bluuebunny/crossref_metadata_2025 huggingface dataset:
FINE ADJUSTMENT OF THYROXINE REPLACEMENT DOSAGE: COMPARISON OF THE THYROTROPHIN RELEASING HORMONE TEST USING A SENSITIVE THYROTROPHIN ASSAY WITH MEASUREMENT OF FREE THYROID HORMONES AND CLINICAL ASSESSMENT
Authors: CARR D. , MCLEOD D. T. , PARRY G. , THORNES H. M
Published: March 2008

Thyroxine replacement therapy for 21 adult patients with primary hypothyroidism was adjusted to the dosage at which each patient had a normal thyrotrophin (TSH) response to thyrotrophin releasing hormone (TRH). Clinical assessment and measurement of TSH (by sensitive immunoradiometric assay), free thyroxine (FT4) and free tri‐iodothyronine (FT3) were made at this dosage and at higher and lower doses of thyroxine. Clinical observations, FT3 and FT4 assays were relatively insensitive to small alterations of thyroxine dosage, in contrast to which basal TSH measurements correlated well with TRH responsiveness and were sensitive to fine adjustments of thyroxine dosage.
THE SIGNIFICANCE OF THE INITIAL FT4‐INDEX FOR THE MANAGEMENT OF SINGLE DAILY DOSE METHIMAZOLE TREATMENT OF HYPERTHYROIDISM
Authors: ARNTZENIUS A. B. , ELTE J. W. F. , FRÖLICH M. , HAAK A.
Published: March 2008

Since the effectiveness of 30 mg methimazole in a single daily dose in gaining initial control of hyperthyroidism may depend largely on patient characteristics, 52 patients (34 with diffuse and 18 with nodular goitre) were investigated in an attempt to determine the relative importance of a number of pretreatment variables. Return to normal thyroid hormone levels after 2 to 6 weeks of treatment appeared to be the rule, although eight of these patients formed notable exceptions (6‐20 weeks). The individual duration of treatment until achievement of biochemical euthyroidism correlated with the initial free thyroxine index (r= 0.75, P<0.001) and the free triiodothyronine index (r= 0.70, P< 0.001). For patients with a diffuse goitre it was also related to the thyroid volume estimated by ultrasound (r= 0.73, P< 0.001). According to multiple linear regression analysis however these variables were found to have no independent prognostic value. The decrease in thyroid volume during initial therapy, the nature of the goitre, a medication compliance score and various other patient variables did not correlate with the effect of treatment. In 12 cases perchlorate discharge tests were performed. The results suggest continued hormone synthesis in patients with highly active iodine trapping as an important mechanism of the postponed attainment of euthyroidism.
RESTORATION OF NORMAL THYROTROPHIN SECRETION REDUCES THE ABNORMALLY HIGH SERUM GLUTATHIONE S‐TRANSFERASE LEVELS FOUND IN PATIENTS RECEIVING THYROXINE REPLACEMENT THERAPY
Authors: GOW S. M. , CALDWELL G. , TOFT A. D. , SWEETING V. M. , BECKETT G. J.
Published: March 2008

The peripheral tissue thyroid status of 12 patients receiving thyroxine replacement therapy was investigated both when pituitary secretion of TSH was suppressed and later, when on a lower dose of thyroxine that restored thyrotroph responsiveness. Heart rate and various analytes in serum known to be sensitive to thyroid status were measured in addition to TSH by immunoradiometric assay. Initially, the serum T4 concentration was raised in seven patients and free T4 raised in nine; all patients had normal T3 concentrations. Later, on the lower dose of thyroxine, most patients had concentrations of thyroid hormones within reference limits. Concentrations of the liver‐specific form of glutathione S‐transferase (GST) in serum decreased (P< 001) after the reduction in thyroxine dose; abnormally high GST levels, found in eight patients when TSH was suppressed, returned to normal in six of these patients when normal basal and TRH‐stimulated TSH concentrations had been restored. The response of the pituitary to excess thyroxine may be more representative of other tissues (e.g. the liver) than previously thought.
THE EFFECT OF OXYTOCIN INFUSION ON ADENOHYPOPHYSIAL AND ADRENAL CORTICAL RESPONSES TO INSULIN‐INDUCED HYPOGLYCAEMIA
Authors: NUSSEY S. S. , PAGE S. R. , ANG V. T. Y. , JENKINS J. S. , WHITE A.
Published: March 2008

The responses of plasma adrenocorticotrophin (ACTH), Cortisol, growth hormone (GH) and prolactin to insulin‐induced hypoglycaemia were studied in six lean male subjects (age 22‐29 years). Intravenous insulin tests were performed with and without oxytocin infusion. Blood sugar nadir occurred at the onset of symptoms (time S) with no significant differences between oxytocin and saline infusion. During the oxytocin infusion mean plasma oxytocin increased from 1.9 pmol/l to 138 pmol/l. Peak increase in plasma ACTH (oxytocin 266 ± 54 ng/l; saline 281+43 ng/l, mean + SEM) was at S +10 min while peak plasma Cortisol (oxytocin 680± 47 nmol/l: saline 656 ± 40 nmol/l) was measured at S ± 60 min, peak GH (oxytocin 96+17.8 mU/l; saline 106 ± 18.6 mU/l) at S + 60 min and prolactin (oxytocin 1332 ± 239 mU/l; saline 1242 ± 273 mU/l) at S + 30 min. There were no significant differences in plasma concentrations of ACTH, Cortisol, GH or prolactin between saline and oxytocin infusion. The results indicate that oxytocin has no effect on plasma ACTH, Cortisol, GH and prolactin responses to insulin‐induced hypoglycaemia. In particular they fail to support previous studies which suggested an inhibitory role for oxytocin in ACTH secretion.
THE ROLE OF A HIGHLY SENSITIVE AMPLIFIED ENZYME IMMUNOASSAY FOR THYROTROPHIN IN THE EVALUATION OF THYROTROPH FUNCTION IN HYPOPITUITARY PATIENTS
Authors: BLUNT S. , WOODS C. A. , JOPLIN G. F. , BURRIN J. M.
Published: March 2008

Using a highly sensitive amplified enzyme‐linked immunoassay (A E I A) for thyrotrophin (T S H), we have assessed the ability of a single basal measurement of T S H to predict the subsequent response of T S H to TRH in a group of 11 patients with known pituitary pathology and some evidence of hypopituitarism. All patients were clinically euthyroid. Basal levels of A E I A‐T S H ranged from <0‐2 mU/1 (‘undetectable’) to 0–9 mU/1; within this range there was no correlation with the subsequent T S H levels at 30 min in the TRH test. The T S H response in the TRH test did not correlate with the direct measurements of prevailing thyroid hormone levels (Total T4 or Free T4).

