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endocriiK) bgica Volume 112
May - August 1986
Copenhagen
CHIEF EDITOR
C . B I N D E R
EDITORS
H. M. M. F R E Y
T. B. v a n W I M E R S M A G R E I D A N U S
C . H A G E N
I. H U H T A N I E M I
P. W. J U N G B L U T
T H . L E M A R C H A N D - B E R A U D
J . - G . L J U N G G R E N
CONSULTING EDITORS
C . H A M B U R G E R
J . S T A R U P
Advisory Panel, page V
Contents Vol. 112, page VII
Authors' Index, page XI
Subject Index, page XV
Un/vers/täts-Ö'bliothek München
Printed in Denmark by Bogtrykkeriet Forum Copenhagen
Advisory Panel
Prof. Asbjorn Aakvaag, Bergen, Norway. \ Prof. Kurt Ähren, Göteborg, Sweden. \ Prof. Michael Apostolakis, Thessaloniki, Greece. . . Dr. Jorgen Arends, Copenhagen, Denmark. Prof. Gustav Asboe-Hansen, Hellerup, Denmark. Dr. Michel L. Aubert, Geneve, Switzerland. Prof. G. M. Besser, London, UK. Prof. Dr. G. Bettendorf, Hamburg, FRG. Prof. S. R. Bloom, London, UK. Prof. J . L. Van den Brande, Utrecht, The Netherlands. Prof. Dr. M. Breckwoldt, Freiburg, FRG. Prof. Hans R. Brunner, Lausanne, Switzerland. Prof. Hans Bürgi, Solothurn, Switzerland. Prof. Marc Bygdeman, Stockholm, Sweden. Dr. Anne Grete Byskov, Copenhagen, Denmark. Dr. Kevin Catt, Bethesda, USA. Prof. Erol Cerasi, Jerusalem, Israel. Prof. Tim Chard, London, UK. Dr. William F. Crowley, Jr, Boston, USA. Prof. Leslie J . DeGroot, Chicago, USA. Prof. Fran ,cois Delange, Brussels, Belgium. Dr. Paul Delost, Aubiere, France. Dr. Pierre A. Desaulles, Basel, Switzerland. Prof. Dr. G. Dhom, Homburg-Saar, FRG. Prof. Dr. E. J . Dorhout Mees, Utrecht, The Netherlands. Dr. John-Fredrik Dymling, Malmö, Sweden. Prof. Kristen B. Eik-Nes, Trondheim, Norway. Dr. Walter Elger, Berlin, FRG. Prof. Dr. F. Ellendorff, Neustadt, FRG. Dr. Ole Faber, Horsholm, Denmark. Dr. Ulla Feldt-Rasmussen, Copenhagen, Denmark. Dr. Per Fernlund, Malmö, Sweden. Prof. J . A. Fischer, Zürich, Switzerland. Prof. H. Fleisch, Bern, Switzerland. Prof. E. Flückiger, Basel, Switzerland. Prof. Y. A. Fontaine, Paris, France. Dr. Maguelone G. Forest, Lyon, France. Prof. P. Franchimont, Liege, Belgium. Prof. E. R. Froesch, Zürich, Switzerland. Dr. Per Ivar Gaarder, Oslo, Norway. Dr. Fulgencio Gomez, Lausanne, Switzerland. Dr. Ariel Gordin, Helsinki, Finland. Prof. Amirav Gordon, Jerusalem, Israel. Prof. F. C. Greenwood, Honolulu, USA. Prof. Kerstin Hall, Stockholm, Sweden. Dr. Johan Halse, Oslo, Norway. Prof. Dr. J . Hammerstein, Berlin, FRG. Dr. Kristian F. Hanssen, Oslo, Norway. Dr. Vidar Hansson, Oslo, Norway. Dr. Egil Haug, Oslo, Norway. Dr. H. N. Haugen, Oslo, Norway.
Prof. Chr. Hedinger, Zürich, Switzerland. Dr. Torbjörn Hillensjö, Göteborg, Sweden. Dr. Jens Juul Hoist, Copenhagen, Denmark. Prof. Bernt Hökfelt, Malmö, Sweden. Prof. Howard S. Jacobs, London, UK. Prof. C. Jaffiol, Montpellier, France. Prof. Dr. Karl H. Jakobs, Heidelberg, FRG. Prof. Elof D. B. Johansson, Uppsala, Sweden. Prof. Alfred Jost, Paris, France. Prof. Dr. Heinrich Karg, Freising-Weihenstephan, FRG. Dr. Anders Karlsson, Uppsala, Sweden. Dr. Knud W. Kastrup, Glostrup, Denmark. Prof. Dr. Rudolf Knuppen, Lübeck, FRG. Prof. Dr. J . Kracht, Giessen, FRG. Prof. Dr. Michael Krieg, Bochum, FRG. Prof. Dr. E. Kuss, München, FRG. Dr. Claus Kühl, Klampenborg, Denmark. Prof. Dr. J . Köbberling, Göttingen, FRG. Prof. Bror-Axel Lamberg, Helsinki, Finland. Prof. Steven W. J . Lamberts, Rotterdam, The Netherlands. Prof. Jorgen Falck Larsen, Herlev, Denmark. Dr. J . J . Legros, Liege, Belgium. Prof. Marc L'Hermite, Bruxelles, Belgium. Prof. Bruno Lunenfeld, Tel Hashomer, Israel. Prof. Dr. Helmut Maske, München, FRG. Prof. Dr. H. P. Meissner, Homburg-Saar, FRG. Prof. Gabriela Morreale de Escobar, Madrid, Spain. Prof. Jürg Müller, Zürich, Switzerland. Prof. Dr. Friedmund Neumann, Berlin, FRG. Prof. Maria I. New, New York, USA. Dr. Karl Olof Nilsson, Malmö, Sweden. Dr. Nils Norman, Oslo, Norway. Prof. Dr. Wolfgang Oelkers, Berlin, FRG. Dr. Risto Pelkonen, Kauniainen, Finland. Prof. Andrea Prader, Zürich, Switzerland. Prof. Dr. Hans-Jürgen Quabbe, Berlin, FRG. Prof. Govind S. Rao, Bonn-Venusberg, FRG. Prof. G. P. van Rees, Leiden, The Netherlands. Prof. Jens F. Rehfeld, Copenhagen, Denmark. Prof. Dr. Horst Schleusener, Berlin, FRG. Prof. Dr. Helmuth Schmidt, Wiesbaden, FRG. Dr. Gerard A. Schuiling, Groningen, The Netherlands. Dr. Nancy B. Schwartz, Chicago, USA. Prof. Dr. H. U. Schweikert, Bonn, FRG. Dr. K. Siersbsek-Nielsen, Copenhagen, Denmark. Prof. Niels Erik Skakkebaek, Hvidovre, Denmark. Prof. Dr. P. G. Smelik, Amsterdam, The Netherlands. Dr. Johan A. Sundsfjord, Tromsö, Norway. Prof. Dr. D. F. Swaab, Amsterdam, The Netherlands. Prof. Dr. H.-D. Taubert, Frankfurt/M, FRG. Prof. J . H. H. Thijssen, Utrecht, The Netherlands.
V
Prof. Dr. Helmut Thomas, Ulm, FRG. Prof. Niels A. Thorn, Copenhagen, Denmark. Dr. George Tolis, Athens, Greece. Prof. Olav Trygstad, Oslo, Norway. Dr. W. M. G. Tunbridge, Newcastle upon Tyne, UK. Prof. Michel B. Vallotton, Geneve, Switzerland. Prof. Tapani Vanha-Perttula, Kuopio, Finland. Dr. J . van der Vies, Oss, The Netherlands. Dr. Hans Vilhardt, Copenhagen, Denmark. Prof. Dr. H. K. A. Visser, Rotterdam, The Netherlands. Prof. Dr. K. D. Voigt, Hamburg, FRG. Prof. Peter Wahlberg, Mariehamn, Finland.
Dr. Jorgen Warberg, Copenhagen, Denmark. Dr. Jorgen Weeke, Arhus, Denmark. Prof. Dr. Klaus von Werder, München, FRG. Prof. E. D. Williams, Cardiff, UK. Prof. Charles B. Wilson, San Francisco, USA. Prof. Milo Zachmann, Zürich, Switzerland. Prof. Jürgen Zapf, Zürich, Switzerland. Prof. G. H. Zeilmaker, Rotterdam, The Netherlands. Prof. Uriel Zor, Rehovot, Israel. Dr. Klaus Olgaard, Copenhagen, Denmark. Prof. Hans Orskov, Arhus, Denmark. Prof. IvarOye, Oslo, Norway.
