1. Healthcare

Thyroid Research
Proceedings of the Seventh International
Thyroid Conference
Boston, Massachusetts, June 9-13, 1975
Editors:
J A C O B R O B B I N S , Bethesda, M d .
L E W I S E . B R A V E R M A N , Boston, Mass.
Co-editors:
F . J . G . E B L I N G , Sheffield, U . K .
I.W. H E N D E R S O N , Sheffield, U . K .
y-.gp,
1 Ol, ' / A ( 57/
Excerpta Medica, Amsterdam — Oxford
American Elsevier Publishing Co., Inc., New York
©) E X C E R P T A M E D I C A
1976
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duced, stored in a retrieval System or transmitted, in
or by any means, electronic, mechanical, photocopying,
or otherwise, without permission in writing from the
I N T E R N A T I O N A L C O N G R E S S S E R I E S N o . 378
I S B N Excerpta Medica 90 219 0309 1
I S B N American Elsevier 0 444 15202 4
L i b r a r y of Congress Cataloging in Publication Data
I n t e r n a t i o n a l Thyroid Conference, 7th, Boston,
Thyroid research.
1975.
( i n t e r n a t i o n a l congress s e r i e s ; no. 378)
Includes index.
1.
T h y r o i d gland—Diseases—Congresses.
2. T h y r o i d hormones—Congresses. 3 . Thyroid gland—
Congresses. I. Robbins, Jacob. I I . Braverman,
Lewis E.
I I I . T i t l e . IV. S e r i e s .
RC655.I65
1975
616.4'4
76-82A
ISBN 0-444-15202-4 (American E l s e v i e r )
Publisher:
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be reproany form
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Contents
Section
I.
T R H , TSH and control
o f thyroid
function
T R H analog antagonists. C. Y. ßowers, H. Sievertsson,
J. C h a n g , J. Stewart,
S. Castensson,
S. B j o r k m a n , D . C h a n g and K. F o l k e r s
The subcellular distribution of thyrotropin releasing hormone ( T R H ) in rat hypothalamus and brain. A . W i n o k u r and R . D . U t i g e r
The significance of urinary thyrotropin releasing hormone ( T R H ) excretion in man.
R . F . Gagel, I . M . D . Jackson,
D . P . Deprez,
P . D . Papapetrou
and S. R e i c h l i n
Estimates of pituitary Stores of T S H and P R L in normal subjects and patients w i t h
primary hypothyroidism by the use of continuous T R H infusion. L .
Wartofsky,
R . C . D i m o n d , G . L . Noel, J . M . E a r l l and A . G . F r a n t z
Inhibition by somatostatin of T S H response to T R H and of basal T S H levels in man.
/. Weeke,
A . P r a n g e H a n s e n , S. Eskjaer
Jensen and K. Lundbaek
Effect of adiphenine on T S H release by rat anterior pituitaries in vitro. D . J o r d a n ,
G. Ponsin
and R . M o r n e x
Comparison of the effects of triiodothyronine (T3) and thyroxine (T4) on serum
T S H and hepatic mitochondrial glycerophosphate dehydrogenase (a-GPD) activities in thyroidectomized hypothyroid rats. P . R . Larsen and R . D . Frumess
Lack of inhibiting effect of small doses of T3 on the T R H - i n d u c e d release of T S H
in the hypothyroid rat. M . D . G a r c i a , F. Escobar
del Rey and G. M o r r e a l e de
Es cobar
An experimental analysis of the pituitary thyrotropin rebound phenomenon in the
goitrous rat. S . A . D ' A n g e l o , D . H . P a u l and N . R . Wall
Primary structure and immunological comparison of porcine thyroid-stimulating
(TSH) and follicle-stimulating ( F S H ) hormones. / . Closset,
G. M a g h u i n - R o g i s t e r ,
J . - L . V a n d a l e m , Y. Combarnous
and G. H e n n e n
The thyroid stimulating activity of highly purified preparations of human chorionic
gonadotropin.
H. U c h i m u r a , S. N a g a t a k i , T. T a b u c h i , M. M i z u n o and K. I t o
Chronic T 3 treatment abolishes the responsiveness of mouse thyroid to b T S H .
M. Gafni, N . Sirkis and J. Gross
Effect of thyroid hormone or iodide on the thyroidal secretion in vitro: inhibition
Of TSH- and dibutyryl-cyclic-AMP-induced endocytosis. Y. Shishiba,
T. S h i m i z u ,
M. T a k a i s h i , Y. M i y a c h i and Y. Ozawa
Section
II.
T h y r o i d morphogenesis.
Structure-function
III.
Mechanisms
o f thyroid
5
8
11
15
18
21
25
29
33
37
41
44
relationship
Morphogenesis of thyroid follicles in vitro. P. C a u , G. F a y e t and M. M i c h e l - B e c h e t
Electron microscope immunohistochemical localization of thyroglobulin in the rat
thyroid. G. Pelletier,
R . P u v i a n i and J . H Dussault
Chronic thyrotropin Stimulation: A n in vivo and in vitro biochemical and ultrastructural approach. P . Ketelbant-Balasse,
P . Rocmans,
N . F r e d e r i c , J.
