CHAPTER 22

Thyroid, lactation, temperature and magnesium requirements

It is quite remarkable that marked magnesium deficiency and thyrotoxicosis caused by hyperthyroidism give rise to similar symptoms.¹ Conversely, similarities are claimed between hypothyroidism (with myxoedema) and certain effects of excess magnesium.
These observations of a general nature seem to indicate the existence of a relationship between the metabolism of thyroxine (thyroid hormone) and that of magnesium.² This is confirmed by recent experimental work.
VITALE and his co-workers at the University of Harvard found (Table 16) in the course of their outstanding experimental work on the relationship between magnesium and arterial and cardiac diseases, that where the ration was very low in magnesium (25 mg./100 kg. ration) the addition of 2 mg. thyroxine (per 100 gm. of ration) diminished very considerably the magnesium content of the blood serum, which fell from 1-87 to 0-50 mg./100 c.c.³ But if the magnesium content of the ration containing the high dosage of thyroxine is increased from 20 to 160 mg. (per 100 gm. ration) the effect of the thyroxine is cancelled and the magnesium content of the blood serum returns more or less to normal, rising from 0-50 to 1-67 mg./100 c.c. The American workers concluded from their various experiments that, in conditions of hyperthyroidism, more magnesium is consumed in the tissues.

Consequently, as a result of activation ⁴ of the thyroid it can happen that the organism is no longer able to meet the increased consumption of magnesium: which means that a state of hyperthyroidisim favours hypomagnesaemia.⁵ It should be noted, moreover, that in human patients suffering from hyperthyroidism the magnesium content of the blood serum tends to be low.
From the point of view of grass tetany it is interesting to observe that a content of 160 mg. magnesium in 100 gm. ration (containing about 85% dry matter) is equivalent to 0 - 19 % in the dry matter. With many reservations ⁶ it may be said that, under the conditions of this experiment, a content of 0 - 19% magnesium in the dry matter of the ration guards against possible excessive secretion of thyroxine by the thyroid. Dutch workers will be seen (Figure 16) to have found that the chances of grass tetany increase considerably when the magnesium content in the dry matter of the herbage is lower than 0 - 20%. The two figures merit comparison, the more so as it appears, as will be seen, that grass tetany is more frequent under certain conditions where the thyroid activity of the animal is increased.
This effect of the thyroid on magnesium is connected perhaps with the very important, but none the less overlooked, observation made by ABELIN more than twenty years ago, namely, that the administration of a diet rich in potassium to a patient suffering from hyperthyroidism creates a state of marked hyper-excitability.⁷

Increased thyroid activity in the lactating female

Although tetany attacks all grazing animals, it is primarily a disease of the lactating female ruminant. It has already been seen that lactation sensitizes magnesium-deficient female rats. It will be seen further that a hypothesis has been advanced to the effect that lactation promotes hypomagnesaemia because it exhausts the organism's magnesium resources. This explanation is far from being wholly satisfactory, far more potassium than magnesium being excreted in milk (Table 30). The thyroid may therefore be considered to afford the better explanation ⁸ of the susceptibility of the lactating female to tetany.⁹
Many workers have confirmed an increase ¹⁰ in the secretion ¹¹ of thyroxine ¹² (thyroid hormone) by the animal, be it rat or ewe, during the peak lactation period.
It has just been seen that thyroxine has an antagonistic effect on magnesium and in certain cases, if the organism is impoverished with regard to magnesium, can accentuate the drop in the magnesium content of the blood serum, with all its attendant consequences for neuro-muscular transmission. More generally, this greater thyroid activity increases the consumption of magnesium in the tissues and helps to deprive of magnesium an organism already deficient in the element, directly or indirectly. It is possible, therefore, if not probable, that the greater thyroid activity in lactating cows and ewes helps to increase their susceptibility ¹³ to grass tetany.

