bers, and 3 delinquent non-resident associate members.

Dr. M. Lampert, formerly of the University of Illinois, ex-interne of Cook County Hospital, associate on the faculty of the University of Illinois, Rhea Scholarship, membership of the Alpha, Omega Alpha, and for the past 16 months located in Cadillac, has located in Grand Rapids. He will limit his practice to Internal Medicine.

On the morning of July 4th, Dr. C. T. Southworth of Monroe, was admitted to Harper Hospital, Detroit, with a ruptured gall-bladder. Immediate drainage was instituted. Last reports are that he is convalescing and was to return home the last of July. His many friends will be pleased to learn of his recovery from so serious a condition.

The Western Michigan Travel club met in Big Rapids on July 19th, as the guests of Doctors Dodge and Lynch. This meeting was a purely social one, taking the form of a field day at the Meceola Golf club. A blind bogey tournament was played and a golf club was the prize to the winner. Our State President did not carry off the honor, proving our statement in the last issue that his only failure was golf.

Dr. Homer T. Clay has located in Grand Rapids and will limit his work to Pediatrics. The doctor graduated from the University of Missouri and Washington University in 1919, receiving his A. B. and M. D. degrees. He served an interneship of one year in the St. Louis City Hospital, an interneship of 18 months in the Chicago Children's Memorial Hospital and for the past year he has been doing research work in the Chicago Institute for Juvenile Research.

The Detroit College of Medicine and Surgery held its Commencement exercises Friday, June 14, in the Knights of Columbus hall, Detroit. The invocation was given by the Rev. Mr. Marsh of Northville, whose son was a member of the graduating class. Dr. Guy L. Kiefer gave a talk to the seniors for the faculty. Dr. A. P. Biddle for the Board of Education administered the Hippocratic Oath. Mr. Devine, president of the Board of Education, presented the diplomas to the graduating class. Dr. Marshall delivered the Valedictory Address for the seniors. Dr. Dodson, Dean of the Medical Department of the University of Chicago, spoke on "The Relation of the Doctor to the Public."

County Society News

SANILAC COUNTY

A meeting of the Sanilac County Medical Society was held at Brown City on June 27. A talk was

given by Dr. B. E. Brush of Port Huron on "Pain as Sympton in Acute Abdominal Troubles." Paper on "Local Anesthesia in Major Surgery" was given by Dr. J. C. Webster of Marlette.

H. H. LEARMONT, Secretary.

GENESEE COUNTY

The Genesee County Medical Society met on Wednesday, June 21, President Miner presiding. Arrangements were made to hold our annual picnic on Wednesday, Aug. 16. A ball game, dinner and dance will be the features of the occasion. Major Young of Saginaw spoke in the interest of recruit ing officers for the Medical Corps, Organized Reserves, United States Army, and made a good plea for preparedness. Dr. W. J. V. Deacon of Lansing spoke on the reporting of communicable diseases and told us what the State Board of Health was try ing to accomplish in the control of venereal diseases. W. H. MARSHALL,

Secretary.

HILLSDALE COUNTY

The regular quarterly meeting of the Hillsdale County Medical Society was held at the high school building Tuesday evening, July 11.

In the absence of both the president and vice president, Dr. E. A. Martindale was made president pro tem.

Minutes of last meeting read and approved. Dr. Louis W. Toles of Lansing then gave a very interesting and instructive address on "Diseased Conditions of the Nose and Throat, Including the Sinuses."

The speaker called attention especially to differentiation of diseased tonsils, laying down the general law that tonsils yielding on suction (the technique of which he described) streptococci and staphylococci, will not get well and should be extirpated. Otherwise, they may be preserved if not too much hypertrophied. He also emphasized the principal importance of early paracusis in disease of the middle ear, meaning by this, a free incision of the tympanum and not a mere puncture. He also called attention to the important role played by diseased tonsils, teeth sinuses and chronic obstructions in the nasal passages in causing focal infections in different parts of the body.

The doctor's address was discussed by Dr.'s Johnson of Hillsdale and Bell of Reading, followed by general discussion and questions.

The address was highly appreciated by all, and a vote of thanks was tendered to Dr. Toles at its close.

