Ann N Y Acad Sci 2000;900:77-88

Thyroidopathies.

Koutras DA

Athens University School of Medicine, Endocrine Unit, Evgenidion Hospital, Greece.

Pregnancy affects thyroid physiology in many ways: (a) The renal iodide clearance rate is increased, hence iodine requirements increase. (b) The fetal requirements for thyroid hormones and iodide are an additional problem. (c) Serum thyroxine-binding globulin increases, thus producing an increase in the levels of total T4 and T3. (d) Chorionic gonadotropin has a thyroid-stimulating activity. This may be compensated for by a decrease in TSH, but in some cases gestational thyrotoxicosis occurs. (e) Thyroid autoimmunity usually subsides during pregnancy, but may rebound a few months after parturition, and postpartum thyroiditis may occur. Because maternal antithyroid autoantibodies cross the placenta readily, fetal and neonatal hyperthyroidism (or hypothyroidism) may develop. Pre-existing thyroid diseases are influenced. Nontoxic goiter increases in size. Iodine and/or thyroxine may be required. Graves' disease may remit. If present, antithyroid drugs should be given in small doses, and quite often they may be stopped altogether. Hypothyroid patients may require a larger T4 dose.

 

Clin Chem 1999 Dec;45(12):2250-8

Thyroid function during pregnancy.

Fantz CR, Dagogo-Jack S, Ladenson JH, Gronowski AM

Department of Pathology and Division of Endocrinology, Washington University School of Medicine, Saint Louis, MO 63110, USA.

BACKGROUND: This Case Conference reviews the normal changes in thyroid activity that occur during pregnancy and the proper use of laboratory tests for the diagnosis of thyroid dysfunction in the pregnant patient. CASE: A woman in the 18th week of pregnancy presented with tachycardia, increased blood pressure, severe vomiting, increased total and free thyroid hormone concentrations, a thyroid-stimulating hormone (TSH) concentration within the reference interval, and an increased human chorionic gonadotropin (hCG) beta-subunit concentration. ISSUES: During pregnancy, normal thyroid activity undergoes significant changes, including a two- to threefold increase in thyroxine-binding globulin concentrations, a 30-100% increase in total triiodothyronine and thyroxine concentrations, increased serum thyroglobulin, and increased renal iodide clearance. Furthermore, hCG has mild thyroid stimulating activity. Pregnancy produces an overall increase in thyroid activity, which allows the healthy individual to remain in a net euthyroid state. However, both hyper- and hypothyroidism can occur in pregnant patients. In addition, two pregnancy-specific conditions, hyperemesis gravidarum and gestational trophoblastic disease, can lead to clinical hyperthyroidism. The normal changes in thyroid activity and the association of pregnancy with conditions that can cause hyperthyroidism necessitates careful interpretation of thyroid function tests during pregnancy. CONCLUSION: Assessment of thyroid function during pregnancy should be done with a careful clinical evaluation of the patient's symptoms as well as measurement of TSH and free, not total, thyroid hormones. Measurement of thyroid autoantibodies may also be useful in selected cases to detect maternal Graves disease or Hashimoto thyroiditis and to assess risk of fetal or neonatal consequences of maternal thyroid dysfunction.

The following study shows that chorionic gonadotropin (hCG) is inversely related to hemoglobin concentration, which means that the more anemic the woman is during pregnancy, the higher the hCG is.

 

 

Lancet 1994 Feb 26;343(8896):511-3

Relation between maternal haemoglobin and placental hormone concentrations in early pregnancy.

Wheeler T, Sollero C, Alderman S, Landen J, Anthony F, Osmond C

Department of Obstetrics and Gynaecology, University of Southampton, Princess Anne Hospital, UK.

Environmental factors that influence placental development are of particular interest because of the reported association between adult hypertension, low birthweight, and large placental size. Maternal anaemia is one environmental factor that is associated with an increase in placental size at birth. We have examined the relation between haematological status and plasma concentrations of chorionic gonadotropin (hCG) and placental lactogen (hPL) in 175 women at about 10 weeks of pregnancy. There were significant negative correlations between maternal haemoglobin concentration and the levels of hCG (p = 0.03) and hPL (p = 0.02). Although 21% of women had low iron stores (ferritin < 13 micrograms/L), no relation was found between serum ferritin and the two placental hormones. There was no association between plasma volume (calculated from maternal weight and height) and hCG or hPL concentrations. We conclude that our observations reflect an influence of the maternal environment on the placenta. The fact that negative correlations with placental hormone concentrations exist across the normal haemoglobin range suggest that they reflect a normal aspect of placental development. We speculate that placental growth is, in part, determined by maternal factors that prevail before conception. One possibility is that these factors modify angiogenesis within the trophoblastic villi.

