Subclinical Hypothyroidism linked to unexplained infertility

Women with unexplained infertility (UI) were twice as likely to have a raised TSH level as compared to women who were not able to conceive because of male factor infertility reports the results of a cross-sectional study published in February issue of Endocrine Society's Journal of Clinical Endocrinology & Metabolism.

About 10-30% of the infertile couples have unexplained infertility, defined as an inability to conceive with 12 months of unprotected intercourse with no explainable cause.

Data on the association between subclinical hypothyroidism and infertility is so far limited because of different levels of TSH cutoffs.

For this study, the Harvard based researchers looked at data from large academic health system over a period of 12 years and recruited 239 women with TSH (≤5 mIU/L) and prolactin levels (≤20 ng/ml) within normal range.  Of these women, 187 were diagnosed as UI (study arm), while in 52 women the male partner suffered from azoospermia or severely oligospermia with no other factor diagnosed for infertility (control arm).

After accounting for age, body mass index, and smoking status, it was seen that nearly 27% of women in UI group had TSH ≥2.5 mIU/L as compared to 13% in control group (P < 0.05).

The prolactin levels were comparable between both the groups.

Pouneh K. Fazeli, study’s senior author and a researcher at Massachusetts General Hospital and Harvard Medical School in Boston said, “Since our study shows that women with unexplained infertility have higher TSH levels compared to women experiencing infertility due to a known cause, more research is needed to determine whether treating these higher TSH levels with thyroid hormone can improve their chances of getting pregnant.”

Abstract

Media courtesy: The National Academy of Hypothyroidism

American Thyroid Association releases new guidelines on thyroid disease in pregnancy.

Courtesy: Thyroid foundation 

Thyroid disease in pregnancy is very common and is the second most common endocrine disorder of women during reproductive age. Pregnancy leads to an increase in size of thyroid gland from 10-40% depending on iodine content of the area. Iodine requirement also increases by 50% with almost 50% increase in production of thyroxine (T4) and triiodothyronine (T3).

American Thyroid Association (ATA) first published its guidelines in 2011 but, significant scientific and clinical advances since then led ATA to revise the guidelines.

These 162 pages of evidence based guidelines were first published online on January 06, 2017 in Thyroid. [1]The 97 recommendations presented deals with nutrient requirements, screening, diagnosing, testing, complications and management of   thyroid disorder in pregnancy and post-partum period. It also includes neonatal morbidity due to maternal thyroid disease and future research in the field.

The full text of the guidelines can be accessed here.

Some of the salient recommendations are summarized here.

Screening for Thyroid disorder in pregnancy.

• All pregnant patient should be verbally and clinically screened for thyroid disease and use of thyroid medications. If any of the risk factors are identified, then testing for TSH is advisable. 
• Universal screening for low free thyroxine concentrations in pregnant women is not recommended. 
• Insufficient evidence  also exists for Universal screening or no screening for TSH level  preconception or in  early pregnancy. 

Hypothyroid in Pregnancy.

• The reference range for serum TSH changes in pregnancy. Hence, population based trimester-specific reference range for TSH should be defined.
• The requirement of Levothyroxine only increases by 20-30% during pregnancy and a simple way of achieving it is to administer 2 additional tablets weekly of the patient’s current daily levothyroxine dosage.
• Subclincal hypothyroidism in pregnancy should be treated according to the reference range for the population and TPO status.
• Overt hypothyroidism should always be treated during pregnancy with Levothyroxine only, Other thyroid preparations such as triiodothyronine (T3) or desiccated thyroid should not be used in pregnancy.
• TSH level tested 6 weeks postpartum and the dose adjusted.

Iodine requirements in pregnancy and before conception

• All pregnant women should have approximately 250 μg iodine daily. 
• All women who are planning to become pregnant should supplement the diet with daily 150 μg of iodine, optimally 3 months before the conception except women with already existing hyper or hypothyroidism.
• Excessive iodine supplements and sustained dietary intake above 500 μg daily should be avoided during pregnancy.

