Thyroid Disease and Fertility
The thyroid gland produces hormones that act on most cells in the body to increase the metabolic rate and to alter sensitivity of cells to other hormones. Thyroid hormones are very important in the development of the human foetus. Disorders of the thyroid gland may be linked to infertility, miscarriage and problems with pregnancy and foetal development. The thyroid gland can be overactive (hyperthyroidism) or underactive (hypothyroidism) and these conditions can be detected by measuring thyroid hormone levels in a blood sample. Many thyroid conditions are caused by an overactive immune system (autoimmune thyroid disorders). This can be diagnosed by measuring the level of thyroid antibodies in a sample of blood. Medical treatment is readily available for both overactive and underactive thyroid disorders, which may include referral to a thyroid specialist (endocrinologist).
The Thyroid Gland
The thyroid is a butterfly shaped gland which wraps around the front and sides of the trachea (windpipe) between the larynx (Adam's Apple) and the top of the breastbone or sternum. Each lobe or "wing" is usually 4 to 5 cm high, 1 to 2 cm wide and about 1 cm thick. The two lobes are joined in front by a narrow isthmus. The thyroid produces two major hormones; thyroxine (often called T4 because it contains 4 iodine atoms) and much less triiodothyronine or T3 which has only 3 iodine atoms. T3 is three to four times more active than T4 and most of it in the circulation is produced in other cells of the body by removal of one of the iodine atoms. T4 has quite a long life in the circulation; in medical terms is said to have a half live of about 7 days, meaning that if thyroid hormone is released one day there will be half of it left in the blood in one week and a quarter in two weeks. T3 has a much shorter half life of only 6 or so hours.
The thyroid hormones act on most cells in the body to increase the metabolic rate to produce heat and to alter sensitivity of the cell to other hormones. Thyroid hormones are very important in the development of the human foetus.
The rate of production of thyroid hormone by the thyroid gland is controlled by a pea sized gland sitting just under the brain known as the pituitary gland. The pituitary also controls the rate of production of other hormones from the adrenal and sex glands (testes and ovaries). The pituitary in turn is controlled by the brain itself. In its role as controller of the thyroid, the pituitary watches the amount of thyroid hormone in the blood and if there is not enough releases Thyroid Stimulating Hormone (TSH) to cause the thyroid gland to produce more. If there is too much thyroid hormone then the pituitary doesn't want any more and the amount of TSH decreases. This is the reason for the somewhat difficult to understand interpretation of thyroid hormone levels in a blood test. A high TSH means that the thyroid is underactive and a low TSH means that either the thyroid is overactive, or too much thyroid treatment is being taken.
Autoimmune Thyroid Disorders
The human body may be compared to a defended military position. We are all hosts to countless numbers of bacteria - thought to be 10 times more numerous than the number of actual cells in our body - and many of these bacteria would attack us given half a chance. The body's immune system deploys an army of white cells to fight off this relentless enemy. In fact the body has the same problem as the military, how to recognise an enemy when you see one. If the military adopts a "shoot first, ask questions later" attitude then an approaching enemy will not get through but there will be some "friendly fire incidents". We are here because our ancestors were able to survive the plague, small pox, cholera etc. since they had a "trigger happy" immune system. There can be a down side of this hyperactive immune system with the "friendly fire" of autoimmune diseases where the immune system attacks part of the body itself. Pursuing the military analogy a bit further; if the base is on high alert then the gunners will shoot at anything. Our immune system also goes to action stations when it is under stress making autoimmune disorders more likely. There are something like 80 autoimmune diseases including Type 1 Diabetes, rheumatoid arthritis and celiac disease but the most common is an immune attack on the thyroid gland.
Women have a more complex situation than men since women have babies and babies are immunologically different to them with half the antigens (proteins recognised by the immune system) of the baby coming from the father. These would not be recognised as self by the mother's immune system, so during pregnancy the immune system is clamped down to prevent an attack on the baby. For this reason, autoimmune diseases tend to improve during pregnancy though often relapse after delivery. The female immune system has to be organised a little differently from the male version so, although women may not get as many heart attacks and strokes as men, they tend to get the autoimmune diseases, especially those that involve an attack on the thyroid.
Hashimoto's Thyroiditis is the most common of the autoimmune disorders and affects something like one percent of women, especially those of child bearing age. It is usually silent and may be unrecognised for years as the immune system slowly damages the thyroid. The thyroid gland is then no longer able to produce adequate amounts of thyroid hormone and levels in the blood drop. Since thyroid hormones control the metabolic rate, persons may complain of tiredness and weight gain but these complaints are very common in the community and so may be ignored. The thyroid gland tends to become enlarged, sometimes quite markedly so, but again this is often not noticed. Autoimmune disorders tend to run in families so often patients will have a family history of, not only Hashimoto's Thyroiditis, but also of celiac disease or pernicious anaemia. Smoking also predisposes persons to autoimmune problems as well as just about everything else.
