bluuebunny/crossref_metadata_2025 huggingface dataset:
SYSTOLIC TIME INTERVALS AND ANKLE REFLEX TIME IN PATIENTS WITH MINIMAL SERUM TSH ELEVATION: RESPONSE TO TRIIODOTHYRONINE THERAPY
Authors: OOI T. C. , WHITLOCK R. M. L. , FRENGLEY P. A. , IBBERTSON H. K.
Published: March 2008

The ankle reflex half relaxation time (ART) and the systolic time intervals (STI) of myocardial contraction have been proposed as useful indices of peripheral thyroid hormone action. In this study, these indices were evaluated in sixteen subjects with minimal serum thyrotrophin (TSH) elevation (5–25 μu/ml) to determine whether they have tissue hypothyroidism. Measurements were made before and after triiodothyronine (T3) therapy at subreplacement doses of 10 μg twice daily for 4 weeks and 20 μg twice daily for another 4 weeks. These results were compared with those of a control group of fifteen subjects with normal serum TSH (0–4 μu/ml), who went through the same protocol. Pretreatment STI were not significantly different between the two groups. Therapy with T3, 10 μg twice daily, did not alter STI in either group. A significant reduction in STI occurred in both groups with T3, 20 μg twice daily but the degree of reduction was not significantly different between the two groups. On the other hand, pretreatment ART was significantly longer in subjects with minimal serum TSH elevation than in normal subjects. T3 therapy at a dose of 10 μg twice daily, did not change ART in either group. However, a significant reduction in ART occurred with T3, 20 μg twice daily only in subjects with minimal serum TSH elevation and not normal controls. Thus, ART, but not STI measurement discriminated between the two groups and suggested that a mild degree of tissue hypothyroidism might exist in subjects with minimal serum TSH elevation, and that STI is less sensitive than ART in reflecting thyroid hormone action. In a further group of four subjects with overt hypothyroidism (serum TSH>25 μu/ml) pretreatment STI and ART were significantly prolonged. A greater fall in these indices occurred in this group with T3 therapy than in normal controls, confirming previous reports that STI and ART are abnormal in unequivocal hypothyroidism.
SERUM CONCENTRATIONS OF METABOLITES OF VITAMIN D IN PATIENTS WITH CHRONIC RENAL FAILURE (CRF). CONSEQUENCES FOR THE TREATMENT WITH 1‐α‐HYDROXY‐DERIVATIVES
Authors: JUTTMANN J. R. , BUURMAN C. J. , DE KAM E. , VISSER T. J. , BIRKENHÄGER J. C.
Published: March 2008

In forty‐two patients with chronic renal failure (CRF), serum concentrations of 25‐hydroxy‐cholecalciferol (25‐OHCC), 24,25‐dihydroxy‐cholecalciferol (24,25‐OH2CC) and 1,25‐dihydroxy‐cholecalciferol (1,25‐OH2CC) were measured before and during intermittent haemodialysis (IHD) and in a few cases also after renal transplantation. 25‐OHCC and 24,25‐OH2CC were measured by means of a competitive protein binding assay after Sephadex LH 20 chromatography and 1,25‐OH2CC by means of a radioimmunoassay after Sephadex LH 20 and high pressure liquid chromatography (HPLC). In our patients serum values for 25‐OHCC and 24,25‐OH2CC showed a seasonal fluctuation as in normal individuals. The concentrations in the serum of 24,25‐OH2CC and 1,25‐OH2CC showed a positive correlation with renal function. With regard to 24,25‐OH2CC this correlation was only found for the 24,25‐OH2CC: 25‐OHCC ratio which was used to eliminate the seasonal fluctuation. For both dihydroxylated metabolites subnormal concentrations were found when the creatinine clearance was 40–50 ml/min and lower. It appears that the decrease of the plasma level of these metabolites of Vitamin D preceeds (or is concomitant with) the changes in the serum values of calcium (Ca), phosphorus (P) and parathyroid hormone (PTH) and the diminution of the intestinal absorption of Ca. These findings indicate that patients with CRF should be treated at an early stage of the disease with 1α‐hydroxy‐derivatives of Vitamin D in order to prevent the development of, or to induce the healing of, bone‐lesions of renal osteodystrophy.
EFFECTS OF ETHINYLOESTRADIOL ON PLASMA LEVELS OF PITUITARY GONADOTROPHINS, TESTICULAR STERIODS AND SEX HORMONE BINDING GLOBULIN IN NORMAL MEN
Authors: VAN LOOK P. F. A. , FRÖLICH MARIJKE
Published: March 2008

Daily measurements of plasma FSH, LH, prolactin, testosterone, 17β‐oestradiol and sex hormone binding globulin (SHBG) activity were made in eight healthy, normal men during treatment with oral ethinyloestradiol (EE2) in a dose of 30 μg/day for 5 days following a 5‐day control period. No significant changes in plasma levels of FSH and prolactin during oestrogen treatment occurred. In contrast, plasma concentrations of both LH and testosterone showed a biphasic pattern. Following an initial suppression during the first 3 days of oestrogen treatment both LH and testosterone increased again to baseline values despite continuation of oestrogen administration. The secondary rise of both hormones was associated with (and probably resulted from) a nearly 100% increase in the plasma concentration of SHBG binding activity, and hence reduction of free testosterone index (FTI). Unlike testosterone, plasma 17β‐oestradiol during EE2 administration did not show a biphasic pattern, but a progressive decline that was positively correlated with the fall in FTI. The rapidity of onset and magnitude of the observed rise in SHBG levels emphasizes the need for measurement of this binding protein (or the free testosterone fraction) in studies on feedback regulation of gonadotrophins employing exogenous EE2 in human males. The observed increase of SHBG to supraphysiological values suggests that currently employed EE2 doses in such studies may be less ‘physiologic’ than is often assumed.
OESTROGEN‐GONADOTROPHIN FEEDBACK MECHANISMS IN THE PUERPERIUM
Authors: GLASS M.R. , RUDD B.T. , LYNCH S.S. , BUTT W.R.
Published: March 2008

The effect of oestradiol benzoate on serum gonadotrophin concentrations before and after LHRH administration was studied in lactating and non‐lactating women at 3 and 6 weeks post‐partum. Except in the non‐lactating women at 6 weeks, basal serum FSH concentrations were suppressed by oestrogen. There were no significant changes in basal concentrations of LH after oestrogen in the lactating women in either the 3‐ or 6‐week studies. Individual increases in the basal LH concentrations in two out of six non‐lactating subjects in the 6‐week study occurred but overall there were no significant changes.

