Friday, March 1, 2013


What is hypothyroidism?

It is a condition where the butterfly-shaped thyroid gland doesn't produce enough thyroid hormone. This gland, found at the base of the front of the neck, releases hormones that play an important role in functions ranging from conception and fetal growth to cardiovascular health, brain development, and metabolism [1].

Hypothyroidism (HT) is not the only thyroid related disorder found in those with DS – others include hyperthyroidism (not common), 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 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 [5] or deficiencies in nutrients – such as zinc – needed for function [6]. Research supports a possible link between the Epstein-Barr virus infection and autoimmune thyroid disorders [2].

While most medical literature report a higher rate of hypothyroidism in the DS population than that in the general population, the results are varied 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 [26], another showed that 73.6% of children had issues [3], and some report that it may reach 80-90% in early childhood [4].

How is hypothyroidism in those with DS detected? Why is it important?

Interestingly, the symptoms of Down syndrome match that of congenital hypothyroidism. The type of hypothyroidism experienced by many children and adults with Down syndrome is not detected by a TSH or T4 lab test. Cellular hypothyroidism is the term that has been used to describe what people with Down syndrome experience. The symptoms of this type of hypothyroidism are the same as hypothyroidism caused by a defect in the thyroid gland itself. The conversion of T4 to the active thyroid hormone T3 is imperative to the function of all cells. A second version of T3 exists that is called reverse T3. It is a stereoisomer, a mirror image, of active T3 and is inactive within the cell.

Physiologic processes that contribute 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 that are so common to people with Down syndrome.

Symptoms of HT include but are not limited to:  hypotonia (low muscle tone), dry skin, short neck, slow rate of growth, delayed development, enlarged tongue, constipation, lethargy and sometimes: a heart murmur and a herniated belly button [7]. These symptoms are all common to people with Down syndrome, making thyroid issues a top priority.

Since hypothyroid symptoms are so similar to the symptoms of Down syndrome, some doctors believe that hypothyroidism is part of the etiology of DS, and when left untreated, can significantly worsen developmental delays [4]. In fact, the thyroid hormones even regulate neurogenesis (production of new neurons) [8], which is vital to people with DS.

It's recommended that a diagnosis be made by taking into consideration classical symptoms such as slower growth; constipation; dry skin and lower basal temperature [9] as well as lab results [10].

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. 

67% of infants with DS were found to have thyroid issues. Before treatment with L-thyroxine, groups with high TSH were significantly shorter and heavier compared to the group with normal TSH. After treatment, the height and weight did not differ between the two groups [26].

There are two ways to detect, monitor and diagnose health of the thyroid gland. One is by observing the symptoms, especially taking the basal body temperature first thing in the morning. If the temperature is low and symptoms are present, HT is suspected. A diagnosis can be made by taking into consideration classical symptoms, such as slower growth; constipation; dry skin and lower basal temperature [9] as well as lab results [10].

The second way is via blood tests that are analyzed for 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 is trying 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 is usually an indication of hypothyroidism. Conversely, a “low” TSH with “high” T3 and/or T4 may mean hyperthyroidism.

Note that some parents hear from pediatricians or endocrinologists who refuse to treat hypothyroid symptoms because it is considered common or even “normal” in those with Down syndrome. This makes little sense, as an under-functioning gland is an under-functioning gland regardless of other diagnosis, 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 1 since elevated levels of circulating thyroid hormone 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 from this website:

TestLab LowOptimal RangeLab High
Free T40.81.2-1.31.8
Free T3230320-330420
Free T3**2.33.2-3.34.2
* New studies support a TSH of below 1 as optimal, rather than low [27].
**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 [15].

The thyroid influences the function of the hippocampus, which is the part of the brain that is responsible for neurogenesis (the creation of neurons) as well as 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) [22, 23]. 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) [22].

Deficiency of triiodothyronine (T3) has been seen to cause decreased growth of new blood vessels in the brain. T3 is also thought to protect against neurotoxicity and support nerve cell development [24].

Hypothyroidism can cause a decrease in the activity of GCL (an enzyme that is important for glutathione [GSH] production). GSH is among the strongest antioxidants in our body and is known to be below “normal” levels in people with Down Syndrome, perhaps due to increased oxidative stress. In fact, administration of thyroid hormone to astrocytes (the largest and most numerous neuroglial cells in the brain and spinal cord) resulted in a rapid increase in GSH levels [25].