VI
Contents Vol. 112
Hypothalamus
Gayo L , Bonet B, Herranz A S, Iglesias R, T o r o M J 8c Montoya E: Postnatal development o f bra in T R H , serum T S H and thyro id hormones in the male and female rat 7
Genazzani A R, Petraglia F, Sinforiani E, Brambil la F, Facchinetti F 8c Napp i G: Dysregulation o f plasma pro-opiomelanocortin-related peptides in neurotic depression 1
Kemppa inen R J, Filer D V, Sar t inJ L & Reed R B : Ovine corticotrophin-releasing factor in dogs: dose-response relationships and effects o f dexa-methasone 12
L a m K S L , Wang C, Ma J T C, Leung S P 8c Yeung R T T : Hypothalamic defects in two adult patients wi th septo-optic dysplasia 305
Y o u n g L a i E V, Pang S ¥ 8c Brown G M : Effects o f d i f fe ren t photoperiods on circulat ing levels o f melatonin and N-acetylserotonin in the female rabbit 145
Pituitary
Baki r i F, Riondel A M , Benmi loud M 8c Vallotton M B : Aldosterone in panhypopi tutar ism: dynamic studies and therapeutic effects in Sheehan's syndrome 329
Brabant G, Ranft U , Ocran K, Hesch R D 8c von zur M ü h l e n A : T h y r o t r o p i n - an episodically secreted hormone 315
Brambi l la F, Petraglia F, Facchinetti F & Genazzani A R: Abnormal beta-endorphin and beta-lipo-t r o p i n responses to T R H and L R H administrat ion in pr imary and secondary affective disorders 481
Bussien J P, Gaillard R C, Nussberger J, Waeber B, Hofbauer K G, T u r n i l l D, B r ö g g e r R 8c Brunner H R: Haemodynamic role o f vasopressin released d u r i n g Finnish sauna 166
Degerblad M , R ä h n T , Bergstrand G 8c Tho ren M : Long- term results o f stereotactic radiosurgery to the pi tui tary gland in Cushing's disease 310
Dickstein G, Lahav M 8c O r r Z S: Single-dose rnetyrapone test at 06.00 h : an accurate method for assessment o f pi tui tary-adrenal reserve 28
Escobar D C, Vicen t in i L M , Ghigo E, Ciccarelli E, Usel l in i L , Capeila C 8c Cocchi D : Growth hormone-releasing factor does not stimulate phos-phoinosit ides breakdown in pr imary cultures o f rat and h u m a n pi tu i ta ry cells 345
Ghigo E, Ciccarell i E, Bianchi S D, Gatti G, M o l i -nat t i G M , Massara F, Mül l e r E E 8c Camanni F: Compar ison between pi tu i tary computed tomographic f indings and tests o f hypothalamo-pitui-tary funct ion in 72 patients wi th hyperprolactin-aemia 20
Gilna P 8c M a r t i n F: T h e effect o f oestriol and tamoxi fen on oestradiol induced prolactin secret ion in anaesthetised rats 71
Goodyer C G, Marcovitz S, Hardy J, Lefebvre Y, Guyda H J 8c Posner B I : Effect o f insulin-like g r o w t h factors on human foetal, adult normal and t u m o u r p i tu i ta ry function i n tissue culture . . 49
Ha l l e r H , Hensen J, Bahr V 8c Oelkers W: Effects o f angiotensin I I infusion on the early m o r n i n g surge o f A C T H and on o-CRH-provoked A C T H secretion i n no rma l man 150
Leiha S, Shindel B , Weinberger I , Fuchs J, Rotenberg Z, M o r C 8c Kaufman H : Cushing's disease coexisting wi th a single macronodule simulating adenoma o f the adrenal cortex 323
Lever E G, But le r J, Moore P, Cox T C S 8c Maccabe J J: Infarc t ion o f a growth hormone-secreting macroadenoma d u r i n g a T R H test . . . . 172
Losa M , Huss R, K ö n i g A , Mül l e r O A 8c von Werde r K : Theophyl l ine blunts the GH-re-sponse to g r o w t h hormone releasing hormone in no rma l subjects 473
L u n d i n S, Ä k e r l u n d M , F a g e r s t r ö m P-O, Hauks-son A 8c M e l i n P: Pharmacokinetics in the hu man o f a new synthetic vasopressin and oxytocin u ter ine antagonist 465
Mi lenkovic L , Bogie L 8c Mart inovic J V : Effects o f oestradiol and progesterone on stress-induced secretion o f prolact in in ovariectomized and/or adrenalectomized female rats 79
VII
Moses N , Goldberg V, Gutman R Sc Cacamo D : C o m b i n e d FSH and L H secreting pi tui tary adenoma in a young fertile woman wi thout p r i mary gonadal failure 58
Rot i E, Robuschi G, Albon i A, d 'Amato L, Monter-m i n i M , Gard in i E, Salvi M , Borciani E, D a l l -A g l i o E, Bisi S, Zammarchi G, Lasagni R, Gnud i A 8c Braverman L E: H u m a n foetal prolactin but not t h y r o t r o p i n secretion is decreased by bromoc r ip t ine 35
Schopohl J , Hauer A , Kaliebe T, Stalla G K, von Werde r K 8c Mül le r O A : Repetitive and cont inuous adminis t ra t ion o f human cor t icotropin releasing factor to human subjects 157
Swartz C M , Wahby V S 8c Vacha R: Characterizat ion o f the pi tui tary response in the T R H test by kinet ic mode l ing 43
Terakawa N , Shimizu I , Aono T , Tanizawa O & Matsumoto K : Dexamethasone inhibits the effects o f oestrogen on the pi tui tary gland in rats . . 64
v a n ' t V e r l a a t J W, Croughs R J M , Hendriks M J, Bosma N J, Nor t i e r J W R & Thijssen J H H : B r o m o c r i p t i n e treatment o f prolactin secreting macroadenomas: a radiological, ophthalmologi-cal and endocrinological study 487
Wide L : T h e regulat ion o f metabolic clearance rate o f h u m a n FSH in mice by variation o f the molecular structure o f the hormone 336
Wogensen L 8c W a r b e r g J : Effect o f prostaglandin D2 o n the release o f lute inizing hormone and p ro lac t in in castrated and intact male rats 180
Thyroid
Benker G, Rasche H , Ulb r i ch t T h , Meinhold H , Teube r J 8c Reinwein D : Response o f total and 'free' t h y r o i d hormones and diiodotyrosine to bovine T S H in subclinical hypothyroidism 509
Boye N : T h y r o x i n e monodeiodinat ion in normal h u m a n kidney tissue in v i t ro 536
del Ca rmen Arqueros M , Niepomniszcze H 8c Moreno J : T h y r o i d glands in patients wi th Graves' disease are sources o f thyro t rop in -b ind ing i n h i b i to ry ( T B I ) activity 35 1
Gutekunst R, Smolarek H , Hasenpusch U , Stubbe P, F r i ed r i ch H-J, Wood W G & Scriba P C : Goitre ep idemio logy : thyro id volume, iodine excretion, t h y r o g l o b u l i n and thy ro t rop in in Germany and Sweden 494
Ha raguch i K, Endo T 8c Onaya T : Effects o f p h o r b o l esters on prote in phosphorylat ion and free T 3 release by mouse thy ro id lobes 217
I i taka M , Tanikawa T , Sakatsume Y, Yanagisawa M , Ha ra Y 8c Ishi i J : Interference wi th thyro t rop i n receptor antibody determinat ion by a spuriously o c c u r r i n g anti-bovine T S H antibody 197
Ikeda T , I to Y, Murakami I , Mokuda O, Tominaga M 8c Mashiba H : Conversion o f T 4 to T 3 in perfused liver o f rats wi th carbontetrachloride-induced liver in jury 89
I m a m u r a M , A o k i N , Saito T , Ohno Y, Maruyama Y, Yamaguchi J 8c Yamamoto T : Inhibi tory effects o f an t i thyro id drugs on oxygen radical fo rma t ion in human neutrophils 210
M o r i t a S, I z u m i M & Nagataki S: Interactions between T S H b ind ing inh ib i t ing - and adenylate cyclase s t imula t ing - antibodies in Graves' disease 5 17
Per r i ld H , Hansen J M , A r n u n g K, Olsen P Z 8c Danielsen U : Intellectual impairment after hyper thy ro id i sm 185
Potter B J, Mc in tosh G H , Mano M T, Baghurst P A , Chavadej J , H u a C H , Cragg B G & Hetzel B S: T h e effect o f maternal thyroidectomy pr ior to conception on foetal brain development in sheep 93
Ramsden D B 8c Crossley D N : Serum concentrations o f 3,5,3',5-tetraiodothyroacetate ( T 4 A ) in subjects w i t h hypo-, hyper- and euthyroidism . . . 192
Schatz H , Pschierer-Berg K, Nickel J-A, Bär R, M ü l l e r F, Bretzel R G, Mül le r H 8c Stracke H : Assay for t hy ro id g rowth st imulat ing immunoglobul ins : s t imulat ion o f [ 3 H ] t h y m i d i n e incorpora t ion in to isolated thyro id follicles by T S H , EGF, and immunoglobul ins f rom goitrous patients in an iodine-deficient region 523
T h o m s o n J A , Wilson R 8c Walker I D : The development o f thyrotoxicosis (Graves' disease) d u r i n g immunosuppression for autoimmune haemolytic anaemia 531
Wadeleux P A 8c Winand R J: T h y r o i d growth modu la t i ng factors in the sera o f patients wi th simple non-toxic goitre 502
van der Gaag R D, von Blomberg-van der Flier M , van de Plassche-Boers E, Kokje-Kleingeld M 8c Drexhage H A : T-suppresor cell defects in eut h y r o i d nonendemic goitre 83
Yamashita S, I z u m i M 8c Nagataki S: Specific s t imulatory effects o f Graves' IgG on the release o f t r i i odo thyron ine f rom the patients' own thyroids 204
Parathyroid
Kristiansen J H , Br0chner-Mortensen J 8c Peder-sen K O : Renal tubular reabsorption o f calcium i n famil ia l hypocalciuric hypercalcaemia 541
Pancreas
G r o o p P-H, Groop L , T ö t t e r m a n K J 8c Fyhrquist F: Effects o f Acarbose on the relationship be-
vm
tween changes in GIP and insulin responses to meals in normal subjects 361
Gross R 8c Mialhe P: Free fatty acids and pancreatic funct ion in the duck 100
Lamas L 8c John T : In t ra thyro ida l thyroglobul in in streptozotocin-diabetic rats 552
MacFarlane I A , Stafford S 8c W r i g h t A D : Circula t ing g r o w t h hormone forms in Type 1 diabetic-subjects: comparison wi th normal subjects and acromegalics 547
M a r t i n o E, Grasso S, Bambini G, Pardo G, V i t t i P, A g h i n i - L o m b a r d i F 8c Pinchera A : Ontogenetic development o f pancreatic thyrotropin-releas-ing ho rmone in human foetuses and in infants . . 372
Svenningsen A , Dyrberg T , Markholst H , Binder C 8c L e r n m a r k Ä : Insul in release and pancreatic insul in is reduced in young prediabetic BB rats . . 367
Y k i - J ä r v i n e n H , Helve E 8c Koivisto V A : Relationship between oral glucose tolerance and insulin sensitivity in healthy man and type 1 diabetic patients 355
Liver
Cavallo-Perin P, B r u n o A , Nuccio P, Dall 'omo A M , Fronda G R, Avagnina P, Mol ino G, Bozzo C & Pagano G : Insul in resistance in human liver cirrhosis is not modi f ied by porto-systemic surgical shunt 377
de Vries C P 8c van der Veen E A : Characterization of insu l in -b ind ing to the hepatoma cell line H 3 5 559
