bluuebunny/crossref_metadata_2025 huggingface dataset:
Thyrotrophin and prolactin responses to thyrotrophin-releasing hormone in patients with streak gonad syndrome
Authors: Bösze P. , Kóvacs Zs. , Egyed J. , László J. , Szilágyi G.
Published: December 2008

Plasma TSH and Prl responses to iv TRH (200 μg) were studied in 21 euthyroid patients with streak gonad syndrome which is characterised by high levels of FSH and LH and low level of oestrogen and in 9 healthy women. The syndrome is associated with a variety of chromosome complements. Basal TSH and Prl responses to TRH were normal in patients with streak gonads irrespective of their chromosomal complements. Peak levels of both the TSH and Prl occurred at 15–30 min following TRH. The data might suggest that in hypergonadotrophic oestrogen deficiency neither the TSH nor the Prl response to TRH are attenuated. It does not seem that the associated chromosome anomalies alter the TSH and Prl responses to TRH in euthyroid affected patients.
Comparison of the LH secretion patterns in the male rat following infusion of LRH and of the LRH-analogue buserelin®. Influence of castration and oestradiol benzoate on the efficiency of LH release
Authors: Schuiling G. A. , Pols-Valkhof N. , Koiter T. R.
Published: December 2008

The LH releasing activities of LRH and the LRH-analogue buserelin® (HOE 766; (D-Ser (But)6-LRH(1–9)nona peptide-ethylamide) were compared in intact and short- and long-term castrated male rats, pre-treated (either 1 or 3 days) with oestradiol benzoate (EB) or oil.

LRH and buserelin were infused iv at the constant rate of 104 ng/h for 21 h. Blood samples were taken from an intracarotid cannula. LH responses were judged on the basis of the mean maximal height of the LH concentration (MH; ng LH/ml plasma) and a parameter of total LH release, i.e. the area under the curve of LH concentrations plotted against time ('area under the curve', AUC; expressed in 'area units'). The release efficiency of LRH and buserelin, E (see for a definition: Materials and Methods), which informs on the total quantity of LH released in relation to pituitary LH content, was calculated by dividing the AUC × 100 by the pituitary LH content at the beginning of stimulation.

Maximal plasma LH concentrations were observed between t= 1.5 and t=3 h after LRH and between t= 1.5 and t=9 after buserelin treatment. Both with LRH and buserelin the rise of LH secretion was greater the longer the animals were castrated and/or pre-treated with EB. The buserelin-induced LH response (with the exception of the responses induced in the EB-pre-treated, 4-weeks castrated rat) were about 2–2.5 times higher (MH) and larger (AUC) than the corresponding LRH-induced responses. The buserelin/LRH potency ratio, therefore, is about 2–2.5.

EB-pre-treatment did not change the pituitary LH content. It therefore enhanced the efficiency of release of LH of both LRH and buserelin. Castration, on the other hand, caused an increase of the pituitary LH content: after 4 weeks it was raised by a factor 4. Since, however, the LH responses induced by LRH and buserelin were proportionally higher and larger, castration did not significantly change the efficiency of LH release.

The results indicate that the efficiency of LH release can be changed by changes in the endocrine environment in the experimental animals, whilst for the magnitude of LH responses the pituitary LH content is also important. It is therefore suggested that the responsiveness of the pituitary gland to LRH (and agonistic analogues) is determined by (1) the state of the LH secretion mechanism and (2) the pituitary LH content.
Variation in the release of thyroxine, triiodothyronine and growth hormone in response to thyrotrophin releasing hormone during development of the domestic fowl
Authors: Decuypere E. , Scanes C. G.
Published: December 2008

In newly hatched chicks, TRH administration was followed by increased circulating concentrations of growth hormone (GH), thyroxine (T4) and 3,3',5-triiodothyronine (T3). Little change in the circulating concentration of 3,3',5'-triiodothyronine (rT3) was however observed. The effect of TRH on the circulating concentration of GH was not found in chick embryos at 17 or 19 days of incubation but was observed during pipping. The T4 response was maximal in newly hatched chicks and present in 17 and 19 days embryos. The magnitude of the T3 responses increased with age while that of T4 decreased.
The effect of thyrotrophin-releasing hormone (TRH) on pancreatic hormone secretion in normal subjects
Authors: Ø. Dolva L. , Hanssen K. F. , Flaten O. , Hanssen L. E. , von Schenck H.
Published: December 2008

Thyrotrophin-releasing hormone (TRH) is present in the pancreas, mainly in the islets of Langerhans.

We studied the effect of iv infused TRH on the plasma levels of pancreatic islet hormones in man, under different experimental conditions:

1) Arginine infusion.

2) Insulin induced hypoglycaemia.

3) Glucose clamp technique (maintainance of normoglycaemia by glucose infusion during insulin infusion).

4) TRH injection.

Except for a minor inhibition of glucagon and pancreatic polypeptide following hypoglycaemic stimulation in one study, TRH had no significant effect on basal, stimulated or inhibited plasma glucagon, on insulin, somatostatin, pancreatic polypeptide or blood glucose.

It is concluded that iv administration of TRH does not produce significant changes in peripheral plasma levels of pancreatic hormones.