Subclinical hypothyroidism.

• All Euthyroid but TPO or Tg antibody positive pregnant women should have serum TSH concentration performed at time of pregnancy confirmation, and every 4 weeks through mid-pregnancy. These women should not be treated with thyroxine just to prevent RPL or preterm delivery.

Infertility and Thyroid disorders.

• All infertility patients should have their thyroid function done and only women with overt hypothyroidism should be treated with levothyroxine. 
• Evidence is insufficient for supplementing levothyroxine to all women with subclinical hypothyroidism to improve fertility.
• Women with subclinical hypothyroid undergoing IVF or ICSI should be treated with levothyroxine. The goal of treatment is to achieve a TSH concentration TSH <2.5.

Hyperthyroidism in pregnancy.

• Managing Hyperthyroidism in pregnancy is very complicated issue. Radionuclide scintigraphy or radioiodine uptake determination is contraindicated in pregnancy.
• Methimazole (MMI) nor propyl thiouracil (PTU) is safe during pregnancy and should be immediately stopped once the pregnancy is confirmed because of its teratogenic potential. If at all required than PTU is preferred over MMI till 16 weeks in the lowest effective dose.
• The fetus should be closely looked at for Goiter or hypothyroidism during the second half of pregnancy.
• Thyroidectomy in Graves’ disease in only indicated in specific situation and should follow the recommendations of ACOG to schedule any surgery during pregnancy.

Other recommendations can be found in the full text of the article.

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[1] http://online.liebertpub.com/doi/pdfplus/10.1089/thy.2016.0457

Iron deficiency in Pregnancy linked to hypothyroidism!

Clinical Pearls:

• The study findings show that prevalence of iron deficiency is still 35% in a developed country like Belgium.
• 10% of pregnant women with iron deficiency will have thyroid autoimmunity and 20% will have subclinical hypothyroidism.

According to WHO the prevalence of anemia in pregnancy is nearly 40% worldwide, with iron deficiency being the major cause.[1]

A small Belgian study published in European Journal of Endocrinology on July 22, 2016 linked low serum iron with increased risk of thyroid autoimmunity and hypothyroidism in pregnancy.[2] It was a nested cross sectional study as a part of ongoing data collection on pregnant woman at a single tertiary center in Université Libre de Bruxelles in Belgium.

The analysis included 1900 study participants in the first trimester of pregnancy. Iron deficiency was diagnosed when ferritin levels were < 15 μg/L, subclinical hypothyroidism was defined as a TSH level > 2.5 mIU/L and thyroid peroxidase antibodies(TPO-abs) was > 60 kIU/L defined thyroid autoimmunity(TAI).

Iron is necessary for the normal functioning of thyroid peroxidase(TPO) which is a  heme-containing enzyme catalyzing the two initial steps in thyroid hormone synthesis.

Nearly one third of the women suffered from iron deficiency, and in these women significant association was found between low iron and thyroid autoimmunity (10% versus 6%) and subclinical hypothyroidism (20% versus 16%) as compared to women with normal iron levels.

The study co-author Kris Poppe, MD, an endocrinologist opined that in his daily practice,  those women who are often referred to him  for thyroid  dysfunction often seems to  have low iron levels concurrently. 

It is a very small study which does not have significant impact on clinical practice, nor does it proves causation. Low Ferritin levels might be due to other nutritional deficiency or poor diet. But, it does emphasize on the need for replicating the study in different population, with larger data.

Dr. Kris Poppe also stressed the need for checking the iron levels in first trimester of pregnancy or before planning the pregnancy so that any nutritional deficiency could be corrected.

The researchers are planning to design studies that look into impact of low iron and thyroid dysfunction on pregnancy outcomes.

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[1] http://www.who.int/vmnis/anaemia/prevalence/summary/anaemia_data_status_t2/en/

[2] http://www.eje-online.org/content/early/2016/07/22/EJE-16-0288.abstract