Thyroiditis and Thyroid Function. Clinical, Morphological, and Physiopathological Studies

347 Pages·1972·13.15 MB·English

by  P. A. Bastenie, A. M. Ermans, P. Alexander and Z. M. Bacq (Auth.)

THYROIDITIS AND
THYROID FUNCTION
CLINICAL, MORPHOLOGICAL, AND
PHYSIOPATHOLOGICAL STUDIES
BY
P. A. BASTENIE and A. M. ERMANS
with the co-operation of
M. BONNYNS, G. DELESPESSE, P. NÈVE and
L. VANHAELST
with a special contribution on
ASSOCIATED P I T U I T A R Y PATHOLOGY
by
M. HERLANT and J. L. PASTEELS
Foreword by
D. DONIACH
PERGAMON PRESS
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Copyright © 1972 P. A. Bastenie and A. M. Ermans
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First edition 1972
Library of Congress Catalog Card No. 76-163852
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08 016628 8
Foreword
THE different forms of subacute and chronic thyroiditis have always stimulated great
interest among thyroid specialists and endocrinologists. In the past fifteen years the
concept of autoimmunity and the application of radioactive iodine uptake and thyroid
antibody tests to the investigation of goitre patients have clarified this group of diseases.
It is now accepted that all forms of lymphoid thyroiditis are an expression of organ
specific auto-immunization based upon a familial predisposition and possibly still un-
known external agents while De Quervain's disease is more clearly virus induced and
non-autoimmune. The controversy about Hashimoto's and Riedel's thyroiditis which
occupied the literature in earlier years is now almost settled and it seems clear that
Riedel's disease is in some way related to a group of unexplained fibrosing conditions
which include retroperitoneal, mediastinal or cholangitic forms but bear little relationship
to struma lymphomatosa or autoimmunity as we now know it.
One of the most interesting problems is the connection of chronic thyroiditis with the
other autoimmune disorders and Paul Bastenie's 1937 monograph on this topic is one of
the pioneer works. He showed not only that primary myxoedema and Hashimoto's
goitre had the same underlying lesion but also that thyroiditis was found associated with
pernicious anaemia, with subclinical hepatitis and several other conditions forming a
spectrum of autoimmune disorders.
In subsequent years Professor Bastenie and his team at the Free University of Brussels
have made important contributions to the detailed understanding of the incipient stages
of hypothyroidism and have revealed important clinical connections with obesity and
atherosclerosis. Their wide clinical experience is summarized in the present book which
also tries to give the practising physician an overall view of iodine metabolism and pitui-
tary thyroid relationships.
The clinical case histories given as examples for each type of thyroiditis add immediacy
to the more didactic chapters, while the recent statistical research on thyroid antibodies in
patients with atherosclerosis gives a foresight into future computer medicine.
DEBORAH DONIACH M.D., M.R.C.P.
Reader in Immunopathology,
The Middlesex Hospital, London
vu
Acknowledgements
NEARLY fifteen years ago the pioneer work of Witebsky and his group and of Doniach and
Roitt in the field of thyroid autoimmunity renewed interest in the clinico-pathological
studies of thyroiditis performed earlier in this department and gave impetus for fresh
efforts. Thanks to the new methods of thyroid investigation and the strenuous endeavours
of a team of enthusiastic co-workers, material soon accumulated from which some new
concepts emerged on the significance of the various forms of thyroiditis. The stimulating
criticism of Dr. D. Doniach is gratefully recognized.
This work could not have been achieved without a great deal of help. In the first place
the authors wish to express their gratitude to Professor P. Dustin. Not only were all
ultrastructural studies performed in his department, but without his help the thyroid
autoradiograph and the studies of Professors Herlant and Pasteels on the pathology of the
pituitary in chronic thyroiditis would have been impossible. Moreover, many illustrations
of this book are due to his kind co-operation.
The authors wish to thank Dr. J. E. Dumont, Dr. Galand, Dr. Decostre, and Mrs.
Golstein who contributed with many valuable documents. They appreciate the skilful
help of Mrs. Wouters, Miss Marchand, and Miss Dubois in the technical studies, of
Mr. De Meire and Miss Procureur in the illustrations, and of Mrs. Delbrassine and Miss
Malbrecq in the preparation of the manuscript. Great thanks are due to Mrs. Jank for her
help in our struggle with the intricacies of the English language.
