bluuebunny/crossref_metadata_2025 huggingface dataset:
Role of thyroid hormone in controlling the concentration of luteinizing hormone/human chorionic gonadotropin receptors in rat ovaries
Authors: Fitko Remigiusz , Szlezyngier Beata
Published: December 2008

Fitko R, Szlezyngier B. Role of thyroid hormone in controlling the concentration of luteinizing hormone/human chorionic gonadotropin receptors in rat ovaries. Eur J Endocrinol 1994;130:378-80. ISSN 0804–4643

Little is known about the mechanism by which thyroid hormones influence ovarian function, especially in gonadotropin receptor formation. In this study the concentration of Iuteinizing hormone (LH)/human chorionic gonadotropin (hCG) receptors in the ovaries of hypo- and hyperthyroid rats was estimated. Rats were made experimentally hypothyroid by thyroidectomy (N = 10) and hyperthyroid by injections of 40 μg of l-thyroxine daily for 21 days (N = 14). After 3 weeks the ovaries were excised, weighed, immersed in liquid nitrogen and then, after 24 h of incubation with 125I-labeled hCG (CR-121), the concentration of receptors (cpm) for one ovary and 1 mg of tissue was counted in their respective homogenates. The ovaries of the hyperthyroid group were diminished in size and consequently the level of receptors per ovary also was reduced when compared with control animals. The number of receptors per ovary and per milligram of tissue of hypothyroid rats was three times higher than in the control. In hyperthyroid animals a significant decrease in these values was noted when compared with hypothyroid rats, especially in the calculation of receptor concentration per ovary. It may be concluded that thyroid function may affect the size of the gland and also the number of LH/hCG-binding sites in rat ovaries. These data may be useful for interpretation of the pathophysiology of polycystic ovary syndrome in women and animals.

R Fitko, Department of Experimental Pathology, Centre for Agrotechnology and Veterinary Sciences, 10-718 Olsztyn, ul. Prawocheñskiego 5, Poland
Drug competition for intracellular triiodothyronine-binding sites
Authors: Barlow John W , Curtis Andrea J , Raggatt Lorna E , Loidl Nicole M , Topliss Duncan J , Stockigt Jan R
Published: December 2008

Barlow JW, Curtis AJ, Raggatt LE, Loidl NM, Topliss DJ. Stockigt JR. Drug competition for intracellular triiodothyronine-binding sites. Eur J Endocrinol 1944;130:417–21. ISSN 0804–4643

A variety of substances, including frusemide, non-esterified fatty acids (NEFAs) and non-steroidal antiinflammatory drugs (NSAIDs), can compete for triiodothyronine (T3)-binding sites in serum and at the cell surface. We examined the competitive potency of these agents at intracellular T3-binding sites in order to assess their potential to act as T3 antagonists. Competition for [125I]T3 binding was determined using hydroxyapatite separation in cytosols and nuclear extracts prepared from livers of Macaca fascicularis. The T3 affinities were 15.8 ± 1.2 nmol/l in cytosol and 0.23 ± 0.02 nmol/l in nuclear extract. Does–response curves were analysed by a four-parameter sigmoid curve-fitting program to determine competitor potency. The nineteen agents tested included various NSAIDs, NEFAs, non-bile acid cholephils (NBACs), frusemide, amiodarone and the flavonoid EMD 21388. In nuclear extract the most active competitors were linoleic acid (8.5 μmol/l) and linolenic acid (7.8 μmol/l), Potencies of NSAIDs varied between 66 μmol/l (meclofenamic acid) and 525 μmol/l (diclofenac). In cytosol, NEFAs were less potent but NSAIDs were stronger competitors than in nuclear extract. Half-inhibitory potencies in cytosol were between 13.2 μmol/l (meclofenamic acid) and 63.1 μmol/l (flufenamic acid). The NBAC bromosulphthalein was one of the most potent inhibitors in both cytosol and nuclear extract. When expressed relative to T3, diclofenac was a more effective competitor in cytosol than it was in nuclear extract. Amiodarone and EMD 21388 were without effect both in cytosol and nuclear extract. Frusemide (759 μmol/l) was weakly active in cytosol only. The action of T3 was assessed by measuring secretion of sex hormone-binding globulin (SHBG) in Hep-G2 cells. After 3 days with total T3 (0.1 μmol/l), SHBG was 155 ± 15% of the control. Amiodarone (100 μmol/l) and meclofenamic acid (100 μmol/l) were cytotoxic. Bromosulphthalein (10 μmol/l), one of the most potent competitors at both the cytoplasmic and the nuclear level, did not influence the T3-induced rise in SHBG secretion. None of the drugs tested affected the magnitude of maximal induction of SHBG by T3. Substances that compete for serum and cell surface T3-binding sites are also weak competitors for intracellular T3-binding proteins, although the heirarchy of potency differs. Frusemide and diclofenac, with a greater relative potency for cytosolic binding than nuclear binding, may have potential use in investigating the function of cytosolic T3-binding. Amiodarone shows no binding activity and is not a hormone antagonist in primate hepatic tissue.

