TPA-UK: Suggestions for an Approach to the Management of Thyroid Deficiency

Suggestions for an Approach to the Management of Thyroid Deficiency

To understand what is happening, it should be clear that five matters have to be considered in planning replacement therapy:

1. Dose

2. Vehicle

3. Conversion T4 - T3

4. Receptor resistance or deficiency

5. Adrenal insufficiency

1. Dose. This has to be infinitely variable. It starts low and will be increased progressively and incrementally, until full response is obtained. Neither doctor nor patient should be satisfied with 60% response, or 80%. 100% is the target. The patient will be asked to monitor her response to treatment. This is satisfactorily done by three simple exercises.

a. Basal Temperature, this is the temperature (10 mins axillary, or 3 mins in mouth) immediately on waking. It is low in hypo-metabolic states, but will rise, albeit slowly, in response to treatment, (as reported elsewhere this is valuable diagnostically). A sudden rise may indicate, all things being equal, the start of overdose.

b. Basal Pulse. This may be taken at the same time as temperature; overdose will result in a rise of the resting pulse. 80 bpm will usually signify overdose.

c. "Feel good factor". It is possible to ask the patient to make a subjective assessment, say, one out of ten, on the same days as temperature or pulse. Since improvement in thyroid replacement may be quite slow, placebo effect does not occur; if the patient feels better, then she is better.

Considerations will be given to actual dosage shortly.

2. Vehicle. There are three options to choose from.

a. Thyroxin (T4)

b. Tertroxin (T3)

c. Dried, natural thyroid U.S.P

a. In this country (Great Britain), Thyroxin (marketed usually as Eitroxin—Synthroid in the US), is almost invariably used. Of the naturally occurring thyroid hormones it is the most plentiful. The thyroid hormone in the natural state is made up of around 80% Thyroxine (T4), 15% Triiodothyronine (Tertroxin T3—Cytomel in the US), and 5% Diiodothyronine (T2),Mono idothyronine (T1), and Thyronine (T0).

Thyroxine has a half-life of 8 days and works fairly well for the more simple, uncomplicated, early, not too severe, hypothyroid patient. But note should be made that this is not how thyroid hormone is naturally produced. There is a body of opinion, sympathetically supported by the writer, that if natural thyroid is not to be used, then at least T4 should be combined with T3 for a more satisfactory and more logical replacement.

b. Triiodothyronine – (T3) Tertroxin or Cytomel. This is quite considerably more potent than T4, four or five times so, but unlike T4, the half life of T3 is about 8 hours.

c. Dried Natural Thyroid. Used from about 1900, desiccated thyroid fell into disfavour in Great Britain and availability ceased in 1985. The synthetic Thyroxine (T4) was considered to be a better, purer preparation. Though, of course, it is purer in that it does not contain the other thyronines. However, this may be its weakness and ignores the fact that thyroid replacement need not be exact. The amount required varies from day to day, even hourly, and this dynamic variation may be compensated for by the patient’s own thyroid - which although deficient, may still be taking some of the load. Natural thyroid is widely used in USA, as Natural Thyroid U.S.P., but in the UK has to be specifically imported. It almost invariably works better than the synthetic T4, and is generally preferred by the patient. About half of the patients in the writer’s practice are maintained on this preparation. (obtained from Gold Line Laboratories, Fort Lauderdale; or Armour thyroid, from The Barnes Foundation, Trumbull, Connecticut).

3. Conversion. Thyroxine (T4) has a low biologic activity and is transported linked to a binding globulin in a non-active state. The removal of one of the four Iodine atoms from the Thyronine molecule converts it to the biologically most active Triiodothyronine (T3) - available as Tertroxin (Cytomel in the US). This is achieved by the (largely liver produced), 5’deiodinase enzyme. In this form, it will be passed, via receptors, into the cell, where passage of protein and sugars across cell membranes is encouraged, and mitochrondrial activity stimulated. It is now clear that prolonged and/or severe hypothyroidism may be associated with partial failure of the 5’deiodinase enzyme. Although suspected, this situation may be diagnosed in default when failure of response in thyroid replacement occurs. The effect of Thyroxine (T4) in this situation is to cause an overload of unused T4 due to conversion failure. This will cause some symptoms of thyroid excess, high pulse, tremor, headache for example, while the hypothyroid symptoms remain (It is of remark that on occasions, high T4 levels in this situation have resulted in inappropriate hypothyroid medication, or thyroid ablation). Thyroid function tests will show high Free T4 and low TSH; resulting in thyroid supplementation actually being withdrawn by the physician.

