Thyroid reference ranges are misleadingly broad, and many are told they are “fine” (when they are actually hypothyroid), simply because they’re within the reference range. My research indicates that most people in good health have values in the upper half of the range for Total T4 and Free T3. Free T4 should be mid-range or higher, but how high depends on the individual. In some, high FT4 seems to correlate with high reverse T3 and different illnesses (poor physical function, mood disorders, liver or kidney problems). [1,2,3] A Total T4 may help determine whether there is room for an increase in T4 medication or not, because sometimes there is a disparity between the Free and Total T4. Where one feels best in this upper half is very individual and one should use non-lab indicators to guide their dose. Some people have a condition called thyroid resistance, and their levels need to be above the thyroid reference ranges for them to feel well. Some bipolar patients have shown improvement taking extremely high doses of levothyroxine (320 mcg T4 daily, on average).  This is rare, however, and non-lab indicators are the best guide to determine someone’s optimal dose. Here are some physical symptoms that can indicate if someone is still somewhat hypothyroid:
- dry skin and rough, cracked heels
- thin hair (hair loss is also common with too much thyroid)
- thin eyebrows; outer third of eyebrow thin or missing
- pulse below 70 or sometimes, over 90 beats per minute
- respiration rate (breaths per minute) less than 12
- morning basal temperature below 97.8 oF or 36.5 oC
- cold hands or feet when others feel fine
- constipation: bowel movements come out as hard pellets after heavy pushing
- nightmares/disturbed sleep
The Free T3 optimal range being above the midpoint is corroborated by three different sources. Dr. Romeo Mariano, a physician psychiatrist in Monterey, California, has found patients achieve both physical and mental wellness once they are at that level.  Elaine Moore, a Graves’ disease specialist, finds patients without a thyroid (RAI or thyroidectomy) do best when their Free T3 is just above-midrange.  And the Director of Quality Assurance at Quest Labs in the State of Florida says the range for T3 is actually a negatively skewed curve.  In other words, the majority of the lab values are in the upper half; it is NOT a symmetrical distribution. The median and mode are to the right of the mean. The curve from the left has a steep ascent, peaks to the right of the midpoint, then has a much more gradual descent to the right. This indicates that while people can theoretically be normal at the bottom of the range, the majority of people have values mid-range or higher. Keep in mind, however, that there are always “outliers” that don’t follow the majority. There may also be other factors (like low iron or ferritin) that prevent some patients from comfortably reaching higher levels. [thyroid requires iron, cortisol, selenium, iodine] Common sense tells us that symptoms should always trump labs.
The best analogy for the T3 reference range is height. According to Wikipedia, the shortest man living today (1/11) is 26”, and the tallest 8’2”. If I were to make a reference range for male height, the chart should have a bottom value of 26” and a top value of 8’2”. Ranges are supposed to be based on a statistical average (mean), with two standard deviations (95%) around the mean at either end defining the range. This would throw out the extreme outliers like the shortest and tallest man. But, for example’s sake, if I took the average of these two values, I would have a height of 5’ 2”. Off the top of my head, I would guess that most men have a height above this midpoint, so this curve is negatively skewed, with more values to the right than left. There are a few healthy, normal men who fall just to the left of this midpoint, but they are few compared to the numbers to the right of the midpoint. Below a certain point, there are hormonal problems (such as lack of growth hormone) affecting the height. This is analogous to the thyroid reference ranges. Many people are not formally diagnosed as hypothyroid, and their lab results become the lower part of the thyroid reference ranges. In healthy people, the majority of the values are above the midpoint.
Research shows that T3 is a much better predictor of thyroid status than T4. One study using levothyroxine showed that patients with over-range T4 levels did not show signs of being clinically hyperthyroid unless their T3 levels were also over range. 
