This Sunday, we bring to you Dr. Alaka Deshpande's article in which she details on the significant damage that undiagnosed thyroid dysfunction can cause to the mother and foetus during pregnancy, while also outlining key practice points for physicians to adopt early on in order to prevent unfavourable outcomes.

It is reported that 1 in 6 pregnant women have thyroid dysfunction. However, hormone estimation by RIA became feasible only about 40 years ago. Clinicians have since noted the changing profile of thyroid disorders after many hypothyroid cases remained asymptomatic for a long time. This makes it prudent to update the management guidelines whenever new evidence comes forth.

Clinicians should be concerned about a hypothyroid mother, the obstetric outcome and of course the foetus as the baby of a hypothyroid mother may develop neurocognitive disorders. The development of foetal thyroid starts in the third week of gestation from the floor of the primitive pharynx and then migrates to its final location in the neck.

Synthesis of thyroid hormone normally begins at about 11 weeks of gestation. Thyroid hormones are essential for growth and development, particularly of the foetal brain. The foetus, therefore, is dependent on maternal thyroxine more so in the first trimester.

Pregnancy is a stress test for the mother’s thyroid. The metabolic needs increase during pregnancy. In most cases, the mother’s thyroid adapts itself to meet this challenge. The thyroid gland increases 10% in size during pregnancy in iodine– replete countries and 20 to 40% in areas of iodine deficiency.

Physiological changes that occur in a mother’s thyroid during pregnancy include:

• Increase in size
• Increased production of T4 and T3 by 50%
• 50% increase in daily requirement of iodine
• Increase in TBG—thyroxine binding globulin (therefore total T4 is elevated)
• Increased levels of human chorionic gonadotropin (hCG) directly stimulate the thyroid gland to increase the production of thyroid hormone which decreases the secretion of TSH. Reference range of TSH is lower throughout pregnancy

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As per the guidelines of the American Thyroid Association, the upper limit of TSH of 2.5 in pregnancy has been accepted only recently. The laboratories which do not give their trimester specific range the following reference intervals may be used.

Trimester	S.TSH
First	0.1 to 2.5 µIU/ml
Second	0.2 to 3.0 µIU/ml
Third	0.3 to 3.0 µIU /ml

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In iodine-sufficient population, it has been estimated that 1 in 6 pregnant women are affected by thyroid disease. Thyroid diseases could be hormonal dysfunctions or morphological anomalies. Due to the paucity of prospective, randomised controlled trials, data is inadequate, making the task more difficult.

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Hypothyroidism during pregnancy

Overt Hypothyroidism- (OH)

• Elevated TSH > 10 µIU/ml or more irrespective of their FT4
• Elevated TSH > 2.5 µIU/ml with low FT4

OH in pregnancy has been shown to be associated with increased risk of adverse complications including miscarriage, premature birth, low birth weight and neuro-cognitive disorders in the foetus. The mother has to be adequately treated with hormone replacement.

Subclinical Hypothyroidism (SCH) in pregnancy

• It is defined as S.TSH levels varying between 2.5 to 10µIU /ml with NORMAL FT4 concentration

SCH is associated with adverse outcomes of pregnancy with possibly an increased risk of neurocognitive disorders in the growing foetus. Risk of pregnancy complications in SCH is more in women who are thyroid peroxidase antibodies positive. .

We in our country with geographical variations in iodine content, dietary habits, ethnicity and lack data about thyroid dysfunctions. Considering the awareness in the community, health-seeking behaviour of our people, medicolegal aspects, and the available scientific evidence with American and other guidelines, the suggested clinical approach would be:

1. All young couples anxious for the child should ideally undergo pre-conception counselling and necessary investigations including TSH estimation before planning conception. There is no unanimity regarding the universal testing of TSH in pregnant women. History of thyroid dysfunction in a woman or in her family members, the presence of thyromegaly in the family may be some of the criteria for TSH estimation in prospective mothers. However, the difficulties that a clinician faces elucidating such history, it is better to estimate serum TSH in a woman as soon as her pregnancy is confirmed.
2. If TSH is > 2.5 µIU/ml, then FT4 and TPO (Thyroperoxidase) antibodies are estimated.

• FT4 helps in differentiating between OH and SCH.
• Secondly, antenatal TPO antibody test in such cases may also help to diagnose post-partum thyroiditis in postnatal period if it occurs

3. The patient should undergo a detailed clinical history and clinical examination.
4. The goal of treatment should be to normalise maternal serum TSH values to trimester-specific reference range throughout the pregnancy with replacement therapy of LT4 (levothyroxine ). The therapy may be started with a smaller dose of LT4 25 to 50 mcg/day on empty stomach in the morning.
5. S. TSH should be monitored every month until delivery. Considering the lab infrastructure and methodology used, it is advisable that follow up be carried out from the same laboratory.

These are pregnancy—specific guidelines for SCH mothers.The consideration has been increased risk of adverse outcome of the pregnancy and foetal neurocognitive disorder.

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Overt hypothyroidism and pregnancy

By definition, OH is S.TSH >10 µIU/ml

There can be:

• A known case of primary hypothyroidism on LT4 treatment in a woman who is anxious for a child
• A pregnant patient detected to be hypothyroid during gestation
• A patient who was found to have low FT4 and TSH during pregnancy more than 2.5 µIU/ml (trimester-specific upper limit of normal

OH in pregnancy has consistently shown an increased risk of adverse outcome of pregnancy. In addition to the adversities described above, OH carries an estimated 60% risk of foetal loss. Literature shows a 22% risk of gestational hypertension in pregnancy. It has a detrimental effect on neurocognitive functions of the foetus.

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Key practice points for Hypothyroidism

1. A woman with hypothyroidism need to be adequately treated with LT4 before planning conception. As soon as the pregnancy is confirmed, S.TSH level should be checked and a dose of LT4 may be increased so that trimester specific TSH level is achieved.
2. Alternatively, a woman who is euthyroid with a once-a-day dose of LT4 (i.e. 7 tablets per week) before gestation should be advised to increase the dose to nine tablets per week as soon as she misses the period. This increment is about 29% in the dose. Or, she should increase her daily dose by 25 to 30%. Simultaneously, confirmation of pregnancy and S.TSH estimation should be carried out.
3. Total body T4 requirement does not remain static throughout pregnancy. Data shows that 20 to 50% increment in total body T4 concentration is necessary to maintain euthyroid state.
4. TSH levels immediately after conception should guide the increment in LT4 dose to maintain trimester-specific TSH levels. A pregnant hypothyroid mother should be followed up every month with TSH estimation to maintain euthyroid status.
5. It is strongly recommended to use LT4 and not other thyroid preparations such as T3 or desiccated thyroid.
6. After the delivery mother can go back to preconception LT4 dose.
7. As per WHO guidelines, a breastfeeding woman should ingest approximately 250 µg of dietary iodine/day.

In the USA all the newborns are universally tested for S.TSH level. Although we have no guidelines, it will be prudent to rule out hypothyroidism in the newborn of a hypothyroid mother by measuring the S.TSH after birth.

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This article was originally published on May 8, 2019.