We suggest that in patients with pituitary disease, the formal TRH test yields additional information regarding residual thyrotroph function that cannot reliably be predicted by a single basal T S H value, even when measured by a sensitive method. The current and potential thyroid status in patients with hypopituitarism must continue to rest on the overall picture provided by clinical assessment, direct measurement of thyroid hormones and the TRH test response. A basal T S H alone gives little useful information regarding thyroid status in such patients.
ACUTE PITUITARY‐OVARIAN RESPONSE DURING CHRONIC LUTEINIZING HORMONE‐RELEASING HORMONE AGONIST ADMINISTRATION IN POLYCYSTIC OVARIAN SYNDROME
Authors: FAURE NACIA , LEMAY ANDRE
Published: March 2008

The purpose of the study was to evaluate the acute effect of daily subcutaneous injections of the GnRH agonist Buserelin on serum concentration of LH (evaluated by radioimmunoassay (iLH), and by bioassay (bioLH)), FSH, oestradiol and testosterone in 20 women with a diagnosis of polycystic ovarian disease (PCO). Buserelin was administered subcutaneously at the dose of 200 ng three times daily for 7 days followed by 500 fig once daily for a total treatment period of 6 months. Blood samples were drawn immediately before and 2,4 and 6 h after the injection on the first day of treatment as well as after 1,2,3,4,12 and 24 weeks. The first injection of Buserelin induced statistically significant rises of iLH, bioLH and FSH as well as of 17β‐oestradiol. The acute response of gonadotrophins was suppressed after 1 week but a partial recuperation of FSH and iLH responses was observed starting after 2 and 4 weeks of treatment. No significant acute changes of bioLH or of 17β‐oestradiol and testosterone could be seen.

The persistence of a small but statistically significant pituitary response in the first hours following the daily injection of the peptide suggests a hyper‐reactive state of the gonadotrophs in PCO patients. Such acute pituitary responses are not seen when a similar treatment is administered to endocrinologically normal women. This observation could be an argument in favour of an initial central defect in the pathogenesis of the syndrome.
DEMONSTRATION OF BLOCKING IMMUNOGLOBULINS G, HAVING A HETEROGENEOUS BEHAVIOUR, IN SERA OF PATIENTS WITH GRAVES' DISEASE: POSSIBLE COEXISTENCE OF DIFFERENT AUTOANTIBODIES DIRECTED TO THE TSH RECEPTOR
Authors: MACCHIA E. , CONCETTI R. , CARONE G. , BORGONT F. , FENZI G.F. , PINCHERA A.
Published: March 2008

Previous studies by us and others have shown that Graves' immunoglobulins G (IgGs) behaved as agonists or even antagonists of TSH. In this paper we have looked for the existence of IgG preparations without any thyroid stimulatory activity but able to significantly block the action of TSH in 128 hyperthyroid Graves' patients. The presence of TSH‐binding inhibiting antibodies (TBIAb) and that of thyroid stimulating antibodies (TSAb) was evaluated by a radioreceptor assay using solubilized thyroid plasma membranes and by assaying the adenylate cyclase (AC) function of thyroid plasma membranes, respectively. Seventeen IgGs were negative for TSAb but positive for TBIAb in the screening, using only one concentration of IgG. Three kinds of activity were investigated in these IgGs at different doses: (1) TSH‐binding inhibiting activity; (2) thyroid AC stimulating activity; and (3) the inhibition of TSH‐induced AC stimulation. The results showed that the level of activity was not always dose‐dependent. A significant (>20%) inhibition of the TSH‐dependent AC stimulation was present in 15 of the 17 IgGs examined: this inhibition was more elevated at lower than at higher doses in two preparations. No significant correlation was found between the three activities. In short, we have been able to demonstrate the existence of ‘blocking’ antibodies, apparently without any stimulatory activity, in some patients with Graves' disease. The diphasic pattern of the dose‐response curves of some IgGs and the lack of correlation between the different activities can be explained by the co‐existence in the sera of Graves' patients of different autoantibodies varying in concentration, binding affinity constant and intrinsic biological activity.
LDL/HDL‐CHANGES IN SUBCLINICAL HYPOTHYROIDISM: POSSIBLE RISK FACTORS FOR CORONARY HEART DISEASE
Authors: ALTHAUS B. U. , STAUB J.‐J. , LÈCHE A. RYFF‐DE , OBERHÄNSLI A. , STÄHELIN H. B.
Published: March 2008

The aim of the present study was to evaluate the lipid profiles (total cholesterol, triglycerides, low‐density lipoprotein‐cholesterol, high‐density lipoprotein‐cholesterol, and the electrophoretic low‐density lipoproteins and high‐density lipoproteins) in patients with subclinical (n= 52) and overt hypothyroidism (n= 18) in comparison to normal controls (28 and 18, respectively), matched for age, sex and body mass index. Subclinical hypothyroidism was defined as a syndrome with normal free thyroxine and total thyroxine but elevated basal thyrotrophin levels and/or an exaggerated TSH response to oral thyrotrophin releasing hormone. In subclinical hypothyroidism there was an elevated LDL concentration (P <0.01), a diminished HDL fraction (P <0.05) and a borderline elevated LDL‐C (not reaching the limit of significance, P=0.07). Total cholesterol and triglyceride concentrations remained unaltered. For the whole group of patients and controls significant negative correlations were found between LDL‐C and T4 (P < 0.04), total cholesterol and free thyroxine‐index (P<0.01); positive correlations could be demonstrated between LDL‐C and basal TSH (P < 0.03), the ratio total cholesterol/HDL‐C and basal TSH (P < 0.03), and triglycerides and basal TSH (P < 0.01). Our data provide a possible explanation for the higher prevalence of coronary heart disease reported in subclinical hypothyroidism. There may well be a case for the detection and early treatment of such individuals.
PHYSIOLOGICAL GROWTH HORMONE (GH) SECRETION DURING THE RECOVERY FROM PSYCHOSOCIAL DWARFISM: A CASE REPORT
Authors: STANHOPE R. , ADLARD P. , HAMILL G. , JONES J. , SKUSE D. , PREECE M. A.
Published: March 2008