Golstein,
and P. Neve
Section
1
48
51
54
Stimulation
Solubilization and partial purification of the thyrotropin receptor. R . L . Täte,
R . J . W i n a n d and L . D . K o h n
The influence of membrane lipids on thyrotropin-receptor interactions. S . Q . M e h d i ,
S.S. Nussey,
R . D . Simpson,
C . L . Bashford,
S.J. H a r r i s o n and G.K. Radda
Hyperpolarization of thyroid cells in vitro by thyrotropin and cyclic A M P .
R . Batt
and J . M . M c K e n z i e
57
61
65
VIII
Cyclic 3',5'-nucleotide Phosphodiesterase in human thyroid gland. A .
Nagasaka
and H. H i d a k a
Effects of thyrotropin and Prostaglandin E i on rat thyroid cyclic A M P .
M. Z a k a r i j a
Role of Prostaglandins in thyroid secretion. J . M . Boeynaems,
P.
Ketelbant-Balasse,
J. Van Sande and J . E . D u m o n t
The properties of cAMP-dependent protein kinase of porcine thyroid plasma
membrane. R . Kobayashi
and A . H a r a d a
Particulate regulator of protein phosphokinases in hypo- and hyperstimulated rat
thyroid glands. M. P a v l o v i c - H o u r n a c and D . D e l b a u f f e
Phosphorylation of purified thyroid plasma membranes in vitro. A . T i r a r d and
M. Roques
Stimulatory effect of T S H or L A T S on C a uptake by thyroid gland. T. H a c h i y a ,
T. M i y a z a k i , I. Kaimasu,
T. M a z i m a , M . Y o s h i m u r a and Y. O c h i
Effects of calcium ionophore (A-23187) on glucose oxidation and iodide transport
in dog thyroid slices. K. Y a m a s h i t a , Y. Aiyoshi,
H. O k a and E . O g a t a
Interrelation of c A M P , c G M P and C a in the regulation of thyroid cell metabolism.
J. Van Sande,
C. Decoster,
G. G r e n i e r and J . E . D u m o n t
Influence of the sympathetic nervous System on thyroid activity in man. A . M e l a n der, K. Bülow, A . Burger,
L . E . E r i c s o n , S. Ingemansson,
J.-G. Ljunggren, K.-A.
Norberg,
B . Persson,
S . - B . Sundqvist,
F. Sundler,
S. T i b b l i n and U. Westgren
The possible role of biogenic amines as the thyroid stimulators in Graves* disease.
A . Sato, K. H a s h i z u m e and T. O n a y a
Isoproterenol activates cyclic-AMP-dependent protein kinase activity in the thyroid.
S.W. Spaulding
68
72
76
78
81
85
4 5
89
93
+ +
Section
I V . Regulation
o f thyroid
protein
V.
T h y r o i d peroxidase,
iodination
100
103
107
synthesis
Regulation of Ornithine decarboxylase activity in the thyroid. D . R . Zusman
and
G.N. B u r r o w
Two modes of T S H action in the Stimulation of thyroidal protein synthesis.
J . R . Sherwin
and W. T o n g
Effect of T S H at the ribosomal level in the thyroid. P. D e Nayer
A c t i o n of thyrotropin on phosphate incorporation into thyroid proteins, in vitro.
F. Lamy,
R . Lecocq
and J . E . D u m o n t
Molecular basis for the action of K I on thyroid protein biosynthesis. M . A .
Pisarev
and L . O . A i e l l o
Studies on a decrease of plasma triiodothyronine concentration produced by
chronic administration of excess iodide in rats. T. Y a m a d a , A . K o j i m a , R . I n o u e
and T. Kawabe
Section
97
mechanisms
and
2
2
114
118
121
124
127
deiodination
Thyroglobulin exocytosis and iodination. R . E k h o l m , L . E . E r i c s o n , G. Engström
and T Öfverholm
Evidence for the oxidation of iodide to I"" by H 0 and peroxidase. N . M . Alexander
Mechanism of thyroid peroxidase catalyzed thyroid hormone synthesis. J.
Pommier,
D . D e r n e , E. F i m i a n i , J . M . Gavaret
and J. N u n e z
Evidence for an enzyme-bound intermediate in thyroid peroxidase catalyzed
iodination. B . Davidson,
J . T Neary,
H. V. Strout,
F . M a l o o f a n d M . Soodak
The mechanism of inhibition of thyroid peroxidase-catalyzed iodination by Propylthiouracil and methylmercaptoimidazole. A . T a u r o g
The electron transport System and peroxidase in thyroid microsomes. S. O h t a k i ,
S. N a k a g a w a , K. Kon and I. Y a m a z a k i
Pyridine nucleotides: Effects on the iodine metabolism of isolated thyroid cells.
M.L. Maayan
4
110
130
134
139
143
147
151
155
IX
Preferential inhibition by Propylthiouracil of diiodotyrosine and thyroxine biosynthesis: a consequence of low thyroglobulin iodination. H. Bürgi, H J .
Osterwalder,
H Kohler
and H. Studer
NADPH-responsiveness of soluble thyroid iodotyrosine deiodinase. A .
Goswami
and I . N . Rosenberg
Increased iodotyrosine deiodinase activity in human goiters and in rats treated with
Perchlorate. A . Conti,
F. Kneubuehl,
H. Studer,
H. Kohler
and H. Bürgi
Section
VI.
lodoproteins:
biosynthesis
and
VII.
Endocytosis
and thyroid
VIII.
T h y r o x i n e transport
166
169
173
I I
180
184
188
192
hormone
Colchicine-binding protein associated with thyroid plasma membranes. B . B h a t t a charyyaandJ.