In the 6‐week study amplification of the LH response to LHRH was found in both groups, the effect being significantly greater in the non‐lactating women. Overall FSH responses were also significantly different in the two groups, being suppression in those lactating and amplification in those not lactating. The LH/FSH ratios following LHRH administration in the 6‐week non‐lactating study were similar to those seen in the early follicular phase in regularly menstruating subjects. The basal ratios in the lactating subjects were, however, significantly less than those seen in the non‐lactating subjects both at 3 and 6 weeks. This difference was associated with the relative enhancement of LH release in non‐lactating subjects and enhancement of FSH release in those lactating.

Taken together the results indicate the presence of an intact negative feedback of oestrogen on gonadotrophin release in both groups being enhanced at 6 weeks post‐partum in the lactating subjects; also in the lactating subjects at 6 weeks there was less amplification by oestrogen of the responsiveness of the anterior pituitary to LHRH. At 6 weeks, however, in the non‐lactating group these responses were similar to those seen in normal regularly menstruating subjects. These dynamic endocrine studies suggest a possible hypothalamic‐ pituitary mechanism which may help to explain the delayed return of ovulatory cycles in lactating women.
ENDORPHINS AND THE REGULATION OF THE HUMAN MENSTRUAL CYCLE
Authors: BLANKSTEIN J. , REYES F.I. , WINTER J.S.D. , FAIMAN C.
Published: March 2008

In order to assess a possible influence of endogenous opioids upon gonadotrophin secretion in women, we examined the effects of i.v. administration of 10 mg naloxone, a specific opiate antagonist, in ten normal menstruating women, in thirteen women with amenorrhoea and/or hyperprolactinaemia and in two women with putative deficiency of gonadotrophin‐releasing hormone (GnRH). In thirteen subjects, a saline vehicle control study (randomized order of administration) was also performed. In the normal women, naloxone failed to elicit changes in serum gonadotrophin levels when administered during the early follicular phase of the menstrual cycle. However, significant increments of LH were observed from 30 to 165 min following naloxone administration during the late follicular phase. Similar LH responses occurred in the amenorrhoeic and hyperprolactinaemic women. There was a tendency towards a concomitant increment in FSH levels, which reached statistical significance variably from 60 to 105 min post‐naloxone. The LH response to naloxone in individual subjects showed a significant (P > 0·01) quadratic (U‐shaped) relationship to the log basal oestradiol concentration. No response to naloxone was observed in the two patients with GnRH deficiency despite a brisk response to an exogenous GnRH bolus. Taken together, these data suggest that central nervous system inhibitory opioid pathways may be involved in the regulation of LH secretion in normal women and that excessive production of endogenous opioids may play a role in the pathophysiology of some amenorrhoeic conditions.
THE EFFECTS OF MILD IODINE DEFICIENCY ON NEONATAL THYROID FUNCTION
Authors: BECKERS C. , CORNETTE C. , GEORGOULIS A. , SOUVATZOGLOU A. , SFONTOURIS J. , KOUTRAS D. A.
Published: March 2008

In order to assess neonatal thyroid function in the endemic goitre areas of Greece, T4 and TSH have been measured. Previous studies had shown that in these endemic areas, adults had low T4 but normal TSH values, probably because of an increase in the serum T3 level. In this study, T4 and TSH were measured in dried blood spots from 259 neonates. The fifty‐four full‐term neonates from the Greek endemic villages had a lower T4 value (8·8 ± 0·66 μg/dl SE) but a higher TSH (15·37 ± 1·12 mu/l) than the seventy‐three full‐ term neonates from the non‐endemic villages (T4:10·0 ± 0·33 μg/dl, TSH: 11·93 ± 0·59 mu/l) or the ninety‐eight from Athens (T4:10·0 ± 0·33 μg/dl, TSH: 10·96 ± 0·64 mu/l). Premature neonates, both from Athens and from the endemic areas, have significantly lower T4 and significantly lower TSH values than the full‐term ones from the same areas, probably because of the immaturity of the pituitary‐thyroidal axis. It is concluded from these observations that (a) Neonates suffer more from the consequences of iodine deficiency than adults. The biochemical hypothyroidism reported here may be relevant to the delayed skeletal maturation previously reported from children of these same areas. This emphasizes the need for correcting even moderate iodine deficiency. (b) The occurrence of non‐toxic goitre with normal TSH levels in adults is best explained by assuming that increased TSH stimulation is necessary for goitre formation during neonatal life, but not for goitre maintainance during adulthood. (c) Newborn screening programmes in these areas should take into account the present findings.
THE EFFECT OF NALOXONE ON PULSATILE GONADOTROPHIN RELEASE IN NORMAL SUBJECTS
Authors: MOULT P. J. A. , GROSSMAN A. , EVANS JOAN M. , REES LESLEY H. , BESSER G. M.
Published: March 2008

The gonadotrophin response to naloxone infusion has been investigated in three adult males, and three adult females in the early follicular phase. The frequency of LH secretory episodes and the mean LH levels increased in both sexes. The data suggest that the pulsatile release of LH is under inhibitory opiate control.
THE EFFECTS OF DIFFERENT DOSE REGIMES OF D‐SER(TBU)6‐LHRH‐EA10 (HOE 766) IN SUBJECTS WITH HYPOGONADOTROPHIC HYPOGONADISM
Authors: MOORE M. P. , SMITH R. , DONALD R. A. , ESPINER E. A. , STRONACH S.
Published: March 2008

