The thyroid is a butterfly-shaped gland found at the base of the front of the neck that releases hormones that play an essential role in functions ranging from conception and fetal growth to cardiovascular health, brain development, and metabolism [1]. Hypothyroidism (HT) is a condition in which the thyroid doesn't produce enough thyroid hormone. HT is not the only thyroid-related disorder found in those with DS – other less common ones include hyperthyroidism, benign or malignant thyroid nodules, and goiter.
Hypothyroidism usually occurs because of autoimmune conditions, congenital disorders, cancer, celiac disease or gluten sensitivity, iodine deficiency, poor nutrition, and the treatment of hyperthyroidism. The high incidence of thyroid disorders in people with DS could be from a malformed or under-developed thyroid gland at birth [2] or deficiencies in nutrients – such as zinc – needed for function [3]. Research supports a possible link between the Epstein-Barr virus infection and autoimmune thyroid disorders [4].
How common is hypothyroidism in the DS population?
While most medical literature reports a higher rate of hypothyroidism in the DS population than in the general population, the results vary because each study may use a different set of criteria to define hypothyroidism. One study showed 67% of infants with DS were found to have thyroid issues [5], another showed that 73.6% of children had problems [6], and some report that it may reach 80-90% in early childhood [7].
How is hypothyroidism in those with DS detected? Why is it important?
Interestingly, the symptoms of Down syndrome match that of congenital hypothyroidism. TSH or T4 lab test can not detect the type of hypothyroidism experienced by many children and adults with Down syndrome. Cellular hypothyroidism is the term used to describe what people with Down syndrome experience. The symptoms of this type of hypothyroidism are the same as those that a defect in the thyroid gland itself can cause.
The conversion of T4 to the active thyroid hormone T3 is imperative to the function of all cells. A second version of T3 exists, which is called reverse T3. It is a stereoisomer, a mirror image, of active T3 and is inactive within the cell.
Physiologic processes contributing to an elevated reverse T3 are low iron, low or high cortisol levels, inflammation, and oxidative stress. People with Down syndrome experience all of these processes. Active thyroid hormone is essential for the functioning of literally every cell of the body. Without it, people experience slow gut motility, slow growth, delayed cognition, and many other symptoms common to people with Down syndrome.
What are the symptoms of hypothyroidism?
Symptoms of HT include but are not limited to hypotonia (low muscle tone), dry skin, short neck, slow growth rate, delayed development, enlarged tongue, constipation, lethargy, and sometimes: a heart murmur and a herniated belly button [8]. These symptoms are all common to people with Down syndrome, making thyroid issues a top priority.
Since hypothyroid symptoms are similar to the common traits of a person with Down syndrome, some doctors believe that hypothyroidism is part of the cause of these symptoms and, when left untreated, can significantly worsen developmental delays [7]. In fact, the thyroid hormones even regulate neurogenesis (production of new neurons) [9], which is vital to people with DS.
A diagnosis should be made by considering classic symptoms such as slower growth, constipation, dry skin, lower basal temperature [10], and lab results [11].
Why should hypothyroidism be treated?
Treating the thyroid at any age is beneficial. The earlier, the better, since HT, untreated, can stunt growth, slow cognitive development, and impair digestion, which can further cause a cascade of developmental issues.
Studies found that 67% of infants with DS have thyroid issues. Before treatment with L-thyroxine, groups with high TSH were significantly shorter and heavier than those with normal TSH. After treatment, the height and weight did not differ between the two groups [5].
How is hypothyroidism detected?
There are two ways to detect, monitor, and diagnose the health of the thyroid gland. One way considers the symptoms, especially by taking the basal body temperature first thing in the morning. If the temperature is low and symptoms are present, HT is suspected. Monitoring classic symptoms such as slower growth, constipation, dry skin, lower basal temperature [9], and lab results [11] can guide the diagnosis.
The second way uses blood tests that analyze levels of thyroxine (T4) and triiodothyronine (T3), both of which are the hormones produced by the thyroid gland and the Thyroid Stimulating Hormone (TSH). TSH levels are higher than the healthy range when the pituitary gland tries to tell the thyroid to secrete more hormones because it detects low levels of T3 and T4 in the blood. Therefore, a “high” TSH combined with “low” T3 and/or T4 usually indicates hypothyroidism. Conversely, a “low” TSH with “high” T3 and/or T4 may mean hyperthyroidism.
Some pediatricians and endocrinologists refuse to treat hypothyroid symptoms because these traits are considered common or even “normal” in those with Down syndrome. This practice makes little sense. An under-functioning gland is an under-functioning gland regardless of other diagnoses and should be treated.