Wolff
The relation between exocytosis and endocytosis in the thyroid gland. L . E . E r i c s o n ,
R . E k h o l m , G. Engström and A . M e l a n d e r
Bimodal model and intracellular processes for thyroid hormonal secretion.
R . M i q u e l i s and C. Simon
The role of the pentose phosphate Shunt in T S H Stimulation of thyroid hormone
secretion in the mouse t h y r o i d . K. H a s h i z u m e , T. O n a y a and A . Sato
Separation of thyroid mitochondria and lysosomes. M . F . Van den H o v e - V a n d e n broucke
and P. D e Nayer
T h y r o x i n e , triiodothyronine and thyroglobulin in the human thyroid l y m p h .
J . G . L j u n g g r e n , B . Persson
and P . O . G r a n b e r g
The effect of iodine on the susceptibility of thyroglobulin to proteolysis by a
thyroid proteolytic fraction. L . Lamas and S . H . I n g b a r
The effects of microunit doses of thyrotropin on iodothyrohine release from
mouse thyroid lobes in vitro. R . S . C h a p m a n , P . G . M a l a n and R . P . E k i n s
Secretion rates of triiodothyronine (T3) and thyroxine (T4) from the human
thyroid gland: Peroperative study in the normal gland and in atoxic goiter.
L . Tegler, S. Almqvist,
F. Baldor,
J. Gillquist,
H Johansson
and B . Lundström
Peroperative studies on thyroid activity: Secretion of T 4 , T 3 and 'reverse T 3 ' ( R T 3 )
in normal man. U. Westgren,
A . Burger,
S. Ingemansson,
A . M e l a n d e r , S. T i b b l i n
and E . W a h l i n
Section
162
properties
Conformational change of iodine-free thyroglobulin molecules induced by peroxidase
in vitro. G. Berg, U. Björkman and R . E k h o l m
Structure o f 27S and larger thyroid iodoproteins. U. Björkman,
G. Berg and
R. Ekholm
The Polypeptide chain structure of thyroglobulin. N . Ui and K. Sorimachi
I
Lipid-saccharide intermediates in thyroid glycoprotein synthesis. M.J. Spiro
and
R.G.Spiro
Iodine and the Polypeptide structure of thyroglobulin. A . H a e b e r l i , G.
Salvatore, H . Edelhoch
and J . E . R a l l
Some properties of the purified microsome-bound hog thyroid thyroglobulins:
Possible intermediates in the maturation process of thyroglobulin. Y.
Kondo
and Y. K a m i y a
Synthesis of 19 S thyroglobulin in Xenopus oocyte following injection of purified
33 S m R N A . G. Vassart,
S. Refeto ff, H . Brocas and J . E . D u m o n t
Section
159
195
198
201
205
209
211
213
217
221
226
proteins
Interaction of plasma T3 and T B G as a possible control mechanism of thyroid
hormonal activity at a peripheral level. M . M . Camus,
A . M . E r m a n s , R . D . Hesch
and K. Sterling
229
X
Increase in T B G , T 4 , F T 4 and T3 in the lysinuric protein intolerance.
0. Simell,
J. Perheentupa
and P. Saar i n e n
Section
IX.
Metabolism
o f thyroid
hormones
and conversion
B.-A.
Lamberg,
232
o f T 4 to T 3
Conversion of thyroxine into triiodothyronine by rat liver homogenate. T..I. Visser,
1. van der Does-Tobe,
R . Docter
and G. H e n n e m a n n
235
Thyroxine metabolism by rat liver slices: Evidence for a specific T3-forming pathway. W.L. Green
239
Formation of triiodothyronine from L-thyroxine in rat kidney homogenate.
P. Chiraseveenuprapund,
U. Buergi,
A . Goswami
and I . N . Rosenberg
244
Iodothyronine metabolism and catecholamine enzymes: Effect of alpha-methylparatyrosine in thyroidectomized euthyroid rats. M . B . D r a t m a n , F . L . C r u t c h field, E . M a r s h , J. A x e l r o d and F.H. Sterling
248
The metabolism of thyroid hormones in rat pituitary. V . A . G a l t o n
251
Role of the conversion of L-thyroxine to triiodo-L-thyronine in the expression of
the activity of thyroxine, as measured by effects on growth hormone ( G H ) in
the hypothyroid rat. F. Hervds,
G. M o r r e a l e de Escobar
and F. Escobar
del Rey
255
The effect of thyrotoxicosis and hypothyroidism on the extrathyroidal conversion
of thyroxine to triiodothyronine in man. S . B . M a g u i r e , A . Dennehy
and
M.J. C u l l e n
259
The effect of thyroxine on the peripheral conversion rate of thyroxine to triiodothyronine in man. T. S h i m i z u , CS. P i t t m a n , J . B . Chambers,
Jr., M. W. Buck
and
C C Thurston
263
Effect of glucocorticoids on serum triiodothyronine (T3) concentrations in man.
M . S . Croxson,
D . S . D u i c k and J . T . N i c o l o f f
266
Triiodothyronine (T3) and thyroxine (T4) kinetics in aged men. K . W .