Eight male patients with hypogonadotrophic hypogonadism were treated with injections of a long acting LHRH analogue, HOE 766. Six of the patients were on daily subcutaneous injections of 5 μg of this analogue at the start of this study and were changed to alternate‐daily injections of the same dose for 1–3 months. They were then treated with twice‐daily injections of 0·5 μg HOE 766, as was another subject not previously treated. The HOE 766 twice‐daily was given alone for 1 or 2 months and then sex steroid replacement therapy was added to this for a further 4–5 months. There was no clinical improvement or rise in plasma testosterone levels until sex steroid therapy was commenced. Basal LH and FSH levels and peak responses to 100 μg LHRH remained low throughout the study. It is concluded that these variations in dose and interval of administration do not overcome the lack of pituitary response which is a feature of prolonged treatment with LHRH analogues.
SERUM LEVELS OF T4, T3, REVERSE T3, 3,3′‐DIIODOTHYRONINE AND 3′,5′‐DIIODOTHYRONINE IN OBESITY, BEFORE AND AFTER JEJUNO‐ILEAL BYPASS
Authors: FABER J. , SØRENSEN T. I. A. , LUMHOLTZ I. B. , KLEIN H. C. , KIRKEGAARD C. , BLICKERT‐TOFT M.
Published: March 2008

Serum T4, 3,5,3′‐triiodothyronine (T3), 3,3′,5′‐triiodothyronine (reverse T3, rT3), 3,3′‐diiodothyronine (3,3′‐T2), 3′,5′‐diiodothyronine (3′,5′‐T2) and thyrotrophin (TSH) levels were studied in nineteen obese patients before and 6, 12, and 18, months after a jejuno‐ileal bypass. Before surgery, the obese patients had increased serum T3 levels compared with a group of lean, matched controls (median: 1·94 nmol/1 v. 1·44 nmol/l, P < 0·01). Serum T3 decreased to normal (1·64 nmol/l) 18 months after surgery. A slight decrease was also observed in serum 3,3′‐T2 levels, whereas progressive reductions in serum concentrations of rT3 and 3′,5′T2 occurred. Eighteen months postoperatively the serum levels of rT3 and 3′,5′‐T2 had decreased from 0·676 nmol/l to 0·430 nmol/l (P < 0·02) and 55–2 pmol/l to 40.0 pmol/l (P < 0·01), respectively, and the values at 18 months were also reduced compared with the control group [0·722 nmol rT3/1 (P < 0·01), 51·4 pmol 3′,5′‐T2/1 (P < 0·01)]. Concomitant with the decrease in serum levels of the iodothyronines, serum TSH concentrations increased from 0 μu/ml to 0·9 μu/ml (P < 0·01).
ENDOCRINE FUNCTION IN THALASSAEMIA
Authors: VANNASAENG S. , PLOYBUTR S. , VISUTKUL P. , TANDHANAND S. , SUWANIK R. , WASI P.
Published: March 2008

Twenty‐one Thai patients with β‐thalassaemia/haemoglobin E and haemoglobin H diseases, 8–20‐years‐old, were studied. These patients had received none or minimal blood transfusions. The important clinical endocrine abnormalities were growth retardation and sexual immaturity. GH secretion was found to be impaired in the majority of patients. Oral GTT showed chemical diabetes in one out of sixteen tested, a much lower incidence than in thalassaemic patients treated by hypertransfusion in the West. The mean insulin levels basally and after glucose loading were lower than those of the normal controls. Thyroid function was normal in all the patients. Serum cortisol and 24‐h urinary oxogenic steroids (17 OGS) levels were normal, as was adrenal cortical reserve in all the patients. The literature on endocrine function in thalassaemia is reviewed.
THE EFFECT OF PARTIAL THYROIDECTOMY FOR GRAVES' DISEASE ON SERUM LONG‐ACTING THYROID STIMULATOR PROTECTOR (LATS‐P)
Authors: HARDISTY C. A. , TALBOT C. H. , MUNRO D. S.
Published: March 2008

The effect of partial thyroidectomy on serum LATS‐P has been investigated in twenty‐one consecutive patients. Before surgery, LATS‐P was detectable in seventeen (81%) but 1 year after operation only five (24%) had activity. The activity did not fall immediately after surgery but declined progressively throughout the year. In no patient was an increase in activity demonstrated; nor did LATS‐P appear in those patients who did not have activity before operation.
HUMAN CORTICOSTEROID BINDING GLOBULIN
Authors: BRIEN T. G.
Published: March 2008

The literature on corticosteroid binding globulin (transcortin) in the human is reviewed under the following headings: physicochemical properties, biosynthesis, measurement, and physiological, pharmacological and pathological variations with particular emphasis of the effects of pregnancy and oral contraceptives. Finally, the physiological implications of corticosteroid binding globulin are discussed.
ADRENOCORTICAL TUMOUR IN UNTREATED CONGENITAL ADRENOCORTICAL HYPERPLASIA ASSOCIATED WITH INADEQUATE ACTH SUPPRESSIBILITY
Authors: VAN SETERS A. P. , VAN AALDEREN W. , MOOLENAAR A. J. , GORSIRO M. C. B. , VAN ROON F. , BACKER E. T.
Published: March 2008

Data are presented concerning a 60‐year‐old woman with untreated congenital adrenocortical hyperplasia due to 21‐hydroxylase deficiency, who presented with a tumour of the left adrenal gland. Steroid excretion was partly suppressed with dexamethasone. After removal of the tumour, the excretion of several steroid fractions decreased substantially, but suppression by dexamethasone remained inadequate. Preoperatively, plasma ACTH was elevated in the afternoon and decreased only slightly after dexamethasone administration. After surgery, cortisol secretion decreased markedly, whereas ACTH dysregulation became more prominent. Negative feedback failure precluded the use of normal suppressive therapy with low doses of glucocorticosteroids and led to the therapeutic removal of the right adrenal gland, which showed histological signs of nodular hyperplasia.
SUPPRESSION BY BROMOCRIPTINE OF THE SERUM LACTALBUMIN PEAK ASSOCIATED WITH HUMAN LACTOGENESIS
Authors: MARTIN R. H. , GLASS M. R. , CHAPMAN C. , WILSON G. D. , WOODS K. L.
Published: March 2008