Is there a common dosage that most people take that one should aim for? Is any type of prescription thyroid replacement better than others? Emphatically, NO! First person testimonies show that people are taking T4-only, T4 + T3, T3-only, desiccated thyroid, and combinations of the above. I have read case studies of people successfully taking 12 grains. Because of the TSH feedback loop, it is very difficult to just “supplement” thyroid hormone; any external dose usually suppresses a person’s normal production. Once a person suppresses their own thyroid production, they must then raise the dose high enough for their hypothyroid symptoms to disappear. Someone who has never been on desiccated thyroid should have labs run once they reach 1.5 grains and have been on that dose for 6 weeks. At that point, some people are already at optimal levels, while others are still in the lower part of the thyroid reference ranges. Or, like me, they will have an imbalance in their FT3 and FT4 levels, with FT3 much higher in the reference range than FT4. This is because desiccated thyroid (from pigs) has a much higher ratio of T3 to T4 than a normal human thyroid gland. Raising to 3 grains can be dangerous for some people; it is a serious overdose for them and can result in typical hyperthyroid symptoms like fatigue, muscle weakness, shortness of breath, hair loss, etc. which can be mistaken for hypothyroid symptoms. And yet, other people need doses higher than 3 grains. That’s why periodic lab work should be performed.
My observation from reading thousands of posts on various thyroid forums is that many need far less than 3 grains of desiccated thyroid. In fact, I know several people who are successfully combining 1 grain with different amounts of T4. Their T4 dose loosely correlates with their weight. These people have lab results that are high in T3 and low in T4 on desiccated thyroid. The addition of T4 balances out their levels. Likewise, others might do better adding some T3 to their dose if their lab results show them high in T4 and low in T3. They might also want to look into conversion problems. Everyone’s optimal thyroid medication and dosage is very individual, and age, weight, and gender have nothing to do with one’s optimal dose. To insist that only one type of medication will work for everyone, be it synthetic T4, natural desiccated thyroid, or synthetic T3-only, is illogical, given that everyone’s biochemistry is different. Symptoms should be used in conjunction with where one’s lab results fall within the thyroid reference ranges to determine an optimal dose. If thyroid lab results (either Free T3 or Free T4) are below the midpoint of the range and someone still exhibits multiple, common hypothyroid symptoms (like dry skin and feeling cold all the time), it would make sense to increase the thyroid hormone that is deficient by adding either a little more T4 or T3, or both. Few people feel well when their thyroid hormone levels are at the bottom of the reference range. Thousands of hypothyroid patients seeking help on internet forums are living proof that reference ranges are too broad.
- Annewieke W. van den Beld, Theo J. Visser, Richard A. Feelders, Diederick E. Grobbee, and Steven W. J. Lamberts. Thyroid Hormone Concentrations, Disease, Physical Function, and Mortality in Elderly Men. The Journal of Clinical Endocrinology & Metabolism . 2005, 90(12):6403–6409. http://jcem.endojournals.org/cgi/content/abstract/90/12/6403
- Stephen T.H. Sokolov, Stanley P. Kutcher, Russell T. Joffe. Basal Thyroid Indices in Adolescent Depression and Bipolar Disorder. Journal of the American Academy of Child & Adolescent Psychiatry – May 1994 (Vol. 33, Issue 4, Pages 469-475). http://www.ncbi.nlm.nih.gov/pubmed/8005899
- Chopra IJ, Chopra U, Smith SR, Reza M, Solomon DH. Reciprocal changes in serum concentrations of 3,3′,5-triiodothyronine (T3) in systemic illnesses. J Clin Endocrinol Metab. 1975 Dec;41(06):1043-9. http://www.ncbi.nlm.nih.gov/pubmed/812882
- Bauer M, London ED, Rasgon N, Berman SM, Frye MA, Altshuler LL, Mandelkern MA, Bramen J, Voytek B, Woods R, Mazziotta JC, Whybrow PC. Supraphysiological doses of levothyroxine alter regional cerebral metabolism and improve mood in bipolar depression. Mol Psychiatry. 2005 May;10(5):456-69. http://www.ncbi.nlm.nih.gov/pubmed/15724143
- Dr. Romeo Mariano, Thyroid Test Results?, July 26, 2010, Neurotransmitters, Hormones, Cytokines and other Intercellular Signals. Definitive Mind Forums.
- Dr. Williams, clinical pathologist, Director of Quality Assurance for Quest Labs in Florida. Phone interview. Oct. 19, 2010.
- M. Rendell, D. Salmon. ‘Chemical Hyperthyroidism’: The Significance Of Elevated Serum Thyroxine Levels In L-Thyroxine Treated Individuals. Clinical Endocrinology. Volume 22, Issue 6, pages 693–700, June 1985. http://www.ncbi.nlm.nih.gov/pubmed/4017260