Joll's Diseases of the Thyroid Gland

526 Pages·1951·19.088 MB·English

by  Francis F. Rundle (Auth.)

CALEB HILLIER PARRY, M.D., 1756—1822
{Reproduced by permission of the Governors of the Royal United Hospital, Bath)
Frontispiece
JOLL'S DISEASES
OF THE
THYROID GLAND
BY
FRANCIS F. RUNDLE
M.D., F.R.C.S.
The Unit of Clinical Investigation, The Royal North Shore
Hospital of Sydney, Australia; Visiting Surgeon, Prince Henry
Hospital, Sydney. Formerly Assistant Surgeon and Assistant
Director of the Surgical Unit, St. Bartholomew's Hospital,
London, England, and Clinical Research Associate, London
County Council Thyroid Clinic. Jacksonian Prizeman and
Hunterian Professor, Royal College of Surgeons of England
SECOND EDITION
LONDON
WILLIAM HEINEMANN · MEDICAL BOOKS LTD.
1951
First Published 1932
Second Edition
(re-set) 1951
This book is copyright. It may not be
reproduced in whole or in part, nor may
illustrations be copied for any purpose
without permission. Application with
regard to copyright should be addressed
to the Publishers.
PRINTED IN GREAT BRITAIN BY
J. W. ARROWSMITH LTD., QUAY STREET AND SMALL STREET, BRISTOL
PREFACE TO THE SECOND EDITION
FOR some years before his untimely death in 1945, Mr. Cecil Ml envisaged
the production of this second edition. It was proposed that we should
revise and rewrite the book jointly. Because of the war this was never pos­
sible and I must accept full responsibility for the subject-matter included in
the new edition, apart from that in the chapters written by Drs. N. F.
Maclagan, J. C. McClintock, S. Rowbotham, and G. Crile, Jnr. I am much
indebted to them for their valuable contributions.
The section on Struma Lymphomatosa (Chapter XXI) was written by
the late Mr. C. A. Joll and published by him in the British Journal of
Surgery in 1939. It is still one of the standard papers on the subject and
has been included in the text with but little modification. We are grateful
to the editors of the British Journal of Surgery for permission to reproduce
it here.
It will be noted that the mode of presentation of thyroid diseases and
general scope of the book have been preserved as in the first edition. Remark­
able advances in our knowledge of the pathology and treatment of goitre
have occurred in the past twenty years. Perhaps the most spectacular are
those resulting from the exploitation of radioactive iodine as an investiga­
tive tool; but hardly less important are those accruing from the use of
the anti-thyroid drugs. Indeed it is a source of wonder and no small
satisfaction how clearly understanding of practically all forms of goitre has
widened.
Thanks chiefly to radioactive iodine, growth of thyroid knowledge con­
tinues apace at the present day. Any large book such as this can only report
the position at one instant of this growth.
Much of the new clinical material included in this second edition was
taken directly from my Jacksonian Prize Essay, " The Pathology and
Treatment of Thyrotoxicosis ". I am grateful to the Council of the Royal
College of Surgeons for permission to do this. I have also drawn freely
on case records and experience gained while working as Clinical Research
Associate in the London County Council Thyroid Clinic. My grateful
thanks are due to all members of the medical and lay staff of the clinic for
their help and co-operation, particularly to Dr. J. Piercy and Miss Dean. I
am also grateful to Sir Ernest Rock Carling, Consulting Surgeon to the
Westminster Hospital, London, for his constant help and guidance with
clinical studies of goitrous patients. Much of the clinical research incor­
porated in this new edition was done with the aid of grants from the Medical
v
vi PREFACE TO SECOND EDITION
Research Council. I am grateful to many authors and publishers for per­
mission to reproduce tables and illustrations. The source of such borrowed
data is acknowledged in each case, the author's name being noted in the
caption (the original paper concerned will be found in the list of references
at the end of the corresponding chapter). I am also grateful to the library
staff of the Royal Society of Medicine for much help with access to reading
matter. Finally it is a pleasure to acknowledge the ready and able help given
during the closing stages of this edition's preparation by Miss D. M. Drake,
Secretary of the Unit of Clinical Investigation at the Royal North Shore
Hospital of Sydney.
