bluuebunny/crossref_metadata_2025 huggingface dataset:
Measurement of plasma free and total growth hormone concentrations in patients with growth hormone antibodies developed in response to therapy
Authors: Demura R. , Ishiwatari N. , Nomuar T. , Demura H. , Shizume K. , Okuno A. , Sanayama K. , Fujieda K.
Published: December 2008

Abstract. Recombinant human growth hormone is more antigenic than pituitary preparations. Since GH antibodies interfere with radioimmunoassay of GH, we measured plasma free and total GH in patients with pituitary dwarfism with GH antibodies during treatment with a recombinant methionyl GH preparation. Plasma free GH was measured in the supernatant after polyethylene glycol precipitation. Total GH was measured after extracting plasma with acid-ethanol. In normal subjects, both free and total GH levels were similar to those measured in plasma by a direct conventional RIA. Peak free GH levels after administration of 4 IU methionyl GH to 3 normal subjects were 38.0,30.7 and 13.2 μg/l, values similar to those measured in most of the patients with GH antibodies. All values were undetectable in one patient with a very high antibody titre. Total GH levels were similar to free GH levels in normal subjects. In patients with GH antibodies, total GH levels were high compared with their free levels, but similar to those assayed by conventional RIA. The patient with the highest antibody titre had total GH levels which were the lowest of those observed in the patients with GH antibodies in spite of having the highest GH levels measured by conventional RIA. The antibody in this particular case may have a high capacity and a high affinity. A relatively poor growth rate in this patient may be associated with the finding of undetectable free GH levels. Measurement of plasma free and total GH may be of value in examining GH dynamics and their relation to the clinical effectiveness of GH treatment in patients with GH antibodies.
Inhibition of binding of gonadal steroids to serum binding proteins by non-esterified fatty acids: the influence of chain length and degree of unsaturation
Authors: Street C. , Howell R. J. S. , Perry L. , Al-Othman S. , Chard T.
Published: December 2008

Abstract. The effect of non-esterified fatty acids (NEFA) on the in vitro binding of testosterone, 5-alpha dihydrotestosterone and estradiol E2 to sex hormone binding globulin (SHBG) was examined using pooled normal female serum, and SHBG and albumin fractions obtained from the partial purification of late pregnancy serum. A range of saturated and unsaturated fatty acids were examined for their effect on steroid-protein binding. In normal female serum, NEFA added at physiological concentrations disrupted steroid-protein binding. The shorter chain (C8–C12) saturated acids and the poly-unsaturated acids proved to be more effective inhibitors than the longer chain saturated or mono-unsaturated acids. The greatest inhibition was obtained with E2 whereas the binding of dihydrotestosterone was least affected. With partially purified SHBG, the same concentrations of NEFA were less effective at inhibiting the binding of dihydrotestosterone and testosterone but elicited the same effect with E2. The binding of steroids to albumin appeared to be unaffected by these concentrations of NEFA.
Increases in testosterone secretion in adult rams with immunoneutralization of endogenous estradiol occur in the absence of increases in pulsatile LH release or testicular LH receptors
Authors: Sanford Lee M.
Published: December 2008

Abstract. The testes of the ram become more responsive to LH stimulation following immunoneutralization of endogenous estradiol. The possibility that testosterone secretion is facilitated by increased LH-binding activity in the testes was investigated in the present study conducted with adult Dorset × Leicester × Suffolk rams during the time of testicular recrudescence. Patterns of episodic LH release and testosterone secretion (days –5, 10 and 24) and LH-binding activity in testicular biopsy samples (days –1, 14 and 28) were assessed on the days indicated relative to the onset of passive immunization and the establishment of relatively low titres (~1:200) of estradiol antiserum. During the experimental period, mean serum testosterone concentration increased by approximately 150% for the immunized rams as basal concentration and pulse amplitude increased, while all characteristics of testosterone secretion remained unchanged for the nonimmunized rams. Characteristics of LH release and the concentration of LH-binding sites in the testes, however, were always similar for both groups of rams. Further, group differences in FSH and PRL secretion and in the concentration of testicular FSH-binding sites did not occur. These results provide evidence for an estradiol direct (gonadotropin independent) negativefeedback component in the regulation of Leydig cell function in the ram.
Continuous subcutaneous octreotide infusion markedly suppresses IGF-I levels whilst only partially suppressing GH secretion in diabetics with retinopathy
Authors: Hyer S. L. , Sharp P. S. , Brooks R. A. , Burrin J. M. , Kohner E. M.
Published: December 2008

Abstract. The response to GH releasing hormone (GHRH 1–29) and 24-h serum GH and IGF-I levels were measured in 9 insulin-dependent diabetics with retinopathy and 6 normal volunteers before and after different treatment regimens with octreotide, a long-acting somatostatin analogue. Octreotide, 50 μg by sc injection, completely suppressed GHRH-stimulated GH release in both groups. Thrice daily sc injections for up to 20 weeks were associated with variable plasma octreotide levels and failed completely to suppress GH secretion in either the patients or the normal controls. Three days of continuous sc pump infusion (500 μg/24-h) resulted in consistently high plasma octreotide levels and completely suppressed 24-h GH in 4 normal subjects, whilst treatment for up to 16 weeks only partially suppressed GH levels in 6 patients (AUC mU · l−1 · h−1;h 209 ± 81 vs 121 ± 82; P=0.01). Mean ± sd IGF-I levels (μg/l) in the patients (but not controls) were suppressed into the hypopituitary range by median 6 weeks (range 2–16) pump administration (203 ± 62 vs 60 ± 25; P= 0.02). Pump treatment achieved total GH suppression in normal subjects; diabetics with retinopathy seem more resistant to the GH suppressing effects of the drug. However, the reduction of serum IGF-I with prolonged treatment may be of clinical value in arresting the progress of diabetic retinopathy.
Epitope mapping of human thyrotropin
Authors: Endo Yuichi , Miyai Kiyoshi , Iijima Yasushi , Nakajima Toshihiro , Eda Yasuyuki , Fujita Haruo , Unoki Masanori
Published: December 2008

