If obesity is always due to one very specific diencephalic deficiency, it follows that the only way to cure it is to correct this deficiency. At first this seemed an utterly hopeless undertaking. The greatest obstacle was that one could hardly hope to correct an inherited trait localized deep inside the brain, and while we did possess a number of drugs whose point of action was believed to be in the diencephalons, none of them had the slightest effect on the fat-center. There was not even a pointer showing a direction in which pharmacological research could move to find a drug that had such a specific action. The closest approach were the appetite-reducing drugs - the amphetamines----- but these cured nothing.

A CURIOUS OBSERVATION

Mulling over this depressing situation, I remembered a rather curious observation made many years ago in India. At that time we knew very little about the function of the diencephalon, and my interest centered round the pituitary gland.

Proehlich had described cases of extreme obesity and sexual underdevelopment in youths suffering from a new growth of the anterior pituitary lobe, producing what then became known as Froehlich's disease. However, it was very soon discovered that the identical syndrome, though running a less fulminating course, was quite common in patients whose pituitary gland was perfectly normal.

These are the so-called “fat boys” with long, slender hands, breasts any flat-chested maiden would be proud to posses, large hips, buttocks and thighs with striation, knock-knees and underdeveloped genitals, often with undescended testicles. It also became known that in these cases the sex organs could he developed by giving the patients injections of a substance extracted from the urine of pregnant women, it having been shown that when this substance was injected into sexually immature rats it made them precociously mature. The amount of substance which produced this effect in one rat was called one International Unit, and the purified extract was accordingly called “Human Chorionic Gonadotropin” whereby chorionic signifies that it is produced in the placenta and gonadotropin that its action is sex gland directed.

The usual way of treating “fat boys” with underdeveloped genitals is to inject several hundred international Units twice a week. Human Chorionic Gonadotrophin which we shall henceforth simply call hCG is expensive and as “fat boys” are fairly common among Indians I tried to establish the smallest effective dose. In the course of this study three interesting things emerged. The first was that when fresh pregnancy-urine from the female ward was given in quantities of about 300 cc. by retention enema, as good results could be obtained as by injecting the pure substance. The second was that small daily doses appeared to be just as effective as much larger ones given twice a week. Thirdly, and that is the observation that concerns us here, when such patients were given small daily doses they seemed to lose their ravenous appetite though they neither gained nor lost weight. Strangely enough however, their shape did change. Though they were not restricted in diet, there was a distinct decrease in the circumference of their hips.

FAT ON THE MOVE

Remembering this, it occurred to me that the change in shape could only be explained by a movement of fat away from abnormal deposits on the hips, and if that were so there was just a chance that while such fat was in transition it might be available to the body as fuel. This was easy to find out, as in that case, fat on the move would be able to replace food.

It should then he possible to keep a “fat boy” on a severely restricted diet without a feeling of hunger, in spite of a rapid loss of weight.

When I tried this in typical cases of Froehlich's syndrome, I found that as long as such patients were given small daily doses of hCG they could comfortably go about their usual occupations on a diet of only 500 Calories daily and lose an average of about one pound per day. It was also perfectly evident that only abnormal fat was being consumed, as there were no signs of any depletion of normal fat. Their skin remained fresh and turgid, and gradually their figures became entirely normal. The daily administration of hCG appeared to have no side-effects other than beneficial ones.

From this point it was a small step to try the same method in all other forms of obesity. It took a few hundred cases to establish beyond reasonable doubt that the mechanism operates in exactly the same way and seemingly without exception in every case of obesity. I found that, though most patients were treated in the outpatients department, gross dietary errors rarely occurred.

On the contrary, most patients complained that the two meals of 250 calories each were more than they could manage, as they continually had a feeling of just having had a large meal.

PREGNANCY AND OBESITY

Once this trail was opened, further observations seemed to fall into line. It is well known that during pregnancy an obese woman can very easily lose weight. She can drastically reduce her diet without feeling hunger or discomfort and lose weight without in any way harming the child in her womb. It is also surprising to what extent a woman can suffer from pregnancy-vomiting without coming to any real harm.

Pregnancy is an obese woman's one great chance to reduce her excess weight. That she so rarely makes use of this opportunity is due to the erroneous notion, usually fostered by her elder relations, that she now has “two mouths to feed” and must “keep up her strength for the coming event.

All modern obstetricians know that this is nonsense and that the more superfluous fat is lost the less difficult will be the confinement, though some still hesitate to prescribe a diet sufficiently low in calories to bring about a drastic reduction.

A woman may gain weight during pregnancy, but she never becomes obese in the strict sense of the word. Under the influence of the hCG which circulates in enormous quantities in her body during pregnancy, her diencephalic banking capacity seems to be unlimited, and abnormal fixed deposits are never formed. At confinement she is suddenly deprived of hCG, and her diencephalic fat-center reverts to its normal capacity. It is only then that the abnormally accumulated fat is locked away again in a fixed deposit. From that moment on she is again suffering from obesity and is subject to all its consequences.

Pregnancy seems to be the only normal human condition in which the diencephalic fat banking capacity is unlimited. It is only during pregnancy that fixed fat deposits can be transferred back into the normal current account and freely drawn upon to make up for any nutritional deficit. During pregnancy, every ounce of reserve fat is placed at the disposal of the growing fetus. Were this not so, an obese woman, whose normal reserves are already depleted, would have the greatest difficulties in bringing her pregnancy to full term. There is considerable evidence to suggest that it is the hCG produced in large quantities in the placenta which brings about this diencephalic change.