We describe a 6.4 year old boy who had reversible GH insufficiency secondary to psychosocial dwarfism. On removal to a more favourable environment we observed the recovery of physiological GH secretion by progressive increase in GH pulse amplitude. These observations are relevant to our understanding of the control of GH secretion in that GH pulse frequency appears invariable and alteration in GH secretion is by pulse amplitude modulation.
3,5,3′‐TRHODOTHYROACETIC ACID MINIMIZES THE PITUITARY THYROTROPHIN SECRETION IN PATIENTS ON LEVO‐THYROXINE THERAPY AFTER ABLATIVE THERAPY FOR DIFFERENTIATED THYROID CARCINOMA
Authors: MUELLER‐GAERTNER H.‐W. , SCHNEIDER C.
Published: March 2008

The aim of this study was to examine the influence of 3,5,3′‐triiodothyroacetic acid (TRIAC) on serum thyrotrophin (TSH) concentration in 25 patients on levo‐thyroxine (L‐T4) therapy after ablative therapy for differentiated thyroid carcinoma. The daily L‐T4 intake amounted to 2.6 ± 0.7 μg/kg body weight (± SD). Serum TSH concentration was determined by means of a sensitive radioimmunometric method (lower detection limit 003 mU/l). The median (x̄) basal TSH concentration under L‐T4 amounted to 0.11 mU/l (range <0.03 mU/l‐7.39 mU/l). During supplementary intake of 500 μg TRIAC daily the median basal TSH decreased to 0 04 mU/l (range <0.03 mU/l‐0.24 mU/l; P<0.0003). The TRIAC‐induced decrease in 17 out of 20 basal TSH‐concentrations exceeding 003 mU/l ranged from 38% to as much as 98%. TRIAC reduced the median TRH‐stimulated TSH concentration from 0.25 mU/l (range <0.03 mU/l‐47.3 mU/l) to 0.04 mU/l (range <003 mU/l‐1.43 mU/l; P<0.0001). A blunted TSH‐response to TRH occurred in 8.7% prior to and in 52% of the patients during TRIAC medication. Side effects such as nervousness, cardiac arrhythmia or tachycardia under supplementary TRIAC (500 μg daily) were observed in four patients. The conclusion is that the supplementary medication of 500 μg TRIAC daily in euthyroid patients on L‐T4 medication after thyroid gland ablation for differentiated thyroid cancer is an effective means to minimize serum‐TSH concentration.
ARTHROPATHY IN ACROMEGALIC PATIENTS BEFORE AND AFTER TREATMENT: A LONG‐TERM FOLLOW‐UP STUDY
Authors: DONS R. F. , ROSSELET P. , PASTAKIA B. , DOPPMAN J. , GORDEN P.
Published: March 2008

The medical records of 90 patients with acromegaly were reviewed. Arthralgias were noted in 76% of the patients with 17% having the onset of joint pain concomitant with the clinical onset of acromegaly. Of 47 patients followed prospectively for 5 or more years after pituitary irradiation, six (12.8%) were unaffected by arthralgias. A statistically higher mean baseline growth hormone level was found for the 19 (40.4%) radiotherapy patients who had severe and disabling arthropathy. Mean intervals between clinical onset of acromegaly and the development of arthropathic symptoms were shorter (4.1 years) for patients over 40 years of age and longer (9.7 years) for those under 31 years of age. Severely affected patients tended to have increased joint spaces in both weight‐bearing and non‐weight‐bearing joints followed by a progressive decrease in joint spaces. Arthropathy is a common complication of acromegaly and may progress independently of a fall in growth hormone, induced by any form of treatment, once significant cartilage overgrowth develops. Cartilage overgrowth is a predisposing factor in the development of an arthropathy associated with the wide range of growth hormone levels characteristic of acromegaly.
PERIPHERAL ANTIGLUCOCORTICOID ACTION OF RU 486 IN MAN
Authors: BERTAGNA X. , BASIN C. , PICARD F. , VARET B. , BERTAGNA C. , HUCHER M. , LUTON J.‐P.
Published: March 2008

In order to evaluate the peripheral antiglucocorticoid activity of RU 486 in man we examined its ability to antagonize the effects of acutely administered glucocorticoids on blood leukocyte counts. The study was performed on eight normal male subjects. They were given 400 mg RU 486 (or placebo) orally at 0730 h and 1 mg dexamethasone (or placebo) orally at 0830 h, using a double‐blind, cross‐over, latin‐square design with a one week interval between each of the four different treatments. Circulating eosinophils, lymphocytes, and neutrophils were counted at 0730 h and 1330 h, and their variations (1330 h counts/0730 h counts × 100) were compared under each treatment. For each cell type, dexamethasone induced variations (eosinophil and lymphocyte drop, neutrophil rise) which were significantly (P < 0.05) different from those under the three other treatments; these latter treatments (placebo, RU 486, and RU 486 + dexamethasone) were equivalent to each other, inducing no variations of leucocyte counts. These data show that RU 486 inhibits dexamethasone induced leukocyte changes; this simple test provides a useful means to further analyse the peripheral antiglucocorticoid activity of RU 486 in man.
IN‐VIVO AND IN‐VITRO ENDOCRINE INVESTIGATION OF PURE GONADAL DYSGENESIS
Authors: WILSON S. C. , OAKEY R. E. , SCOTT J. S.
Published: March 2008