The above results make it abundantly clear that a lot of cognitive delay in children with Down syndrome (and other conditions) could potentially be a result of hypothyroidism.

Since there is a normal TSH surge soon after birth, neonatal screening tests for hypothyroidism may not give an accurate reflection of 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 [27].

Respiratory problems due to enlarged tongue, episodes of apnea, noisy respiration and nasal obstruction could point towards a hypothyroid state in older infants. Affected infants cry little, sleep more, have poor appetite and show general sluggishness. An umbilical hernia, low temperature and slow pulse are also signs that should be taken seriously [16].

By 6 months of age, the clinical diagnosis of hypothyroidism could be easier to measure. But if not treated, older children may show severe delays from the hypothyroidism and may stand out in stark contrast to age related peers with Down syndrome [16].

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.

The most common treatment is taking the synthetic version of the hormone thyroxine (T4). T4 converts to triiodothyronine (T3), which is 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 or inhibit the effects of the medicine, including soy products, high-fiber foods, iron and calcium supplements and antacids that contain aluminum or magnesium [17].

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 [29]). [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 [18]. Natural thyroid, due to its source, has a much more varied spectrum of thyroid hormones available for the body to use including T3. “Stop the Thyroid Madness” [19] reports anecdotal evidence: many patients report feeling better on natural thyroid medication over synthetic medication. One study showed that in the majority of cases, treatment with 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 [20].

Along with treatment, it can be helpful to add these changes to your diet and lifestyle. Some parents choose to 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 restoration of the thyroid function with diet and nutrition alone.

  • Iodine supplementation: It is important to note that too much iodine can also cause hypothyroid, so it is important to monitor this and take this with consultation with your physician.
  • Selenium, Zinc, Iron, and Copper are all needed for healthy thyroid function. Supplementation with Zinc has been shown to improve thyroid function [5]. Selenium, in particular, is needed to synthesize T3 in the body. Note that iron can interfere with 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: there is some evidence that these can help improve thyroid hormone action.
  • L-Tyrosine is an amino acid used by the thyroid gland to synthesize the hormones.
  • Avoid soy products (soy is widely considered a goitrogen).
  • Avoid or filter tap water. Fluoride and chloride are added to most public drinking water supplies. These are halogens and can replace iodine (which is 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:

  3. Any of the references below are good sources of thyroid related information`
  1. Catherine C. Thompson and Gregory B. Potter. Thyroid Hormone Action in Neural Development. Oxford Journals Volume 10, Issue 10 Pp. 939-945
  2. 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.
  3. 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.
  4. D. Michael, MD, Personal Communication
  5. Len Leshin MD:
  6. 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.
  7. Coleman M. Thyroid dysfunction in Down syndrome: A review. Down Syndrome Research and Practice. 1994;2(3);112-115.
  8. Desouza LALadiwala UDaniel SMAgashe SVaidya RAVaidya VA. Thyroid hormone regulates hippocampal neurogenesis in the adult rat brain. Mol Cell Neurosci. 2005 Jul;29(3):414-26.
  9. Stop the Thyroid Madness:
  10. Andi Durkin:
  12. 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.
  13. 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.
  16. Prasher VP. Down Syndrome and Thyroid Disorders: A Review. Down Syndrome Research and Practice. 1999;6(1);25-42.
  17. Mayo Clinic:
 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
  19. Stop The Thyroid Madness:
  20. Gaby AR. Sub-laboratory hyperthyroidism and the empirical use of Armour thyroid. Altern. Med. Rev. 2004 Jun;9(2):157-79.
  21. 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.
  22. Thyroid hormone regulates hippocampal brain neurogenesis in the adult rat Mol Cell Neurosci. 2005 Jul;29(3):414-26.
  23. Thyroxin regulates BDNF expression to promote survival of injured neurons. Mol Cell Neurosci. 2009 Dec;42(4):408-18. Epub 2009 Sep 16.
  24. Modulation of adult hippocampal neurogenesis by thyroid hormones: implications in depressive-like behavior. Mol Psychiatry. 2006 Apr;11(4):361-71.
  25. 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.
  26. 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.
  27. 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.
  28. 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 Paediatrics. 13th edition, London: W.B. Saunders Company.
  29. Stop The Thyroid Madness:
  • 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