Wenzel
and W.R. H o r n
270
Organ distribution of triiodothyronine (T3) in man as studied by in vivo kinetics methods. R . R . C a v a l i e r i , F . D . R o l l o , M. Chew,
P. M a r t i n , D . Shames
and
V. Perez-Mendez
214
Mechanisms of high reverse T3 and low T3 in the fetus. /../. C h o p r a , J. Sack and
D . A . Fisher
278
The metabolism of 1-3,5,3'-triiodothyroacetic acid (triac) and its conversion
to tetraiodothyroacetic acid. A . Burger and M . B . V a l l o t t o n
282
f
125
Section
X . Symposium
on thyroid
hormone
structure-activity
relation
The evolution of the dual role of the thyroid hormone. E. F r i e d e n and A . B . Kent
Conformational characteristics of thyroid hormones: Structure-function relationships and hormone binding. V. Cody
Studies on the binding site for thyroxine on human serum prealbumin. S.-Y.
Cheng,
H J . C a h n m a n n and M. W i l c h e k
The binding of thyroid hormone analogues to thyroxine binding globulin ( T B G ) .
S . M . Snyder,
R . R . C a v a l i e r i , I . D . G o l d f i n e , E . C . Jorgensen
and S . H . I n g b a r
Structure-function relationships of thyroid hormone analogues in an in vitro rat
thymocyte assay. I . D . G o l d f i n e , G.J. S m i t h , C G . Simons,
S . H . I n g b a r and
E . C. Jorgensen
The nature of the thyroid hormone reeeptor. Contributions of the substituents
of triiodothyronine (T3) and analogs to the free energy of binding to the T 3 reeeptor of isolated rat liver cell nuclei. E . C . Jorgensen
and T . A . A n d r e a
Section
XI.
T h y r o i d hormone
reeeptors
and mechanisms
of
286
290
294
297
300
303
action
Evidence for the existence of two different classes of binding Sites for triiodothyronine in rat liver and kidney nuclei. R . Docter,
T.J. Visser, N . L . van den H o u t Goemaat
and G. H e n n e m a n n
307
XI
T h y r o i d hormone binding Sites in human lymphocytes from normal, hyper- and
h y p o t h y r o i d subjects. A . C . H o l m , B . R . Scazziga
and T. L e m a r c h a n d - B e r a u d
Absent nuclear thyroid hormone receptors and failure of T3-induced T R H suppression in the Syndrome o f peripheral resistance to thyroid hormone. ./.
Bemal,
L . J . DeGroot,
S. Refetoff,
V.S. F a n g and C Barsano
Binding of nuclear triiodothyronine binding protein-T3 complex to chromatin.
L . J . DeGroot,
L . H i l l , H . Seo and J. B e r n a l
Binding of T 3 in liver nuclei: Time dependent displacement of T3 between two
nuclear binding proteins. A . K u b i c a , A . N a u m a n , E . Witkowska
and ./. N a u m a n
Effect o f alpha-amanatin on the induction of hepatic enzymes by triiodothyronine.
W. D i l l m a n n , H L . Schwartz,
E . S i l v a , M.I. Surks and J.H. Oppenheimer
Evidence that L-triiodothyronine (T3) exerts its biological action not only through
its effects on nuclear activity. ./. Segal, A . Gordon
and J. Gross
Structural changes in rat liver ribosomes following the administration of triiodothyronine. S. Jothy,
J . - L . Bilodeau
and H. Simpkins
Cytosol receptors for thyroxine (T4) and triiodothyronine (T3) in human liver.
S. H a m a d a and M . F u k a s e
The mitochond<ria as a site o f thyroid hormone action. K. Sterling
and P . O . M i l c h
Mitochondrial inner membranes in hypothyroidism. F . L . H o c h , Y . - D . I . C h e n ,
T . C . Evans, M.J. Shaw and M . A . N e y m a r k
T h y r o i d hormone action on electrophoresis patterns of proteins of rat liver and
muscle mitochondria. M. Baudry,
J.P. Cht, J. B o u h n i k , O. M i c h e l and R . M i c h e l
Section
XII.
T h y r o i d hormone
311
316
320
324
326
331
334
338
342
347
351
effects
Regulation of the synthesis of malic enzyme by thyroid hormone in liver cells in
culture. A . G . Goodridge
Regulation of L-triiodothyronine aminotransferase activity by T3 in normal and
neoplastic tissues. R . S . R i v l i n , Y.P. H u a n g , M . Benson,N.
F i s h m a n and D . Tergis
Effect of thyroxine on the enzymatic characteristics of cardiac myosin: Possible
mechanism of inotropic action. Y. Y a z a k i and M . S . Raben
Significance of the different normalization rates of red cell carbonic anhydrase B
and serum iodothyronines in
1 treated hyperthyroidism. G.
Stalldecker,
M . Weinstein,
G. Sartorio
and R . J . Soto
Characteristic plasma lipoprotein pattern in hyperthyroid patients. ./.
Bommer,
H . W i e l a n d and D . Seidel
The effect of triiodothyronine (T3) on the number of ( N a + K )-activated adenosine
triphosphatase i n rat renal cortex. CS. L o and L S . E d e l m a n
Sodium concentration and N a - K dependent ATPase activity in red cells of hyperthyroid subjects. M. Weinstein,
G. M i g l i o r a and R . J . Soto
355
359
362
1 3 1
+
Section
XIII.
Autoimmunity
and thyroid
366
369
+
372
373
disease
Association in Japanese of Graves' disease with the H L - A specificity W5.