Okahata H , Nish i Y, M u r a k i K, Sumii K, Miyachi Y 8c Ueda K : Development o f gastric somatostatin-like immunoreact iv i ty in response to corticoste-rone acetate and dietary changes in young rats . . 383
Gastrointestinal tract
Bailey C J , Flatt P R, Kwasowski P, Powell C J 8c Marks V : Immunoreact ive gastric inhibi tory polypept ide and K cell hyperplasia in obese hyperglycaemic (ob/ob) mice fed high fat and high carbohydrate cafeteria diets 224
Adrenals
D u p o u y J P 8c Chatelain A : Effects o f progesterone induced postmaturi ty on CBG and pitui tary-adrenal activities in the rat foetus 396
Kenyon C J , Clark S A , Hannah J A M , Holloway C D, I n g r a m M C, L i n d o p G, Towr ie A & Ball S G: T h e relative importance o f glucocorticoids and mineralocorticoids in the development o f adrenal regeneration hypertension i n rats 389
Magalhaes M C, V i t o r A B 8c Magalhaes M M : Effects o f A C T H on R N A synthesis and migrat i o n in the adrenal cortex cells o f the young rat, as shown by radioautography 114
M ü l l e r J : Divergent effects o f dietary chloride res t r ic t ion on aldosterone biosynthesis and the renin-angiotensin system in rats 105
Nakano K , Suzuki S, Chanho O & Yamashita K : Possible role o f glucocorticoids in a complement-acti-vated state induced by cobra venom factor in rats 122
T o u r n i a i r e J , Chalendar D, Rebattu B, Fevre-Mon-tange M , Bajard L , Mazenod B, Dechaud H , A b o u Samra A B & van Cauter E: T h e 24-h Cortisol secretory pattern i n Cushing's synd r o m e 230
Ovaries
Gross D J , Landau H , K o h n G, Farkas A , Elrayyes E, El-Shawwa R, Lasch E E & Rosier A : Male pseudohermaphrodi t i sm due to l 7 ß - h y d r o x y -steroid dehydrogenase deficiency: gender reassignment i n early infancy 238
H o o p e r S B , Walker D W 8c T h o r b u r n G D : Cannula t ion o f the utero-ovarian vein i n intact ewes: hormone concentrations and blood gas levels d u r i n g the oestrous cycle and early pregnancy 253
Robba C, Rebuffat P, Mazzocchi G 8c Nussdorfer G G : Long- te rm t rophic action o f a-melanocyte-s t imula t ing hormone on the zona glomerulosa o f the rat adrenal cortex 404
Rosberg S, Norjavaara E, Sender Baum M & Khan I : Adenylate cyclase activity i n rat corpora lutea evidence for a rap id development o f the regulatory N s - p r o t e i n 565
Sender-Baum M G 8c Ä h r e n K E B : Effects o f forskol in , lu te iniz ing hormone and prostagland i n F 2 a on isolated rat corpora lutea 571
van der Schoot P 8c de Greef W J : Development o f ovarian follicles d u r i n g lactation in rats 247
Weusten J J A M , Blankenstein M A , Gmelig-M e y l i n g F H J, Schuurman H J, Kater L 8c Thijssen J H H : Presence o f oestrogen receptors i n h u m a n blood mononuclear cells and thymocytes 409
Uterus
Papapetrou P D & Nicopoulou S C h : T h e o r ig in o f a human chorionic gonadotropin ß - s u b u n i t - c o r e fragment excreted in the ur ine o f patients wi th cancer 415
IX
Pregnancy Miscellaneous
Buch I , Hornnes P J & K ü h l C: Glucose tolerance i n early pregnancy 263
H o n j o H , Ki tawaki J , I t o h M , YasudaJ , Yamamoto T , Yamamoto T , Okada H , O h k u b o T 8c N a m -bara T : Serum and u r i n a r y oestrone sulphate in pregnancy and del ivery measured by a direct radioimmunoassay 423
J u l k u n e n M : H u m a n decidua synthesizes placental p ro te in 14 (PP14) in v i t r o 271
Koyama K, Toda K, Kur iyama D 8c Isojima S: A f f i n i t y to lect in, biological and immunologica l characteristics o f h u m a n chorionic gonadotropins f rom pregnant women and trophoblastic t u m o u r patients 579
Sairam M R, Kato K , Mukhopadhyay A K & Bohnet H G : Preparat ion and properties o f h u m a n chor ionic gonado t rop in antagonist for biological studies: an t i fe r t i l i ty effects in the female rat 586
Stegner H , Fischer K , Pahnke V G, Kitschke H J 8c Commentz J C: T h e r e is evidence that amniot ic fluid arginine vasopressin is a marker for foetal stress i n rhesus erythroblastosis 267
Testes
Garza-Flores J , Vi lchis F, Garcia G A , Menjivar M 8c Perez-Palacios G : A - r i n g reduc t ion enhances the ant igonadotropic potency o f norethisterone . 278
Lemarchand-Beraud T h , Jaussan V 8c Zür i ch M G: Dose and t ime effects o f t reatment w i t h low doses o f a L R H agonist on testicular axis and accessory sex organs in rats 595
Vawda A I & Davies A G : Effects o f cisplatin on the mouse testis 436
V i h k o K K, T o p p a r i J , Saksela O, Suominen J J O 8c Parvinen M : Testicular plasminogen activators d u r i n g postnatal development in the rat . . . . 43 1
Bigazzi M , Del Mese A , Petrucci F, Casali R 8c Novel l i G P: T h e local administrat ion o f relaxin induces changes in the microcirculat ion o f the rat mesocaecum 296
Caufriez A , Golstein J, Tad je rouni A , Bosson D, Cantraine F, Robyn C 8c Copinschi G: Modulat ion o f immunoreact ive somatomedin-C levels by sex steroids 284
H a m m o n d G L 8c Langley M S: Identif ication and measurement o f sex hormone b ind ing globul in (SHBG) and corticosteroid b ind ing globul in (CBG) i n human saliva 603
Lakshmanan J : Neonatal hyper thyroidism causes impa i rmen t in submandibular gland-nerve g r o w t h factor (SMG-NGF) ontogeny in mice . . . . 138
Lakshmanan J 8c Perheentupa J : Reduced urinary-ep idermal g rowth factor levels in Snell d w a r f mutan t mice 461
L u n d i n S & V i l h a r d t H : Absorpt ion o f 1-deamino-8-D-arginine vasopressin f rom different regions o f the gastrointestinal tract in rabbits 457
MacFarlane M & Skett P :Time course o f the effect o f streptozotocin on serum concentration o f g lucose and triglycerides and on hepatic d r u g metabolism i n the male rat 300
M i n e t t i C A S A , Valle L B S , Fava-De-Moraes F, Roma ld in i J H 8c Oliveira-Filho R M : Ontogenesis o f androgen receptors in the mouse submand ibu la r g land : correlat ion wi th the developmental profiles o f c i rculat ing thyro id and testicular hormones 290
M y k i n g O, Aakvaag A 8c O h m O J : Splanchnic-ext rac t ion o f oestrone and oestradiol and produc t ion o f oestrone sulphate in man 442
Takano K, Hizuka N & Shizume K : Treatment o f Turne r ' s syndrome wi th methionyl human g r o w t h hormone for six months 130
Zondek T , Mansfield M D, Attree S L 8c Zondek L H : H o r m o n e levels in the foetal and neonatal prostate 447
x
Authors' Index
Aakvaag A, 442 Cacamo D , 58 Flat t P R, 224 A b o u Samra A B, 230 Camann i F, 20 F r i e d r i c h H-J , 494 A g h i n i - L o m b a r d i F, 372 Cantraine F, 284 F r o n d a G R , 3 7 7 A h r e n K E B , 5 7 l Cape l l aC ,345 FuchsJ , 323 A l b o n i A , 35 Carmen Arqueros M del , 351 Fyhrqu i s t F, 361 A o k i N , 2 1 0 Casali R, 296 A o n o T, 64 Caufriez A , 284 Gaag R D van der, 83 A r n u n g K, 185 Cauter E v a n , 230 G a i l l a r d R C , 166 At t ree S L , 447 Cavallo-Perin P, 377 Garcia G A , 278 Avagnina P, 377 C h a l e n d a r D 2 3 0 G a r d i n i E, 35
C h a n h o O , 122 Garza-Flores J , 278 Baghurs tP A , 93 Chatelain A, 396 Ga t t i G, 20 Bailey C J 224 Chavade jJ ,93 Gayo L , 7 Bajard L , 230 Ciccarell i E, 20, 345 Genazzani A R, 1, 481 B a k i r i F, 329 Clark S A , 389 G h i g o E, 20, 345 Bal l S G , 389 Cocchi D, 345 G i l n a P , 71 Bambin i G, 372 Commentz J C, 267 G m e l i g - M e y l i n g F H J, 409 B e n k e r G , 509 Copinschi G, 284 G n u d i A , 35 Benmi loud M , 3 2 9 Cox T C S , 172 G o l d b e r g V, 58 Bergstrand G, 310 Cragg B G, 93 Gols te in J , 284 B i a n c h i S D , 2 0 C r o s s l e y D N , 192 Goodye r C G, 49 Bigazzi M , 296 Croughs R J M , 487 Grasso S, 372 Binder C, 367 G r e e f W J de, 247 Bis iS , 35 Da l l 'Ag l io E, 35 G r o o p L , 361 Blankenstein M A, 409 Dal l 'omo A M , 377 G r o o p P - H , 3 6 1 Blomberg-van der Flier M von, 83 d ' A m a t o L , 35 Gross D J , 238 Bogie L , 79 Danielsen U , 185 Gross R, 100 Bohnet H G, 586 Davies A G , 436 Gutekuns t R, 494 Bonet B, 7 D e c h a u d H , 2 3 0 G u t m a n R, 58 Borciani E, 35 D e g e r b l a d M , 3 l ( ) G u y d a H J , 4 9 B o s m a N J , 4 8 7 Del M e s e A , 2 9 6 Bosson D, 284 Dickstein G, 28 H a l l e r H , 150 Boye N , 536 Drexhage H A , 83 H a m m o n d G L , 603 BozzoC, 377 D u p o u y J P, 396 H a n n a h J A M , 389 B r a b r a n t G , 3 1 5 D y r b e r g T , 367 H a n s e n J M , 185 Brambi l la F, 1,481 H a r a Y, 197 Braverman L E, 35 Elrayyes E, 238 H a r a g u c h i K , 217 B r e t z e l R G , 5 2 3 El-Shawwa R, 238 H a r d y J , 49 B r o w n G M , 145 Endo T , 217 Hasenpusch U , 494 B r u n n e r H R, 166 Escobar D C , 345 H a u e r A , 157 B r u n o A , 377 Hauksson A , 465 Br0chne r -Mor t ensen j , 541 Facchinetti F, 1, 481 He lve E, 355 B r ö g g e r R, 166 F a g e r s t r ö m P-O, 465 H e n d r i k s M J , 487 Buch I , 263 Farkas A , 238 H e n s e n J , 150 BussienJ P, 166 Fava-De-Moraes F, 290 H e r r a n z A S, 7 B u t l e r J , 172 Fevre-Montange M , 230 H e s c h R D , 3 1 5 Bahr V, 150 Fi ler D V, 12 Hetze l B S, 93 B ä r R, 523 Fischer K, 267 H i z u k a N , 130
XI
Hofbauer K G , 166 Losa M , 473 Nicopou lou S Ch, 415 Hol loway C D, 389 L u n d i n S , 4 5 7 , 4 6 5 Niepomniszcze H , 351 H o n j o H , 423 Nishi Y, 383 H o o p e r S B , 253 M a J T C , 3 0 5 Norjavaara E, 565 H o r n n e s P J , 2 6 3 MaccabeJJ , 172 N o r t i e r J W R . 4 8 7 H u a C H , 9 3 MacFarlane I A , 547 Novel l i G P, 296 H u s s R , 4 7 3 MacFarlane M , 300 Nuccio P, 377
Magalhaes M C , 114 NussbergerJ , 166 Iglesias R, 7 Magalhaes M M , 114 Nussdorfer G G, 404 I i t a k a M , 197 M a n o M T , 93 Ikeda T , 89 Mansf ie ld M D, 447 O c r a n K , 315 I m a m u r a M 210 Marcovi tz S, 49 Oelkers W, 150 I n g r a m M C , 389 Markhols t H , 367 O h k u b o T , 423 I s h i i J , 197 Marks V, 224 O h m O J , 442 Isojima S, 579 M a r t i n F, 71 O h n o Y, 210 I t o Y, 89 M a r t i n o E, 372 O k a d a H , 4 2 3 I t o h M , 423 Mar t inov ic J V, 79 Okahata H , 383 I z u m i M , 204, 517 Maruyama Y, 210 O l b r i c h t T h , 5 0 9