The endocrine environment necessary for human lactation has not yet been clearly defined. In particular the role of prolactin is uncertain, since levels of this hormone usually fall to the normal non‐lactating range during the course of prolonged lactation. We have found that the immediate post‐partum peak of serum lactalbumin associated with lactogenesis was abolished by treatment with bromocriptine. This suggests a direct relationship between prolactin and lactalbumin production at this time.
THYROID HORMONES IN ACUTE MYOCARDIAL INFARCTION
Authors: WIERSINGA W. M. , LIE K. I. , TOUBER J. L.
Published: March 2008

Thyroid hormones were serially measured over a 2‐week period in thirty‐four consecutive patients with acute myocardial infarction (AMI). A transient increase in plasma rT3 and a decrease in plasma T3 was found, with the maximum changes occurring on the third day after the onset of AMI. The changes in plasma rT3 and T3 were greater in the seventeen patients with a complicated AMI (mean peak SGOT 145 u/l) than in the seventeen patients with an uncomplicated AMI (mean peak SGOT 79 u/l). A correlation was found between infarct size (as estimated by the peak SGOT value) and the following indices: ΔrT3, ΔT3, highest rT3/T3 and highest rT3/T4 ratios. A transient increase in plasma TSH (peak on days 4 and 5) and in plasma T4 and FT4 index (peak on days 6 and 7) was also observed, whereas T3 resin uptake (T3U) decreased. These findings suggest that the following sequence of events occurs in thyroid hormone metabolism during AMI: (1) inhibition of the 5′‐deiodination of T4, resulting in increased plasma rT3 and decreased plasma T3 values, and in a lower metabolic clearance of T4. (2) Increased secretion of TSH (provoked by the lower T3 levels) resulting in increased thyroidal secretion of T4 and T3, which is then switched off by the negative feedback of thyroid hormones on the pituitary.
ABNORMAL HYPOTHALAMIC‐PITUITARY FUNCTION IN POLYOSTOTIC FIBROUS DYSPLASIA
Authors: ALBIN JOAN , WU R.
Published: March 2008

Hypothalamic‐pituitary dysfunction was found in two patients with polyostotic fibrous dysplasia and leontiasis ossea. Both patients probably had McCune‐Albright syndrome with early sexual development, disfiguring craniofacial bone lesions, cutaneous hyperpigmentation and gigantism in childhood. Endocrinological studies revealed measurable plasma growth hormone throughout a 24‐h sampling period with preservation of sleep augmented rises. The mean 24‐h values were 329 and 7 ng/ml, respectively. Both their mean plasma prolactin concentrations, 385 and 45 ng/ml, and the 24‐h secretory patterns of prolactin were abnormal. One patient had an elevated mean plasma cortisol concentration of 8·5 μg/dl but the 24‐h pattern of cortisol secretion was normal. Basal plasma LH, FSH, TSH, T4 and T3 concentrations were normal but neither patient had a TSH response to TRH. Prolactin and growth hormone secretions were, however, increased after TRH. Oral glucose resulted in partial suppression of GH but an exaggerated insulin response in both patients. Post‐mortem in one patient revealed a thick calvarium with bony encasement of the pituitary gland. The pituitary and hypothalamus appeared normal on gross, light microscopic and electronmicroscopic examination. These data strongly suggest the presence of hypothalamic‐pituitary dysfunction in these two patients.
METABOLIC RESPONSE TO SUBTOTAL THYROIDECTOMY IN PROPRANOLOL‐TREATED THYROTOXIC PATIENTS
Authors: RASMUSSEN ULLA , CLEMENTSEN H. J. , JØRGENSEN J. V. , GULDHAMMER BIRGITTE , MOLLERUP CHARLOTTE , KEHLET H.
Published: March 2008

Changes in plasma cortisol, glucose, cyclic AMP, blood leucocytes, pulse rate and body temperature were measured during and for 24 h after subtotal thyroidectomy in eight propranolol‐treated (120–160 mg per day) mild to moderate thyrotoxic patients and eight patients with a non‐toxic goitre. The results showed a similar metabolic response to surgery in the two groups without any trends towards a hypermetabolic response in the toxic group. The accumulating evidence of the safety of preoperative preparation with propranolol in patients with mild to moderate thyrotoxicosis is thus supported by our results.
PATTERNS OF PLASMA CORTISOL AND ACTH CONCENTRATIONS IN PATIENTS WITH ADDISON'S DISEASE TREATED WITH CONVENTIONAL CORTICOSTEROID REPLACEMENT
Authors: FEEK C. M. , RATCLIFFE J.G. , SETH J. , GRAY C. E. , TOFT A. D. , IRVINE W. J.
Published: March 2008

Plasma cortisol and adrenocorticotrophin hormone (ACTH) profiles were estimated in twelve patients with Addison's disease following randomized oral administration of either cortisone acetate (25 mg) or hydrocortisone (20 mg) alternately, at 0900 h on consecutive days. Normal corticosteroid replacement therapy was discontinued from 1200 h on the day prior to the study period.

In four patients elevated basal plasma ACTH concentrations were not suppressed to the limit of detection following the administration of either drug, and in three of these no suppression was found following the prolonged administration of pharmacological doses of dexamethasone. Diminished sensitivity of pituitary ACTH secretion to cortisol inhibition may result from chronic loss of negative feedback before and/or after diagnosis and treatment. In three patients elevated basal plasma ACTH concentrations were suppressed adequately during the administration of either drug, but in five, low basal ACTH concentrations following corticosteroid withdrawal suggested chronic inhibition of anterior pituitary corticotrophs by over‐replacement with glucocorticoid. However, further study is necessary to determine whether the estimation of ACTH profiles is a more accurate reflection of the adequacy of corticosteroid replacement than the estimation of cortisol profiles alone, and whether this estimation leads to an improvement in patient management.

