endcxrino fagiea Volume 106

May - August 1984

Copenhagen

CHIEF EDITOR J. STARUP . DENMARK

EDITORS H. M. M. FREY . NORWAY

T. B. van WIMERSMA GREIDANUS .THE NETHERLANDS

C. HÄGEN . DENMARK

P. W. JUNGBLUT. FEDERAL REPUBLIC OF GERMANY

TH. LEMARCHAND-BERAUD . SWITZERLAND

J.-G. LJUNGGREN . SWEDEN

M.SEPPÄLÄ. FINLAND

CONSULTING EDITOR C. HAMBURGER . DENMARK

Advisory Panel, page V

Contents Vol . 106, page VII

Au thors ' Index, page XI

Subject Index, page XV

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, England. Prof. Dr. G. Bettendorf, Hamburg, FRG. Dr. Christian Binder, Gentofte, Denmark. Prof. S. R. Bloom, London. England. 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, England. Dr. William F. Crowley, Jr, Boston, USA. Prof. Leslie J. DeGroot, Chicago, USA. Dr. Francois 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. Frantz H. Enzmann, Bad Homburg, 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. Fulgencto 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 Holst, Copenhagen, Denmark. Prof. Bernt Hökfelt, Malmö, Sweden. Prof. Howard S. Jacobs, London, England. 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. Dr. 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. Siersbaek-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. Prof. Dr. Helmut Thomas, Ulm, FRG. Prof. Niels A. Thorn, Copenhagen, Denmark.

v

Dr. George Tolis, Athens, Greece. Prof. Olav Trygstad, Oslo, Norway. Dr. W. M. G. Tunbridge, Newcastle upon Tyne, England. Prof. Michel B. VaNorton, 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 Wahiberg, Mariehamn, Finland. Dr. Jorgen Warberg, Copenhagen, Denmark.

Dr. Jorgen Weeke, Ärhus, 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. Dr. 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. Ivar 0ye, Oslo. Norway.

VI

Contents Vol. 106

Hypothalamus

Donoso A O 8c Ranzau A M : Effects o f increase o f brain G A B A levels on the hvpothalamic-pituitarv-lute iniz ing hormone axis in rats 298

Stalla G K. H a r t w i m m e r J. von Werder K & Müller O A : Ovine (o) and human (h) corticotrophin releasing factor (CRF) in man: GRF-stimulation and CRF-immunoreactivitv 289

T o u i t o u Y, Fevre M , Bogdan A, Reinberg A, De Prins J. Beck H 8c T o u i t o u C: Patterns of plasma melatonin wi th ageing and mental condit ion: stability o f nvctohemeral rhvthms and differences in seasonal variations 145

V a k k u r i O , Leppäluoto J & Vuolteenaho O : Devel­opment and validation o f a melatonin radioim­munoassay using radioiodinated melatonin as tracer 152

Yasuda N . Yasuda Y, Aizawa T . Maruta S 8c Greer M A : In vivo and in vitro comparisons of biologi­cal activities o f bovine, ovine and rat GRF (cortico-trophin-releasing factor) 158

Pituitary

Boehm N , Plas-Roser S & A r o n CI : Prolactin and the control o f cycle length in the female rat 188

Eigen mann J E, Patterson D F 8c Froesch E R: Body size parallels insulin-like growth factor I levels but not growth hormone secretory capacity 448

Glänzer K, Appenheimer M , Krück F, Vetter W 8c Vetter H : Measurement o f 8-arginine-vasopressin bv rad ioim m u noassay 317

G r u n t J A , H o w a r d C P, & Daughaday W H : Comparison o f growth and somatomedin C re­sponses fo l lowing growth hormone treatment in ch i ldren wi th small-for-date short stature, signifi­cant idiopathic short stature and hypopituitarism 168

Hagen C, Nyboe Andersen A 8c Djursing H : Evi­dence o f altered dopaminergic modulation o f Prl, L H . FSH, G H and T S H secretion d u r i n g chronic part ia l dopamine receptor blockade in normal w o m e n 1

Hagen C, Petersen K, Djurs ing H 8c Nyboe Ander­sen A : Evidence o f altered dopaminergic modula­t i o n o f Pr l , L H and T S H secretion in patients with normoprolact inaemic amenorrhoea 8

H e u l i n M - H . A r t u r \L Geschier C. Straczek J . Yescovi G. Belleville F. Paysant P 8c Nahet P: The biological assay of human somatomedin A : im­provement bv small molecular weight natural molecules 43

H u l t i n g A - L . Hall K & Werner S: Somatomedin A increments are diminished in acromegaly with concomitant h\ perprolactinaemia 305

Ishibashi M . Hara T . Tagusagawa Y. Fukushima T . Numata H , H o r i T 8c Yamaji T : Effects o f ovine corticotrophin-releasing factor and hydrocor­tisone on growth hormone secretion bv pituitary adenoma cells o f acromegaly in culture 443

I.aszlo F A . Csati S & Balaspiri L : Effect o f the vasopressin antagonist d/CH 2 /5Tvr•"Et/VAVP on the ant idiuret ic action o f exogenous and endo­genous vasopressin 52

Laszlc') F A . Csati S & Balaspiri L : Prevention o f hvponatraemia and cerebral oedema bv the vaso­pressin antagonist d / C H 2 5Tvr/Et/VAVP in rats treated w i t h pitressin tannate 56

McKenna T J, Cunningham S, Culliton M , Daly L, Moore A, Magee F 8c Smyth P P A : Prolactin in hirsute w o m e n : possible roles for androgens in suppressing basal levels, and for oestrogens in enhancing T R H - i n d u c e d responses 15

N o r t i e r J VV R, Croughs R J M . Donker G H , Thijssen J H H 8c Schwarz F: Changes in plasma G H levels and clinical activity d u r i n g bromocrip­tine therapy in acromegaly. The value of predic­tive tests 175

N o r t i e r J W R, Croughs R J M , Thijssen J H H 8c Schwarz F: Long-term fol low-up of five untreated acromegalic patients 437