Diagnosis of XY pure gonadal dysgenesis was established in a patient of female phenotype, with female internal genitalia, but with a chromosomal constitution of 46 XY. Streak gonads had undergone neoplastic transformation–gonado‐blastoma and dysgerminoma. Before operation the concentrations of gonadotropins in plasma were high and of oestradiol was low. Administration of oestradiol benzoate initially suppressed and then stimulated an increase in the plasma concentration of LH. These changes were not accompanied by changes in blood levels of endogenous sex steroids. A single injection of hCG failed to stimulate steroid secretion. The activities in vitro of steroid‐metabolizing enzymes in the dysgenetic gonadal tissue more closely resembled those of ovarian tissue from a premenopausal and from a postmenopausal woman than those in testes from two androgen‐insensitive patients. However, aromatase activity was higher in the dysgenetic gonads than in the pre or post‐menopausal ovaries. Examination of enzymes in genital skin fibroblasts demonstrated normal activities of 3α/β‐β‐hydroxysteroid dehydrogenase and 17β‐hydroxys‐teroid dehydrogenase (oxidative and reductive directions). However, 5α‐reductase activity was low in minces and fibroblasts of genital skin from the patient. Androgen binding was within the range for male controls.
BIOLOGICAL AND IMMUNOLOGICAL ACTIVITY OF HUMAN CHORIONIC GONADOTROPHIN IN MATERNAL SERUM DURING EARLY PREGNANCY
Authors: RANTA TAPIO , YLINEN KARI , STENMAN ULF‐HAKAN , NIKULA HANNU , HUHTANIEMI ILPO
Published: March 2008

Serum chorionic gonadotrophin (hCG) levels were measured by three different assay methods in 20 women admitted to legal abortion and 21 patients having insulin‐dependent diabetes, both during 8 to 14 weeks of pregnancy. Biological activity of hCG was determined with a mouse Leydig cell in‐vitro bioassay, binding activity of the hormone to LH receptors by rat testis radiorecep‐torassay, and immunoreactivity by fluorimmunoassay. Bioassay and radioreceptorassay gave 1.4 and 1.7‐fold higher hCG concentrations than fluoroimmunoassay using the same standard. Correlations between hCG levels measured by bioassay and fluoroimmunoassay (r = 0.81; P<00) and radioreceptorassay and fluoroimmunoassay (r = 0.95; P<001) were good. The results emphasize the heterogeneity of hCG in the pregnancy serum. Different domains of the molecules are recognized by assay methods based on antigenicity, receptor binding and biopotency of the hormone.
SERUM ANDROSTANEDIOL GLUCURONIDE CONCENTRATIONS IN NORMAL AND HIRSUTE WOMEN AND PATIENTS WITH THYROID DYSFUNCTION
Authors: SCANLON M. J. , WHORWOOD C. B. , FRANKS S. , REED M. J. , JAMES V. H. T.
Published: March 2008

There is currently much interest in measurements of 5α‐androstane‐3α, 17β‐diol glucuronide (AdiolG) as a marker of peripheral androgen metabolism. We have therefore developed an assay to measure serum AdiolG levels and report that mean concentrations in hirsute (2.9± 1.9 nmol/1, mean ± SD, n= 15) and non‐hirsute (1.9 ± 0.6 nmol/1, n= 7) women with polycystic ovaries do not differ significantly from concentrations in normal women (2.2 ± 0.8 nmol/1, n= 20). However, a correlation was found between serum AdiolG levels and Body Mass Index (r = 0.48, P & 0.05) for women with polycystic ovaries, suggesting that weight may be an important factor in determining concentrations of this steroid conjugate. Serum AdiolG levels were significantly reduced in hypothyroid women (0.6 ± 0.4 nmol/1, n= 5) and women receiving oral contraceptive therapy (0.6 ± 0.4 nmol/1, n= 28) but increased in hyperthyroid women (4.0 ± 0.6 nmol/1, n= 5). The results from this study do not support the hypothesis that serum AdiolG levels provide a marker of peripheral androgen metabolism in hirsute women and show that it is essential to exclude from such investigations any women with thyroid abnormalities or receiving oral contraceptive therapy.
CHANGES IN ENDOGENOUS INSULIN SECRETION DURING CHILDHOOD AS EXPRESSED BY PLASMA AND URINARY C‐PEPTIDE
Authors: LARON Z. , AURBACH‐KLIPPER Y. , FLASTERSTEIN B. , LITWIN A. , DICKERMAN Z. , HEDING L. G.
Published: March 2008

Basal fasting values of plasma C‐peptide (CP), plasma insulin and 24 h urine CP were determined in 224 normal non‐obese subjects of both sexes ranging in age from 1 to 20 years. Analysis of the results by age, pubertal rating, sex and bone age (BA) during childhood showed that mean±SD plasma CP levels in both sexes rose from 0.07 ± 0.08 pmol/ml at the age of 1–2 years to 0.21 ±0.11 pmol/ ml at 8–10 years. Mean ± SD plasma insulin levels in both sexes rose from 3.2 ± 4.3 μU/rnl at the age of 1–2 years to 5.9±4.5 μU/ml at 8–10 years. Mean ± SD urine CP levels rose from 6.5 ± 2.8 pmol/mg creatinine per 24 h at the age of 2.8 years to 7.7 ± 3.5 pmol/mg creatinine per 24 h at 8.11 years in both sexes. During puberty, plasma and urine CP and plasma insulin levels rose further to peak at pubertal stage P3, the values in females being higher (CP = 0.32 ± 0.06 pmol/ml) than those in males (CP = 0.22 ± 0.06 pmol/ml) (P < 0.005). Plasma insulin levels in females were 13.2 ± 6.9 μU/ml and 6.4 ± 3.1 μU/ml in males (P<0.05). Urine CP levels were 14.5 ± 5.7 pmol/mg creatinine per 24 h and 10.8 ± 5.4 pmol/mg creatinine per 24 h in females and males respectively (P<0.05). With the rise in age, CP and insulin levels declined and towards adulthood were 0.23 ± 009 pmol/ml for plasma CP, 5.1 ± 4.2 μU/ml for plasma insulin and 8.7 ± 4.1 pmol/mg creatinine per 24 h for both sexes. There was a correlation between plasma CP and plasma insulin (P=0.32, P< 0.001, n = 89) and in pubertal males and females plasma CP correlated with BA (r = 0.32, P<0.02). It is concluded that endogenous insulin secretion during childhood varies with age, pubertal stage and sex. The index of choice for the most accurate and discriminative estimation of insulin secretion would appear to be CP rather than insulin itself, due to the differences in metabolism of these substances.
SECRETION OF INTACT PTH BY DISPERSED HUMAN HYPERPARATHYROID CELLS
Authors: ASTON J. P. , BROWN R. C. , CURLEY I. , WHEELER M. H. , WOODHEAD J. S.
Published: March 2008