Abstract. Epitope mapping of hTSH was carried out using 19 monoclonal antibodies prepared with hTSH or its β-subunit as antigen. The affinity constants of the monoclonal antibodies ranged from 9.6 × 107 to 5.7 × 109 mol/l for hTSH. The binding activities of monoclonal antibodies were maintained or in some cases rather enhanced after removal of the sugar moeity of the subunits of hTSH, and completely diminished after reduction of intramolecular S-S bonds in the subunits of hTSH. Ten monoclonal antibodies recognized the epitopes on hTSH (α:β subunit combined form) and on free α-subunit form. Eight other antibodies recognized the epitopes on free/or combined form of β-subunit, all of which did not recognize any other human glycoprotein hormones. The monoclonal antibodies directed against the α-subunit could bind also other human glycoprotein hormones to a varying extent. On the basis of results from competitive binding studies, the antibodies directed against α-subunit and those against β-subunit were each classified into five subgroups recognizing different antigenic determinants. The remaining one antibody recognized an epitope expressed only by hTSH and not by the free subunits. In addition, a positive cooperativity on the binding of hTSH was observed between monoclonal antibodies directed towards a particular epitope on the α-subunit and those towards an epitope on the β-subunit. From these data, two-dimensional map of epitopes on hTSH was constructed. The epitopes on each subunit were found to form a cluster with complicated overlapping, suggesting a highly conformational structure.
Serum calcitonin levels in anesthetized rats
Authors: Feinstein Ricardo E. , Bucht Elisabet , Grimelius Lars , Iwarsson Krister , Rönnbäck Curt , Sjöberg Hans-Erik
Published: December 2008

Abstract. In order to determine whether a short period of general anesthesia influences the levels of serum calcitonin (CTs) and whole blood ionized Ca2+ and pH, 10 rats were sequentially anesthetized at 5-day intervals by halothane, ether, or CO2/O2, respectively, and retroorbital blood samples were collected during anesthesia. We noticed significant differences of serum calcitonin but the role of the anesthetics remains unclear, since other factors also could have accounted for the observed variations. Blood pH was strongly decreased by CO2/O2. Whole blood ionized calcium exhibited marked changes, but no correlation was found between whole blood ionized calcium and serum calcitonin.
Resistant hyperthyroidism induced by sodium iopodate used as treatment for Graves' disease
Authors: Caldwell G. , Errington M. , Toft A. D.
Published: December 2008

Abstract. Sodium iopodate has recently been advocated for long-term control of hyperthyroidism in Graves' disease. Its advantages over conventional therapy are a rapid fall in thyroid hormones and control of symptoms with a simple dosage regime. We report a case in which severe resistant hyperthyroidism developed during treatment of Graves' disease with sodium iopodate. Sodium iopodate may not be suitable for long-term use in all patients with Graves' disease.
Presence of androgen receptors in the hen hypothalamus and pituitary
Authors: Kawashima Mitsuo , Kamiyoshi Michiharu , Tanaka Katuhide
Published: December 2008

Abstract. Soluble and insoluble fractions in a hypotonic buffer solution of hypothalamic-preoptic and median eminence areas, and of the anterior pituitary of the hen were found to contain a specific androgen binding component having the properties of a receptor. Administration of testosterone in vivo caused a marked decrease in specific [3H]R1881 (a synthetic androgen) bindings in the soluble fraction with a concomitant increase in the bindings in the insoluble fraction, whereas the sum of the bindings did not change. A similar relationship between the bindings of the two fractions was also observed during an ovulatory cycle. The results may provide an evidence for a direct action of androgens on the hen hypothalamus and pituitary.
Immunoreactive oxytocin and vasopressin in the non-pregnant human uterus and oviductal isthmus
Authors: Lundin S. , Forman A. , Rechberger Thomasz , Svane D. , Andersson K. E.
Published: December 2008

Abstract. The regional distribution of immunoreactive OT and AVP in the human uterus was investigated. Specimens of non-pregnant human uterus and oviduct were homogenized and extracted. The tissue levels exceeded the plasma concentrations of the peptides. The largest quantities of both peptides were found in the cervix and oviductal isthmus. The amounts found in the uterine fundus and isthmus were, however, not significantly different. Only 23% of immunoreactive OT eluted in the position of standard peptide on high-performance liquid chromatography. All immunoreactive AVP eluted with standard AVP after additional ether extraction of octadecasilyl extracts. We conclude that the human uterus contains materials immunologically and chromatographically identical to oxytocin and vasopressin.
Effects of gastrin-releasing peptide on basal and stimulated thyroid hormone secretion in the mouse
Authors: Ahrén Bo
Published: December 2008