M a s h i b a H , 8 9 O l i v e i r a - F i l h o R M , 2 9 0 Jaussan V, 595 Massara F, 20 Olsen P Z , 185 J o l i n T , 552 Matsumoto K, 64 Onaya T , 2 1 7 J u l k u n e n M , 2 7 1 Mazenod B, 230 O r r Z S, 28
Mazzocchi G, 404 K a l i e b e T , 157 M c i n t o s h G H , 93 PaganoG, 377 Kater L , 409 M e i n h o l d H , 5 0 9 Pahnke V G, 267 Kato K, 586 M e l i n P, 465 Pang S F, 145 Kaufman H , 323 Menj ivar M , 278 Papapetrou P D, 415 Kemppa inen R J , 12 Mia lhe P, 100 P a r d o G , 372 K e n y o n C J , 3 8 9 Mi lenkovic L , 79 Parvinen M , 431 K h a n I , 565 M i n e t t i C A S A , 290 Pedersen K O , 541 Ki t awak i J ,423 Miyach i Y, 383 Perez-Palacios G, 278 K i t s c h k e H J , 2 6 7 M o k u d a O, 89 PerheentupaJ ,461 K o h n G, 238 M o l i n a t t i G M , 20 P e r r i l d H , 185 Koivisto V A , 355 M o l i n o G , 3 7 7 Petraglia F, 1,481 Kokje-Kleingeld M , 83 M o n t e r m i n i M , 35 Petrucci F, 296 Koyama K, 579 Montoya E, 7 Pinchera A , 372 Kris t iansenJ H , 541 M o o r e P, 172 Plassche-Boers E van de. K ü h l C, 263 M o r C , 3 2 3 Posner B 1,49 K u r i y a m a D, 579 M o r e n o J , 351 Potter B J , 93 Kwasowski P, 224 M o r i t a S, 517 Powell C J , 224 K ö n i g A , 473 Moses N , 58 Pschierer-BergK, 523
M ü h l e n A von zur, 315 Lahav M , 28 M ü l l e r E E , 20 Ramsden D B, 192 Lakshmanan J, 138,461 M ü l l e r F, 523 Ranft U , 315 L a m K S L , 305 M ü l l e r H , 523 Rasche H , 509 Lamas L , 552 M ü l l e r J , 105 Rebattu B, 230 Landau H , 2 3 8 M ü l l e r O A , 157,473 Rebuf fa tP ,404 Langley M S, 603 Mukhopadhyay A K, 586 Reed R B, 12 Lasagni R, 35 M u r a k a m i I , 89 Reinwein D , 509 Lasch E E, 238 M u r a k i K, 383 Riondel A M , 329 Lefebre Y, 49 M y k i n g O , 442 Robba C, 404 Leiba S, 323 Robuschi G, 35 Lemarchand-Beraud T h , 595 Nagataki S, 204,517 R o b y n C , 2 8 4 L e r n m a r k Ä, 367 N a k a n o K , 122 R o m a l d i n i J H , 290 L e u n g S P, 305 Nambara T , 423 Rosberg S, 565 Lever E G , 172 N a p p i G , 1 Rotenberg Z, 323 L i n d o p G , 389 Nicke l J -A, 523 Rot i E, 35
R ä h n T , 310 T a n i k a w a T , 197 Wadeleux P A , 502 Rosier A , 238 Tanizawa O, 64 W a e b e r B , 166
Terakawa N , 64 Wahby V S, 43 Sairam M R, 586 T e u b e r J , 509 Walker D W, 253 Sa i toT , 210 Th i j s senJ H H , 409, 487 Walker I D , 531 Sakatsume Y, 197 T h o m s o n J A , 531 W a n g C, 305 SakselaO,431 T h o r b u r n G D , 253 W a r b e r g J , 180 Salvi M , 35 T h o r e n M , 310 Weinberger I , 323 Sart in J L , 12 T o d a K, 579 Werde r K von, 157,473 Schatz H , 523 T o m i n a g a M , 89 Weus t enJ J A M , 409 Schoot P van der, 247 T o p p a r i J , 431 W i d e L , 336 SchopohlJ , 157 T o r o M J , 7 Wi l son R, 531 Schuurman H J, 409 T o u r n i a i r e J , 230 W i n a n d R J, 502 S c r i b a P C , 4 9 4 T o w r i e A , 389 Wogensen L , 180 Sender Baum M G, 565, 571 T u r n i l l D , 166 W o o d W G, 494 Shimizu I , 64 T o t t e r m a n K J , 3 6 1 W r i g h t A D, 547 Shindel B , 323
W r i g h t A D, 547
Schizume K, 130 Ueda K , 383 Yamaguchi J , 210
Sinfor ian i E, 1 Use l l in i L , 345 Yamamoto T, 210,
Skett P, 300 Use l l in i L , 345
Yamamoto T, 423 Smolarek H , 494 Yamashita K, 122 Stafford S, 547 Vacha R, 43 Yamashita S, 204 S t a l l a G K , 157 Valle L B S , 290 Yanagisawa M , 197 Stegner H , 267 Va l lo t ton M B, 329 YasudaJ ,423 Stracke H , 523 V a w d a A I , 4 3 6 Y e u n g R T T , 305 Stubbe P, 494 Veen E A van der, 559 Y k i - J ä r v i n e n H , 3 5 5 Sumi i K , 3 8 3 Ver l aa t J W v a n ' t , 4 8 7 Y o u n g L a i E V, 145 SuominenJ J O, 431 V i c e n t i n i L M , 345 SuzukiS , 122 V i h k o K K , 4 3 1 Zammarch i G, 35 Svenningsen A , 367 Vi lch is F, 278 Zondek L H , 447 S w a r t z C M , 4 3 V i l h a r d t H , 4 5 7 Zondek T, 447
V i t o r A B , 114 Z ü r i c h M G, 595 Tad je roun i A , 284 V i t t i P, 372 Takano K, 130 Vries C P de, 559 A k e r l u n d M , 4 6 5
XIII
Subject Index
A C A R B O S E effects in the relationship between changes in GIP
and insul in responses to meals in normal subjects, 361
A C R O M E G A L Y c i rcu la t ing g rowth hormone forms in acromegalic
patients, 547
A D A P T A T I O N S Y N D R O M E stress; effects o f oestradiol and progesterone on
stress-induced prolact in secretion in rats, 79 stress; foetal stress in rhesus erythroblastosis, 267
A D E N Y L A T E C Y C L A S E activity i n rat corpora lutea, 565
A D R E N A L C O R T E X adrenal regeneration hypertension in rats, 389 effect o f A C T H on R N A synthesis and migrat ion in
adrenocort ical cells o f rats, 114 effects o f a -MSH on zona glomerulosa in rats, 404 macronodule s t imula t ing adenoma o f the adrenal
cortex coexisting wi th Cushing's disease, 323 pi tui tary-adrenal reserve; assessment by a single dose
metyrapone test at 06.00 h, 28
A L D O S T E R O N E biosynthesis; divergent effects o f chloride restriction
on aldosterone biosynthesis and the renin-angiotensin system in rats, 105
i n panhypopi tu i ta r i sm; dynamic studies and effect in Sheehan's syndrome, 329
A N D R O G E N S in the foetal and neonatal prostate, 447 ontogenesis o f androgen receptors in the mouse
submandibular gland, 290
A N G I O T E N S I N divergent effects o f chloride restriction on
aldosterone biosynthesis and the renin-angiotensin system in rats, 105
effects o f angiotensin 11 on the m o r n i n g surge o f A C T H and on o-CRF-provoked A C T H secretion in man, 150
A N T I G O N A D O T R O P I N S A - r i n g reduct ion enhances the ant igonadotropic
potency o f norethisterone, 278
A N T I O E S T R O G E N S tamoxi fen ; effect on oestradiol-induced Prl secretion
i n rats, 71
A N T I T H Y R O I D C O M P O U N D S inh ib i t o ry effects on oxygen radical fo rmat ion in
human neutrophils , 210
B L O O D au to immune haemolytic anaemia; development o f
Graves' disease d u r i n g immunosuppression, 531 haemodynamic role o f vasopressin released d u r i n g
Finnish sauna, 166 inh ib i to ry effects o f an t i thyro id compounds on
oxygen radical format ion in human neutrophi ls , 210
oestrogen receptors in human blood mononuclear cells, 409
B R A I N effect o f maternal thyroidectomy on foetal bra in
development in sheep, 93 intellectual impai rment after hyper thyro id ism, 185
B R O M O C R I P T I N E h u m a n foetal Prl but not T S H secretion is decreased
by bromocr ip t ine , 35 t reatment o f Prl-secreting pi tui tary macroadenomas,
487
C A L C I U M renal tubular reabsorption o f calcium in famil ia l
hypocalciuric hypercalcaemia, 541
C A N N U L A T I O N o f the utero-ovarian vein in intact ewes, 253
C A R B O N T E T R A C H L O R I D E l iver in ju ry in rats; conversion o f T 4 to T 3 i n the
perfused liver, 89
xv
C H O R I O N I C G O N A D O T R O P I N af f in i ty to lectin, biological and immunological
characteristics o f hCG f rom pregnant women and t rophoblact ic t umour patients, 579
hCG antagonist; preparat ion and properties; an t i f e r t i l i t y effects in rats, 586
o r i g i n o f a hCG ß- subun i t - co re fragment excreted in the u r i n e o f patients wi th cancer, 415
C I S P L A T I N effects o n the mouse testis, 436
C O B R A V E N O M role o f glucocorticoids in a complement-activated
state induced by cobra venom factor in rats, 122
C O M P L E M E N T SYSTEM role o f glucocorticoids in a complement-activated
state induced by copra venom factor in rats, 122
CORPUS L U T E U M adenylate cyclase activity i n rat corpora lutea, 565 effects o f forskol in , L H and prostaglandin F 2 a on
isolated rat corpora lutea, 571
C O R T I C O S T E R O I D S cort icosteroid b ind ing globul in i n human saliva, 603 relative importance o f gluco- and mineralocorticoids
i n development o f adrenal regeneration hyper tension i n rats, 389
role o f glucocorticoids in a complement-activated state induced by copra venom factor in rats, 122
C O R T I C O S T E R O N E effect o f progesterone-induced postmaturity on CBG
i n the rat foetus, 396
C O R T I C O T R O P I N effect o n R N A synthesis and migra t ion in the
adrenocort ical cells o f rats, 114 effects o f angiotensin I I on the m o r n i n g surge o f
A C T H and on o-CRF-provoked A C T H secretion i n man , 150
ovine ACTH-re l eas ing factor in dogs; dose-response relat ionships and effects o f dexamethasone, 12
repet i t ive and continuous administrat ion o f h-CRF o n A C T H secretion i n human subjects, 157
C O R T I S O L plasma level in patients wi th neurotic depression, 1 the 24-h Cortisol secretory pattern in Cushing's
syndrome, 230
C U S H I N G ' S S Y N D R O M E Cushing's disease coexisting w i th a macronodule
s t imu la t ing adenoma o f the adrenal cortex, 323
stereotactic radiosurgery to the hypophysis in Cushing's disease, 310
the 24-h Cortisol secretory pattern in Cushing's syndrome, 230
D E C I D U A h u m a n decidua synthesizes placental protein 14 in
v i t ro , 271
D E X A M E T H A S O N E effects on ovine CRF in dogs, 12
D I A B E T E S M E L L I T U S c i rcu la t ing g rowth hormone forms in type 1 diabetic
subjects, 547 in t r a thy ro ida l thyroglobul in in
streptozotocin-diabetic rats, 552 rela t ionship between O G T and insulin sensitivity in
type 1 diabetes and in healthy man, 355
D W A R F I S M reduced u r ina ry epidermal g rowth factor levels in
Snell d w a r f mutant mice, 461
E N D O R P H I N abnormal ß - e n d o r p h i n responses to T R H and L R H
i n patients wi th affective disorders, 481 ß - e n d o r p h i n dysregulation in neurotic depression, 1
E N Z Y M E S an alpha-glucosidase inh ib i to r : Acarbose, 361 17 ß - h y d r o x y s t e r o i d dehydrogenase deficiency; male
pseudohermaphrodi t i sm, 238 N-acetyl transferase; effects o f photoperiods on
