My 10-year-old daughter was diagnosed with hypothyroidism in 2022. She started having constipation in 2020 but it was difficult to get appointments to investigate this. She had also suffered with pain behind her ears for many years. This flares up and causes her considerable pain, to the point where she struggles to walk. When she was younger she would wake up in the middle of the night screaming and writhing in pain. The doctors just said that she had growing pains.

As she has grown older (and possibly now that she is on levothyroxine), the incidents of these flare-ups have reduced. We have ruled out things like rheumatoid arthritis. Is there a possible link to her thyroid condition? 

Also, we had thought that her constipation would improve once she was treated for hypothyroidism. This unfortunately hasn’t been the case. Was I incorrect to think it would improve? 

Finally, my daughter suffers quite severely with fatigue despite being on levothyroxine. At the beginning of the webinar there was mention of selenium. Is this something she should be tested for? 

It must have been so hard to deal with your daughter’s illness in the middle of the pandemic. Please note that I am unable to provide medical advice for your daughter for many reasons, but most importantly because for a healthcare professional to construct an opinion and propose solutions about your daughter’s symptoms, it is vital that he/she makes a thorough assessment, which consists of getting to know your daughter, listening to her symptoms, taking a full medical history, perform a careful physical examination and, if appropriate, do tests. Without the above the job is half done. What I can do is summarise what the evidence suggests given a particular scenario, but how applicable that is to your daughter can only be decided by the doctor who has had the opportunity to assess her as outlined above.

Is there a link between pains behind the knee and the diagnosis of hypothyroidism? Aches and pains in people with hypothyroidism are common, especially in untreated ‘overt’ hypothyroidism (‘overt’ usually means hypothyroidism associated with symptoms and a serum TSH greater than 10 mU/L). Some of these get better following treatment, but some persist. Among such cases there will be specific diagnoses, like rheumatoid arthritis, but very often no cause can be found. Modern medicine generally is good at ruling out serious diseases, but not so good at finding the cause for all symptoms. So there is an association, but it is not certain if the hypothyroidism, or thyroid autoimmunity is the cause (Kotak PS, Kadam A, Acharya S, Kumar S, Varma A. Beyond the Thyroid: A Narrative Review of Extra-thyroidal Manifestations in Hashimoto's Disease. Cureus. 2024 Oct 9;16(10):e71126. doi: 10.7759/cureus.71126. PMID: 39525250; PMCID: PMC11544504). https://pmc.ncbi.nlm.nih.gov/articles/PMC11544504/

From a practical perspective, it is good to know that no serious underlying problem has been found and there is a good chance that her symptoms will continue to get better. I think in these circumstances, while parents should not ignore their children’s symptoms, it helps to try to maintain a normal daily routine and encourage physical activity.

Was I incorrect to assume that the constipation would get better with the introduction of levothyroxine? Constipation is a common symptom of hypothyroidism, but it has many other causes. If it is caused by the hypothyroidism one would expect it to get better or resolve with treatment.

Should her selenium be tested? It would be very unusual for people who live in the UK, and who have a reasonably balanced diet, to become selenium deficient. One large study found that selenium supplements in people with Hashimoto’s disease made no difference to symptoms or quality of life. Just one comment about persistent fatigue. To be confident that the treatment for hypothyroidism is optimal, one has to be certain that no tablets are missed, that they are taken on an empty stomach and no food or drink (other than plain water) is consumed for at least 30 minutes. Thyroid hormone levels need to be normal and stable for at least six months before one can assume that there are other contributors to fatigue. This seems easy to achieve, but unfortunately not so in practice. At any one time, about half of people on levothyroxine have thyroid blood tests outside the normal range. I am not suggesting that your daughter should be subjected to more regular blood testing than she already has to endure, but attention to the above simple rules is important.

One more thought, drawn from my own experience as an endocrinologist, physician, patient and parent: perhaps the single most helpful course of action is to share your concerns with your daughter’s doctor. The doctor will be in a position to provide the right kind of support and most appropriate advice. I would encourage you to trust him/her and, if possible, avoid trying to find answers to these questions unaided. I appreciate that there are significant hurdles that one has to negotiate to have lengthy and meaningful consultations with our healthcare providers, but there are ways around that. I wish you and your daughter all the best.

My thyroid peroxidase (TPO) antibodies are high but I have normal thyroid function tests, does this mean I have Hashimoto's?

Having TPO antibodies means a higher chance of developing hypothyroidism than the general population. The risk is around 2% per year. Some people, including some experts, will call this ’Hashimoto’s’, or ’Hashimoto’s thyroiditis’ or ‘Hashimoto’s disease’. I personally do not find any of these descriptors useful, not least because they medicalise something which merely describes potential risk. On principle, it is no different to the fact that height defines the risk of having a fracture of the neck of femur in post-menopausal women. It has been shown that the risk increases by 21% for every 10 cm increase in height (Armstrong ME, et al. Relationship of Height to Site-Specific Fracture Risk in Postmenopausal Women. J Bone Miner Res. 2016;31:725-31).  https://pubmed.ncbi.nlm.nih.gov/26572496/  Calling what you describe ‘Hashimoto’s disease’ is as misplaced in my view as calling tall post-menopausal women as having ‘tall stature disease'.

