1. Healthcare

The Journal of
Clinical Endocrinology
and Metabolism
VOLUME
43
JULY-DECEMBER
WILLIAM H . DAUGHADAY, LOUIS V. AVIOLI,
EDITORIAL
GUY E.
ABRAHAM
CLAUDE D.
EDWARD
JEROME M.
ARNAUD
G. BIGLIERI
L E W I S E . BRA V E R M AN
RICHARD
BOARD
HERSHMAN
HORTON
L A U R E N C E S.
JACOBS
HOWARD LUND
K E V I N J.
CATT
SELNA L.
I N D E R J.
CHOPRA
ABBA J. KASTIN
PHILIP E .
CRYER
L E O N A R D J.
MICHEL
ABBAS E .
DEFTOS
FERIN
EDITORS
JUDD
KAPLAN
KITABCHI
STANLEY G.
KORENMAN
HOWARD E.
KULIN
GIRGIS
MIKHAIL
P A T R I C K J.
H O W A R D R.
MARIA I.
JACK H .
NEW
JOHN R. K.
DAVID L.
FISHER
HAROLD E.
LEBOVITZ
ROBERT L.
FRANTZ
W I L L I A M J.
LEMAIRE
LOUIS E.
FROHMAN
GÖRDEN
WILLIAM L.
J O S E P H B.
GREEN
JOHN G . HADDAD,
VIRENDRA B.
JR.
MAHESH
MARTIN
PREEDY
RIMOIN
D E L B E R T A.
L A W R E N C E A.
ROSENFIELD
UNDERWOOD
ROBERT D.
UTIGER
JUDITH L. VAITUKAITIS
THOMAS J.
MERIMEE
JOHN F.
C L A U D E J.
MIGEON
S A M U E L S. C .
COPYRIGHT ® 1976
BY T H E ENDOCRINE SOCIETY
ISSUED MONTHLY FOR T H E ENDOCRINE SOCIETY
BY J. B. LIPPINCOTT COMPANY, PUBLISHERS
MURPHY
NANKIN
OPPENHEIMER
ANDREW G.
PHILLIP
MULROW
B E V E R L E Y E . P.
WILBER
YEN
C O N T E N T S O F V O L U M E 43
Secretion of Alpha Subunit of Glycoprotein
Hormones by Pituitary Adenomas
/. A . Kourides, B. D. Weintraub, S. W. Rosen,
E. C . Ridgway, B. Kliman, and F. Maloof
T h e Effect of Aspirin and Indomethacin on the
T R H Response in Man
/ . N . Ramey, G. N. Burrow, S. W.
Spaulding,
R. K. Donabedian,
L. Speroff, and A. G.
Frantz
Circadian Rhythm and Effect of Posture on
Plasma Aldosterone Concentration in Primary'
Aldosteronism
M . Schambelan, N. L. Brust, B. C. F. Chang,
K. L. Slater, and E. G. Biglieri
Pituitary Function in Psudocyesis
S. S. C . Yen, R. W. Rebar, and W. Quesenberry
Recurrent Goiter, Hyperthyroidism, Galactorrhea and Amenorrhea D u e to a Thyrotropin
and Prolactin-Producing Pituitary Tumor
K. Horn, F. Erhardt,
R. Fahlbusch,
C. R.
Pickardt, K. v. Werder and P. C. Scriba
No. 1, July 1976
Effect of Fluoxymesterone on the PituitaryGonadal Axis: T h e Role of Testosterone-Estradiol-Binding Globulin
R. A. Vigersky, R. B. Easley, and D. L. Loriaux
Changes in Serum Triiodothyronine, Thyroxine,
and Thyrotropin During Treatment with
Thyroxine in Severe Primary Hypothyroidism
M. Maeda, N. Kuzuya, Y. Masuyama, Y. Imai,
H. Ikeda, H. Uchimura, F. Matsuzaki, L. F.
Kumagai, and S. Nagataki
T h e Effects of Insulin on Urinary Urea and
Ammonia Production
T. P. Stein, M. J. Leskiw, H. W. Wallace,
and
W. S. Blakemore
Effect of Halofenate on Serum T h y r o i d Hormone Determinations in Vitro
F. E. Karch, J. P. Morgan, N. P. Kubasik,
and
H. E. Sine
Diurnal T S H Variations in Hypothyroidism
J. Weeke and P. Laurberg
Effect of 7/3,17a-Dimethyltestoste rone (Calusterone) on Cortisol Metabolism in Women
with Advanced Breast Cancer
D. K. Fukushima, B. Zumoff, W. Bulkin, and L.
Hellman
Gonadotropin Determinations in T i m e d 3-Hour
Urine Collections During the Menstrual C y c l e
and L H R H Testing
I. Z . Beitins, K.O'Loughlin,
T. Ostrea,
and
J. W. McArthur
Specific Metabolic Pathways of Steroid Sulfates
in Human L i v e r Microsomes
K. Einarsson, J.-A. Gustafsson> T. Ihre,
and
M.
Ingelman-Sundberg
Thyrotoxicosis Secondary to Involvement of
the Thyroid with Malignant L y m p h o m a
K. Shimaoka,A.J.
VanHerle, and A.
Dindogru
Comparison of Prostaglandin E , and T S H
Stimulation of C y c l i c A M P Synthesis in
Thyroid Tissues from Euthyroid Subjects
and Thyrotoxic Patients
N. Takasu, S. Sato, T. Tsukui, T. Yamada,
M. Miyakawa, M. Makiuchi, and R. Furihata
Plasma Cortisol and Cortisone in Pregnancies
with Normal and Anencephalic F e t u s e s
M. DeM. Fencl, R. Osathanondh,
and D.
Tulchinsky
Human Serum Binding Capacity and Affinity
for 25-Hydroxyergocalciferol and 25-Hydroxycholecalciferol
]. G. Haddad, L. Hillman, and S. Rojanasathit
Diagnosis and Nomenclature of the Disorders
of the Terminal Portion of the Aldosterone
Biosynthetic Pathway
S. Ulick
1
10
18
26
32
38
Studies on Phenolic Steroids in Human Subjects. X I X . Renal Conjugation of 15a-Hydroxy
estradiol-3-sulfate
Y. Yamamoto, M. Ishihara, R. Y. Kirdani, Y.
Osawa, and A. A, Sandberg
E f f e c t of Antithyroid Agents, 6-Propyl-2Thiouracil and
l-Methyl-2-Mercaptoimidazole, on Human Thyroid Iodide Peroxidase
46
A. Nagasaka and H.
64
69
P. A. Lee, L. P. Plotnick,
Thompson,
and R. M.
Visscher,
86
and M.
137
144
152
159
168
173
178
Couvreur-Eppe
4
4
ii
132
R. E. Steele, R. G .
Assessments of the Functional Capacity of the
Gonadotrophs in M e n . Effects of Estrogen
and Clomiphene
B. L . Lasley, C. F. Wang, and S. S. C . Yen
T h e Role of 19-Hydroxy-A -androstene-3,17dione in the Conversion of Circulating A Androstene-3,17-dione to Estrone
W. G. Kelly, O. de Leon, and T. H. Rizkallah
92
115
Blizzard
Aldosterone Response to Hypoglycemia, E v i dence of A C T H Mediation
S. Hata, H. Kunita, and M. Okamoto
Secretory Activity of Isolated T h y r o i d Adenomas
M. F. van den Hove-Vandenbroucke,
M. De
80
107
Hidaka
Secretion Rates of L H and F S H D u r i n g Infusion
of L H - F S H / R H in Normal Women and in Patients with Secondary Amenorrhea: Suggestive E v i d e n c e for T w o Pools of L H and
FSH
P. Koninckx,
R. De Hertogh,
W. Heyns,
E.
Meulepas, I. Brosens, and P. De Moor
Integrated Concentrations of L u t e i n i z i n g Hormone and Puberty
56
97
182
190
CONTENTS OF VOLUME
Sex Hormone Binding G l o b u l i n : T h e Carrier
Protein for d-Norgestrel
A. Victor, E. Weiner, and E. D. B. Johansson
Uptake of I-19-Iodocholesterol by an Adrenal
Cortical Carcinoma and Its Metastases
F . Chatal, B. Charbonnel,
B. P. Le Mevel,
and D. Guihard
COMMENTS
Gonadotropin and Sex Steroid Response to
L u t e i n i z i n g Hormone-Releasing
Hormone
in Patients with Premature Adrenarche
P. A. Lee and F. J. Gareis
Prolactin and Testosterone: Independent Circulating L e v e l s in Hyperprolactinemic and
Normoprolactinemic
Amenorrhea.
The
Effect of Prolactin Suppression by Bromocriptine
M. Seppälä,
E. Hirvonen,
H.-A.,
Unnerus,
T. Ranta, and T. Laatikainen
Effect of Norepinephrine Infusion on Plasma
Vasopressin L e v e l s in Normal Human Subjects
K. Shimamoto and M. Miyahara
Somatostatin Does Not Suppress Plasma Parathyroid Hormone
L . J. Deftos, LM. Lorenzi, N. Bohanon,
E.
Tsalakian, V. Schneider, and J . E. Gerich
Placental Sulfatase Deficiency: A Case Study
R. Osathanondh,
J. Canick, K. J. Ryan, and
D.