The next speaker, Dr. Barnes of Waldron, being absent, the society then listened to a brief report of the proceedings of the State Society at Flint, from the delegate, Dr. Fenton. This was confined almost entirely to the business part of that society and the House of Delegates, as the valuable scien

tific papers and addresses will be better and more fully presented in The Journal.

Under the head of unfinished business the proposal to contribute to the legislative and educational fund of the State Society, which was tabled at the last meeting, was taken from the table and after discussion, it was voted to instruct the secretary to ask each member of the society to contribute $2 to this fund.

All the members present then paid in this assessment. Dr. Toles contributed valuable information in regard to this work by the state society.

Under the head of new business it was moved by Dr. Bell and supported by Dr. Miller that the president pro tem appoint a committee of three to take immediate action with the prosecuting attorney in enforcing the laws governing medical practice in the county. Carried.

The committee so appointed was Dr. W. H. Sawyer, Dr. T. H. E. Bell and Dr. O. G. McFarland.

It was then moved and supported that the president on his return home be requested to appoint without delay the regular committees on program, legislation and entertainment. Carried. Adjourned.

D. W. FENTON, Secretary-Treasurer.

MAIMONIDES MEDICAL SOCIETY

At the annual meeting of the Maimonides Medical Society, June 13, 1922, for the next season, Dr. M. B. Kay was elected president; Dr. L. B. Cowen, vice president; Dr. A. Shoenfield, secretary, and Dr. R. L. Cowen, treasurer. Dr. N. E. Aronstam again heads the editorial board.

Book Reviews

APPLIED CHEMISTRY.

An Elementary Text Book for Secondary Schools. Fredus N. Peters, Ph. D., Instructor in Chemistry in Central High school, Kansas City, Mo.; More Recently Vice-Principal; Author of "Chemistry for Nurses," etc. 461 pages, 32x5%, with 72 illustrations. Price, silk cloth binding, $3.50.

This is an elementary test on general chemistry for use in secondary schools and one which is written in popular style, but this, at the same time, does not detract from its scientific value. The book is well illustrated and contains special reference tables and a complete glossary. All the facts are presented in a very readable form and on this account is more interesting than the usual "cut and dried" chemistry text-book.

THE MEDICAL SOCIETY OF THE MISSOURI VALLEY AT ST. LOUIS

The thirty-fifth annual meeting of this association will be held in St. Joseph, under the presidency of Dr. Paul E. Gardner, on September 22

22. The Buchanan County Medical Society is preparing for a series of clinics to be held at the various hospitals of St. Joseph on Tuesday and Wednesday, preceding the meeting, September 19. 20. St. Joseph has a proverbial reputation for warm-heated hospitality, and the arrangement committee, under the leadership of Dr. Floyd H. Spencer, announces that the "tang" of his city for entertainment and good fellowship will be fully sustained upon this occasion. The famous hotel Robidoux will be headquarters, and all sessions will be held in the beautiful Crystal Room. The

One of the features of the second day will be a exhibits will be on the same floor. symposium on the "Early Recognition of Cancer" participated in by a number of men who have won national distinction in research work and clinical investigation. On Thursday evening at 7:30 o'clock, Dr. C. W. Hopkins, chief surgeon of the C. & N. W. railway, will give an illustrated lecture on "Injuries and Surgery of the Spine," sent a paper on "Hypertension in Cardio-Vascular and Dr. N. M. Keith, of the Mayo Clinic, will preDisease," illustrated by lantern slides. Following the evening session will be a smoker and other entertainments. Members are urged to bring their ladies, who will be entertained while the fellows are attending the sessions.

Reservations of rooms at the Robidoux should be made early to avoid disappointment. The medical profession of adjoining states cordially invited to attend the clinics whether or not they are members of the society.

"Causes of Duodenal Ulcer," Dr. E. P. Sloan, The preliminary program follows: president Illinois State Medical Society, Bloomington, Ill.

"Toxic Factors in Intestinal Obstruction," Dr. T. G. Orr, Kansas City.

"Convulsions in Children," S. Grover Burnett, Kansas City, Mo.

"The Phosphatic Index," Dr. J. Henry Dowd, Buffalo, New York.

"Some Phases of the Relation of Dental Focal Injections and Systemic Diseases," (lantern slides), Dr. Russell L. Haden, Kansas City, Mo.