John W Barlow, Ewen Downie Metabolic Unit, Alfred Hospital, Commercial Road, Melbourne, Victoria 3181, Australia
Lanreotide, a somatostatin analogue, reduces insulin-like growth factor I accumulation in proliferating aortic tissue in rabbits in vivo. A preliminary study
Authors: Howell Marcus , Ørskov Hans , Frystyk Jan , Flyvbjerg Allan , Grønbæk Henning , Foegh Marie
Published: December 2008

Howell M, Ørskov H, Frystyk J. Flyvbjerg A, Grønbæk H, Foegh M. Lanreotide, a somatostatin analogue, reduces insulin-like growth factor I accumulation in proliferating aortic tissue in rabbits in vivo. A preliminary study. Eur J Endocrinol 1994;130:422–5. ISSN 0804–4643

Coronary artery restenosis following percutaneous transluminal angioplasty occurs with a very high incidence. Major efforts have been aimed at revealing the mechanisms and at developing therapies that might prevent or delay the myointimal proliferation. Most clinical trials have been unsuccessful. Endothelial denudation was induced in 30 rabbits using balloon catheterization of iliac arteries and aorta. Immunoreactive insulin-like growth factor I (IGF-I) was measured in arterial tissue samples obtained 1, 2 and 4 days postoperatively using a double extraction procedure to remove IGF-I binding proteins. Half of the animals were treated with subcutaneous injections of lanreotide, 10 μg/kg twice daily, and the other half served as controls. In the latter group, arterial IGF-I was unaltered from baseline at day 1 and increased by 300 and 400% at days 2 and 4. No increase was observed in the rabbits treated with lanreotide. The results indicate that initial local accumulation of IGF-I may be one of the mechanisms involved in myointimal proliferation after experimental arterial injury. The reduction of local IGF-I accumulation by lanreotide may be involved in the previously observed reduction in myointimal proliferation.

Hans Ørskov, Institute of Experimental Clinical Research, University Hospital, DK-8000 Aarhus C, Denmark
Relationship between calcitrophic hormones and blood pressure in elderly subjects
Authors: John Andrew St , Dick Ian , Hoad Kirsten , Retallack Robert , Welborn Timothy , Prince Richard
Published: December 2008

St John A, Dick I, Hoad K, Retallack R, Welborn T, Prince R. Relationship between calcitrophic hormones and blood pressure in elderly subjects. Eur J Endocrinol 1994;130:446–50. ISSN 0804–4643

The relationship between calcitrophic hormones and blood pressure has been investigated in 583 elderly subjects who were untreated for hypertension. Univariate analysis demonstrated that serum parathyroid hormone, calcitriol, albumin and calcium were correlated significantly with mean blood pressure (r = +0.15, +0.10, +0.14 and +0.11, respectively), as were body mass index and age (r = +0.19 and +0.10, respectively). Parathyroid hormone also was correlated positively with both age and calcitriol (r = +0.34 and +0.15, respectively) and negatively with plasma calcium and albumin (r = −0.09 and −0.09, respectively). Multivariate analysis demonstrated that when allowing for age and body mass index, parathyroid hormone and calcitriol were both significant independent determinants of the mean blood pressure. When other independent variables were included in the analysis, parathyroid hormone but not calcitriol remained a significant predictor of mean blood pressure. This study has demonstrated a weak but significant relationship between blood pressure and calcitrophic hormones in a group of elderly people. The data are consistent with the hypothesis that hypertension may be due in part to calcium deficiency.

Andrew St John, Department of Biochemistry, Royal Perth Hospital, GPO Box X2213, Perth, Western Australia
Efficacy of intermittent therapy in growth hormone-deficient children
Authors: Bougnères Pierre
Published: December 2008

Bougnères P. Efficacy of intermittent therapy in growth hormone-deficient children. Eur J Endocrinol 1994;130:459–62. ISSN 0804–4643

Eighty-six growth hormone-deficient children treated with extractive growth hormone were transferred to recombinant growth hormone (rGH): 57 children were transferred directly to rGH, but 29 experienced a 9.7 ± 1-month pause in growth hormone administration. The retrospective analysis of growth from 1 year before to 1 year after initiation of rGH showed that the interruption of growth hormone administration did not modify the final height gain. During the 2 years, children with continuous therapy gained 12.2 ± 0.5 cm with a cumulative growth hormone dose of 43 ± 3 U/kg, while those who paused gained 12.1 ±0.3 cm with a cumulative growth hormone dose of only 24 ± 2 U/kg (p < 0.0005). As expected, during the year preceding the onset of rGH, the children who paused gained less height than those treated continuously, but grew more rapidly during the first year of rGH administration. This was due to an important re-acceleration of growth rate at re-initiation of therapy after the pause. Our observation suggests that regimens of discontinuous rGH administration could be as efficient as continuous treatment. If confirmed in prospective randomized trials, this could have important consequences for improving the clinical efficiency of a given dose of rGH, as well as for the patient's comfort, secondary effects and cost of therapy.

Pierre Bougnères, Service d'Endocrinologie Pédiatrique, Hôpital Saint Vincent de Paul, 82 avenue DenfertRochereau, 75014 Paris, France
Effect of interleukin 2 on the production of progesterone and prostaglandin E2 in human fetal membranes and its consequences for preterm uterine contractions
Authors: Ohno Yasumasa , Kasugai Masahide , Kurauchi Osamu , Mizutani Shigehiko , Tomoda Yutaka
Published: December 2008

Ohno Y, Kasugai M, Kurauchi O, Mizutani S, Tomoda Y. Effect of interleukin 2 on the production of progesterone and prostaglandin E2 in human fetal membranes and its consequences for preterm uterine contractions. Eur J Endocrinol 1994;130:478–84. ISSN 0804–4643

Our objective was to clarify the mechanism of uterine contraction induced in pregnant women by intrauterine bacterial infection. The concentration of interleukin 2 (IL-2) was measured in amniotic fluids that had been obtained by amniocentesis, transvaginal amniotomy or by transuterine amniocentesis performed at cesarean section in 50 pregnant women. The concentration of IL-2 in those cases with intrauterine infection was significantly higher than that of those without intrauterine infection at preterm. The same tendency was found at term. Scatchard analysis demonstrated the presence of an IL-2 receptor in the fetal membranes. We collected the fetal membranes aseptically for the measurement of progesterone and prostaglandin E2 by radioimmunoassay following incubation with various concentrations of Interleukin I (IL-1) and IL-2 at 37°C for 16 h. The production of progesterone was inhibited significantly by 10 pmol/l IL-2 but not by 10 pmol/l IL-1. The production of prostaglandin E2 was accelerated significantly by either IL-1 or IL-2 at a dose of 10 pmol/l. The inhibitory effect of IL-2 on the production of progesterone was unaffected by indomethacin, which inhibits the production of arachidonate cycloxygenase metabolites such as prostaglandin E2. Our present data suggest that the presence of intrauterine bacterial infection may stimulate the intrauterine production of IL-2, and that the stimulation of IL-2 and the reduction of progesterone caused by IL-2 may in part explain the mechanism of uterine contraction associated with intrauterine infection during pregnancy.

