association of thyroid function with maternal a... - Thyroid UK

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association of thyroid function with maternal and neonatal homocysteine concentrations


We have seen much speculation over the interrelationship of thyroid hormones and B12. A paper discussing exactly that seemed to have much potential. Though have to say, I am still scratching my head about the real meaning of this paper. :-)

Nonetheless, in case someone can interpret it for us, and simply to confirm that there really is something to investigate, here is the abstract:

J Clin Endocrinol Metab. 2017 Sep 5. doi: 10.1210/jc.2017-01362. [Epub ahead of print]

association of thyroid function with maternal and neonatal homocysteine concentrations.

Barjaktarovic M1,2,3, Steegers EAP4, Jaddoe VWV1,5, de Rijke YB3,5, Visser TJ2,3, Korevaar TIM1,2,3, Peeters RP2,3.

Author information

1 The Generation R Study Group.

2 Internal Medicine.

3 Academic Center for Thyroid Diseases.

4 Obstetrics and Gynecology.

5 Pediatrics.



High homocysteine concentrations are associated with maternal pregnancy complications and low birth weight, jaundice and cerebrovascular accidents in neonates. Thyroid hormone may interfere with homocysteine metabolism via stimulation of vitamin B12- and folate-dependent processes and via effects on enzymes of the re-methylation pathway.


Investigating the associations of maternal and neonatal thyroid function with homocysteine during pregnancy and after delivery, respectively.

Design, setting and participants:

Within Generation R study, a population-based prospective cohort, we studied the associations of maternal and neonatal TSH and FT4 with homocysteine, folate and vitamin B12 concentrations using multiple linear regression analyses.

Main outcome measures:

Thyroid stimulating hormone (TSH), free thyroxine (FT4), homocysteine, folate and vitamin B12 concentrations were determined in early pregnancy (<18 weeks; N=1094 women without folic acid supplementation) and in cord blood of 4475 neonates.


In neonates, there was a positive association of FT4 with homocysteine and an inverse association of TSH with homocysteine. The latter associations attenuated after adjustment for folate and vitamin B12 concentration (β change: for FT4 0.00559 ±0.001, P<0.0001 to 0.00310 ±0.001, P=0.015; and for TSH -0.00165 ±0.001, P=0.005 to -0.00086 ±0.001, P=0.11). In mothers, there was a positive association of FT4 with homocysteine (P=0.026) but no association of FT4 with folate or vitamin B12 (P≥0.08).


Higher thyroid function is associated with higher homocysteine concentrations in pregnant women and in neonates. These data provide new insights into the effects of thyroid hormone on folate and vitamin B12-dependent processes during early growth and development.

PMID: 28938431

DOI: 10.1210/jc.2017-01362

Full paper, as so often, behind a paywall.

7 Replies

I can't comment on this but I am taking Letrozole following breast cancer and I had to do much searching etc to find that Letrozole inhibits thyroid meds. In this day and age I was shocked this wasn't documented and that I should increase my medication. To me it's apparent that more research needs to be done around the affects that are occurring and guidance given how to minimise the adverse effects.

My late husband, a research science base endocrinologist was trying to get cord blood for his research, don't know where it was leading , but although the head of department was willing to ask patients for permission no one wanted the follow up on the children years later. So the idea fell at the first hurdle. May be that wasabout 30:25 years ago.

helvellaAdministrator in reply to silverfox7


There is a deep mud bath between the research which highlights an interaction and the doctors and pharmacists who should take it on board.

Seems ridiculous, but nowadays we often see more awareness and understanding here in Thyroid UK forum (and many other forums on HU and elsewhere) than in the surgery or pharmacy.

Even when identified, accepted and documented, it is still all too common to see it ignored.

silverfox7 in reply to helvella

There is a huge gulf between science and medicine. This is often brought about because scientists use a lab rat and medics can use a patient if going through the correct channels. In my husbands case the medic in charge of the department was on board so ok but from experience and day to day routine I was aware of things much sooner from his observations than when the doctors got to know but there again we also know many are never 'with it'! So you are spot on, the ones that could make a difference are often the last to know

Do you know if Letrozole is the only oestrogen suppressor implicated? I have been taking Anastrozole for several years, the current recommendation is to take it for 10 years. Since being prescribed Anastrozole the myxedema is much worse, feel as if I am getting puffier by the day. I hadn't considered that there could be a connection until I read your post. I was given Letrozole for a few months but stopped it as I became so depressed, not a normal state for me. Back on Anastrozole and the depression went but not the myxedema. I was not given any information that either drug would inhibit the Levo.

Well I was in the same boat. I saw the info in the details on the Thyroid Uk site who run this forum butvit referred to Tamoxifen which was used before these new ones. Neither the pharmacist at the cancer hospital or the doctor had heard it could be a possibility but all the symptoms I had were mentioned as problems with the drug but were also thyroid problems. I was getting more and more tired and knew that I was going to have to snap out of it as something important to do in the coming couple of weeks. I'd offered to help an overseas visitor look around my home city where her ancestors came from so lots of preparation to do and think about as only two days to cram it all in and I was struggling to even potter around the house.

So I increased my NDT by a quarter and immedicately felt an improvement and my brain started working. I gradually increased the days and succeeded in what I needed to do. I then went back to the Pharmacist and shared this and I understand she was going to contact Thyroid Uk for evidence. I don't know the outcome and she was moving to Birmingham so I never saw her again but at this point it was 6 weeks to my Endo appointment so remained on that dose and my results were spot on so oestrogen blockers do inhibit absorption of thyroid meds QED


Your story is similar to mine, not a single mention or warning that Anastrozole could be a problem in treating an underactive thyroid. I was asked if I would become part of new radiotherapy trial whereby treatment is over seven days instead of seven weeks. Part of this was agreeing that I would present myself at the oncology department once a year for the next ten years to be monitored. I agreed to this and duly turn up. Every time I am asked if I have any symptoms, I always mention extreme tiredness and the need to sleep for an hour or two every afternoon. Never has the thyroid problem been mentioned, one helpful doctor suggested that gluten could be a factor. It was, and I do feel a little better, but it has done nothing for the myxedema. My GP thought it could be fluid build up in my arms as I had a lymph node removed and sent me to St. Lukes for treatment. The lymph nurse there pointed out that only the side without the lymph node would be affected and was at a loss to understand why both arms were so swollen. In fairness, it was not her job to diagnose me.

The treatment I had for BC was faultless, everyone so kind and knowledgeable, if only we have a little of this for our thyroid problems. My apologies for taking so long to reply, I have just started on NDT and have come to the conclusion that a couple of glasses of wine every evening don't help.

Thank you for your reply. I think the big problem with medicine is that it's put in boxes and overlaps and wider issues are not considered. When I was first but on it I got conflicting comments on here, basically a yes and a no! Plus it's difficult when symptoms overlap so easy to see that any research could well be flawed. But S I felt I couldn't continue as I was I tried to change it. It worked for me but it might not work for others and there will also be others that will say it's a coincidence as no proper trials etc but for me it works so I am happy to continue. I was before this stable on NDT , prior to that I had taken Levo sucessfully for many years but things changed around the menopause and I found I had stopped converting well so addressed and corrected that before changing back to NDT ( I had started my thyroid journey on NDT). So I don't think NDT was implicated in my wellness as I was stable on that before the BC. So all I can do is share my story and suggest what may have helped. Be interesting to see how things work out for you though it could take you a while to get stable on your NDT. Just take increases slowly. I thought I had but I missed my sweet spot and went over! It may not be as clear cut though with changing medication as you will be titrating that again how you feel now rather than how you were feeling before.

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