Current Tests for Thyroid & Adrenal Function

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The first thing to be said about tests in general is that they should be used to help or clarify a diagnosis. They should not be an end in themselves, and should be secondary to a clinical diagnosis. In this present day, far too much reliance is placed on a multiplicity of tests, many expensive and not necessarily appropriate; and this done in place of a proper clinical appraisal as a sort of shortcut. This tendency in modern medicine, which pushes commonsense aside and replaces it with unbending establishment belief in medical technology so that doctors simply don’t think, is to be deeply deplored.

Having said this, there is certainly a place for proper testing, but tests should not, and must not, take precedence over listening to the patient and undertaking a proper examination.

The appropriate tests fall into several categories.

1. Blood Tests

a) General Tests

1. A complete “work up” should include a full blood count (FBC) which will include:
   Haemoglobin (Hb) and Red Cell Count (RBC) – to check for anaemia, commonly found in hypothyroidism.
   White Cell Count (WBC) and Differential (Diff) – to check for general health.
   Erythrocyte Sedimentation Rate (ESR) – also for general health.
   Ferritin – for iron level.  Low in anaemia, and necessary for proper thyroid metabolism.
2. Additionally should be carried out:
   Blood Sugar – a rise may indicate diabetes; a deficiency, hypoglycaemia.
   Urea and Electrolytes – checking kidney function.  Kidney efficiency declines in hypothyroidism.
   Bilirubin and Liver Function Tests – checking liver function, which also depends on thyroid health.
   Cholesterol – usually raised in hypothyroidism and deficient liver function.
   Parathyroid Hormone (PTH) – to check on parathyroid and calcium status. (Deficiencies may occur due to the accidental removal of parathyroid glands during a total thyroidectomy).
3. Finally, sex hormones:
   Oestrogen and Progesterone – for the ladies
   Testosterone – for the gentlemen

These tests are necessary, particularly for any patient in middle life or beyond, since they affect thyroid hormone transport and uptake.

b) Thyroid Tests

1. Thyroid Stimulating Hormone (TSH) – widely considered the most useful of thyroid tests, it is nevertheless nothing like as sensitive as doctors like to think, especially for mild to moderate hypothyroidism.  In low thyroid function, the TSH is expected to rise above its reference range.  Unfortunately, this reference range varies from laboratory to laboratory and from doctor to doctor, but anything over 2.5mU/L should be considered highly suspicious. The reasons the TSH test fails to show the true picture are related to a general depression of the metabolism (as with hypothyroidism) making the pituitary gland unresponsive to low blood thyroid levels, so that the rise above 2.5 may not occur or only insignificantly.  A very low level is likely to be due to primary hyperthyroidism.  Also, the pituitary or hypothalamus may be damaged anyway (secondary or tertiary hypothyroidism), again making the tests unreliable.
2. Free T4 (FT4) and Total T4 (TT4) – most of the circulating thyroxine is attached to transport proteins called binding globulins and the Total T4 indicates the total amount of thyroid circulating in the bloodstream, that is, both unusable bound thyroid and the usable free thyroid.  The thyroxine free of the binding globulin (FT4) indicates the amount of thyroid hormone actually available for use in the bloodstream, prior to its conversion to the active thyroid hormone tri-iodothyronine (T3).  The reference range for TT4 is 54-142 nmol/L.  The range for FT4 is 9-23 pmol/L.  Values significantly above the top end of both ranges would suggest hyperthyroidism.
3. Free T3 (FT3) and Total T3 (TT3) – if T3 is measured, the free form is almost invariably used since it is attached to a transport protein in a very limited amount.  The Free T3 therefore indicates for the amount of converted active thyroid hormone available.  The reference range of FT3 is 0.8-2.5 nmol/L.  The range for TT3 is 3-8 pmol/L.  Values significantly above the top end of the ranges would suggest hyperthyroidism.
4. Reverse T3 (rT3) – excess conversion of T4 into reverse T3 as suggested by Dr Wilson, is a possible cause of hypothyroidism.  A measurement may therefore be made of the unusable rT3, whose range is between 0.2-6.7 nmol/L.
5. Thyroxine Binding Globulin (TBG) – this test is not as used quite so much today as previously, although a raised level of globulin may be associated with a hypothyroid state due to thyroid being taken out of circulation and therefore bound and unusable.  A low TBG may also be associated with thyroid transport failure and this makes the test difficult to interpret.  Normal range is 6-17 mg/L.
6. Antithyroid Peroxidase Antibody (TPO Ab), Antithyroglobulin Antibody (TG Ab) and Thyroid Stimulating Immunoglobulin (TSI Ab) – in general there should be no antibodies present, or at least at very low levels.  The presence of antibodies indicates an autoimmune situation and thyroid damage: Hashimoto’s disease is the most common example of this.  Antibodies diminish with treatment or as the immune thyroiditis progresses.  The reference range for TPO Ab is anything less than 150 mUI/ml or Ab Index less than 0.9; the TG Ab is 200 mUI/ml or Ab Index less than 0.9.  If the TSI shows any antibodies at all, it is evidence of hyperthyroidism (Graves’ disease), though these antibodies may also appear in Hashimoto’s disease.

