner\*:**

S. N. is a 27 y/o G5P3 at 10 weeks gestation who is complaining of
severe nausea and vomiting. Her physical exam is unremarkable. She has a
viable intrauterine pregnancy on ultrasound. Her lab work reveals the
following:\
TSH: 0.01 mIU/mL (nl: 0.46-4.68)\
Free T4: 2.01 ng/dL (nl: 0.78-2.19)\
ALT/AST: within normal limits\
Electrolytes: normal except K+=3.1 mEq/L\
\
Your BEST plan of action at this point is:

Ms Nooktak most likely has hyperemesis gravidarum. She has a markedly
suppressed TSH and a high normal free T4. Because high hCG levels are
associated with hyperemesis, and because hCG may inhibit TRH, TSH levels
often may become undetectable, suggesting the diagnosis of
hyperthyroidism. Nevertheless, unlike women with true Graves' disease,
our patient has no clinical signs of hyperthyroidism. The best plan for
her would be to treat her symptomatically and repeat her thyroid
functions in the second trimester. It would be inappropriate at this
point to diagnose her with Graves' disease and begin thionamide therapy
that might result in maternal or fetal hypothyroidism.

**\*Perinatologist Corner module: Thyroid Disease in Pregnancy**

<http://www.ihs.gov/MedicalPrograms/MCH/M/Thyr01.cfm>

**Let's review the reasons why:**

**Signs of hyperthyroidism**

If you have read the Perinatologist Corner on Nausea and Vomiting in
Pregnancy\*\*, you will recall that these women, who typically have high
human chorionic gonadotrophin (HCG) levels, will frequently have an
assay for TSH that often returns very low, suggesting hyperthyroidism.
  This may occur in up to 20% of pregnant women in whom the newer third
generation, ultrasensitive TSH assays are obtained. These women may even
have a mildly elevated free T4, but they will be clinically euthyroid,
without tremor, tachycardia, hyperreflexia, or the other signs of
hyperthyroidism.

Both these biochemical abnormalities will resolve by 18 weeks and
anti-thyroid medications should not be started. (They will not help the
nausea and vomiting either!) They may cause the fetus, who is totally
dependent on its mother's thyroxine until its own gland becomes
functional at about 18 weeks, to become hypothyroid, with the
accompanying later intellectual deficits. 

Features that distinguish the transient hyperthyroidism of hyperemesis
gravidarum from hyperthyroidism of other causes (which in a pregnant
woman is most likely to be due to Graves\' disease) are the vomiting,
absence of goiter and ophthalmopathy, and absence of the common symptoms
and signs of hyperthyroidism (heat intolerance, muscle weakness,
tremor). In addition, serum free T4 concentrations are only minimally
elevated and serum T3 concentrations are not elevated in women with
hyperemesis gravidarum, whereas both are usually unequivocally elevated
in pregnant women with true hyperthyroidism. Treatment of
hyperthyroidism should not be undertaken without clear evidence of a
primary thyroid disorder (eg, goiter, elevated free thyroid hormone or
elevated TSH receptor antibody levels).

**\* \* Perinatologist Corner module: Nausea and Vomiting** **in
Pregnancy**

<http://www.ihs.gov/MedicalPrograms/MCH/M/NVP06.cfm>

**Resources**

**Thyroid-stimulating hormone decreases significantly during the first
trimester**

OBJECTIVE: To estimate a normal reference range for thyroid-stimulating
hormone (TSH) at each point in gestation in singleton and twin
pregnancies.

METHODS: All women enrolling for prenatal care from December 2000
through November 2001 underwent prospective TSH screening at their first
visit. Separate nomograms were constructed for singleton and twin
pregnancies using regression analysis. Values were converted to
multiples of the median (MoM) for singleton pregnancies at each week of
gestation.

RESULTS: Thyroid-stimulating hormone was evaluated in 13,599 singleton
and 132 twin pregnancies. Thyroid-stimulating hormone decreased
significantly during the first trimester, and the decrease was greater
in twins (both *P* \< .001). Had a nonpregnant reference (0.4--4.0 mU/L)
been used rather than our nomogram, 28% of 342 singletons with TSH
greater than 2 standard deviations above the mean would not have been
identified. For singleton first-trimester pregnancies, the approximate
upper limit of normal TSH was 4.0 MoM, and for twins, 3.5 MoM.
Thereafter, the approximate upper limit was 2.5 MoM for singleton and
twin pregnancies.

CONCLUSION: If thyroid testing is performed during pregnancy, nomograms
that adjust for fetal number and gestational age may greatly improve
disease detection. Values expressed as multiples of the median may
facilitate comparisons across different laboratories and populations.

LEVEL OF EVIDENCE: II-2

Dashe JS et al Thyroid-Stimulating Hormone in Singleton and Twin
Pregnancy: Importance of Gestational Age--Specific Reference Ranges.
Obstetrics & Gynecology 2005;106:753-757

<http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=retrieve&db=pubmed&list_uids=16199632&dopt=Abstract>

#### OB/GYN CCC Editorial comment: 

This article above presents more evidence that we must remember that
thyroid-stimulating hormone decreases significantly early in pregnancy .
This is clinically significant because many patients have their TSH
level checked for various clinical indications during the first
trimester and early second trimester, e.g., hyperemesis gravidarum.
Though the TSH is physiologically decreased some clinicians assume the
decreased TSH is related to true hyperthyroidism and the patient is
begun on antithyroid agents.

If the patient is not clinically hyperthyroid, then a better approach is
not to consider treatment based on TSH levels until after 20 weeks
gestation.

See pseudohyperthyroidism below.

**Pearl:**

The best way to screen / evaluate a pregnant woman for thyroid disease
is to look at the free T4. The free T4 tells you directly what amount of
thyroid hormone she and the fetus are seeing. If it\'s normal, and you
still suspect hyperthyroidism, then get a free T3. In the woman with
known hypothyroidism, the free T4 may still be low normal, but a then a
high TSH may clue you that you need more L-thyroxine replacement.

The Indian Health system continuing education module(s) (free CEU / CME)
on this topic offers many more details and resources.

**Thyroid Disorders in Pregnancy Module**

<http://www.ihs.gov/MedicalPrograms/MCH/M/THYR01.cfm>

**Hyperemesis Gravidarum \"Pseudohyperthyroidism\" page**

<http://www.ihs.gov/MedicalPrograms/MCH/M/THYR05.cfm#top>

Lastly, if the patient in fact has hyperthyroidism clinically, or if her
labs have not normalized by 18-20 weeks, then there are several
treatment options. See UpToDate

**Diagnosis and treatment of hyperthyroidism during pregnancy,
UpToDate**

<http://www.uptodateonline.com/utd/content/topic.do?topicKey=thyroid/7568&type=A&selectedTitle=11~135>

**Other Resources**

**Thyroid-stimulating hormone decreases significantly during the first
trimester**

<http://www.ihs.gov/MedicalPrograms/MCH/M/obgyn1005_Feat.cfm>

(scroll down to Perinatology Picks section)

**Other Perinatology Corner Modules**

<http://www.ihs.gov/MedicalPrograms/MCH/M/perCrnr.cfm>