Abstract. Recently, gastrin releasing peptide (GRP) was demonstrated to occur within normal thyroidal C cells. In the present study, the effects of GRP on basal and stimulated thyroid hormone secretion were investigated in the mouse according to the McKenzie technique. Iodine-deficient mice were pretreated with 125I and thyroxine. GRP was found dose-dependently to increase the basal radioiodine levels after iv injection, reflecting a stimulation of basal thyroid hormone secretion. The effect was maximal at a dose level of 3.0 nmol/animal, and at 2 h after injection, when GRP had increased blood radioiodine levels to 152 ± 8% compared with 96 ± 5% in controls (P< 0.001). GRP seemed to exert additive effects on thyroid hormone secretion with vasoactive intestinal peptide and with TSH at a threshold dose level. In contrast, GRP did not influence the stimulatory effects of either a half-maximal dose level of TSH or noradrenaline. Furthermore, neither L-propranolol nor methylatropine influenced the GRP-induced thyroid hormone secretion. It is concluded that GRP has the capacity to stimulate basal thyroid hormone secretion in the mouse.
Sex hormones and sex hormone binding globulin in males with compensated and decompensated cirrhosis of the liver
Authors: De Besi L. , Zucchetta P. , Zotti S. , Mastrogiacomo I.
Published: December 2008

Abstract. The present work investigates the sex hormone profiles in 50 male patients with liver cirrhosis of different etiology according to the degree of liver dysfunction. The only hormonal impairment in well-compensated cirrhotics (group A) was an increase in mean serum concentrations of estrone, androstenedione, and sex hormone binding globulin. In decompensated cirrhotic patients with ascites (group B), low mean levels of total and free testosterone were found along with normal gonadotropins mean levels. Estrone and androstenedione levels were still elevated, whereas sex hormone binding globulin levels were not different from controls. In decompensated cirrhotics patients with encephalopathy (group C), total and free testosterone mean levels were lower than in group B, and LH mean levels were elevated; estrone levels were markedly high, but androstenedione levels were subnormal; sex hormone binding globulin concentrations were again not different from controls. The few patients with high prolactin levels belonged primarily to this group. Estradiol mean levels were not significantly elevated in any of the groups. It is concluded that the various hormonal patterns of gonadal failure and of the impairment of steroid metabolism and transport, observed in cirrhosis, can be attributed to the degree of liver dysfunction.
A new pituitary protein 7B2 is increased in patients with high α- or β-hCG
Authors: Leonhardt U. , Eriksson B. , Oberg K. , Wide L. , Ghatei M. A. , Bloom S. R.
Published: December 2008

Abstract. The presence of 7B2 (a 180 amino acid peptide first extracted from the porcine pituitary) was investigated by a specific radioimmunoassay and gel filtration chromatography in the plasma of three groups of patients known to have increased levels of α- and β-hCG subunits. Plasma 7B2 immunoreactive equivalents (7B2-IE) were increased in postmenopausal women (range 67–143 pmol/l, median: 94 pmol/l, N = 20, P< 0.05), in patients with Klinefelter's syndrome (range 195-230 pmol/l), median 213 pmol/l, N = 4, P< 0.01) and in 17 patients with malignant endocrine gastrointestinal tumours (range 66–20 000 pmol/l, N = 32) compared with healthy controls (range 23.6–98.2 pmol/l, median 41.5 pmol/l, N = 40). Tumour tissue from 4 patients with endocrine pancreatic tumours had significantly higher 7B2-IE concentrations than normal pancreatic tissue, with the highest concentration in an insulinoma (449 pmol/g, normal: 28 pmol/g). During therapy almost parallel changes in plasma 7B2 and other hormones were noted and 7B2-IE therefore might be an additional marker for cancers of the APUD system.
Anti-goat immunoglobulin antibodies in diabetic children at diagnosis and follow-up: comparison with islet cell antibodies and other autoantibodies
Authors: Di Mario U. , Crisa L. , Anastasi E. , Contreas G. , Andreani D. , Raponi M. P. , Napoleone E. , Candela A. , Vela M. , Campea L.
Published: December 2008

Abstract. The presence of antibodies reacting with human as well as animal immunoglobulins in sera from recent onset Type I diabetic patients has been recently demonstrated by some of our group. In the present study, the occurrence of these antibodies has been evaluated in sera from 19 Type I diabetic patients, at diagnosis and at follow-up within three years, and from 26 normal subjects, and has also been compared with the presence of islet cell antibodies and other organ-specific autoantibodies. A solid-phase radioimmunoassay has been used: serum was incubated in goat immunoglobulin-coated wells and the binding of 125-I-anti-human immunoglobulin antibodies was evaluated. Anti-goat immunoglobulin antibodies were above the 90th percentile of normal values in all diabetic patients at diagnosis (median, interquartile range, in μg 125I-antibody bound/1 serum: 83, 77.5–88, versus 51.5, 44.5–62 in normal subjects, P < 0.001) and significantly declined with time after diagnosis (P < 0.001). Islet cell antibodies were present in 79% of patients at diagnosis, whereas at least one other auto-antibody was found in 21% of patients. In the follow-up study the decline in anti-goat immunoglobulin antibody levels was different from that of islet cell antibody positivity. A circulating immunoglobulin reacting with other immunoglobulins is thus present in the early stages of Type I diabetes and may well play a part in the complex immunopathogenetic interactions.
Parathyroid hormone stimulates prostanoid formation in mouse calvarial bones
Authors: Ljunggren Östen , Lerner Ulf H.
Published: December 2008