FRANCIS F. RUNDLE.
135 Macquarie Street,
Sydney, Australia.
November, 1950.
CHAPTER I
HISTO-PHYSIOLOGY OF THE THYROID GLAND
The Thyroid Follicle — The Endogenous Iodine Cycle — Iodide Uptake — Hormone
Synthesis — The Thyroglobulin Compartment — The Definitive Secretion of the
Follicle — Radio-iodine Uptake and Clearance as Indicators of Thyroid Function —
Regulation of Thyroid Sscretion — Pituitary Thyrotropic Hormone in Health and
Disease —Thyrotropic Hormone in the Blood—Iodine Absorption and Excretion—
The Role of the Lh er in the Endogenous Iodine Cycle—The modus operandi of the
Thyroid Hormone—Dosage and Activity of Thyroxine—Thyroid Hormone and
Tissue Oxidations.
Iodine, present in the external environment in the pelagic, cellular stage of
animal evolution, is also essential for the proper maintenance of tissue activity
in man. The function of the thyroid gland is to trap and concentrate iodine,
harness it in organic combination, and then to secrete it into the blood in
the form required by the tissues. The gland thus governs the endogenous
iodine cycle and variations in its activity profoundly influence tissue
metabolism.
The Thyroid Follicle
The thyroid is unique in that it has the faculty of storing a provisional
secretion outside its cells; hence it can store greater quantities than can other
glands. It is also remarkable in that, when it is stimulated, it can probably
call on a two-way method of secretion, viz., directly from the basal cytoplasm
into the adjacent blood capillaries, and indirectly into the follicle and back
by transcellular secretion to the capillaiy blood. It cannot be over-empha­
sized that the thyroid follicle is a dynamic unit, subject to a wide range of
physiological influences. In ordinary histological sections, we catch this
changing pattern at only one instant in its life history.
Thomas (1934) in a valuable monograph, expounds a concept of thyroid
histology (Fig. 2) which helps to explain many of the appearances in normal
and abnormal glands. The height of the epithelial cells indicates their degree
of activity. The flat endothelioid cells secrete colloid only very slowly into
the follicle. Tall, cylindrical cells mobilize the stored hormone and excrete
it into the blood stream. Such tall cells occur in segments (excretory segments)
of the follicle wall and their appearance indicates a phase of considerable
activity (Figs. 3 and 4). The original follicle (macrofollicle) tends to collapse
as colloid is lost; then microfollicles appear beneath and round the excretory
segment.
If as the result of severe physiological or pathological demands, intense
resorption of colloid occurs, the macrofollicle may collapse and fragment
more or less completely. The whole field is then occupied by microfollicles.
If another wave of stimulation sweeps over the complex, the microfollicles
become further reduced in size and progressively greater numbers of solid
clumps of cells are seen.
1
2 DISEASES OF THE THYROID GLAND
Usually, however, after a period of excretory activity the complex enters
a phase of intra-follicular secretion. Colloid re-accumulates in the follicles;
they fuse successively to re-form the macrofollicle.
The papilliferous formations of the thyrotoxic gland may be regarded as
a further development of Thomas excretory segments. His microfollicles,
with their cuboidal epithelium, correspond to the microfollicular type of
FIG. 2.
hyperplasia also seen in thyrotoxicosis. Finally, great sheets of solid epi­
thelium occasionally occur in intensely hyperplastic goitres (regenerative
epithelial hyperplasia of Broders, 1929). On the contrary, during periods of
involution after hyperplasia, fusion of many more follicles than existed
originally would result in the colloid micro-cysts and other features of colloid
goitre.