In January 2003, the America Association of Clinical Endocrinologists set suggested guidelines for doctors to consider treatment of patients who test outside the target TSH level of 0.3 to 3.0. [11] Patients who test outside the target TSH have sub-clinical hypothyroidism. In fact, 87% of children with Down syndrome have sub-clinical hypothyroidism [12]. Parents have seen positive results with doctors who treat their children with thyroid symptoms and sub-clinical hypothyroidism instead of waiting for the TSH to increase to an out-of-range level.
A 2016 study supports treatment when the TSH is below one since elevated circulating thyroid hormone levels do not cause hyperthyroidism [13].
Dr. Rind’s website [14] has an in-depth analysis of different thyroid parameters and how to interpret them. Here is a range of “normal” values posted on this website:
| Test | Lab Low | Optimal Range | Lab High |
| TSH* | 0.5 | 1.3-1.8* | 5.0 |
| Free T4 | 0.8 | 1.2-1.3 | 1.8 |
| Free T3 | 230 | 320-330 | 420 |
| Free T3** | 2.3 | 3.2-3.3 | 4.2 |
| * New studies support a TSH of below 1 as optimal, rather than low [15]. **Some labs divide FT3 results by 100 thus 230 is the same as 2.3, etc. |
Typically, hypothyroid shows low T4 and T3 (which is usually more elevated than T4). For a full analysis of all possible combinations of TSH/T4/T3, please refer to Dr. Rind’s Thyroid Scale Matrix [16].
What role does the thyroid play in the nervous system/brain function?
The thyroid influences the operation of the hippocampus, which is the part of the brain responsible for neurogenesis (the creation of neurons) and memory formation, organization, and storage. The thyroid hormone affects how a cell develops and matures into glial cells (cells that surround neurons, providing support and insulation between neurons) and also helps regulate the production of neural stem cells. After neuron injury, thyroxin adjusts the expression of the Nerve Growth Factor (BDNF) [17, 18]. In one study, hypothyroidism caused a 30% reduction in neuron generation in the hippocampus along with impairment in learning, short-term and long-term memory, and synaptic plasticity (the ability of neurons to change the strength and intensity of connections between them) [17].
A triiodothyronine (T3) deficiency can cause decreased growth of new blood vessels in the brain. T3 protects against neurotoxicity and supports nerve cell development [19].
Hypothyroidism can cause a decrease in the activity of GCL (an enzyme that is important for glutathione [GSH] production). GSH is among the most potent antioxidants in our body and is usually low in people with Down Syndrome, perhaps due to increased oxidative stress. In fact, administering thyroid hormone to astrocytes (the largest and most numerous neuroglial cells in the brain and spinal cord) caused a rapid increase in GSH levels [20]. These results make it abundantly clear that hypothyroidism could produce a cognitive delay in children with DS (and other conditions).
How should hypothyroidism be evaluated in infants?
Since there is a natural TSH surge soon after birth, neonatal screening tests for hypothyroidism may not accurately reflect thyroid function. So, careful monitoring of symptoms, such as body temperature, is needed instead. Clues such as feeding difficulties, slow movement, lack of interest, excessive sleepiness, and choking spells during nursing can also be early signs of hypothyroidism [21].
Respiratory problems due to an enlarged tongue, apnea episodes, noisy respiration, and nasal obstruction could point toward a hypothyroid state in older infants. Affected infants cry little, sleep more, have a poor appetite, and show general sluggishness. An umbilical hernia, low temperature, and slow pulse are also signs that should be taken seriously [22].
By six months of age, the clinical diagnosis of hypothyroidism could be easier to measure. But if not treated, older children may show severe delays from hypothyroidism and stand out in stark contrast to age-related peers with DS [22].
Parents can request a thyroid finger-prick test to make testing for all ages easier. Not all insurance will cover the cost of this test (approximately $56), but parents may choose to use self-pay.
What is the treatment for hypothyroidism?
The most common treatment is taking the synthetic version of the hormone thyroxine (T4). T4 converts to triiodothyronine (T3), the most bioactive or usable form in the blood. Some people may not respond well to T4 and may need a synthetic version of T3. Remember that it is best to wait 4 hours after thyroid medication before consuming anything that may interact with or inhibit the effects of the medicine, including soy products, high-fiber foods, iron and calcium supplements, and antacids that contain aluminum or magnesium [23].
Desiccated thyroid extracts (natural thyroid hormone supplements) made from the thyroid glands of mammals, usually pigs, are also available. Natural brands include Acella; Naturethroid; Westhroid; Thyroid-S; Thiroyd; Armour (if chewed, not swallowed [24]). [Note: In Australia, “thyroid extract” is found in compounding pharmacies; in Canada, Thyroid is a popular brand.]