Oosterom R, Verleun T , Uit ter l inden P, Hackeng W H L, Burbach J P H , Wiegant V M 8c Lamberts S W J : A C T H and ß-endorphin secretion by three cort icotrophic adenomas in culture. Effects o f cul ture t ime, dexamethasone, vasopressin and synthetic cort icotrophin releasing factor 21

Perheentupa J . Lakshmanan J, Macaso T 8c Fisher D A : G r o w t h hormone increases neonatal mouse u r i n e epidermal growth factor 184

Poirier J C, Combarnous Y & Blanc M R: Highly specific antisera against native ovine Follitropin (oFSH) obtained f r o m crude antisera by affinity chromatography on solid-phase undissociable l u t r o p i n ( L H ) column 38

VII

R e v m o n d M J. Dale Nansel D. Howard Burrows C. Neaves VV B & Porter J C: A new clonal strain of rat p i tui tarv t u m o u r cells: a model for l ion-regu­late secretion o f prolactin 159

Schui l ing G A . Moes H & Koiter T R: Desensiti/a-t ion o f the pituitary gland induced in vivo bv lute in iz ing hormone-releasing hormone ( L R U ) or bv the LRH-analogue buserelin does not affect the autonomous secretion o f luteinizing hormone a n d follicle st imulating hormone as observed in v i t r o 4")-I

Seki K, Lcsato I " , Kato K & Shima K: Twenty- four h o u r secretory pattern of prolactin in hv perpro-lactinaemic patients with pituitary micro- and macroadenomas 43.3

V i e r h a p p e r H , [org |, Favre L, V'allotton M B <x-VValdhäusl VV: Comparative therapeutic benefit o f indomethac in , hydrochlorothiazide, and acetvl-salicvlic acid in a patient with nephrogenic dia­betes insipidus 311

Wogensen I . & Warberg J: Cyclic and diurnal altera­tions in the response of luteinizing hormone and prolac t in to prostaglandin F 2 d u r i n g the rat oe-strousevele 30

T h y r o i d

Aratan-Spire S, W o l f B & Czernichow P: Effects o f h v p o - and hyperthyroidism on pancreatic I R I I -d e g r a d i n g activity and T R H concentrations in developing rat pancreas 209

Bidey S P. Ryder K, Caines-Das R. Marshall N J & Ekins R P: A comparison o f the bioactivity o f h u m a n and bovine t h y m t r o p h i n preparations, as d e t e r m i n e d by intracellular cyclic A M P responses of cu l tured FRTI.-5 cells and human thyroid cell monolayers 482

Emmertsen K, Meisen F, Mosekilde L. L u n d Bi, L u n d Bj , S0rensen O H . Charles P & Moller |: V i t a m i n D levels and trabecular bone remodell ing before and after surgery for medullary thyroid carcinoma 340

H a l l e n g r e n B. Melander A & Thesleff S: Local anaesthesia and immunomodulatory effects o f a n t i t h y r o i d drugs 336

Ikeda H , Cheng Chiu S, Kuzuya N . Uchimura H & Nagataki S: Effects o f in vivo t r i iodothyronine and l o n g acting thyroid stimulator (EATS) admi­nis trat ion on the in vitro thyroid c A M P response to t h v r o t r o p h i n and L A T S 193

K j x r u l ' f f H , Bech K 8c Bliddal H : Isolation o f t h y r o i d st imulating immunoglobulins by af f in i ty chromatography using protein A sepharose 79

Lazarus J H , B u r r M L, McGregor A M , Weetman A P, Ludgate M . Woodhead J S 8c Hal l R: T h e pre­valence and progression o f autoimmune thyro id disease in the elderly 199

l . io S. Pontecorvi A. Caruso M . Monaco E & D' .Ai-mienlo M : Transitory subclinical and permanent hypothyroidism in the course o f subacute thy­roiditis (de Quervain) 07

Naafs M A B. van der Yelclcn P C, Fischer I I R A, koorevaar C. van Duin S. Hackeng \V H L. Schopman W & Silberbusch J: Changes in ne­phrogenous cyclic A M P excretion and plasma cvclic A M P fol lowing treatment o f hyperthyroid­ism 477

Orl iz -Caro J. Obregon M [, Pascual A & John T : Decreased T 4 to T 3 conversion in tissues of strep-tozotocin-diabetic rats 80»

Perrild H . Feldt-Rasmussen l \ Bech K, Ahlgren P & M o l h o l m Hansen J : The differential diagnostic problems in unilateral euthyroid Graves'ophthal­mopathy 17 I

Perri ld I L Hegedüs L & A r m i n g K: Sex related goitrogenic effect o f l i th ium carbonate in healthv young subjects 203

Schaison G. Thomopoulos P. Leguillouzic D. Thomas G & Moatti M : Effects of sodium ipodate and propylthiouraci l in athvreotic human sub­jects, role o f tr i iodothyronine and pituitary thy­roxine monodeiodination in thvrotrophin regula­tion 338

Shiota K. Voshida K. Noguchi C & Xakavama R: In vi tro thvrot rophin release with thvrotrophin-releasing hormone and an analogue. OX-1 1 1 7 . . . 71

Swart S. OMal lev B P. Vora J, Barnett D B & Rosen­thal F D : T h e effects o f dopaminergic blockade on serum T S H and prolactin levels in thyrotoxi ­cosis 330

Wajchenberg B L. Tsanaclis A M C & Marino R Jr: TSH-conta in ing pituitary adenoma associated with pr imary hypothyroidism manifested bv amenorrhoea and galactorrhoea 61

W i l k i n I ] & Casev C: The distribution of immuno-globulin-containing cells in human autoimmune thyroidit is 490

Parathyroid

A u w e r x ] , Demedts M 8c Bouillon R: Altered para­t h y r o i d set point to calcium in familial hypo-calciuric hvpercalcaemia 215

Balabanov S, Töllner U , Richter H-P, Pohlandt F. Gaedicke G 8c Tel ler W M : Immunoreactive para­t h y r o i d hormone, calcium, and magnesium in h u m a n cerebrospinal f lu id 227