Our sincere gratitude goes to the authors (mentioned in the text) and the editors of the
journals who permitted reproduction of published data:
Journal of Clinical Endocrinology
Act a endocrinologica
Journal de Microscopie
Pathologia europea
Virchows Archiv für pathologische Anatomie
Acta clinica belgica
The original studies on which the present monograph is based mainly, were supported
by grants from the Fonds National de la Recherche Scientifique, the Fonds de la Recherche
Médicale Scientifique (Belgium), the Centre de Recherches Endocrinologiques (Brussels),
and the Fondation Tournay-Solvay (Brussels). Several of these studies were the results of
a Contract Euratom/Universities of Pisa and Brussels (No. BIAC 026-63-4).
P.A.B.
A.M.E.
viii
Introduction
P. A. BASTENIE
(24)
"Chronic thyroiditis: a potentially confusing picture"
THE subject of chronic thyroiditis is surrounded by many confusing concepts and
denominations. The main cause of this situation is our ignorance of the aetiology of the
various disorders which are included under this term.
Early clinico-pathological studies ascribed all forms of chronic lymphocytic thyroiditis
(25,28)
to some infectious process and blamed tuberculosis, syphilis, and non-specified
infections as the pathogenic agents. Other non-specified infections were thought to invade
the thyroid through the remnants of the thyroglossal duct.
It is doubtful whether, except in a few cases of tuberculous infection, any of these
agents have ever played an important role in the genesis of lymphocytic thyroiditis. It is,
however, most likely that certain viral infections are responsible for the development of
acute, subacute, and possibly chronic reactions of the thyroid parenchyma. The des-
cription of all conditions of lymphocytic thyroiditis under the single heading of non-
specific chronic thyroiditis has not helped matters.
Many years ago the study of a number of well-delineated nosological entities (myxoe-
dema, Hashimoto's struma lymphomatosa, toxic goitre) showed that these conditions
have in common identical parenchymatous and inflammatory lesions, varying only in
(4)
degrees.
Alongside these conditions of diffuse chronic lymphocytic thyroiditis, offering a
definite clinical appearance, identical focal or diffuse inflammatory lesions were described
(4,25)
in otherwise normal thyroids which had produced no clinical symptoms.
The presence of the same lesions observed in such different conditions suggested that
they were part of the same pathological process superimposed on different thyroid states.
No evidence of an infectious origin was found, and the lymphocytes and plasma cell
infiltrates were explained as inflammatory reactions to particular metabolic cell lesions
4,11}
leading to cell degeneration and lysis/
At the present time, the fundamental sameness of the process, as first suggested by
10,19,22,26
microscopical study, is generally admitted/ * This view is based on very strong
evidence. Electron microscopy has confirmed the previous observations by showing
(18)
identical lesions in different variants of lymphocytic thyroiditis. Biochemical studies
have identified the same alterations of iodine metabolism in the hypertrophie thyroiditis
(5) 6,7)
of Hashimoto's disease and in atrophie thyroiditis/ Finally, immunological studies
have detected the same thyroid antibodies in most variants of lymphocytic thyroi-
10,21
ditis/ *
1
2 THYROIDITIS
The discovery of thyroid antibodies circulating in the blood of subjects affected with
20)
chronic lymphocytic thyroiditis by Roitt et alS and the experimental production of
(30)
autoimmune thyroiditis in the rabbit by Witebsky and Rose have been of capital
importance in the study of this pathology. There is no doubt that the autoimmune pro-
cess corresponds to important tissue alterations, possibly leading to the development of a
self-maintaining destructive process.
The concept of lymphocytic thyroiditis as an autoimmune disease naturally led to the
(9)
use of the general term "autoimmune thyroiditis" for all the clinical entities previously
(27)
described as individual variants of "non-specific chronic thyroiditis". Thus, as Wayne
put it so well, "the definition of the disease is switched from histological bases to an
immunological aetiology". This attitude assumes that the autoimmune process is solely
responsible for all forms of lymphocytic thyroiditis. It implies, as the essential cause of the
12,14,23
disease, the existence of a primary inborn anomaly of the autoimmune apparatus/ *
However, the basis for such an attitude is not proven. A viral or metabolic anomaly may
well trigger off the inflammatory process.
13,17,27) 3 15)
In many textbooks on thyroid diseases* or on autoimmune diseases/
the section on chronic thyroiditis is entitled "Hashimoto's disease", and in many papers
the terms "chronic thyroiditis" and "Hashimoto's thyroiditis" are used synonymously.