Application of techniques, which allow studies closer to the pancreatic islet, is probably necessary to assess the role of TRH in the regulation of endocrine pancreas.
CuZn superoxide dismutase, Mn superoxide dismutase, catalase and glutathione peroxidase in lymphocytes and erythrocytes in insulin-dependent diabetic children
Authors: Hägglöf Bruno , Marklund Stefan L. , Holmgren Gösta
Published: December 2008

CuZn superoxide dismutase, Mn superoxide dismutase, catalase and glutathione peroxidase activities in lymphocytes and erythrocytes were studied in 9 children with insulin-dependent diabetes mellitus (IDDM) as well as in 21 healthy children. The mean erythrocyte CuZn superoxide dismutase and glutathione peroxidase were statistically significantly lower in the IDDM group compared with the controls although almost all IDDM results fell within the mean ± 2 sd limits of the controls. The small differences found can hardly be assigned biological significance. Erythrocyte catalase as well as lymphocyte CuZn superoxide dismutase and Mn superoxide dismutase did not differ from the controls.
Reductions in plasma catecholamines and blood pressure during weight loss in obese subjects
Authors: Tuck Michael L. , Sowers James R. , Dornfeld Leslie , Whitfield Larry , Maxwell Morton
Published: December 2008

The effect of weight reduction on levels of upright plasma norepinephrine (NE) and epinephrine (E) was studied in 20 obese patients maintained on a hypocaloric protein diet. Subjects were divided into 2 groups on either a constant 120 (N=13) or 40 (N=7) mmole sodium intake. Initial upright NE levels were higher (P < 0.001) in obese subjects (610 ± 52 pg/ml) than in non-obese controls (325 ± 25 pg/ml). Initial NE in obese subjects correlated (r=0.6, P < 0.01) with mean arterial pressure. Weight loss in both sodium intake groups was accompanied by a progressive decline in upright NE and by 8 weeks levels were decreased in all study subjects by a mean of 42 per cent (P < 0.01) from baseline. Reductions in upright E from baseline were not as pronounced but were significant (P < 0.05) at 8 weeks on both sodium intakes. We have previously shown that mean arterial pressure and PRA decrease significantly in obese subjects during supplemented fasting independent of sodium intake. In the present study reductions in body weight correlated (r=58, P < 0.05) with both the fall in NE levels at 8 weeks (r=0.5, P < 0.05) and with reduction in upright PRA (r=0.49, P < 0.05) at weeks 4 to 8. Changes in upright E did not correlate with weight and blood pressure reductions. We conclude that reduction in caloric intake in obese patients is accompanied by significant reductions in upright NE and E that may contribute to the decline in resting blood pressure. The decrease in upright PRA with weight loss could result from depression in sympathetic nervous system activity.
Active and inactive renin in primary and secondary adrenal insufficiency and during ACTH infusion
Authors: Belkien Lutz , Exner Petra , Oelkers Wolfgang
Published: December 2008

Prolonged low-dose ACTH infusion leads to a transient stimulation of plasma renin activity (PRA) and angiotensin II.

In part 1 of the present study (infusion of 10 IU of ACTH per day for 38 h into 6 normal young males), it was shown that the concentration of active renin (aPRC) increases in parallel to PRA. Thus, the rise in PRA is either due to net active renin secretion by the kidney or to increased conversion of inactive into active renin. Since the plasma concentration of inactive renin (iPRC) tended to rise rather than to fall during ACTH infusion, peripheral activation of inactive renin is probably not the cause of the rise in aPRC.

Part 2 of the study consisted in the measurement of plasma ACTH, cortisol, PRA, aPRC and iPRC in 10 patients (group I) with primary adrenocortical insufficiency (8 Addisonians, 2 adrenalectomized Cushing's) and in 9 patients with hypopituitarism (group II) after short-term withdrawal of hydrocortisone substition therapy. ACTH was 1770 ± 390 pg/ml in the former and 20 ± 4 pg/ml in the latter group. PRA and aPRC were higher and the ratio iPRC:aPRC lower in group I than in group II. This might indicate stimulation of active renin formation by ACTH. However, it is unlikely that the higher aPRC levels in group I are due to increased peripheral activation of inactive renin, since the relationship between aPRC and the ratio iPRC:aPRC fell on the same curve in both groups.

ACTH or an ACTH-dependent mechanism raises aPRC, probably by stimulating its renal secretion rather than by peripheral activation of inactive renin.
Increased serum reverse triiodothyronine in patients with hyperemesis gravidarum
Authors: Juras N. , Banovac K. , Sekso M.
Published: December 2008

Thyroid function and pituitary responsiveness to TRH were studied in patients with hyperemesis gravidarum.

Serum T3 and T4 concentrations were normal. Serum TBG levels in hyperemesis were normal for gestation, and the T4: TBG ratio was in the euthyroid range. In all patients a normal TSH response to TRH was found.

Mean serum rT3 concentration was increased by 31% as compared to a control group of normal pregnant women (P< 0.001).

The data suggest that in patients with hyperemesis gravidarum there is: (a) normal function of the thyroid gland and pituitary-thyroid axis, (b) an enhanced peripheral conversion of T4 to rT3.
Ram hypothalamic - pituitary - gonadal - interactions. Effects of castration and cryptorchidism
Authors: Caraty A.
Published: December 2008

The changes in hypothalamic LRH content, serum levels of LH, FSH and testosterone, and pituitary gonadotrophin contents were systematically compared in three experiments with rams. The first experiment was designed to identify specific endocrine changes at 15, 30 or 180 days after castration; the second, the influence of injections of testosterone (2 × 30 mg/day) for 15 days in castrated rams and the third, the effects of surgical cryptorchidism.

The rapid decrease in plasma testosterone levels after castration (P < 0.05) was associated with an increase in plasma gonadotrophins (P < 0.01). By 2 weeks post-castration, hypothalamic LRH content was significantly reduced. This reduction (∼ 60% of intact controls) remained unchanged at 30 and 180 days after castration. In the second experiment the post-castration rise of plasma gonadotrophins was entirely prevented by testosterone administration and no difference was observed in hypothalamic LRH content of intact control and testosterone treated castrate rams. In the third experiment cryptorchidism induced a significant increase in plasma gonadotrophins which was intermediate between those of intact and castrate rams. Pituitary gonadotrophin content increased in cryptorchid rams without a concomitant change in hypothalamic LRH content.