mela tonin and N-acetyl-serotonin in rabbits, 145
E P I D E R M A L G R O W T H F A C T O R reduced ur inary EGF levels i n Snell dwar f mutant
mice, 461
E R Y T H R O B L A S T O S I S amniot ic vasopressin is likely to be a marker for foetal
stress, 267
F E R T I L I T Y ant i fe r t i l i ty effects o f a hCG antagonist in female rats,
586
F I N N I S H S A U N A haemodynamic role o f vasopressin released d u r i n g
Finnish sauna, 166
F O E T A L E N D O C R I N O L O G Y effects o f insulin-l ike g rowth factors on human foetal
p i tu i ta ry funct ion i n cul ture, 49
xvi
effects o f progesterone-induced postmaturity on CBG and pi tui tary-adrenal function in the rat foetus, 396
hormone p roduc t ion in the foetal and neonatal prostate, 447
h u m a n foetal Prl but not T S H secretion is decreased by b romocr ip t ine , 35
ontogenetic development o f pancreatic T H R in h u m a n foetuses, 372
F O L L I C L E S T I M U L A T I N G H O R M O N E h u m a n F S H ; regulat ion o f the clearance rate in mice
by variat ion o f the molecular structure, 336 p i tu i ta ry adenoma secreting FSH and L H in a young
ferti le woman wi thout p r imary gonadal failure, 58
F O R S K O L I N effects on isolated rat corpora lutea, 571
G A S T R I C I N H I B I T O R Y P O L Y P E P T I D E effects o f Acarbose on the relationship between
changes i n GIP and insulin responses to meals in normal subjects, 361
i n obese hyperglycaemic (ob/ob) mice; influence o f diet, 224
G A S T R I C S O M A T O S T A T I N - L I K E I M M U N O R E A C T I V I T Y see S O M A T O S T A T I N
G A S T R O I N T E S T I N A L T R A C T absorption o f l-deamino-8-D-arginine vasopressin
f rom di f fe rent regions o f the gastrointestinal tract i n rabbits, 457
G E N D E R R E A S S I G N M E N T in male pseudohermaphrodi t ism in early infancy, 238
G E S T A G E N S norethisterone; A - r i n g reduction enhances its
ant igonadotropic potency, 278
G L U C O S E glucose tolerance in early human pregnancy; insulin
and glucagon responses, 263 serum levels in male rats; time course o f the effect o f
streptozotocin, 300
G O I T R E assay for t h y r o i d g rowth s t imulat ing
immunoglobul ins in goitrous patients, 523 goitre epidemiology; thyro id volume, iodine
excret ion, T g and T S H in Germany and Sweden, 494
t h y r o i d g r o w t h modula t ing factors in sera o f patients wi th non-toxic goitre, 502
T-suppressor cell defects in eu thyroid non-epidemic goitre, 83
G O N A D O T R O P I N S h u m a n F S H ; regulation o f the clearance rate in mice
by variat ion o f the molecular structure, 336
G R A V E S ' DISEASE development o f Graves' disease d u r i n g
immunosuppression for haemolytic anaemia, 531 Graves' I g G ; specific st imulatory effects on release o f
T 3 f r o m the patients' own thyroids, 204 interactions between T S H b ind ing inh ib i t i ng — and
adenylate cyclase s t imulat ing — antibodies i n Graves' disease, 517
t h y r o i d glands in Graves' disease are sources o f T S H -b i n d i n g inh ib i to ry activity, 351
G R O W T H inu l in - l ike g rowth factors; effect on human foetal,
adul t no rmal and t u m o u r pi tui tary funct ion i n cul ture , 49
G R O W T H H O R M O N E ci rcula t ing G H forms in type I diabetic subjects, 547 G R H does not stimulate phophoinositides breakdown
i n cultures o f rat and human pi tu i tary cells, 345 in fa rc t ion o f a p i tu i tary GH-secreting macroadenoma
d u r i n g a T R H test, 172 me th iony l h G H ; treatment o f Turner ' s syndrome,
130 theophyl l ine blunts the GH-response to G R H i n
no rma l subjects, 473
H E P A T O M A S insu l in b i n d i n g to hepatoma cell line H 35, 559
H U M A N C H O R I O N I C G O N A D O T R O P I N see C H O R I O N I C G O N A D O T R O P I N
H Y P E R C A L C A E M I A renal tubular reabsorption o f calcium in famil ial
hypocalciuric hypercalcaernia, 541
H Y P E R G L Y C A E M I A gastric inh ib i to ry polypeptide and intestinal K cell
hyperplasia in obese hyperglycaemic (ob/ob) mice; effect o f diet, 224
H Y P E R P R O L A C T I N A E M I A comparison between pi tui tary computed
tomographic findings and tests o f hypothalamo-pi tu i ta ry funct ion, 20
H Y P E R T E N S I O N adrenal hypertension regeneration in rats; relative
importance o f gluco- and mineralocorticosteroids, 389
XVII
H Y P E R T H Y R O I D I S M intellectual impairment after hyperthyroidism, 185 neonatal hyper thyroidism causes impairment in
submandibular gland-nerve growth factor ontogeny in mice, 138
H Y P O P H Y S I S ( A N T E R I O R L O B E ) caracterization o f the pi tui tary response in the T R H
test by kinetic model ing, 43 effect o f insulin-like g rowth factors on human foetal,
adul t normal and t umour pi tui tary function in cul ture , 49
effects o f oestrogens on the rat hypophysis; i nh ib i t ion by D X M , 64
episodical secretion o f T S H , 315 GH-secreting macroadenoma; infarction d u r i n g a
T R H test, 172 panhypopi tu i ta r i sm; aldosterone; dynamic studies
and effect in Sheehan's syndrome, 329 p i tu i ta ry adenoma secreting FSH and L H in a young
fert i le woman wi thout p r imary gonadal failure, 58 pi tui tary-adrenal reserve; assessment by a single-dose
metyrapone test at 06.00 h, 28 p i tu i ta ry computed tomographic Findings;
comparison with tests o f hypothalamo-pituitary funct ion in hyperprolactinaemia, 20
pro-opiomelanocort in-related peptides; dysregulation in neurotic depression, 1
stereotactic radiosurgery to the hypophysis in Cushing's disease, 310
H Y P O T H A L A M U S brain T R H ; postnatal development in male and
female rats, 7 effect on dysregulation o f plasma
pro-opiomelanocort in-related peptides in neurotic depression, 1
hypothalamic defects in patients wi th septo-optic dysplasia, 305
hypothalamo-pi tui tary function tests in hyperprolact inaemia; comparison wi th pi tui tary computed tomographic Findings, 20
ovine CRF in dogs; dose-response relationships and effects o f dexamethasone, 12
H Y P O T H Y R O I D I S M subclinical hypothyro id ism; responses o f total and
'free' t hy ro id hormones and D I T to bovine T S H , 509
I M M U N O G L O B U L I N S assay for thyro id g rowth st imulat ing
immunoglobul ins f rom goitrous patients, 523
I M M U N O L O G Y inh ib i to ry effects o f an t i thyro id compounds on
oxygen radical format ion in human neutrophils, 210
interference wi th T S H receptor antibody de terminat ion by a spuriously occurr ing anti-bovine T S H antibody, 197
role of glucocorticoids in a complement-activated state induced by cobra venom factor in rats, 122
specific s t imulatory effects o f Graves' IgG on release o f T 3 f r om the patients' own thyroids, 204
T-suppressor cell defects i n euthyroid non-epidemic goi tre , 83
I N S U L I N Acarbose; effects on the relationship between
changes in GIP and insulin responses to meals in healthy subjects, 361
characterization o f insul in b ind ing to hepatoma cell l ine H 35, 559
glucose tolerance in early human pregnancy; plasma insul in and glucagon responses, 263
relat ionship between O G T and insul in sensitivity in type 1 diabetes and in healthy man, 355
release and pancreatic insul in ; reduct ion in young pre-diabetic rats, 367
resistance in liver cirrhosis; no modificat ion by portosystemic surgical shunt, 377
I N S U L I N L I K E G R O W T H FACTORS effects on human foetal, adult normal and t umour
p i tu i ta ry funct ion in cul ture, 49
I N T E L L E C T U A L I M P A I R M E N T fo l lowing hyper thyro id ism, 185
I N T E S T I N A L K CELLS hyperplasia in obese hyperglycaemic mice; effect of
diet, 224
K I D N E Y S renal tubular reabsorption o f calcium in familial
hypocalciuric hypercalcaemia, 541 T 4 monodeiodina t ion in normal human kidney tissue
in v i t ro , 536
L A C T A T I O N development o f ovarian follicles d u r i n g lactation in
rats, 247
L I P I D S free fatty acids and pancreatic function in the duck,
100
L I P O T R O P I N abnormal ß - l i po t rop in response to T R H and L R H in
patients wi th affective disorder, 481 ß - l i p o t r o p i n dysfunction in neurotic depression, 1
XVIII
L I V E R CCl 4 - induced l iver in jury in rats; conversion o f T 4 to
T 3 , 89 characterization o f insulin b ind ing to hepatoma cell
line H 35, 559 chirrhosis; insul in resistance is not modif ied by
porto-systemic surgical shunt, 377 d r u g metabolism in male rats; t ime course o f the
effect o f streptozotocin, 300
L U T E I N I Z I N G H O R M O N E effect on isolated rat corpora lutea, 571 p i tu i ta ry adenoma secreting L H and FSH in a young
woman wi thout p r imary gonadal failure, 58 secretion in male rats; effect o f prostaglandin D 2 , 180
L Y M P H O C Y T E S T-suppressor cell defects in euthyroid non-endemic
goitre, 83
M E L A N O C Y T E S T I M U L A T I N G H O R M O N E long- term t rophic action o f a -MSH on zona
glomerulosa in rat adrenals, 404
M E L A T O N I N effects o f photoperiods on melatonin and
N-acetylserotonin in rabbits, 145
M E N S T R U A T I O N menstrual cycle; changes o f somatomedin-C levels by
sex steroids, 284
M E T Y R A P O N E single-dose metyrapone test at 06.00 h ; an accurate
method for assessment o f pi tui tary-adrenal reserve, 28
M O N O N U C L E A R CELLS presence o f oestrogen receptors on human blood
mononuclear cells, 409
N - A C E T Y L S E R O T O N I N effects o f photoperiods on N-acetylserotonin in
rabbits, 145
N E U R O T I C DEPRESSION dysregulation o f pro-opiomelanocortin-related
peptides in the patients, 1
N E U T R O P H I L S inh ib i to ry effects o f an t i thyro id compounds on
oxygen radical funct ion in human neutrophils, 210
N O R E T H I S T E R O N E A - r i n g reduction enhances its antigonadotropic
potency, 278
O E S T R A D I O L effect on stress-induced Prl secretion in rats, 79 oestradiol-induced Prl secretion in rats; effects o f