But chronic thyroiditis may occur with several variants which display different clinical
characteristics, follow different courses, and require different treatments.
Further confusion arises from the assignment of an autoimmune origin to thyro-
(2) 16)
toxicosis by Adams and by McKenzie/ This disease is claimed to be induced and
maintained by a particular factor—the long-acting thyroid stimulator (LATS) discovered
1}
jn the serum of hyperthyroid subjects* and displaying the characteristics of a thyroid
TABLE 1.1. CLASSIFICATION OF THYROIDITIS (AM. THYROID
Assoc. 1969)
"Diseases characterized by euthyroidism"
5. Acute thyroiditis
suppurative
subacute non-suppurative
6. Chronic thyroiditis
1. Lymphocytic (Hashimoto) :
(a) variants (1) fibrous
(2) adolescent
(3) atrophie*
(4) focal
(b) with eye changes of Graves' disease
2. Invasive fibrous (Riedel)
3. Suppurative
4. Non-suppurative
* This condition is further mentioned under the heading
"II. Diseases primarily characterized by hypothyroidism."
INTRODUCTION 3
antibody. Some authors consider that thyrotoxicosis and Hashimoto's disease are two
(10)
facets of the same pathological process. Moreover, it is believed that thyrotoxicosis
might originate during the course of lymphocytic thyroiditis of the Hashimoto type, and
the term "Hashitoxicosis" has even been proposed. Thus autoimmune lymphocytic
thyroiditis might lead in some cases to the progressive destruction of the gland, with
ensuing hypothyroidism, and in others to the development of thyrotoxicosis.
Lastly, it should be remembered that in certain types of chronic thyroiditis no
serological signs of thyroid autoimmunity are observed. This is the case in invasive
fibrous thyroiditis, described at the end of the last century by Riedel, and which has
since been confused with the sclerotic variant of Hashimoto's thyroiditis.
It is therefore understandable that a paper describing such developments was entitled
(24)
"Chronic thyroiditis; a potentially confusing picture".
The classification of thyroid diseases recently proposed by the Committee of Nomen-
(29)
clature of the American Thyroid Association goes a long way to combat these in-
tricacies (Table 1.1). Thyroiditis is mentioned under "Diseases primarily characterized by
euthyroidism", and atrophie thyroiditis (a variant of lymphocytic chronic thyroiditis)
is also referred to under the heading of "Diseases primarily characterized by hypothy-
roidism". However, chronic thyroiditis is still identified with Hashimoto's disease,
although different variants are recognized. Moreover, thyroiditis is not listed under the
"Diseases primarily characterized by hyperthyroidism."
These preliminary remarks underline the importance of the new concepts introduced
in the study of thyroid diseases. The interest of chronic thyroiditis extends far beyond the
narrow limits assigned to it by the textbooks. Study of the subject must embrace the
aetiology of idiopathic myxoedema, the mechanism of thyrotoxicosis, and many im-
portant problems of diagnosis and therapy in general thyroidology.
The aim of the present monograph is to clarify this complex pathological picture as far
as possible. Material for such an endeavour is provided by recent progress in morpholo-
gical, biochemical, and serological thyroid studies, and by work currently under way in
our own department of medicine and in the laboratories of Nuclear Medicine (Dr. J. E.
Dumont), Radioisotopes (Dr. A. M. Ermans), and Pathological Anatomy (Prof. P.
Dustin) of this University.
References
1. ADAMS, D. D., The presence of an abnormal thyroid stimulating hormone in the serum of some
thyrotoxic patients, / . din. Endocr. 18, 699 (1958).
2. ADAMS, D. D., Pathogenesis of the hyperthyroidism of Graves' disease, Brit. med. J. 1, 1015 (1965).
3. ANDERSON, J. R., BUCHANAN, W. W. and GOUDIE, R. B., Auto-immunity: clinical and experimental,
C. C. Thomas, Springfield (1967).
4. BASTENIE, P. A., Étude anatomo-clinique et expérimentale des inflammations chroniques et des
scléroses du corps thyroïde, Arch. int. Méd. exp. {Liège) 12, 1 (1937).
