Published by : PROFESSIONAL MEDICAL PUBLICATIONS
January - March 2009
When Antithyroid Drugs must be started in
patients with Hyperemesis Gravidarum?
Najafipour Farzad1, Aliasgarzadeh Akbar2,
Aghamohammadzadeh Naser3, Mobasseri Majid4
Objective: To find out role of anti-thyroid drugs in patients with Hyperemesis gravidarum and thyroid dysfunction.
Methodology: One hundred thirty five patients with hyperemesis gravidarum who were admitted to obstetric and gynecology hospital were enrolled in this study. Thirty two patients were excluded because of diabetes mellitus and thyroid diseases. Hence, one hundred three patients underwent investigations including thyroid function test and ▀-hCG (Human chorionic gonadotropin).
Results: Thirty five women were found with abnormal thyroid function test with FT4I (Free Thyroxin Index) 4.74▒0.54 and in another group (68 women) was 2.9▒0.39 (P<0.0001). B-hCG in first group was 59406▒14899 miu/ml and in second group was 6750▒3476 miu/mL (P<0.0001). In five patients PTU (propylthiouracil) was started due to severe sign and symptoms of hyperthyroidism. Thyroid function test was rechecked for all of 35 patients after four weeks routine therapy for hyperemesis gravidarum. Thyroid function test was normalized in 11 patients with hyperemesis graridarum but remained abnormal in 22 patients.
Conclusion: In our study thyroid dysfunction in hyperemesis gravidarum was 35% and, 20% of patients needed anti-thyroid therapy. Routine assessment of thyroid function is necessary for women with hyperemesis gravidarum especially in patients with clinical features of hyperthyroidism. We must consider PTU (propylthouracil) in hyperemesis gravidarum with severe weight loss, vomiting and biochemical hyperthyroidism.
KEY WORDS: Hyperemesis Gravidarum, Thyroid Function Test, Hyperthyroidism.
Pak J Med Sci January - March 2009 Vol. 25 No. 1 61-64
How to cite this article:
Farzad N, Akbar A, Naser A, Majid M. When Antithyroid Drugs must be started in patients with Hyperemesis Gravidarum?. Pak J Med Sci 2009;25(1):61-64.
1. Najafipour Farzad,
2. Aliasgarzadeh Akbar,
3. Aghamohammadzadeh Naser,
4. Mobasri Majid,
1-4: Department of Endocrinology and Metabolisem,
Emam Reza Hospital,
Tabriz University of Medical Sciences,
Dr. Najafipour Farzad,
* Received for Publication: May 13, 2008
* Revision Received: November 28, 2008
* Revision Accepted: December 5, 2008
Hyperemesis gravidarum is marked by profound vomiting during early gestation, which may result in electrolyte imbalance and dehydration. High serum free T4 (Thyroxin) and T3 (Tri-iodothyronin) concentrations are a common finding in women with hyperemesis gravidarum, having been reported in 25% to 75% of patients in various series.1 Women with hyperemesis and high serum free T4 and T3 concentrations have higher serum hCG (Human chorionic gonadotropin) concentrations than normal pregnant women.1 Their serum hCG concentrations correlate with the degree of elevation of serum free T4 and T3 concentrations and with serum thyroid-stimulating activity, as measured by bioassay. Vomiting is also more severe in women who have higher serum hCG concentrations, suggesting that another factor induced by hCG, perhaps estradiol, may be responsible for the vomiting.2,3 The hyperthyroxinemia is usually transient, resolving by 18 weeks gestation without antithyroid therapy.4 The degree of thyroid stimulation varies with the hCG concentration and correlates with the symptoms of hyperemesis.3,5 Antithyroid therapy should be considered for women with persistent hyperemesis and hyperthyroxinemia past 20 weeks gestation.6
One hundred thirty five women were admitted with hyperemesis gravidarum and 32 patients were excluded due to other illness such as diabetes mellitus and thyroid disease or patients who had history of specific drugs such as antithyroid drugs or levothyroxine. Each woman was examined for clinical signs of thyroid disease and underwent investigations including electrolytes, liver enzyme test, ▀-hCG, urine ketone and thyroid function test.