Though we may be able to increase the diencephalic fat banking capacity by injecting hCG, this does not in itself affect the weight, just as transferring monetary funds from a fixed deposit into a current account does not make a man any poorer; to become poorer it is also necessary that he freely spends the money which thus becomes available. In pregnancy the needs of the growing embryo take care of this to some extent, but in the treatment of obesity there is no embryo, and so a very severe dietary restriction must take its place for the duration of treatment.

Only when the fat which is in transit under the effect of hCG is actually consumed can more fat be withdrawn from the fixed deposits. In pregnancy it would be most undesirable if the fetus were offered ample food only when there is a high influx from the intestinal tract. Ideal nutritional conditions for the fetus can only be achieved when the mother's blood is continually saturated with food, regardless of whether she eats or not, as otherwise a period of starvation might hamper the steady growth of the embryo. It seems that hCG brings about this continual saturation of the blood, which is the reason why obese patients under treatment with hCG never feel hungry in spite of their drastically reduced food intake.

THE NATURE OF HUMAN CHORIONIC GONADOTROPIN

hCG is never found in the human body except during pregnancy and in those rare cases in which a residue of placental tissue continues to grow in the womb in what is known as a chorionic epithelioma. It is never found in the male. The human type of chorionic gonadotrophin is found only during the pregnancy of women and the great apes. It is produced in enormous quantities, so that during certain phases of her pregnancy a woman may excrete as much as one million International Units per day in her urine - enough to render a million infantile rats precociously mature. Other mammals make use of a different hormone, which can be extracted from their blood serum but not from their urine. Their placenta differs in this and other respects from that of man and the great apes. This animal chorionic gonadotrophin is much less rapidly broken down in the human body than hCG, and it is also less suitable for the treatment of obesity.

As often happens in medicine, much confusion has been caused by giving hCG its name before its true mode of action was understood. It has been explained that gonadotrophin literally means a sex-gland directed substance or hormone, and this is quite misleading. It dates from the early days when it was first found that hCG is able to render infantile sex glands mature, whereby it was entirely overlooked that it has no stimulating effect whatsoever on normally developed and normally functioning sex-glands. No amount of hCG is ever able to increase a normal sex function. It can only improve an abnormal one and in the young hasten the onset of puberty. However, this is no direct effect. hCG acts exclusively at a diencephalic level and there brings about a considerable increase in the functional capacity of all those centers which are working at maximum capacity.

THE REAL GONADOTROPHINS

Two hormones known in the female as follicle stimulating hormone (FSH) and corpus luteum stimulating hormone (LSH) are secreted by the anterior lobe of the pituitary gland. These hormones are real gonadotropilins because they directly govern the function of the ovaries. The anterior pituitary is in turn governed by the diencephalon, and so when there is an ovarian deficiency the diencephalic center concerned is hard put to correct matters by increasing the secretion from the anterior pituitary of FSH or LSH, as the case may be. When sexual deficiency is clinically present, this is a sign that the diencephalic center concerned is unable, in spite of maximal exertion, to cope with the demand for anterior pituitary stimulation. When then the administration of hCG increases the functional capacity of the diencephalon, all demands can be fully satisfied and the sex deficiency is corrected. That this is the true mechanism underlying the presumed gonadotrophic action of hCG is confirmed by the fact that when the pituitary gland of infantile rats is removed before they are given hCG, the latter has no effect on their sex-glands. hCG cannot therefore have a direct sex gland stimulating action like that of the anterior pituitary gonadotrophins, as FSH and LSH are justly called. The latter are entirely different substances from that which can be extracted from pregnancy urine and which, unfortunately, is called chorionic gonadotrophin. It would be no more clumsy, and certainly far more appropriate, if hCG were henceforth called chorionic dienccphalotrophin.

HCG NO SEX HORMONE

It cannot he sufficiently emphasized that hCG is not sex-hormone, that its action is identical in men, women, children and in those cases in which the sex-glands no longer function owing to old age or their surgical removal. The only sexual change it can bring about after puberty is an improvement of a pre-existing deficiency. But never stimulation beyond the normal. In an indirect way via the anterior pituitary, hCG regulates menstruation and facilitates conception, but it never virilizes a woman or feminizes a man. It neither makes men grow breasts nor does it interfere with their virility, though where this was deficient it may improve it. It never makes women grow a beard or develop a gruff voice. I have stressed this point only for the sake of my lay readers, because, it is our daily experience that when patients hear the word hormone they immediately jump to the conclusion that this must have something to do with the sex- sphere. They are not accustomed as we are, to think thyroid, insulin, cortisone, adrenalin etc, as hormones.

IMPORTANCE AND POTENCY OF HCG

Owing to the fact that hCG has no direct action on any endocrine gland, its enormous importance in pregnancy has been overlooked and its potency underestimated. Though a pregnant woman can produce as much as one million units per day, we find that the injection of only 125 units per day is ample to reduce weight at the rate of roughly one pound per day, even in a colossus weighing 400 pounds, when associated with a 500-calorie diet. It is no exaggeration to say that the flooding of the female body with hCG is by far the most spectacular hormonal event in pregnancy. It has an enormous protective importance for mother and child, and I even go so far as to say that no woman, and certainly not an obese one, could carry her pregnancy to term without it.

If I can be forgiven for comparing my fellow-endocrinologists with wicked Godmothers, hCG has certainly been their Cinderella, and I can only romantically hope that its extraordinary effect on abnormal fat will prove to be its Fairy Godmother. hCG has been known for over half a century. It is the substance which Aschheim and Zondek so brilliantly used to diagnose early pregnancy out of the urine. Apart from that, the only thing it did in the experimental laboratory was to produce precocious rats, and that was not particularly stimulating to further research at a time when much more thrilling endocrinological discoveries were pouring in from all sides, sweeping, hCG into the stiller back waters

Next Page
Previous Page