Chin Chao C, Brown R D 8c Deftos L J: Seasonal levels o f serum parathyroid hormone, calcitonin and alkaline phosphatase in relation to antler cycles in white-tailed deer 234

VIII

Oavics M . Adams P I I , I .umh G A, Berry J 1. & Loveridge N : Familial hypocalciuric hvpcrcalca-emia: evidence for continued enhanced renal tubular reabsorption o f calcium fol lowing total parathyroidectomy 499

K h o u r v S & Tucci J R: I ' r i n a r y and nephrogenous evelic A M P and renal phosphate handling in normal subjects and patients with parathyroid dysfunction -19

Pancreas

Aratan-Spire S, Wol f B & Czernichow P: Develop­mental pattern o f T R H - d e g r a d i n g activity and L R U content in rat pancreas 102

( i r o o p I . , Marno K & Tolppanen F - M : The combi­nation o f insulin and sulphonvlurea in the treat­ment o f secondary d r u g failure in patients with tvpe 11 diabetes 97

( i r o o p I . & Tolppanen F - M : Factors influencing beta-cell function and insulin sensitivity in pa­tients with type 2 (non-insulin-dependent) dia­betes 505

Heine R |. Ponchner M , Harming I , Home P D. B r o w n M , Williams D & Alberti K G M M : A comparison o f the effects o f semisynthetic human insulin and porcine insulin on transmembrane ion shifts and glucose metabolism d u r i n g eu-glvcaemic c lamping 241

Lindström P: Kinetics o f 5-hvdroxvtryptophan po­tentiation o f glucose-induced insulin release 248

MacFarlane I A. Sheppard M C. Black R G, Gilbev S & Wright A D : T h e hypothalamic-pituitary-thy­ro id axis in Tvpe 1 diabetes: influence of diabetic mcmbolic control 92

Müller-Esch G. Ball 1\ Heidbüchel K. Graham Wood W & Scriba P G: Insulin hypoglycaemia test guided bv a glucose controlled insulin infusion svstem 350

Liver

Conte N . Gecchettin M , Manente P. Valmachino G, Roiter I & Pavan P: Calcitonin in hepatoma and cirrhosis 109

Gastro-intestinal tract

Rasmusson B: Gastro-intestinal polypeptides in pa­tients treated for medullary carcinoma o f the t h v r o i d 112

A d re rials

Hamstra W V Dorav D & Dunn J D : The effect o f methane on piluiiarv-adrenal function o f female rats 362

Mannel l i M , Maggi M , De Feo M L, Cuomo S, Delitala G, Giusti G & Serio M : Effects o f nalox­one on catecholamine plasma levels in adult men. A dose-response studv 357

Mills E H , Goghlan J P, Denton D A, Spence C D, W h i t w o r t h J A & Scoggins B A : T h e effect o f potassium loading and sodium depletion on DOC induced hypertension in sheep 521

N o m u r a K. Naruse M . Xaruse K. Demura H & Shizume K: In vivo evidence of Cortisol secretion bv aldosterone-producing adenomas 516

Sienström G. Sjöström L & Smith U : Diabetes mellitus in phaeochromoevtoma. Fasting blood glucose levels before and after surgery in 60 patients with phaeochromoevtoma 511

Ovaries

Bennegard B. Dennefors B & Hamberger L : Inter­action between catecholamines and prostaglandin F 2 « in human luteolvsis 532

de Reviers M M . Viguier-Martinez M C & Mariana J C: FSH, L H and prolactin levels, ovarian fol l icu­lar development and ovarian responsiveness to FSH in the Snell d w a r f mouse 121

Duursma S A, Bijlsma J W J, Van Paassen H C, van Buul-Offers S C & Skottner-Lundin A : Changes in serum somatomedin and growth hormone con­centrations after 3 weeks oestrogen substitution in post-menopausal women; a pilot study 527

Farish E. Fletcher C. I ) , Hart D M . Azzawi E A l , Abdalla H I & Grav C E: Ehe effects o f hormone implants on serum lipoproteins and steroid hor­mones in bilaterally oophorectomised women . . . . 116

Eraser H M & Shaw R W : Effects o f chronic luteinizing hormone-releasing hormone agonist treatment on dysfunctional uterine bleeding in the stumptailed macaque 381

H o n jo H , Otsubo K. Yasuda J, Kitavvaki J, Okada H , O h k u b o T & Nambara T : Conjugated oestrogen d u r i n g the menstrual cycle measured by a direct radioimmunoassay with an antiserum prepared against oestradiol-17-glucosiduronate-[C-6]-BS A conjugate 374

M o r i T , Saito H , Ohno Y, Irahara M , Hosoi E 8c Saito S: Evidence for existence of somatostatin-Iike immunoreactivity with molecular heterogen­eity in porcine ovaries 254

Patwardhan V V & Lanthier A : Concentration o f cyclic A M P in rabbit ovaries in the preovulatory period after administration o f luteinizing hor­mone or human chorionic gonadotrophin 260

IX

Smith C 8c Perks A M : T h e effects o f brads kinin on the contractile activity of the isolated rat ovarv . . . 387

Sogn J, Abrahamsson G & Janson P O : Release of evelic A M P and progesterone f r o m the isolated perfused luteal ovary o f the PMSG treated rat . . . . 265

VVilks J VV: Inhibi t ion of folliculogenesis in the monkev fol lowing early foll icular phase admini ­stration o f an ERH agonist 538

Zachmann M , Manella B, Eiholzer U . Bucher H & Prader A : Influence o f oestrogen in high and low-doses on plasma steroid concentrations in girls w i t h tall stature and T u r n e r syndrome 368

Uterus

Wiqvist I . Norström A, O'Bvrne E & Wiqvist N : Regulatory influence o f relaxin on human cervi­cal and uterine connective tissue 127

Pregnancy

Andersen J R, Borggaard B. Schmeder E. Olsen E B, Stimpel H & N y h o l m H C: T h e dependence of h u m a n decidual prolactin product ion and secre­t ion on the osmotic environment in vi tro 405

