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ions； toxins； etc。＇*＇ It would appear； then； that these three organs take the stress of life the brain is the 〃battery；〃 the adrenals the 〃oxydizer；〃 and the liver the 〃gasoline tank。〃 This clear…cut insomnia experiment corresponds precisely with our other brain…adrenal observations。
＇*＇ Further studies have given evidence that the elimination of the acids resulting from energy…transformation as well as the conversion of energy stored in the kinetic organs causes histologic changes in the liver； the adrenals； and possibly in the brain。
With these three kinetic organs we may surely associate also the 〃furnace；〃 the muscles； in which the energy provided by the brain； adrenals； and liver； plus oxygen； is fabricated into heat and motion。
Benedict； in his monumental work on metabolism； has demonstrated that in the normal state； at least； variations in the heart…beat parallel variations in metabolism。 He and others have shown also that all the energy of the body； whether evidenced by heat or by motion； is produced in the muscles。 In the muscles； then； we find the fourth vital link in the kinetic chain。 The muscles move the body； circulate the blood； effect respiration； and govern the body temperature。 They are the passive servants of the brain…adrenal…liver syndrome。
Neither the brain； the adrenals； the liver； nor the muscles； however； nor all of these together； have the power to change the rate of the expenditure of energy； to make possible the increased expenditure in adolescence； in pregnancy； in courting； and mating； in infections。 No one of these organs； nor all of them together； can act as a pace…maker or sensitizer。 The brain acts immediately in response to the stimuli of the moment； the adrenals respond instantly to the fickle brain and the effects of their actions are fleeting； the liver contains fuel only and cannot activate； and the muscles in turn act as the great furnace in which the final transformation into available energy is made。 The Thyroid
Another organthe thyroidhas the special power of governing the RATE OF DISCHARGE of energy； in other words； the thyroid is the pace…maker。 Unfortunately； the thyroid cannot be studied to advantage either functionally or histologically； for there is as yet no available test for thyroid secretion in the blood as there is for adrenalin； and thyroid activity is not attended by striking histologic changes。 Therefore the only laboratory studies which have been satisfactory thus far are those by which the iodin content of the thyroid has been established。 Iodin is stored in the colloid lacunae of the thyroid and； in combination with certain proteins； is the active agent of the thyroid。
Beebe has shown that electric stimulation of the nerve supply of the thyroid diminishes the amount of iodin which it contains； and it is known that in the hyperactive thyroid in Graves' disease the iodin content is diminished。 The meagerness of laboratory studies； however； is amply compensated by the observations which the surgeon has been able to make on a vast scaleobservations which are as definite as are the results of laboratory experiments。
The brain…cells and the adrenals are securely； concealed from the eye of the clinician； hence the changes produced in them by different causes escape his notice； but the thyroid has always been closely scrutinized by him。 The clinician knows that every one of the above…mentioned causes of increased brain…cell； adrenal； liver and muscle activity may cause an increase in the activity of both the normal or the enlarged thyroid； and lie knows only too well that in a given case of exophthalmic goiter the same stimuli which excite the brain； the adrenals； the liver； and the muscles to increased activity will also aggravate this disease。
The function of the thyroid in the kinetic chain is best evidenced； however； by its role in the production of fever。 Fever results from the administration of thyroid extract alone in large doses。 In the hyperactivity of the thyroid in exophthalmic goiter one sees a marked tendency to fever； in severe cases there is daily fever。 In fact； in Graves' disease we find displayed to an extraordinary degree an exaggeration of the whole action of the kinetic mechanism。
We have stated that in acute Graves' disease there is a tendency to the production of spontaneous fever； and that there is a magnified diurnal variation in temperature which is due to an increased output of energy in even the normal reaction producing consciousness。 In Graves' disease there is； therefore； a state of intensified consciousness； which is associated with low brain thresholds to all stimuliboth to stimuli that cause muscular action and to stimuli that cause fever。 The intensity of the kinetic discharge is seen in the constant fine tremor。 It is evident that the thresholds of the brain have been sensitized。 In this hypersensitization we find the following strong evidence as to the identity of the various mechanisms for the production of fever。 In the state of superlative sensitization which is seen in Graves' disease we find that the stimuli that produce muscular movement； the stimuli that produce emotional phenomena； and the stimuli that produce fever are as nearly as can be ascertained equally effective。 Clinical evidence regarding this point is abundant； for in patients with Graves' disease we find that the three types of conversion of energy resulting from emotional stimulation； from infection stimulation； and from nociceptor stimulation （pain）； are； as nearly as can be judged； equally exaggerated。 In the acute cases of Graves' disease the explosive conversion of latent energy into heat and motion is unexcelled by any other known normal or pathologic phenomenon。 Excessive thyroid secretion； as in thyrotoxicosis from functioning adenomata； and excessive thyroid feeding； cause all the phenomena of Graves' disease except the exophthalmos and the emotional facies （Figs。 15 and 23）。 The ligation of arteries； the division of its nerve supply； or the excision of part of the gland； may reverse the foregoing picture and restore the normal condition。 The patient notes the effect on the second day and often within a week is relatively quiescent。 On the contrary； if there is thyroid deficiency there results the opposite state； a reptilian sluggishness。
At will； then； through diminished； normal； or excessive administration of thyroid secretion； we may produce an adynamic； a normal； or an excessively dynamic state。 By the thyroid influence； the brain thresholds are lowered and life becomes exquisite； without its influence the brain becomes a globe of relatively inert substance。 Excessive doses of iodin alone cause most of the symptoms of Graves' disease。 As we have stated； the active constituent of the thyroid is iodin in a special protein combination which is stored in the colloidal spaces。 Hence one would not expect to find changes in the cells of the thyroid gland as a result of increased activity unless it be prolonged。
We have thus far considered the normal roles played by the brain； the adrenals the liver； the muscles； and the thyroid in transforming latent into kinetic energy in the form of heat and motion as an adaptive response to environmental stimuli。
The argument may be strengthened； however； by the discussion of the effect of the impairment of any of these links in the kinetic chain upon the conversion of latent into kinetic energy。
Effect Upon the Output of Energy of Impaired or Lost Function of Each of the Several Links in the Kinetic Chain
（1） _The Brain_。In cerebral softening we may find all the organs of the body comparatively healthy excepting the brain。 As the brain is physically impaired it cannot normally stimulate other organs to the conversion of latent energy into heat or into motion； but； on the contrary； in these cases we find feeble muscular and intellectual power。 I believe also that in patients with cerebral softening； infections such as pneumonia show a lower temperature range than in patients whose brains are normal。
（2） _The Adrenals_。In such destructive lesions of the adrenals as Addison's disease one of the cardinal symptoms is a subnormal temperature and impaired muscular power。 An