Hydrocortisone (20 mg) achieved higher mean cortisol levels and lower mean ACTH levels than cortisone acetate (25 mg), but either drug may be suitable for glucocorticoid replacement provided the dose is tailored to the individual needs.
TESTICULAR FUNCTION AFTER RENAL TRANSPLANTATION
Authors: HANDELSMAN D. J. , RALEC V. L. , TILLER D. J. , HORVATH J. S. , TURTLE J. R.
Published: March 2008

Gonadal function was assessed in seventeen adult male renal transplant recipients, with well established good homograft function, for a mean of 4·9 years. Patients were assessed clinically and by measurement of basal concentrations of FSH, LH, prolactin, testosterone and oestradiol, FSH and LH responses to bolus injections of LHRH and semen analysis. Retrospectively all had symptoms consistent with marked hypogonadism prior to transplantation but in nine out of sixteen this was reversed with transplantation. Residual hypogonadism was evident in seven of sixteen patients and correlated with duration of haemodialysis longer than 1 year (P < 0·01). Even among patients with clinically normal gonadal function, defects in the hypothalamic‐pituitary‐testicular axis remained. Elevated basal serum FSH, excessive FSH responses to LHRH and lowered basal serum testosterone were found. In the group with residual hypogonadism more marked changes, including elevated basal LH and excessive LH responses to LHRH, were also found. Fertility was recorded in two men on three occasions since transplantation. Sperm counts were normal in five and abnormal in four patients. Testicular volume and sperm density were inversely correlated with basal and stimulated FSH and LH levels.
SECRETION OF LH, FSH AND PRL SHOWN BY CELL CULTURE AND IMMUNOCYTOCHEMISTRY OF HUMAN FUNCTIONLESS PITUITARY ADENOMAS
Authors: MASHITER K. , ADAMS E. , VAN NOORDEN SUSAN
Published: March 2008

Hormone secretion by ten functionless human pituitary adenomas in cell culture has been measured, and compared with tissue immunocytochemistry and electron microscopy, as well as results with a normal pituitary. Patients presented following routine x‐ray and had no clinical or biochemical endocrine abnormality apart from one male with raised serum FSH and PRL, normal LH, and low testosterone. Of the ten adenomas, nine secreted both LH and FSH in cell culture and five of these also secreted PRL, one did not secrete any anterior pituitary hormones (ACTH was not measured). No GH or TSH was detectable in the cultures of the nine LH/FSH secretors excluding the possibility of contamination by normal anterior pituitary. The normal pituitary cells secreted all anterior pituitary hormones; the amounts of FSH/LH being comparable with those of the adenomas. Immunostaining confirmed the cell culture results and showed the adenoma FSH/LH cells to be scattered singly or in small groups of two to five cells with both hormones usually being in the same cell. PRL where found was in separate cells. Hormone granules were small (50–160 nm), round or irregular and scattered in the cytoplasm of rounded cells of low secretory activity. The negatively staining cells were not different ultrastructurally to those staining positively. It is concluded that a significant proportion of functionless pituitary adenomas have detectable low levels of LH/FSH secretion often accompanied by PRL when examined by cell culture or immunocytochemistry. Although these adenomas were endocrinologically quiescent activity could have been masked because of post‐menopausal secretion and one male probably had an FSH‐secreting adenoma.
EFFECTS OF CIMETIDINE ON PITUITARY FUNCTION: ALTERATIONS IN HORMONE SECRETION PROFILES
Authors: VALK T. W. , ENGLAND B. G. , MARSHALL J. C.
Published: March 2008

Cimetidine, an H2 receptor antagonist, was given for 6 weeks to six normal male volunteers to study the effects on pituitary, adrenal, thyroid, and testicular hormone secretion. Patients were studied before (day 1) and after (day 42) cimetidine (300 mg four times daily) therapy, and four of the six were restudied after discontinuing cimetidine for 1 month (day 72). Basal TSH concentrations and responses to TRH administration as well as T3 RIA and T4 resin uptakes did not change during or after cimetidine therapy. The diurnal rhythm of plasma cortisol and maximum cortisol response to insulin (0·15 u/kg) were similar on days 1 and 42, but urinary free cortisol excretion fell 31% (P < 0·01). Response of GH to exercise, 100 g carbohydrate ingestion and insulin were unchanged, but mean nocturnal GH secretion decreased 33% (P < 0·025) on cimetidine, and returned to baseline on day 72. The 24‐h plasma prolactin profile was unchanged as was the prolactin response to insulin and TRH stimulation. Plasma FSH was not altered, but mean LH concentrations decreased 20% on cimetidine and continued to decline (45% of day 1 levels) after discontinuation of cimetidine (P < 0·01). Spontaneous LH pulse amplitude declined slightly on day 42, but became significantly lower on day 72 (P < 0·01) while pulse frequency increased modestly on day 72 (P < 0·05). Peak LH responses to gonadotropin‐releasing hormone were also reduced on cimetidine therapy (P < 0·02). Plasma testosterone concentrations did not change but plasma oestradiol concentrations were 38% lower (P < 0·025) after cimetidine was discontinued.