The data show that:

1) the mode of regulation of pituitary gonadotrophin concentration differs from that observed in the rat,

2) factors other than testosterone are implicated in the regulation of gonadotrophin secretion and synthesis and,

3) testosterone supplementation was able to maintain a normal hypothalamic LRH content.
Differences in the hepatic and renal extraction of insulin and glucagon in the dog: evidence for saturability of insulin metabolism
Authors: Polonsky K. , Jaspan J. , Emmanouel D. , Holmes K. , Moossa A. R.
Published: December 2008

The metabolism of exogenously infused porcine insulin and glucagon was assessed concurrently in normal fasted dogs under anaesthesia. Hepatic and renal extraction of glucagon were 25.6 ± 2.3 and 43.7 ± 3.9 %, respectively, and its metabolic clearance 16.5 ± 0.8 ml/kg/min. Hepatic and renal extraction accounted for 28.5 ± 4.2 and 28.7 ± 3.7% of total glucagon clearance, respectively. Insulin MCR was 18.3 ± 1.5 ml/kg/min and its hepatic and renal extraction were 49.6 ± 3.4 and 41.7 ± 4.4% accounting for 51.9 ± 4.4 and 27.3 ± 3.9% of total insulin clearance, respectively. Neither total glucagon metabolic clearance nor its hepatic or renal components saturated even in the face of circulating glucagon levels extending into the pharmacologic range up to 14 ng/ml. In contrast however, with increasing arterial concentrations of insulin, saturability of metabolism was apparent as evidenced by significant reductions in MCR as well as hepatic and renal extraction. This demonstration of saturability of hepatic insulin metabolism occurred at levels encountered in the portal vein after meals and is compatible with the concept that the hepatic capacity for extraction of this hormone may be an important site of control of the proportion of secreted insulin reaching the periphery.

The metabolic handling of each hormone was shown to be independent of the other. Despite similarities in the interaction of insulin and glucagon with the target cell, there are important differences in the mechanisms of metabolism of these peptides at the major degradative sites.
Prolonged remission of a case of Cushing's disease following cessation of cyproheptadine therapy
Authors: Wiesen M. , Ross F. , Krieger D. T.
Published: December 2008

A case of a patient with Cushing's disease is presented who underwent clinical and laboratory remission after the initiation of cyproheptadine therapy and who has sustained such a remission for more than 3 years after discontinuing the drug.
Serotonin stimulates prolactin secretion in the hypophysectomized adenohypophyseal grafted rat
Authors: Stobie K. M. , Shin S. H.
Published: December 2008

Normal male, oestrogen (E2) primed male and hypophysectomized adenohypophyseal grafted male rats (HAG rats) were used in the experiments. Serotonin creatinine sulphate was injected as a bolus via an indwelling atrial cannula in the conscious free moving rat. Serotonin caused a dose-dependent increase in plasma prolactin (Prl) in normal (1, 3 and 10 mg/kg serotonin) and E2 primed (1 and 3 mg/kg serotonin) male rats that began immediately after injection and reached a peak within 12–15 min of injection. Oestrogen priming significantly increased the magnitude of the response to serotonin. To analyze the site of action of serotonin in the rat, serotonin (1 mg/kg) was injected into HAG rats. Serotonin increased plasma Prl in this rat preparation, indicating that serotonin acts directly on the ectopic pituitary.
Relation between plasma insulin and blood glucose in a cross-sectional population study of the oral glucose tolerance test
Authors: Berntorp K. , Trell E. , Thorell J. , Hood B.
Published: December 2008

In a material of 3596 oral glucose tolerance tests (OGTT) performed in a population investigation of middle-aged males in Malmö, fasting and 120 min values of blood glucose and plasma insulin immunoreactivity (IRI) were studied while taking factors like body weight, smoking, alcohol, gastric resection and selfreported diabetes heredity into account. The fasting as well as the 120 min levels of both glucose and IRI were markedly influenced by body weight and smoking habits but not by the hereditary background. At 120 min, but not in the fasting state, there was a linear correlation between the IRI and glucose levels. The increase of IRI on glucose was significantly steeper in most of the hereditary subjects in comparison with their non-hereditary controls.
Sites of RNA synthesis and migration in the adrenal cortex cells of the young rat, as shown by radioautography
Authors: Magalhães Maria C. , Magalhães M. M. , Coimbra A.
Published: December 2008

The sites of RNA synthesis, processing and migration were studied with light and electron microscope radioautography in adrenal zona fasciculata cells of the young rat. Animals were injected iv with [3H]uridine and sacrificed at various time intervals. A marked radioactive peak was found in blood at the 20 min interval, later time intervals being considered as chase periods. Labelling was high over nucleoli of fasciculata cells at 1 h, with the silver grains concentrated over the fibrillar component. Simultaneous though lower peaks occurred over the condensed chromatin and the interchromatin space. Nucleolar and extranucleolar values were decreased at 8 and 24 h, most silver grains overlaying the cytoplasm at this time period. At 8 h, the granular component of the nucleolus was more heavily labelled than the fibrillar component.

