THE INFORMATION IN THE OBPHARMTM
IS INTENDED SOLELY FOR USE BY THE MEDICAL PROFESSION. IT IS NOT INTENDED FOR LAY PERSONS.
When maternal thyroid stimulating hormone (TSH) is elevated, measurement of serum
free thyroxine (FT4)
concentration is necessary to classify the patient's status as either subclinical (SCH) or overt hypothyroidism (OH). SCH is defined as a serum TSH
between 2.5 and 10 mIU/L with a normal FT4 concentration[6]
Isloated hypothyroxinemia
- The American
Thyroid Association recommends isolated hypothyroxinemia
should not be treated
in pregnancy [6,9]
Subclinical Hypothyroidism (SCH)
- Women
with SCH who are thyroid peroxidase antibody positive (TPO-Ab+) should
be treated with levothyroxine
[6,7]
- Women
with SCH who are thyroid peroxidase antibody negative (TPO-Ab-)
- The American
Thyroid Association recommends :
There is
insufficient evidence to recommend
for or against universal LT4 treatment
[6]
- The Endocrine
Society recommends treatment with
levothyroxine . Starting dose 50 mcg or more if serum TSH is
between 2.5 and 10 mIU/L [7].
Overt
Hypothyroidism (OH)
Women with a TSH
concentration above the trimester-specific reference interval with a decreased
FT4, and all women with a TSH concentration above 10.0 mIU/L irrespective of the
level of FT4 are
considered to have OH. [6]
- Women who are
euthyroid on levothyroxine should increase their LT4 dose by 25 to 30%
immediately after a missed period or positive pregnancy test [6]
- The goal of LT4
treatment is to normalize maternal serum TSH values within the
trimester-specific pregnancy reference range [6]
- Monitor the TSH every
4 weeks during first half of pregnancy
-
Following delivery, LT4 should be reduced to the
patient's preconception dose.
Thyroid Medications
Levothyroxine sodium (Levoxyl ®
, Synthroid®)
Synthetic levothyroxine T4 ,LT4
- Replacement or supplemental therapy in the treatment of
hypothyroidism except the treatment of transient hypothyroidism in the
recovery phase of subacute thyroiditis.
For Nonpregnant Healthy Women
1.7 mcg/kg/day
PO once daily.
Clinical and laboratory evaluations should be performed at 6 to 8 week
intervals (2 to 3 weeks in severely hypothyroid patients), and the dosage
adjusted by 12.5 to 25 mcg increments until the serum TSH concentration is normalized and signs and symptoms resolve.
For Pregnant Healthy Women Some Authorities Recommend an Initial Dose [2-4]
150 mcg PO once per day OR day or 2 mcg/kg per day.
Clinical and laboratory evaluations should be performed at 4 week intervals
until the TSH is stable. The dosage adjustment according to
the following algorithm has been suggested:
| For TSH (mU/ml) |
Increase levothryoxine dosage
by |
| 4 to 10 |
41 +/- 24 mcg / day |
| greater than 10 but less
than or equal to 20 |
65 +/- 19
mcg / day
|
| greater than 20 |
105 +/- 32
mcg /day
|
For Nonpregnant or Pregnant Women with a history of cardiovascular disease
12.5 to 50 mcg once daily
Adjustments of 12.5 to 25 mcg every 3 to 6 weeks until TSH is
normalized.
-
Myxedema coma:
300- 500 micrograms IV once.
The initial dose is followed by daily intravenous doses of 75 to 100 mcg until
the patient is stable and oral administration is feasible. Normal T4
levels are usually achieved in 24 hours.
- Pituitary TSH suppression in the treatment or prevention of various types of
euthyroid goiters including thyroid nodules, subacute or chronic lymphocytic thyroiditis (Hashimoto's thyroiditis), multinodular goiter and, as an adjunct to surgery and
radioiodine therapy in the management of thyrotropin-dependent well-differentiated
thyroid cancer.
As an adjunct to surgery and
radioiodine therapy in the treatment of well differentiated (papillary and
follicular) thyroid cancer.