Fluctuation in potency has been in question for natural hormones, but the FDA has also found that problem in synthetic thyroid medication [25]. Due to its source, natural thyroid has a much more varied spectrum of thyroid hormones available for the body, including T3. “Stop the Thyroid Madness” [26] reports anecdotal evidence: many patients report feeling better on natural thyroid medication over synthetic medication. One study showed that in most cases, the use of thyroid hormone resulted in significant improvement in chronic symptoms that had failed to respond to various conventional and alternative treatments. In some cases, the desiccated thyroid produced better results than levothyroxine [27].
How can diet and nutrition support the thyroid?
Along with treatment, adding these changes to your diet and lifestyle can be helpful. Some parents support their loved one's thyroid health with nutritional intervention in hopes of weaning them off thyroid medications. Although not common, some parents have seen the restoration of thyroid function with diet and nutrition alone.
- Iodine supplementation: Too much iodine can also cause hypothyroidism, so monitoring and taking it under a physician’s guidance is recommended.
- Selenium, Zinc, Iron, and Copper are all needed for healthy thyroid function. Supplementation with Zinc improves thyroid function [2]. Selenium, in particular, is needed to synthesize T3 in the body. Note that iron can interfere with the absorption of medication. Also, copper is usually high in the T21 population, so supplementation is not usually necessary; individual evaluation is warranted.
- Omega-3 fatty acids: evidence shows that these can help improve thyroid hormone action.
- L-Tyrosine is an amino acid the thyroid gland uses to synthesize hormones.
- Avoid soy products since it is widely considered goitrogen.
- Avoid or filter tap water. Fluoride and chloride are added to most public drinking water supplies. These halogens can replace iodine (also a halogen) in the body and potentially cause iodine deficiency.
Video on Down syndrome and Hypothyroidism
The research is not as up-to-date as this article, but this is an excellent overview and explanation: http://m.youtube.com/watch?v=6si37L76bdk
What are good thyroid forums to join?
http://forums.about.com/ab-thyroid
Where can I go for more information?
http://www.drrind.com/thyroid-scale
Any of the references below are good sources of thyroid-related information`
- Catherine C. Thompson and Gregory B. Potter. Thyroid Hormone Action in Neural Development. Oxford Journals Volume 10, Issue 10 Pp. 939-945
- Len Leshin MD: http://www.ds-health.com/ (6)Calcaterra V, Crivicich E, De Silvestri A, Amariti R, Clemente AM, Bassanese F, Regalbuto C, Vinci F, Albertini R, Larizza D. Timing, prevalence, and dynamics of thyroid disorders in children and adolescents affected with Down syndrome. J Pediatr Endocrinol Metab. 2020 Jul 28;33(7):885-891. doi: 10.1515/jpem-2020-0119. PMID: 32653879.
- Licastro, F., Mocchegiani, E., Zannotti, M., Arena, G., Masi, M. & Fabris, N. (1992). Zinc affects the metabolism of thyroid hormones in children with Down's syndrome: Normalization of thyroid stimulating hormone and of reversal triiodothyronine plasmic levels by dietary zinc supplementation. International Journal of Neuroscience, 65, 259-268.
- Dittfeld A, Gwizdek K, Michalski M, Wojnicz R. A possible link between the Epstein-Barr virus infection and autoimmune thyroid disorders. Cent Eur J Immunol. 2016;41(3):297-301. doi: 10.5114/ceji.2016.63130. Epub 2016 Oct 25. PMID: 27833448; PMCID: PMC5099387.
- AlAaraj N, Soliman AT, Itani M, Khalil A, De Sanctis V. Prevalence of thyroid dysfunctions in infants and children with Down Syndrome (DS) and the effect of thyroxine treatment on linear growth and weight gain in treated subjects versus DS subjects with normal thyroid function: a controlled study. Acta Biomed. 2019 Sep 23;90(8-S):36-42. doi: 10.23750/abm.v90i8-S.8503. PMID: 31544805; PMCID: PMC7233681.
- Calcaterra V, Crivicich E, De Silvestri A, Amariti R, Clemente AM, Bassanese F, Regalbuto C, Vinci F, Albertini R, Larizza D. Timing, prevalence, and dynamics of thyroid disorders in children and adolescents affected with Down syndrome. J Pediatr Endocrinol Metab. 2020 Jul 28;33(7):885-891. doi: 10.1515/jpem-2020-0119. PMID: 32653879.