The severity of the hyperemesis gravidarum was evaluated by the degree of ketonuria and weight loss. An ultrasound to confirm the gestational age and multiple gestation and to exclude a trophoblastic disease was carried out. In patients with abnormal thyroid function test (biochemical hyperthyroidism) AntiľTPO (Thyroid Peroxidase) was measured. In patient with severe sign and symptoms of hyperthyroidism, PTU (propylthiouracil) was started and thyroid function test was repeated four weeks later. SPSS softwere version 11 was used for statistical analysis and t-test was performed for comparisons between groups. Values of P<0.05 were considered statistically significant, and all data are presented as mean▒SD.
Baseline characteristics of 103 patients whit hyperemesis gravidarum are shown in Table-I. Mean age of pregnancy at the admission was 15.34▒2.61 weeks and age of starting vomiting was 7.42▒2.14 weeks of gestation.
Twenty eight patients (27%) had positive family history of hyperemisis gravidarum in first degree relative families. Forty patients had gravida two or more and 25 (62.5%) of them had history of hyperemisis gravidarum in previous pregnancy. Thirty five patients (34%) had biochemical hyperthyrodism (suppressed thyroid stimulathing hormone and incressed FT4I). Sixty eight patients (66 %) had normal thyroid test. Camparison of two groups are show in Table-II.
Propylthiouracil was started in five patients at time of diagnosis because of severe biochemical and clinical signs and symptomes of hyperthyroidism. Mean dose of PTU was 170▒55 mg/d. Thyroid function test was repeated after one month. Thyroid function tests normalized in 11 patients (31.42%) and two patients were lost to follow up while 22 patients (68.85%) still had abnormal thyroid function test. They were put on propylthiouracil therapy with mean dose of 60 mg/d and followed with thyroid frnction tests mounthly. Anti TPO was measured in 22 patients with abnormal thyroid function tests and it was found positive in three of them.
Hyperemesis gravidarum is characterized by nausea and vomiting, which in severe cases may lead to dehydration and require hospitalization.4 Mild hyperthyroidism may be associated with hyperemesis gravidarum, perhaps due to higher serum concentrations of human chorionic gonadotropin which may have more thyroid stimulating activity.7
In several studies thyroids dysfunction is reported from 25% to 75%.6 In our study thyroid dysfunction was 34% in hyperemesis gravidarum. Most of patients had greater than 5% weight loss (4.88▒1.1 kg) especially in patient with thyroid dysfunction (Table-II). Score of nausea and vomiting with Rhodes index8 criteria was higher in patients with thyroid dysfunction (P<0.0001). Hyperthyroid patients were more likely than euthyroid patients to have abnormal electrolyte level or increased liver enzyme (Table-II). This finding also show that the severity of hyperemsis and weight loss were found to vary directly with the degree of hyperthyroidism. The etiology of transient hyperthyroidism of hyperemesis gravidarum is unclear. Some investigator feel that the hyperthyroidism is the cause of the hyperemesis, whereas others disagree.9
Hyperthyroidism in trophoblastic tumor is higher than hyperemesis gravidarum.10,11 In our study ▀-hCG in hyperthyroid patients was significantly higher than patients with normal thyroid function (Table-II) and thyroid stimulating hormone was significantly suppresed in first group (Table-II).
Twin or more gestation are more often associated with sustained elevation of ▀-hCG and 60% suppression of thyroid stimulating hormone and hyperemesis gravidarum is more frequent in these groups than single fetus.12,13 In this study stage of goiter was higher in hyperthyroid patients than patients with normal thyroid function. The result of the present research also show that higher stage goiter are see more in hyperemesis gravidarum with thyroid dysfunction that is not reported in other studies.
Our results are suggestive of the involvement of hyperthyrodism and fetal sex in the pathegenesis of hyperemesis gravidarum and several other studies have also reported this finding.14,15 We observed a famale predominance among the offspring of mothers with hyperemesis gravidarum. In this study 14 famale infants and 9 male were delivered. It included 16 uni fetus, 2 twins and one triple fetus.
