| Introduction |
The second most commonly diagnosed endocrine disorders are those of the thyroid gland (the first is diabetes). Ultrasound studies have shown thyroid nodular disease in at least 40% of healthy adults.
In addition, about 10% of the US population at large, show circulating thyroid antibodies which are important predictors of auto-immune thyroid disease- the most common cause of thyroid
dysfunction
|
| Thyroid Hormones |
The secretory products of the thyroid are the following hormones in descending order:
T4 > T3 > rT3 > T2 in addition to calcitonin, (Table 1). |
| Organ Distribution of T3 and T4 |
| In humans, the extra thyroidal pool of T3 and T4 is distributed as follows: (Table 2). |
Table 1: Facts about Thyroid Hormones
|
T4 |
T3 |
rT3 |
Remarks |
| mean serum concentration ng/ml |
80 |
1.4 |
0.25 |
serum T4 is 60xmore abundant than T3 |
| body distribution Volume (L) |
10 |
38 |
90 |
T4 is mostly confined to vascular space |
| production rates mg/day |
88 |
30 |
28 |
T3 distributes in vascular and ECF space |
% derived fromT4 |
- |
>80 |
>95 |
rT3 distributes in total body |
|
Table 2: Distribution of the extra thyroidal pool of T3 and T4
| Organ |
T4 |
T3 |
| Liver & Kidney |
33% |
5-7% |
| Skin, muscle, brain |
44% |
75% |
| Plasma |
22% |
18% |
|
T4 and T3 Dynamics |
It is generally agreed that it is the "Free" or unbound fraction of T3 and T4 that can enter the cell. In serum T3 and T4, bind to thyroid binding globulin TBG, prealbumin and albumin.
There is an ongoing dissociation of T3 and T3, from the binding protein during capillary passage with a more rapid T3 dissociation contributing to the shorter T3 halflife. In the liver, kidney and heart > 90 of intracellular T3 is derived from plasma T3, while in the brain and adipose tissue about 50-90 of T3 is derived locally by iodine removal of circulating T4. |
| T4 ® T3 conversion is catalyzed out by two enzymes: |
| Type 15' deiodinase is considered the enzyme that converts T4 ® T3 for the whole body via plasma distribution. While Type II 5' deiodinase is important in tissues that convert T4 ® T3 locally as in brain and brown adipose tissue. These tissue types in part utilize circulating (Type I produced) T3 but rely heavily on T4 intake for local conversion to T3 to augment circulating T3. |
| Peripheral conversion of T4 ® T3 is reduced by: |
1. Carbohydrate intake restriction
2. Chronic illness
3. Hypothyroidism
4. Increased glucocorticoids - or high stress states
5. Estrogens
6. Deficits in tissue cofactors
7. Beta-Blockers
|
| Evaluation of Thyroid Function |
There is a general consensus that the unbound circulating fraction or "free" hormones gain access into the extracellular and thereafter the intracellular space. They account for the bulk of hormone activity. The free Fractions of T3 and T4, fT3 and fT4 each constitutes less than 1% of the total circulating amounts. |
| A) Total Hormone Measurements |
Total serum thyroid hormone measurement usually has a low confirmation yield of the clinical Index of suspicion. Total serum T4 and T3 measurements are poor indicators of thyroid associated thermometabolism. More sensitive methods of diagnosis are needed. |
| B) Index Methods |
These are indirect measures ie. estimates of the free fractions of T3 and T4. The fT4 index is calculated by multiplying total T4 by T3 resin uptake.
Most methods involving indirect estimates of the free fractions of T3 and T4 are susceptible to a wide range of interferences, drugs, illness, change in equilibrium between bound and Free during transport of serum specimen, and liver function among others
|
| Thyroid Antibodies |
The salivary panel includes a measurement of the antibody level against thyroperoxidase (TPO). TPO antibodies (known as anti-microsomal) are the most clinically useful antibodies. TPO antibodies are positive in 95% of patients with autoimmune thyroiditis and in 10 of the adult US population. This antibody inhibits thyroid hormone synthesis.
TPO antibody prevalence in women rises with age. Autopsy studies have shown a close correlation between positive TPO findings and thyroid infiltration by lymphocytes even in the face of normal thyroid function. Therefore, positive findings of TPO antibodies in clinically normal individuals almost certainly indicate occult autoimmune thyroid disease.
|
| The Power of Multiple Free Fraction Measurements |
To enhance clinical correlation of laboratory thyroid assessments the new salivary panel (STP)* includes:
Direct measurement of fT3
Direct measurement of fT4
Direct measurement of TSH
Thyroid Microsomal Antibody
This panel gives no estimates and no indirect measurements. It introduces the concept of thyroid hormone "tissue delivery". How much thyroid hormone are the tissues actually receiving? It does not necessarily correlate with blood values because there are several filteration and intervening steps between the bulk hormone in the blood and "tissue availability and delivery".
This panel constitutes an excellent addition to the clinical tools to help discriminate primary from secondary hypothyroid and hyperthyroid states.
|
| Major Symptoms of Thyroid Diseas |
Hypothvroid
Fatigue/Lethargy
Dry skin/hair
Cold Intolerance
Constipation
Facial Swelling
Weight loss/gain
Menorrhagia
Menstrual Irregularities
Hyperthyroid
Nervousness/Anxiety
Palpitations/Arrhythmia
Fatigue
Insomnia
Weight loss
Increased appetite
Bowel hyperactivity
Increased sweating
|
| Advantages of Using Saliva Diagnos-Techs |
1. Economy
2. Convenience
• Non Invasive
• Saliva specimens
• Convenient home collection
• Good patient compliance
3. Scientific Superiority
• Direct Free Fraction measurement
4. Practicality
• Quick result turn around, within 5 working days
• Courtesy phone consult, one patient at a time, to interpret results and discuss therapeutic implications
|
| Examples of findings and their implications: |
| ê fT4 |
 |
No tissue reserver, |
| ê fT3 |
destroyed |
| é TSH |
thyroid gland |
| +TPO |
may be caused by autoimmune disease |
|
| éN fT4 |
|
Peripheral hyperthyroid |
| é fT3 |
not centrally mediated, |
| ê TSH |
subclinical/clinical |
| +TPO |
thyroiditis |
|
| é fT4 |
|
Centrally mediated |
| é fT3 |
hyperthyroid possible |
| é TSH |
smicroadenoma of |
| N TPO |
pituitary |
|
| é/NfT4 |
|
Poor blood conversion |
| ê fT3 |
of T4® T3 – cofactor and |
| ê TSH |
modulator problem. |
| N TPO |
Brain T4® fT3 normal
leading to low/normal
TSH |
|
| é |
Hight |
K |
| ê |
Low |
E |
| N |
Normal |
Y |
|
|
| |
| |
| المجلد الثالث - العدد 2 - ذي القعدة 1424 - كانون الثاني 2004 |
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