Gomez F, Monnier B 8c Lemarchand-Beraud T : Foetal exposure to low doses o f cyproterone acetate i n the rat leads to functional endocrine abnormalities despite normal sexual morpho­genesis 411

Perez-Lopez F R, Robert J 8c Te i je i ro J : Prl , T S H . FSH, ß-hCG and oestriol responses to repetitive (triple) L R H / T R H administration in the t h i r d trimester o f human pregnancy 400

Roti E, Robuschi G. Alboni A, Emanuele R, d 'Amato L , Gard in i E, Salvi M . D a l f A g l i o E, G n u d i A & Braverman E E: Inhibi t ion o f foetal growth hor­mone ( G H ) and t h y r o t r o p h i n ( T S H ) secretion after maternal administration o f somatostatin . . . . 393

Schams D 8c Lahlou-Kassi A : Circulat ing concentra­tions o f oxytocin d u r i n g pregnancy in ewes 277

Wiqvist I , Norström A 8c Wiqvist N : Effects o f oxytocin on cervical and uterine connective tissue 271

Yki-Jürvinen H & Wahlström T : Imtnunohistoche-mical demonstrat ion of relaxin in the placenta after removal o f the corpus luteum 54 1

Testes

Allenberg M . Bartoov B 8c Mavevskv A : T h e effect of testosterone on ram spermatozoa collective mot i l i ty treated bv antimvein A 1.33

X a m i k i M . Koide T , Okuvama A. Sonoda T . Itatani H . Mivake A. A o n o T . Terada N & Matsumoto K: Abnormal i ty o f testicular FSH receptors in infer­tile men 548

Miscellaneous

Baxter R C. Mar t in J L & Handelsman D J : Ident i f i ­cation of human semen insulin-like growth factor-I somatomedin-C immunoreactivitv and binding prote in 420

Das D K. Bandvopadhvav D, Bandvopadhvav S & \eog i A : T h v r o i d hormone regulation o f ß-adrenergic receptors and catecholamine sensi­tive adenylate cyclase in foetal heart 509

H a u J. Chemnitz J. Teisner B. Tornehave D & Svendsen P: Induct ion o f murine a-foetoprotein synthesis by oestradiol 14 1

Jones R C: T h e effect o f a luteinizing hormone releasing hormone ( L R H ) agonist (Wv-40,972), Ievonorgestrel, danazol and ovariectomy on ex­perimental endometriosis in the rat 282

Maruvama Y. A o k i N , Suzuki Y, Sinohara H 8c Yamamoto T : Variat ion with age in the levels o f sex-steroid-binding plasma protein as determined by radioimmunoassay 428

Ralston S H , Cowan R A, Robertson A G, Gardner M D 8c Boyle I T : Circulating vitamin D metabo­lites and hvpercalcaemia of malignancy 550

Sjöden G O J, Johnell O, Del.uca H F & Lindgren J U : Effects o f l a O E I D 2 on bone tissue. Studies o f l a O H D 2 and I C X O H D 3 in normal rats and in rats treated with prednisolone 564

x

Authors' Index

Abdalla H I , 116 Abrahamsson G, 265 Adams P H , 499 A h l g r e n P. 471 Al lenberg M , 133 Aizawa T , 158 A l b e r t i K G M M 241 A l b o n i A , 393 d ' A m a t o L. 393 Andersen J R, 405 A o k i N . 4 2 8 A o n o T , 548 Appenhe imer M , 317 Aratan-SpireS, 102,209 A r n i n g K, 203 A r o n C. 188 A r t u r M , 43 A u w e r x J. 215 Azzawi F A, 116

Balabanov S, 227 Balaspiri L, 52, 56 Ball P, 350 Bandyopadhyay D , 569 Bandyopadhyay S, 569 Banzan A M , 298 Barnett D B, 330 B a r t o o v B , 133 Baxter R C . 420 Bech K , 7 9 , 4 7 1 Beck H , 1 4 5 Belleville F, 43 Bennegärd B, 532 Berry J L, 499 Bidev S P, 482 B i j l s m a ] W J . 5 2 7 Black E G , 92 Blanc M R, 38 Bl iddal EL 79 Boehm N , 188 Bogdan A, 145 Borggaard B, 405 Boui l lon R, 215 Boyle I T, 556 Braverman L E, 393 B r o w n M , 241 B r o w n R D , 234 Bucher H . 3 6 8 Burbach J P H , 21

B u r r M L, 199 Burrows G H , 4 5 9 van B u u l - O f f e r s S C . 5 2 7

Caruso M , 67 Casey C. 490 Cecchettin M , 109 Charles P, 346 Chemnitz J, 141 Cheng Chiu S. 193 C h i n C h a o C, 234 CoghlanJ P, 52 1 Combarnous Y, 38 C o n t e N , 109 Cowan R A, 556 Croughs R J M . 175,437 Csati S, 52, 56 Cul l i ton M , 15 C u n n i n g h a m S, 15 C u o m o S, 357 Czernichow P, 102,209

Dal l 'Agl io E, 393 Daly E 15 D A r m i e n t o M , 67 Das D K, 569 Daughaday W EE 168 Davies M , 499 De Feo M E, 357 D e f t o s L [ ,234 Delitala G, 357 DeLuca H F, 564 Demedts M , 215 Dem ura H , 516 Dennefors B, 532 Denton D A , 521 De PrinsJ , 145 Djurs ing EI, 1,8 Donker G H , 175 Donoso A O, 298 Doray D , 362 van D u i n S, 477 D u n n J D, 362 Duursma S A , 527

Eigenmann J E,448 Eiholzer U , 368 Ekins R P, 482 Emanuele R, 393

Emmertsen K. 346

Farish E, 116 Favre L, 311 Feldt-Rasmussen L\ 471 Fe vre M , 145 Fischer H R A , 477 Fisher D A . 184 Fletcher C D , 116 Fräser H M , 381 Froesch E R. 448 Fukushima T , 443