The rate of secretion of intact PTH by cells dispersed from adenomatous and hyperplastic human parathyroid tissue was measured using a two‐site immuno‐chemiluminometric assay specific for the intact peptide. Secretion rates were monitored following incubation in high and low‐calcium media. The mean rate of secretion from hyperplastic cells was significantly greater (P<005) at low calcium and significantly more suppressible at high calcium (P<001) compared with adenomatous cells. These studies have demonstrated: (1) the calcium‐dependent secretion of intact PTH, (2) that intact hormone release contributes to the non‐suppressible component of secretion, and (3) differences in the secretory characteristics of adenomatous and hyperplastic parathyroid cells.
PLASMA INHIBIN LEVELS IN MEN WITH CHEMOTHERAPY‐INDUCED SEVERE DAMAGE TO THE SEMINIFEROUS EPITHELIUM
Authors: TSATSOULIS A. , SHALET S. M. , ROBERTSON W. R. , MORRIS I. D. , BURGER H. G. , DE KRETSER D. M.
Published: March 2008

Immunoreactive plasma inhibin levels and free testosterone index (FTI) were estimated in 17 patients who had previously received combination chemotherapy for Hodgkin's disease and in 16 age‐matched controls. In the same patients we had previously found significantly raised FSH and LH levels in the presence of normal basal and HCG‐stimulated total testosterone levels. Mean plasma inhibin levels were not different between the patients (601 ± 321 U/l) and controls (530 ± 174 U/l) nor were FTI values (81.5 ± 35 vs 91 ± 47 respectively). There was a positive correlation (r = 0.53, P< 0.05) between FSH and inhibin levels and a negative correlation between FSH and FTI(r=–0.51, P<0.05)in the patients but not in the controls. No such correlations with inhibin or FTI existed for LH but there was a positive correlation between LH and FSH levels in the patients. In four patients inhibin levels were pathologically raised and in this group mean FSH values (21.7 ± 4.7 IU/1) were higher (P<0001) and mean FTI (59.1 ±22.6) lower (P<0.001) than respective values (13.6 ± 5.3 IU/1 and 88.4±35) for the remainder of the patients. These data are not compatible with the hypothesis that inhibin is the major negative feedback signal for the control of FSH secretion.
VASOACTIVE INTESTINAL PEPTIDE AND ANTERIOR PITUITARY FUNCTION
Authors: PRYSOR‐JONES R. A. , JENKINS J. S.
Published: March 2008

Vasoactive intestinal peptide (VIP) is a highly basic 28 amino‐acid peptide which was first isolated from porcine small intestine (Said & Mutt, 1970). It is related to several other peptides including PHI (peptide with N‐terminal histidine and C‐terminal isoleucine amide), secretin, glucagon, and has some sequences similar to those of growth hormone releasing hormone (Fig. 1). The amino‐acid sequence of human VIP is identical with that of the porcine form (Itoh et al., 1983). It has been shown that human VIP is cosynthesized with PHM (peptide with N‐terminal histidine and C‐terminal methionine amide, the human analogue of PHI) from the same large precursor protein (Itoh et al., 1983).
GLYCOPROTEIN HORMONE ALPHA‐SUBUNIT AND PROLACTIN RELEASE BY CULTURED PITUITARY ADENOMA CELLS FROM ACROMEGALIC PATIENTS: CORRELATION WITH GH RELEASE
Authors: HOFLAND L. J. , VAN KOETSVELD P. M. , VERLEUN T. M. , LAMBERTS S. W. J.
Published: March 2008

In‐vitro data of pituitary adenoma cells from 28 acromegalic patients were evaluated. In addition to GH, PRL was produced by 16 adenomas (57%) and alpha‐subunit by 15 adenomas (54%) while there was a significantly higher incidence of tumours producing PRL and alpha‐subunit simultaneously.

From 26 pituitary adenomas enough cells were obtained in order to perform secretion studies. Percentage basal hormone release (medium: (medium + intra‐cellular hormone)) ± 100% of GH and alpha‐subunit by 11 adenomas showed a close correlation while such a correlation for GH and PRL was present only in a subgroup of 10 of 13 adenomas. The responses of GH and alpha‐subunit release to 10nM SMS201–995, 10nM bromocriptine, 100nM TRH and 10nM GHRH were closely related in that a response or an absent response of GH release to the four secretagogues was virtually always attended with a response or an absent response respectively of alpha‐subunit release. Such a relationship was less evident with respect to the effects of SMS201–995, bromocriptine, TRH and GHRH on GH and PRL release.

We conclude that basal and secretagogue‐induced alpha‐subunit release by cultured pituitary adenoma cells from acromegalic patients closely follows the pattern of GH release while such a relationship for GH and PRL is present only in a subgroup of the adenomas secreting GH and PRL simultaneously.
CHANGES IN BLOOD PRESSURE AND PLASMA NORADRENALINE IN SHORT‐TERM HYPOTHYROIDISM
Authors: BROWN ROBERT T. , LAKSHMANAN MARK C. , BAUCOM CELESTE E. , POLINSKY RONALD J.
Published: March 2008

Thirteen patients who had undergone thyroidectomy for thyroid cancer stopped thyroid hormone replacement prior to follow‐up radioactive iodine scans. Thyroxine was replaced by triiodothyronine (T3) for 4 weeks and T3 was stopped 2 weeks before the scan and 16 to 19 days before blood pressure measurement and venipuncture for obtaining plasma noradrenaline samples. During this time, a small but significant decrease in systolic blood pressure occurred, both supine and standing, while the corresponding plasma noradrenaline levels increased significantly. These findings indicate that the acute cardiovascular effect of brief thyroid hormone withdrawal is a decrease in blood pressure rather than the increase often observed in chronic hypothyroidism, and that plasma noradrenaline levels may increase much sooner than previously reported after onset of hypothyroidism.
FAILURE OF LONG‐TERM CYPROHEPTADINE THERAPY IN LOWERING GROWTH HORMONE LEVELS IN ACROMEGALY
Authors: DASH R. J. , AHMAD J. , SETHI B. K. , SIALY R.
Published: March 2008

