DISEASES OF THE THYROID GLAND* A CORRELATION OF CLINICAL AND PATHOLOGICAL MATERIAL

FRANK GLENN, M.D. AND CUYLER Y. HAUCH, M.D.

NEW YORK

T HE increase in recent years in the number of patients operated upon for goitre, has enIarged our knowledge

of the cIinica1 manifestations of thyroid disease and has made avaiIabIe for study a Iarge amount of pathoIogica1 material. Separately and on the basis of their pecuIiar experience and observations, the cIinicians and pathoIogists have devised cIassifica- tions of thyroid disease. These different types of cIassification confuse the student encountering the probIem of goitre.

peared. Disfigurement of the neck by the mass is the most common compIaint. There may be symptoms of pressure upon other cervica1 structures by the enIarged gIand; these in order of frequency are cough, tendency to repeated swaIIowing, hoarse- ness, stridor and pain.

The Committee on Nomenclature and CIassification of Disease,l in 1931 grouped a11 diseases of the thyroid excIusive of maIignant lesions, inffammation and the rarer types of disturbances, under four headings : non-toxic diffuse goitre, toxic diffuse goitre, toxic noduIar goitre and non-toxic noduIar goitre. In reviewing the cIinica1 findings in over 300 cases of thyroid disease and studying the gIands removed at operation from the same cases, it was apparent that a definite relationship existed between the cIinica1 picture and the pathoIogica1 changes in the thyroid gland. Some of the facts determined by this study are embraced in the foIlowing pages for the purpose of grouping clinica and pathologica data under the mentioned headings and presenting a simpIe, concise conception of thyroid disease.

The gIand may be diffuseIy enlarged or one lobe or the isthmus aIone may be af- fected. The degree of enIargement varies but when signs of pressure exist, the gland is usuaIIy many times its norma size. Compression of the veins of the neck may be produced by the gIanduIar enIargement.

Gross Examination. The thyroid in non-toxic diffuse goitre appears lighter in coior than the norma gland. Sometimes it presents a mottIed aspect due to inter- ference with the circuIation through its vesseIs. The consistency of the gland is uniformIy soft. On section it is moist and Iight amber in color. When a knife bIade is drawn across its cut surface, a honey- comb appearance is reveaIed and when pressure is appIied to it, the surface exudes a thin, watery, Iight yeIIow substance.

NON-TOXIC DIFFUSE GOITRE

The emargement of the thyroid gIand commonIy referred to as “simpIe”2 or “endemic”3 goitre, occurs during adoles- cence and earIy aduIt Iife. It is more com- mon in women than in men in a ratio of 6 to I. So insidious is the onset of the dis- ease that the patient rareIy is abIe to recaI1 the exact time when the goitre first ap-

Microscopic Examination. Sections of the thyroid show the acini varying in size but usuaIIy Iarge and distended with a uniformIy staining coIIoid. The waIIs are thin and Iined with Iow cuboidal or ffattened epitheIium. The cytopIasm of the ceIIs stains deepIy; the nucIei are smaI1, round and centraIIy located. There are areas in which the acina1 waIIs show severa Iayers of ceIIs; these abutments are known as “Sanderson’s po1sters.“4 In some acini thin, withered spurs of epitheIia1 ceIIs may be seen projecting into the lumen. Because of the ceIIuIar proliferation and the enIargement of the acini, the con- nective structures appear inconspicuous

* From the Department of Surgery of the New York HospitaI and CorneII Medical CoIIege.

I2

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and avascuIar. There are, however, areas psychic shock. The course of the disease of Iymphoid hyperpiasia around the vesseIs in the interacina1 spaces. (Fig. I .)

may be rapidly progressive or it may be interrupted by periods of regression of

FIG. I. The acini are large and distended with a uniformly staining colloid. The celIs lining the acini are of low cuboidal or flattened epi- thelium. The nuclei are uniform in size and staining properties, and are .Iocated in the center of the cell.