As an endocrinologist and physician, I always discouraged my students and trainees from ordering unnecessary tests. By that I mean tests that were unlikely to alter decision-making or treatment of a patient. Ordering a TPO antibody test is only useful if the thyroid blood tests show hypothyroidism, as it provides an answer to the cause of the underactive thyroid. Otherwise, it is of no value and indeed can lead to unnecessary concern. 

Are Graves’ disease patients more susceptible to having dental problems?

The literature suggests that hyperthyroidism is associated with increased risk of caries (decay and crumbling of a tooth or bone) and periodontal (gum) disease. When attempting to find the primary sources for these opinions, there is very little/reliable evidence, apart from the association of Graves’ disease with another autoimmune condition called Sjogren’s syndrome. Sjogren’s causes reduction of salivary secretions and it is well established that Sjogren’s causes significant dental problems. So, I am rather sceptical about the connection between Graves’ disease and dental problems. For what it’s worth, during my 40-odd years of treating patients with Graves’ disease I cannot recall encountering anyone with serious dental problems. 

Following a thyroidectomy or Radioactive Iodine treatment and therefore taking thyroxine, are there any particular foods you should avoid?

We hear an awful lot about diets but the evidence does not support the notion that special diets are of any value, unless there is an underlying medical diagnosis, for instance coeliac disease or lactose intolerance, made by a qualified medical practitioner and supported by appropriate tests (Larsen D, et al. Thyroid, diet, and alternative approaches. JCEM. 2022;107: 2973) https://pubmed.ncbi.nlm.nih.gov/35952387/
I hope this helps. 

It seems that while on a low dose of antithyroid medication very long term, it’s possible to become very low in T4 and T3, while your TSH is still non-existent and you still have positive TRAbs. Could this push you over into hypo and if so should your doctor then prescribe a low dose of levothyroxine to make up for the T4 deficit? 

Some people with Graves’ disease who are treated with antithyroid drugs or radioiodine can go through a phase whereby the serum TSH remains low, while they become hypothyroid (T4 and T3 become low and may experience symptoms of hypothyroidism). We think that in these cases the hypothalamus and pituitary are slow to recover from being suppressed by the thyroid overactivity. It is possible that TSH receptor antibodies play a role in this. However, this usually happens in patients who have severe hyperthyroidism, which has been untreated/poorly controlled for a long time. Furthermore, this phenomenon (low TSH associated with low T3 and T4) is transient and does not last beyond a few weeks or months, unless there is separate unrelated problem with the hypothalamus or pituitary. 

You are quite right that in the early phases of treatment of Graves’ disease, the serum TSH may be misleading. This is why the European Thyroid Association guidelines for the treatment of Graves’ disease, state that ‘thyroid function tests are reviewed 3–4 weeks after starting treatment, and the dose is titrated based on free T4 and free T3 levels.’(https://etj.bioscientifica.com/view/journals/etj/7/4/ETJ490384.xml). 

You will have noticed that the emphasis is on the free T4 and free T3, not the TSH, for this very reason. To avoid hypothyroidism, the dose of antithyroid drugs should be reduced, or levothyroxine in full replacement doses should be added while the initial full dose of antithyroid drugs is continued (what is known as ‘block and replace’).

It's my understanding a fully synthetic hormone like levothyroxine does not provide calcitonin which is needed to regulate calcium in the body, and the body’s natural mechanism is to steal the calcium from the bones. Why isn't naturally desiccated thyroid extract given?

Calcitonin is involved in calcium regulation. However, its role is unclear in adult humans. People with low or undetectable calcitonin show no adverse effects (https://www.yourhormones.info/hormones/calcitonin/). Calcitonin is a protein, so if taken by mouth it is broken down to its constituent amino acids and therefore has no biological activity if given orally. It is for the same reason that other protein hormones (like insulin) have to be given by injection. So any traces of calcitonin contained in desiccated thyroid extract are not absorbed. The roles of T1 and T2 in humans are unclear. 

Desiccated thyroid extract has been studied in two randomised controlled trials and compared to levothyroxine. Both studies showed no difference in quality of life compared to levothyroxine (Hoang Thanh D, et al. Desiccated thyroid extract compared with levothyroxine in the treatment of hypothyroidism: a randomized, double-blind, crossover study. JCEM. 2013:98;1982-1990 https://pubmed.ncbi.nlm.nih.gov/23539727/ and Shakir MKM, et al. "Comparative effectiveness of levothyroxine, desiccated thyroid extract, and levothyroxine+ liothyronine in hypothyroidism. JCEM. 2021;106: e4400-e4413 https://pubmed.ncbi.nlm.nih.gov/34185829/ 

Is there any research into the ongoing symptoms which some hypothyroid patients continue to suffer from? Research seems to be just about proving that they are not  caused by hypothyroidism, rather than any new thinking or ideas as to what is causing these symptoms.