Basal and post‐glucose growth hormone (GH) responses were evaluated in 10 acromegalics receiving cyproheptadine (cypro) 4 mg 6 hourly at 2 and 21 days after initiating therapy. Of the 10 patients, six had macroadenomas with varying degree of suprasellar extensions, one a microadenoma and three had persistent hypersomatotropism despite pituitary adenomectomy due to residual tumour. The basal and post‐glucose GH showed no significant change in all, except one with a pituitary microadenoma. His GH was reduced from 680 to 108 mU/L on the second and 82 mU/I on the 21st day of cypro therapy. These data do not suggest any therapeutic role of cypro in the management of acromegaly.
EFFECTS OF THE GABAERGIC AGENT SODIUM VALPROATE ON THE ARGININE VASOPRESSIN RESPONSES TO HYPERTONIC STIMULATION AND UPRIGHT POSTURE IN MAN
Authors: CHIODERA P. , GNUDI A. , VOLPI R. , MARCHESI C. , MARCHESI M. , DAVOLI D. , CAPRETTI L. , COIRO V.
Published: March 2008

In order to evaluate the possible influence of GABAergic neurotransmission on the arginine vasopressin (AVP) response to osmotic and pressure volumetric stimuli, the GABAergic drug sodium valproate was administered by mouth (200 or 400 mg 16 h, 8 h and just before tests) to eight normal men before osmotic (i.v. infusion of 0.51 m NaCl for 2 h) and orthostatic (standing upright and maintaining an orthostatic position for 20 min) tests. In both experimental conditions, the AVP rise was significantly lower in the presence than in absence of sodium valproate. The maximum AVP responses in the control orthostatic and osmotic tests were respectively 2.3 and 2.5 times higher than basal levels. When 600 mg sodium valproate was given, the maximum AVP rise in response to hypovolaemic and osmotic stimuli were respectively 1.75 and 2.1 times higher than basal value. Similar results were obtained giving 1.2 g sodium valproate. These results suggest that in man a GABAergic pathway is involved in the AVP responses to hypovolaemic and hyperosmotic stimuli.
URINARY GROWTH HORMONE DURING PUBERTY IN NORMAL AND DIABETIC CHILDREN
Authors: EDGE J. A. , HOURD P. , EDWARDS R. , DUNGER D. B.
Published: March 2008

The measurement of GH in urine may have many clinical applications, particularly in childhood. We have used a highly sensitive direct immunoradiometric assay to examine urinary GH excretion in children during puberty.

Fifty‐five healthy schoolchildren collected timed overnight urine samples. A further 36 children (15 normal, six of short stature and 15 diabetic) collected urine samples during a total of 50 ovenight plasma GH secretory profiles (15‐min sampling).

Overnight urinary GH excretion increased during puberty, with a peak at breast stage 2 in girls, and genital stage 4 in boys, before declining at stage 5. There was a positive correlation (r = 0.57, p = 0.003) with height velocity in girls, but not in boys. At each puberty stage except 2, the diabetics excreted more urinary GH than the normal children.

There was a highly significant correlation (r= 0.79, p<50.001) between mean overnight plasma GH concentrations and urinary GH excretion, suggesting that the latter accurately reflects physiological GH secretion.
CIRCULATING MONOCYTE (MACROPHAGE)‐SPECIFIC ANTIBODIES IN PATIENTS WITH AUTOIMMUNE THYROID DISEASES
Authors: ZEKI K. , SHIRAKAWA F. , FUJIHIRA T. , KANATANI M. , WATANABE K. , SUZUKI H. , ETO S.
Published: March 2008

We investigated the presence of circulating monocyte‐specific antibodies (monocytotoxic activities) by a complement‐dependent cytotoxicity test and the relations between these monocytotoxic activities and other immunological indices in patients with autoimmune thyroid diseases. Antibodies reactive for monocytes (macrophages) were found in the sera from patients with autoimmune thyroid diseases. These antibodies were present in both IgG and IgM fractions and specific for monocytes since they were absorbed by monocytes but not by lymphocytes or granulocytes; furthermore, lymphocytotoxic and granulocytotoxic activities were not changed after the absorption of the sample sera by monocytes. Also, these antibodies did not have cross‐reactivity to thyroid‐specific antigens demonstrated by absorption tests and their specificity was different from anti HLA‐DR antibody demonstrated by a flow cytofluorometric analysis. Monocyte‐specific antibodies are reactive for autologous monocytes as well as allogenic monocytes. Patients who had positive monocytotoxic activities had high levels of TSH receptor antibodies (TRAb) and antimicrosomal antibodies in Graves’disease, and monocytotoxic activities were significantly correlated with the levels of TRAb in Graves’disease. These results suggest that the monocyte‐specific antibodies (monocytotoxic activities) were significantly correlated with the immunological activities in Graves’disease.
CORRECTION OF LOW CIRCULATING LEVELS OF 1,25‐DIHYDROXYVITAMIN D BY 25‐HYDROXYVITAMIN D DURING REVERSAL OF HYPOMAGNESAEMIA
Authors: FUSS M. , BERGMANN P. , BERGANS A. , BAGON J. , COGAN E. , PEPERSACK T. , VAN GOSSUM M. , CORVILAIN J.
Published: March 2008

