Thyroid hormones

Until recently, occurring hormonal changes that perceptibly inhibit physical, sexual, cognitive functions etc. were attributed to growing old, and victims of these changes were expected to accept the fact that their bodies were entering into a long degenerative process that would someday result in death.

 A remarkable amount of data has been compiled that indicates many of the diseases that this middle-aged population begins experiencing, (including depression, chronic fatigue syndrome, and heart disease) are directly related to hormone imbalances that are correctable with currently available drug and nutrient therapies. To the patients’ detriment, conventional doctors are increasingly prescribing drugs to treat depression, elevated cholesterol, angina and a host of diseases that may be caused by an underlying hormone imbalance.

In particular, insufficiency of the Thyroid hormone causes bodily functions to slow down and is often mistaken for depression. Other effects of low thyroid status include panic attacks, constipation, impotence, unexplained weight change, paranoid psychosis and dementia. Also, hair becomes coarse and dry and skin becomes dry, scaly and thick, the eyelids droop and the outside ends of the eyebrows slowly fall out. Many people develop carpal tunnel syndrome and their facial expression become dull.

Many structural or functional abnormalities of the Thyroid gland can lead to deficient production of thyroid hormones. The clinical state resulting therefrom is termed hypothyroidism. Hypothyroidism is one of the most under-diagnosed and important conditions in the world. It has been called the “unsuspected illness” and accounts for a great number of complaints in children, adolescents and adults.

Hypothyroidism has been known to cause serious adverse effects on the cardiovascular system (decreased heart rate and pulse pressure; low-output congestive heart failure), gastrointestinal system (decreased appetite), musculo-skeletal system (stiffness and muscle fatigue), renal system (impaired renal blood flow), and metabolic system (increased cholesterol, triglycerides and homocysteine; decreased hormone degradation). 

Now a day, the diagnosis of this illness by conventional doctors and endocrinologists is made almost exclusively from blood tests. Routinely, Thyroxin (T4) and Thyroid Stimulating Hormone (TSH) are measured in plasma or serum. In addition to that, a protein that binds (TBG) to T4 is also measured. From this protein and T4, a Free T4 is calculated. Another approach is the use of the “analogue” method, where a synthetic molecule similar to T4 (T4 analogue) is created that does not bind to TBG but competes with non-bound (Free) T4 for anti-T4 antibody. This analogue is labeled with an isotope or enzyme system, so that the amount of analogue bound to the antibody is proportional to the amount of Free T4 available. Apparently, these types of tests are assumed to differentiate euthyroid persons from hyperthyroid and hypothyroid patients.

With respect to plasma T3, it is somewhat paradoxical that although T3 is the major metabolically active thyroid hormone, its plasma concentration does not necessarily connote any clinical symptom. Concentration of T3 in plasma changes in fasting, in acute and chronic non-thyroidal diseases and with age. For all these reasons T3 value is too non-specific to serve as a useful routine diagnostic test. Approximately 6 ug of T3 are secreted by the thyroid gland each day, with 80% of the total daily production of T3 (24ug) arising from peripheral deiodination of T4; of this only 0.3% is in Free form. Plasma concentration of Free T3 in normal adults is 300 pg/dl and that of Total T3 is 120 ng/dl. The sensitivity of the presently available assay for Free T3 is 125 pg/dl and that of Total T3 is 30 ng/dl. 

The Free thyroid hormones in plasma are in equilibrium with protein-bound thyroid hormones in the tissues. Free thyroid hormones are added to the circulating pool by the thyroid. It is the Free hormones in plasma that are physiologically active form to enter cells and to exert metabolic control.  

T4 is considered to be the prohormone for the metabolically active thyroid hormone T3. The production of T3 by 5’monodeiodination of T4 by the peripheral tissue is known to be tightly autoregulated so as to maintain a normal circulating T3 level in the face of T4 fluctuation. These considerations suggest a circulating T3 level, and thereby a euthyroid state is maintained despite wide fluctuation of Total T4. In the case of the mild hypothyroid patient, T4 is generally decreased and T3 is normal. But, it is also known that certain physiological and pathological factors such as, old age, fasting, malnutrition, systemic illness, trauma etc. do impair conversion of T4 to T3. (1)

So far the most sensitive indicator of thyroid abnormalities, whatever the etiology is an elevation of the plasma TSH concentration, often occurring before a fall of the plasma T4 concentration into the hypothyroid range. As mentioned earlier, in some patients with a “failing thyroid”, the plasma T3 concentration is normal even though the plasma T4 concentration is low since the TSH stimulated thyroid preferentially secretes T3. Patients with central hypothyroidism, (secondary: primary or metastitic tumor of the pituitary; pituitary necrosis; and tertiary: skull fracture; tumor; infections; and degenerative disease) constitute only about 15% of the total population of hypothyroid patients, the remaining 85% having primary thyroid failure. The diagnosis and management of hypothyroidism in patients with pituitary or hypothalamic failure present a more complex problem, primarily because of the lack of utility of plasma TSH in these situations. The level of TSH in such patients may be reduced, normal or slightly elevated. The normal and raised values presumably representing hormone with reduced biologic potency due to defects in the glycosylation pattern. The precise level of TSH, which delineates hypothyroidism, has not been established. (2)

Judging from these arguments, one can safely conclude that none of the above diagnostic parameters T3, T4 and TSH in plasma can predict mild or moderate hypothyroidism.

The onset of hypothyroidism may be subtle and often may go undetected for many years while the patient’s health gradually deteriorates. If untreated, hypothyroidism can eventually cause anemia, low body temperature, heart failure and a decrease in blood flow to the brain.  

If a patient has a normal TSH and a normal Free T4, the conventional physician will tell the patient that they do not have hypothyroidism, no matter how many symptoms or signs of hypothyroidism they have. This is a regrettable yet all too common error, because these tests only pick up most severe cases of hypothyroidism and miss virtually all of the milder cases that would respond favorably to 

thyroid hormone treatment. Now the question is that if most hypothyroid cases cannot be diagnosed by the conventional blood test, how can they be diagnosed?

best assay system is 0.25ng/dl for Free T4 and that of Total T4 is 1.5 ug/dl. In patients with mild hypothyroidism of thyroid origin, the Free T4 by any method is very insensitive.

RT3 reduces the activity of T3 by reducing the metabolism. Although T3 in the urine has the best correlation with the clinical picture. For more specific cases it may be valuable: Cortisol, DHEA, Aldosterone, Total 17-ketosteroids and 17-hydroxysteroids and the individual fractions of keto- and hydroxysteroids, pregnanediol and triol ect. to decide. (8)

To determine the clinical value of RT3 in the urine, as well as other factors such as selenium, copper and zinc in the urine are also important . (8) The precursors of thyroid hormones are the amino acids Phenylalanine and Tyrosine, which are located in the amino acid panel. The amino acid panel (40 amino acids) also provides other valuable information: status of other amino acids, function of certain vitamins / minerals etc. Which may also be of importance to reduce symptoms that are seen in hypothyroidism such as fatigue, low energy, depression, constipation etc .