oestriol and tamoxifen, 71 splanchnic extraction o f oestradiol in human subjects,
442
O E S T R I O L effect o f oestriol and tamoxifen on
oestradiol-induced Prl secretion in rats, 71
O E S T R O G E N S effects on the rat hypophysis; inh ib i t ion by
dexamethasone, 64 i n the foetal and neonatal prostate, 447 oestrogen receptors; presence i n human blood
mononuclear cells and thymocytes, 409 splanchnic extraction o f oestrone and oestradiol and
p roduc t ion o f oestrone sulphate i n man, 442
O E S T R O N E serum and ur inary oestrone sulphate in pregnancy
and delivery, 423 splanchnic extraction o f oestrone and oestradiol and
p roduc t ion o f oestrone sulphate i n man, 442
O E S T R O U S C Y C L E ho rmone concentrations and blood gas levels d u r i n g
the oestrous cycle i n ewes, 253
O V A R I E S adenylate cyclase activity in rat corpora lutea, 565 development o f ovarian follicles d u r i n g lactation i n
rats, 247 effects o f forskol in , L H and prostaglandin F 2 a on rat
corpora lutea, 571
O X Y T O C I N pharmacokinetics in the human o f a new vasopressin
and oxytocin uter ine antagonist, 465
P A E D I A T R I C S ontogenetic development o f pancreatic T R H in
h u m a n foetuses and i n infants, 372
P A N C R E A S free fatty acids and pancreatic function in the duck,
100 pancreatic insul in is reduced in young prediabetic BB
rats, 367 pancreatic T R H ; ontogenetic development i n human
foetuses and i n infants, 372
P A R T U R I T I O N effects o f progesterone-induced postmaturity on
C B G and pi tui tary-adrenal function in the rat foetus, 396
XIX
serum and ur inary oestrone sulphate d u r i n g del ivery , 423
P H O R B O L ESTERS effects o n protein phosphorylat ion and free T 3
release by mouse thyroids, 217
P H O S P H O I N O S I T I D E S G R H does not stimulate the breakdown in cultures o f
ra t and human pi tu i ta ry cells, 345
P H O S P H O R Y L A T I O N effects o f phorbol esters on protein phosphorylation
and free T 3 release by mouse thyroids, 217
P H O T O P E R I O D S effects o f different photoperiods on melatonin and
N-acetylserotonin i n rabbits, 145
P I N E A L B O D Y effects o f different photoperiods on melatonin and
N-acetylserotonin i n rabbits, 145
P L A C E N T A placental protein 14; synthesis by human decidua in
v i t r o , 271
P L A S M I N O G E N A C T I V A T O R S i n testis d u r i n g postnatal development in the rat, 431
P O R T O - S Y S T E M I C S U R G I C A L S H U N T no modi f i ca t ion o f insul in resistance i n human liver
cirrhosis , 377
P O S T M A T U R I T Y effects o f progesterone-induced postmaturity on
C B G and pi tui tary-adrenal function in the rat foetus, 396
P R E G N A N C Y a f f in i t y to lectin, biological and immunological
characteristics o f hCG, 579 amnio t i c f l u i d vasopressin is likely to be a marker for
foetal stress in rhesus erythroblastosis, 267 glucose tolerance in early human pregnancy, 263 h o r m o n e concentrations and blood gas levels d u r i n g
pregnancy in ewes, 253 h u m a n decidua synthesizes placental protein 14 in
v i t r o , 271 se rum and ur inary oestrone sulphate in pregnancy
and delivery, 423
P R O G E S T E R O N E effect o n stress-induced Prl secretion in rats, 79 effects o f progesterone-induced postmaturity on
C B G and pitui tary-adrenal funct ion i n the rat foetus, 396
P R O L A C T I N b romocr ip t ine treatment o f Prl-secreting
macroadenomas, 487 h u m a n foetal Pr l but not T S H secretion is decreased
by bromocr ip t ine , 35 hyperprolact inaemia; comparison between pituitary
computed tomographic findings and tests o f hypothalamo-pi tu i tary funct ion, 20
release o f Prl in rats; effect o f prostaglandin D 2 , 180 secretion in rats; effect o f oestriol and tamoxifen on
the oestrogen-induced secretion, 71 stress-induced secretion i n rats; effects o f oestradiol
and progesterone, 79
P R O O P I O M E L A N O C O R T I N related peptides; dysregulation i n neurotic
depression, 1
P R O S T A G L A N D I N S effect o f P G D 2 on release o f L H i n rats, 180 effect o f PGF 2 a on isolated rat corpora lutea, 571
P R O S T A T E h o r m o n e levels in the foetal and neonatal prostate,
447
P S E U D O H E R M A P H R O D I T I S M gender reassignment i n early infancy, 238
P S Y C H I A T R Y abnormal ß - e n d o r p h i n and ß- l ipo t rop in responses to
L R H and T R H i n affective disorders, 481 ß - l i p o t r o p i n dysregulation in neurotic depression, 1
R A D I O I M M U N O A S S A Y S direct R I A o f serum and urinary oestrone sulphate in
pregnancy and delivery, 423
R E L E A S I N G H O R M O N E S CRF; effect o f angiotensin I I on o-CRF-provoked
A C T H secretion in man, 150 CRF; o-CRF in dogs; dose-response relationships and
effects o f dexamethasone, 12 CRF; repetitive and continuous administration o f h-
CRF to human subjects, 157 G R H ; no stimulation o f phosphoinositides breakdown
in cultures o f rat and human pituitary cells, 345 G R H ; theophylline blunts the GH-response to G R H in
normal subjects, 473 L R H ; abnormal ß - e n d o r p h i n and ß-l ipotropin
responses to L R H and T R H in patients with affective disorders, 481
L R H ; dose and time effects o f treatment with an L R H agonist on testicular axis and accessory sex organs in rats, 595
XX
T R H ; abnormal ß - e n d o r p h i n and ß- l ipotropin responses to T R H and L R H in patients with affective disorders, 481
T R H ; bra in T R H ; postnatal development in male and female rats, 7
T R H ; characteristics o f the pituitary response in the T R H test by kinetic modeling, 43
T R H ; infarc t ion o f a GH-secreting pituitary macroadenoma d u r i n g a T R H test, 172
T R H ; ontogenetic development o f pancreatic T R H in h u m a n foetuses and i n infants, 372
R E L A X I N local adminis t rat ion induces changes in the
microcirculat ion o f the rat mesocaecum, 296
R E N I N divergent effects o f chloride restriction on aldosterone
biosynthesis and the renin-angiotensin system in rats, 105
R I B O N U C L E I C A C I D effect o f A C T H on RNA synthesis and migration in
adrenocortical cells o f rats, 114
S A L I V A ident if icat ion and measurement o f sex hormone
b i n d i n g globul in and corticosteroid binding globulin in h u m a n saliva, 603
S A L I V A R Y G L A N D S submandibular gland-nerve growth factor ontogeny in
mice; impairment by neonatal hyperthyroidism, 138
SEP T O - O P T I C DYSPLASIA hypothalamic defects in two patients, 305
S E R O T O N I N effects o f photoperiods on melatonin and
N-acetylserotonin in rabbits, 145
SEX H O R M O N E B I N D I N G G L O B U L I N in human saliva, 603
S H E E H A N ' S S Y N D R O M E dynamic studies and therapeutic effects o f aldosterone,
329
S O M A T O M E D I N changes o f somatomedin-C levels by sex steroids
d u r i n g the menstrual cycle, 284
S O M A T O S T A T I N gastric somatostatin-like immunoreactivity;
development in young rats in response to corticosterone and dietary changes, 383
S O M A T O T R O P I N see G R O W T H H O R M O N E
S T R E P T O Z O T O C I N time course o f the effect on serum glucose and
triglycerides and on the hepatic d rug metabolism in rats, 300
STRESS see A D A P T A T I O N S Y N D R O M E
S U B M A N D I B U L A R G L A N D S neonatal hyperthyroidism causes impairment in the
submandibular gland-nerve factor ontogeny in mice, 138
o f the mouse; ontogenesis o f androgen receptors and correlation with thyro id and testicular hormones, 290
T A M O X I F E N effect on oestradiol-induced prolact in secretion i n
rats, 71
T E S T E S cisplat in; effects on the mouse testis, 436 dose and t ime effects o f an L R H agonist on testicular
axis and accessory sex organs in rats, 595 testicular plasminogen activators d u r i n g postnatal
development i n the rat, 431
T E S T O S T E R O N E developmental profiles o f circulat ing testicular
hormones in the mouse submandibular g land, 290 testosterone and D H T i n the foetal and neonatal
prostate, 447
3, 5, 3', 5 - T E T R A I O D O T H Y R O A C E T I C A C I D serum levels i n hypo-, hyper- and euthyroid ism, 192
T H E O P H Y L L I N E blunts the GH-response to G R H in normal subjects,
473
T H Y M U S presence o f oestrogen receptors i n human
thymocytes, 409
T H Y R O G L O B U L I N goi t re epidemiology; t hy ro id volume, iodine
excret ion, T g and T S H in Germany and Sweden, 494
in t r a thy ro ida l T g i n streptozotocin-diabetic rats, 552
T H Y R O I D assay o f t hy ro id g rowth s t imulat ing
immunoglobu l ins , 523 development o f Graves' disease d u r i n g
immunosuppression for haemolytic anaemia, 531
XXI
diseases; serum levels o f 3, 5, 3', 5'-tetraiodothyroacetic acid in hypo-, hyper- and eu thy ro id i sm, 192
goi t re ep idemiology; thyro id volume, iodine excre t ion , T g and T S H in Germany and Sweden, 494
hormones ; developmental profiles o f c i rcula t ing t h y r o i d hormones in the mouse submandibular g land , 290
ho rmones ; postnatal development in male and female rats, 7
h y p e r t h y r o i d i s m ; intellectual impa i rment in the patients, 185
h y p e r t h y r o i d i s m (neonatal) causes impa i rment in submandibula r gland-nerve growth factor ontogeny i n mice, 138
subclinical hypo thyro id i sm; responses o f total and Tree ' t h y r o i d hormones and D I T to bovine T S H , 509
t h y r o i d glands o f Graves' disease are sources o f T S H - b i n d i n g inhib i tory activity, 351
t h y r o i d g r o w t h modula t ing factors in sera o f patients w i t h non-toxic goitre, 502
T-suppressor cell defects in eu thyroid non-endemic go i t re , 83
T H Y R O I D E C T O M Y effect o f maternal thyroidectomy on foetal bra in
deve lopment in sheep, 93
T H Y R O T R O P I N character izat ion o f the pi tui tary response in the T R H