5. BUCHANAN, W. W., KOUTRAS, D. A., ALEXANDER, W. D., CROOKS, J., RICHMOND, M. H., MCDONALD,
E. M. and WAYNE, E. J., Iodine metabolism in Hashimoto's thyroiditis, / . clin. Endocr. 21, 806 (1961).
6. BUCHANAN, W. W., HARDEN, R. M C G . , KOUTRAS, D. A. and GRAY, K. G., Abnormalities of iodine
metabolism in euthyroid non-goitrous women with complement-fixing anti-microsomal thyroid
antibodies, / . din. Endocr. 25, 301 (1965).
4 THYROIDITIS
7. CAMUS, M., ERMANS, A. M. and BASTENIE, P. A., Alterations of iodine metabolism in asymptomatic
thyroiditis, Metabolism 17, 1064 (1968).
8. D E GROOT, L. J., Current concepts in management of thyroid disease, Med. Clin. N. Am. 54, 117
(1970).
9. DONIACH, D., HUDSON, R. V. and ROITT, I. M., Human auto-immune thyroiditis: clinical studies.
Brit. med. J. 1, 365 (1960).
10. DONIACH, D. and ROITT, I. M. Auto-immune thyroid disease, in Textbook of Immunopathology
(P. A. Miescher and H. J. Müller-Ebernard, eds.), Grune & Stratton, New York and London,
Vol. Ill, p. 516 (1969).
11. FRIEDMAN, N. B., Cellular involution in the thyroid gland: significance of Hürthle cells, / . clin.
Endocr. 9, 874 (1949).
12. HALL, R., OWEN, S. G. and SMART, G. A., Evidence for genetic predisposition to formation of thyroid
antibodies, Lancet ii, 187 (1960).
13. HEIMPEL, H. and MÜLLER, W., Die Immun-thyreoditis, in Ergebnisse der inneren Medizin, Springer,
Berlin, Neue Folge, 19, 380 (1963).
14. IRVINE, W. J., Thyroid auto-immunity as a disorder of immunological tolerance, Quart. J. exp.
Physiol. 49, 324 (1964).
15. MACKAY, I. R. and BURNET, F . M., Auto-immune Diseases, C. C. Thomas, Springfield (1963).
16. MCKENZIE, J. M., Etiology of Graves' disease, / . clin. Endocr. 25, 424 (1965).
17. MEANS, J. H., D E GROOT, L. J. and STANBURY, J. B., The Thyroid and its Diseases, 3rd edn., McGraw-
Hill, New York, Toronto and London (1963).
18. NÈVE, P., The ultrastructure of thyroid in chronic autoimmune thyroiditis, Virchows Arch. 346, 302
(1969).
19. PERSSON, P. S., Cytodiagnosis of thyroiditis, Acta. med. scand., suppl., 483 (1967).
20. ROITT, I. M., DONIACH, D., CAMPBELL, P. N. and HUDSON, R. V., Auto antibodies in Hashimoto's
disease (lymphadenoid goitre), Lancet ii, 820 (1956).
21. ROITT, I. M. and DONIACH, D., Human auto-immune thyroiditis: serological studies, Lancet ii,
1027 (1958).
22. SENHAUSER, D. A., Immunopathologic correlations in thyroid diseases, in The Thyroid (Hazard and
Smith, eds.), Williams & Wilkins, Baltimore, p. 167 (1964).
23. SERAFINI, V., MASALA, C , COSTANZI-LANGER, M. and PALA, A. M., Autoimmune diathesis and
thyroid diseases, First Congress of European Society of Pathology, Warsaw, 1966, pp. 111-115.
24. SHANE, L. L., VALENSI, Q. J., SOBREVILLA, L. and GABRILOVE, J.L., Chronic thyroiditis: a potentially
confusing clinical picture, Am. J. med. Sei. 250, 532-41 (1965).
25. SIMMONDS, M., Über chronische Thyreoiditis und fibröse Atrophie der Thyreodea, Virchows Arch.
246, 140 (1923).
26. SMART, G. A. and OWEN, S. G., Thyroiditis and hypothyroidism, / . chron. Dis. 14, 537 (1961).
27. WAYNE, E. J., KOUTRAS, D. A. and ALEXANDER, W. D., Clinical Aspects of Iodine Metabolism,
Blackwell, Oxford (1964).
28. WEGELIN, C , Schilddrüse, in Handbuch der speziellen pathologischen Anatomie und Histologie
(Henke and Lubarsch, eds.), Springer, Berlin (1926).