Abstract. Bovine parathyroid hormone (bPTH 1–34) caused a time- and dose-dependent enhanced formation of the two prostanoids PGE2 and 6-keto-PGF1α in cultured neonatal mouse calvarial bones, with threshold for action at 0.1 nmol/l. The PGE2 response to PTH was completely blocked by indomethacin, but insensitive to calcitonin. By contrast, indomethacin was without effect on 45Ca release induced by PTH. The PTH analogues (Nle 8, 18, Tyr 34)-bPTH (3–34) amide and (Tyr 34)-bPTH (7–34) amide, which are putative PTH antagonists, did not affect basal production of PGE2, nor did the analogues affect bPTH 1–34 induced PGE2 formation. The data show that PTH stimulates prostanoid formation in mouse bone cells and that this response is not directly linked to PTH-induced bone resorption.
Elevated angiotensin II and vasopressin in primary hyperparathyroidism. Angiotensin II infusion studies before and after removal of the parathyroid adenoma
Authors: Jespersen B. , Pedersen E. B. , Charles P. , Danielsen H. , Juhl H.
Published: December 2008

Abstract. In order to evaluate the role of calcium metabolism in blood pressure regulation, 15 patients with primary hyperparathyroidism and 9 healthy control subjects were studied before and during angiotensin II infusion. The patients were re-investigated 2–5 months after removal of the parathyroid adenoma. Blood pressure, plasma levels of angiotensin II, aldosterone, arginine vasopressin, and atrial natriuretic peptide, and creatinine clearance were determined. Blood pressure and the blood pressure response to angiotensin II infusion were both the same before and after the operation. Angiotensin II and arginine vasopressin during basal conditions were significantly higher before than after the operation (angiotensin II: 17 (median) to 10 pmol/l, P < 0.02; arginine vasopressin: 2.9 to 1.9 pmol/l, P < 0.01), whereas aldosterone, atrial natriuretic peptide, and creatinine clearance were unchanged. During angiotensin II infusion, aldosterone, arginine vasopressin, and atrial natriuretic peptide increased to approximately the same levels before and after the operation. Blood pressure was not correlated to any of the hormones measured. Thus, patients with primary hyperparathyroidism have elevated plasma levels of angiotensin II and arginine vasopressin which may be compensatory phenomena counteracting volume depletion owing to a decreased renal concentrating ability induced by hypercalcemia, and owing to PTH-induced inhibition of renal sodium reabsorption.
Effects of repetitive administration of thyrotropin-releasing hormone at short intervals in acromegaly
Authors: Losa Marco , Alba-Roth Julia , Sobieszczyk Sylwester , Schopohl Jochen , Müller O. Albrecht , von Werder Klaus
Published: December 2008

Abstract. We investigated the pattern of GH secretion in response to repetitive TRH administration in patients with active acromegaly and in normal subjects. Nine acromegalic patients and 10 normal subjects received three doses of 200 μg of TRH iv at 90-min intervals. There was a marked serum GH rise in acromegalic patients after each TRH dose (net incremental area under the curve [nAUC]: first dose = 4448 ± 1635 μg · min · 1−1; second dose = 3647 ± 1645 μg · min · 1−1; third dose = 4497 ± 2416 μg · min · 1−1; NS), though individual GH responses were very variable. In normal subjects TRH did not elicit GH secretion even after repeated stimulation. Each TRH administration stimulated PRL release in acromegalic patients, though the nAUC of PRL was significantly higher after the first (1260 ± 249 μg · min · 1−1) than after the second and the third TRH administration (478 ± 195 and 615 ± 117 μg · min · 1−1, respectively; P < 0.01). In normal subjects too, PRL secretion was lower after repeated stimulation (first dose = 1712 ± 438 μg · min · 1−1; second dose = 797 ± 177 μg · min · 1−1; third dose = 903 ± 229 μg · min · 1−1 P < 0.01), though different kinetics of PRL secretion were evident, when compared with acromegalic patients. TSH secretion, assessed in only 4 patients, was stimulated after each TRH dose, though a minimal but significant reduction of nAUC of TSH after repeated TRH challenge occurred. Both T3 and T4 increased steadily in the 4 patients. The same pattern of TSH, T3, and T4 secretion occurred in normal subjects. Our study demonstrates that repetitive TRH administration in acromegalic patients leads to similar, but individually heterogeneous GH responses. A qualitative difference in PRL responsiveness occurred in acromegalic patients compared with normal subjects, whereas TSH, T3, and T4 secretion was qualitatively and quantitatively similar in both groups.
Gonadotropin therapy of female infertility
Authors: Dale Per Olav , Tanbo Tom , Henriksen Tore , Magnus Øystein , Åbyholm Thomas
Published: December 2008

Abstract. Anovulatory infertility in 134 women was treated with gonadotropins for a total of 318 cycles. The patients were classified into WHO group I, hypothalamic-pituitary failure (72 patients), and WHO group II, hypothalamic-pituitary dysfunction (62 patients). All patients in this group had failed to achieve pregnancy with clomiphene citrate therapy in repeated cycles. The pregnancy rate in group I was 72.2% vs 17.7% in group II. The 'take home' baby rate was 57.1% in group I vs 13.1% in group II. The rate of miscarriages was 14.3% without any significant difference between the groups. Multiple pregnancies occurred only in group I patients (19.2%). The conception rate was highest in the first four cycles, whereas no patient became pregnant after the sixth treatment cycle. Ovarian hyperstimulation syndrome occurred most frequently in group II patients, however, overall only 2.2% of the patients needed hospitalization because of hyperstimulation. Gonadotropin therapy must be considered an efficient and successful treatment of infertility in patients with hypothalamic-pituitary failure, whereas the success rate is rather poor in patients with hypothalamic-pituitary dysfunction.
Final height of patients with idiopathic growth hormone deficiency after long-term growth hormone treatment
Authors: Hibi Itsuro , Tanaka Toshiaki , _ _
Published: December 2008