Levothyroxine sodium dose of greater than 2 mcg/kg/day. Generally, TSH is suppressed to <0.1 mU/L. However, in patients with high-risk tumors, the target level for TSH
suppression may be <0.01 mU/L.
In the treatment of benign nodules and
nontoxic multinodular goiter.
" TSH is generally suppressed to a higher target
(e.g., 0.1—0.5 mU/L for nodules and 0.5—1.0 mU/L for multinodular goiter) than
that used for the treatment of thyroid cancer. Levothyroxine sodium is
contraindicated if the serum TSH is already suppressed due to the risk of
precipitating overt thyrotoxicosis "
Contraindicated in uncorrected adrenal insufficiency, untreated subclinical or
overt thyrotoxicosis, and acute MI.
Levoxyl ® is supplied as:
(0.025, 0.05, 0.075, 0.088, 0.1, 0.112, 0.125,
0.137, 0.15, 0.175, 0.2, and 0.3 mg tablets ).
Synthroid®
is supplied as:
(0.025, 0.05, 0.075,
0.088, 0.1, 0.112, 0.125, 0.137, 0.15, 0.175, 0.2, and 0.3 mg tablets Powder for
intravenous injection: 6 and 10 ml vials containing 0.2 mg or 0.5mg of levothyroxine per vial.
The recommended treatment of maternal hypothyroidism is with administration of
oral levothyroxine It is strongly recommended not to use other thyroid
preparations such as T3 or
desiccated thyroid. [6, 7]
Approximate Equivalent Strengths of Various
Thyroid Preparations
| Drug → |
Thyroid
Tablets, USP
(Armour® Thyroid) |
Liotrix
Tablets, USP
(Thyrolar™) |
Liothronine Tablets, USP
(Cytomel®) |
Levothyroxine Tablets, USP
(Unithroid® , Levoxyl® , Levothroid® ,
Synthroid® ) |
| Approx. Dose Equivalent |
1/4 grain
(15 mg) |
1/4 |
|
25 mcg (.025 mg) |
| Approx. Dose Equivalent |
1/2 grain
(30 mg) |
1/2 |
12.5 mcg |
50 mcg (.05 mg) |
| Approx. Dose Equivalent |
1 grain
(60 mg) |
1 |
25 mcg |
100 mcg ( .1 mg) |
| Approx. Dose Equivalent |
1 1/2 grains (90 mg) |
1 1/2 |
37.5 mcg |
150 mcg (.15 mg) |
| Approx. Dose Equivalent |
2 grains
(120 mg) |
2 |
50 mcg |
200 mcg (.2 mg) |
| Approx. Dose Equivalent |
3grains
(180 mg) |
3 |
75 mcg |
300 mcg (.3 mg) |
United States Pharmacopoeia — Drug Information 2000, 20th Edition, Drug
Information for the Health Care Professional; Vol. 1, pp. 2980-2986. World
Color Book Services, Versailles, KY.
Hyperthyroidism
- When maternal TSH is less than 0.1mIU/L a FT4
should be obtained. Subclinical hyperthyroidism is defined as
low or undetectable serum TSH with normal free
thyroxine (FT4) . Overt
hyperthyroidism is defined as low or
undetectable serum TSH with elevated free thyroxine (FT4)
. TSH
receptor antibody (TRAb) and/or total T3 (TT3) levels may help to
clarify the cause of the hyperthyroidism if the patient has a
prior history of thyroid disease or has findings such as ophthalmopathy,
goiter, or
thyroid nodules on examination
Subclinical hyperthyroidism
- Treatment of
subclinical hyperthyroidism does not appear to improve pregnancy outcome but
may adversely affect the fetus [7]
Gestational (transient) hyperthyroidism
- Elevated hCG
may cause increased FT4 and suppressed or undetectable serum TSH . This occurs
commonly with hyperemesis gravidarum. FT4 typically returns to normal by 15 to
18 weeks .Treatment with antithyroid drugs (ATDs) is not indicated. [6]
Overt Hyperthyroidism
- The most common cause of hyperthyroidism is Graves disease.