Tulchinsky
Plasma Gonadotropin and Gonadotropin-Releasing Hormone L e v e l s After Intranasal Adm i n i s t r a t i o n of G o n a d o t r o p i n - R e l e a s i n g
Hormone
M. Katz, B. L. Fimstone, P. J. Carr, and S.
Hendricks
Failure of Endogenous Plasmin to Convert
H u m a n Growth Hormone to its "Activated"
Isohormones
G . Baumann
Insulin Binding to Monocytes and Total Mononuclear Leukocytes from Normal and D i a betic Patients
J. M. Olef sky and G. M. Reaven
Letter to the Editor: Improvement in the
Quality and Quantity of Growth Hormone
Isolated from Acetone-Preserved
Human
Pituitaries for Clinical Usage
A. F . Parlow and B. Shome
131
244
248
No. 2, August 1976
201
205
208
215
222
226
229
RAPID COMMUNICATIONS
T h e Effect of Acetyl salicylic Acid on T S H and
P R L Secretion After T R H Stimulation in
the Human
]. H. Dussault, R. Turcotte, and H. Guyda
Effect of Carbidopa on Prolactin, Growth Hormone and Cortisol Secretion in Man
G . M. Brown, P. E. Garfinkel, J. J'. Warsh, and
H. C. Stancer
Actions of Growth Hormone-Release Inhibiting
Hormone (Somatostatin) on the Renin Aldosterone System
A. Gomez-Pan, M. H. Snow, D. A. Piercy, V.
Rohson, R. Wilkinson, R. Hall, and D. C .
Evered
43
232
236
240
Unusual L o w Plasma Renin Hypertension in a
Child
L. Sann, A . Revol, M. Zachmann,
J. C.
Legrand, and M. Bethenod
Serum 17/3-Estradiol and L e v e l s in Postmenopausal Woman With and Without Endometrial
Cancer
H. L. Judd, W. E. Lucas, and S. S. C. Yen
Normal Glucagon Response to Arginine I n fusion in "Prediabetic" Pima Indians
S. L. Aronoff, P. H. Bennett, N. B. Rushforth,
M. Miller, and R. H. Unger
Dissociation of Renin and Aldosterone During
Dehydration: Studies in a Case of Diabetes
Insipidus and Adipsia
M. A. D . H. Schalekamp,
S. C . Bever
Donker,
A. Jansen-Goemans,
T. D. Fawzi, and A.
Muller
Rapid Appearance of Transient Secondary
Adrenocortical Insufficiency After AlphaParticle Radiation Therapy for Cushing's
Disease
D. M. Cook, R. M. Jordan, J. W. Kendall, and
J. A. Linfoot
T h e Effect of Oral Administration of Thyrotropin-Releasing Hormone on Lactation
A. Zärate,H. Villalobos, E. S. CanalesJ.
Soria,
F. Arcovedo, and C .
MacGregor
Effect of an Antiserotoninergic Drug, Metergoline, on the A C T H and Cortisol Response
to Insulin Hypoglycemia and Lysine-Vasopressin in Man
F. Cavagnini,
U. Raggi, P. Micossi, A. Di
Landro, and C. Invitti
Prolactin Secretion by Metoclopramide in Man
S. J. Judd, L. Lazarus, and G. Smythe
Effect of Normal and Reversed Sleep-Wake
Cycles upon Nyctohemeral Rhythmicity of
Plasma Thyrotropin: E v i d e n c e Suggestive
of an Inhibitory Influence in Sleep
D. C. Parker, A. E. Pekary, and J. M. Hershman
T h y r o i d A n t i g e n Stimulates Lymphocytes
from Patients with Graves' Disease to Produce Thyroid-Stimulating Immunoglobulin
(TSI)
A. J. S. Knox, C. Von Westarp, V. V. Row, and
R. Volpe
T h e Effect of Glucocorticoid Administration on
265
272
279
287
295
301
306
313
318
330
338
iv
CONTENTS OF VOLUME
Human Pituitary Secretion of Thyrotropin
and Prolactin
R. N. Re, J. A. Kourides, E. C. Ridgway, B. D.
Weintraub, and F. Maloof
T h e Effects of Ovarian Wedge Resection on
Circulating Gonadotropin and Ovarian Steroid
L e v e l s in Patients with Polycystic Ovary Syndrome
H. L. Judd, L. A. Rigg, D. C. Anderson,
S. S. C . Yen
COMMENTS
347
and
Inhibitory Effect of an Ergoline Derivative,
Methergoline, on Growth Hormone and Prolactin L e v e l s in Acromegalic Patients
P. G. Chiodini, A. Liuzzi, E. E. Midler, L.
Botalla, G . Cremascoli, G. Oppizzi, G. Verde,
and F. Silvestrini
356
E v i d e n c e for Higher Proportion of " L i t t l e "
Growth Hormone with Increased Radioreceptor Activity in Acromegalic Plasma
P. Görden, M. A. Lesniak, R. Eastman, C. M.
Hendricks, and J. Roth
364
Influence of Purified Plasma Proteins O n
Testosterone Uptake and Metabolism by
Normal and Hyperplastic Human Prostate in
"Constant F l o w Organ C u l t u r e "
C. Mercier-Bodard,
M. Marchut, M. Perrot,
M.-T. Picard, E.-E. Baulieu, and P. Röbel
374
T h e Fate of 17/3-Estradiol in the Plasma of Premenopausal and Postmenopausal
Patients
with Cancer
C . B. Vaughn, D. Kolakowski, V. Zylka, and
S. C. Brooks
387
Hypothalamic-Pituitary Function in Patients
with Craniopharyngiomas
J. S. Jenkins, C. J. Gilbert, and V. Ang
394
T h e Response of Pituitary Gonadotropes to a
Constant Infusion of Luteinizing HormoneReleasing Hormone ( L H R H ) in Normal Prepubertal and Pubertal Children and in C h i l dren with Abnormalities of Sexual Development
E . O. Reiter, A. W. Root, and G. E. Duckett
Unconjugated Cortisol in Human Amniotic
F l u i d : Relationship to Lecithin/Sphingomyelin Ratio
400
S. Y. Tan, I. H. Gewolb,
and J. C.
H. Heath HI, G. W. Sizemore,
and J. A.
446
449
453
457
462
466
470
Bromocriptine Increases Plasma Estradiol17/3 Concentration in Amenorrhea Patients
with Normal Serum Prolactin
M. Seppälä,
H.-A. Unnerus,
E.
Hirvonen,
and T. Ranta
T h e Failure of Physiologic Doses of Reverse
T to Effect Thyroid-Pituitary Function in
Man
P. Nicod, A. Burger,
G. Strauch,
A. G .
Vagenkais, and L. E.
Braverman
474
478
3
412
No. 3, September
419
428
Carney
Free and Protein-Bound Plasma Estradiol-17/3
During the Menstrual C y c l e
C.-H. Wu, T. Motohashi, H. A.
Abdel-Rahman,
G. L. Flickinger, and G. Mikhail
Dissociation of Plasma Renin Activity and
Aldosterone in Essential Hypertension
G . P. Guthrie, Jr., J. Genest, W. Nowaczynski,
R. Boucher, and O. Kuchel
E n d o c r i n o l o g i c C h a r a c t e r i s t i c s of Partial
Ovarian Failure
A. K. Razdan, R. L. Rosenfield, and M. H. Kim
Suppression by Thyrotropin-Releasing Hormone ( T R H ) of Growth Hormone Release I n duced by Arginine and Insulin-Induced
Hypoglycemia in Man
K. Maeda, Y. Kato, K. Chihara, S. Ohgo, Y.
Iwasaki, H. Abe, and H. Imura
Deficient 17/3-Hydroxysteroid Oxidoreductase
Activity-* in Testes from a Male Pseudohermaphrodite
D. E. Pittaway, R. N. Andersen,
and J. R.
Givens
Circadian Rhythm of I n s u l i n - I n d u c e d Hypoglycemia in Man
S. Sensi and F. Capani
T h y r o i d Peroxidase, Thyroglobulin c A M P
and D N A in Human Thyroid
L. J. Valenta
Pituitary Hormone L e v e l s in Plasma of Human
Fetus after Administration of L R H
G. Gennser, P. Liedhohn, and J. Thorell
RAPID COMMUNICATIONS
Hobbins
Pituitary-Thyroid Regulation in E u t h y r o i d
Patients wioS Graves' Disease Previously
Treated with Antithyroid Drugs
E. M. Buerklin, M. Schimmel, andR. D. Utiger
Preoperative Diagnosis of Occult Parathyroid
Hyperplasia by C a l c i u m Infusion in Patients
with Multiple Endocrine Neoplasia, T y p e 2a
JCE & M • 1976
Vol 43 • No 6
43
436
1976
Body Weight and the Pituitary Response to
Hypothalamic Releasing Hormones in Patients with Anorexia Nervosa
P. J. V. Beumont, G. C . W. George, B. L.
Pimstone, and A. I. Vinik
Intestinal Metabolism of Estrogens
H. Adlercreutz,
F. Martin, M.
Pulkkinen,
H. Dencker, U. Rimer, N.-G. Sjöberg,
and
M. J. Tikkanen
Endocrine Studies in a Phenotypic Girl with
X Y Gonadal Agenesis and Hemaphroditism
R. H. Wu, R. M. Boyar, R. Knight, L. Hellman,
and J. W. Finkelstein
487
497
506
CONTENTS OF VOLUME
Serum Thyroglobulin in Inhabitants of an
E n d e m i e Goiter Region of N e w G u i n e a
A.J. Van Hede, I.J. Chopra,].