Management, where this problem is believed to be present, consists in discontinuing some or all T4 and substituting with T3, preferably in divided doses. Since poor conversion may be associated with a raised sex hormone binding globulin (SHBG) and high levels of exogenous oestrogen, re-appraisal of any HRT may need to be considered. Ensuring correct levels of vitamins A & B, Iron and Magnesium (as above), is also mandatory.

4. Receptor resistance or deficiency:

Resistance to the passage of T3 via the receptors has been seen in a number of cases. Why this occurs is not clear, but long periods of thyroid dysfunction are associated. The replacement dose of the chosen thyroid hormone has to be much larger than usual, which may cause some heart searching. Deficiency results from a protracted low thyroid state; prolonged low levels de-sensitizes the receptors. This will improve with time, and treatment of any Adrenal insufficiency present.

5. Adrenal Insufficiency

This might be more properly described as low adrenal reserve. Since hypothyroidism adversely affects every cell, every tissue, and every gland in the body it is clear that the endocrine system as a whole will be also similarly affected. The adrenals will be subject firstly to lowered efficiency resulting from a lowered vitality primary to hypothyroidism, and secondarily, to reduced ACTH stimulation from the pituitary. As a result, in general, patients with a protracted and/or severe hypothyroid state will have some degree of adrenal insufficiency. A significant level of this will be suspected in these situations:

a. Longstanding and severe hypothyroidism.

b. Episodes of extreme exhaustion, or collapse.

c. Bad response to minor illness.

d. Multiple allergies.

e. Digestive problems – alternate diarrhea and constipation

f. Flatulence

g. Weight loss

h. Increasing arthralgia (fibromyalgia) and morning stiffness.

i. Pallor, yellow pigmentation (due to poorly metabolized carotene)

j. Fainting, dizziness

These patients often present with dark rings under their eyes, looking quite ill. Blood pressure is low, with a positive Raglan’s sign. (Pressure fails to rise on standing). These symptoms and signs, it will be appreciated, are those of the early phases of Addison’s Disease.

A single estimation of blood Cortisol is usually unhelpful, but De-hydroepiandrosterone sulphate (DHEA), the main hormone output from the adrenals, will be found to be low. Depressed levels in the endocrine system as a whole are likely to be found. The low adrenal reserve means patients are more or less well, until challenged by the stress of illness or life events--even the thyroid replacement therapy itself initially. And this partial failure will affect adversely T4-T3 conversion and the integrity of the thyroid receptors.

It is essential to manage this insufficiency where present, or where suspected. Remarkably, patients with symptoms, signs and blood pathology of low thyroid, may improve completely on management and correction of the adrenal problems alone; as conversion and receptor efficiency improves, the thyroid hormone circulating - partly unused - is brought into play.

Adrenal insufficiency is dealt with by the provision of the two hormones most likely to be lacking; Cortisonehydrocortisone, and DHEA. (as pointed out above, low DHEA may be used to infer low cortisone output). The treatment therefore, is the exhibition of, ideally, Hydrocortisone. This should be given in divided doses initially of 5mg qds; after a week, 10 mg qds may be used. This remains a physiological dose, not challenging or suppressing the adrenal function, but supplementing it. In these doses all of the usual anxieties associated with

cortisone do not apply, since restoration of normality is being aimed at.

This may need to be explained to patients long subject to media-induced fears of the horrors of corticosteroids (Their physicians may share these anxieties, unnecessarily). Dr McCormack Jeffries’ papers on the subject are most worthy of study. DHEA has reached prominence in recent times as a hormone of multiple, and magic properties. Certain it is that the adrenals secrete more DHEA than anything else, and the amount is inversely proportional to age. It is metabolized to oestrogen and/or testosterone, but also has been shown to play a role in reducing obesity; in reducing atherosclerosis and cholesterol; it inhibits the glucose -6-dehydrogenase enzyme in cancer; it improves immune response, and, possibly, acts as a neural facilitator. In physiological doses, there seems to be no problem in its long-term use. If levels are demonstrably low, it is reasonable to provide replacement therapy.