F . C . Grumet,
J. Konishi,
R . O . Payne and J . P . Kriss
Studies on the mechanism of experimental exophthalmos. J. E t i e n n e , L . D . K o h n
and R . J . W i n a n d
Tissue specific gammaglobulins in the human thyroid. G . B . Salabe
and C. D a v o l i
Nitroblue tetrazolium ( N B T ) reduction by neutrophils in patients with hyperthyroid Graves' disease. J . R . Wall, R . Sobel,
S . - L . F a n g , A . G . Vagenakis,
CM.
A b r e a u , S . H . I n g b a r and L . E . B r a v e r m a n
A n immunological comparison of the antigens present in the thyroid glands from
patients with non-toxic goitre, Graves' and Hashimoto's diseases. C V o n Westa r p , A . J . S . Knox,
V. V. Row and R . Volpe
376
380
384
387
391
XII
Studies on the nature of thyroid antigens involved in thyroid autoimmune disorders.
A . P i n c h e r a , S. M a r i o t t i , P. V i t t i , G . F . F e n z i , L . Grasso,
F .Pacini, L .
Baschieri
and J . B . Stanbury
Thyroid autoimmunity and insulin secretion in rabbits. B . N . P r e m a c h a n d r a
The nature and significance of LATS-protector. S. D i r m i k i s , P . K e n d a l l - T a y l o r
and D . S . M u n r o .
Human thyroid adenyl cyclase stimulator in Immunoglobulin G (IgG) of patients
with Graves' disease. J. Orgiazzi,
D . E . W i l l i a m s , I.J. C h o p r a and D . H . Solomon
Thyroid-stimulating Immunoglobulins and hyperthyroidism in Graves' disease.
B . Rees S m i t h , E . D . M u k h t a r , G . A . Pyle, P . K e n d a l l - T a y l o r and R . H a l l
Comparison and evaluation of the radio-ligand reeeptor assay and the mouse bioassay
for the detection of human thyroid stimulating immunoglobulins. H.
Schleusener, P. K o t u l l a , I. Krück, G. Krück, D . Geissler and F . Adlkofer
Evidence that the antigens to the human thyroid stimulators of Graves' disease are
located i n the thyroid gland. A . J . S . Knox,
C. V o n Westarp,
V.V. Row and
R . Volpe
Section
XIV.
Treatment
of
395
399
403
407
411
414
417
hyperthyroidism
Measurement of total thyroidal iodine Stores in thyrotoxic patients by in vivo
activation analysis. M.J. Hooper,
I. Robertson,
K. Boddy,
R.D.
Stevenson,
T. M c G h i e , W . A . Alexander
and G . M . Wilson
Effect of chronic administration of Propylthiouracil on its disposition during the
treatment of hyperthyroidism. D . S . Sitar,
A . A b u - B a k a r e , R . J . G a r d i n e r and
R.I. Ogilvie
Propranolol as the sole therapy for thyrotoxicosis: Long term follow up. D . C.
Lowe,
D . R . H a d d e n , D . A . D . Montgomery
and J . A . Weaver
Thermoluminescent measurement of thyroidal radioiodine effective half life for
use in radiation dosimetry of the thyroid. M. C u l l e n , E.J. W i l l i a m s and J . F .
Mahne
Resin hemoperfusion: A potential new treatment for thyroid storm. K . D . B u r m a n ,
H C . Yeager,
W . A . Briggs, J.M. E a r l l and L . Wartofsky
Significance o f elevated serum T S H after
1 therapy for thyrotoxicosis. D . Bell a b a r b a , B . B e n a r d and R . Belanger
Dissociation of responsiveness to thyrotropin-releasing hormone from thyroid
suppressibility and outcome of hyperthyroidism following antithyroid drug
therapy. E . M a r t i n o , A . P i n c h e r a , R . C a p i f e r r i , E . M a c c h i a , N . Ambrosino
and
L . Baschieri
Changes in responsivity to T R H and T3-suppression tests after surgical treatment
of hyperthyroidism. H . T a m a i , H. Suematsu,
N . K u r o k a w a , H. Aoki,
M. E z a k i ,
K. K u m a , K. Shizume
and S. N a g a t a k i
421
425
429
434
437
131
Section
XV.
Defective
thyroid
hormone
441
445
449
synthesis
Further studies on abnormal thyroglobulin from congenital goitres likely related
to defective thyroglobulin export. J. T o r r e s a n i and S. Lissitzky
453
Sheep congenital goitre with thyroidal icdoalbumin and i c d o g l c b u l i n replacing
thyroglobulin. C E. D o l l i n g and B . F. Good
457
Carbohydrate incorporation into thyroglobulin and thyroid hormone formation in
' c o l d ' and *hot' nodules of the human thyroid gland. F. M o n a c o , G. M o n a c o
and M. A n d r e o l i
461
Congenital goitre with thyroglobulin deficiency. G. Wägar, B . - A . Lamberg
and
P. Saar i n e n
463
Peroxidase and thyroglobulins from different goitres. ./. N u n e z , J.
Pommier,
R . D o m i n i c i , B . R a h m o u n , D . D e r n e and J. T o u r n i a i r e
461
XIII
Familial goiter with partial iodine incorporation block and euthyroidism due to the
deficient peroxidase defect. H. Niepomniszcze,
O.J. Degrossi,
L . M . Scavini
and
H P . Curutchet
470
Peroxidase activity in human benign thyroid disorders: measure and localization.
E . Regard,
P. F r a g u , A . Beaumont
and B . M . N a t a f
474
Iodide sensitivity in the hemithyroidectomized patient. O . H . C l a r k , C
Moser,
R . R . C a v a l i e r i , M . E . H a m m o n d and S . H . I n g b a r
A l l
Section
XVI.