M.
Hershman,
and R. W.
Hornabrook
T h e Absorption of Inorganic Phosphate in the
H u m a n Jejunum and its Inhibition by Salmon
Calcitonin
D. Juan, P. Liptak, and T. K. Gray
Effects of Phosphorus Supplementation on
on Serum Parathyroid Hormone and Bone
Morphology in Osteoporosis
R. S. Goldsmith, J. Jowsey, W. J. Dube, B. L.
Riggs, C. D. Arnaud, and P. J. Kelly
Plasma Thyrotropin, Thyroxine, and Triiodothyronine Relationships in Man
M. Azukizawa, A. E. Pekary,]. M.
Hershman,
and D. C. Parker
Dissociation of Responsiveness to ThyrotropinReleasing Hormone and T h y r o i d Suppressibility F o l l o w i n g Antithyroid D r u g Therapy of
Hyperthyroidism
E. Martino, A. Pinchera,
R. Capiferri,
E.
Macchia, G . Sardano, L. Bartalena, F. Mazzanti, and L. Baschieri
Thyroid-Stimulating Immunoglobulins and the
Control of Thyroid Function
R. Clague, E. D . Mukhtar, G. A. PyleJ.
Nutt,
F. Clark, M. Scott, D. Evered, B. Rees Smith,
and R. Hall
Estrone and Estradiol in Patients with Cirrhosis
of the L i v e r : Effects of A C T H and Dexamethasone
H. K. Kley, E. Keck, and H. L .
Kruskemper
Effects of Estrogens on Adrenal 3ß-Hydroxysteroid Dehydrogenase in Ovariectomized
Women
D. C . Anderson and S. S. C. Yen
Hypothyroid-Like Alterations in Testosterone
Metabolism in Anorexia Nervosa
H. L. Bradlow, R. M. Boyar, J.
O'Connor,
B. Zummoff, and L. Hellman
Familial Partial Target Organ Resistance to
Thyroid Hormones
A. Elewaut, M. Mussche, and A. Vermeiden
Effect of the Antihistamine Agents Meclastine
and Dexchlorpheniramine on the Response of
Human Growth Hormone to Arginine Infusion
and Insulin Hypoglycemia
A. E. Pontiroli, G. Viberti, A. Vicari,
and
G. Pozza
Lymphocyte Transformation in Response to
Human Thyroid Extract in Patients with
Subacute Thyroiditis
] . R. Wall, S.-L. Fang, S. H. Ingbar, and L. E.
Braverman
Reversal of Decreased Human Adipose T i s s u e
Lipoprotein Lipase and Hypertriglyceridemia
After Treatment of Hypothyroidism
O. Pykälistö,A. P. Goldberg, and J. D. Brunzell
512
517
523
533
543
550
557
561
571
43
v
Thyroid-pituitary Feedback D u r i n g Iodine Repletion
M. C . Gershengorn,].
Wolff, and P. R. Larsen
Sensitivity to L i t h i u m in Treated Graves'
Disease: Effects on Serum T , T and Reverse
T,
K. D. Bunnan, R. C. DimondJ.
M. Earll, F. D.
Wright, and L. Wartofsky
Growth Hormone, Prolactin and Chorionic
Somatomammotropin in Normal and Molar
Pregnancy
M, Mochizuki,
H. Morikawa, K.
Kawaguchi,
and S. Tojo
Cortisol-Induced Suppression of Plasma T e s tosterone in Normal Adult Males
P. Doerr and K. M. Pirke
Abnormal T S H , P R L and G H Response to T S H
Releasing Factor in C h r o n i c Renal Failure
P. Czernichow,
M. C. Dauzet, M. Broyer, and
R.
Rappaport
Suppression of Prolactin Secretion by L - D o p a in
the Stalk-Sectioned Rhesus Monkey
W. P. Diefenbach, P. W. Carmel, A. G . Frantz,
and M. Ferin
F a i l u r e of Endogenous Prolactin to Alter Renal
Salt and Water Excretion and Adrenal F u n c tion in Man
G . Baumann and. D. L. Loriaux
F S H - S e c r e t i n g Pituitary Adenomas: Stimulation and Suppression Studies in T w o Patients
/ . N. Friend, D. M. Judge, B. M. Sherman, and
R. J. Santen
Effects of L u t e i n i z i n g Hormone Releasing Hormone ( L H R H ) Upon Bioactive and Immunoreactive Serum L H L e v e l s in Normal Subjects
M. L. Dufau, 1. Z . Beitins, J. W.
McArthur,
and K. J. Catt
Effects of Dopamine Infusion on Pituitary
Hormone Secretion in Humans
H. Leblanc, G. C. L. Lachelin, S. Abu-Fadil,
and S. S. C . Yen
4
601
606
3
614
622
630
638
643
650
658
668
575
COMMENTS
582
587
A C T H and Cortisol Responses to Glucagon
Stimulation
W. Waldhäusl, H. Haydl, and P. Nowotny
Comparison of Metoclopramide with Other
D y n a m i c Tests of Prolactin Secretion
J. R. Sowers, R. W. McCallum,].
M. Hershman,
H. E. Carlson,
R. A. L. Sturdevant,
and
N. Meyer
675
679
RAPID COMMUNICATIONS
591
A Radioimmunoassay for Measurement of 3,3'L-Diiodothyronine ( T )
S.-Y. Wu, 1. J. Chopra, Y. Nakamura, D. H.
Solomon, and L. R. Bennett
2
682
vi
CONTENTS OF VOLUME
Comparison of Androgen Metabolites in Benign
Prostatic Hypertrophy ( B P H ) and Normal
Prostate
/. Geller, J. Albert, D. Lopez, S. Geller,
and
G . Niwayama
Plasma Prolactin Response to L u t e i n i z i n g Releasing Hormone in Acromegalic Patients
A. Catania, L. Cantalamessa,
and E. Reschini
Blood Pressure F a l l by Angiotensin I I Antagonist in Patients With Bartter's Syndrome
T. Kono, F. Oseko, S. Shimbo,
M.
Nanno,
F. Ikeda, and J. Endo
17-Deoxygenation: A N e w Pathway of Cortisol
Metabolism Isolation of 17-Deoxycortolonic
Acids
G . Weiss, C. Monder, and H. L. Bradloiv
Effect of Sulpiride-Induced Hyperprolactinemia
on Serum Testosterone Response to H C G in
Normal Men
B. Ambrosi,
P. Travaglini,
P.
Beck-Peccoz,
R. Bara, R. Elli, A. Paracchi, and G. Faglia
Measurement of Glucose T u r n o v e r in the
H u m a n Newborn With G l u c o s e - l - C
S. C . Kalhan, S. M. Savin, and P. A . / . Adam
Production of Specific Antisera for Radioimmunoassay of Human Luteinizing Honnone
( L H ) in the Presence of H u m a n C h o r i o n i c
Gonadotropin ( h C G )
/. /. Thorell, S. Jeppsson, and B.
Holmström
Competition by 24,25-Dihydroxycholecalciferol
in the Competitive Protein B i n d i n g Radioassay of 25-Hydroxycalciferol
J. G . Haddad, Jr., C. Min, J. Walgate,
and
T. Hahn
686
689
692
696
700
704
1 3
No. 4, October
3im
712
1976
Studies of Human Diploid Fibroblast G r o w t h .
I. Responses of Normal and Hypopituitary
C e l l s to Fibroblast Growth Factor, I n s u l i n ,
and Serum
K. L. Jones and J. Addison
Thyrotoxic Periodic Paralysis: A Peculiar C a s e
with Unusual Dystonie Behavior and Variable
Relations of Paralysis to Serum Potassium
Levels
T. Kusakabe, M. Yoshida, and M. Nishikawa
Effect of N -Methyl-Thyrotropin R e l e a s i n g
Hormone on the Human Pituitary-Thyroid Axis
J. R. Sowers, J. M. Hershman,
A. E. Pekary,
M. G. Nair, and C. M. Baugh
Prolactin Response to N - M e t h y l - T h y r o t r o p i n
Releasing Hormone in E u t h y r o i d Subjects
J. R. Sowers, J. M. Hershman,
H. E.
Carlson,
A. E. Pekary, M. G. Nair, and C . M. Baugh
T h e Effects of Dietary Sodium on the D i u r n a l
Activity of the Renin-Angiotensin-Aldosterone
System and the Excretion of Urinary Electrolytes
3ün
708
721
730
741
749
756
43
J C E & M • 1976
Vol 43 • No 6
H. Kunita, T. Ohara, T. Komatsu, S. Hata, and
M. Okamoto
H u m a n Lactational Response to Oral Thyrotrophin Releasing Hormone
J. E. Tyson, A. Perez, and J. Zanartu
Hypertensive Virilizing Adrenal Hyperplasia
with Minimal Impairment of Synthetic Route
to Cortisol
T. Gregory and L. I. Gardner
Puberty in Girls: Correlation of Serum L e v e l s of
Gonadotropins, Prolactin, Androgens, Estrogens, and Progestins With Physical Changes
P. A. Lee, T. XenakisJ.
Winer, and S. Matsenbaugh
Aromatization of Androstenedione by Cultured
H u m a n Fibroblasts
H. U. Schweikert, L. Milewich, and J. D. Wilson
Propionic Acidemia and Hyperlysinemia in a
Case With Ornithine Transcarbamylase ( O T C )
Deficiency
I. Krieger, C. Bachmann, W. H.
Gronemeyer,
and J. Cejka
Radioimmunoassay of 18-hydroxy-ll-deoxycorticosterone in Plasma
S. L. Dale, P. Komanicky,].
H. Pratt, and J. C.
Melby
Preclinical Hyperthyroidism in Multinodular
Goiter
E. Gemsenjäger, J. J. Staub,]. Girard, and P. H.
Heitz
A n Androgen Binding Protein in the C y s t F l u i d
of Patients with Polycystic Ovary Syndrome
R. A. Vigersky and D. L. Loriaux
Improving the Diagnostic Reliability of Rapidly
Fluctuating Plasma Honnone L e v e l s by O p timized Multiple-Sampling Techniques
J. E. Goldzieher,
T. S. Dozier, K. D. Smith,
and E.