test by kinetic model ing, 43 episodical secretion o f T S H , 315 go i t r e ep idemiology; thy ro id volume, iodine
excre t ion , T g and T S H in Germany and Sweden, 494
h u m a n foetal Prl but not T S H is decreased by b romocr ip t i ne , 35
interact ions between T S H b ind ing i n h i b i t i n g — and adenylate cyclase s t imulat ing — antibodies in Graves' disease, 517
in ter ference wi th T S H receptor antibody de t e rmina t ion by a spuriously occur r ing ant i -bovine T S H antibody, 197
postnatal development o f T S H in male and female rats, 7
responses o f total and 'free' thyro id hormones and D I T to bovine T S H in subclinical hypo thyro id i sm, 509
T S H - b i n d i n g inhib i tory activity; t hy ro id glands i n patients w i t h Graves' disease are sources, 351
T H Y R O X I N E conversion o f T 4 to T 3 i n perfused liver o f rats with
CCI 4 - induced liver in jury , 89 T 4 monodeiodina t ion in normal kidney tissue in
v i t ro , 536
T R I G L Y C E R I D E S serum levels in male rats; t ime course o f the effect o f
streptozotocin, 300
T R I I O D O T H Y R O N I N E conversion o f T 4 to T 3 i n perfused liver o f rats with
CCU-induced liver in jury , 89 effects o f phorbol esters on free T 3 release by mouse
thyroids , 217 release o f T 3 f rom the patients' own thyroids; specific
s t imulatory effects o f Graves' IgG, 204
T U M O U R S hepatomas; characterization o f insul in b i n d i n g to
hepatoma cell line H 35, 559 p i tu i ta ry adenoma secreting FSH -I- L H in a young
fert i le woman, 58 p i tu i ta ry GH-secreting macroadenoma; infarct ion
d u r i n g a T R H test, 172 p i tu i ta ry Prl-secreting macroadenomas;
b romocr ip t ine treatment, 487 trophoblastic tumours ; aff ini ty to lectin, biological
and immunologica l characteristics o f hCG, 579
T U R N E R ' S S Y N D R O M E treatment wi th meth ionyl human growth hormone*
130
U T E R U S cannulat ion o f the utero-ovarian vein in intact ewes,
253 pharmacokinetics in the human o f a new vasopressin
and oxytocin uterine antagonist, 465
VASOPRESSIN amniot ic f l u id arginine vasopressin is likely to be a
marker for foetal stress in rhesus erythroblastosis, 267
l-deamino-8-D-arginine vasopressin; absorption f r o m di f ferent regions o f the gastrointestinal tract in rabbits, 457
haemodynamic role o f vasopressin released d u r i n g Finnish sauna, 166
pharmacokinetics in the human o f a new vasopressin and oxytocin uterine antagonist, 465
XXII
Acta Endocrinologica 1986,112:494-501
Goitre epidemiology: thyroid volume, iodine excretion, thyroglobulin
and thyrotropin in Germany and Sweden
R. Gutekunst, H. Smolarek, U. Hasenpusch2, P. Stubbe2, H.-J. Friedrich1,
W. G. Wood and P. C. Scriba
Klinik für Innere Medizin, Institutfür Medizinische Statistik und Dokumentation1,
Medical University of Lübeck
Zentrum für Kinderheilkunde2, University Göttingen, FRG
Abstract. Thyroid volume of 1397 German and 303 Swedish adults were estimated by sonography. Thyroid size of 6—16 year old Germans (n = 619) was determined and compared with findings on palpation. T h y roid volume was more than twice as great in German (21.4 ± 15.6 ml, mean ± SD) than in Swedish adults (10.1 ± 4.9 ml). T h e echopattern was abnormal in 16% of the Germans and in 3.6% of the Swedes. German children have a thyroid volume ranging from 1.8 ± 0.4 ml at 6 years to 10.8 ± 6.0 ml at 16 years of age. Palpation is by comparison an unreliable method for determining thyroid size. I n Germany, the iodine excretion was less in children (n = 619, 39.5 ± 30.5, 34.1 \ig I /g creatinine, mean ± SD, median) than in adults (n = 1193, 83.7 ± 94.4, 62.6), (P < 0.001) and much lower than that observed in Sweden (adults n = 98, 170.2 ± 93.3, 141.4; 13 year olds n = 113, 172.9 ± 224.1, 124), (P < 0.0001). Serum thyrotropin concentration was significantly higher (P < 0.001) in Sweden (n = 62, 1.49 ± 0.82 mU/ml) , than in Germany (n = 91, 0.97 ± 0.52 mU/ml ) , while serum thyroglobulin was increased in Germany (n = 91, 72.6 ± 50.6 \ig/\) as compared to Sweden (n = 62, 23.5 ± 17.4), (P < 0.0001). These results indicate the goitrogenic effect of iodine deficiency and the continuing need for an effective iodine prophylaxis in the F R G .
Alimentary iodine supply in Germany is insufficient and goitre is endemic (Horster et al. 1975).
There are, however, no iodine excretion measure-Dedicated to Prof. Dr. med. E . Buchhorn, Munich, at
the occasion of his 65th birthday.
ments for adults available. Urinary iodine excretion is generally considered to be equivalent to alimentary iodine intake. Habermann et al. (1975) found an iodine excretion of 25—35 jig I/g creatinine in 13- 15 year olds. This was far below the iodine intake recommended by WHO with an optimum of 150-300 \ig iodine daily (Dunn et al. 1974) .
Previous epidemiological studies on goitre in adults were obtained by evaluating chest-X-rays from public health service screening programmes, (Finger et al. 1982; Schoknecht & Barich 1975) , as well as by palpation of military recruits' necks (Horster et al. 1975). Goitre prevalence studies for children were solely based on palpation (Habermann et al. 1975; Stubbe 8c Heide-mann 1983). A representative study of the general population has not yet been undertaken.
Sonographic volumetry is now considered the most reliable method to determine thyroid volume (Brunn et al. 1981; Gutekunst et al. 1985; Hedegüs et al. 1983). Since iodine supply in Sweden is sufficient (Gutekunst et al. 1985) a comparison of iodine excretion, thyroid size and thyroid function in Germany and Sweden was carried out. In this study we examined the reliability of palpation for goitre epidemiological studies in children. Furthermore, we attempted to gain new data about alimentary iodine supply and goitre prevalence.
494
Subjects and Methods
T h y r o i d volume from 1397 G e r m a n adults in 7 towns ( from north to south, K i e l n = 46, L ü b e c k n = 70, B e r l i n n = 111, Wolfsburg n = 313, Frankfurt n = 226, T u t z i n g n = 339, Penzberg n = 293), from 619 childr e n , 6—16 year old from two schools near G ö t t i n g e n a n d from 303 adults from Stockholm, Sweden, were determined by ultrasound. Length , width, and thickness o f both thyroid lobes were measured with portable u l trasound equipment (Sonoline 1300, Siemens, E r l a n gen, F R G ; transducer 4 M H z ) . E c h o structure deviations were recorded and reported to the subjects' physi-cans. T h e volume was estimated by multiplication of thickness, width, length and a corrective factor (0.479) ( B r u n n et al. 1981). T h e r e was no selection process for the adult volunteers who were employees of large companies .
Chi ldren's necks were palpated for estimation of thyroid size according to W H O staging (Dunn et al. 1974), by an independent experienced paediatrician.
Spot ur ine samples were collected from 1812 Ger mans (adults, n = 1193, chi ldren, n = 619) and 211 Swedes (adults n = 98, 13 year old children n = 113). T h e determination of urinary iodine excretion was per formed by a modified eerie arsenious acid wet ash method according to Wawschinek, (1985). T h e kinetic determination o f creatinine followed Jaffe's method ( B e c k m a n creatinine analyser, A S T R A - I V ) .
S e r u m thyrotropin ( T S H ) from a random selection of 91 G e r m a n adults and 62 Swedes was measured by a hypersensitive immunoradiometric assay ( I R M A ) from B e h r i n g company (Wood et al. 1985), and serum thyro-globulin by an immunoluminometric assay ( I L M A ) (Ga-dow et al. 1984).
Final ly , the use of iodized salt (20 mg iodine as potassium iodate per kg), which is available only on a voluntary basis in the F R G , was investigated by interrogation.
Results I. Thyroid volume Among Swedish adults, women have a thyroid volume of 7.7 ± 4.3 ml (mean ± SD) with a range of 2.5-34.0 ml and a median of 6.9 ml; and men I I . 1 ± 4.7 ml (range 3.3-27.4 ml) and median 9.1 ml. German adults had much larger volume: women, 16.5 ± 12.2 ml, median 13.3 ml, range 2 .6 - 124.1 ml; men 26 .9 ± 17.0 ml, median 23.1 ml, range 3 .8- 105.0 ml. The difference between the thyroid volume in Swedes and Germans is highly significant (P < 0.0001). Fig.l shows the distribution of volume in both countries. The frequency distribution in Germany as compared
n = 1397 n= 303
iGermany x = 21.4 ±15 .6 x=17.0 range 2.6 124.1 ^Sweden x = 10.1 ± 4.9 x= 9.1 range 2.5 34.0
I • • - • 0 - 5 5 -10 10-15 15-20 20-25 25-30 35-40 40-45 45-50 >50 volume(mt)
Fig. 1. Frequency distribution of thyroid volume (ml) in Germany and Sweden.
495
40.8 27.8 41.6 30.4
- | — f — i — i — i — i — i — i — i — i — i — i — i — i — i — i — i — i — ' — i — i — i 1
U 16 20 33 32 39 23 30 26 36 53 60 31 35 27 19 38 23 21 24 U 7 n 1 = 6 1 9
6 7 8 9 10 11 12 13 K 15 16 Years Fig. 2.
T h y r o i d volume (ml) in 6 - 1 6 years old from G ö t t i n g e n , F R G .
to Sweden is shifted toward larger volume ( P < 0.0001).
Six year old German children had volume of 1.8 ± 0.4 ml which progressively increased to 10.8 ± 6.0 ml at age 16 years (P < 0.001) (Fig. 2). Palpation in children for thyroid size is rather unreliable. As seen in Figs. 3 and 4, ranges of thyroid volume determined sonographically overlap widely in the respective age groups with volume estimated by palpation (goitre 0,1, II) .
2. Echopattems (Table 1) Eighty-four per cent of the German adults had a normal echopattern; 2.5% had a scattered sonolu-cent pattern and 0.1% a scattered echocomplex pattern; 13.4% had unifocal and/or multifocal echo alterations; 5.9% had cysts; 2.1% had calcifi
cations; 3.2% had sonolucent nodules; 2.1% had echosolid nodules; and 0.1% had echocomplex nodules.
Ninety-six per cent of the Swedes had a normal echopattern; 1% had scattered sonolucent thyroids; 0.3% had calcifications; 1.3% had cysts; 0.3% had sonolucent nodules; and 0.7% had echosolid nodules.