GaedickeG, 227 Gaines-Das R, 482 G a r d i n i E, 393 Gardner M D, 556 Geschier C, 43 Gilbey S, 92 Giusti G, 357 Glänzer K, 317 G n u d i A , 393 Gomez F. 411 Graham Wood W, 350 G r a y C E, 116 Greer M A . 158 G r o o p E, 97, 505 G r u n t J A, 168

H a c k e n g W H L, 21,477 Hagen C, 1,8 H a l l K, 305 Hal l R, 199 Hal lengren B ,336 Hamberger L, 532 Hamstra W N , 3 6 2 Handelsman D J , 420 H a n n i n g I , 241 Hara T , 443 H ä m o K, 97 H a r t D M , 116 H a r t w i m m e r J, 289 H a u J , 141 Hegedüs L, 203 Heidbüchel K, 350 Heine R J, 241 H e u l i n M - H , 4 3 H o m e P D , 241 H o n j o H , 3 7 4

XI

H o r i T . 443 Maisumoto K. 548 Perez-Löpez F R, 400 Hosoi E. 254 Mavevskv V 133 PerheentupaJ,184 H o w a r d C P. 168 McGregor A M , 199 Perks A M . 3 8 7 H u l t i n g A - L . 305 McKenna T J . 15 Perri id FL 203. 471

Melander A. 336 Petersen K, 8 Ikeda H , 193 Meisen F. 346 Pias-Roser S. 188 I rahara M , 254 Mills E H . 521 Pohlandt F, 227 Eshibashi M , 443 Mivake A. 548 Poir icr J G. 38 I ta tan i H , 548 Moatt i M . 338 P o n c h n e r M . 2 4 1

Moes H . 454 Pontecorvi A. 67 Janson P O , 265 Monaco F. 67 Porter J G. 459 J ö r g J ,31I Monnier B , 4 1 I P r a d e r A . 368 Johne l l O , 564 Moore A. 15 De PrinsJ . 145 J o l i n T . 86 M o r i T . 254 Jones R C, 282 Mosekilde L. 346 Ralston S H . 556

Müller O A , 289 Rasmusson B. 112 Kato K. 433 Müller-Esch G, 350 Reinberg A, 145 K h o u r y S . 219 M o l h o l m Hansen J, 471 de Reviers M M . 121 Ki tawaki J , 374 Möller J. 346 Revmond J YL459 Kjaerulf f H , 79 Richter H-P. 227 K o i d e T , 548 Xaafs M A B.477 R o b e r t ] , 400 K o i t e r T R, 454 Xabet P. 43 Robertson A G, 556 Koorevaar G, 477 XagatakiS, 193 Robuschi G. 393 Krück F, 317 Xakavama R. 71 Roiter I , 109 K u z u y a N , 193 X a m b a r a T . 374 Rosenthal F D, 330

X a m i k i M , 548 Roti E, 393 Lahlou-Kassi A, 277 Xansel D D. 459 R y d e r K . 482 Lakshmanan J, 184 Xaruse K. 516 Rve Andersen J. 405 Lamberts S W J, 21 X a r u s e M , 5 1 6 L a n t h i e r A , 260 Xeaves W B, 459 Saito H , 254 Laszlö F A , 52, 56 Neogi A, 569 Saito S, 254 LazarusJ H , 199 Noguchi C, 71 Salvi M , 393 Leguil louzic D, 338 N o m u r a K, 516 Schaison G, 338 Lemarchand-Beraud T, 411 Norström A. 127, 271 Schams D, 277 Leppäluoto J, 152 N o r t i e r J W R, 175,437 Schopman W, 477 L i n d g r e n J U , 564 Numata Fl, 443 Schroeder E, 405 Lindström P, 248 Nvboe Andersen \, 1, 8 Schuil ing G A. 454 L i o S, 67 X v h o l m H C.405 Schwarz F, 175, 437 Lover idge N , 499 Scoggins B A, 52 1 Ludgate M , 199 Obregon M J, 86 Scr ibaPG,350 L u m b G A , 4 9 9 O ' B y r n e E , 127 Seki K,433 L u n d B i ,346 O h k u b o T , 374 Serio M , 357 L u n d B j , 346 O h no Y, 254 Shaw R W , 381

Okada H , 374 Sheppard M C, 92 MacasoT, 184 Okuyama A, 548 Shima K, 433 MacFarlane I A, 92 Olsen E B,405 Shiota K, 71 M a g g i M , 357 O'Malley B P, 330 Shizume K, 5 16 Magie F, 15 Oosterom R, 21 Silberbusch J, 477 M a n e l l a B , 368 Ort iz -CaroJ .86 Sinohara H , 428 ManenteP , 109 Otsubo K, 374 S j ö d e n G O J , 5 6 4 M a n n e l l i M , 357 Sjöström L, 511 M a r i a n a J C , 121 Van Paassen H C, 527 Skot tner -Lundin A, 52 M a r i n o RJr, 61 Pascual A , 8 6 Smith C, 387 Marshal l N J , 482 Patterson D F, 448 Smith U . 511 M a r t i n J L , 420 Patwardhan V V, 260 Smyth P P A , 15 M a r u t a S , 158 Pavan P, 109 S o g n ] , 2 6 5 M a r u y a m a Y, 428 Paysant P, 43 Sonoda T , 548

Spence C 0 , 5 2 1 Stalla G K, 289 Stenström G, 5 11 St impel H,4()6 StraczekJ, 43 Suzuki Y, 428 Svendsen P, 141 SwartS , 330 Stfrensen O H , 346

Tagusagawa Y, 443 Te i j e i ro J ,400 Teisner B. 14 1 Te l le r VV M , 227 Terada N . 548 EhesleffS,336

Thijssen J H H . 175.437 T h o m a s G. 338 T h o m o p o u l o s P, 338 Töl lner 1 . 2 2 7 T o l p p a n e n E-M. 97, 505 Tornehave D, 141 T o u i t o u C, 145 T o u i t o u Y. 145