29. WERNER, S. C , Classification of thyroid disease, Report of the Committee on Nomenclature,
American Thyroid Association, / . clin. Endocr. 29, 860 (1969).
30. WITEBSKY, E. and ROSE, N. R., Studies in organ specificity: IV, Production of rabbit thyroid anti-
bodies in the rabbit, / . Immunol. 76, 408 (1956).
CHAPTER 1
Structure and Function of the Normal Thyroid Gland
A. M. ERMANS, P. NÈVE, and P. A. BASTENIE
1. Introduction
The role of the thyroid is to convert inorganic iodine into thyroid hormones and to
maintain a sufficient quantity of these hormones in the tissues. The gland performs this
role by a complex mechanism which is at present only partially understood; the main
stages are sketched out in Fig. 1.1.
LIVER
FIG. 1.1. Schematic representation of thyroid physiology.
The thyroid concentrates the iodide ion of the circulating blood during its passage
through the gland (phase 1). The iodine is then oxidized (phase 2) and bound to the
"tyrosyl" or "iodotyrosyl" groups of thyroglobulin. Inside this large molecule, the
iodotyrosyl groups of amino acids are converted into thyroxine and triiodothyronine, i.e.
into metabolically active hormones (phase 3). The thyroglobulin accumulates in the
follicular lumen in the form of colloid (phase 4). The hormone compounds are released
by a process of enzymatic proteolysis and secreted into the circulation (phase 5), where
they are almost totally bound to blood proteins and constitute the organic iodine of the
plasma (PBI). These hormones are concentrated partially in the liver (phase 6). A very
5
6 THYROIDITIS
small non-protein-bound fraction penetrates the peripheral tissues by unknown mechan-
isms (phase 7) and there produces a characteristic metabolic effect.
The speed and duration of certain of these phases are partly governed by the hypo-
physial thyrotropic hormone (TSH) (phase 8), whose secretion is itself dependent on a
hypothalamic centre. The quantity of thyroid hormones in the circulation controls the
degree of thyrotropic stimulation through the intermediary of the hypothalamo-hypo-
physial axis (phase 9).
The physiological or biochemical effect of the thyroid hormones is influenced by the
interference of other hormonal factors such as cortisone, epinephrine, and oestrogens.
Finally, the principal pathway competing with the thyroid iodide cycle is represented
by the renal clearance and urinary excretion (phase 10).
Currently held concepts on these different stages of iodine metabolism will be briefly
reviewed in this chapter: special attention is given to certain parameters which are
critically altered in thyroiditis.
2. Morphology
Human thyroid tissue, even under normal conditions, displays a less uniform structure
than that of thyroid glands of the usual laboratory animals. The morphological unit of the
thyroid gland is represented by the thyroid follicle, made up of a single layer of cells
surrounding a mass of colloid. Some controversy exists about the arrangement and the
interlinking of the follicles in the thyroid gland. Certain authors hold that the follicles
are always isolated whereas others maintain that they communicate with each other via
(62,78 121)
a central duct. '
(94)
A recent study using three-dimensional models reconstructed from serial sections
of rat thyroid tissue seems to solve this controversy. The authors report that the follicular
lumen and colloid masses are rarely connected: almost all the follicles are therefore
individual, consisting of epithelial cells completely surrounding the colloid. On the other
hand, epithelial contacts exist between the follicles, which thus form a chain and only
retain their individuality by virtue of their own lumen.
Apart from the follicular cells proper, there are some parafollicular cells also referred
to by the name of "light cells". They occupy an extrafollicular position and produce
22 151 ,152)
calcitonine, a factor which lowers serum calcium/ ' Finally, in rats and mice,
there exists a second system of follicles alongside the classic thyroid follicles. The structure
of the second series is very special, often with desquamation of the cell debris into the
(93 134 208,214)
colloid. ' ' These follicles, sometimes termed "ultimobranchial follicles" have
(208)
also been reported in man. Their significance is at present unknown.
It is possible that the peculiar cell accumulations, often resembling parathyroid tissue,
which appear in thyroiditis glands, take their origin in "ultimobranchial structures".
The appearance of the follicular epithelium reflects to some extent the state of activity
of the thyroid gland. In conditions of hyperactivity or intense stimulation, the usually
cubic epithelium is replaced by a cylindrical epithelium with nuclei located at the base of
the cells. The follicular lumen is reduced. By contrast, hypoactive glands (for instance,