Persistent symptoms may be due to a variety of different causes. Maybe we have not perfected how we replace thyroid hormones. This has been explored very extensively over the past 30 years and studies have been done to assess whether combination of T4 + T3, or T3 alone or desiccated thyroid extract, could address this problem. None of these treatments seem to be more effective than levothyroxine in alleviating symptoms. 

It is possible that a ‘slow release’ formulation of T3 can produce better results. There are at least three such formulations that I am aware of and at least two are currently undergoing clinical studies. We shall find out in the next 2-5 years. It could be that it is not the imperfections of the formulation of thyroid hormones that drives persistent symptoms, but the underlying autoimmune inflammation. 

Several other possibilities have also been proposed ( Perros P, et al. The enigma of persistent symptoms in hypothyroid patients treated with levothyroxine: A narrative review. Clinical Endocrinology. 2023; 98:461 (https://pubmed.ncbi.nlm.nih.gov/33783849/). In addition, there is a large proportion of the population (maybe as high as 10%) that suffers from ‘medically unexplained symptoms’, and people with hypothyroidism are as likely as anyone else to be affected by it. The book by Suzanne O’Sullivan ‘Sleeping Beauties’ gives a fascinating insight into this. I agree there is not enough research on persistent symptoms.

I am a 27-year-old male and for 8 years I’ve had TSH levels between 3.72 and 4.86 (FT4 is consistently lower end of normal). Symptoms include feeling colder than other people, daytime fatigue, and dry skin. I recently tested positive for thyroid peroxidase antibodies. Over the past 12 months I’ve had terrible insomnia,  This has had a massive impact on my ability to work/study and my social life, rendering me unable to function most days and having to drop out of university.
 I was told by GPs that TSH needs to be above 8 for treatment (even with antibodies and symptoms).
I have 3 interconnected questions relating to my experience:
1.    Do you think that mildly elevated TSH with high thyroid peroxidase antibodies could be impacting my sleep quality and maintenance negatively (not sleep onset)?
2.    If so, could treatment with levothyroxine help?
3.    If yes, do you have any tips on navigating the NHS to get a trial of treatment? 

I am sorry to hear that you have not been well. 

The association between insomnia and subclinical hypothyroidism is just an association. It may or may not be causally related. In fact it is possible that insomnia may have an effect on thyroid blood tests as has been shown in some studies (Xia L, et al. Alterations in hypothalamus-pituitary-adrenal/thyroid axes and gonadotropin-releasing hormone in the patients with primary insomnia: a clinical research. PloS one. 2013;8:e71065) https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0071065 The largest, most robust study has shown that people with subclinical hypothyroidism do not have any more symptoms than the background population (Carlé A, et al. Does subclinical hypothyroidism add any symptoms? Evidence from a Danish population-based study. The American Journal of Medicine. 2021;134:1115-26) https://pubmed.ncbi.nlm.nih.gov/33872585/ 

The diagnosis of subclinical hypothyroidism is based on biochemical tests. A single slightly elevated TSH is insufficient to make the diagnosis, because in up to 50% of cases it normalises after a few months without intervention (Calissendorff J, Falhammar H. To Treat or Not to Treat Subclinical Hypothyroidism, What Is the Evidence? Medicina (Kaunas). 2020;56:40) https://pubmed.ncbi.nlm.nih.gov/31963883/ Provided that a person has sustained subclinical hypothyroidism, a trial of treatment with levothyroxine is supported by NICE (https://cks.nice.org.uk/topics/hypothyroidism/management/subclinical-hypothyroidism-non-pregnant/) and other international guidelines like the European Thyroid Association (Pearce SH, et al. Management of subclinical hypothyroidism. Eur. Thyroid J. 2013;2:215–228). However, to offer thyroid hormone replacement to someone whose assessment shows no features of thyroid disease and thyroid blood tests are normal, would be inappropriate in my view. 

With regard to your three specific questions
1.On the grounds of probability it is unlikely that subclinical hypothyroidism in itself causes insomnia, but one has to have an open mind and not rule out that possibility. 

2. This can only be answered by the doctor who is involved in one’s care, and in addition requires consideration of how reliable the assessment of the effect on sleep will be, what would the course of action be if deemed unhelpful as well as helpful, how will potentially a placebo effect be handled, and most importantly have the numerous other potential causes of insomnia been addressed adequately? 

3.The best advice that I could give is this: if possible build a good and trusting relationship with your doctor and let him/her do the navigating with you. I hope this is of some help.