Tsanaclis A M G, 61 Tucci J R , 219

U c h i m u r a H , 193 Uesato T , 433 U i t t e r l i n d e n P, 21

V a k k u r i O , 152 Val lotton M B, 3 11 V a l m a c h i n o G , 109 van der Velden P C, 477 Verleun T . 21 Vescovi G. 43 Vetter H , 317 Vetter VV. 317 Vierhapper H , 3 11 Viguier -Mart inez M C, 121 Vorn J .330 Vuolteenaho O, 152

Wahlström T , 544 Wajchenberg B E, 61 Waldhäusl W, 3 1 1 Warberg J . 30 Weetman A P, 199

von Werder K, 289 W e r n e r S, 305 W h i t w o r t h J A . 5 2 1 Wiegant V M , 2 1 W i l k i n T J, 490 Wilks J W . 5 3 8 Wi l l iams D, 241 Wiqvist I , 127,271 VViqvis tN. 127,271 Wogensen E, 30 W o l f B, 102,209 W o o d W G. 350 Woodhead J S, 199 W r i g h t A D, 92

Yamaji T . 443 Yamamoto T . 428 YasudaJ ,374 Yasuda N , 158 Yasuda Y, 158 Yki-Järvinen H , 544 Yoshida K, 7 1

Zach m a n n M . 368

Acta Endocrinologica 1984,106: 350-356

I n s u l i n hypoglycaemia test guided by a glucose contro l led insul in in fus ion system

Gert Müller-Esch, Peter Ball 1, Karen Heidbüchel,

William Graham Wood and Peter C. Scriba

Klinik für Innere Medizin und Institutfür Biochemische Endokrinologie*,

Medizinische Hochschule, Lübeck, FRG

Abstract. Insulin hypoglycaemia test ( I H T ) for assess­ment o f hypothalamic-pituitary-adrenocortical (HPA) funct ion in patients with pituitary tumours is usually p e r f o r m e d by bolus injection o f insulin, a procedure which includes the risk of overdosage and/or the need o f repeated administration. This study describes that a glucose controlled insulin infusion system (GCIIS) per­mits to p e r f o r m the I H T with standardized hypoglycae­mia. T e n healthy volunteers and 10 patients wi th p i tu i ­tary tumours were studied using the GCIIS (Biostator®) on static control (Mode 1:1, B I 35, Q I 10, R I 20, F I 300). Insul in administration was discontinued and the GCIIS used only for moni tor ing o f blood glucose (BG), when BG had fallen below 40 mg/dl and initial clinical symp­toms for hypoglycaemia were observed. I n controls, the G C I I S guided I FIT achieved a sufficient degree of hypo­glycaemia (BG 27.6 ± 2.0 mg/dl ; mean ± SEM) and physiological responses for G H (peak 49.4 ± 6.7 ng/ml) , Prl (peak 1766 ± 614 f iU/ml) , A C T FI (peak 76.0 ± 8.7 pg/ml) and Cortisol (peak 252 ± 15 ng/ml). The total amount o f insulin given was 0.115 ± 0.012 U/kg. I n the patients w i t h pituitary tumours however, the required insulin dose varied markedly from 0.090 (pituitary insuf­ficiency) to 0.340 U / k g (Cushing's syndrome). M i n i m u m BG obtained was 32.5 ± K9 mg/dl . Partial impairment o f hypothalamic-pituitary function and, in particular, pa­tients r e q u i r i n g exogenous Cortisol supplementation d u r ­i n g stress, could be identi f ied. I n conclusion, special advantages o f the G C I IS-guided I H T are: 1) O p t i m a l insulin dosage with standardized hypoglycae­mia due to automatic adjustment to the individual insulin sensitivity.

Presented in part at the X l V t h Acta Endocrinologica Congress, Stockholm, 1983. Supported by the Federico Foundation.

2) Patients' safety by earlier recognition of due insulin discontinuation as a result o f continuous blood glucose analysis.

T h e insulin hypoglycaemia test ( I H T ) is a sensitive procedure for the assessment of hypothalamic-pituitary-adrenocortical (HPA) function (Faglia et al. 1973; Greenwood et al. 1966; Jenkins & Else 1968; Landon et al. 1966). It may detect subtle abnormalities of pituitary-adrenal function in pa­tients with hypothalamic and pituitary diseases, thus identifying patients who require exogenous Cortisol supplementation during severe stress such as trauma or surgery (Borst et al. 1982; Delaloye et al. 1982).

Usually, I H T is performed by bolus injection of insulin, a technique, which includes the risk of severe side effects because of overdosage. On the other hand insulin requirements can be under­estimated and the subsequent need of repeated insulin administration may alter pituitary hormone responses. We therefore used a glucose controlled insulin infusion system (GCIIS) for performing the I H T on the basis of a standardized hypoglycaemia with optimal insulin delivery due to automatic adjustment to the individual insulin sensitivity.

T h e aim of this study was 1) to show that the GCIIS-guided I H T achieved a sufficient degree of hypoglycaemia and physiological hormone re­sponses in healthy subjects and 2) that it permitted the assessment of HPA function in the patients with pituitary tumours studied as examples.

350

Table 1. Clinical data o f the patients studied.

Patient Sex Age

(years) Diagnosis

1. H . H . - B . M 54 hormone inactive pituitary adenoma 2. P. H . F 56 hormone inactive pituitary adenoma 3. W. W. M 48 hormone inactive pituitary adenoma 4. E. C. F 29 acromegaly 5. K. H.-P. M 36 acromegaly 6. H . H . F 45 Cushing's syndrome 7 B . W . M 46 prolactinoma 8 F. G. F 27 prolactinoma (MEA I) 9 P. D. M 46 pituitary insufficiency postoperative

(acromegaly) 10 M . K. M 47 pituitary insufficiency postoperative

(Cushing's syndrome)

Material and Methods

T e n healthy volunteers (4 females, 6 males, 25 ± 0.9 years, 174 ± 4 cm, 66 ± 4 kg; mean ± SF.M) and 10 patients wi th pi tui tary tumours were studied. In formed consent was obtained f rom the volunteers. Some clinical data o f the patients are given in Table 1.