H2 histamine receptors are involved in the control of multiple hormone secretory patterns and blockade of these receptors by cimetidine alters hormone profiles. These changed patterns have to be considered in the interpretation of hormone measurements in patients receiving cimetidine therapy.
INDICES OF SERUM ANDROGENS IN NORMAL PUBERTY: CORRELATIONS OF TWO INDICES WITH CHRONOLOGICAL AGE, BONE AGE AND PUBERTAL DEVELOPMENT IN BOYS AND GIRLS*
Authors: PENFOLD J. L. , SMEATON T. C. , GILLILAND J. M. , BOULTON T. J. C. , THOMSETT M. J. , PREECE M. A. , VIMPANI A.
Published: March 2008

Two indices of free serum androgenic activity, the normalized androgen ratio (NAR) and the free androgen index (FAI) were determined in 218 normal children aged 8–17·9 years. Before the onset of puberty and between chronological age 8 and 11·9 years, NAR and FAI were similar in both sexes, the NAR being < 0·8 and FAI < 0·1. In boys mean NAR value increased from 0·87 to 1·39 between 12·5 and 17·5 years, and mean FAI from 0·14 to 1·85, between 12·5 and 17·5 years. In girls mean NAR increased from 0·79 to 0·85 between 12·5 and 15·5 years, and mean FAI from 0·11 to 0·23, between 12·5 and 15·5 years. Both indices did not change significantly between 15·5 and 17·5 years in girls. A rapid increase in NAR and FAI occurred in boys from a mean testicular volume of 4·1 to >20 ml and from genital stage G2+ to 5+. In girls a gradual increase in NAR and FAI occurred from breast stage B2 + to 5+. Although the androgen indices increased in both sexes between pubic hair stages PH2 + and 6 +, the values in girls were always less than in boys at corresponding stages suggesting an increased androgen sensitivity of the female pubic hair follicle during adolescence.

The peak rise in NAR and FAI in boys between 13 and 15 years correlated closely with the timing of the pubertal growth spurt in this sex. A similar rise was not seen in girls at the time of their peak growth velocity between 11 and 13 years and suggested that androgens play only a minor or complementary part in the female growth spurt.
DEVELOPMENT OF A RADIOIMMUNOASSAY FOR AN AMINO‐TERMINAL PEPTIDE OF PRO‐OPIOCORTIN CONTAINING THE γ‐MSH REGION: MEASUREMENT AND CHARACTERIZATION IN HUMAN PLASMA
Authors: HOPE J. , RATTER SALLY J. , ESTIVARIZ F. E. , McLOUGHLIN LORRAINE , LOWRY P. J.
Published: March 2008

A radioimmunoassay has been developed for the N‐terminal region of human pituitary pro‐opiocortin (N‐POC), the common precursor protein of ACTH and β‐LPH, using an antiserum which recognizes residues near the γ‐MSH region. The concentrations of greater than 300 ng/l of immunoreactive peptide were determined in unextracted human plasma, the relative molecular mass of the reacting fragments corresponding to a seventy‐seven amino acid glycoprotein. The concentrations of immunoreactive N‐POC peptides were correlated with those of ACTH in plasma obtained from patients with various disorders of the hypothalamic‐pituitary‐adrenal axis.
A POSSIBLE DIRECT EFFECT OF 24,25‐DIHYDROXYCHOLECALCIFEROL ON THE PARATHYROID GLAND IN PATIENTS WITH CHRONIC RENAL FAILURE
Authors: CHRISTIANSEN C. , Rødbro P. , NÆSTOFT J. , CHRISTENSEN MERETE S.
Published: March 2008

Seventeen undialysed adult patients with chronic renal failure took part in a controlled study of the effects of 1,25(OH)2D3 and D3. After a 6‐month observation period the patients were allocated at random to two groups for 6 months of treatment with either 1,25(OH)2D3 (mean dose 0·5 μg daily) or D3 (dose 100 μg daily). The treatment was then discontinued and the patients were studied for a further 3 months.

In the 1,25(OH)2D3 group the mean serum concentration of 1,25(OH)2D rose significantly during treatment, whereas serum concentrations of 25OHD and 24,25(OH)2D remained unchanged. In the D3 group there was a highly significant increase in serum concentrations of 25OHD and 24,25(OH)2D, whereas serum 1,25(OH)2D remained unchanged.

There was a significant fall in serum iPTH in both treatment groups. This fall was unrelated to serum calcium in the D3 group unlike the findings in the 1,25(OH)2D3 group. The data support previous experimental evidence that serum iPTH can be suppressed by 24,25(OH)2D3 and suggest that this analogue may be of clinical importance in the treatment of chronic renal failure without inducing hypercalcaemia.
THE INFLUENCE OF CARBAMAZEPINE ON THYROID HORMONES AND THYROXINE BINDING GLOBULIN IN HYPOTHYROID PATIENTS SUBSTITUTED WITH THYROXINE
Authors: AANDERUD SYLVI , MYKING O. L. , STRANDJORD R. E.
Published: March 2008

Carbamazepine (CBZ) decreases the serum concentration of thyroid hormones. It is proposed that CBZ increases the extra‐thyroidal metabolism of thyroid hormones. In order to test this hypothesis CBZ was given to nine hypothyroid patients substituted with thyroxine (T4). A significant decrease in serum concentrations of T4, calculated free T4 (FT4), triiodothyronine (T3), and calculated free T3 (FT3) was found after 3 weeks of CBZ medication. The serum concentrations of TSH and the T4:T3 ratios were unaltered, while the serum concentrations of T4‐binding globulin (TBG) increased markedly in eight of the nine patients. These findings support the hypothesis of a CBZ induced increase in the extra‐thyroidal metabolism of thyroid hormones.
LIMITATIONS OF A NEW FREE THYROXINE ASSAY (AMERLEX® FREE T4)
Authors: STOCKIGT J. R. , GARIS M. De , CSICSMANN J. , BARLOW J. W. , WHITE E. L. , HURLEY D. M.
Published: March 2008