Steinberger
C h e m i c a l Characterization of Ectopic A C T H
Purified From a Malignant T h y m i c Carcinoid
Tumor
P. J. Lowry, L. H. Rees, S. Tomlin, G. Gillies,
and J. Landon
G e l Filtration Profile of Immunoreactive T h y rotropin and Subunits of H u m a n Pituitaries
L . Vanhaelst and J.
Golstein-Golaire
Stimulation of R N A and Protein Synthesis in
Isolated Chondrocytes by H u m a n Serum
J. T. Garland and F.
Buchanan
Stimulation of D N A Synthesis in Isolated
Chondrocytes by Somatomedin. I I . Validation
of the Assay for Clinical Use and Comparison
with the Stimulation of Protein Synthesis
/. T. Garland, J. Jennings, L. L. Levitsky, and
F.
Buchanan
Hypergastrinemia in Hyperthyroidism
7. Seino, S. Matsukura, Y. Miyamoto, Y. Goto,
T. Taminato, and H. Imura
Dose-Response of Prolactin and Thyrotropin to
760
769
775
785
796
803
810
817
824
831
836
842
847
852
856
CONTENTS OF VOLUME
N - M e t h y l - T h y r o t r o p i n Releasing Hormone
in E u t h y r o i d M e n
]. R. Sowers, J. M. Hershman,
H. E.
Carlson,
A. E. Pekary, A. W. Reed, M. G . Nair, and
C . M. Baugh
Serum L i p i d Changes during Contraceptive
Administration in O b ese Women: Relation to
Serum Insulin L e v e l s
H. Gershberg, M. Hülse, and M. Galler
A Study of Pituitary Function in Patients with
Idiopathic Hemochromatosis
C . H. Walsh, A. D. Wright,]. W. Williams, and
G. Holder
Changes i n Serum Thyrotropin ( T S H ) in Man
during Halofenate Administration
P. J. Davis, F. B. Davis, R. D. Utiger, and S. F.
Kulaga,Jr.
Radioimmunoassay and Chromatographic Similarity of Circulating Endogenous Gonadotropin Releasing Hormone and Hypothalamic
Extracts in Man
C . H. Mortimer, A. S. McNeilly, L. H. Rees,
P. J. Lowry, D. Gilmore, and H. G. Dobbie
Failure of a Serotonin Inhibitor to Effect Nocturnal G H and Prolactin Secretion in Patients
with D u c h e n n e Muscular Dystrophy
W. B. Malarkey and J. R. Mendell
Delayed Pituitary Hormone Response to L R F
and T R F in Patients with Anorexia Nervosa
and with Secondary Amenorrhea Associated
with Simple Weight Loss
R. A. Vigersky, D. L. Loriaux, A. E.
Andersen,
R. S. Mecklenburg, and J. L. Vaitukaitis
Endogenous Estrogen Modulates Phenothiazine
Stimulated Prolactin Secretion
M. T. Buckman, G. T. Peake, and L. S. Srivastava
Partial Characterization of Somatomedin Bioactivity in T e r m Human Amniotic F l u i d
R. M. Bala and G. R. Smith
Periodic Remission in Cushing's Disease with
Paradoxical Dexamethasone Response: An
Expression of Periodic Hormonogenesis
B. Liberman,
B. L. Wajchenberg,
M. A.
Tambascia, and C. H. Mesquita
3ün
861
trated W o m e n by the Administration of Human
Chorionic Gonadotropin
A. Miijake, O. Tanizawa, T. Aono, M. Yasuda,
and K. Kurachi
Gonadotropin Output in Congenital Adrenal
Hyperplasia before and after Adrenal Suppression
G . / . Klinge?ismith,
A. C. Wentz, W. J. Meyer,
HI, and C. J. Migeon
933
866
RAPID COMMUNICATIONS
873
Methylphenidate Increases Serum Growth Hormone Concentrations
W. A. Brown and B. W. Williams
Biological Activity of des-asp\-ileu -Angiotensin
I I (ileu -Angiotensin I I I ) in Man
T. Kono, F. Oseko, F. Ikeda, M. Nanno, and
J. Endo
Study on the Relationship Between Prolactin
L e v e l s and Androgen Metabolism in Man
G. Magrini, J. R. Ehiner, P. Burckhardt,
and
J. P. Felber
8
937
940
8
882
944
889
No. 5, November
893
901
907
913
COMMENTS
Alpha Subunit Contamination of Human A l bumin Preparations: Interference in Radioimmunoassay
I. A. Kourides, B. D. Weintraub,
M. A. L.
Martorana, and F. Maloof
Hyperthyroidism with Elevated Plasma T S H
Levels and Pituitary Tumor: Study with
Somatostatin
E. Reschini, G. Giustina, L.
Cantalamessa,
and M. Peracchi
Suppression of Luteinizing Hormone in Cas-
vii
43
919
924
928
1976
Modification of R e n i n Reactivity by L i p i d s
Extracted from Normal, Hypertensive and
Uremic Plasma
T. A. Kotchen, R. T. Talwalker, M. C . Miller,
and W. J. Welch
Unconjugated Dehydroepiandrosterone Plasma
L e v e l s in Normal Subjects from Birth to Adolescence in H u m a n : T h e Use of a Sensitive
Radioimmunoassay
E. de Peretti and M. G. Forest
Effects of G r o w t h Hormone in Osteoporosis
J. F. Aloia, I. Zanzi, K. Ellis, J.
Jowsey,
M. Roginsky, S. Wallach, and S. H. Cohn
Effect of Megestrol Acetate (Megace®) on Steroid
Metabolism and Steroid-Protein Binding in
the H u m a n Prostate
/. Geller, J. Albert,
S. Geller,
D.
Lopez,
T. Cantor, and S. Yen
L a c k of in Vivo Transformation of H u m a n
Growth Hormone to Its "Activated" Isohormones in Peripheral Tissues of the Rhesus
Monkey
G. Baumann and G. Hodgen
Rapid Oscillation of Circulating Gonadotropins
in Postmenopausal Women
M. Medina,
H. E. Scaglia,
G.
Vazquez,
S. Alatorre, and G.
Perez-Palacios
Effect of Thyrotropin-Releasing Hormone on
Secretion of Thyrotropin, Prolactin, Thyroxine,
and Triiodothyronine in Pregnant and Fetal
Rhesus Monkeys
M. Azukizawa, Y. Murata, T. Ikenoue, C. B.
Martin, Jr., and J. M. Hershman
971
982
992
1000
1009
1015
1020
viii
CONTENTS OF VOLUME
Impaired Glucose, I n s u l i n , and Adenosine
3',5'-Monophosphate Responses to Glucagon
in Growth Hormone Deficient C h i l d r e n
G . P. August and W. Hung
Effects of Ethinylestradiol on the Renin-Angiotensin-Aldosterone-System and on Plasma
Transcortin in Women and Men
W. Oelkers, A. Blümel, M. Schöneshöf er, U.
Schwartz, and J. Hammerstein
Isolated Thyrotropin Deficiency With T h y rotropin-Releasing-Hormone Induced T S H
Secretion and Thyroidal Release
T. M. Boehm, R. C. Dimond, and L. Wartofsky
T h e L a c k of Effect of Chronic Metabolic
Acidosis on 25-OH-Vitamin D Metabolism
and Serum Paradiyroid Hormone in Humans
H. P. Weber, R. W. Gray, J. H. Dominguez, and
J. Lemann,
Jr.
Dietary Phosphate Deprivation in Women and
M e n : Effects on Mineral and A c i d Balances,
Parathyroid Hormone and the Metabolism of
25-OH-Vitamin D
J. H. Dominguez, R. W. Gray, and J.
Lemann,
Jr.
Somatomedin-C Receptor Ontogeny and L e v e l s
in Porcine Fetal and Human C o r d Serum
A. J. D'Ercole,
D. B. Foushee, and L. E.
Underwood
Plasma 16/3-Hydroxydehydroepiandrosterone in
Normal and Padiological Conditions in Man
H. SekiharaJ.
A. Sennett, G. W. Liddle, T. J.
McKenna, and L. R. Yarbro
Chlorpropamide-Induced Hyponatremia
K. Piters
Effects of Carbohydrate Restriction on the
Hypoglycemic Phase of the Glucose Tolerance
Test
M. A . Permutt, J. Delmez, and W. Stenson
Visual F a i l u r e During Replacement Therapy in
Primary Hypothyroidism with Pituitary E n largement
/. R. Stockigt, W. B. Essex, R. H. West, R. M. L.