Abstract. One hundred and 8 patients with idiopathic growth hormone deficiency with spontaneous pubertal maturation (group A), were followed until they reached their final height after hGH treatment lasting between 2 and 11.1 (average 5.5) years. Their standard deviation scores of final height averaged 3.3 sd below the population mean, which was significantly lower than 1.1 standard deviation below the mean in 29 GH deficient patients without spontaneous puberty (group B) who were treated with hGH and sex hormones. The presence of gonadal function was found to be unbeneficial for final height. The final height of the patients in both groups was not related to either 1) age at the start of hGH treatment, 2) age at the onset of puberty, or 3) the duration of hGH treatment. It was, however, significantly related to the standard deviation score of height at the start of hGH treatment in both groups and to that of height at the onset of puberty in group A. The findings demonstrated that earlier introduction of hGH treatment resulted in earlier onset of puberty in group A, because the chronological age at the onset of puberty was positively correlated to the chronological age at the start of hGH treatment. It was also confirmed that the later puberty began, the taller the final height in GH deficient patients who had the same degree of standard deviation score of height for chronological age before puberty.
Regulation of uterine insulin-like growth factor I mRNA and insulin-like growth factor II mRNA by estrogen in the rat
Authors: Norstedt Gunnar , Levinovitz Agneta , Eriksson Håkan
Published: December 2008

Abstract. IGF-I and IGF-II are peptides with mitogenic properties. In this study mRNA for IGF-I and IGF-II was analysed in rat uterine tissue after different endocrine manipulations and the possibility of an estrogenic regulation of IGF expression was investigated. Both IGF-I and IGF-II mRNA were present in uterine tissue. The level of IGF-I mRNA, but not IGF-II mRNA, was reduced following ovariectomy. Administration of estradiol (2.5 μg/day for 4 days) to ovariectomized rats increased IGF-I mRNA 8-fold to levels seen in intact animals. In adult animals hepatic IGF-I mRNA did not appear to be increased by estrogen treatment. Low levels of IGF-II mRNA were detected in the uterus, but showed no dependence on estrogen. The inductive effect of estrogen on uterine IGF-I mRNA could not be substituted for by growth hormone administration (0.5 mg/100 g, ip for 6 h). The present results suggest IGF-I as a potential candidate for a mediator of estrogen-induced growth. Both estrogen and GH induce IGF-I mRNA and a tissue specificity for these hormones is indicated where GH regulates hepatic and estrogen uterine IGF-I mRNA.
Growth hormone stimulates the growth of mouse neonatal condylar cartilage in vitro
Authors: Maor Gila , Hochberg Zeev , Silbermann Michael
Published: December 2008

Abstract. This study used an organ culture system of neonatal condylar cartilage to study the in vitro effects of recombinant human growth hormone on the growth of cartilage and its inherent cell populations: progenitor cells, chondroblasts and early hypertrophic chondrocytes. Growth hormone at a dose of 2.5 nmol/l enhanced the overall growth of cartilage explant and stimulated the differentiation of its cells. Hence, growth hormonetreated explants revealed a substantial increase in the number of chondroblasts and young hypertrophic chondrocytes. Along with its effects upon cartilage the hormone also stimulated new bone formation adjacent to mineralized hypertrophic chondrocytes. These results provide support to the notion that growth hormone stimulates cartilage growth which in turn is followed by endochondral ossification. In spite of its in vitro effect it is not as yet clear whether the effect of growth hormone is indeed a direct one or is mediated via the local production of IGF-I.
Decrease of serum sex hormone-binding globulin as a marker of androgen sensitivity. Correlation with clinical response
Authors: Ciaccio Marta , Rivarola Marco , Belgorosky Alicia
Published: December 2008

Abstract. An evaluation of the usefulness of determining the decrease in serum sex hormone-binding globulin after exogenous testosterone was studied in 55 prepubertal patients with ambiguous external genitalia or micropenis. The biochemical response (androgen sensitivity test) was compared with the clinical response as judged by signs of androgen stimulation of external genitalia. Patients were divided in two groups according to age. Group I, 11 patients younger than 3 months and Group II, 44 patients older than 3 months. Only in 54% of Group I was there a correlation between the androgen sensitivity test and the clinical response to androgens in either a positive (4 patients) or negative sense (2 patients). On the other hand, the androgen sensitivity test and the clinical response to androgens correlated in 91% of the patients of Group II in either a positive (35 patients) or negative sense (5 patients). Two of the 4 patients with lacking correlation had a negative androgen sensitivity test and micropenis secondary to pituitary deficiency. It is concluded that in prepubertal patients older than 3 months with abnormalities of sex differentiation, the androgen sensitivity test and the clinical response to androgens are useful for evaluating androgen sensitivity. The clinical response to androgens is useful in early life when a positive response is found.
The management of differentiated thyroid cancer in Europe in 1988.
Authors: Baldet Line , Manderscheid Jean-Claude , Glinoer Daniel , Jaffiol Claude , Coste-Seignovert Béatrice , Percheron Christine
Published: December 2008