This sequence of events suggests a relatively slow uptake of the labelled nucleotides and slow formation of pre-rRNA molecules in the fibrillar component of the nucleolus, with the processing into smaller subunits occurring in the granular component during initial chase. Extranucleolar RNAs were synthesized simultaneously but in a smaller rate. Most nucleolar RNA was finally transferred to the cytoplasm. This pattern will serve as a basis for studying the effects of ACTH on the different steps of RNA synthesis and transport in adrenal cortex cells.
Serum concentrations of gonadotrophins in hypergonadotrophic patients following stimulation by a long-acting analogue of luteinizing hormone-releasing hormone
Authors: Vierhapper H. , Waldhäusl W. , Klaushofer G. , Stackl W.
Published: December 2008

The effect of D-Ser(TBU)6-EA10-LRH, a long-acting analogue of luteinizing hormone-releasing hormone (LRH), was studied in patients with hypergonadotrophism due to orchidectomy (n = 8) or due to Klinefelter's syndrome (n = 6). Patients orchidectomized less than 7 days prior to the administration of the compound presented with maximum concentrations of LH (63.8 ± 29.9 mIU/ml) within 60 min following iv injection of the LRH-analogue (10 μg). This behaviour of LH was qualitatively similar to that seen in healthy men. In patients orchidectomized more than 40 days prior to the administration of the LRH-analogue and in patients with Klinefelter's syndrome the occurrence of maximum serum LH-concentrations (115.0 ± 39.4 and 149.4 ± 134.5 mIU/ml, respectively) was delayed up to 240–360 min following iv LRH-analogue. This pattern of LH secretion is similar to that of healthy women. No qualitative differences in stimulated FSH-concentrations were observed between the described groups of hypergonadotrophic patients. These findings demonstrate a time-dependent increase in the 'second pool' of LH following orchidectomy. The similar behaviour of stimulated LH-release in healthy women and in male patients with long-term hypergonadotrophic hypogonadism could indicate an augmented production of endogenous LRH in these individuals as compared to healthy men, providing an explanation for the sexually related differences in the LH-response upon the administration of the LRH-analogue.
Altered Leydig cell function in patients with testicular cancer: evidence for a bilateral testicular defect
Authors: Willemse P. H. B. , Sleijfer D. Th. , Sluiter W. J. , Koops H. Schraffordt , Doorenbos H.
Published: December 2008

In search of an abnormality in Leydig cell function in patients with testicular cancer, serum levels of testosterone, oestradiol, LH and FSH were compared in 3 groups of men.

Group I comprised 26 patients studied after recent orchidectomy for a testicular carcinoma, group II 8 patients operated for benign testicular lesions and group III 8 normal controls. In group II normal testosterone values were found as a result of increased LH release. In group I patients, however, testosterone levels often were low, despite elevated LH levels and increased LH capacity. Evidently, in these patients a partial Leydig cell insufficiency may be present, which does not recover within one year of orchidectomy.

After removal of one testis for benign disease, normal testosterone levels are maintained by increased LH levels. After orchidectomy for testicular carcinoma a partial Leydig cell insufficiency may be revealed, which seems to have a permanent character. A pre-existent Leydig cell insufficiency of the remaining testis in patients with testicular cancer indicates a bilateral testicular defect.
17-ketosteroid reductase deficiency in an adult patient without gynaecomastia but with female psychosexual orientation
Authors: Millán M. , Audí L. , Martinez-Mora J. , de Osaba M.J. Martinez , Viguera J. , Esmatjes E. , Peig M. , Vilardell E.
Published: December 2008

Abstract1

A 24 years old male with pseudohermaphroditism due to a deficiency in 17-ketosteroid reductase activity is described. Plasma Δ4 is 21 times higher than normal for an adult male, Δ4/T is greater than 6, both E1 and E2 are elevated and E1/E2 = 3.

There is very slight modification of Δ4 on administration of ACTH, dexamethasone, hCG and fluoxymesterone. Steroid concentrations in the spermatic veins and arteries confirm the testicular origin of the increased secretion of Δ4 and E1 and show a lower secretion by the cryptorchidic testis.

In vitro testicular tissue incubation and fibroblast studies confirm the 17-ketosteroid reductase deficiency and rule out any other anomaly as the cause of the ambiguous genitalia.

Psychologically the patient seemed to be identified with a female social and sexual role in spite of her advanced degree of virilization.
A study of thyroid function after subtotal thyroidectomy for Graves' disease: particularly on TRH tests, T3 suppression tests and antithyroid antibodies in euthyroid patients
Authors: Fukino Osamu , Tamai Hajime , Fujii Shinichi , Ohsako Noriyuki , Matsubayashi Sunao , Kuma Kanji , Nagataki Shigenobu
Published: December 2008

Abstract. Of 305 patients who underwent subtotal thyroidectomy for Graves' disease between 1969 and 1975, recurrent hyperthyroidism was found in 31 (10.2%) and hypothyroidism in 18 (5.9%). The remaining 256 patients were clinically euthyroid, but an elevated serum TSH level was found in 104 (34.1%) and an elevated serum T3 level in 19 (6.28%). In 57 of 133 clinically and biochemically euthyroid patients, a TRH test, T3 suppression test and measurement of antithyroid antibodies were performed. Twenty-nine of the 57 patients (50.9%) showed an abnormal response to TRH. Eight of these (14.0%) showed an impaired or absent response. The T3 suppression test showed that 15 of the 57 patients (26.3%) were non-suppressible. Positive antithyroid antibodies, especially antimicrosomal antibodies, were more frequent in non-suppressible and TRH-non-responsive patients than in suppressible and TRH-responsive patients. It is suggested that after operation for Graves' disease: 1) only half of the clinically euthyroid patients were biochemically euthyroid, 2) of the clinically and biochemically euthyroid patients, there were many with abnormalities in TRH responsiveness and T3 suppressibility, and 3) thyroid functional status is unstable and long careful follow-up is important after operation for Graves' disease.
Failure to find evidence of immunoglobulin inhibitor(s) of thyroid hormone binding to serum proteins in non-thyroid illnesses
Authors: Benvenga S. , Costante G. , Melluso R. , Luzza G. , Pustorino S. , Turiano S. , Trimarchi F.
Published: December 2008