Iodine
deficiency
Changes in plasma thyroxine, triiodothyronine, and T S H during adaptation to
iodine deficiency and resupplementation with iodine. H . F u k u d a , N . Yasuda,
M . A . Greer,
M. Kutas
and S . E . Greer
T h y r o i d c A M P and iodine, plasma and pituitary T S H during goiter development i n
rats. C. B e r t h i e r and T. L e m a r c h a n d - B e r a u d
Acute and chronic responses to iodine deficiency in rats. G. Riesco,
A . Taurog,
P . R . Larsen and L . K r u l i c h
Evidence for fetal hypothyroidism i n severe endemic goiter. F. D e l a n g e , C. T h i l l y ,
M. Camus,
H. Berquist,
N . Cremer,
R . D . Heseln and A . M . E r m a n s
T h y r o i d funetion studies in endemic goiter and endemic cretinism. G . A .
MedeirosNeto,
Y. I m a i , K. K a t a o k a and CS. H o l l a n d e r
Hypothyroidism in cretins and non-cretinous subjects in an area of severe iodine
deficiency in Central Java. B . M . Goslings,
R .Djokomoeljanto,
R.
Docter,
C Van Hardeveld,
G. H e n n e m a n n , D . Smeenk
and A . Querido
Roles of fetal and maternal thyroid funetion in development of the young rat.
E . Spindel,
P . K . W h i t e and J . B . Stanbury
Section
XVII.
Goiter
and other
thyroid
481
485
490
493
497
501
505
diseases
Clinical features of goitre i n Ireland. D . K . O ' D o n o v a n , P . P . A . Smvth
and J.J.
Turner
509
A thirteen year follow up of sporadic non-toxic goitre. J . L . W . P a r k e r and
W . D . Alexander
510
The possible role for T S H in Controlling thyroid hormone secretion in patients
with toxic multinodular goiters. E . G . Levy, D . S . D u i c k , T D . H a l l and J . T N i c o loff
513
Recurrent goiter and amenorrhea-galactorrhea Syndrome in a patient with a thyrotropin ( T S H ) and prolactin ( P R L ) producing pituitary adenoma. K. H o r n , R .
F a h l b u s c h , U. Hochmeister,
C R . Pickardt,
K. Von W e r d e r a n d P . C . Scriba
517
The prevalence of thyroid disorders in an English Community. W . M . G . T u n b r i d g e ,
D . C. Evered,
R . H a l l , D . Appleton,
M . Brewis,
F. C l a r k , J . G r i m l e y
Evans,
E . Young,
T. B i r d and P. Smith
520
Sequential alterations in serum triiodothyronine, thyroxine and thyrotropin levels
in developing hypothyroidism. Y. I m a i , K. K a t a o k a and CS. H o l l a n d e r
523
Respiratory functional abnormalities in hypothyroidism. M . P . Koenig
and M .
Sc h e r r e r
521
A new type of primary hypothyroidism: Post-partum transient hypothyroidism.
N . A m i n o , K. M i y a i , T Onishi,
T. H a s h i m o t o , K. A r a i , K. Ishibashi
and Y. K u m a hara
532
T h y r o i d funetion in molar pregnancy. S. N a g a t a k i , M. M i z u n o , S.
Sakamoto,
M. I r i e , K. Shizume,
K. N a k a o , V . A . G a l t o n , R . A . Arky and S . H . I n g b a r
535
Natural
Ra and
T h i n thyroids o f cattle from Nigeria, West Africa.
L . O . V . Ekpechi
and L . van Middlesworth
539
2 2 6
2 2 8
XIV
Section
XVIII.
Thyroid
tumors
Regulation of phosphofructokinase in normal rat t h y r o i d and in an experimental
rat thyroid tumor. M . F . Meldolesi,
P . Laccetti
and V. M a c c h i a
Abnormal iodotyrosine deiodinase activity in cold thyroid nodules. R .
Belanger,
R . B e l l a b a r b a and B . B e n a r d
Biochemical heterogeneity and diminished T S H responsiveness in human thyroid
Carcinoma. J . B . F i e l d , P . R . L a r s e n , M . Kotani,
T. K a r i y a , M . Kerins
and G.
Bloom
Isolation by affinity chromatography of rat thyroid tumor proteins related to
thyroglobulin. M . I z u m i , H J . C a h n m a n n and J. Robbins
High level of nerve growth factor ( N G F ) in the serum of a patient w i t h medullary
Carcinoma of the thyroid gland. M . Bigazzi,
R . Revoltella
and S. Casciano
T h y r o i d neoplasia: A delayed complication of low-dose head and neck irradiation.
A . R . Guansing,
N . E n g b r i n g , J. Cerletty,
R . Holmes,
S. W i l s o n , T . C . H a g e n , P . S .
Rosenfeld,
R . Komorowski
and K . R . Shetty
Clinicopathological studies on latent and occult Carcinoma of the thyroid.
./. Sasaki,
K. Seta, S. T a k a h a s h i , T. M u r a t a , K. Saito and K. Yagawa
The role of needle biopsy in evaluating solitary cold t h y r o i d nodules. C . - A .