"Renal Function in Prostatic Hypertrophy," Dr. Raymond L. Latchem, Sioux City, Iowa.

Dr. Leigh F. Watson, Chicago, subject to be announced.

"Myoclonic Type of Epidemic Encephalitis," Dr. Lloyd James Thompson, St. Joseph.

Dr. Lynne B. Greene, Kansas City, subject to be announced.

"Cancer: Its Early Recognition," a symposium. (a) Address, Dr. Fred J. Taussig, St. Louis, Mo., "How Far Can the Cancer Death Rate Be Decreased by Educating the Profession and the Laity."

(b) "Superficial Cancers," Dr. E. H. Skinner, Kansas City, Mo.

(c) "Gastro-Intestinal Cancers," Dr. John M. Bell, St. Joseph, Mo.

(d) "Cancer of the Breast," Dr. Donald Macrea, Council Bluffs, Iowa.

(e) "Cancer of the Uterus," Dr. Palmer Findley, Omaha, Neb.

Complete program will be issued September 1; if you do not receive a copy notify the secretary, Dr. Charles Wood Fassett, Kansas City, Mo.

Vol. XXI

Original Articles

THE PATHOLOGY OF HYPERTHYROIDISM*

LOUIS B. WILSON, M. D.

ROCHESTER, MINN.

Fifteen years ago the use of the term hyperthyrodism to indicate Graves' disease or exophthalmic goiter would have been considered begging the question. Indeed, there are even yet certain physicians, particularly neurologists, who hesitate to accept the thyroid as the primary cause of the symptoms of exophthalmic goiter. But the studies of the internist, the surgeon, the pathologist, the physiologist, and the chemist have now proceeded to such a degree, and on the whole are in such harmony, that it would appear we may safely use the term hyperthyroidism as indicating that the over-activity of the thyroid is at least the direct antecedent, that is the immediate cause of the symptoms of exophthalmic goiter, even if the thyroid itself may be later shown to be only an intermediate link between the symptoms and the primary cause originating in some other organ.

The internist has more definitely differentiated symptomatic goiter from conditions simulating it. The surgeon has demonstrated that the removal of a portion of the thyroid in exophthalmic goiter relieves the symptoms. The pathologist has shown that the morphology of the thryoid in exophthalmic goiter is that of an overfunctioning organ. The physiologist has shown that by causing the thyroid to overfunction some of the symptoms of exophthalmic goiter may be produced in experimental animals. And the chemist has shown that thyroxin, the essential part of the secretion of the thyroid, will produce experimentally the essential symptoms of exophthalmic goiter.

These five groups of workers have approached the question from different viewpoints, but all have discovered data which point

*Presented before the Michigan State Medical Society as Part 1 of a Symposium on Hyperthyroidism, June 8, 1922.

No. 9

to the same conclusion, namely that a certain syndrome consisting essentially of markedly increased basal metabolism, lowered threshold of the nervous system, tachycardia, certain other circulatory disturbances, and an enlarged thyroid, accompanied usually by ocular symptoms, may all be explained directly if not primarily by hyperthyroidism. I assume that the present symposium is for the purpose of restating briefly from the different viewpoints the facts and hypotheses of each.

PATHOLOGIST'S DIFFICULTIES

From the pathologic viewpoint we have to consider first the morphologic evidence of overfunction in the thyroid itself. The greatest difficulty of the pathologist in attempting to associate the histologic conditions in the thyroid with clinical phenomena has been due to the failure of clinicians readily to come to any settled agreement concerning the grouping of various clinical syndromes. On the pathologic side difficulty has also arisen from the fact that aside from tumors and inflammations most of the changes met with in the thyroid merely represent varying degrees of progressive or retrogressive stages in physiologic phenomena and are therefore difficult to evaluate. Pathologists for a long time labored under the difficulty of not having a sufficiently large number of thyroids from accurately diagnosed cases to compare with each other and to study in relation to evidence of exacerbation or reduction of the physiologic processes of the patients from which they came. In making such a study the pathologist must not be satisfied with studying sections from one or two blocks of tissue. He must remember that each follicle of the thyroid is a unit in itself and that his estimate of the working capacity of the entire gland must be based on a study of a sufficiently large number of units to enable him to form a conception of what the gland as a whole is doing. Of course, estimates based on such studies cannot be accurate in a hundred per cent of the cases. They are, however, more accurate than one might be lead to suppose; this is due to the apparently large factor of safety in the human body, that is, its ability apparently to get along with a relatively