The following study shows that there is a correlation between zinc levels and hCG levels, at least in women with hyperemesis gravidum (nausea during pregnancy). This suggests that high zinc levels can lead to high hCG levels, and consequently to high thyroid hormone levels.

 

Acta Obstet Gynecol Scand 1988;67(7):599-604

Plasma zinc concentration and thyroid function in hyperemetic pregnancies.

Lao TT, Chin RK, Mak YT, Panesar NS

Department of Obstetrics and Gynaecology, Prince of Wales Hospital, Shatin, Hong Kong.

Low zinc concentrations in plasma have been reported in pregnancy complications such as pre-eclampsia and intra-uterine growth retardation, as well as in non-pregnant individuals with gastrointestinal and eating disorders. The present study looked at the plasma zinc concentration in hyperemetic and normal pregnant women at the same stage of gestation, as well as total thyroxin concentration in these two groups, since abnormal thyroid function is a common phenomenon in hyperemetic women. No difference in plasma zinc concentration was found between normal and hyperemetic women, which suggests that hyperemesis gravidarum is not associated with a low plasma zinc concentration. Hyperemetic women did have, however, significantly higher total thyroxin concentrations, and on further examination, a significant correlation was found between plasma zinc concentration and total and free thyroxin, free tri-iodothyronin, and human chorionic gonadotropin. The significance of our findings is discussed.

The following study indicates that the rise in hCG during pregnancy is not due to cadmium toxicity, since exposure to cadmium results in a decrease in hCG.

 

Teratology 1995 Apr;51(4):266-72

Cellular adaptation to chronic cadmium exposure: intracellular localization of metallothionein protein in human trophoblast cells (JAr).

Breen JG, Nelson E, Miller RK

Department of Obstetrics and Gynecology, University of Rochester Medical Center, New York 14642-8668, USA.

Trophoblast cells are the first embryonic cells that modulate the transfer of a variety of compounds (oxygen, amino acids, xenobiotics, metals) from the maternal to the fetal circulation in the human placenta. Human placental exposure to the toxic metal, cadmium (Cd) results in a decrease in the production of human chorionic gonadotropin (hCG), a decrease in the maternal to fetal transport of zinc (Zn), and trophoblastic necrosis. Thus, the ability of trophoblast cells to adapt to exposure to the toxic metal Cd has been considered crucial. In this study, the expression and intracellular localization of metallothionein (MT), a small molecular weight, metal binding protein, was examined in trophoblast cells (JAr) grown in normal media and in cells exposed chronically (6 months) to 2 microM CdCl2. Conventional and confocal fluorescence microscopy were used to examine the intracellular localization of MT protein in control cells and cells grown chronically in Cd. In unexposed trophoblast cells, MT protein was primarily perinuclear with low level, punctate expression in the cytosol. Following both chronic and 24 hour exposure to Cd, MT protein levels were increased (at least 3-fold in both chronic and acute exposures) and the protein was now concentrated inside the nucleus with a lacy, cytoskeletal pattern of expression in the cytosol. To determine if the nuclear accumulation of MT protein was dependent on new protein synthesis, control cells were exposed to CdCl2 (2 microM) and cycloheximide (2 micrograms/. ml) for 24 hours.

 

Clin Endocrinol (Oxf) 2000 Aug;53(2):177-81

Thyroid function in wholly breast-feeding infants whose mothers take high doses of propylthiouracil.

Momotani N, Yamashita R, Makino F, Noh JY, Ishikawa N, Ito K.