Yasumasa Ohno, Department of Obstetrics and Gynecology, Nagoya University School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466, Japan
Does early administration of thyroxine reduce the development of Graves' ophthalmopathy after radioiodine treatment?
Authors: Tallstedt Leif , Lundell Göran , Blomgren Henric , Bring Johan
Published: December 2008

Tallstedt L, Lundell G, Blomgren H, Bring J. Does early administration of thyroxine reduce the development of Graves' ophthalmopathy after radioiodine treatment? Eur J Endocrinol 1994:130: 494–7. ISSN 0804–4643

The roles of thyroid hormones and thryotropin (TSH) in the development of Graves' ophthalmopathy are not clear. Some studies suggest a protective effect of thyroid hormones on experimental exophthalmos and an adverse effect of increased TSH levels. In September 1988 we introduced early thyroxine (T4) administration after 131I therapy for hyperthyroidism caused by Graves' disease. We carried out a retrospective study of records from all patients with this disease treated with 131I for 4 years. During the first 2 years 248 patients were treated (group A). They received T4 when the serum concentration of TSH and/or T4 indicated hypothyroidism. During the next 2 years 244 patients were treated (group B). They were all given 0.05 mg of T4 daily, starting 2 weeks after therapy, and 0.1 mg after a further 2 weeks. With a follow-up of 18 months, 45 patients (18%) in group A and 27 patients (11%) in group B developed or deteriorated in an already present ophthalmopathy (p = 0.03, relative risk = 1.64, 95% confidence interval = 1.05–2.55). Twenty-six patients in group A required specific therapy for the ophthalmopathy (e.g. antithyroid drugs, steroids, etc.) compared to 11 patients in group B (p = 0.02, relative risk = 2.33; 95% confidence interval = 1.18–4.60). Our results suggest that early administration of T4 after 131I therapy reduces the occurrence of Graves' ophthalmopathy.

L Tallstedt, Department of Ophthalmology, Huddinge University Hospital, S-146 81 Huddinge, Sweden
Thyrotropin-releasing hormone (TRH) binding sites and thyrotropin response to TRH are regulated by thyroid hormones in human thyrotropic adenomas
Authors: Le Dafniet Michèle , Brandi Anne-Marie , Kujas Michèle , Chanson Philippe , Peillon Françoise
Published: December 2008

Le Dafniet M, Brandi A-M, Kujas M, Chanson P, Peillon F. Thyrotropin-releasing hormone (TRH) binding sites and thyrotropin response to TRH are regulated by thyroid hormones in human thyrotropic adenomas. Eur J Endocrinol 1994:130:559–64. ISSN 0804–4643

In order to see whether, in thyrotropic adenomas with thyrotoxicosis, plasma thyroid hormones regulate the thyrotropin-releasing hormone (TRH) binding sites and the thyrotropin (TSH) response to TRH, we investigated: the presence of TRH binding sites in two cases of thyrotropic adenomas associated with hyperthyroidism and in one case of thyrotropic adenoma secondary to thyroid failure; and the in vitro effect, in a perifusion system, of triiodothyronine (T3) on the response of TSH to TRH in three cases of TSH-secreting adenomas associated with hyperthyroidism. The TRH binding sites were absent in the adenomas associated with high levels of circulating thyroid hormones, whereas they were present in the adenoma secondary to primary thyroid failure (K4 =47 nmol/l, Bmax = 40 nmol/ kg membrane proteins). In vitro, the three adenomas spontaneously released TSH in the perifusion medium (1.49 ±0.06 (mean ± sem), 7.25±0.12 and 16.73±0.36 mIU·−1·106 cells−1·2 min−1) and exhibited an ample TSH response to 10−7 mol/l TRH pulses. In two cases, tumoral secretion of fragments was compared with those of fragments maintained since the time of surgical removal in the presence of 10−8 mol/l T3. The TSH responses to TRH were abolished in the presence of T3 in these two cases. We conclude that thyrotropic adenomas associated with hyperthyroidism are still controlled in vivo by T3. In particular, T3 regulates the TSH response to TRH, probably via a down-regulation of the TRH binding sites.

Michèle Le Dafniet, Unité INSERM 223, Faculté de Médecine, Pitié-Salpêtrière, 105 Boulevard de l'Hôpital, 75013 Paris, France
Single amino acid substitution (840Arg → His) in the hormone-binding domain of the androgen receptor leads to incomplete androgen insensitivity syndrome associated with a thermolabile androgen receptor
Authors: Imasaki Kyosuke , Hasegawa Tomonobu , Okabe Taijiro , Sakai Yoshiyuki , Haji Masafumi , Takayanagi Ryoichi , Nawata Hajime
Published: December 2008

Imasaki K, Hasegawa T. Okabe T. Sakai Y. Haji M. Takayanagi R, Nawata H. Single amino acid substitution (840Arg → His) in the hormone-binding domain of the androgen receptor leads to incomplete androgen insensitivity syndrome associated with a thermolabile androgen receptor. Eur I Endocrinol 1994;130:569–74. ISSN 0804–4643

We have characterized the androgen receptor in a Japanese girl and her maternal cousin in a family with incomplete androgen insensitivity syndrome, and have investigated the molecular basis. Wholecell androgen binding assay in cultured genital skin fibroblasts from both patients showed a normal maximum binding capacity and a normal apparent dissociation constant. However, androgen binding in fibroblasts from both patients decreased to 30% when the assay temperature was raised from 30°C to 41°C, indicating the presence of the thermolability of ligand binding to the androgen receptor. Sequence analysis of the coding exons of the androgen receptor gene from the patients revealed a single nucleotide substitution at position 2881 in exon G, resulting in the conversion of arginine (CGT) to histidine (CAT) at amino acid position 840 in the hormone-binding domain of the androgen receptor. The family study showed that the mothers and the maternal grandmother of the patients are heterozygous carriers for this mutation, whereas the father does not carry it, supporting the view that androgen insensitivity syndrome is an X chromosome-linked disorder. The single amino acid substitution may explain the qualitative abnormality of the androgen receptor displaying thermolability, which is thought to be the pathogenesis of incomplete androgen insensitivity syndrome in the patients.