Abstract. In order to verify the hypothesis of the presence of IgM (or an IgM-like substance) capable of inhibiting thyroid hormone binding to serum proteins and, therefore, capable of enhancing serum free thyroid fractions in non-thyroid illnesses (NTI), we measured TBG and TBPA maximum binding capacities and TBG concentration by an immunoradiometric system in normal pooled sera (NPS) before and after enrichment with purified immunoglobulins (IgM and IgG) from euthyroid NTI sera (free T4, free T3 and TSH levels were normal). A known amount of TBG was diluted 1:2–1:6 with deionized water or with IgM from NPS or from each of 6 NTI sera; the measured values were not different from these expected on theoretical grounds. Likewise, IgM or IgG from normal or from each of 7 NTI sera failed to modify both TBG and TBPA capacities of different NPS, and NTI immunoglobulins showed no binding activity directed to [125I]T4, [125I]T3 or [125I]TBG. In addition, no inhibitory influence of TBG and TBPA capacities was observed when the whole euglobulin fraction obtained by precipitating the same 7 NTI sera by PEG was mixed with NPS. On the other hand, a significant IgM inhibitory effect on the binding of labelled T4 to TBG was found, only when IgM concentrations were experimentally rendered 41 times greater than that requested in the working mixtures. We conclude that no immunoglobulin inhibitor of thyroid hormone binding to transport proteins was evident in the NTI sera investigated.
Effects of prolonged administration of thyrotrophin on serum concentration, release and synthesis of thyroid hormones in mice
Authors: Chiu S. C. , Kubota K. , Kuzuya N. , Ikeda H. , Uchimura H. , Nagataki S.
Published: December 2008

Abstract. Mice were injected sc with TSH (0.5 U) at 12 h intervals for 5 days. Groups of mice were sacrificed daily to determine serum T4 and T3 concentrations, 4 h thyroidal 125I uptake, distribution of 125I among thyroidal iodoamino acids, and thyroidal content of T4 and T3. Serum T4 and T3 concentrations increased significantly after the initial injection of TSH and gradually decreased thereafter, reaching initial levels on the 3rd and 4th days, respectively. In contrast to serum hormone levels, thyroidal 125I uptake, incorporation of 125I into T4 and T3 increased significantly on the first day and remained elevated throughout the period of TSH-treatment. Thyroidal T4 content expressed as μg/mg weight of tissue decreased significantly on the first day and thereafter remained constant. Thyroidal T3 content did not change significantly throughout the experimental period. The differences between thyroidal synthesis and thyroidal contents of T4 and T3 strongly suggest that thyroid hormone secretion is being continuously stimulated. Transient increases in serum T4 and T3 concentrations are probably due to a gradual increase in the rate of peripheral degradation of thyroid hormones. These results suggest that TSH-induced refractoriness in thyroidal iodine metabolism does not appear to exist, at least when TSH is given in vivo for 5 days.
Effect of thyroxine on immune response in C57B1/6J mice
Authors: Gupta Manjula K. , Chiang Theresa , Deodhar Sharad D.
Published: December 2008

Abstract. The effect of T4 treatment (40 μg, 5 times/week) on immune function in C57B1/6J mice was studied. The primary antibody synthesis as measured by the plaque-forming cell (PFC) assay demonstrated significant suppression in mice treated with T4 for 30 days. Mitogen assays using PHA and Con A demonstrated significant suppression of cellular immune responses as measured by [3H]thymidine incorporation. The effect was reversed when the treatment was discontinued and a normal response reappeared after 14 days. Allogeneic skin grafts (donor A/J mice) showed prolonged survival (median survival time, 13.5 days) in T4-treated mice as compared to control untreated mice (median survival time, 11 days). Further experiments using Chromium 51 assay for delayed type hypersensitivity also showed suppressed response. These results suggest that treatment with T4, in the above doses and duration, cause immunosuppression in C57B1/6J mice.
Effects of KCIO4 in propylthiouracil-hypothyroid rats
Authors: Ortiz-Caro Javier , Pastor Rosa M. , Jolin Trinidad
Published: December 2008

Abstract. In this study we investigated further the antigoitrogenic effect of ClO4 in rats on a low iodine diet (LID) and 6-propyl-2-thiouracil (PTU). The thyroid weight of rats on the mixed goitrogen was initially similar to that of animals on PTU, decreasing to values obtained in rats treated with ClO4 alone by 10 days. Despite the differences in thyroid weight, rats treated during an identical period with PTU or mixed goitrogen develop hypothyroidism to a comparable degree as far as can be assessed by the thyroidal 127I content, plasma T4, T3 and TSH concentrations, and pituitary TSH content. Moreover, it was observed that there were differences in plasma insulin and glucose levels in these hypothyroid animals. The plasma insulin and glucose levels of rats on PTU are comparable to those found in control rats. In rats on mixed goitrogen, both plasma insulin and glucose levels are initially maintained within the normal ranges, and then decline over the subsequent days of treatment. Within the treatment period studied here, plasma insulin and glucose levels were higher for rats on PTU than for animals on ClO4, PTU + ClO4, or thyroidectomized (Th) animals.