Hashimoto's Thyroiditis may be precipitated by some major event which in women wishing to become pregnant is often a recent marriage which rates very highly on stress scales. The thyroid is damaged by the autoimmune attack and the first sign on a blood test is the TSH starting to rise as the pituitary tries to stimulate the thyroid to produce more thyroid hormone. As time goes on the thyroid will be too damaged to respond and thyroid hormone levels in the blood will start to decline. The actual proteins the white cells produce to attack the thyroid with, anti-peroxidase (peroxidase is an enzyme in the thyroid cells) and anti-thyroglobulin (thyroglobulin is the protein in the thyroid that stores the thyroid hormone prior to release) are able to be measured and may be the first sign of Hashimoto's, sometimes being detected before the TSH even starts to rise. Hashimoto's Thyroiditis is unlikely to go into remission (get better) in adults. The treatment is not aimed at the disease itself, an autoimmune attack on the thyroid, but to simply replace the hormone usually made by the thyroid.
This autoimmune condition is virtually unique since rather than destroy the target organ as is the case with Hashimoto's and other autoimmune problems such as rheumatoid arthritis, in Graves' Disease the thyroid gland is stimulated to become overactive. Since the thyroid controls the metabolic rate this will result in tremors, fast heart rate, weight loss and hyperactivity in younger persons though fatigue in older ones. There can also be bulging eyes due to an immune attack on the tissue behind the eye.
Graves' Hyperthyroidism, like Hashimoto's Thyroiditis is also predisposed to by a family history of other autoimmune disorders and smoking and precipitated by major life events. The aim of the treatment is not to stop the autoimmune attack on the thyroid, since this would require suppression of the entire immune system with all the accompanying problems this would entail such as the body being unable to defend itself against infections. The cure would be worse than the disease. The plan is to use treatment to block the thyroid gland from responding to the stimulating immune attack, and to control thyroid hormone production until the attack goes away, which it does in about half of the patients in the next couple of years. Since the thyroid is stimulated rather than destroyed as in other autoimmune disorders, patients may recover completely though there is a risk the disorder will return at some stage.
Thyroid Disorders and Fertility
Thyroid antibodies themselves have been associated with decreased fertility even when the TSH hormone level is in the high normal end of the range, through mechanisms that aren't clear. Perhaps they are just a marker of immune problems with a tendency for the mother's immune system to prevent the implantation or retention of the fetus. Since thyroid treatment has been shown to decrease the level of thyroid antibodies, probably by shutting down the thyroid and making it less of a target for the immune system, some doctors advocate treating patients desiring pregnancy if they have positive thyroid antibodies even though the TSH level is in the upper end of the normal range.
Thyroid Disorders and Pregnancy
Thyroid hormone is necessary for the development of the foetus. Though the foetal thyroid appears in the first two months, it doesn't really begin to produce much thyroid hormone until about three months down the track and the developing foetus relies on thyroid hormone from the mother during this time. Thyroxine or T4 is able to cross the placenta from mother to baby reasonably well though triiodothyronine or T3 is not. This placental transfer is able to maintain normal development in the foetus even in cases where the foetal thyroid is absent.
The problem arises when the thyroid gland in the mother is damaged and unable to produce adequate amount of the vital thyroid hormones. The usual cause is Hashimoto's Thyroiditis which may be present at an early stage and not be causing any symptoms in the mother at all. This can be checked by performing blood tests of Thyroid Stimulating Hormone (TSH) to see if the pituitary is trying too hard to keep thyroid levels in the mother normal. A normal range of TSH is between 0.4 and 4.0 milliUnits per ml. Even TSH levels at the upper end of normal, say over 2.5, might mean that there is not enough thyroid hormone for the baby. In fact even high normal TSH levels in the mother, when the thyroid hormone levels themselves are still normal, have been associated with a mild loss of IQ points in the baby.
Once pregnancy has occurred, the amount of thyroid hormone required increases probably due to destruction of the thyroid hormone by the placenta. After 20 weeks of pregnancy the amount of thyroid hormone required to keep the TSH in the normal range stabilises.
There are several reasons why thyroid hormone levels may be elevated during pregnancy. A woman may be taking too much treatment by mistake or she may have Graves' Hyperthyroidism or one of several other rarer causes of an overactive thyroid. In the early stages of pregnancy the foetus produces a hormone known as hCG (human Chorionic Gonadotrophin) to assist in maintaining the pregnancy. Later the placenta continues to produce it. HCG is similar in structure to TSH and can have a mild stimulating effect on the thyroid causing thyroid hormone levels to become a little elevated. HCG levels seem to be linked to the severity of morning sickness so women who suffer from severe vomiting might well have higher levels of thyroid hormone in the blood and low levels of TSH. This effect wears off so the usual treatment for mildly elevated thyroid hormone levels in pregnancy is to wait and see. Sometimes however the thyroid hormone levels may be high enough to threaten the success of the pregnancy. This is often the case with Graves' Disease and so this condition usually requires treatment especially in the earlier stages of the pregnancy. Later the immune attack decreases as the body moves to suppress the entire immune system to prevent an immune attack on the foetus itself. The standard treatment in this type of situation is to block production of the thyroid hormone by the thyroid gland.
We are grateful to Associate Professor Christopher Strakosch for his help in developing this webpage.