small output of thyroxin and to withstand a relatively large output without in either case showing untoward symptoms. It is only when excessive degrees of physiologic changes occur that the body rapidly responds. In the presence of excessive degrees of physiologic depression or exacerbation, theoretically, there should always be corresponding morphologic changes in the gland. If there is a relatively smaller increase of output extending over a long period, especially in glands in which this relatively small increase is associated with the formation of new follicles in adenomas or

other nodular types of goiter, the histologic evidence of increased function may be much more difficult to determine. However, notwithstanding all the difficulties arising from inaccuracies of clinical diagnoses, failure of the surgeon accurately to determine the postoperative history of his patients, failure of the pathologist in cases in which operation is performed to get all of the thyroid for examination, difficulty of getting normal thyroids and thyroids from cretins and myxedematous patients for comparison, and the enormous labor of examining several sections from each of a large number of areas in each of a large number of thyroids to make his experience worth while; yet it is true that the experienced pathologist can demonstrate in properly fixed and stained tissues morphologic evidence of overfunction of the thyroid in 90 to 95 per cent of all patients in whom there is sufficient evidence in the history and in results of treatment to warrant a diagnosis of hyperthyroidism. Most of the five or more per cent of error. I believe must be laid to inaccuracy of judgment on the part of clinical, surgeon and pathologist. It is barely possible that a small fraction of one per cent in this margin of error may be due to some unexplained intercurrent factor.

The morphologic changes in the thyroid indicating its increased activity are in brief, hyperemia, parenchymal cell hypertrophy, parenchymal cell hyperplasia, and the formation of new follicles.

HYPEREMIA

The thyroid of exophthalmic goiter is hyperemic. Grossly and histologically there is indisputable evidence of the high vascularity of the gland. It should be noted, however, that this increase in vascularity is not due to increase in the size of a few large vessels, but to a diffuse general increase in the size of the smaller arterioles and capillaries as well as of the larger arteries and veins. Indeed, in many intensely hyperplastic thyroids the larger arteries in the interior of the gland are certainly not increased in diameter in proportion to the increase in diameter of the gland. The

smaller arterioles and capillaries, however, are swollen and engorged with blood.

HYPERTROPHY

Hypertrophy of the parenchymal cells, that is, an increase in size of the individual cells, is always present in hyperthyroidism, though it is not always easily demonstrated in adenomatous conditions. Distinction must be made between true cell hypertrophy and cellular edema. Edematous thyroid parenchymal cells are commonly found either in the lax walls of soft cysts or on papilliform projections into the cysts. Occasionally, though very rarely, we must distinguish between true cell hypertrophy and distention of the cell by colloid granules retained within it. True hypertrophy of a parenchymal cell is indubitable evidence that the cell has overworked. It is not an evidence that the cell is ready to begin to work, but that it has already worked. A blacksmith's biceps does not enlarge in preparation for his labor, but as a result of and during his labor. Similarly thyroid parenchymal cells do not increase in size merely as a result of a demand on the part of the tissues for more thyroid secretion, they enlarge only because of the secretion and as they actually do the work of supplying the secretion.

HYPERPLASIA

The term hyperplasia in the thyroid, meaning an increase in the actual number of cells within a given follicle, is sometimes misapplied to simple hypertrophy. In the histologic examination of sections of thyroid, unless the tissue has been fixed and cut so as to preserve the integrity of the entire follicle, it is almost impossible to form a correct estimate of the

number of cells to be found even on the walls of a single follicle in a section which includes only one complete layer of parenchymal cells. When the picture is complicated by infoldings of the walls of the follicle it is even more difficult. Anyone, however, who will take the trouble to count the actual number of cells lining the follicular rings constituted each by a 10 microne section through a considerable area of normal thyroid, and then will similarly count the number of cells lining follicular rings in similar sections from an active exophthalmic goiter, will find that there is a very material

increase in the actual number of cells in the latter instance. Parenchymal cell hyperplasia is even more unequivocal evidence of hyperfunction than is simple cell hypertrophy. It cannot be mistaken for edema and it indicates greater functional stress.