We have obtained further evidence of the hypothyroid state of rats on these goitrogen regimens based on measurements of pituitary and plasma GH levels and liver mitochondrial alpha-glycerophosphate dehydrogenase (α-GPD). The PTU-treatment decreased the liver α-GPD activity to a comparable degree to that of mixed goitrogen. Moreover, both PTU + ClO4 and PTU-treatment resulted in a state of hypothyroidism intense enough to induce effects on growth, and plasma and pituitary GH levels comparable to that of Th animals. However, the values for rats on mixed goitrogen appear to be below the PTU data. The present findings appear to be consistent with the view that TSH is not the unique factor determining the size of the resulting goitre. The results are discussed in relation to the hypothesis that: 1) the antigoitrogenic effect of ClO4 could be associated with changes in the ability of the thyroid tissue to bind TSH, or with a step beyond TSH binding, and 2) the different endocrine and metabolic states of rats on PTU or PTU + ClO4, shown by their different plasma insulin, GH and glucose levels, may play an important role in determining the thyroid weight response to TSH.
Difficulties in the diagnosis of congenital adrenal hyperplasia in early infancy: the 11 β-hydroxylase defect
Authors: Honour J. W. , Anderson J. M. , Shackleton C. H. L.
Published: December 2008

Abstract. Investigations of steroid metabolism in a newborn infant with steroid 1 1β-hydroxylase deficiency are described. Deficiency of this enzyme, like other forms of congenital adrenal hyperplasia (CAH) can be difficult to characterise in the neonatal period. In the first days of life the excretion of cortisol was low but most other hormonal parameters were normal and the major metabolite of 11-deoxycortisol (tetrahydro-S, THS) was not detectable in the urine. Using mass spectrometry, the presence of THS was confirmed in urine collected on the 12th day of life and from this time the excretion rates increased until approximately 300 μg were measured in urine on the 27th day of life. A new metabolite of 11-deoxycortisol was tentatively identified as 6α-hydroxy-THS. This steroid is not a significant metabolite in 1 1β-hydroxylase deficiency at other periods of life.
Plasma LRH levels in chronic renal failure before and during haemodialysis
Authors: Matsubara Miyao , Nakagawa Koji , Nonomura Katsuya , Hirota Noriaki
Published: December 2008

Abstract. Endogenous immunoreactive luteinizing hormone – releasing hormone (LRH) in plasma was determined in 6 male and 7 female patients with chronic renal failure before and during haemodialysis. Basal plasma LRH levels ranged from 5.8 to 23.0 pg/ml and, in 11 out of 13 patients, were above the levels seen in healthy subjects (less than 7 pg/ml for men and less than 8 pg/ml for women). This immunoreactivity was eluted in identical fractions with synthetic LRH and plasma extracts from climacteric women on Sephadex G-25 chromatography, and the dilution gave a displacement curve parallel to the standard. Within 5 h of haemodialysis, these high LRH levels declined into the normal range. The concentraions of LH in plasma in these patients were also elevated, but those of testosterone in male patients were decreased. These results suggest 1) that elevated plasma LRH reflects decreased feedback inhibition by primary gonadal failure and might in turn be responsible at least in part for high concentrations of plasma LH in chronic renal failure, and 2) that plasma LRH is mainly not bound to plasma proteins.
Oxytocin determination by radioimmunoassay
Authors: Schams D.
Published: December 2008

Abstract. An improved RIA for measurement of oxytocin in blood is described by using an extraction method with SEP-PAK C18 cartridges, which allows also concentration of the sample, a new antiserum with a higher sensitivity to standard oxytocin and preparation of the standard curve in buffer. The lower limit of assay sensitivity was 0.25 pg/tube, corresponding to 0.25–1.0 pg/ml plasma depending on the amount of plasma extracted. Hence, it was no problem to measure oxytocin basal concentrations in peripheral blood in the range of 0.6–4 pg/ml plasma depending on the stage of the oestrous cycle. The highest oxytocin concentrations occurred during the early and mid-luteal phase. The method has been applied also for samples from women, sheep, pigs and horses. Mean (± sd) recovery of oxytocin added to plasma or only buffer after extraction was 71.3 ± 8,1%, and the coefficient of variation (CV) = 11.4% (n = 27 assays). The intra-assay CV of two control samples was 7.9 ± 2.8 and 7.8 ± 2.4% (n = 17 assays). The inter-assay CV of 5 control samples with low and high oxytocin concentrations varied between 10.8 ± 17.3% (n = 25 assays). The 50% intercept was 2.5 ± 0.3 pg, CV = 11.3% (n = 29 assays).
Maximum calorie (sub-threshold) dieting of the obese and its hormonal response
Authors: Wilkin T. J. , Choquet R. C. , Schmouker Y. , Rouquette N. , Baldet L. , Vannereau D.
Published: December 2008

Abstract. Severe calorie restriction for treating the obese reduces serum triiodothyronine (T3) and energy expenditure, and may be counterproductive. In order to avoid severe calorie deficiency, we measured the individual minimum energy requirements (threshold, T) in 17 obese females and fed each on a sub-threshold diet, comprising the maximum number of calories commensurate with weight loss (T-200 cals). Mean T-200 was 1318 ± 96 cals, but the mean weight loss after 16 weeks on a sub-threshold diet (STD) was identical (17 kg) to that obtained by 22 age-matched female controls on a classical diet of 659 ± 59 cals, exactly half the intake. Weight loss on the classical diet was initially rapid but decelerated sharply after 8 weeks, while on the sub-threshold diet the rate of loss remained constant throughout.