Kyosuke Imasaki, Third Department of Internal Medicine, Faculty of Medicine, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812, Japan
Detection of autoantibodies to the 65-kD isoform of glutamate decarboxylase by radioimmunoassay
Authors: Lühder Fred , Woltanski Klaus-Peter , Mauch Ludwig , Haubruck Heinz , Kohnert Klaus-Dieter , Rjasanowski Ilona , Michaelis Dietrich , Ziegler Manfred
Published: December 2008

Lühder F, Woltanski K-P, Mauch L, Haubruck H, Kohnert K-D, Rjasanowski I, Michaelis D, Ziegler M. Detection of autoantibodies to the 65-kD isoform of glutamate decarboxylase by radioimmunoassay. Eur J Endocrinol 1994:130:575–80. ISSN 0804–4643

Autoantibodies (AAb) to glutamate decarboxylase (GAD) occur with a high prevalence in sera of newly diagnosed type I (insulin-dependent) diabetic patients. The aim of this study was to establish a GAD-AAb radioimmunoassay using 125I-labelled GAD65 and to evaluate this assay in a cross-sectional study with newly diagnosed type I diabetic patients (diabetes duration < 6 weeks). Furthermore, subjects at high risk of developing type I diabetes and individuals suffering from other autoimmune diseases were examined in this assay. For GAD-AAb detection, 125I-labelled GAD65 was incubated with 10 μl of human serum overnight on ice. Thirty of 51 (59%) type I diabetic patients but none of the 54 healthy blood donors tested were found to be positive. A displacement step using 100 000 g supernatant from rat brain containing or not containing GAD showed the specificity of the binding of 125I-GAD65. Concerning the individuals at high risk of developing diabetes, 9/12 (75%) islet cell antibody (ICA)-positive non-diabetic and 4/34 (12%) ICA-negative subjects with metabolic abnormalities were GAD-AAb positive. These results show the association between type I (insulin-dependent) diabetes mellitus and the occurrence of GAD65-AAb, which possibly predicts a risk of developing the disease.

F Lühder, Department of Immunochemistry, Institute of Diabetes "Gerhardt Katsch", Greifswalder Str. I la, D-17495 Karlsburg, Germany
Effect of octreotide on glucose tolerance in acromegaly
Authors: Koop Brenda L , Harris Alan G , Ezzat Shereen
Published: December 2008

Koop BL, Harris AG. Ezzat S. Effect of octreotide on glucose tolerance in acromegaly. Eur J Endocrinol 1994;130:581–6. ISSN 0804–4643

To determine the effect of the somatostatin analog octreotide on glucose tolerance in acromegaly, we examined glucose profiles, oral glucose tolerance and the insulinogenic index in patients treated with this analog. Ninety patients participated in a long-term, prospective, open-label study. There was no significant change between mean daily blood glucose profiles at baseline or during octreotide treatment. Using glucose tolerance test criteria, 61% of 90 patients had normal baseline glucose tolerance. While on octreotide, 20% and 29% of these patients, respectively, developed impaired glucose tolerance or became frankly diabetic. Conversely, three of the patients who were diabetic at baseline (N = 11) became normal (18%) or developed impaired glucose tolerance (9%) during octreotide therapy. There was no relationship between the dose of octreotide and change in glycemic state. The insulinogenic index (insulin/glucose) response to a glucose challenge decreased uniformly in octreotide-treated patients. Female patients and those with elevated baseline insulin levels were more likely to develop diabetes mellitus during octreotide therapy. In conclusion, octreotide significantly alters glucose tolerance in patients with acromegaly, mandating glucose monitoring during this form of therapy.

Alan G Harris, Division of Clinical Pharmacology, Department of Medicine, Cedars-Sinai Medical Center, 8700 Beverly Blvd., Los Angeles, CA 90048, USA
The degree of inhibition of thyroid follicular cell proliferation by iodide is a highly individual characteristic of each cell and differs profoundly in vitro and in vivo
Authors: Aeschimann Simon , Gerber Hans , von Grünigen Christine , Oestreicher Madeleine , Studer Hugo
Published: December 2008

Aeschimann S, Gerber H, von Grünigen C, Oestreicher M, Studer H. The degree of inhibition of thyroid follicular cell proliferation by iodide is a highly individual characteristic of each cell and differs profoundly in vitro and in vivo. Eur J Endocrinol 1944;130:595–600. ISSN 0804–4643

Pharmacological concentrations of iodide (>1 × 10−6 mol/l) are known to inhibit thyroid follicular cell growth in vitro. However, the inhibitory effect varies widely, depending on experimental conditions, and usually does not exceed 50%. We demonstrate that iodide (10−4 mol/l) inhibits the growth of FRTL-5 cells in different passages by 11–67%. When five subclones of FRTL-5 cells were compared to the wild type, iodide-induced growth inhibition varied between 25% and 46%. The individual degree of inhibition of each clone was reproducible in two subsequent passages, suggesting that it is a stable constitutive trait. When FRTL-5 cells were grown first in three-dimensional clusters and then transplanted onto nude mice with high endogenous thyrotropin secretion, iodide at a serum concentration of less than 5.7 × 10−7 mol/l nearly completely blocked cell replication in the transplants but not in the mice's own thyroid. Five cell lines, prepared from autonomously growing hyperthyroid feline multinodular goiters, were nearly completely resistant to the growth-inhibitory effect of iodide. These observations suggest that the sensitivity towards the growth-inhibiting effect of iodide is a highly variable, stable trait of each thyrocyte, even in cloned cell populations. Some FRTL-5 cells and, even more so, cells prepared from autonomously growing nodular feline goiters are resistant constitutively to the growth-inhibiting effect of iodide. Three-dimensional clusters of FRTL-5 cells growing as transplants in recipient mice are growth-arrested totally by iodide concentrations more than 175 times lower than those partially inhibiting monolayer cultures, while growth of the intact thyroid of the recipient mouse remains unaffected or is even enhanced. Thus, the sensitivity of thyrocytes toward iodide is different fundamentally in vitro and in vivo.