- Untreated maternal thyrotoxicosis is associated with an increased risk of
intrauterine growth restriction, preeclampsia, congestive heart failure ,
thyroid storm , and
fetal death [7].
- For overt hyperthyroidism the goal of treatment is to maintain FT4 values at, or just above the upper limit of normal,
while utilizing the smallest possible dose of antithyroid drugs
[6,7].
-
Propylthiouracil (PTU) is preferred for pregnant women in the first trimester because methimazole
(MMI) may be associated an increased risk for congenital birth defects [10].
-
Because PTU may rarely be associated with severe
liver toxicity it is recommended that methimazole be used after the first trimester
[6, 7,10].
- 10
mg of MMI is approximately equivalent to 100–150 mg of PTU [6, 7]
Antithyroid drugs
Thyroid Storm
Order
set (needs to be updated)
Propylthiouracil (PTU)
Antithyroid drug. Suppresses thyroid hormone production by interfering with the organification of iodine. Inhibits peripheral conversion of thyroxine (T4) to triiodothyronine (T3).
The total daily dosage is usually given in 3 divided doses at approximately
8-hour intervals.
- Treatment of hyperthyroidism [5].
Starting dose is 50 to 100 mg orally every 8 hours. In patients
with severe hyperthyroidism, very large goiters, or both, the beginning
dosage usually should be 400 mg daily; an occasional patient will require 600
to 900 mg/daily initially. The usual maintenance dosage is 100 to 150 mg
daily
- Free T4 is tested every two weeks and the dosage is adjusted
to keep the FT4 in upper
third of normal range. Reduce the dosage by 1/2 after FT4
begins to improve. The TSH will
remain suppressed for weeks or months. Thyroid tests usually
normalize within 3 to 8
weeks.
Consider obtaining a baseline leukocyte count and prothrombin time.
Agranulocytosis is potentially the most serious adverse reaction.
Symptoms include fever, sore throat, and malaise. Other adverse reactions
include but are not limited to , aplastic anemia, metallic taste in mouth,
arthralgia, myalgia, nausea, hepatitis, jaundice, lupus-like syndrome,
vasculitis, hypothrombinemia, neuropathies,headache, vertigo, interstitial pneumonitis, insulin autoimmune syndrome (hypoglycemia).
Discontinue drug if agranulocytosis, aplastic anemia, hepatitis, fever,
or exfoliative dermatitis
occur.
(50 mg tablets)
May produce fetal goiter and hypothyroidism.
Breast feeding appears to be safe in mothers taking less than 300 mg of
PTU per day. PTU should be given after feeding in divided doses [6]
Methimazole (MMI) (Tapazole)
[6,12]
Antithyroid drug. Suppresses thyroid hormone production by interfering with the organification of iodine.
The total daily dosage is usually given in 3 divided doses at approximately
8-hour intervals.
- Treatment of hyperthyroidism .
The initial daily dosage is 5 to 15 mg for mild hyperthyroidism, 30 to 40 mg
for moderately severe hyperthyroidism, and 60 mg for severe hyperthyroidism,
divided into 3 doses at 8-hour intervals. The maintenance dosage is 5 to 15
mg day
- Free T4 is tested every two weeks and the dosage is adjusted to
keep the FT4 in upper
third of normal range. Reduce the dosage by 1/2 after FT4
begins to improve. The TSH will
remain suppressed for weeks or months. Thyroid tests usually
normalize within 3 to 8
weeks.
Consider obtaining baseline leukocyte count and prothrombin time.
Agranulocytosis is potentially the most serious adverse reaction.
Symptoms include fever, sore throat, and malaise. Other adverse reactions
include but are not limited to , aplastic anemia, metallic taste in mouth,
arthralgia, myalgia, nausea, hepatitis, jaundice, lupus-like syndrome,
vasculitis, hypothrombinemia, neuropathies,headache, vertigo, interstitial pneumonitis, insulin autoimmune syndrome (hypoglycemia).