In a second study, thyroid hormone measurements were performed three times weekly in 27 obese females during the 4 week period required to establish T. The mean weight loss was 4.02 ± 0.3 kg, but T3 levels varied minimally and very transiently. STD produces short-term results similar to those obtained by severe calorie deprivation, but is more acceptable to the patient. It appears not to provoke the fat-saving reflexes provoked by the classical, low-calorie diet.
Effect of betamethasone treatment on iodothyronines and thyroid hormone-binding proteins during controlled nutrition
Authors: Gamstedt Anders , Järnerot Gunnar , Kågedal Bertil
Published: December 2008

Abstract. Forty patients with ulcerative colitis and Crohn's disease were divided into four groups. They were given betamethasone (6 mg daily) either iv or orally in combination with either iv or oral administration of nutrients. The glucocorticoid reduced the serum T4 significantly (11–16%) when the nutrition was given iv and the same trend occurred (7–9%) in the orally nutriated groups. Corticosteroids reduced the serum T3 by 20–39%, TSH 29–67%, Δ TSH 45–76% and TBG 11–18% and increased the rT3 by 19–66% and the T3-uptake 6–16% irrespective of the mode of administration of the steroids although the changes did not reach statistical significance (P < 0.05) in all groups. A significant increase of serum TBPA by 24% occurred only in the group receiving both steroids and nutrition iv with only minor or no changes (0–12%) in the other three groups. Except for the serum T4 the results were not influenced by the mode of nutrition (iv or oral).
Iodide enhances IgG synthesis by human peripheral blood lymphocytes in vitro
Authors: Weetman A. P. , McGregor A. M. , Campbell H. , Lazarus J. H. , Ibbertson H. K. , Hall R.
Published: December 2008

Abstract. Several studies have suggested that iodide may increase thyroiditis and autoantibody synthesis. We have investigated the effect of iodide in vitro at physiologically relevant concentrations on immunoglobulin synthesis by normal human peripheral blood lymphocytes stimulated with pokeweed mitogen.

Both the number of cells which synthesised IgG and the amount of IgG released into the culture supernatant increased significantly after culture in a medium with added iodide compared to a medium with added chloride. No effect of increasing concentrations of the added iodide from 10−3 mm to 10 mm was observed.

These findings suggest that iodides may have a role in enhancing antibody synthesis which may be important when programmes of iodide supplementation are introduced into areas which are deficient.
A clinical comparison of the enzyme-linked immunosorbent assay (ELISA) and haemagglutination (TRC) in the routine detection of antithyroglobulin antibodies
Authors: Ewins David L. , Wilkin Terence J.
Published: December 2008

Abstract. The enzyme-linked immunosorbent assay (ELISA) has been proposed as an alternative to haemagglutination (TRC) in the routine examination of sera for autoantibodies such as thyroglobulin antibody (Anti-Tg). However, very few clinical comparisons of the two tests, incorporating matched controls and an independent standard, have so far been published. We have compared the performance of ELISA and TRC as screening procedures in 814 patients referred to our atuoimmune profile laboratory with clinically suspected thyrotoxicosis, Hashimoto's thyroiditis or myxoedema. Radioimmunoassay (RIA) was used as the independent standard, and the normal range for each test was established from 100 carefully age and sex-matched controls. Sixty-five % of the sera were negative in all three tests. The results from ELISA and RIA were very similar (r = 0.88, P < 0.001), with no major discrepancy. TRC, however, was negative in 101 (40.2%) of 251 RIA positive sera (r = 0.61, P < 0.001) and in 118 (44.2%) of 267 ELISA positive patients (r = 0.69, P < 0.001). Some of the TRC negative sera were strongly RIA and ELISA positive. ELISA is fully quantitative, cheap, and was found to be more accurate than TRC in indentifying anti-Tg positive individuals. It has the potential to replace TRC in the routine screening of sera for anti-Tg antibodies.
Thyroid function in adrenocortical insufficiency during withdrawal and re-administration of glucocorticoid substitution
Authors: Grubeck-Loebenstein B. , Vierhapper H. , Waldhäusl W. , Nowotny P.
Published: December 2008

Abstract. The regulatory function of glucocorticoids on thyroid hormone concentrations was studied in patients with adrenocortical insufficiency (ACI, n = 8) and in healthy subjects (n = 6). In patients with ACI withdrawal of glucocorticoid substitution for 84 h led to an increase in serum concentrations of total triiodothyronine (TT3) from 110 ± 20 to 133 ± 22 ng/dl and a decrease of serum reverse-T3 (rT3) from 23 ± 6 to 18 ± 6 ng/dl, whereas subsequent administration of dexamethasone (0.5 mg po q.i.d. for 3 days) induced a fall in TT3 (129 ± 22 to 88 ± 16 ng/dl) and a rise in rT3 (17 ± 5 to 37 ± 11 ng/dl) concentrations. Serum levels of total thyroxine (TT4) were unchanged by either withdrawal or re-administration of glucocorticoids. Basal plasma thyrotrophin (TSH) concentrations were unchanged by glucocorticoid withdrawal and fell from 2.2 ± 1.5 to 1.1 ± 0.8 mU/l during subsequent dexamethasone therapy.