The effect of 25‐hydroxyvitamin D (250HD), given orally during the reversal of hypomagnesaemia, was studied in five patients with hypomagnesaemic hypocalcaemia and low serum levels of 25OHD and 1,25‐dihydroxyvitamin D (1,25(OH)2D). The results were compared to those obtained in five other patients with similar initial levels of magnesium, calcium, 25OHD and 1,25(OH)2D who did not receive 25OHD. Serum levels of 1,25(OH)2D in the ten hypomagnesaemic patients were lower than in ten control subjects with low serum levels of 25OHD. The reversal of hypomagnesaemia was similar in the two groups of patients and elicited a similar increase of circulating iPTH levels. The expected increase of circulating 25OHD was observed in patients supplemented with 25OHD; their circulating 1,25(OH)2D rose within 48 h to normal levels, contrasting with the delayed and poor increase of 1,25(OH)2D in patients receiving no 25OHD. The evolution of serum calcium was however identical in the two groups. Our results suggest that vitamin D deficiency was a significant factor leading to low circulating levels of 1,25(OH)2D in hypomagnesaemic hypocalcaemic patients. The biological consequences of low serum 1,25(OH)2D in these patients remain unclear, but clearly, normal levels of 1,25(OH)2D are not essential for the correction of hypomagnesaemic hypocalcaemia.
STUDIES OF TWO THYROTROPHIN‐SECRETING PITUITARY ADENOMAS: EVIDENCE FOR DOPAMINE RECEPTOR DEFICIENCY
Authors: BEVAN J. S. , BURKE C. W. , ESIRI M. M. , ADAMS C. B. T. , BALLABIO M. , NISSIM M. , FAGLIA G.
Published: March 2008

Of 22 previously reported patients with TSH‐secreting pituitary adenomas challenged with dopamine agonists, 18 showed no decrease in serum TSH. There have been few in‐vitro studies of these rare tumours so the mechanism of the dopaminergic resistance has remained obscure. We describe two further patients with thyrotrophinomas; the first was thyrotoxic (T3 6.1 nmol/l, TSH 7 mU/l) and the second was diagnosed after radioiodine for presumed Graves’disease. The second patient had an α‐subunit: TSH molar ratio less than unity (0.27). In‐vivo TSH responses to TRH, bromocriptine and domperidone were compared with those of the resected tumour cells in vitro, the latter studied using a continuous perifusion system. Dopamine receptors were sought in membranes from each tumour using a radioreceptor assay employing 3H‐spiperone. Patient 1 showed significant increases in serum TSH (7 to 13 mU/l) and α‐subunit (18.7 to 385 ng/ml) after 200 μg TRH (i.v.) but patient 2 showed no such increases (TSH: 69 to 72 mU/l, α‐subunit: 4.9 to 5.2 ng/ml). Neither patient showed a change in serum TSH following bromocriptine 2.5 mg (orally) or domperidone 10 mg (i.v.), though serum PRL responded normally. Serum TSH from patient 1 was of apparently normal molecular size but increased bioactivity (B/I ratio 3.8) and that from patient 2 was of increased molecular size but reduced bioactivity (B/I ratio 0.1). Tumour cells from each patient immunostained for TSHβ and α‐subunit, and secreted TSH in vitro. The first showed dose‐dependent TSH release after TRH (1–100 ng/ml) which could not be inhibited by dopamine (5 μmol/l) but the second was unresponsive to TRH in vitro. Neither tumour showed inhibition of TSH release by dopamine (5 μmol/l) or bromocriptine (0.01–10 nmol/l) and neither contained membrane‐bound dopamine receptors. The results suggest that the dopaminergic resistance typical of most TSH‐secreting pituitary adenomas may be due to altered or absent membrane‐bound dopamine receptors.
URINARY EXCRETION OF HUMAN EPIDERMAL GROWTH FACTOR IN THE VARIOUS STAGES OF DIABETIC NEPHROPATHY
Authors: DAGOGO‐JACK S. , MARSHALL S. M. , KENDALL‐TAYLOR P. , ALBERTI K. G. M. M.
Published: March 2008

Epidermal growth factor (EGF) is a polypeptide mitogen first isolated from mouse submaxillary glands and later from human urine. We have examined the pattern of urinary excretion of human EGF (hEGF) in normal subjects and in diabetic patients with varying degrees of nephropathy. hEGF was measured by homologous radioimmunoassay and expressed in terms of urinary creatinine excretion. On the basis of their albumin excretion rate, the diabetic patients were divided into those with normoalbuminuria (albumin excretion rate 3.5 (1.4–9.8) μg/min; mean (range)), microalbuminuria (albumin excretion rate 75 (30–128) μg/min) and macroalbuminuria (289 (169–879) μg/min). The albumin excretion rate for the normal subjects was 3.7 (1.6–9.7) μg/min. The mean (range) hEGF excretion (nmol hEGF/mmol creatinine) was 0.69 (0.47–1.29) for 19 healthy subjects, 0.60 (0.16–1.36) for the normoalbuminuric group (n= 18; NS), 0.47 (0.10–0.83) for the microalbuminuric patients (n = 19; P < 0.001 vs controls and normoalbuminuric diabetics) and 0.38 (0.10–0.63) for the macroalbuminuric group (n=18; P < 0.001 vs controls and normoalbuminuric diabetics). There was an inverse correlation between albumin excretion rate and hEGF: creatinine ratio (r =−0.49; P= 0.02). These results show a progressive decline in hEGF excretion in diabetic patients with varying degrees of nephropathy and do not support the hypothesis that increased kidney size seen in early nephropathy is due to excessive amounts of EGF in the urine.
ACUTE DEXAMETHASONE SUPPRESSION OF ACTH SECRETION STIMULATED BY HUMAN CORTICOTROPHIN RELEASING HORMONE, AVP AND HYPOGLYCAEMIA
Authors: HOHNLOSER J. , VON WERDER K. , MÜLLER O. A.
Published: March 2008