Treatment Protocol

Before reading the following text, it can be helpful to know that Armour Thyroid USP, has the weight of the pill measured in "grains" on the bottle. Additionally, the conversion to "milligrams" (mg) appears alongside. For example: 2 GRAIN (120mg). Thyroxine, however, is measured in micrograms (mcg). For example: 50mcg.

1. General consideration. Correction of Nutritional deficiencies, and elimination of environmental challenges and toxins, has been noted above.

2. Simple, early hypothyroidism. Readily available tablets of Levothyroxine 50mcg may be used. Initial dose is low (in the elderly as low as 25mcg daily) and will usually start at 50mcg daily. This may be increased 25mcg daily every two or three weeks. The ceiling is reached at the judgement of the physician with feedback from the patient. It is unusual to go higher than 300mcg.

3. Moderate hypothyroidism. If the synthetic products are to be used, many patients will benefit if, when a dose of 100mcg or more levothyroxine is used, Tertroxin (T3) is added. 10mcg for each 100mcg of T4 is to be preferred. The dose may be increased incrementally at the physician (and patient’s) discretion.

If natural thyroid is to be used, a start may be made with 1/2 grain (30 mg). (Commensurate with its 100 years of use by the medical profession, natural thyroid is still measured in grains). Dosage is increased by 1/2 gr. every two weeks; usually by six weeks the dose will level off. Improvement on any given dose continues for weeks and weeks, and the temptation, scenting victory, to increase the dose too soon, should be resisted. The definitive dose may remain unchanged for months or years, but the patients should be allowed to make small adjustments themselves, depending on activity, ambient temperature, for example.

4. Severe hypothyroidism. As indicated above, simple replacement is unlikely to be sufficient. Receptor block and adrenal insufficiency require adrenal support; preferably initiated a week before thyroid supplementation is started. A satisfactory protocol is to, start with 5mg hydrocortisone qds, and after a week, double the dose. Alternatively Prednisolone 2.5 mg (or the enteric-coated Deltacortril) may be used, doubling after a week. Clinical judgment, based on the patient’s condition being normal - perhaps after about three months - will enable the dose then to be halved, and then discontinued. It will be a matter of clinical judgment and preference to use T4 and T3, or natural thyroid.

Some patients already on levothyroxine (T4), but far from well, have to be considered separately. If the condition is really quite severe, and increasing thyroxine makes matters worse, it should be stopped for a short while and cortisone prescribed. The sudden improvement in thyroid uptake brought about by the cortisone may actually result in overdose symptoms if exogenous thyroid is continued. The treatment of choice is to restart thyroid hormone, using instead T3, after a 7 day interim period; 10 mcg for a few days, then 20 mcg and so on. After the improvement is seen to be full, and sustained, natural thyroid can be reintroduced. The general improvement may, secondarily, improve endogenous thyroid production, which can result in the overall exogenous dose being reduced.

As regards DHEA, its significance in the management of adrenal insufficiency is unsure, but where low levels have been found, it seems proper and logical to restore them to normality. In women 25mg daily, and men 50mg daily sometimes produces significant benefit. In this practice, its use has always been an advantage.

The management of hypothyroidism in children requires fine clinical judgement; but one quarter to one half of the adult dose seems to be a satisfactory starting point. Reliance on blood testing should be modified by clinical appraisal of the child and his parents’ observations. The diagnosis is often missed in children; and should be considered in any child often ill. The basal temperature test may prove a helpful pointer.

Thyroid insufficiency may have a number of different causes and its symptoms may masquerade as a number of different illnesses. It should always be considered in patients with prolonged ill health, and the diagnosis rely on history and examination. The reliance of the profession on the pathological tests in favor of thoughtful appraisal is to be deplored. The treatment is inexpensive and low tech, requiring a few simple guidelines and a listening approach by the physician. Rarely is consultant advice necessary; the family physician is well able to initiate and monitor the treatment even in quite severe cases. The rewards are invariable; with no fuss, and with delight, the patients always get better. This common condition is one of few where simple measures can transform patients’ lives.

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Suggestions for an Approach to the Management of Thyroid Deficiency