TOXIC DIFFUSE COITRE

Toxic diffuse goitre is a disease char- acterized by diffuse enIargement of the thyroid associated with hyperfunction which stimuIates abnorma1 activity of the vegetative nervous system; the mani- festations of the disease are nervousness, increased metaboIic rates, increased pulse rates and, in many cases, exophthaImos. This condition is referred to in the Iitera- ture variously as “exophthaImic goitre,“5 “ Graves’ disease,“6 “ Basedow’s disease “’ and “ hyperthyroidism.”

Toxic goitre has its onset more commonIy in the second or third decades of life, though it has been observed from infancy to old age. It affects women more often than men, the ratio being g to I. In the majority of cases the onset of symptoms may be traced to a period of emotiona strain or

FIG. 2. There is marked epitheiia1 overgrowth, the ceIIs Iining the acini have proIiferated and become heaped up so as to encroach upon the lumen by papilIary projections. The acini contain scant coIIoid, with large vacuolated areas at their. periphery. The individuai ceIIs are Iarge and usuaIIy high cuboida1 or even columnar. The nucIei are irregular in size and location.

symptoms. In either case, the administra- tion of iodine may resuh in rapid disap- pearance of the signs of hyperthyroidism. The improvement in the clinical picture is accompanied by changes in the thyroid gIand which appear both on gross and microscopic examination.

Gross Examination. In toxic diffuse goitre the thyroid usuaIIy is symmetricahy enlarged; rareIy the enlargement is con- fined to one portion of the gIand, but with- out exception there is a demonstrabIe increase in its tota size. In comparison with the norma thyroid it is dark in color and its vascuIarity is increased. The cut surface is bhrish red and resembIes tran- sected striated muscle and when a knife bIade is drawn across it, a brown viscid

14 American Journal of Surgery GIenn & Hauch-Thyroid Diseases OCTOBER, 1936

materia1 is expressed, Ieaving a granuIar the connective tissue is inconspicuous be- surface. The appearance of the gIand is cause of the epitheIia1 proIiferation; the aItered after adequate iodine therapy; interacina1 structures show increased vas-

FIG. 3. The acini contain coIIoid which takes a deeper stain; there are areas of vacuolization. The papillary spurs of epitheIium have re- ceded. The ceils are smaIIer, having returned to a low cuboidal type. The nuclei are more reguIar in size and are centraIIy located. The interacina1 stroma is more prominent.

then it becomes Iighter in coIor, firmer in consistency and it exudes a transIucent geIatinous material. This change is due to the Iarger amounts of coIIoid in the acini after the administration of iodine.

Microscopic Examination. The acini are irregular and their lumen, normaIIy fiIIed with coIIoid, is encroached upon by the Iining ceIIs which are increased in number and size. In some of the acini the epitheIia1 overgrowth resuks in such heaping up of ceIIs as to form papiIIary projections into the Iumen. (Fig. 2.) In spite of the dimin- ished space in the acini, the Iumen is onIy partly fiIIed with coIIoid of a poorIy stain- ing quaIity surrounded by vacuoIated areas. In comparison with the normaI thyroid,

FIG. 4. There is no definite arrangement of the acini which are smaI1 and contain very IittIe or no coIIoid. The lining ceIIs are pale and contain smaI1 acini. The interacinal tissues are of a paIe structureless materia1. In the center of the section may be seen a smaI1 cyst lined by Aattened epithelium. Scattered through the interacina1 structures are many individua1 epitheIia1 cells.

cuIarity with scattered areas of Iymphoid hyperpIasia. The most significant change in the individua1 ceI1 is its metamorphosis from the Iow cuboida1 to a high coIumnar type. Under a high power Iens the ceIIs are seen to have Iost their characteristic structure; they vary in size, shape and staining quaIities. The nucIei aIso are irreguIar in structure and are not pIaced in the center of the ceI1; mitosis may occasionaIIy be observed.