In order to obtain more insight into the mechanisms regulating endogenous ACTH secretion in humans we studied the inhibitory effect of acute i.v. dexamethasone administration on ACTH release under various conditions. Six male volunteers were subjected to six different protocols. After combined i. v. injection of 100 μg corticotrophin releasing hormone (CRH) and 100 μg growth hormone releasing hormone (GRH) there was the expected rise in ACTH (area under the curve, 1053 ± 204 (SE) (pmol/l) min) and cortisol (59788 ± 10098 (nmol/l) min) rise which was suppressed by prior i. v. injection of 2 mg dexamethasone (ACTH: 444 ± 63 (pmol/l) min; cortisol: 28528 ± 2152 (nmol/l) min). Insulin hypoglycaemia (IH) led to a more pronounced ACTH and cortisol rise compared with CRH (6307 ± 817 (pmol/l) min and 82080 ± 21934 (nmol/l) min, respectively) which was not completely suppressed by prior pretreatment with dexamethasone (ACTH, 580 ± 103 (pmol/l) min; cortisol: 55649 ± 5821 (nmol/l) min). Combined AVP/CRH injection (10 IU/100 fig) after pretreatment with dexamethasone (344 ± 41 (pmol/l) min for ACTH; 32832 ± 3173 (nmol/l) min for cortisol) could not reproduce the ACTH secretion following IH after pretreatment with dexamethasone (579 ± 103 (pmol/l) min for ACTH and 55649 ± 5821 (nmol/l) min for cortisol). In all subjects a saline control with 2 mg dexamethasone was performed. These findings confirm the acute inhibitory effect of glucocorticoids on CRH‐stimulated ACTH secretion. Since CRH‐induced ACTH secretion is almost completely abolished by administration of dexamethasone the ACTH rise following IH after dexamethasone can not be mediated by endogenous CRH alone. Moreover, since the addition of AVP to CRH (after dexamethasone suppression) could not reproduce the ACTH rise during IH after dexamethasone pretreatment, an additional, yet unknown factor stimulating ACTH secretion may be involved. In the same protocols, no significant difference could be observed comparing IH and GRH induced GH secretion (4948 ± 1172 (mU/l) min vs 3596 ± 820 (mU/l) min, NS); furthermore, in contrast to results obtained by chronic steroid administration, acute i. v. dexamethasone pretreatment did not affect IH or GRH‐induced GH secretion (4110 ± 666 (mU/l) min vs 2916 ± 462 (mU/l) min, NS). The GRH‐stimulated GH secretion (3596 ± 820 (mU/l) min) was not suppressed by prior intravenous treatment with dexamethasone (2916 ± 504 (mU/l) min, NS).
THE LONG‐TERM OUTCOME OF THYROIDECTOMY FOR SPORADIC NON‐TOXIC GOITRE
Authors: BERGHOUT A. , WIERSINGA W. M. , DREXHAGE H. A. , VAN TROTSENBURG P. , SMITS N. J. , VAN DER GAAG R. D. , TOUBER J. L.
Published: March 2008

To study the long‐term outcome after thyroidectomy, 113 sporadic non‐toxic goitre patients who underwent thyroidectomy in our hospital in the period 1974–1983, were studied. Five patients complained of recurrent goitre; a goitre was found on inspection and palpation in these five and in 15 others. There were no differences between the 20 patients with goitre and the 93 patients without goitre with regard to sex, age, duration of goitre, indication and type of thyroidectomy, postoperative thyroid hormone medication, period of follow‐up, and T4, T3, or TSH plasma values at the time of follow‐up examination. Twenty‐three patients complained of voice changes since thyroidectomy. In a case control study, included in this follow‐up study, 19 patients with goitre, i.e. thyroid size I and II as estimated by inspection and palpation (cases), and 16 patients without goitre, i.e. thyroid size OA and OB (controls), were studied in more detail. No difference between cases and controls was found in any of the above mentioned parameters that could explain the recurrence of goitre. Thyroid volume (median) was greater in the cases (34–1 ml, range 7.9–83.4) than in the controls (10.3 ml, range 2.5–48.7) (P < 0.001), although a considerable overlap between the two groups was observed. One or more thyroid nodules were found in 89.5% of the cases and in 62–5% of the controls (NS). Serum thyroid growth stimulating immunoglobulin (TGI) was present both in cases (68%) and controls (50%). TGI was present in high titres in all five patients who complained about recurrent goitre. Thyroid volume was negatively related to the plasma level of TSH (r =−0.36, P < 0.05), and positively but not significant to serum TGI. In conclusion: (1) a goitre is found in 17.7% of sporadic non‐toxic patients at long‐term follow‐up after thyroidectomy, not related to age, sex, duration of goitre, indication or type of operation, postoperative thyroid hormone medication, period of follow‐up, or plasma T3, T4, or TSH; (2) TGI is more prevalent in patients who complain of recurrent goitre after thyroidectomy; (3) thyroidal nodular disease persists in the majority of patients after thyroidectomy.
SERUM GROWTH HORMONE BINDING PROTEIN ACTIVITY IN HEALTHY NEONATES, CHILDREN AND YOUNG ADULTS: CORRELATION WITH AGE, HEIGHT AND WEIGHT
Authors: SILBERGELD A. , LAZAR L. , ERSTER B. , KERET R. , TEPPER R. , LARON Z.
Published: March 2008

Serum growth hormone binding protein (GHBP) activity was estimated in healthy neonates (n=6), children and adolescents (n=97) and young adults (n=19). GHBP activity was measured by incubating 125I‐hGH (human growth hormone) (˜ 25 000 c. p. m.) with serum (100 μ1) in the presence and in the absence of excess unlabelled hGH, followed by separation of specifically bound 1251‐hGHBP complexes from free 125I‐hGH by gel filtration on Ultrogel AcA44 minicolumns. The results are expressed as the percentage specific binding relative to an adult reference serum (%RSB), after correction for endogenous hGH of the unknown serum. The between‐assay coefficients of variation for two sera of %RSB activity of 51.2 and 115.4% were 6.0 and 7.0% respectively. In neonates, low values of serum GHBP were found (%RSB = 27.1 ± 5.0 SEM) followed by a major rise during the first 6 years of life to a mean value (%RSB = 68.3 ± 4.1 SEM) which more than doubled that of neonates. Thereafter, values rose progressively throughout childhood and puberty to reach maximum values in young adults (%RSB =95.0 ± 3.1 SEM). A novel observation was that serum GHBP activity correlated significantly with height standard deviation score (SDS) (males: r= 0.77, P < 0.001; females: r= 0.56, P= 0.01) and weight SDS (P < 0.001) for both sexes before puberty. During puberty GHBP correlated only with weight SDS in males (r=0.60, P < 0.01). In all age groups studied, no correlation could be found between serum GHBP and height velocity.