Hugo Studer, Medizinische Universitaetsklinik, Inselspital, CH-3010 Bern, Switzerland
Growth hormone (GH) treatment increases serum insulin-like growth factor binding protein-3, bone isoenzyme alkaline phosphatase and forearm bone mineral content in young adults with GH deficiency of childhood onset
Authors: Juul Anders , Pedersen Søren A , Sørensen Steen , Winkler Kjeld , Jørgensen Jens OL , Christiansen Jens S , Skakkebæk Niels E
Published: December 2008

Juul A, Pedersen SA, Sørensen S, Winkler K, Jørgensen JOL, Christiansen JS, Skakkebæk NE. Growth hormone (GH) treatment increases serum insulin-like growth factor binding protein- bone isoenzyme alkaline phosphatase and forearm bone mineral content in young adults with GH deficiency of childhood onset. Eur J Endocrinol 1994;131:41–9. ISSN 0804–4643

Recent studies have demonstrated that growth hormone (GH)-deficient adults have a markedly decreased bone mineral content compared to healthy adults. However, there are conflicting results regarding the effects of GH treatment on bone mineral content in GH-deficient adults. Therefore, we evaluated the effect of GH treatment on a marker of bone formation (bone alkaline phosphatase), hepatic excretory function and distal forearm bone mineral content in GH-deficient adults. Growth hormone was administered subcutaneously in 21 adults (13 males and 8 females) with GH deficiency of childhood onset for 4 months in a double-blind, placebo-controlled GH trial, while 13 of the patients then received further GH for an additional 14 months. Serum insulin-like growth factor I (IGF-I) increased significantly from 100 to 279 μg/l and IGF binding protein-3 (IGFBP-3) from 1930 to 3355 μg/l after 4 months of GH treatment (p < 0.0001). In addition, the molar ratio between IGF-I and IGFBP-3 increased significantly from 0.22 to 0.33 after GH treatment (p < 0.0001), Bone alkaline phosphatase increased significantly from 38.6 to 92.9 U/l during GH therapy in male patients (p < 0.0001), whereas liver-derived alkaline phosphatase was unaltered by GH. In the females, the increase in bone alkaline phosphatase did not reach statistical significance (19.1 vs 40.0 U/l, p = 0.06). The GH-induced increase in bone alkaline phosphatase correlated significantly with the increase in serum IGFBP-3 (r = 0.46, p = 0.04) but not with the increase in serum IGF-I (p = 0.16). Liver function as assessed by the galactose elimination capacity was within the normal range for healthy adults and did not change after GH treatment. Bone mineral content increased significantly between 7 and 14 months of GH treatment (mean increase in bone mineral content Z score = 0.24 sd/ 7 months), but remained low even after 14 months of GH treatment (Z score = –2.2 ± 0.24 (mean ± sem)). We conclude that GH administration increases serum levels of bone-derived alkaline phosphatase in male patients and has a potentially beneficial impact on bone mineral content in young adults with GH deficiency of childhood onset.

Anders Juul, Department of Growth and Reproduction, Rigshospitalet, Blegdamsvej 9, DK-2100 Copenhagen, Denmark
ACTH-independent massive bilateral adrenal disease (AIMBAD): A subtype of Cushing's syndrome with major diagnostic and therapeutic implications
Authors: Lieberman Steven A , Eccleshall T Ross , Feldman David
Published: December 2008

Lieberman SA, Eccleshall TR, Feldman D. ACTH-independent massive bilateral adrenal disease (AIMBAD): a subtype of Cushing's syndrome with major diagnostic and therapeutic implications. Eur J Endocrinol 1994:131:67–73. ISSN 0804–4643

A 49-year-old man with classic manifestations of Cushing's syndrome had undetectable levels of ACTH, lack of suppression of hypercortisolism with dexamethasone in doses of 2, 8, or 16 mg per day, bilaterally enlarged adrenal glands on MRI, and bilateral adrenal uptake of iodocholesterol. Preoperative treatment with ketoconazole lowered blood pressure and serum cortisol and produced symptoms of steroid withdrawal. Bilateral adrenalectomy revealed massively enlarged adrenal glands (left: 199 g, right: 93 g). Sequencing of the gene encoding the stimulatory G protein, Gsα, did not show either of two activating mutations previously reported in patients with McCune–Albright syndrome or acromegaly. Twenty-three previous cases of Cushing's syndrome due to ACTH-independent massive bilateral adrenal disease (AIMBAD) have been reported. AIMBAD may cause confusion in the differential diagnosis of Cushing's syndrome as endocrine testing suggests a unilateral, ACTHindependent process while adrenal imaging demonstrates bilateral abnormalities. Bilateral adrenalectomy is curative and appears to carry little risk of Nelson's syndrome. The pathogenesis of AIMBAD appears to be heterogeneous, as recent reports have demonstrated GIP-mediated hypercortisolism and familial AIMBAD. Transition from Cushing's disease to ACTH-independence is not supported by the available data. Future cases of AIMBAD should be investigated carefully to further elucidate the pathogenesis of this disorder.