We have assessed a new method of free T4 measurement (Amerlex®) which uses a novel unidentified T4‐labelled analogue, said to be unreactive with T4 binding proteins in serum, together with an antibody that binds both analogue and T4. Free T4 is assessed by competition with analogue for antibody binding‐sites. The test method has been compared with free T4 measured by equilibrium dialysis and with a technique using an immobilized T4 antibody. All methods gave the expected free T4 levels in normal, hyperthyroid and hypothyroid subjects and normal free T4 levels with high or low levels of T4 binding globulin. However, in autosomal dominant familial euthyroid T4‐excess, where T4 is abnormally bound to albumin, the test method gave apparent high free T4 levels suggestive of hyperthyroidism. In a selected group of severely‐ill euthyroid patients the new method gave apparent low free T4 levels. In view of these discrepancies, binding of labelled analogue was evaluated by dextran‐charcoal separation at 4°C. Familial euthyroid T4‐excess sera showed greater analogue binding and samples with low prealbumin concentration showed less binding than did normal sera. Despite its validity with variations in TBG, it appears that Amerlex® Free T4 is influenced by lower‐affinity, high‐capacity T4 binding sites in serum, so that apparent free T4 concentration may vary with changes in the concentration of such sites.
AUTORADIOGRAPHIC COMPARISON OF GROWTH FACTORS: INFLUENCE OF GROWTH HORMONE AND SOMATOMEDIN B ON PATTERNS OF PROLINE INCORPORATION
Authors: RUDMAN C. G. , PARSONS J. A.
Published: March 2008

Patterns of incorporation of 14C proline have been compared by whole body autoradiography to study the action of growth factors, infused for 1 week to hypophysectomized rats by subcutaneously implanted minipumps. Human growth hormone (hGH) caused dose‐related increases in the width of the tibial epiphyseal cartilage and obvious weight gain, whereas only at 640 μg/week did Somatomedin B have a barely significant effect on these two parameters. Samples of tissues showing significant proline uptake by autoradiography were burned for direct measurement of 14C content. Both hGH (80–160 μg/week) and SMB (160–640 μg/week) significantly enhanced proline uptake in skin, tibia, liver and kidney. Whereas the Somatomedin was less active than hGH on skin it showed a greater effect on bone, significantly exceeding the apparently maximal response to hGH. The autoradiographic technique can be used not only to compare different growth factors but also to study the growth process by use of appropriate tracers.
THE METABOLIC EFFECTS OF CHRONIC HYPERGLUCAGONAEMIA
Authors: NANKERVIS ALISON , PROIETTO J. , NG K. W. , ALFORD F. P. , LARKINS R.
Published: March 2008

A subject with a benign glucagonoma was studied before and after complete resection of his pancreatic tumour. Studies were undertaken pre‐and post‐operatively to determine the effects of chronic hyperglucagonaemia on glucose tolerance and glucose kinetics both in the fasting state and during physiological insulin infusions, employing the [3H]‐3‐glucose technique. In addition the plasma cyclic AMP response to an acute infusion of glucagon was studied pre‐and post‐operatively.

The basal immunoreactive glucagon levels pre‐and post‐operatively were 10492 ± 1296 and 149 ± 15 pg/ml respectively. Pre‐and post‐operative oral glucose tolerance tests did not differ but were abnormal. Pre‐operatively basal hepatic glucose production was normal and it was suppressed rapidly by the low dose insulin infusion, despite continuing hyperglucagonaemia. The metabolic clearance rate of glucose was slightly reduced. There was no plasma cyclic AMP response to a glucagon infusion, suggesting down‐regulation of the glucagon receptor by the chronic hyperglucagonaemia. Post‐operatively the hepatic glucose production and clearance rate of glucose fell, whereas the plasma cyclic AMP responses to the glucagon infusion reverted to a normal pattern.

It is concluded that chronic hyperglucagonaemia is not a major factor in the development of the glucose intolerance, but it may lead to down‐regulation of the biological action of glucagon.
LACK OF SUPPRESSION OF INSULIN SECRETION BY EXERCISE IN PATIENTS WITH INSULINOMA
Authors: JARHULT J. , ERICSSON M. , HOLST J. , INGEMANSSON S.
Published: March 2008

Serum glucose, insulin and glucagon concentrations were measured in three patients with insulin‐producing tumours of the pancreas while performing an exercise test. In contrast to the normal adrenergic inhibition of insulin release in response to exercise, plasma insulin concentration remained at a constant and high level during exercise in patients with insulinomas. Their plasma glucose concentrations fell during exercise and in the post‐exercise period. No significant changes occurred in plasma glucagon concentration. An exercise test may be a useful new diagnostic tool in organic hyperinsulinism.
EVIDENCE AGAINST AN INTERACTION OF ANGIOTENSIN II WITH THE SYMPATHETIC NERVOUS SYSTEM IN MAN
Authors: NICHOLLS M. G. , ESPINER E. A. , MILES K. D. , ZWEIFLER A. J. , JULIUS S.
Published: March 2008

Animal experiments indicate that angiotensin II can, under some circumstances stimulate the sympathetic nervous system at a number of different sites. In order to determine whether such a relationship of the renin‐angiotensin and sympathetic nervous system exists in man, we increased (by intravenous infusion), or decreased (by administering the oral converting enzyme inhibitor captopril) circulating angiotensin II levels and monitored plasma adrenaline and nor‐adrenaline responses. Angiotensin II infusions did not increase plasma catechol‐amines, and lowering of angiotensin II by captopril treatment in patients with severe hypertension or congestive heart failure failed to alter plasma adrenaline or nor‐adrenaline levels. Whether physiological levels of angiotensin II are capable of interacting directly with the sympathetic nervous system in man remains to be demonstrated.
COMPARISON BETWEEN DOSE‐RESPONSES OF PROLACTIN, THYROID STIMULATING HORMONE AND GROWTH HORMONE TO TWO DIFFERENT HISTAMINE H2‐RECEPTOR ANTAGONISTS IN NORMAL MEN
Authors: KNIGGE U. , WOLLESEN F. , DEJGARRD A. , THUESEN B. , CHRISTIANSEN P. M.
Published: March 2008