Glucose controlled insulin infusion system. T h e details o f the GCIIS used for our study (Biostator, L i fe Science Instruments, Miles Laboratories, Elkhart,

USA) have been described elsewhere (Clemens et al. 1978; Fogt et al. 1978; Pfeiffer et al. 1974). T h e Biostator was used on static control . T h e fol lowing constants were chosen: B I 3 5 , Q I 10, R I 20, F I 300.

Experimental protocol A f t e r an overnight fast, the subjects were connected to the G C I I S between 08.00 and 09.00 a.m. Feedback control led insulin infusion (Insulin Hoechst CS, Frank­f u r t , FRG) was discontinued and the device was only used for blood glucose moni tor ing when blood glucose had

T . R . y , 26y infused insulin: 0.103 U/kg

120 min

Fig. 1. Blood glucose (BG) and insulin infusion rate (IR) d u r i n g GCIIS-guided I H T in a healthy volunteer.

Total amount o f insulin infused by the GCIIS 0.103 U/kg.

351

fallen below 40 mg/dl and initial clinical symptoms of hypoglycaemia occurred (palpitations, headache, sweat­i n g , tachycardia, drowsiness) (see Fig. I ) .

Venous blood samples were drawn at ± 0, SO, 45, 60, 90 and 120 m i n , respectively, f r o m an indwell ing catheter placed in an antecubital vein. For measuring serum insul in concentration, additional samples were collected at 10 and 20 m i n .

Analytical methods Serum G H (CIS), prolactin (CIS), Cortisol (clinical assays, SP), A C T H ( I N C , without extraction), insulin (CIS) and C-peptide (Byk Mall inckrodt) were measured by radio­immunoassay.

Statistical methods The results obtained f r o m the healthy volunteers are expressed as mean ± S E M .

BGlmg/dl)

Results Healthy volunteers

Fig. 2 shows the mean values for blood glucose, serum insulin and serum C-peptide in the healthy volunteers. Peak insulin levels occurred between 10 and 20 min after start of feedback controlled insulin infusion. The secretion of endogenous in­sulin represented by serum C-peptide levels was clearly inhibited by the exogenous administered insulin, reaching its minimum 60 min after the beginning of the I H T . The intervals until discon­tinuation of insulin administration was 26.7 ± 1.7 min. T h e total amount of insulin given by the G C I I S was 0.115 ± 0 . 0 1 2 U/kg and 4146 ± 347 m U / m 2 body surface, respectively. Clinical symp­toms of hypoglycaemia included palpitations, sweating, headache, tachycardia and drowsiness. No severe side effects were observed and there was no need of dextrose administration.

Fig. 3 shows the serum G H , prolactin, Cortisol and A C T H responses obtained in the healthy sub­jects. T h e mean basal and maximum values (x

± SEM) observed were: G H : 2.8 ± 1.1 vs 49.4 ± 6.7 ng/ml; prolactin: 193 ± 25 vs 1766 ± 614 fxU/ml; Cortisol: 100 ± 12 vs 252 ± 15 ng/ml and A C T H : 21.6 ± 2.6 vs 76.0 ± 8.7 pg/ml.

Pituitary tumour patients

Table 2 gives the results obtained from the patients with pituitary tumours expressed as basal and maximum values. The total amount of insulin

45

160-

0 10 20 30 45 60 C-Peph'deUg/l)

12

1.0

0,6

0.6

0.4

0.2

120 min

Fig. 2. Blood glucose (BG), serum insulin and C-peptide (mean ± S E M ) d u r i n g GCIIS-guided I H T in 10 healthy

volunteers.

given (U/kg body weight) is also shown. Minimum blood glucose was 32.5 ± 1.9 mg/dl. In the 3 pa­tients with hormone inactive pituitary adenoma there was an impairment of G H secretion during I H T . T h e patients with acromegaly, when studied preoperatively, had an impaired HPA function.

352

They showed a blunted or deficient Cortisol in­crease. In patient E . G . insulin requirements were markedly high; moreover, abnormal G H secretion was accompanied by elevated prolactin levels. Post­operatively, basal G H levels had returned to nor­mal in both patients. In patient E . G . , prolactin levels were now in the normal range, and insulin requirements had decreased from 0.200 to 0.106 U/kg (see Fig. 4). One of the prolactinoma patients studied (B.W.) had complete pituitary insuffi­ciency, whereas the other one (F.G.) showed nor­mal values and sufficient responses for G H , Cortisol and A C T H . Complete impairment of the HPA axis was shown postoperatively in patients with acrome­galy (P.D.) and Cushing's syndrome (M.K.). In patient H . H . (Cushing's syndrome) insulin re­quirements for inducing hypoglycaemia were highest (0.335 U/kg) as shown in Fig. 5.

In this patient blood glucose had fallen below 40 mg/dl after 70 min without producing distinct clinical signs of hypoglycaemia so that insulin administration had to be continued for another 10 min.

Discussion

This study indicates that the GCIIS-guided I H T is a safe and sensitive procedure in the assessment of H P A function. Using appropriate constants for the preprogrammed algorithms of the G C I I S , a suffi­cient degree of hypoglycaemia was achieved in healthy subjects as well as in patients with hypo-thalamic-pituitary disease. The range of hypogly-

Table 2. G C I I S - g u i d e d I H T in 10 patients with pituitary tumours (numbers 1 — 10 refer to Table 1). Insulin requirements ( infused insulin) for inducing hypoglycaemia, basal and minimal blood glucose values (BG), basal values and maximal h o r m o n e responses for G H , prolactin, A C T H and Cortisol are shown. In addition, the corresponding times are

mentioned (min after beginning of the test).