David Feldman, Division of Endocrinology, Dept. of Medicine, Room S-005, Stanford University Medical Center, Stanford, CA 94305, USA
Primary hypothyroidism manifested in childhood with special reference to various types of reversible hypothyroidism
Authors: Okamura Ken , Sato Kaori , Ikenoue Hiroshi , Nakagawa Mizuho , Kuroda Takeo , Yoshinari Mototaka , Fujishima Masatoshi
Published: December 2008

Okamura K, Sato K, Ikenoue H, Nakagawa M, Kuroda T, Yoshinari M, Fujishima M. Primary hypothyroidism manifested in childhood with special reference to various types of reversible hypothyroidism. Eur J Endocrinol 1994;131:131–7. ISSN 0804–4643

The clinical courses of 15 patients with overt primary hypothyroidism manifested in childhood were studied. Nine female patients with goitrous hypothyroidism due to chronic thyroiditis showed almost normal height and became euthyroid spontaneously during iodine restriction. The other 6 non-goitrous patients (3M and 3F) (atrophic thyroiditis in 2, lingual goiter in 2 and probable hypoplastic thyroid in 2) showed physical growth retardation and remained irreversibly hypothyroid requiring replacement therapy. In the reversible group, the characteristic findings were high thyroidal radio-active iodine uptake (58 ± 19%/24 h, N = 8) and positive perchlorate discharge test. Serum non-hormonal iodine levels were high in 4 of 6 patients measured. During the long-term follow-up period of 6 years in 6 patients, 2 patients remained euthyroid with normal growth and regular menstrual cycle and 4 patients became hypothyroid again (after eating seaweed in 1, despite iodine restriction in 2 and after the episode of painless thyroiditis in 1). Transient retardation of growth was observed during the second episode of hypothyroidism. In the irreversible group, one patient with blocking type TSH binding inhibitor immunoglobulin (TBII) became thyrotoxic 4 years later with the decrease in activity of blocking type TBII. These results suggested that reversible recovery of the thyroid function could be expected in patients with juvenile hypothyroidism due to chronic thyroiditis after (1) iodine restriction, (2) improvement of immunological perturbation, or (3) disappearance of blocking type TBII. However, careful follow-up is necessary, because hypothyroidism would recur again with transient retardation of growth in children.

Ken Okamura, Second Department of Internal Medicine, Faculty of Medicine, Kyushu University, 3-1-1 Maidashi, Higashiku, Fukuoka 812, Japan
No evidence for reduced spontaneous or growth-hormone-stimulated serum levels of insulin-like growth factor (IGF)-I, IGF-II or IGF binding protein 3 in women with spinal osteoporosis
Authors: Kassem M , Brixen K , Blum W , Mosekilde L , Eriksen EF
Published: December 2008

Kassem M, Brixen K, Blum W, Mosekilde L, Eriksen EF. No evidence for reduced spontaneous or growth-hormone-stimulated serum levels of insulin-like growth factor (IGF)-I, IGF-II or IGF binding protein 3 in women with spinal osteoporosis. Eur J Endocrinol 1994;131:150–5. ISSN 0804–4643

To test the hypothesis that a dysfunctional growth hormone (GH)–insulin-like growth factor (IGF) axis may play a role in the pathogenesis of osteoporosis, we compared the levels of IGF-I, IGF-II and IGF binding protein 3 (IGFBP-3) in 15 women with spinal osteoporosis (i.e. at least one non-traumatic vertebral fracture) and 15 normal age-matched women. Furthermore, the response to 3 days' treatment with recombinant human GH (r-hGH) (0.2 IU kg−1·day−1) was determined. The basal levels of IGF-I, IGF-II and IGFBP-3 were similar in patients and controls (mean ± sem): IGF-I, 16.5 ± 1.3 versus 16.0 ± 1.3 nmol/l (NS); IGF-II, 79.9 ± 3.6 versus 72.5 ± 4.1 nmol/l (NS); and IGFBP-3, 125.7 ± 6.5 versus 130.3 ± 7.8 nmol/l (NS). Stimulation with r-hGH elicited increased levels of IGF-I, IGF-II and IGFBP-3 within both groups (p < 0.001). The maximal values expressed as a percentage of baseline were: IGF-I, 341 ± 26% versus 369 ± 22%, IGF-II, 125 ± 4% versus 119 ± 5%, IGFBP-3, 141 ± 5% versus 147 ± 7% in osteoporotic patients and controls, respectively. No significant differences were observed between patients and controls in either their maximal response or in the area under the response curves. Our results do not support the hypothesis of a dysfunctional GH–IGF axis in women with spinal osteoporosis.

Kim Brixen, University Department of Endocrinology and Metabolism, Aarhus Amtssygehus, Tage-Hansens gade 2, DK-8000 Aarhus C, Denmark
Corticotrophin-releasing hormone and β-endorphin in labour
Authors: McLean Mark , Thompson David , Zhang Hong-Ping , Brinsmead Max , Smith Roger
Published: December 2008

McLean M, Thompson D, Zhang H-P, Brinsmead M, Smith R. Corticotrophin-releasing hormone and β-endorphin in labour. Eur J Endocrinol 1994;131:167–72. ISSN 0804–4643

The objectives of this study were to determine whether the maternal plasma corticotrophin-releasing hormone (CRH) concentration influences the amount of uterine contractility induced by infused oxytocin during induction of labour, and secondly to assess changes in CRH and β-endorphin in response to stress during labour. Serial plasma CRH and β-endorphin measurements were made in 40 women undergoing induction of labour and correlated with uterine contractility, cervical dilatation, length of labour, analgesic usage and fetal distress. The plasma CRH concentration did not change throughout labour. In subjects receiving infused oxytocin there was a significant positive correlation between plasma CRH and the amount of uterine activity, and a high plasma CRH level was associated with shorter labour. The plasma β-endorphin level rose with progressive cervical dilatation and fell after epidural anaesthesia. The plasma CRH level did not correlate with the plasma β-endorphin level or rise with fetal distress. We conclude that high levels of maternal plasma CRH are associated with an increase in the uterine contractile response to infused oxytocin. The maternal plasma CRH level does not vary in response to maternal or fetal stress, but β-endorphin secretion does rise in response to the stress of labour and is influenced by pain perception.