Cold stimulates the thyroid

A drop in external temperature increases thyroid activity; in rats, for example, it has been observed that thyroxine secretion is five times greater at 32° F. (1° C.) than at 95° F. (35° C.). The low temperature does not act immediately on the thyroid. When rats that had previously been kept in a room at normal temperature (68° F. or 20° C.) were placed in an atmosphere of 32° F. (or 0° C.), one to three days passed before the secretion of thyroxine increased; the activity does not reach its maximum until the 26th day, by which time it is three times greater than at 68° F. (20° C.). A "syndrome of adaptation" to cold subsequently develops, and after 40 days in the cold atmosphere the activity of the thyroid returns to normal. If, on the other hand, rats are transferred from a normal temperature of 68° F. (20° C.) to a warm atmosphere (93° F. or 34° C.) the thyroid activity begins to diminish one day later and continues to do so for about 20 days. Then the "adaptation syndrome" appears and the activity returns to more or less normal.

Influence of external temperature on magnesium requirements

Two phenomena are therefore at work, namely:

	(a) The increase in thyroid activity increases the magnesium requirements of the animal.
	(b) A low temperature increases thyroid activity.

It was logical, therefore, to conclude that at a low temperature the magnesium requirements of the animal would be increased. This appears all the more reasonable, as the first workers to investigate the problem found that the symptoms of magnesium deficiency were analogous to the changes observed in animals kept at a low temperature: in particular, vaso-dilation observable particularly in the ears, tail and feet. Various experiments were subsequently to confirm that, in a cold atmosphere, the animal has greater magnesium requirements.
This is illustrated in Figure 10, showing the growth curves of young rats as a function of the logarithm of the magnesium content in the ration. It will be seen that the requirements of magnesium are clearly higher in the rats that were kept in the coldest atmosphere. For example, to obtain a weight gain of 50 gm. in 24 days, 100 gm. ration had to contain:

	4 mg. magnesium at 77° F. (25° C.)
	16 mg. magnesium at 50° F. (13° C.)

which is four times more.
When the magnesium content of the purified ration reaches a certain figure, any further increase in this content does not lead to a greater weight gain. But the magnesium content above which the gain in weight remains constant varies with the temperature. This content, for 100 gm. ration, is:

	25 mg. at 77° F. (25° C.)
	50 mg. at 50° F. (13° C.)

which is twice as much.¹⁴
In fact, the ration is much less efficiently utilized in the cold when the rate of growth is halved and the amount of food ingested 20% higher than in the warmest atmosphere. This demonstrates the proportion in which the magnesium requirements are altered: they are increased almost four-fold in the coldest atmosphere.

Figure 10:Weight gain in weaned rats receiving rations with varying magnesium contents and kept in atmospheres with different temperatures

Variations in temperature, by affecting. the thyroid, can favour grass tetany

It will be seen that temperature exerts a considerable influence on the incidence of grass tetany, be it spring, autumn or winter tetany. The hypomagnesaemic effect of under-nourishment is also much more marked in a cold atmosphere. Moreover, when sheep are starved the fall in magnesium is both much greater and more rapid in the animals exposed to cold out of doors than in those kept under shelter. This helps to explain why winter grass tetany appears when the temperature suddenly becomes very low with icy winds.
If an animal that has been kept in the heat (in the stall) is put out to grass in low but not very low temperatures, the activity of its thyroid is increased, and this state persists for at least 20-30 days.¹⁵ If, during this period, the atmosphere heats up rapidly, promoting the growth of herbage liable to cause hypomagnesaemia, the animal will be sensitized by the increased and persistent activity of its thyroid to the tetany-producing effects of this herbage. This is exactly the situation that presents itself when, after emerging from the stall, cattle are put out to graze in temperatures that are still low. The first rise in temperature triggers a growth of grass with exaggerated tetanigenic characteristics (see Figure 22). This grass will be acting on an animal whose thyroid activity is still very high, thus increasing considerably its requirement of magnesium and favouring the appearance of tetany (see Figure 21).