3. Iodine excretion Adults. Urinary iodine excretion was significantly lower in Germany as compared to Sweden (83.7 ± 94.4, 62.6 jig I/g creatinine, vs 170.2 ± 93.3, 141.4, mean ± SD, median), (P < 0.0001). Thirty-one urine samples from German subjects were contaminated with iodine (> 1063.5 \ig I/g creatinine). Fig. 5 illustrates the frequency distribution
496
Age - Volume - Goiter Stage 9
Rang
i) -- $
x (Mean)
<t>x (Median)
j 4 0 i j 2 7 8
11 3 19 12 2 24 12 3 17 9 4 19 14 3 38 11 11 16 13 6 3 9 7 10 9 2 2 5 13 6 2 1 4 nZ = 320 %
0 ' la 0 1 l a ' lb 0 1 la* lb 0 ' l a ' lb 0 ' la ' b 0 ' l a 1 lb 0 ' l a ' lb 0 ' l a ' lb 0 la * lb' H 0 ' l a ' l b O ' l a ' l b Stages
6y. 7y. 8y. 9y. 10y. 11y. 12y. 13 y. U y . 15 y. 16 y. Age
Fig. 3. Sonographically determined thyroid volume as compared with respective palpatory goitre stages
for girls 6—16 years old.
for iodine excretion in both countries. The Swedish distribution shows clearly higher values.
Children. Urinary iodine excretion was low in all age groups in Germany (39.6 ± 30.5, 34.1 \ig I/g creatinine, mean ± SD, median) and more than twice as high in Sweden (172.9 ± 224.1, 124), (P< 0.0001).
4. Comparison of iodine excretion to thyroid volume in German adults Table 2 shows the median iodine excretion and thyroid volume from cities extending from north to south. The variation from north to south is hardly noticeable, although iodine excretion is higher and thyroid volume is smaller in coastal towns compared to the rest of Germany.
5. Iodized salt There is little difference between iodine excretion of subjects (children and/or adults) using iodized
salt and those not ingesting iodine salt (P > 0.05). Thyroid volume also did not differ.
6. TSH and TG levels (Table 3) Surprisingly, basal serum T S H levels were lower in German adults (0.97 ± 0.52 mU/ml) than in Swedes (1.49 ± 0.82; P< 0.001), whereas the mean serum thyroglobulin concentrations in German adults (72.6 ± 50.6 jig/1) was more than twice as high as in the Swedes (23.5 ± 17.4; P < 0.0001).
Discussion
The observation that iodine deficiency has a goitrogenic effect was again supported by the comparison of thyroid volume and iodine excretion between Germans and Swedes. The German adults' thyroids are more than twice as large as those observed in Swedish adults. These findings
32 Acta endocr. 112,4 497
22
21
20
19
18 H
17
16 -
15
U
13
12
11
10
9
8
7
6
5 -
L -
3 -
2
1
Age - Volume - Goiter Stage <?
Range JT * ( M e a n ) o Sc (Median)
4. 6 27.8 3 0 / 2 9 . 5 2U
11 3 U 6 21 11 16 k 1 18 7 1 29 13 11 16 12 3 16 8 3 18 U 6 9 9 2 1 9 3 2 nE«299 0 ' I a 0 ' I a 0 1 Ia 0 ' Ia ' Ib 0 ' l a ' l b 0 ' l a ' l b 0 ' Ia ' lb 0 ' la ' Ib 0 ' Ia ' Ib 0 ' l a ' l b ' n o ' l a V Stages 6y. 7y. 8y- 9y. 10y. 11 y. 12y 13y. H y . I5y. 16 y. Age
Fig. 4. Sonographically determined thyroid volume as compared with respective palpatory goitre stages
for boys 6 - 1 6 years old.
confirm the results of our previous study of 2468 13 year old children in Germany and Sweden, (Gutekunst et al. 1985). In this study, 9 year old German children already exhibited larger thyroid volume compared to those in 13 year old Swedish children. Since it is impossible to define normal thyroid volume in Germany, goitre prevalence cannot be determined on the basis of thyroid volumetry. However, almost one third of the German thyroids are larger than those observed in Sweden (99% range, mean + 3 SD). Thirteen per cent of the German thyroids are above the largest measured Swedish volume. Accordingly, a thyroid volume larger than 20 ml for women and 25 ml for men should be treated or at least controlled. Forty-two per cent of the German men and 25% of the women studied belong in this category. Similarily, 'normal ranges' were defined by Olbricht et al. (1982) and Hegedüs et al. (1983).
The traditional view that goitre is predominantly a problem in Southern Germany can no longer
Table 1. Echopatterns in Swedish and German adults.
Echopattern Sweden Germany
Normal 96.4% 84.0%
(n = 292) (n = H74)
Scattered sonolucent 1.0% 2.5% (n = 3) (n = 35)
Scattered echocomplex - 0.1% ( n = l )
U n i - and/or 2.6% 13.4%
multifocal alterations (n = 8) (n = 187)
Cyst(s) 1.3% 5.9%
(n = 4) (n = 82) Calcification(s) 0.3% 2.1%
( n = l ) (n = 29)
Sonolucent nodule(s) 0.3% 3.2%
( n = l ) (n = 46)
Echosolid nodule(s) 0.7% 2.1%
(n = 2) (n = 29)
Echocomplex nodule(s) - 0.1% ( n = l )
498
% prevalence
2 5 -
2 0 -
Germany Sweden
|n = 1193 x 83 .7±94 .4 jn= 98 x170.2±93.3
x 62.6 S141.4
range range
0.1-1063.5 61.2- 656.2
I iodine contaminated n=31 I iodine contaminated n= 0
0.1-19.9 40-59.9 80-99.9 120-1399 160-179 9 200-219 9 240-2599 280-300 >300
20-39.9 60-79.9 100-139.9 UO-159.9 - 180-199.9 220 -239.9 260 -279.9 >ug J / g creatinine
Fig. 5. Frequency distribution of iodine excretion in Germany and Sweden.
be maintained. As previously found with children in 23 German towns, (Gutekunst et al. 1985), there is likewise no clear-cut increase of thyroid
Table 2. Comparison of medians of iodine excretion (\ig I /g creatinine) and thyroid volume (ml) from Northern to
Southern Germany.
Iodine Thyroid volume (jig I /g creatinine) (ml)
Kie l 67.3 14.3 (n = 46) (n = 46)
Lübeck 104.7 12.5 (n = 63) (n = 70)
Berl in 61.9 15.2 (n = 98) ( n = 111)
Wolfsburg 48.2 18.7 (n = 230) (n = 313)
Frankfurt 64.2 18.8 (n = 201) (n = 224)
Tutzing 64.8 18.5 (n = 291) (n = 339)
Penzberg 66.0 14.5 (n = 264) (n = 293)
Total 62.6 17.0 ( n = 1193) (n = 1397)
size in adults from north to south. Similarily, endemic nests have to be expected especially in the central region of the FRG. However, in order to obtain a satisfactory mapping of goitre prevalence and iodine deficiency in the FRG, and extensive investigation at further locations would be necessary.
In the German population, 12.4% more abnormal sonographic echopatterns - a sign of diffuse or focal alteration of the gland — were observed than in the Swedish population. These findings are in accordance with the well-known fact that nodular goitre is mainly the consequence of thy-
Table3. Comparison of T S H and T G serum levels in Germany
and Sweden.
Germany Sweden (n = 91) (n = 62)
x = 72.6 ± 50.6 x = 23.5 ± 17.4 T G ( | i g / l ) x = 43 x = 2 1 . 2
range 1.6-234.7 range 15.0-86.0
x = 0.97 ± 0.52 x = 1.49 ± 0.82 T S H (mU/1) x = 0.9 x = 1.55
range 0.02-2.82 range 0.08-3.98
32' 499
roid enlargement following iodine deficiency, (Hedinger 1980).
From our present observations and those in an earlier study (Gutekunst et al. 1985) it is apparent that thyroid palpation is of limited value for epidemiological goitre studies. Palpation is even less reliable in younger subjects. It is almost useless in children below 10 years of age. Although the sensitivity of palpation in adults was acceptable (91%), the specificity decreased dramatically to 63.5%.
There is no statistical relation between thyroid volume and iodine excretion in Germany, since all Germans are similarily iodine deficient. Furthermore, iodine excretion is very close to the minimum daily iodine excretion, i.e. individuals with increased tendency to develop goitre cannot be distinguished from the normal population.
This is also true for children and adults who use iodized table salt. The iodized salt in Germany contains 20 mg iodine per kg. To counteract this iodine deficiency, a salt intake of 5 g per person per day is necessary. Since iodized table salt can only be added by the individual to his own food, 5 g daily is obviously unrealistic. Hintze et al. (1985) reported in a 4 year follow-up that there is no significant difference in iodine excretion and goitre stages in children who use iodized salt compared to those who do not. The study of Kersting et al. (1985) suggests that a daily additional intake of more than 1-3 g salt is impractical.
As expected, serum thyroglobulin concentration was higher in German subjects than in those living in Sweden. This is probably due to abnormal thyroid metabolism of thyroglobulin during iodine deficiency, (Pezzino et al. 1978) as well as a greater thyroglobulin leak in degenerative goitre (Gebeletal. 1983).
The surprisingly lower T S H levels in Germany could partially be explained by a higher prevalence of 'preclinical autonomy'. This is a well-known consequence of iodine deficiency (Fenzi et al. 1985; Pickardt et al. 1972). Our results concur with those of Delange et al. (1971) who observed no relationship between serum T S H and thyroid volume. Pickardt et al. (1972) also found no difference in serum T S H in an endemic goitre area in Bavaria. A rise in serum T S H is only observed when iodine deficiency leads to inadaequate production of T 4 and T 3 as has been reported in severe endemic goitre areas (Chopra et al. 1975).
Studies in the rat have shown that iodine depleted thyroids are much more sensitive to T S H than those with normal iodine content (Bray 1968). Possibly, the reduced T S H level is a physiological response to protect the thyroid from additional growth. It is currently disputed whether T S H is indeed a growth factor for the thyroid cell (9th Int. Thyroid Congr. 1985).
However, these explanations do not conclusively explain the significantly lower levels of serum T S H in the German population. Further investigation with supersensitive TSH-immunoassays will be necessary.
Conclusions It is evident from the present study and those reported earlier that the iodine supply in Germany is insufficient. Goitre prevalence can be substantially decreased by an effective program of iodine prophylaxis. Since compulsory iodination of salt is at this time not possible there must be a gradual increase to 50 mg iodine per kg table salt. Further ways to supply people with appropriate iodine should be considered. Increased public awareness of this problem is essential.
Acknowledgments
W e thank the following companies for giving the employees time to participate in this study: Boehringer Mannheim, B r u n n e n g r ä b e r Lübeck, Ferring Kie l , Henning Ber l in , Hoechst Frankfurt , L K B Stockholm and Volkswagenwerk, Wolfsburg.
We are grateful for the support of the Freunde und F ö r d e r e r of the Medical University of Lübeck.
We thank Prof. D r . K l . Lorentz and Dr . E . Kraas for the technical advice to measure creatinine.
T h e authors gratefully acknowledge the critical reading and help with the manuscript by Prof. L . Braver-man, Worcester, M A , U S A .
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Received December 2nd, 1985. Accepted February 17th, 1986.
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