NEW FOLLICLE FORMATION

New follicles may form even in adult thyroids within circumscribed areas surrounded by definite capsules; they are thus properly desig

nated adenomas, or they may be indefinitely localized and without the development of a recognizable capsule, in which case the process should be designated adenomatosis. This latter histologic picture may be simulated by the breaking down of the capsule of a true adenoma. But extensive experience in the histologic study of thyroids will lead anyone to conclude that the weight of evidence is strongly in favor of the development of groups of new follicles within adult thyroids without encapsulation. This formation of new follicles apparently may take place from Wolfer's rests in the walls of follicles in which the epithelium has previously become atropic, thus constituting a true regenerative process.

We, then, conceive of the thyroid as a gland which even in the later years of adult life is capable of performing more than a normal amount of work and that as it performs this increased work the working parenchymal cells within a follicle increase in size and may increase in number, a process which requires an increased blood supply. Besides this, new follicles may be formed, lined with epithelium which may or may not develop to an adult functioning stage.

CELLS NOT "SICK"

It seems to me of great importance that we do not consider these progressive changes, that is, hypertrophy and hyperplasia, simple multiplication of follicles or regeneration, as disease processes. In these processes in no sense are the cells "sick" but on the contrary they are more than usually well. They are merely cells that are performing a normal physiologic function, that is growth or secretion, at an unusual stage of development of the individual or to an unusual degree. The hypertrophic or hyperplastic thyroid cell is no more a diseased cell than any other stimulated cell. Theoretically, of course, it is possible that it may overwork so as to degenerate, but it apparently possesses a large factor of safety for itself in the regulatory mechanism which switches off its activity by directing it to the storage of excess colloid within the follicle and thus automatically reducing its capillary blood supply.

It should be remarked, however, that the hypertrophic or hyperplastic thyroid cell of exophthalmic goiter which is apparently only performing a normal function in an excess degree, in reality may be producing a secretory product which is not normal. It is, of course, perfectly possible that the ingredients furnished this small chemical laboratory may be lacking in some essential, and that the molecule of the product as delivered to the tissues may thus

lack those atoms which make of it normal thyroxin.

SECRETION INTO CAPILLARIES AND FOLLICLES

It is probable that the active chemical constituent, thyroxin, or an incomplete antecedent of thyroxin is secreted into the capillaries in colloid material of low density, although the experimental proof is not conclusive. Several observers have found colloid, that apparently had been derived from the thyroid, in the vessels and lymphatics of animals after they had ficult to distinguish this from the other colloids undergone certain experiments; but it is dif

of the blood. The substance which fills the capillary ends of parenchymal cells in hyperplastic goiter and has been designated a secretory antecedent, is most probably colloid containing thyroxin. That this colloid is transferred directly into the capillaries, has been questioned because the hyperplastic thyroid contains very little thyroxin. On the other hand, it is difficult to understand how thyroxin, which is insoluble in water, can be passed into the circulation except in adsorption in colloid. We know positively that when colloid is excreted into the follicle, it contains thyroxin in large amounts and that in general the more dense the colloid in follicles the larger the amount of thyroxin therein. The facts that thyroid parenchymal cells lining empty follicles are large and that those lining follicles filled with colloid are greatly reduced in volume would strongly suggest that the bulk of a hypertrophic thyroid cell consists of colloid or colloid antecedents which in the storage phase is excreted into the follicle.

DEGREES OF MORPHOLOGIC CHANGES

The morphologic changes in the thyroid in true exophthalmic goiter may be divided into three general stages:

1. In early exophthalmic goiter, with moderate increase in basal metabolism, usually moderate exophthalmos, and moderate thyroid enlargement, the parenchymal cells show marked hypertrophy and moderate hyperplasia. There is diffuse hypermia throughout the gland.

2. In advanced exophthalmic goiter with a high metabolic rate, usually marked exophthalmos, a well marked nervous syndrome, and usually marked thyroid enlargement, there is advanced parenchymal cell hypertrophy and hyperplasia and little, if any, stored colloid. There is diffuse hypermia throughout the gland.

3. In late exophthalmic goiter with high but sometimes declining metabolic rate, exophthalmos, and a well-marked nervous syndrome; the changes in the gland are similar to those in the earlier stages of exophthalmic goiter, but with beginning of well marked storage of col