Murray, and H. D. Breidahl
T h e Effect of A C T H and Cortisol on Aldosterone
and Cortisol Clearance and Distribution in
Plasma and Whole Blood
R. D. Zipser, P. F. Speckart, P. K. Zia, W. A.
Edmiston,
F. Y. K. Lau, and R. Horton
Size Heterogeneity of Human Serum Somatomedin
R. M. Bala, E. D. Blakeley, and G . R. Smith
T h e C i r c a d i a n Periodicity of Urinary 17Ketosteroids, Corticosteroids, and Electrolytes
in Congenital Adrenal Hyperplasia
W. / . Meyer, III, E. C. Diller, F. C.
Bartter,
and F.
Halberg
Spontaneous Hypercortisolism without C u s h ing's Syndrome
A. C . M. Vingerhoeds, J. H. H. Thijssen,
and
F.
Schwarz
1029
1036
1041
1047
1056
1069
I C E & M • 1976
Vol 43 • No 6
43
In Vivo Studies on the Metabolism of Estrogens
by Muscle and Adipose T i s s u e of Normal
Males
C . Longcope,J.
H. Pratt, S. H. Schneider, and
S. E. Fineberg
G H , A C T H , T S H , L H , and F S H Reserve in
Prepubertal Girls with Congenital Adrenal
Hyperplasia
E. Cacciari,
A. Cicognani,
P.
Pirazzoli,
P. Tassoni, F. Zappulla, S. Salardi, F. Bernardi,
L. Mazzanti, and P. Vianelli
An Increase of Plasma Triiodothyronine C o n centration in Man in a C o l d Environment
H. Nagata, T. Izumiyama, K. Kamata, S. Kono,
Y. Yukimura,
M. Tawata, T. Aizawa,
and
T. Yamada
T h e Secretion of Progesterone D u r i n g the
Periovulatory Period in Women with Certified
Ovulation
N. Laborde, M. Carril, S. Cheviakoff, H. D.
Croxatto, E. Pedroza, and J. M. Rosner
A Bioassay for N S I L A - S in Individual Serum
Samples and Its Relationship to Somatotropin
R. C . Franklin, G. C. Rennie, H. G. Burger,
and D. P. Cameron
Mineralocorticoid Receptors in Human Kidney
D. T. Matulich, B.J. Spindler, M. Schambelan,
and J. D. Baxter
1134
1146
1153
1157
1164
1170
1078
COMMENTS
1085
1088
Urinary Kallikrein Excretion in Bartter's Syndrome
A. Lechi, G. Covi, C . Lechi, F. Mantero,
and
L. A . Scuro
1175
RAPID COMMUNICATIONS
1094
1101
1110
1122
1128
Effectiveness of Cyproheptadine in Decreasing
Plasma A C T H Concentrations in Nelson's
Syndrome
D. T. Krieger and M. Luria
Effect of the Dopamine Receptor Blocking
Agent Pimozide on the Growth Hormone
Response to Arginine and Exercise and on the
Spontaneous Growth Hormone Fluctuations
G . Schwinn, H. Schwarck, C. Mcintosh,
H.-R.
Milstrey, B. Willms, and J.
Köbberling
Use of Receptors in the Preparation of L H - F r e e
Serum
T. Saito and B. B. Saxena
Increased Insulin Binding by Lymphocyte
Receptors Induced by /3-OH Butyrate
T. / . Merimee, A. J. Pulkkinen, and S. Lofton
No. 6, D e c e m b e r
1179
1183
1186
1190
1976
Changes of Circulating Thyroxine, Triiodothyronine and Reverse Triiodothyronine After
Radiographic Contrast Agents
1203
CONTENTS
H. Bürgi, C. Wimpfheimer,
A. Burger, W.
Zaunbauer,
H. Rosier, and T.
LemarchandBeraud
Binding of Progesterone by Human Uterine
Cytosol
R. D. Dyer, G. E. Sarto, and A. E. Colas
Serum D e h y d r o e p i a n d r o s t e r o n e
Sulfate in
Premature Infants and Infants with Intrauterine G r o w t h Retardation
M. R. Turnipseed,
K. Bentley,
and J. W.
Reynolds
T h e Effects of Diethylstilbestrol and Medroxyprogesterone Acetate on Kinetics and Production of Testosterone and Dihydrotestosterone
in Patients with Prostatic Carcinoma
W. E. Nolten, L. J. Sholiton, L. S. Srivastava,
H. C . Knowles, Jr., and E. E. Werk, Jr.
Presence of H - Y Antigen and Testis in 46,XX
T r u e Hermaphroditism, E v i d e n c e for YChromosomal F u n c t i o n
P. Saenger, L. S. Levine, S. S. Wachtel, S.
Korth-Schutz,
Y . Doberne, G. C . Koo, R. W.
Lavengood, Jr., J. L. German, HI, and M. I.
Neic
Correlation B e t w e e n Integrated L H and F S H
L e v e l s and the Response to L u t e i n i z i n g Hormone R e l e a s i n g Factor ( L R F )
R. H. Mortimer, N. Fleischer, M. Lev-Gur, and
R. G. Freeman
Androgens in Patients with Benign Prostatic
Hyperplasia Before and After Prostatectomy
A. Vermeiden and W. De Sy
Cerebrospinal F l u i d Prolactin: A Reflection
of Abnormal Prolactin Secretion in Patients
with Pituitary Tumors
L. L. Schroeder, J. C. Johnson,
and W. B.
Malarkey
Luteal Phase Defects in the Rhesus Monkey:
T h e Significance of Serum F S H : L H Ratios
J. W. Wilks, G. D. Hodgen, and G. T. Ross
C l i n i c a l and Laboratory Heterogeneity in Idiopathic Hypogonadotropic Hypogonadism
R. M. Boyar, R. H. K. Wu, S, Kapen, L. Hellman, E. D. Weitzman, and J. W. Finkelstein
T h e Circadian Rhythm of Renin
R. S. Modiinger, K. Sharif-Zadeh, N. H. Ertel,
and M. Gutkin
E v i d e n c e for an Unidentified A C T H - I n d u c e d
Steroid Hormone Causing Hypertension
M. / . New, R. E. Peterson, P. Saenger, and L. S.
Levine
Studies on Phenolic Steroids in Human Subjects. X X . In Vivo Conjugation and Metabolism of Estradiol-17/3 in the Human Kidney
H. Honjo, N. R. Barua, Y. Osawa, R. Y. Kirdani,
and A. A. Sandberg
Inhibition of Human Plasma R e n i n Activity
by Pepstatin
T. T. Guyene, C. Devaux, J. Menard, and P.
Corvol
OF VOLUME
1211
1219
1226
1234
1240
1250
1255
1261
1268
1276
1283
1294
1301
43
Nonautonomous Function of a Pancreatic I n sulinoma
E. J. Rayfield, M. Pulini, A. Golub, A. H.
Rubenstein,
and D. L. Horwitz
Propranolol i n the Treatment of Thyrotoxicosis
by Subtotal Thyroidectomy
A. D . Toft, W.J. Irvine, D. Mcintosh, D. A. D.
MacLeod, J. Seth, E. H. D. Cameron, and G . P.
Lidgard
AVAndrostenediol: Kinetics of Metabolism and
B i n d i n g to Plasma Proteins in Normal M e n
and W o m e n
C . E. Bird, L. Morrow, Y. Fukumoto, S. Marcellus, and A. F. Clark
Urinary C y c l i c Nucleotide L e v e l s in Patients
with H y p e r - and Hypothyroidism
/. R. Tucci and L. Kopp
Plasma Prostaglandin E in Patients with C a n c e r
with and Without Hypercalcemia
R. P. Robertson,
D. J. Baylink, S. A. Metz,
and K. B.
Cummings
Preferential B i n d i n g of Testosterone O v e r E p i testosterone by H u m a n Plasma
P. F. Brüning, A. Kowarski, and C.J.
Migeon
Regulation of R e n i n Release by C a l c i u m and
A m m o n i u m Ions in Normal Man
E. S. Kisch, R. G. Dluhy, and G. H. Williams
Measurements
of 3 , 3 ' , 5 ' - T r i i o d o t h y r o n i n e
(Reverse T 3 ) , 3,3'-L-Diiodothyronine, T 3 ,
and T 4 in H u m a n Amniotic F l u i d and i n C o r d
and Maternal Serum
K. D. Btirman, J. Read, R. C. Dimond,
D.
Strum, F. D. Wright, W. Patow, J. M. Earll,
and L. Wartofsky
Inappropriate T S H Secretion. Paradoxical R i s e
in Serum T S H in Response to Thyroxine
Therapy
S . Hood, J. D. Vaughan-Jackson,
and N. R.
Farid
Hashimoto's Thyroiditis Presenting as a Solitary
F u n c t i o n i n g T h y r o i d Nodule
P. Bialas, S. Marks, A. Dekker, and J. B. Field
Restoration of Plasma Testosterone L e v e l s i n
U r e m i c M e n With Clomiphene Citrate
V. S. Lim and V. S. Fang
ix
1307
1312
1317
1323
1330
1336
1343
1351
1360
1365
1370
COMMENTS
Somatomedin i n C o r d Blood: Relationship to
Gestational Age and Birth Size
P. D. Gluckman
and M. W.