1. Such as vaso-dilation, hyper-irritability of the nervous system, cardiac irregularity, increased calcium secretion in the urine, loss of weight and, finally, fever. *

2. Possible relationships of the parathyroid and pituitary glands with magnesium metabolism are not dealt with in this book. Suffice it to say that such relationships exist, but cannot be defined exactly in the present state of our knowledge and in the light of the contradictory results available. Neither is it possible, therefore, to derive theoretical or practical information of importance to grass tetany. The reader is referred in this connexion to the publications of that outstanding, young French doctor DURLACH.
   It should be pointed out, however, that in the course of the last few years some research workers have come to the general and important conclusion that a reduced content of magnesium in the blood serum produces effects similar to those of an excess of Vitamin D or parathyroid hormones. *

3. Note that intravenous injections of thyroxine administered to calves and adult cattle cause the excretion of magnesium and calcium in the urine to increase considerably. A German experiment may be compared with this American work. SCHMIDT administered thyroxine bucally to calves fed exclusively on whole milk. In every case he found the magnesium content of the blood serum reduced. *

4. This appears to be confirmed by the following experiment. SWAN gave cows a supplement of thyroprotein (iodinated casein) and noted a fall in the magnesium content of the blood serum, which could be marked in certain cases. This could be described as an effect of physiological under-nourishment. *

5. The results are not always so clearly obvious, and it appears that, in certain cases of hyperthyroidism, there is no diminution in the total magnesium content of the blood serum. There is, however, a fall in the level of ionized magnesium, also described as biologically active magnesium. It has been recorded, moreover, that in the case of diffuse toxic goitre the contents of both total magnesium and ultrafiltrable magnesium in the blood serum are diminished simultaneously. *

6. Recent experiments have shown that numerous factors (fatty acids, cholesterol in the blood, etc.) can alter the antagonistic effect of magnesium on thyroxine. *

7. It is interesting to note that raising the diet's content of sodium, an antagonist of potassium, cancels out this marked excitatory effect of potassium in the patient with hyperthyroidism. *

8. BEGOVIC, of the University of Sarajevo, put forward an interesting hypothesis, namely, that milk is very rich in acetyl-choline and it is possible that this acetylcholine, passing into the organism under certain conditions, gives rise to nervous disorders. The Yugoslav worker studied the problem in the case of milk fever; it should likewise be studied in relation to grass tetany. *

9. One of the factors that may contribute to the triggering of tetany is oestrus (or heat), and oestrus is equally associated with an increase in thyroid activity. In the case of a woman suffering from latent tetany attacks frequently take place just before menstruation. *

10. From the histological point of view RACADOT established in female cats that the onset of lactation was accompanied by a diminution in the thyroid of the colloid that contains the thyroxine reserve. *

11. On the other hand, some authors have not observed any difference in thyroid activity between lactating goats and non-lactating pregnant goats. *

12. Note that this greater secretion of thyroxine corresponds with an increase in the basal metabolism and with a higher magnesium requirement. In addition, administration of certain substances similar to the thyroid hormone, such as thyroprotein, increases milk production. *

13. Another factor may perhaps help to make the lactating female more susceptible to tetany. It has been said that an excess of potassium in the ration, as well as any emotion, increases the secretion of adrenaline, which probably plays a very important part in triggering convulsions in the hypomagnesaemic animal. There is a marked synergism between thyroid hormone and adrenaline in their action on the peripheral mechanisms of the cells. It has long been known, moreover, that patients with hyperthyroidism are extremely sensitive to the effects of adrenaline, and that hypothyroid patients with myxoedema, on the other hand, exhibit a moderate reaction to adrenaline. It is not impossible, therefore, that the increased secretion of adrenaline caused by factors inherent in tetanigenic herbage will have a more marked tendency to trigger off tetany in an animal suffering from hyperthyroidism, e.g. a lactating female. *

14. This influence of external temperature on the metabolism of magnesium becomes clearly obvious when the magnesium balance of adult rats is studied. *

15. One might even say 40 days because it has just been seen that thyroid activity in the animal suddenly put into a cold atmosphere increases continuously over about 26 days, whereupon it diminishes only slowly. *