Abstract. In order to know how thyroid nodules and differentiated thyroid cancers are investigated and treated in 1988, an international inquiry was performed by mean of a questionnaire based on a well-defined case report of a 35-year-old female with a solitary small thyroid nodule. Clinicians were asked to indicate their diagnostic and therapeutic approaches to the reported case and to some variations. Analysis of the 157 responses from thyroid experts showed that three in vitro tests (sensitive-TSH, free T4 and total T4) and three in vivo tests (99mTc or radioiodide scintiscan, fine needle aspiration and ultrasonography) were performed most frequently. In the case of a solid and cold nodule and in the absence of fine needle aspiration results, 19% of respondents advocated suppressive therapy and 81% surgery. In the same clinical case, but whom fine needle aspiration had been performed and cytology was benign, surgery was advocated by 24%, suppressive therapy by 48% and a regular follow-up without treatment by 28% of respondents. When surgery was performed and the diagnosis was a differentiated thyroid cancer, (near) total thyroidectomy was more frequently chosen than partial thyroidectomy in both papillary (60 and 40%, respectively, of respondents) and follicular (74 and 26%, respectively, of respondents) cancers; 80% of clinicians did not change their surgical technique in relation to histological type of the tumour. Total thyroidectomy was more often recommended in most of the clinical or anatomical variations compared with the basic case report. Pre- or postoperative hormonal therapy was initiated with L-T4 and TSH suppression was controlled by sensitive-TSH and thyroglobulin determinations. After total thyroidectomy, 131I was used with similar modalities for papillary and follicular cancers to ablate a thyroid remnant.
Urinary orosomucoid excretion rate in patients with non-insulin-dependent diabetes mellitus
Authors: Ito Seiki , Tsuda Akiko , Momotsu Takeshi , Igarashi Kazumasa , Kasahara Shin , Satoh Koozi , Shibata Akira
Published: December 2008

Abstract. Urinary excretion rate and clearance of α1-acid glycoprotein (orosomucoid), a major serum glycoprotein which is more anionic (pI 2.7) than albumin (pI 4.7) were measured by RIA in timed overnight urine samples from non-insulin-dependent diabetic patients with different urinary albumin excretion rate and from healthy controls. The 50th percentiles of urinary orosomucoid excretion rate in patients with normo-, micro-, and macroalbuminuria were larger than those in healthy controls. Urinary excretion rate and clearance of orosomucoid increased in parallel with increase in albumin excretion rate in diabetic patients with an albumin excretion rate of more than 10 μg/min. On the basis of their levels of urinary orosomucoid excretion, patients with normoalbuminuria of less than 10 μg/min could be divided into two groups, one with a normal and the other with an elevated urinary orosomucoid excretion rate. The findings suggest that kidneys of diabetic patients with an albumin excretion rate of more than 10 μg/min are unable to distinguish the difference in pI between albumin and orosomucoid, and that a subgroup with an elevated orosomucoid excretion rate may be present among diabetics with normoalbuminuria.
Insulin-like growth factor I and daily growth hormone profile in the assessment of active acromegaly
Authors: Barreca Antonina , Ciccarelli Enrica , Minuto Francesco , Bruzzi Paolo , Giordano Giulio , Camanni Franco
Published: December 2008

Abstract. A poor correlation exists between growth hormone levels and the severity of disease in patients with acromegaly. It has been suggested that insulin-like growth factor I correlates better with the clinical condition than GH itself, but the presence of a correlation between GH and IGF-I is still a matter of debate. We therefore studied the fasting concentration of acid-extracted IGF-I and the daily GH profile (at 08.00, 12.00, 16.00, 20.00 h) in 28 acromegalic patients, both in basal condition and at different times after treatment. All patients studied before treatment exhibited a GH mean daily concentration always above 5 μg/l (range 5.15–147 μg/l), and IGF-I values (1.99–6.85 U/l) always above the normal range (0.38–1.90 U/l). During the follow-up after medical, surgical or radiation therapy we did not observe normalization of the IGF-I concentration for a GH day curve value above 5 μg/l. Compared with the GH day curve, a single morning GH value was slightly less sensitive and definitely less specific. The analysis of covariance evidenced a good correlation (P< 0.001) between the GH day curve and IGF-I concentration during the first 6 months of medical as well as during the first year of radiation therapy, and after surgical treatment. Our data indicate that a single determination of acid-extractable IGF-I is as reliable as GH multiple sampling to assess the acromegalic disease activity.
Estrogen stimulates gonadotropin-releasing hormone release from rat hypothalamus independently through catecholamine and histamine in vitro
Authors: Ohtsuka Shirou , Nishizaki Takamichi , Tasaka Keiichi , Miyake Akira , Tanizawa Osamu , Yamatodani Atsushi , Wada Hiroshi
Published: December 2008

Abstract. Estradiol is known to stimulate gonadotropin-releasing hormone release from the rat mediobasal hypothalamus. Studies were made in an in vitro perifusion system on whether catecholamine and/or histamine was involved in estradiol-induced GnRH release. Normal cycling female rats were decapitated in diestrus II and their medio-basal hypothalami were combined and, perifused with Earl's balanced salt solution containing 0.01% bovine serum albumin bubbled with 95% O2 and 5% CO2. The levels of norepinephrine, dopamine, and histamine and of GnRH in the effluent were measured by HPLC and radioimmunoassay, respectively. Administration of 10−6 mol/l estradiol resulted in releases of norepinephrine, dopamine, histamine and GnRH at levels of 98, 70, 91 and 288%, respectively, of initial values. Administration of 10−6 mol/l norepinephrine or dopamine resulted in no increase in histamine release, and administration of 10−6 mol/l histamine did not increase release of norepinephrine or dopamine. These data suggest that estradiol stimulates the releases of GnRH, catecholamine and histamine from the rat medio-basal hypothalamus, and that it increases GnRH release independently through catecholamine and histamine. As we found previously that norepinephrine or histamine stimulates GnRH release from the mediobasal hypothalamus, we conclude that estradiol stimulates releases of norepinephrine and histamine, resulting in GnRH release from the medio-basal hypothalamus.
Acute administration of alpha-melanotropin exerts a stimulatory control on puberty
Authors: Durando Patricia , Ferreira Adriana , Celis María Ester
Published: December 2008