FoIIowing the administration of iodine, certain definite changes may be observed under the microscope. The acini are f!iIIed with uniformIy staining coIIoid surrounded

New SERIES VOL. XXXIV. No. I GIenn & Hauch-Thyroid Diseases American Journal of Surgery 15

by a smaI1 zone of vacuolization. The acina1 Iumen appears Iarger than previousIy. The ceIIuIar spurs have receded and diminished in size. The connective tissue is prominent and retains its Iymphoid hyperpIasia. The individua1 ceI1 is smaIIer and displays greater uniformity in staining properties. The nucIei tend to occupy the center of the ceI1 (Fig. 3).

The changes in the thyroid produced by the spontaneous regression of the disease or by the administration of iodine are referred to as invoIution. This process of transition from hyperfunction to norma physioIogica1 activity may be compIete, or it may be confined to one part of the grand when it is known as incomplete invoIution. Uniform return to norma function of the entire gIand is rareIy seen and commonIy a11 grades of transition may be observed in one specimen. InvoIution is accompanied by scarring of the connec- tive tissue with persisting hyperpIasia of the Iymphoid eIements.

TOXIC NODULAR GOITRE

NoduIar goitre with hyperthyroidism occurs more commonly in the fourth and fifth decades of Iife and more frequentIy in women than men, the ratio being 5 to I. The manifestations of hyperthyroidism are not so severe as in toxic diffuse goitre. The onset of symptoms is more msidious and the disease, therefore, Iess acute but of Ionger duration. Because of the proIonged strain upon the system in toxic noduIar goitre, the disease may be associated with genera1 organic disturbances; cardiac dam- age, for instance, is a frequent accompani- ment of this type of goitre. In response to iodine therapy, the changes are Iess dra- matic than in toxic diffuse goitre and the resuIts of thyroidectomy not so pronounced.

Gross Examination. In toxic noduIar goitre the gIand is irreguIarIy enIarged by the presence within its substance of one or more nodules. These noduIes vary in size, distribution and structure and a singIe gland may contain any one or severa

different types. According to their struc- ture the noduIes may be cIassified as foIIows :

I. NoduIes composed of norma thyroid (pseudonoduIes) ;

2. NoduIes composed of hyperpIastic thyroid tissue;

3. NoduIes composed of cohoid thyroid;

4. “ FetaI adenomas” of the thyroid; 5. Cysts of the thyroid; 6. True adenomas of the thyroid. A description of the six types of noduIes

is given to cIarify the compIex picture presented by noduIar goitre.

I. The noduIe composed of norma thyroid may we11 be defined as a pseudo- noduIe for it assumes the shape of a noduIe onIy because of compression and distortion by the surrounding structures. Under the microscope the tissue shows no variation from normaI thyroid tissue.

2. The toxic noduIe varies in size and consistency. The tissue of which it is com- posed is indistinguishabIe grossIy or micro- scopicaIIy from the gIand in toxic diffuse goitre and, Iike it, it undergoes the changes of involution after iodine therapy. The process of invoIution may be compIete in one noduIe and non-existant in neighboring noduIes in the same goitre; even in the individual noduIe there may be Iack of uniformity in this respect. When compIete involution has occurred, the noduIe as- sumes the appearance of involuted tissue in toxic diffuse goitre.

3. The noduIes composed of “coIIoid” tissue are Iighter in color than either norma thyroid or the hyperpIastic gIand. They are usually smaI1. Under the micro- scope a section is identical with one from a non-toxic diffuse goitre.