Pituitary adenoma hormone inactive

Acromegaly preoperative

Acromegaly postoperative

Cushing's syndrome

Prolactinoma Pituitary insuff.

postoperative

1 2 3 4 5 4 5 6 7 8 9 10

I n f u s e d insul in ( U / k g ) 0.129 0.127 0.151 0.200 0.242 0.106 0.138 0.335 0.114 0.161 0.093 0.124

B G (mg/dl )

Basal 90 100 83 90 81 77 80 117 78 92 88 81 M i n i m a l 19 21 37 28 37 37 40 37 33 37 34 30 T i m e (min) 48 40 34 42 60 24 40 70 30 32 40 30

G H (ng/ml)

Basal 0.6 0.7 0.5 42 78 1.1 1.5 2.3 < 0.5 1.4 0.8 1.1 M a x i m a l 0.9 1.4 0.6 56 230 15.2 2.7 9.5 < 0.5 50 0.8 11.7 T i m e (min) 30 60 30 120 60 60 60 45 90 45

Prolact in ( f iU/ml)

Basal 267 670 547 1470 260 177 114 252 13 640 2290 < 100 < 100 M a x i m a l 330 1049 563 3990 359 872 117 366 15 750 2800 < 100 218 T i m e (min) 60 90 45 45 60 30 30 60 60 60 60

A C T H (pg/ml)

Basal 99 38 16 36 59 27 28 26 34 25 < 35 38 M a x i m a l 148 49 18 39 77 37 44 41 39 72 < 35 38 T i m e (min) 60 45 60 90 45 45 30 120 120 60

Cort iso l (ng/ml)

Basal 120 114 20 86 39 60 30 281 < 20 103 < 2 0 < 2 ( ) M a x i m a l 195 205 35 109 45 149 46 281 22 313 < 20 < 20 T i m e (min) 90 60 60 60 90 60 90 90 120

caemia from 19 to 40 mg/dl (mean: 32.5 ± 1.9 mg/dl) in the pituitary tumour patients compares favourably with the bolus technique where values below 15 mg/dl are achieved more frequently. As a consequence of feedback-controlled insulin admi­nistration, an optimal insulin dosage was given according to the individual insulin sensitivity. The total amount of insulin per kg body weight in controls was comparable to the recommended dos­age for performing I H T by bolus injection (Borst et al. 1982; Landon et al. 1966), but in the patients with pituitary disease studied, there was a wider range of insulin requirements (see Table 2). So, if

I H T is performed by bolus injection in patients with altered insulin sensitivity, the degree of which can not always be predicted exactly, there can be the risk of overdosage or the need of repeated injections, which is avoided by GCIIS-guided insu­lin administration. In the patients with partial or complete pituitary insufficiency no severe side ef­fects were observed and there was no need of dextrose administration due to suspected insulin overdosage. On the other hand, appropriate insu­lin supply in the cases with decreased insulin sensi­tivity was guaranteed by the G C I I S . In healthy volunteers, the GCIIS-guided I H T produced phy-

354

Pat: E C.(9,29y) Acromegaly preop. infused insulin: 0.200U/kg

Fig. 4. Blood glucose (BG) and insulin infusion rate (IR) d u r i n g GCIIS-guided I H T in

a patient with acromegaly preoperative!}' and postoperatively.

23* 355

siological hormone responses for G H , prolactin, Cortisol and A C T H (see Fig. 3), which were com­parable to those obtained by bolus injection. In the patients with pituitary tumours, subtle or distinct impairment of HPA function could be detected (see Table 2).

In conclusion, the GCIIS-guided I H T can be recommended as a safe and sensitive procedure in the evaluation of pituitary function in patients with pituitary disease. Compared to the bolus method, it has several advantages:

1) Continuous documentation of blood glucose values.

2) Optimal insulin dosage with standardized hypoglycaemia due to automatic adjustment to the individual insulin sensitivity.

3) Patients' safety by earlier recognition of due insulin discontinuation and the need of dextrose.

Moreover, the use of the G C I IS-guided I H T may not be restricted to the assessment of HPA function in patients with pituitary disease. It seems to be of particular usefulness in studying glucose counterregulation following insulin induced hypo­glycaemia in various conditions e.g. counterregula­tion in diabetes mellitus or hormonal and metabolic effects of different insulin preparations.

References

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Clemens A I I , Chang P I I 8c Myers R W (1978): The development o f Biostator®, a glucose controlled insulin infus ion system (GCIIS). H o r m Metab Res, Suppl 7: 2 3 - 3 3 .

Delaloye J F, Gomez F 8c Buckhardt P (1982): Discordant Cortisol response in pituitary disease. N Engl J Med 307: 1218.

Faglia G, Ambrosi B, Beck-Peccoz P 8c Travagl ini P (1973): Hypothalamic-pituitary-adrenal funct ion in patients wi th pituitary tumours. Acta Endocrinol (Copenh) 73: 2 2 3 - 2 3 2 .

Fogt E J , Dodd L M , Jenning E M 8c Clemens A H (1978): Development and evaluation o f a glucose analyzer for a glucose-controlled insulin infusion system (Bio-stator). Cl in C h e m 2 4 : 1366-1372.

Greenwood F C, Landon J 8c Stamp T C B (1966): The plasma sugar, free fatty acid, Cortisol and growth hormone response to insulin. I . In control subjects. J Cl in Invest 45: 429 -436 .

Jenkins J S 8c Else W (1968): Pituitary-adrenal function tests in patients w i t h untreated pituitary tumours. Lancet 2 : 940 -943 .

L a n d o n J, Greenwood F C, Stamp T C B 8c Wynn V (1966): T h e plasma sugar, free fatty acid, Cortisol, and g r o w t h hormone response to insulin, and the compari­son o f this procedure with other tests o f pituitary and adrenal funct ion. I I . I n patients with hypothalamic or pi tui tary dysfunction or anorexia nervosa. J Clin Invest 4 5 : 4 3 7 - 4 4 9 .

Pfeif fer E F, T h u m Ch 8c Clemens A H (1974): The artif icial beta cell — a continuous control o f blood sugar by external regulation o f insulin infusion (glucose control led insulin infusion system). H o r m Metab Res 6: 3 3 9 - 3 4 2 .

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