Brinsmead
Growth Hormone and Prolactin Release in
Acromegalic Patients F o l l o w i n g Metergoline
Administration
G . Delitala, A. Masala, S. Alagna, L. Devilla,
and G. Lotti
Spironolactone Stimulation of Gonadotropin
Secretion i n Boys with D e l a y e d Adolescence
R. J. Santen, H. E. Kulin, D. L. Loriaux,
and
J. Friend
1378
1382
1386
CONTENTS
X
L i t h i u m Does Not Inhibit the Parathyroid Hormone-Mediated Rise in Urinary C y c l i c A M P
and Phosphate in Humans
A. M. Spiegel, R. H. Gerner, D. L.
Murphy,
and G. D. Aurbach
Overnight F o l l i c l e Stimulating Hormone ( F S H )
and Luteinizing Hormone ( L H ) Excretion
in Normal Males
R. Penny, I. P. Goldstein,
and S. D.
OF VOLUME
1390
J C E & M • 1976
Vol 4} • No 6
T h e in Vitro Suppression of L e c t i n I n d u c e d
H - T h y m i d i n e Incorporation into D N A of
Peripheral Blood Lymphocytes After the
Addition of Propylthiouracil
J. R. Wall, G . L. Manwar, D. M.
Greenwood,
and B. A. Walters
A L o w Molecular Weight Substance Obtained
from Serum W h i c h Has L u t e i n i z i n g Hormone
L i k e Activity ( " M i n i - L H " )
F . A. Leidenberger, D. Graesslin, H.J.
Scheel,
N. Hess, V. Lichtenberg,
and G.
Bettendorf
Primate Chorionic Gonadotropins: Antigenic
Similarities to the Unique Carboxyl-Terminal
Peptide of HCG/3 Subunit
H.-C. Chen and G. D. Hodgen
Human Puberty: 24-Hour Estradiol Patterns in
Pubertal Girls
R. M. Boyar, R. H. K. Wu, H. Roffwarg,
S.
Kapen, E. D. Weitzman,
L. Hellman,
and
J. W. Finkelstein
1406
3
1394
Frasier
RAPID COMMUNICATIONS
Ovarian Refractoriness to Gonadotropins in
Cases of Inappropriate Lactation: Restoration
of Ovarian Function With Bromocryptine
A. M. Mroueh and T. M.
Siler-Khodr
Urinary Progesterone as an Index of Ovulation
and Corpus Luteal F u n c t i o n
S. C . Chattoraj, J. S. Rankin, A. K. Turner,
and E. W. Lowe
43
1398
1402
1410
1414
1418
Recurrent Goiter, Hyperthyroidism, Galactorrhea and
Amenorrhea due to a Thyrotropin and
Prolactin-Producing Pituitary Tumor
K. H O R N , * F. E R H A R D T , * R. F A H L B U S C H , * * C. R. P I C K A R D T , *
K. v. W E R D E R , * A N D P. C. S C R I B A *
//. Medizinische
Klinik*
and Neurochirurgische
Klinik,**
A B S T R A C T . A 22-year-old woman with recurrent
goiter, hyperthyroidism, galactorrhea, and amenorrhea due to a pituitary tumor is described. She
had been treated surgically twice for recurrent goiter
with tracheal compression. Despite clinical signs of
hyperthyroidism and slightly elevated plasma thyroid
hormone levels ( T : 11 /xg/dl; T : 189 ng/dl), without
thyroid hormone replacement therapy the basal T S H
level was elevated up to 23 /-tU/ml and could not
be suppressed by exogenous thyroid hormones:
even w h e n the serum thyroid hormone levels were
raised into the thyrotoxic range ( T : 16.2 /u,g/dl T :
392 ng/dl), the basal T S H fluctuated between 12 and
29 /xU/ml. T h e basal P R L level was elevated up to
:
of Munich,
Munich,
Germany
6000 /LtU/ml. T h e administration of T R H (200 fxg
iv) led only to small increments of T S H and P R L
levels. Bromocriptin (5 mg p.o.) or L-dopa (0.5 g p.o.)
suppressed T S H and P R L values significantly. After
transsphenoidal hypophysectomy, T S H and P R L
were below normal and the patient developed panhypopituitarism. T h e adenoma showed two cell types
which could be identified as lactotrophs and thyrotrophs by electronmicroscopy and immunofluorescence. From these data we conclude that the patient had a pituitary tumor with an overproduction
of thyrotropin and prolactin, (j Clin
Endocrinol
Metab 43: 137, 1976)
3
4
University
3
H
Y P E R T H Y R O I D I S M due to a thyrot r o p i n - p r o d u c i n g p i t u i t a r y adenoma is
extremely rare. To our k n o w l e d g e , there are
only a f e w w e l l d o c u m e n t e d cases i n the
literature ( 1 , 2 , 3 ) . I n contrast, female patients
w i t h p r o l a c t i n - p r o d u c i n g tumors a n d w i t h
amenorrhea and galactorrhea have been described f r e q u e n t l y d u r i n g recent years ( 4 , 5 ) .
W e have n o w observed a patient w i t h recurrent proliferation o f the t h y r o i d gland,
h y p e r t h y r o i d i s m , galactorrhea, and amenorrhea due to the simultaneous hypersecretion
of T S H and P R L .
H e a l t h Bethesda, M a r y l a n d , U S A , a n d the N a tional
Institute
for M e d i c a l R e s e a r c h ,
(MRC),
L o n d o n . Thyrotropin a n d P R L were expressed in
/ x U / m l . T w e n t y ^tU o f the b P R L r e s e a r c h s t a n d a r d
A-71/222
(7,8).
were
e q u i v a l e n t to 1 n g V L S - h P R L
H u m a n growth
hormone
and L H were
m e a s u r e d , as d e s c r i b e d p r e v i o u s l y (8), u s i n g o u r
o w n a n t i s e r a a n d G H (2 I U / m g ) from K a b i C o m p . ,
S w e d e n a n d pituitary L H (2135 I U of 2 n d I R P hMG/mg)
as s t a n d a r d
a n d tracer
preparation.
T h e F S H preparation h a d a biological
activity
of 3 5 0 0 I U 2 n d I R P / m g a n d a radioimmunol o g i c a l a c t i v i t y o f 2 3 3 0 I U 68/39 M R C a n d w a s
obtained togedier with a specific F S H antiserum
from C E A / G i f - s u r - Y v e t t e , F r a n c e . A f t e r extraction from t h e s e r u m b y m e a n s
Materials and Methods
raphy
T S H (6), P R L (7), G H , L H , a n d F S H (8) w e r e
on
sephadex
columns
of
in
chromatogautomatized
p r o c e d u r e s , as d e s c r i b e d p r e v i o u s l y , T
3
was de-
measured by double-antibody radioimmunoassay
t e r m i n e d b y r a d i o i m m u n o a s s a y (9), a n d T
t e c h n i q u e s . T h e reagents for t h e T S H a n d P R L
a n d Cortisol (9,10) b y competitive protein-bind-
4
(9)
r a d i o i m m u n o a s s a y w e r e o b t a i n e d from t h e N a -
i n g a n a l y s i s . T h e T - u p t a k e test w a s performed
tional
b y d e x t r a n g e l filtration (10).
Pituitary Agency,
National
Institutes
3
of
T h e normal ranges
Received May 19, 1975.
Supported by the Deutsche Forschungsgemeinschaft, S F B 51.
This observation was presented in part at the 7th
International Thyroid Conference, Boston, 1975.
Reprint requests to: D r . M e d . Klaus Horn, I I . Med.
Klinik der Universitaet, 8 Muenchen 2, Ziemssenstrasse 1, F R G .
were: T : 80-150
3
ng/dl;
T : 4 , 5 - 1 0 / i g / d l ; T - u p t a k e test: 3 2 - 4 2 % ; B a s a l
4
3
TSH:
<1.0-3.8
/xU/ml
(women).
Endocrine
137
/iU/ml;
stimulation
Basal
P R L : 150-650
and suppression
tests
T R H s t i m u l a t i o n test: 2 0 0 fig T R H ( H o e c h s t ,
F r a n k f u r t , F R G ) w a s i n j e c t e d iv. L - D o p a s u p p r e s -
H O R N ET
138
. I C E & M • 1976
Vol 13 • X u 1
AL.
s i o n test: 5 0 0 m g L - d o p a ( H o f f m a n n - L a R o c h e
There
A G , G r e n z a c h , F R G ) was given orally. Bromo-
w i t h d r a w a l o f t h y r o i d h o r m o n e t h e r a p y for four
c r i p t i n ( C B - 1 5 4 ) s u p p r e s s i o n test: 5 m g C B - 1 5 4
weeks,
(Sandoz,
T
B a s e l , S w i t z e r l a n d ) was given orally.
were
T
resin
3
4
no visual
(11.0
uptake
field
/xg/dl),
T
(41.5%)
defects.