c) Why Tests Go Wrong

The ranges given above are broadly those used by most laboratories.  All these tests are subject to errors which have to be carefully borne in mind when interpreting them:

1. The blood tests themselves are not sensitive enough and each laboratory that undertakes them uses different methods and may have different reference ranges.
2. They represent a snapshot of levels of thyroid hormones in the bloodstream which are subject to daily, even hourly, variation, so that the time of day and circumstances of the test may cause inaccuracies.
3. In hypothyroidism the circulation is slowed to a variable degree, interfering with accurate estimation.
4. In hypothyroidism the blood is subject to a degree of concentration, also resulting from the slowed circulation, and this has the effect of raising blood levels above their true figure.
5. Most important is the slowed T4 to T3 conversion, together with the slowed uptake of T3 into tissues affected by low metabolism, so that the mechanisms within the cell to aid the passage of thyroid hormones into the cell are damaged.  The action of the cellular power source, the mitochondrion, is similarly slowed.  This means blood levels may be raised because thyroid hormone is not being used in the normal way.
6. Many doctors lack the basic training in thyroid medicine to interpret the results of the tests correctly.  Frequently they hope that the laboratory results will do the interpretation for them; but without a full clinical history, and perhaps other tests available, the interpretation may be wrong.

d) Adrenal Tests

1. Serum Cortisol – while this would appear to be the most obvious check on adrenal function, as well as the most important from our point of view, in fact it is almost completely useless.  The daily output varies widely from morning to evening, and almost from minute to minute.  This variation is worsened by moment to moment challenges: for example, a white coated (but well meaning) physician, advancing on his patient syringe in hand, may double the cortisol in the bloodstream in moments.  The morning range is 220-770 nmol/L and the evening range is 55-250 nmol/L.
2. DHEA (dehydroepiandrosterone)  Sulphate – this is of more value than serum cortisol.  The adrenals produce more of this hormone than any other, so that a low level may indicate poorly functioning adrenal glands.  On the other hand, the levels may be raised, which indicates that the production of cortisol from the glucocorticoid pathway, is likely to be interrupted by an enzyme failure. Both situations will result in an insufficiency of cortisone.
3. Synacthen Test – this is an adrenal function test widely approved of by hospital consultants.  Adrenocorticotrophic Hormone (ACTH) in the form of synacthen is given by injection.  This stimulates adrenal production of cortisone, which is then measured 30 minutes or more later.  It may be given in a weakened form, the Short Synacthen Test.  A normal response, where the amount of cortisone is doubled, is considered to be proof of a normal adrenal response.  Certainly, Addison’s disease will be demonstrated by this test since the adrenal response is absent or very weak.  Low adrenal reserve, however, is likely to be swamped by the synacthen; the adrenals, under such a powerful stimulus, may produce - for a short while - an apparently normal response.  There is no specific reference range for this, but the accepted response is for the base line level of cortisol (that is, before the test) to double.

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