Abstract. The present experiments were undertaken to throw light on the physiological role played by α-MSH in the advent of female puberty. The serum and pituitary α-MSH concentrations were determined in prepubertal rats 5, 15, 25, 30, 33 days old and at vaginal opening. The serum levels showed a significant increase on day 30 and the pituitary α-MSH levels increased steadily from day 5 to day 33. To determine if a relation exists between the increase in α-MSH levels and the peak of LH prior to vaginal opening, prepubertal rats of the same age range as above received an injection of α-MSH or saline solution and were sacrificed 30 min later. The peptide increased LH serum levels only at 30 days of age. To examine the hypothesis that α-MSH was involved in determining the timing of puberty, prepubertal rats pretreated with estradiol benzoate received an injection of α-MSH or saline solution on day 28. This treatment advanced the time of vaginal opening by 2 days in the experimental animals. With the same experimental procedure, an increase in serum levels of LH and progesterone was also observed at 29 days of age. The action of α-MSH on GnRH was analysed by incubating median eminence from prepubertal rats 20, 25 and 30 days of age, with the peptide. α-MSH increased GnRH release only in 25-day-old rats. The above results show that acute treatment with α-MSH induces modifications in the hormones related to puberty and hence allows us to include α-MSH in the chain of neuroendocrine events involved in reproductive maturation.
The hidden, nonexchangeable pool of 3,5,3'-triiodothyronine and 3,3',5'-triiodothyronine in man: does it exist?
Authors: Faber Jens , Kirkegaard Carsten , Jørgensen Bo , Kludt Jørgen
Published: December 2008

Abstract. The validity of estimation of the production rates of T3 and rT3 in man based on noncompartmental analysis of blood-derived data has been questioned owing to incomplete exchangeability of T3 and rT3 between plasma and extrathyroidal tissues in which a local production of these iodothyronines takes place. The possible existence of a nonexchangeable or hidden pool of T3 and rT3 would result in an underestimation of the daily production. By contrast, the production rate of T4 can be estimated reliably using noncompartmental analysis. We have studied 16 women with pretreatment severe hypothyroidism on constant levothyroxine therapy. Simultaneous measurements of T4, T3 and rT3 production rates were performed using bolus injection of radiolabelled iodothyronines. The tracers were isolated from plasma using gel separation/antibody extraction, and production rates were calculated by noncompartmental analysis. Mean (± sd) production rate of T4, T3 and rT3 were: 119 ± 43, 40.0 ± 22.0 and 54.9 ± 20.0 nmol · day−1 · (70 kg)−1, respectively. Thus 79.5 ± 7.0% of T4 was deiodinated into T3 and rT3. This leaves 20.5% to other metabolic pathways of T4 and to a possible underestimation of T3 and rT3 production rate. Based on conservative estimates from the literature, the other metabolic pathways of T4 amount: oxidative deamination 1.1%; ether link cleavage 0%; urinary excretion 2.5%; and fecal excretion 14%. Thus, the various metabolic pathways seem to explain 97% of daily produced and degradated T4 in man. Therefore the understimation of T3 and rT3 production rates in man using noncompartmental analysis seems of little if any importance, and existence of a hidden pool of these iodothyronines may be questioned.
The antimycotic drug terbinafine in contrast to ketoconazole lacks acute effects on the pituitary-testicular function of healthy men: a placebo-controlled double-blind trial
Authors: Nashan D. , Knuth U. A. , Weidinger G. , Nieschlag E.
Published: December 2008

Abstract. Among the side-effects of the antimycotic drug ketoconazole, inhibition of testosterone biosynthesis is highly pronounced. The decrease in testosterone may cause impotence and gynecomastia, and this side-effect has been exploited in drug tests for the treatment of androgen-dependent tumours. Terbinafine, an allylamine derivate, from a new group of antifungal substances, did not show similar inhibiting effects on steroid synthesis in vitro and in vivo in animal experiments. In a double-blind, placebo-controlled study the influence of terbinafine and ketoconazole on the pituitary-testicular axis in normal young men were compared. Serial blood sampling for 12 h was followed by the ingestion of the placebo, ketoconazole (200 mg) or terbinafine (500 mg) on three different occassions in random order. Ketoconazole administration caused a steep decrease of serum testosterone reaching a nadir after 4–5 h. Simultaneously an increase in 17-hydroxyprogesterone occurred with peak values after 5 h. During 12 h after the administration of ketoconazole no changes in LH pulse frequency and amplitude were found, although testosterone serum levels were in the subnormal range for about 8–9 h. Terbinafine showed no effects on testosterone and 17-hydroxyprogesterone levels or on LH pulse frequency and amplitude. Estradiol, prolactin and FSH remained unchanged after ketoconazole and terbinafine ingestion compared with placebo treatment. The study confirms the acute effect of ketoconazole on serum testosterone and 17-hydroxyprogesterone, whereas terbinafine shows no acute influence on the pituitary-gonadal axis.
Evidence for direct action of calcitonin in the rat pituitary gland
Authors: Morel G. , Chabot J.-G. , Enjalbert A. , Priam M. , Dubois P. M.
Published: December 2008