3
(189
were
A f t e r the
ng/dl),
and
slightly
ele-
B l o o d s a m p l e s w e r e t a k e n at d i f f e r e n t t i m e s h e -
vated. S u r p r i s i n g l y , the basal T S H was 23 /xU/ml,
fore a n d after t h e a d m i n i s t r a t i o n o f t h e s e
agents,
b u t c o u l d not b e f u r t h e r e l e v a t e d b y T R H . T h e
i n F i g . 1 - 3 . T h e T - s u p p r e s s ion
b a s a l P R L l e v e l w a s 4 8 0 0 /xU/ml a n d o n l y rose
as
indicated
3
t e s t w a s p e r f o n n e d w i t h 100 fig T
(Thybon®,
3
to 5 4 0 0 /xU/ml 3 0 m i n after T R H .
H o e c h s t , Frankfurt, F R G ) per day orally over a
period of 4 w e e k s . L H R H
and
F S H levels were
before a n d
3 0 m i n after t h e i n j e c t i o n of 2 5 fig L H R H
intra-
venously (Hoechst, Frankfurt, F R G ) . Insulin hyp o g l y c e m i a test: regular i n s u l i n (0.15 U/kg bodyweight) w a s injected iv, a n d blood was drawn
b e f o r e a n d 3 0 , 4 5 , 60, a n d 9 0 m i n after t h e i n s u l i n
injection.
T h e nadir of blood glucose
was 35
m g / d l 4 5 m i n after t h e i n s u l i n i n j e c t i o n .
Case
report
In
1968
a
16-year-old
girl
noticed
a
rapid
g r o w t h o f a goiter w i t h d y s p n e a a n d stridor. I n
addition,
she complained
of weight
loss a n d
h y p e r p h a g i a , m u s c l e w e a k n e s s , heat intolerance,
and nervousness without ophthalmopathy. Since
t h e p a t i e n t w a s a d m i t t e d to a s u r g i c a l w a r d of
a s m a l l hospital no more detailed clinical records
and no thyroid honnone
l e v e l s o f that
period
a r e a v a i l a b l e . A subtotal r e s e c t i o n o f h e r g o i t e r
was
perfonned
in
1969,
mainly
because
of
t r a c h e a l c o m p r e s s i o n . P o s t o p e r a t i v e l y , 6 0 fig T
3
d a i l y w a s g i v e n , but t w o years later h y p e r t h y r o i d ism a n d goiter recurred. A g a i n , tracheal compress i o n l e d to a s e c o n d t h y r o i d r e s e c t i o n , this t i m e
c o m b i n e d w i t h a plastic surgical reconstruction of
a part o f the trachea b e c a u s e of tracheomalacia.
A f t e r t h e s e c o n d o p e r a t i o n , t h e r a p y w i t h 100
fig T
4
a n d 2 0 fig T
recurrence
3
p e r d a y d i d not p r e v e n t t h e
o f t h e goiter. T h e r e f o r e , t h e p a t i e n t
w a s a d m i t t e d to o u r h o s p i t a l i n 1 9 7 3 for the first
time.
On
a d m i s s i o n , she had no complaints
con-
c e r n i n g h e r t h y r o i d , b u t s h e r e p o r t e d that t h r e e
years ago h e r periods h a d b e c o m e irregular a n d
that o n e y e a r
later
she observed
galactor-
r h e a from both breasts.
T h e p h y s i c a l examination revealed a diffusely
e n l a r g e d t h y r o i d gland. E a c h lobe h a d a size of
about 4 x 3 c m . T h e r e w e r e no signs of tracheal
compression by clinical a n d X-ray examination.
h a d no clinical
Effect of thyroid hormone
on serum TSH levels
administration
After four weeks of therapy w i t h 100 /xg
T and 20 fig T per day, the T level
was 10.2/xg/dl. T h e basal T S H level was still
elevated a n d showed only a small increase
from 18 /xU/ml to only 23 /xU/ml 30 m i n after
T R H injection. Raising the daily dosage o f
t h y r o i d hormones to 150 /xg T and 30 peg
T for a p e r i o d o f 24 days l e d to an i n crease i n the serum T l e v e l up to 16.2 /xg/dl,
b u t the basal T S H level was persistently
elevated a n d resistant to T R H stimulation
(22.9 and 23.2 /xU/ml, respectively).
I n order to exclude a disturbance o f the
peripheral conversion o f T to T , the patient was treated w i t h 300 /xg T per day over
a p e r i o d o f 4 weeks. D u r i n g this p e r i o d ,
the T level increased to 17.5 /xg/dl and the
T uptake test to 63.7%. T h e basal T S H level
was still significantly elevated (13.6 /xU/
ml) although t h e conversion o f T to T was
documented b y an increase i n the T level
up to 392 ng/dl. F u r t h e r m o r e , f o l l o w i n g
therapy w i t h 100 /xg T per day over a p e r i o d
of four weeks, the basal T S H level r e m a i n e d
elevated (25.6 /xU/ml). T h e basal P R L level
was clearly elevated throughout all these
observations a n d ranged from 4000 to 6000
/xU/ml.
4
3
4
4
3
4
4
3
4
4
3
4
3
3
3
amenorrhea.
S i n c e that time, s h e h a d also o b s e r v e d
She
Results
s t i m u l a t i o n test: L H
determined
signs of G r a v e s ' disease.
TSH and PRL levels after TRH stimulation
T h e T R H stimulation test was p e r f o r m e d
t w i c e , first after a p e r i o d o f four weeks
w i t h o u t exogenous t h y r o i d hormones, a n d
second d u r i n g therapy w i t h t h y r o i d hormones (100 /xg T a n d 20 /xg T p.o. daily).
4
3
TSH
AND PRL-PRODUCING PITUITARY
TRH
U n d e r b o t h conditions, the T S H and P R L
levels s h o w e d no significant increase after
T R H i n j e c t i o n ( F i g . 1).
TSH
and
pression
PRL
levels
after
L-dopa
139
TUMOR
200 pg - v
sup-
L - D o p a and b r o m o c r i p t i n suppression
tests were done w i t h o u t t h y r o i d hormone
therapy.
Both hormones decreased from elevated
levels to a nadir 120 m i n after the L - d o p a
administration ( F i g . 2). W h e n 200 fig T R H
was injected 60 m i n after L - d o p a was g i v e n ,
no increase, b u t a further decline i n T S H
and P R L levels was observed, reaching the
lowest values 120 m i n after L - d o p a ( F i g . 2).
TSH
and
(CB-154)
PRL
levels
after
bromocriptin
F o l l o w i n g 5 m g b r o m o c r i p t i n , P R L and
T S H levels fell i n a parallel fashion. H o w ever, normal values c o u l d not be reached
after this single oral dose ( F i g . 3).
Immunologic
PRL
characterization
of TSH
and
I
I
-15
0
I
I
I
I
I
I
I
I
I
I n order to prove the i m m u n o l o g i c a l
i d e n t i t y o f the c i r c u l a t i n g T S H and P R L
w i t h the respective standard preparations,
T S H and P R L w e r e estimated in different
serum d i l u t i o n s . T h e r e s u l t i n g displacement
curves were parallel w i t h the standard
curves (not shown).
F I G . 1. Plasma T S H and P R L levels before and after
T R H stimulation without (closed symboles) and with
thyroid replacement therapy (open symboles). T h e two
tests were performed with an interval of four weeks.
T h e shadowed area represents the response of T S H and
P R L in normal controls (mean ± 2 S D ) .
Additional
Clinical
clinical
studies
I n s u l i n h y p o g l y c e m i a i n d u c e d a rise i n
Cortisol from a normal basal value o f 14
ptg/dl to 31 ju,g/dl, and a rise i n G H from
2.0 ng/ml to 9 ng/ml 90 m i n after i n s u l i n
injection. After L H R H s t i m u l a t i o n , L H rose
f r o m 3.9 to 10.1 ng/ml and F S H from 3.4
to 8.0 ng/ml. T h e sella turcica was enlarged;
pneumencephalography revealed a cisterna
optochiasmatica o f normal size i n t e r p r e t e d
as an intrasellar g r o w t h o f the t u m o r w i t h out suprasellar extension. T h e visual fields
were n o r m a l .
30
60
90
120 mm
course
O n A p r i l 22, 1974, a transsphenoidal
hypophysectomy was p e r f o r m e d by curettage c o m b i n e d w i t h a cryoresection of the
p i t u i t a r y tumor. As shown i n F i g . 4, b o t h
T S H and P R L levels d e c l i n e d i n parallel
fashion after the removal o f the t u m o r . Six
hours after the operation, b o t h h o r m o n e
levels were w i t h i n the normal range. Postoperatively, the patient had no r a d i o i m munoassayable T S H and v e i y l o w P R L
levels i n her serum. A t present, t h e
patient receives replacement therapy w i t h
H O R N ET
140
oh PRL
pE/ml
• TSH
>iE/ml
35-
500mg
\CE
& M • 1976
Vol 43 • No 1
AL.
L-Dopa
2 0 0 g TRH iv
H
500 mg L - D o p a
4
6000 -
30
F I G . 2. Plasma T S H and P R L
responses due to L-dopa alone
(left panel) and to L-dopa and
subsequent T R H injection (right
p a n e l ) . T h e broken lines represent the upper limit of the
normal range of the basal values
for both hormones.
5000 -
25
4000
20
3000-
15 H
2000-
10
1000-
5
0-
0
J
60
120
60
180 mm
A D H , Cortisol, t h y r o i d hormones, a n d
gonadal steroids. She has no t h y r o i d enlargement, has ceased to lactate and is w i t h o u t
complaints and f u l l y active as a nurse.