Lever (1948) enumerates the histological criteria of increased thyroid
activity as follows.
(i) An increase in height and number of the follicle cells.
(ii) Resorption of colloid.
HISTO-PHYSIOLOGY OF THYROID GLAND
FIG. 3.—Thomas' concept: excretory segment and subjacent microfollicles.
(x 150).
FIG. 4.—Thomas'Type II cells (X 500).
4 DISEASES OF THE THYROID GLAND
(iii) An increase in the interfollicular space due to enlargement of the
blood capillaries.
(iv) The nucleus changes its position from the base towards the apex of
the cells.
The average height of the follicular epithelium (mean cell height) has been
widely used as a measure of the activity of a particular gland (Rawson and
Starr, 1938). The method of fixation must be standardized to avoid errors
due to cell shrinkage (Holmgren and Nilsonne, 1948).
Williams (1937-1944), has developed interesting techniques for studying
the thyroid follicle in vivo. In some cases he has transplanted living follicles
into small transparent glass and mica chambers in the rabbit's ear. In others
he has observed the reactions and appearance of the follicles in the thyroid
FIG. 5.—Cycle of changes in the living thyroid follicle (after Williams).
The insert on the right shows the steps in colloid resorption.
isthmus of the mouse, by transillumination through the trachea and suitable
micro-dissection.
He has been able to trace cyclic changes in the living follicles (Fig. 5).
Colloid release is followed by partial collapse. The follicle enters a phase of
colloid secretion and gradually recovers its shape. The number of cycles
which a follicle can complete is apparently indefinite, and the time required is
extremely variable, from nineteen hours to twenty-one days or more.
Prolonged arrest of the cycle can occur at almost any stage. Most follicles
are stationary at any given time, or are undergoing slow oscillation between
repletion and partial collapse. The great majority are resting and constitute
a potential reserve.
Williams stresses the great activity of the free borders of the cells. In­
dentations appear in the inner margin of the follicle, colloid flows in. The
apical protoplasm finally flows across and cuts off an intramural colloid
HISTO-PHYSIOLOGY OF THYROID GLAND 5
droplet. But the droplet never enters the interfollicular space as such. It
slowly diminishes in size within the follicle wall, and finally disappears. The
time required for the ingestion and assimilation of a colloid droplet is usually
about one half-hour.
After stimulation with thyrotropic hormone, the follicle wall may appear
loaded with droplets (Williams, 1939). But the intrafollicular vacuoles so
common in fixed sections are extremely rare in the living follicle (Williams,
1941).
The classical picture of the normal follicle, one which is round, lined by
cuboidal cells, with distinct inner and outer cell boundaries, is only occasion­
ally seen in living follicles; more often the inner cell boundary is faint,
extremely irregular or even invisible. The inner cell membrane is seen best
when the follicle is inactive.
Williams also observed adjacent follicles fusing. During the exhibition
of thyrotropic hormone more follicles had thicker walls and less colloid than
FIG. 6.—De Robertis's Concept
normal and the colloid appeared and disappeared more rapidly, but the
essential character of the follicular cycle was unchanged.
The capillaries around the follicles are numerous and of large calibre.
The rate of flow in them is rapid and does not fluctuate. No empty vessels
are seen. Williams (1944) believes that the ordinary thyroid requirements
of the body are met, not by basal secretion, but by the slow utilization of the
colloid. This is not necessarily associated with visible changes in cell struc­
ture or colloid volume.
The work of de Robertis (1948a) illustrates the approach of the cyto-
logical chemist. In earlier studies (1941a) he applied a freezing-drying tech­
nique which preserves the different cellular components, particularly the
proteins, taking part in secretion. Close study suggests that the normal
direction of secretion is towards the follicle (Fig. 6). This is best seen in certain
tall, cylindrical cells. The nucleus is basal, the Golgi apparatus and mito­
chondria are apical. Minute droplets first appear near the nucleus, gradually