Abstract. Classic concepts of calcitonin (CT) function have focused on the effects of CT on calcium homeostasis. More recently CT actions on brain and pituitary have been investigated. In order to evaluate the effects of CT on the anterior pituitary gland we studied the action(s) of CT in vitro and visualized endogenous CT in adult male rat pituitary gland by immunocytochemistry on ultrathin sections obtained by cryoultramicomy. In vitro study using dispersed anterior pituitary cells indicated that CT stimulated the secretion of PRL, whereas the secretion of GH, TSH and LH was not affected. CT-like immunoreactivity was observed in lactotropes only. The other pituitary cell types were not immunoreactive. In lactotropes, immunostaining was observed in the cytoplasm and in the nucleus. In the cytoplasm, CT-like immunoreactivity was visuzalized in the cytoplasmic matrix and in the secretory granules. In the nucleus, immunostaining was distributed primarly in the euchromatin, in the vincinity of heterochromatin region. CT-like immunoreactivity was also observed at the plasma membrane but was only scarce. No reaction product was found when anti-CT serum pre-incubated with CT was used. In conclusion, these results bring evidence for a direct action of CT on lactotrope regulation in vitro as well as in intact animals.
Prospective multicentre study on the prediction of relapse after antithyroid drug treatment in patients with Graves' disease
Authors: Schleusener H. , Schwander J. , Fischer C. , Holle R. , Holl G. , Badenhoop K. , Hensen J. , Finke R. , Bogner U. , Mayr W. R. , Schernthaner G. , Schatz H. , Pickardt C. R. , Kotulla P.
Published: December 2008

Abstract. Graves' disease is an autoimmune disease characterized by a course of remission and relapse. Since the introduction of antithyroid drug treatment, various parameters have been tested for their ability to predict the clinical course of a patient with Graves' disease after drug withdrawal. Nearly all these studies were prospective and often yielded conflicting results. In a prospective multicentre study with a total of 451 patients, we investigated the significance of a variety of routine laboratory and clinical parameters for predicting a patient's clinical course. Patients who had positive TSH receptor antibodies activity at the end of therapy showed a significantly higher relapse rate than those without (P< 0.001). However, the individual clinical course cannot be predicted exactly (sensitivity 0.49, specificity 0.73, N = 391). The measurement of microsomal (P=0.99, sensitivity 0.37, specificity 0.63, N = 275) or thyroglobulin antibodies (P= 0.76, sensitivity 0.18, specificity 0.84, N = 304) at the end of antithyroid drug therapy did not show a statistically significant difference in the antibody titre between the patients of the relapse and those of the remission group. Additionally, HLA-DR typing (HLA-DR3: P=0.37, sensitivity 0.36, specificity 0.58, N = 253) was proven to be unsuitable for predicting a patient's clinical course. Patients with abnormal suppression or an abnormal TRH test at the end of antithyroid drug therapy relapse significantly more often (P< 0.001) than patients with normal suppression or normal TRH test. Patients with a large goitre also have a significantly (P< 0.001) higher relapse rate than those with only a small enlargement. The sensitivity and specificity values of all these parameters, however, were too low to be useful for daily clinical decisions in the treatment of an individual patient. This is also true for the combinations of different parameters. Though the highest sensitivity value (0.94) was found for a combination of the suppression and the TRH test at the end of therapy, the very low specificity value (0.13) for this combination reduced its clinical usefulness.
Antidiuretic effect of Sandostatin® (SMS 201-995) in healthy volunteers
Authors: Berthold Heiner , del Pozo Emilio
Published: December 2008

Abstract. Ten male healthy volunteers were studied in order to determine whether the synthetic somatostatin analogue Sandostatin® (SMS 201-995) has effects similar to those of natural somatostatin on renal water and electrolyte excretion. The study was carried out in three separate placebo-controlled randomized double-blind cross-over trials. The subjects received single sc injections of 100 μg Sandostatin and placebo under conditions of mild diuresis (trial 1), water load with enhanced diuresis (trial 2), and water load with exogenous lysin-vasopressin (5 IU sc) induced antidiuresis (trial 3). The following parameters were measured: urine flow rate, serum and urine osmolalities, osmolar clearance, free water and creatinine clearances, excretion rates of sodium, potassium, calcium, chloride, and phosphate, and immunoreactive insulin. A marked antidiuretic effect was observed within 2 h after dosing in all three trials. Urine flow rates were reduced by 45% in trial 1 and by 29 and 31% in trials 2 and 3, respectively (all P< 0.05). There were no differences in effects on serum and urine osmolalities between Sandostatin and placebo. Osmolar clearance was significantly reduced in trial 1 (P< 0.01). Free water clearance significantly decreased only in trial 2 (P< 0.05). Sodium excretion decreased by 49, 48 and 67%, respectively, the differences being significant in trials 1 and 3 (P< 0.05). Calcium excretion decreased by 66, 70 and 54% (all P< 0.001). Chloride excretion decreased by 28, 22 and 44%, the differences being significant in trials 2 and 3 (P< 0.05). Potassium excretion, phosphate excretion and creatinine clearance were not significantly altered. These results agree with previous findings with natural somatostatin in man under the condition of high urine flow (trial 2). We suggest that Sandostatin has a direct vasopressin-like effect on the renal tubule. However, the results of trials 1 and 3 are consistent with the involvement of osmolar mechanisms. The question of the clinical relevance of these observations remains open, since during long-term treatment with Sandostatin the drug's antidiuretic effect might be overridden by other mechanisms regulating the water and electrolyte balance.