Histology
of the pituitary
tumor
T h e l i g h t microscopic investigations revealed a p i t u i t a r y adenoma w i t h both acidop h i l i c and chromophobe cell, elements. I n
the electronmicroscopic picture t w o cell
types were f o u n d . O n e showed i n d e n t e d
n u c l e i a n d dense n u c l e o l i , the cytoplasm
was rich i n rough endoplasmatic r e t i c u l u m .
These cells were i n d i s t i n g u i s h a b l e from the
1 actotrophic cells seen i n pregnancy and in
lactotrophic p i t u i t a r y tumors. T h e other cell
type, w i t h l o n g cell bodies, frequently
showed secretory phenomena at the cell
membrane. T h e granules o f these cells, w i t h
a diameter o f 90 to 200 n m , were smaller
than those i n t h e lactotrophic cells. These
cells reacted w i t h an a n t i h u m a n T S H serum
by an immunoperoxidase sandwich techn i q u e . Therefore, i t seems l i k e l y that these
cells are T S H - p r o d u c i n g adenoma cells.
1
2
We are indebted for these results to Prof. D r . O.
Stochdorph, Abt. für Neuropathologie, Patholog. Institut, University of M u n i c h .
W e are indebted for these results to Prof. D r .
U . Hachmeister, Zentrum für Pathologie, University
of G l e s s e n , F R G .
1
2
120
180 mm
Discussion
T h e present study is, to our k n o w l e d g e ,
the first report o f a patient w i t h a pituitary
adenoma w i t h simultaneous hypersecretion
of t h y r o t r o p i n and prolactin. T o explain
this hypersecretion o f T S H a n d PRL, one
has to consider the possible pathophysiological mechanisms ( 1 1 - 1 3 ) :
a. T h e concomitant hypersecretion of prolactin and T S H was due to primary hypothyroidism.
b. T h e p i t u i t a r y adenoma p r o d u c e d only
T S H a n d i n h i b i t e d by suprasellar extension
the p r o d u c t i o n and/or the portal vessel
transport o f t h e hypothalamic prolactini n h i b i t i n g factor ( P I F ) .
c. T h e patient had enhanced hypothal a m i c T R H secretion, w h i c h led to a p i t u i tary adenomatous hyperplasia o f the thyrot r o p h ic a n d lactotrophic cells.
d. Both hormones, T S H and PRL, were
p r o d u c e d b y an " a u t o n o m o u s " pituitary
adenoma, w h i c h was not suppressed by thyr o i d hormones and was n o t stimulated b y
TRH.
T h e first theoretical possibility can be e l i m i n a t e d , since our patient was never hypot h y r o i d . I n a d d i t i o n , the P R L levels i n hypot h y r o i d i s m are o n l y slightly higher and decrease towards n o r m a l , parallel w i t h the fall
o f T S H levels d u r i n g t h y r o i d hormone rep l a c e m e n t therapy (14). I n o u r patient,
TSH
A N DP R L - P R O D U C I X G PITUITARY
A—A
141
TUMOR
CB - 154
5mq oral
TSH
jjE/ml
12-
0-
h PRL
\
3000 -T
F I G . 3. Plasma T S H and P R L
levels before a n d after the
administration of 5 mg
CB-154
(bromocriptin). T h e broken line
represents the upper limit of the
normal basal values of both hormones.
-A
2000 6-
4 -
1 000 -
0-1
n
-15 0
neither her T S H levels nor t h e P R L levels
were l o w e r e d to normal b y t h y r o i d hormones, even w h e n t h e peripheral t h y r o i d
hormone levels w e r e elevated. T h e d e v e l o p ment o f T S H p r o d u c i n g tumors as a conseTSH
hPRL
1
30
1
60
1
90
r120
240
300 mm
quence o f long-standing h y p o t h y r o i d i s m
occurs i n t h e rat (15). Analogous p i t u i t a r y
adenomas i n humans are observed i n areas
w i t h severe i o d i n e deficiency a n d e n d e m i c
cretinism (16).
Curtttop Cryo
o—o
20
F I G . 4 . Plasma T S H and P R L
levels before, during neurosurgery, and after transsphenoidal resection of the pituitary
(curettage) and cryohypophx sectomy (cryo). T h e broken line rep.esents the upper limit of the
normal basal values of both hormones. T h e time in hours is
shown on the abscissa.
4000
3000
2000
1000 -
0 J
—I—|—
5
24 46
192 SM
142
H O R N ET
I C E & M • 1976
Vol 13 • X o 1
AL.
I t is d i f f i c u l t to differentiate diffuse hyperplasia f r o m an adenoma on histological
grounds. T h e pituitary t u m o r of our patient
s h o w e d t w o closely associated cell types,
of w h i c h one c o u l d be i d e n t i f i e d as a 1 autot r o p h , the other as a T S H - p r o d u c i n g c e l l .
Since these t w o different cell types were
e v e n l y d i s t r i b u t e d i n the adenomatous tissue, i t is u n l i k e l y that a T S H - p r o d u c i n g
t u m o r i n d u c e d the h y p e r p r o l a c t i n e m i a i n
this case b y P I F i n h i b i t i o n . I n a d d i t i o n ,
this t u m o r d i d not show any suprasellar
extension, and i n s u l i n hypoglycemia i n d u c e d a normal rise of Cortisol and h G H i n
our patient, i n d i c a t i n g an intact hypothal a m i c - p i t u i t a r y axis. This does not favor the
theory of any disturbances i n the h y p o thalamus or i n the pituitary stalk.
l e v e l , since L - d o p a i n h i b i t s the normal T S H
response i n d u c e d by T R H (4,20). Furthermore, a hypothalamic i n h i b i t o r for T S H release is not k n o w n . F i n a l l y , the parallel
decrease i n both P R L and T S H in our patient
suggests that the i n h i b i t o r y effect of these
drugs occurs at the p i t u i t a r y level for both
hormones. Thus, the results of the pharmacologic studies support the concept of an
autonomous pituitary adenoma. H o w e v e r ,
the endocrine studies alone cannot rule out
hypothalamic T R H hypersecretion as a possible cause for a p i t u i t a r y adenoma. For this
to be excluded w i t h absolute certainty,
T R H levels w o u l d have to be measured i n
the portal vessels, w h i c h is not feasible i n
humans.
T h e results o f the endocrine tests i n our
p a t i e n t do not exclude an adenoma due to
endogenous T R H hypersecretion. H o w e v e r ,
the elevated basal levels o f T S H and P R L
c o u l d n o t be stimulated n o r m a l l y w i t h
synthetic T R H . Furthermore, the lack of
suppression o f T S H and P R L by t h y r o i d
hormones suggests an autonomous product i o n o f b o t h hormones by a p i t u i t a r y
adenoma.
T h e pharmacologic suppressors for prolactin, L - d o p a and b r o m o c r i p t i n caused a
parallel fall i n both hormones. The i n h i b i t i o n of elevated prolactin levels by bromoc r i p t i n occurs at the pituitary level (4).
E v i d e n c e has been accumulated that this
i n h i b i t i o n is not specific for the lactot r o p h i c cells, since i t has been shown
that b o t h the elevated T S H levels i n primary
h y p o t h y r o i d i s m (17) and the elevated G H
levels i n patients w i t h acromegaly can be i n h i b i t e d b y b r o m o c r i p t i n (18). We n o w
demonstrate that the hypersecretion o f T S H
by a p i t u i t a r y t u m o r can also be i n h i b i t e d
b y this d r u g . The i n h i b i t i o n of prolactin
secretion by L - d o p a is i n part due to the
s t i m u l a t i o n o f the hypothalamic P I F (12).
A n a d d i t i o n a l direct effect of L - d o p a on
p i t u i t a r y p r o l a c t i n secretion has also been
postulated (19). T h e i n h i b i t i o n of T S H by
L - d o p a occurs probably at the pituitary
References
1. Hamilton, C . R., L . D . Adams, and F . Maloof,
Hyperthyroidism due to thyrotropin-producing
pituitary chromophobe adenoma, ,V Engl J Med
283: 1077, 1970.
2. Linquette, U . , U. Herlant, P. Fossati, J. P. May, M.
Decoulx, and J. C . Fourlinne, Adenome hypophys ä r e ä cellules thyrotopes avec hyperthyreoidie,
Ann Endocrinol
(Paris) 30: 731, 1969.
3. Faglia, G . , C . Ferrari, V. Neri, P. Beck-Peccoz, B
Ambrosi, and F . Yalentini, High plasma thyrotroph in levels in two patients with pituitary tumors,
Acta Endocrinol
(Kbh) 69: 649, 1972.
4. F r i e s e n , H . , G . Tolis, R. Shiu, and P. Hwang,
Studies on human prolactin: Chemistry, radioreceptorassay and clinical significance,//? Pasteels,
J. L . , and C . Robyn (eds.), Human Prolactin, E.\cerpta Medica, Amsterdam, 1973, p. 23.
5. Turkington, R. YV., Secretion of prolactin by patients with pituitary and hypothalamic tumors, /
Clin Endocrinol
Metal) 34: 159, 1972.
6. Erhardt, F . , J. Marschner, C . R. Pickardt, and P. C .
Scriba, Verbesserung und Qualitätskontrolle der
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