Ito Hospital, Tokyo, Japan. momotani@blue.ocn.ne.jp

BACKGROUND: Propylthiouracil (PTU) might theoretically be preferred over methimazole (MMI) during breast-feeding because of its lower milk/serum concentration ratio (0.1 vs. 1.0). The problem is that Graves' disease often relapses during the postpartum period, and high doses of PTU are sometimes needed to control maternal hyperthyroidism) during breast-feeding. However, there are virtually no data on the effects of maternal PTU on thyroid status of infants whose mothers take more than 300 mg PTU daily and who are wholly breast-feeding. OBJECTIVES: To investigate whether mothers can breast-feed without adverse effects on infants' thyroid status while taking 300 mg or more daily of PTU. SUBJECTS AND DESIGN: Eleven infants who were wholly breast-fed while their mothers took PTU 300-750 mg daily for Graves' hyperthyroidism were included in this study. In one of the 11 infants, the mother also took iodine 6 mg daily for a limited period. Thyroid status in these infants was evaluated. MEASUREMENTS: Free T4 (FT4), thyrotrophin (TSH), and TSH binding inhibiting antibody (TBIAb) concentrations were examined at least once in the age range 6 days to 9 months. Maternal blood was also examined for FT4 and TBIAb on the same day, or within a week, of the infants' blood tests. FT4, TSH and TBIAb concentrations at birth were examined, using cord blood, in cases where antithyroid drugs had been continued through delivery. RESULTS: Three of the 11 infants had TSH concentrations higher than the normal range for adults. In one of the three infants, the TSH concentration, which was determined 19 weeks after birth, was just above the normal range. In the remaining two infants whose mothers had taken PTU through delivery, TSH concentrations, determined within 7 days after birth, were distinctly high, but they became normal while maternal PTU doses were the same as or higher than those at the initial examination. Maternal PTU doses or FT4 concentrations were not significantly correlated with infants' TSH concentrations. CONCLUSION: Mothers can breast-feed while taking propylthiouracil at doses as high as 750 mg daily without adverse effects on thyroid status in their infants.

Subj: Re: [hyperthyroidism] High Levels - should I worry??
Date: 5/16/00 10:40:44 PM Pacific Daylight Time
From: Tina
Reply-to: hyperthyroidism@egroups.com
To: hyperthyroidism@egroups.com

Michelle,
I am SO glad that I am actually reading my 'thyroid' mail tonight! Please bear with my LONG reply!

You did not mention how long you have NOT been taking Tapazole. At first I had the impression that you were still taking the Tapazole and ended up with these HIGH thyroid levels. Since I don't know any more about your situation, than what you have shared in this post, let me tell you about me.

I, too, have Graves'. I only took Tapazole for 40 days, at MOST, early in 1996.  During that time I gained more than 30 pounds and the only help the endo offered was to push myself back from the table!! I couldn't stand the stress of the weight gain (I struggled the year before to lose 40 pounds, now it was back a pound a day!) and of the 'quack' of a doctor I had, so I did the only thing I thought possible: resort to denial! HA! That's the first time I've ever said that! Looking back, I know that I made the right decision for me by running from the things that caused me so much stress at that time! I believe that it was choosing to end the STRESSors, that enabled me to figure out what would be the healthiest choice(s) for ME!

I lived the next 3.5 years doing NOTHING for my thyroid. At least once a year my family doctor would order the usual thyroid panel and refer me to an endocrinologist. I refused to go until after my yearly exam last summer. It was at that point that I decided I wanted to do whatever it took to be able to have another baby~all the docs agreed that it was my extremely overactive thyroid that was keeping me from conceiving! I even considered asking for RAI. It took me more than a month to get an appt with the only local endo listed on my insurance. When I saw him in Sept 99, he shared his amazement that I had never needed hospitalization, since my numbers were so high! They were: T3=498 (up from 398 in 2/98), Free T4=5.4 (down from 6.04 in 2/98), and TSH=0.02 (<0.03 in 2/98). Other than noticing my heart beating faster at different times, I really didn't have the typical HYPER symptoms.

The doctor only prescribed a thyroid scan and a beta blocker for my heart rate (which ALWAYS increases when I'm nervous!) He said to keep watch on my pulse and adjust the meds accordingly. Well, I think I only took 3-5 day's worth of the meds, since every time I checked my pulse was NORMAL! How have you been feeling since coming off the Tapazole? Did you gradually stop taking it or did you quit 'cold turkey'?

Back to last Sept. I found the thyroid list at onelist and joined! Over and over again I heard, what I call, horror stories of what HYPOthyroid is really like! Doctors don't tell you the negatives of going hypo, only how easy it is to treat!! I chose to NOT have another thyroid scan done last fall, figuring WHY subject my body to ANY unnecessary radiation!! I found power in making my own medical decisions!! In January of this year I began taking a multi vitamin and a B-complex! Within a month I had added several other supplements on the supplement list put out by John.  What I did not realize until the end of March, was that I had gotten pregnant in Feb!! I can not help but believe my body was waiting for some nutrient in those supplements!!