Discontinue drug if agranulocytosis, aplastic anemia, hepatitis, fever,
or exfoliative dermatitis
occur.
May produce fetal goiter and hypothyroidism.
Breast feeding appears to be safe in mothers taking less than 30 mg of
MMI per day. MMI should be given after feeding in divided doses [6]
(5, 10 mg tablets).
Propranolol (Inderal®)
Beta blocker
- For the relief of the adrenergic symptoms of hyperthyroidism such as
tremor, palpitations, heat intolerance, and nervousness.
20 to 40 mg every 6 to 8 hours. Adjust dose to keep heart rate at 70 to 90 beats
per minute. Beta blockade can be tapered after the free T4 has returned to normal range (~ 3
weeks) [5].
Avoid abrupt cessation of drug. Contraindicated in asthma, AV block, and
overt heart failure.
(10, 20,40,60, 80 mg tablets)
REFERENCES
1.ACOG practice bulletin. Thyroid disease in pregnancy. Number 37, August
2002. American College of Obstetrics and Gynecology. Int J Gynaecol Obstet.
2002;79(2):171-80.
PMID: 12481755
2. Hollowell JG, Staehling NW, Flanders WD, et
al. Serum TSH, T(4), and thyroid antibodies in the United States
population (1988 to 1994): National Health and Nutrition Examination Survey (NHANES
III). J Clin Endocrinol Metab. 2002;87:489-499.PMID: 11836274
3. Montoro MN.Management of hypothyroidism during pregnancy.Clin
Obstet Gynecol. 1997;40(1):65-80. pp 77
PMID:9103950
4. Kaplan MM Monitoring thyroxine treatment during pregnancy.Thyroid. 1992 ;2(2):147-52.
PMID:1525583
5. Mestman JH. Hyperthyroidism in pregnancy.Clin
Obstet Gynecol. 1997 Mar;40(1):45-64.
PMID:9103949
6. Stagnaro-Green A, ert al. American Thyroid Association
Taskforce on Thyroid Disease During Pregnancy and Postpartum.Guidelines of
the American Thyroid Association for the diagnosis and management of thyroid
disease during pregnancy and postpartum. Thyroid. 2011
Oct;21(10):1081-125.PMID .21787128
7.De Groot L, et. al. Management of thyroid dysfunction during pregnancy and
postpartum: an Endocrine Society clinical practice guideline.. J Clin
Endocrinol Metab. 2012 Aug;97(8):2543-65. doi: 10.1210/jc.2011-2803. Review.
PMID: 22869843
8. Haddow JE, Palomaki GE,
Allan WC, et al. Maternal thyroid deficiency during pregnancy and subsequent
neuropsychological development of the child. N Engl J Med. 1999;341:549–555. [
9.. Lazarus JH, et. al., Antenatal thyroid screening and childhood cognitive
function.
N Engl J Med. 2012 Feb 9;366(6):493-501. doi: 10.1056/NEJMoa1106104. Erratum in:
N Engl J Med. 2012 Apr 26;366(17):1650. PMID: 22316443
10. Hackmon R, et al., The safety of methimazole and propylthiouracil in
pregnancy: a systematic review.
J Obstet Gynaecol Can. 2012 Nov;34(11):1077-86. PMID: 23231846
11
Propylthiouracil packae insert NCS HealthCare of KY, Inc dba Vangard Lab
http://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=c46c4f31-121c-43a8-9538-53ae1288812e
12. Tapazole package insert. Pfizer Laboratories Div Pfizer Inchttp://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=4280e008-bbaf-4cc7-b588-3b4303016067
13. Goodwin TM et al. Transient hyperthyroidism and hyperemesis gravidarum:
clinical aspects. Am J Obstet Gynecol. 1992 Sep;167(3):648-52. PMID: 138238914.
14. Tan JY, et. al., Transient hyperthyroidism of hyperemesis gravidarum. BJOG.
2002 Jun;109(6):683-8. PMID: 1211864
For corrections or comments please contact
Mark Curran, M.D., F.A.C.O.G. : hawk112_1@hotmail.com |