Mark McLean, Endocrine Unit, John Hunter Hospital, Locked Bag 1, Newcastle Mail Centre, Newcastle, NSW 2310, Australia
Abnormalities in the renin–angiotensin–aldosterone system in normotensive subjects with a positive family history of hypertension
Authors: Herlitz Hans , Widgren Bengt , Wikstrand John , Aurell Mattias
Published: December 2008

Herlitz H, Widgren B, Wikstrand J, Aurell M, Abnormalities in the renin–angiotensin–aldosterone system in normotensive subjects with a positive family history of hypertension. Eur J Endocrinol 1994:131:179–83. ISSN 0804–4643

Non-hypertensive men with a positive family history of hypertension in two generations (N = 16) were compared with weight-matched (N = 13) and lean (N = 12) control groups with a negative family history of hypertension with respect to the activity of the renin–angiotensin–aldosterone system at baseline and during an oral glucose tolerance test. Blood pressure was measured phonographically after 30 min of semirecumbent rest and the oral glucose tolerance test was performed after a 10-h overnight fast with 100 g of glucose given orally. Blood samples were drawn from a peripheral catheter at baseline, 30 and 120 min after the glucose challenge. Systolic and diastolic blood pressures did not differ between subjects with a positive or a negative family history of hypertension. At baseline, blood glucose and plasma insulin were similar in the three groups while the group with a positive family history of hypertension had a significantly lower plasma renin activity (PRA) (0.85 ± 0.09 compared with the weight-matched but not with the lean control group (1.36 ± 0.13 and 1.06 ± 0.15 ng AI·ml−1 · h−1; p < 0.01 and NS, respectively). The PRA increased significantly after the glucose challenge in all groups (p < 0.01), while the plasma aldosterone concentration decreased after 30 min and then showed an increase at 120 min. The PRA response was less pronounced in the group with a positive family history of hypertension compared with the weight-matched and lean control groups (p < 0.05 and p < 0.01, respectively). Serum potassium did not change significantly in either group after the glucose challenge. Urinary sodium excretion was similar in the three groups. In conclusion, non-hypertensive subjects with a positive family history of hypertension are characterized by a lower activity of the renin–angiotensin–aldosterone system at baseline and a diminished PRA response during hyperinsulinemia compared with normotensive individuals without such heredity. Whether this is due to volume expansion or to a tendency to a higher blood pressure remains to be clarified.

Hans Herlitz, Department of Nephrology, Sahlgrenska sjukhuset, S-413 45 Göteborg, Sweden
Association of a nocturnal rise in plasma α-atrial natriuretic peptide and reversed diurnal blood pressure rhythm in hospitalized normotensive subjects with non-insulin dependent diabetes mellitus
Authors: Nakano Shigeru , Uchida Kenzo , Ishii Takashi , Takeuchi Mihoko , Azukizawa Sadahide , Kigoshi Toshikazu , Morimoto Shinpei
Published: December 2008

Nakano S, Uchida K, Ishii T, Takeuchi M, Azukizawa S, Kigoshi T, Morimoto S. Association of a nocturnal rise in plasma alpha-atrial natriuretic peptide and reversed diurnal blood pressure rhythm in hospitalized normotensive subjects with non-insulin dependent diabetes mellitus. Eur J Endocrinol 1994;131:184–90. ISSN 0804–4643

Diurnal changes in plasma atrial natriuretic peptide (ANP), plasma renin activity (PRA) and plasma aldosterone as related to those in blood pressure (BP) were studied under hospital conditions in 18 diabetic subjects without proteinuria and 8 age-matched control subjects. Of 18 diabetic subjects, 10 had a normal diurnal BP rhythm with the peak value in the afternoon (group 1) and 8 had a reversed BP rhythm with the peak value during the night (group 2). Autonomic dysfunction estimated by measuring orthostatic BP and heart-rate changes and beat-to-beat heart-rate variations was more pronounced in group 2 than in group 1. Fasting plasma glucose and HbA1c were similarly high in both diabetic groups. Group 1 showed modestly elevated mean 24-h MBP and plasma ANP levels, modestly low mean 24-h PRA and plasma aldosterone levels, and a lack of diurnal ANP changes similar to that in controls. Group 2 showed markedly elevated mean 24-h BP and plasma ANP levels, markedly low mean 24-h PRA and plasma aldosterone levels, and nocturnal rises in plasma ANP and BP. PRA and plasma aldosterone exhibited circadian rhythms with their peak values found in the early morning in all three groups. The daytime/overnight excretion ratios of sodium and water were normal in group 1 and low in group 2. These results indicate that diurnal changes in plasma ANP, PRA and plasma aldosterone are altered in diabetic subjects with normal and reversed diurnal BP rhythms, predominantly in the latter.