It took me until the end of April to get an appt with the OB I chose. When he realized that I had not followed up with the endo the previous fall, he decided that I was in a crisis! I spent that afternoon waiting for him to 'discuss' my case with a fellow medical doctor in his office and then talk the endo into seeing me RIGHT AWAY! I had to see him before I could even have the regular pregnancy blood tests drawn! Good news is that I got to have a sonogram that day also!! Baby appeared healthy and measured exactly the right age~11 weeks!

I was surprised to leave the endo's office without orders to fill a prescription for PTU that day! Instead, he prescribed more beta blockers (only 10 mg doses - said if I wasn't' pregnant, he'd start me at 100mg doses) and ordered thyroid tests. Last week when I saw him, here is what I learned: T3=315 (down almost 200 points), Free T4=4.64 (down from 5.04), TSH=<0.002 (yikes, looks like this has almost stopped producing!), and Thyroid-Stimulating Immunoglob (???? what is this?????) = 1.7 (should be 0-1.3). That day, he said to start taking 50mg of PTU, 2xs daily. He commented how worried he is about my T4 number being 'toxic'. I always thought the T3 was the important level, now I'm confused!! My philosophy is, my numbers have DECREASED! Isn't this a GOOD thing? I was really hoping to find that my TSH had RISEN instead of decreasing!

What will the PTU do? How will it affect the baby? This endo, seems to think he'll end up sending me for surgery during the second trimester! I'm believing that I've come this far WITH my thyroid and this baby has survived it's first 14 weeks!! That in itself is a wonderful sign~why risk taking my thyroid OUT!!!! Oh, I forgot to mention that the day I found out I was pregnant was the day I became ill with strep throat! I had to take 2 rounds of antibiotics over the course of 3 weeks! I forgot to ask the endo if being ill or on antibiotics may have caused the drastic change in my test results. Does anyone know?

I'm scheduled from another round of thyroid blood tests at the end of this week, before return to endo next week. I have no idea how quickly PTU can make a difference, but I suppose I'll be an expert by the end of this pregnancy!!!

All in all, Michelle, what I want to share with you the most is that YOU have to live with YOU! No one else does!! You have to be comfortable with the decisions you make for your body!! I totally understand your 'fear' and even your desire to start a family! My husband even considered being tested to see if it was HE who was sterile since we had not conceived in over two years!!! I can't get over God's timing for this child! It totally surprised me to discover I was pregnant!! I have to trust that God will protect this child from negative effects of my excess hormones and/or
the meds that I'm taking!!

I guess in the end, the meds are the only thing I still have some control over. If he says to take 500mg, I can if I agree, or take less if I don't! Surgery and RAI are one time decisions for the doctor!! I'm not ready to entrust the rest of my life to either yet!!

You are in my prayers,
Tina:)

From Journal of the American Board of Family Practice Transient Hyperthyroidism of Hyperemesis Gravidarum: A Sheep in Wolf's Clothing CPT Timothy J. Caffrey, MC, USA, US Army Health Clinic - Vicenza, Italy. Abstract Background. Transient hyperthyroidism of hyperemesis gravidarum (THHG) is a self-limiting hyperthyroidism occurring in the context of hyperemesis gravidarum. Methods. A literature search of MEDLINE was undertaken, and a case report of a woman with THHG in pregnancy is described. Results and Conclusions. Because thyroid function tests cannot distinguish Graves disease from THHG, the diagnosis of THHG rests largely on the concurrent development of hyperemesis and hyperthyroidism and the absence of signs and symptoms of hyperthyroidism before and during pregnancy. THHG might be responsible for 40% to 70% of thyroid function abnormalities in pregnancy. Both the thyroid function abnormalities and hyperemesis are related to elevated levels of human chorionic gonadotropin. THHG resolves by 18 weeks of pregnancy without sequelae. No treatment is required. Diagnosis of THHG by the primary care provider can prevent unnecessary treatment or referral for specialty care. [J Am Board Fam Pract 13(1):35-38, 2000. © 2000 American Board of Family Practice]

 

Email to BU007: I just found out that I have hyperthyroidism. My husband and I were trying to start a family. What would be the side effects to having a baby with RAI and PTU pills.