Wang,
A . L . Vickery
and F. M a l o o f
" Tc
Bleomycin scintigraphy in the diagnosis of thyroid Cancers. K. T o r i z u k a ,
T. M o r l , T. Odori,
K. E n d o , K. I k e k u b o , J. Konishi
and R . M o r i t a
Response to oral thyrotropin releasing hormone in athyreotic patients w i t h thyroid
Carcinoma. M . C . Gershengorn,
B . D . W e i n t r a u b and J. Robbins
F o l l o w up study of surgery for well differentiated Carcinoma of the thyroid.
S. N o m u r a , M. M i y a k a w a , M. M a k i u c h i and R . F u r i h a t a
Cytostatic drug therapy of thyroid Cancer. G. Riccabona,
W. Z e c h m a n n and H. F i l l
Chemotherapy of thyroid Carcinoma. Ä'. S h i m a o k a and J. Reyes
542
547
551
555
558
561
565
568
m
Section
XIX.
Diagnostic
methods
and special
571
575
579
583
586
techniques
Early thyroidal iodide and pertechnetate kinetics: New approach with a scintillation
camera and a Computer. P. Decostre,
P. Brooke,
A . Dobbelcir
and F . E r b s m a n n
590
Specificity of competitive protein binding radioassay of serum thyroxine determination. Ä'. Rootwelt
594
The radioimmunoassay of free thyroid hormones in serum. R . P . E k i n s and
S M . El Iis
597
Screening for neonatal hypothyroidism: Comparison of neonatal dried capillary
blood thyroxine (T4) to cord serum T4 and thyrotropin (TSH). P . G .
Walfish,
J. O ' D o n n e l , T. U l b r i g h t , G. Shachter
and A . F r a n k l
601
The value of the glucagon induced rise in plasma adenosine 3 ,5 -cyclic monophosphate in assessing thyroid Status. J.H. L a z a r u s , K . J . Shetty
and K. Siddle
606
Measurement of thyrotropin and thyroid stimulating immunoglobulins with the
cytochemical bioassay. V.B. Petersen,
B . R . Smith
and R . H a l l
610
Binding of T R F analogs to TRF-antiserum. J.P. Leppäluoto
614
Thyrotropin secretion from superfused rat anterior pituitary cells. M . P .
Schrey,
B . L . B r o w n and R . P . E k i n s
617
Computed axial tomography of the orbit in patients with Graves' ophthalmopathy.
J . P . Kriss, W.H. M a r s h a l l Jr., D . R . E n z m a n n and A . R . Rosenthal
621
Blockade of breast iodine by Perchlorate in estrogen deficiency. B . A . E s k i n ,
J . A . M e r i o n , T . B . Krouse
and R . S h u m a n
625
f
Index of keywords
Index of authors
f
630
635
517
Recurrent goiter and amenorrhea-galactorrhea
Syndrome in a patient with a thyrotropin (TSH)
and prolactin (PRL) producing pituitary
adenoma
K. H O R N , R. F A H L B U S C H , U . H A C H M E I S T E R , C R . P I C K A R D T , K . V O N
and P . C . S C R I B A
M e d i c a l C l i n i c II, University
o f M u n i c h , F e d e r a l Republic
of
WERDER
Germany
The pathophysiological mechanisms of the simultaneous hypersecretion of T S H and P R L
due to a pituitary adenoma are discussed on the basis of one very unusual patient.
CASE HISTORY
In 1968 the female patient suffered from rapid goitral growth and clinical signs of
hyperthyroidism. In 1969 the first resection of the goiter was performed, mainly because
of tracheal compression. T w o years later, she complained of recurrent goiter with Stridor
and dyspnea. Therefore, in 1971 thyroid surgery with plastic reconstruction of the trachea had to be performed. In 1972, at the age of 20 years, she was admitted to hospital
because of a third period of goitral growth despite prophylactic thyroid hormone therapy. A t this time amenorrhea and galactorrhea became apparent.
RESULTS AND
DISCUSSION
On admission the levels of T 4 (10.8 /ig%), of T 3 (189 ng%) and of the R T U (43%) were
slightly elevated (normal ranges: T 4 = 4.5-10.0 jug%; T3 = 80-150 ng%; R T U = 32-42%).
The basal T S H level was elevated (23 juU/ml; normal ränge: 0.4-3.8 p.U/ml).
The basal
P R L level was grossly increased up to 4800 juU/ml, corresponding to 240 ng V L S Standard/
ml (normal ränge in females: 1 5 0 - 6 5 0 / i U R S A 71/222/ml).
The history and the findings indicated a hormonally active anterior pituitary tumor.
The sella turcica was enlarged, but visual fields were normal. Other pituitary functions
were not impaired, as shown by a normal rise of growth hormone and cortisol during the
insulin hypoglycemia test and of L H and F S H after application of 25 /ig L R F .