Shigeru Nakano, Division of Endocrinology, Department of Internal Medicine, Kanazawa Medical University, 1-1 Daigaku, Uchinada, Ishikawa 920-02, Japan
Inhibition by rat diazepam-binding inhibitor/acyl-CoA-binding protein of glucose-induced insulin secretion in the rat
Authors: Östenson Claes-Göran , Ahrén Bo , Karlsson Sven , Knudsen Jens , Efendic Suad
Published: December 2008

Östenson C-G, Ahrén B, Karlsson S, Knudsen J, Efendic S. Inhibition by rat diazepam-binding inhibitor/ acyl-CoA-binding protein of glucose-induced insulin secretion in the rat. Eur J Endocrinol 1994;131:201–4. ISSN 0804–4643

Diazepam-binding inhibitor (DBI) has been localized immunohistochemically in many organs. In porcine and rat pancreas, DBI is present in non-B-cells of the pancreatic islets. Porcine peptide also has been shown to suppress insulin secretion from rat pancreas in vitro. Recently, acyl-CoA-binding protein (ACBP) was isolated from rat liver and shown to be identical structurally to DBI isolated from rat brain. Using this rat DBI/ACBP, we have studied its effects on glucose-stimulated insulin secretion in the rat, both in vivo and in isolated pancreatic islets. Infusion iv of rDBI/ACBP (25 pmol/min) during glucose stimulation induced a moderate and transient reduction of plasma insulin levels. Moreover, rDBI/ACBP suppressed insulin release from batch-incubated isolated islets, stimulated by 16.7 mmol/l glucose, by 24% at 10 nmol/l (p < 0.05) and by 40% at 100 nmol/l (p < 0.01). The peptide (100 nmol/l) also inhibited the insulin response to glucose (16.7 mmol/l) from perifused rat islets by 31% (p < 0.05), mainly by affecting the acute-phase response. Finally, incubation of isolated islets in the presence of rDBI/ACBP antiserum (diluted 1:100 and 1:300) augmented the insulin response to 16.7 mmol/l glucose (p < 0.05 or even less). We conclude that rDBI/ACBP, administered iv or added to the incubation media, suppresses insulin secretion in the rat but that the effect is moderate despite the high concentration used. It is therefore unlikely that the peptide modulates islet hormone release, acting as a classical hormone via the circulation. However, the occurrence of DBI/ACBP in the islets and the enhancing effect by the rDBI/ACBP antibodies on glucose-stimulated insulin release suggest that the peptide is a local modulator of insulin secretion.

C-G Östenson, Department of Endocrinology, Karolinska Hospital, S-171 76 Stockholm, Sweden
Effect of growth hormone treatment on insulin secretion and glucose metabolism in prepubertal boys with short stature
Authors: Åman Jan , Rosberg Sten , Albertsson-Wikland Kerstin
Published: December 2008

Aman J. Rosberg S, Albertsson-Wikland K. Effect of growth hormone treatment on insulin secretion and glucose metabolism in prepubertal boys with short stature. Eur Endocrinol 1994;131:246–50. ISSN 0804–4643

The purpose of this study was to evaluate the effect on insulin secretion and glucose metabolism of daily growth hormone (GH) treatment, 0.1 U/kg. for up to 3 years in 42 short prepubertal boys without GH deficiency. Their median height standard deviation (sd) score increased from −2.7 to −1.7, whereas their weight for height sd score was unchanged after 3 years of treatment. Fasting plasma glucose concentrations were unchanged, but median fasting insulin concentrations increased from 6.0 mU/l before treatment to 7.8 mU/l (p < 0.05) after the first year. No further increase was seen during the second or third years. The median insulin area under the curve 10–60 min after an intravenous glucose tolerance test increased from 480 mU·1−1·min−1 before treatment to 799 mU·1−1 · min−1 (p < 0.05) after 1 year. The median glucose disposal rate (K value) before GH treatment, 2.2%/min, was unchanged after 1 year of treatment. A significant positive correlation was found between the change in the height sd score and the change in fasting insulin concentration during the first (r = 0.45; p < 0.01) and second (r = 0.56; p < 0.05) years of GH treatment. It was concluded that GH treatment in prepubertal children without GH deficiency caused a moderate increase in fasting and stimulated insulin concentrations during the first year of treatment. There was no further change during the following years of treatment, and there were no negative effects on fasting plasma glucose concentrations or glucose disposal rates. The increase in insulin concentration was related positively to the growth response.

Jan Åman, Department of Pediatrics, Örebro Medical Centre Hospital, S-701 85 Örebro, Sweden
Beneficial metabolic effects of insulin-like growth factor I in patients with severe insulin-resistant diabetes type A
Authors: Zenobi Peter D , Glatz Yvonne , Keller Annamarie , Graf Susanne , Jaeggi-Groisman Silvia E , Riesen Walter F , Schoenle Eugen J , Froesch E Rudolf
Published: December 2008

Zenobi PD, Glatz Y, Keller A, Graf S, Jaeggi-Groisman SE, Riesen WF, Schoenle EJ, Froesch ER. Beneficial metabolic effects of insulin-like growth factor I in patients with severe insulin-resistant diabetes type A. Eur J Endocrinol 1994;131:251–7. ISSN 0804–4643

Severe insulin resistance type A is due to mutations in the insulin receptor gene and is characterized by glucose intolerance or diabetes mellitus, despite extreme hyperinsulinemia, virilization and acanthosis nigricans. At present, there is no therapy for this condition. Recently, we showed that glucose levels in three such patients are promptly lowered by an iv bolus of recombinant human insulin-like growth factor I (rhIGF-I). In the present study, we investigated two of these rare patients again and determined fasting and postprandial glucose, insulin, C-peptide, proinsulin and lipid levels during five control, five treatment and three wash-out days while on a constant diet. Treatment consisted of 2 × 150 μg rhIGF-I/kg sc per day, which elevated total IGF-I levels 4.5-fold above the control. Fasting glucose levels (days 1–5) in the two patients were 9.6±1.3 and 9.2 ± 1.2 mmol/l, respectively, and fell to 4.4±0.4 and 5.1±0.5 mmol/l on treatment days 8–10. Fasting insulin (2950±450 and 690±125 pmol/l), C-peptide (2217±183 and 1317±235 pmol/l) and proinsulin control levels (125±35 and 66±0 pmol/l) also decreased by ~65% during rhIGH-I treatment, as did the respective postprandial levels. Lipid levels hardly changed at all. In conclusion, IGF-I appears to correct partially some metabolic sequelae of severe insulin resistance and may, hence, be used as a new therapeutic agent.

E Rudolf Froesch, Department of Internal Medicine, University Hospital, Rämistrasse 100, 8091 Zurich, Switzerland