Although clinical features of thyrotoxicosis are usually absent, or overlooked, in women with hyperemesis gravidarum, some have clinically evident thyrotoxicosis.12 In our study hyperthyroidism was severe in five patients in which PTU was started after diagnosis. Three of them were Anti-TPO antibody positive. In another patients throid function test was repeated four weeks later. In patients with Anti-TPO antibody positive, PTU was started with mean dose 170▒57 mg/d with 5.33▒0.5 months during pregnancy and continued one month after delivery. Serial throid function test was done monthly. FT4I and thyroid stimulating hormone in hyperthyroid patients with Anti-TPO negative were 4.73▒0.3 and 0.11A▒0.08/mu mL respectivily. PTU was started during pregnancy with mean dose 60 mg/d and duration of 2.67▒2.16 months in this group. In this study PTU therapy significantly improved hypermesis in several weeks. Improvement of nausea, vomiting and significant weight gain (1.25▒0.38 kg/month) were noted. Finally routine assessment of thyroid function is necessary for women with hyperemesis gravidarum especially in patients with clinical features of hyperthyroidism. Symptoms of hyperemesis gravidarum usually resolve by 18th week of gestation, regardless of therapy. Antithyroid therapy should be considered for women with persistent hyperemesis and hyperthyroxinemia past 18-20th week gestation especially in patients with hyperemesis gravidarum and severe weight loss, vomiting and biochemical hyperthyridism.6,13-15
1. Skjoldebrand L, Brundin J, Carlstrom A, Pettersson T. Thyroid Associated Components in Serum During Normal Pregnancy. ACTA Endocrinol 1982;100:504-11.
2. Larsen PR, Davies TF, Schlumberger MJ, Hay ID. In: Williams textbook Endocrinology, l0th ed. Saunders, Philedelphia 2003;331-490.
3. Wartofsky L. The thyroid gland. in: Becker kL. Principles and Practice of Endocrinology and Metabolism, 3 rd ed. Lipincott, Philadelphia 2001;308-427.
4. Carrasco N. Thyroid Hormone Synthesis. In: Braverman LE, Utiger RD. The thyroid, 8th ed. Lippincott, Philadelphia 2000;52-61.
5. Glinoer D. Thyroid Disease During Pregnancy. in: Braverman LE, UtigerRD. The Thyroid, 8th ed. Lippincott, Philadelphia 2000;1014-27.
6. Burrow GN, Dffy T. Medical Complications During pregnany, 5th ed. Saunders, Philadelphia 1999;134-61.
7. Yamazaki K, Sato K, Shizume K. Potent Thyrotropic Activity of Human Chorionic Gonadotropin Variants in Terms of 1251 Incorporation and de Novo-synthesized Thyroid Hormone Release in Human Thyroid Follicles. J Clin Endocrinol Metab 1995;(80):473.
8. Rhodes V, Daniel R. The Index of Nausea, Vomiting, and Retching: A New Format of The Index of Nausea and Vomiting. Oncol Vurs Ferum 1999;(26):889-94.
9. Arturi F, Presta I, Scarpelli D. Stimulation of Iodide Uptake by Human Chorionic Gonadotropin in FRTL-5 cells: Effects on Sodium/iodide Symporter Gene and Protein Expression. Eur J Endocrinl 2002;(147):655.
10. Rodien P, Bremont C, Sanson M, Pamma J, Van sande J, Costagliola S, et al. Familial gestational hyperthyroidism caused by a mutant thyrotropin receptor hypersensitive to human chorionic gonadotropin. N Engl J Med 1998;(339):1823-6.
11. Goodwin TM, Montoro M, Mestman JH. The Role of Chorionic Gonadotropin in Transient Hyperthyroidism of Hyperemesis Gravidarum. J Clin Endocriuol Metab 1992;75,1333.
12. Burrow GN. Thyroid Function & Hyperfunction During Gestation. Endocrine Reviews. 1993;11(2):194-200.
13. Kuscu NK, Koyuncu F. Hyperemesis gravidarum: Current Concepts and Management. Post Grad Med J 2002;78(916):76-9.
14. Atkins P, Cohen SB, Phillips BJ. Drug Therapy for Hyperthyroidism in Pregnancy. Drug Saf 2000;23(3):229-44.
15. Deruelle P, Dufavr P, Subtil D, Houfflin-Debarge V, Dherbomez A, wemeau JLO, et al. Hyperemesis in the First Trimester of Pregnancy: Role of Biological Hyperthyroidism and fetal sex. Gynecol Obstet Fertile 2002;30(3):204-9.
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