- D. Michael, MD, Personal Communication
- Coleman M. Thyroid dysfunction in Down syndrome: A review. Down Syndrome Research and Practice. 1994;2(3);112-115. http://www.down-syndrome.org/reviews/40/
- Desouza LA, Ladiwala U, Daniel SM, Agashe S, Vaidya RA, Vaidya VA. Thyroid hormone regulates hippocampal neurogenesis in the adult rat brain. Mol Cell Neurosci. 2005 Jul;29(3):414-26.
- Stop the Thyroid Madness: http://www.stopthethyroidmadness.com/temperature/
- http://dsdaytoday.blogspot.com/2011/04/thyroid-ds-go-hand-in-hand.html
- http://thyroid.about.com/od/gettestedanddiagnosed/a/tshtestwars.htm
- Szeliga K, Antosz A, Skrzynska K, Kalina-Faska B, Januszek-Trzciakowska A, Gawlik A. Subclinical Hypothyroidism as the Most Common Thyroid Dysfunction Status in Children With Down's Syndrome. Front Endocrinol (Lausanne). 2022 Jan 4;12:782865. doi: 10.3389/fendo.2021.782865. PMID: 35058880; PMCID: PMC8764180.
- Kelly T, Denmark L, Lieberman DZ. Elevated levels of circulating thyroid hormone do not cause the medical sequelae of hyperthyroidism. Prog Neuropsychopharmacol Biol Psychiatry. 2016 Nov 3;71:1-6. doi: 10.1016/j.pnpbp.2016.06.001. Epub 2016 Jun 11. PMID: 27302764.
- http://www.drrind.com
- Thyroid hormone promotes glutathione synthesis in astrocytes by up regulation of glutamate cysteine ligase through differential stimulation of its catalytic and modulator subunit mRNAs. Free Radic Biol Med. 2007 Mar 1;42(5):617-26. Epub 2006 Dec 15.
- http://www.drrind.com/therapies/thyroid-scale-matrix
- Thyroid hormone regulates hippocampal brain neurogenesis in the adult rat Mol Cell Neurosci. 2005 Jul;29(3):414-26.
- Thyroxin regulates BDNF expression to promote survival of injured neurons. Mol Cell Neurosci. 2009 Dec;42(4):408-18. Epub 2009 Sep 16.
- Modulation of adult hippocampal neurogenesis by thyroid hormones: implications in depressive-like behavior. Mol Psychiatry. 2006 Apr;11(4):361-71.
- Stimulatory effects of thyroid hormone on brain angiogenesis in vivo and in vitro. J Cereb Blood Flow Metab. 2010 Feb;30(2):323-35. Epub 2009 Oct 28.
- Prasher VP. Down Syndrome and Thyroid Disorders: A Review. Down Syndrome Research and Practice. 1999;6(1);25-42. http://www.down-syndrome.org/reviews/95/
- Mayo Clinic: http://www.mayoclinic.com/health/hypothyroidism/DS00353/
- Stop the Thyroid Madness: http://www.stopthethyroidmadness.com/2010/04/25/how-to-make-reformulated-armour-and-naturethroid-work/
- http://www.thyroid-info.com/articles/synthroidproblems.htm Synthroid Has a Long History of Problems, Says FDA In Denying Synthroid's Request for Special Approval Status, FDA's Scathing Letter Outlines History of Subpotent Product, Inconsistency and Poor Stability by Mary Shomon
- Stop The Thyroid Madness: http://www.stopthethyroidmadness.com/armour-vs-other-brands/
- Gaby AR. Sub-laboratory hyperthyroidism and the empirical use of Armour thyroid. Altern. Med. Rev. 2004 Jun;9(2):157-79.
- Behrman, R.E., Vaughan, V.C. & Nelson, W.E. (1987). Disorders of thyroid gland. In R.E. Behrman, V.C. Vaughan, and W.E. Nelson (Eds.). Nelson Text Book of Pediatrics. 13th edition, London: W.B. Saunders Company.
- apnea - a pause in external breathing.
- bioactive - a substance that, in a chemical state, reacts with any cell tissue in the body.
- central nervous system - consisting of the brain and spinal cord.
- etiology - the cause of a disease or condition.
- glial cells - specialized cells that surround neurons, providing mechanical and physical support and electrical insulation between neurons.
- goitrogens - a substance that interferes with thyroid function.
- hippocampus - the part of the brain that is involved in memory forming, organizing and storing.
- metabolism- the process of breaking down food or other organic molecules in the body to create energy, and/or using energy to create different cell components.
- nervous system - a complex, sophisticated system that regulates and coordinates body activities. It is made up of two major divisions, including the following:
- neurogenesis - the process by which new nerve cells are generated.
- peripheral nervous system - consisting of all neural elements.
- sub-clinical hypothyroidism - patients who test outside the target TSH range