4. The so-caIIed “feta1 adenoma”s of the thyroid forms another type of nodule. On gross section a glazed, grey substance is seen; it is we11 encapsuIated and flecked with areas of necrosis. SmaII cysts con- taining a cohoid-Iike material or degener- ated bIood and choIestero1 crystals may be found. Calcification may aIso be present. On microscopic examination of the smaIIer

I 6 American journal of Surgery GIenn & Hauch-Thyroid Diseases OCTOBER, IQ36

noduIes of adenomatous structure, the section shows a marked absence of the normaI arrangement of the acini into IobuIes. The acini are smaI1 and wideIy separated by a pecuIiar structureIess mate- rial resembIing colloid. (Fig. 4.) Scattered through this substance there may be found cIumps of red blood ceIIs and many epi- thelial ceIIs, either separated or arranged in groups. SmaII cysts fiIIed with bIood and groups of ceIIs containing Iipoid eIements may aIso be present. The Iarger nodules of adenomatous tissue have a different ap- pearance. In them there is greater evidence of degeneration; the cysts are Iarger and ceIIs with Iipoid content are more numer- ous. Areas of hyaIine degeneration and caIcification may be encountered. The dense fibrous capsule around the noduIe often contains caIcium deposition.

5. Cysts of the thyroid forming a dis- tinct noduIe of themseIves or Iocated within coIIoid or adenomatous noduIes, vary greatIy in size. They may be thin waIled and fiIIed with coIIoid-Iike materia1 or with a chocoIate coIored substance flecked with crystaIs of choIestero1. The waIIs may be thick with gritty, caIcified areas and soIid cartiIagenous projections may extend into the cavity of the cyst. Under the microscope it is possibIe to foIIow the successive stages of cyst forma- tion and deveIopment. The rupture of several adjacent acini distended with cohoid, forms a smaI1 cyst. Subsequently, neighboring acini rupture into the cyst and increase its size. The process continues in this manner until an acina1 bIood vessel is injured; the resuIting hemorrhage mixes blood with the content of the cyst to which phagocytes containing Iipoid are Iater added. The consequent inflammatory reac- tion Ieads to fibrous thickening of the waI1 with hyahne degeneration and calcium deposition.

6. True adenomasg of the thyroid. There is a smaI1 group of cases in which the noduIe has the features of a true tumor. In such noduIes the tissue is composed of strands

of epitheIia1 ceIIs separated by a delicate stroma containing many Iarge vesseIs. Under higher magnification the strands are seen to be composed of soIid cIusters of ceIIs in which no Iumen can be detected.

These types of tissue are not always restricted to the noduIes; often any one of them may form a portion of the tissue lying between the nodules.

NON-TOXIC NODULAR GOITRE

The noduIar goitre without hyperthy- roidism is seen in earIier Iife than the toxic noduIar goitre; however, it may occur in the extremes of age as weI1. It is encoun- tered in women more often than in men, the ratio being 5 to I. The goitre may be present for a Iong time before symptoms reIating to it force the patient to consuIt a physician. The symptoms depend upon the degree of pressure the gIand exerts upon neighboring cervica1 structures. Occasion- aIIy a patient wiI1 compIain of manifesta- tions commonIy associated with hyper- thyroidism. On cIose questioning it wiI1 be found that these compIaints were imposed upon the imaginative patient by state- ments made by reIatives or friends famiIiar with the story of hyperthyroidism. True signs of toxicity are absent.

Gross Examination. In gross appear- ance, this goitre is indistinguishable from toxic nodular goitre.

Microscopic Examination. The out- standing difference between this and toxic noduIar goitre is the absence of nodules of hyperplastic tissue. The areas of involu- tion and of a11 stages of cyst formation and degenerative changes are simiIar to those described under toxic noduIar thyroid.

In the previous description of noduIes the faI.se adenomas have been considered. Their formation is the result of two factors, first, the physioIogica1 changes fohowing hyperplasia and second, mechanica dam- age to the circmation. This view is upheId by MarinelO in his recent work and the mechanical factor has been emphasized and described by Wangensteenll in his

NEW SERIES var. XXXIV, No. I GIenn & Hauch-Thyroid Diseases American Journal of Surgery 17

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