In healthy subjects a decrease of TT3 (89 ± 8 to 69 ± 8 ng/dl) and an increase in rT3 (19 ± 5 to 32 ± 8 ng/dl) concentrations were seen after stimulation of endogenous cortisol production by prolonged infusion of ACTH1-24 (0.5 mg, t = 8 h on 2 consecutive days), whereas concentrations of TT4 remained unchanged. During subsequent administration of dexamethasone serum level of both, TT3 and rT3 returned to basal levels. Thus, changes in thyroid hormone concentrations are induced by alterations of substitution therapy in patients with ACI. In healthy subjects the application of 2 mg dexamethasone/day following prolonged maximal stimulation of endogenous cortisol by iv ACTH may represent a state of relative glucocorticoid deficiency, thus explaining the observed hormonal changes, which are inverse to those generally induced in healthy man by endogenous or exogenous glucocorticoids.
Tubero-infundibular dopaminergic function in cirrhotic patients: evaluation by nomifensine and domperidone
Authors: Monza G. C. , Lampertico M. , Locatelli S. , Sali L. , Cocchi D.
Published: December 2008

Abstract. Cirrhotic patients reportedly show alterations of anterior pituitary hormone secretion, which may reflect an underlying defective central neurotransmitter function. In this study, we have investigated the catecholaminergic control of prolactin (Prl) and growth hormone (GH) secretion in cirrhotic patients by means of an indirectly acting dopamine (DA) and norepinephrine agonist, nomifensine (Nom), and a DA receptor antagonist, domperidone (Dom).

Basal GH levels were higher in the 12 female and male cirrhotic patients than in the 12 age- and sex-matched normal controls, while no difference was present in basal Prl values.

Administration of Nom (200 mg po) suppressed basal Prl levels (at least 30% inhibition at three consecutive times post-drug administration) in 6/12 controls and in 6/12 cirrhotic patients, the frequency of negative responses not being different between the two groups. Nom induced a slight elevation of GH levels in controls, and evoked a more marked and sustained GH increase in cirrhotic patients.

Administration of Dom (4 mg iv) induced similar Prl increments in 6 male controls and 6 male cirrhotic patients.

Normal Prl responsiveness to Nom and Dom points to the existence of preserved tubero-infundibular DA function and modulation of pituitary DA receptors in the cirrhotic patients investigated. Higher GH responsiveness to Nom is compatible with a different bioavailability of the drug.
Influence of a prostaglandin inhibitor and a mineralocorticoid on the antidiuretic and hormonal response to an osmolar load
Authors: Bonhomme Martine , Favre Laurent , Vallotton Michel B.
Published: December 2008

Abstract. To examine the influence of prostaglandins (PGs) and sodium-volume status on the urinary excretion and action of arginine-vasopressin (AVP), we studied the response to a hypertonic saline infusion (2.5% NaCl, 0.06 ml/kg/min for 3 h) in 8 healthy males under three different conditions: 1) on an ad libitum salt diet (C), 2) after 4-day treatment with indomethacin (IDM) 150 mg/d, 3) after 4-day treatment with fluorohydrocortisone (9αFF) 0.6 mg/d. The rise of urine osmolality and the decrease of free water clearance were identical in all three studies. Basal urinary PGE2, PGF2α and AVP were decreased during IDM and unchanged during 9αFF, compared to C. The increment of urinary AVP was similar during C and IDM but significantly greater with 9αFF (P < 0.02) although urinary PGs were higher at the end of the infusion. In conclusion, despite markedly different hormonal patterns and sodium status in the three protocols, the antidiuretic response to an osmolar load is preserved suggesting an adaptive mechanism maintaining a constant balance between AVP and PGs.
A sensitive method for assaying thyroid stimulating immunoglobulins of Graves' disease: use of the guanyl nucleotide-amplified thyroid adenylate cyclase assay
Authors: Macchia E. , Carayon P. , Fenzi G. F. , Lissitzky S. , Pinchera A.
Published: December 2008

Abstract. The purpose of this study was to develop and validate a sensitive method for evaluating adenylate cyclase stimulation by thyroid-stimulating antibodies (TSAb), based on the measurement of thyroid membrane adenylate cyclase activity in the presence of a non-hydrolyzable GTP analogue, guanyl-5'-yl imidodiphosphate (Gpp(NH)p).

The addition of Gpp(NH)p (10−5 m) produced a 10-fold increase of the sensitivity of the system for both TSH and TSAb. Immunoglobulin G preparations from sera of 30 patients with Graves' disease were tested for the adenylate cyclase stimulation either in the presence or in the absence of Gpp(NH)p: a significant stimulation was observed in 27/30 patients when the GTP analogue was added to the system, while only 20/30 patients were positive in the absence of the nucleotide. The advantage of Gpp(NH)p addition was also evident in a large series which included 57 patients with Graves' disease, 15 with Hashimoto's thyroiditis or primary myxoedema and 22 normal subjects. In fact, 88% of patients with Graves' disease resulted positive, while no significant stimulation was elicited by Hashimoto's thyroiditis, primary myxoedema and by normal immunoglobulins.

The sensitivity achieved in our system which employs thyroid plasma membranes was similar to that obtained by other investigators with the use of thyroid slices or thyroid cells in primary culture. Furthermore, methods based on thyroid plasma membranes are supposed to have a better reproducibility, since the same tissue preparation, if appropriately stored, may be used in several different tests.
Failure of exogenous secretin to induce secretion of calcitonin in man
Authors: Ericsson Mats , Berg Bertel , Ingemansson Stig , Månsson Bertil , Nobin Anders
Published: December 2008

Abstract. The effect of secretin on calcitonin secretion from the human thyroid gland was studied in 15 patients undergoing thyroid and parathyroid surgery. Secretin was administered into the inferior thyroid artery at two different doses (0.75 and 7.5 CU) and into a peripheral vein at a dose of 75 CU. Blood samples for measurements of calcitonin and calcium were collected from thyroid or peripheral veins. However, neither intraarterially nor iv administered secretin was able to evoke any significant calcitonin response as measured in thyroid or peripheral venous blood. The calcium level was unaffected by secretin. The results demonstrate that secretin does not act as a calcitonin secretagogue in man.