In healthy subjects T S H and P R L increase after T R H Stimulation (normal ranges after
200 /ig T R H i . V . ; A T S H 30 min: 2.7-23.6 / i U / m l ; A P R L 20 m i n : 500-1700 / i U / m l ) . The
T S H and P R L responses to T R H are suppressed ( T S H ) or diminished (PRL) i n hyperthyroidism, but increased in hypothyroidism. In this patient, the rise of the elevated basal
T S H and P R L levels after T R H Stimulation were inadequate ( A T S H 30 m i n : 0.5 / z U / m l ;
A P R L 20 m i n : 605 / i U / m l ) . Such impaired responsiveness of P R L to T R H has been
demonstrated i n patients with a prolactin-producing pituitary adenoma ( V o n Werder,
1975). The non-suppressibility of T S H and P R L could be demonstrated by the application of thyroid hormones up to 150 /zg T 4 plus 3 0 / i g T 3 which raised the T 4 to
16.2 /ig% and the T 3 uptake to 52%. A disturbance of peripheral conversion of T 4 to T 3
could be excluded, since the T 3 level increased to 392 ng% (T4: 19.1 /ig%) after administration of 300 /ig T 4 per day. However, both T S H and P R L levels remained elevated,
fluctuating between 13.6 and 2 5 . 6 / i U / m l ( T S H ) , and between 3100 and 6 6 0 0 / i U / m l
( P R L ) . This indicated that T S H and P R L could not be physiologically regulated by T R H
and thyroid hormones.
Pharmacological studies showed that both T S H and P R L levels could be lowered by
3
3
518
K . H o r n et a l
500 mg L-dopa with a nadir after 120 min. T S H decreased from 26.0 / i U / m l to 1 9 . 0 / i U /
ml and P R L from 4 4 0 0 j u U / m l to 1800juU/ml. As expected, 5 mg of bromocriptine
decreased the P R L levels from 3100 to 7 4 0 / i U / m l and in parallel decreased the T S H
levels from 11.9 to 6.4 /zU/ml with a nadir after 180 min.
The unknown proliferative potency of T S H and P R L producing tumors prompted us
to have this hormonally active tumor removed by transsphenoidal hypophysectomy and
cryoresection of possible remnants of tumor tissue. This decreased T S H and P R L levels in
parallel to unmeasurable values (Fig. 1). Today, the patient has panhypopituitarism, but
she is fully active as a nurse under replacement therapy with cortisol, thyroxine and
gonadal Steroids.
TSH
pU/ml
hPRL
(iU/ml
Curellpge Crjo
"
—i—i—
V. 48
FIG. 1. Parallel decline of PRL
and TSH d u r i n g and after
transsphenoidal
surgery.
Several possible
pathophysiological
mechanisms
may explain the simultaneous
hypersecretion
o f TSH and P R L :
1. Concomitant hypersecretion of P R L with T S H . In primary hypothyroidism, the elevated T S H and P R L can be normalized by thyroid hormone therapy; this was not so in our
patient. The development of TSH-producing tumors i n rats can result from chronic hypothyroidism. Analogous pituitary tumors in humans can occur in areas with severe iodine
deficiency and cretinism (König, 1968). However, this explanation is not applicable to
our patient, since hypothyroidism was never experienced.
2. P R L hypersecretion due to a suprasellar extension of the TSH-producing tumor resulting in P I F inhibition. Our patient had no ophthalmological, laboratory or pneumencephalographic signs of suprasellar extension.
3. Autonomous T S H and P R L hypersecretion by the pituitary tumor. The inadequate
increase of both T S H and P R L after T R H Stimulation and the lack of suppression by
thyroid hormones indicated an autonomous hormone secretion. In addition electronmicroscopic and immunofluorescent findings revealed no signs of a diffuse hyperplasia of
the pituitary gland, but instead two closely associated cell types were found throughout
the adenoma, of which one was idcntified as lactotroph and the cther thyrotroph.
4. Primary T R H hypersecretion leading to a hyperplasiogenic T S H and P R L producing
pituitary adenoma. This is excludable only by measuring T R H in the portal vessels,
something not feasible in humans. The results of long-term oral treatment with T R H
argue against an endogenous T R H excess causing hyperthyroidism. Daily application of
40 mg T R H orally over a period of 4 weeks diminished the T S H response after 200 jitg
T R H i . V . , while the T 4 and T 3 levels were not increased (Table 1), whereas transitory
increases of the thyroid hormone levels within the normal ränge after each oral application of T R H occur more acutely (unpublished data). This indicates that the suppressive
effect of thyroid hormones on T S H release overrules the stimulatory effect of T R H as
TSH
TABLE l Effect
of 4 weeks)
of oral TRH application
and P R L producing
to healthy
subjects
pituitary
adenoma
519
(N = 1 2 ; 4 0 mg per day over a
period
Before TRH
After TRH
40 mg per day
Serum TSH
(MÜ/ml)
Basal
A
T
S
2.0 ± 0.8
H
3
Q
^
g
{
±
3
Q
1.0 ± 0.5*
3
0
±
Serum T4
( g/100 ml)
6.2 ± 1.9
6.5 ± 1.8
Serum T3
(ng/100 ml)
112 ± 22
109 ± 32
M
*
p < 0.005
shown by repetitive i.v. administration o f T R H (Snyder and Utiger, 1973). Thus endogenous T R H excess is unlikely to cause the hypersecretion o f T S H and P R L , resulting i n a
toxic goiter and amenorrhea-galactorrhea Syndrome, as observed i n this patient.
In conclusion, the patient studied is the first presenting a pituitary adenoma w i t h
autonomous T S H and P R L hypersecretion.
REFERENCES
König, M.P. (1968): D i e Kongenitale
Hypothyreose
und der Endemische
Berlin-Heidelberg-New York.
Snyder, P.J. and Utiger, R.D. (1973): /. clin. Invest., 5 2 , 2305.
Von Werder, K. (1975): Wachstumshormone
und Prolactin-Sekretion
Schwarzenberg, Munich-Berlin-Vienna.
Kretinismus.
Springer Verlag,
des Menschen.
Urban und