The effects of the histamine H2‐receptor antagonists, ranitidine and cimetidine on prolactin (PRL), thyroid stimulating hormone (TSH), and growth hormone (GH) were studied in six normal males. Intravenous bolus injections of saline and of 50, 100, and 200 mg ranitidine and 300 mg cimetidine were tested. Ranitidine (100 and 200 mg) and cimetidine (300 mg) caused a significant increase in PRL secretion, whereas saline and ranitidine (50 mg) did not. TSH and GH secretion were unaffected by all doses. A dose‐response relationship between ranitidine and PRL was established, and a dose of 65 mg ranitidine was found to be the minimal effective PRL‐releasing dose. Plasma ranitidine concentration was measured by specific RIA. The results indicate an effect of H2‐receptor antagonists on physiological functions in the control of PRL secretion. Histamine, therefore, may play a role in the regulation of PRL secretion.
PRE‐OPERATIVE LOCALIZATION OF ALDOSTERONE‐SECRETING ADRENAL ADENOMAS
Authors: MCAREAVEY D. , BROWN J. J. , CUMMING A. M. M. , DAVIDSON J. K. , DUNCAN J.G. , FRASER R. , LEVER A. F. , MEEK D. , ROBERTSON J. I. S.
Published: March 2008

Techniques for pre‐operative localization of aldosterone‐secreting adrenal adenomas were studied in thirty‐seven patients, each with hypertension and biochemical evidence of primary hyperaldosteronism and each later having adrenal surgery (thirty‐two adenomas, five bilateral adrenal hyperplasia).

Bilateral adrenal vein catheterization was attempted in all cases; it was successful on the left side in all patients and in 92% of cases on the right. Adrenal vein plasma samples were obtained from the left side in 92% and from the right in 73% of cases. Adrenal vein plasma aldosterone measurements correctly indicated the presence of tumour in twenty‐eight cases but falsely predicted unilateral adenoma in two cases of bilateral adrenal hyperplasia. Adrenal venography also correctly predicted unilateral adrenal adenomas in twenty‐six cases but falsely suggested the presence of tumour in three cases of bilateral adrenal hyperplasia.

Computed tomography (CT) was used in the last eight cases. In seven instances the predictions (six adenomas, one bilateral adrenal hyperplasia) were confirmed at surgery. However, the remaining patient harboured an adenoma 20 mm in diameter which was not detected by CT although diagnosed both by adrenal venography and adrenal vein aldosterone measurements.

Ultrasound detected adenoma in only three of twenty‐two cases examined. Although further comparative studies of the type described here are required, the results of computed tomography are promising and suggest that this non‐invasive technique might well become the first choice procedure in localizing aldosterone‐secreting adenomas.
DIURNAL HORMONE‐METABOLITE PROFILES IN HYPOTHYROIDISM
Authors: McCULLOCH A. J. , JOHNSTON D. G. , BURRIN J. M. , HODSON A. W. , CLARK F. , WAUGH C. , ØRSKOV H. , ALBERTI K. G. M. M.
Published: March 2008

To investigate the influence of thyroid hormones on intermediary metabolism in man, hormone and metabolite profiles were obtained over a 12‐h period of normal meals and activity in eight hypothyroid subjects before and during thyroxine replacement therapy, and in sixteen matched controls.

The fasting blood glucose concentration and the mean 12‐h blood glucose concentration were normal in hypothyroid subjects but the blood glucose response to breakfast was exaggerated. Fasting blood lactate and pyruvate levels were normal but post‐prandial hyperlactataemia and hyperpyruvicaemia were found and mean 12 h values for lactate (hypothyroid 1·08 ± 0·06 v. control 0·77 ± 0·03 mmol/l, P<0·01) and pyruvate (0·10 ± 0·01 v. 0·08 ± 0·003 mmol/l, P < 0·01) were elevated. Blood alanine concentrations were elevated only in the evening. Although plasma non‐esterified fatty acid levels were normal, fasting blood glycerol levels were decreased (0·06 ± 0·01 v. 0·08 ± 0·01 mmol/l, P <0·001) and this decrease persisted throughout the 12‐h period. Blood total ketone body concentrations did not differ from controls, but, as for plasma NEFA and blood glycerol, the normal preprandial rise in concentration was absent. Serum insulin, glucagon and growth hormone concentrations did not differ from control values at any time.

Six months of thyroxine (T4) treatment produced a rise in blood glycerol concentrations (mean 12 h value during T4 therapy, 0·06 ± 0·01; before T4 therapy, 0·04 ± 0·005 mmol/l; P<0·01) but not to control values (0·08 ± 0·01 mmol/l). Concentrations of glucose and other gluconeogenic precursors were unaltered by therapy but the insulin response to meals and the mean 12 h serum insulin concentration were increased.
LONG‐TERM EVALUATION OF THYROIDAL RESPONSE TO PARTIAL CALORIE RESTRICTION IN OBESITY
Authors: MOREIRA‐ANDRÉS M. N. , DEL CAÑIZO‐GÓMEZ F. J. , BLACK E. G. , HOFFENBERG R.
Published: March 2008

Twenty obese patients were treated as out‐patients with a 3·35 MJ (800 Kcal) per day diet, and, by the double‐blind method, ten of the patients were prescribed 40 μg of triiodothyronine (T3) daily and the other ten placebo. Body weight and serum thyroxine (T4), T3 and reverse T3 (rT3) concentrations were measured before treatment, then monthly over 6 months.

No significant difference in mean weight loss was found between the patients receiving T3 and those on placebo. Serum T3 concentration decreased slightly in patients on placebo and increased in those on T3 but these changes were not statistically significant. However, patients on T3 maintained a significantly higher concentration of T3 in serum than those on placebo. Mean serum T4 and rT3 concentrations remained essentially unchanged in the patients on placebo, whereas both decreased significantly in patients receiving T3. We conclude that changes in serum T3 during dietary treatment of obesity are of minor significance in limiting the expected weight loss in the patients.
HORMONE BINDING GLOBULIN LEVELS IN PATIENTS WITH HEREDITARY ANGIOOEDEMA DURING TREATMENT WITH DANAZOL *
Authors: SCHWARZ S. , TAPPEINER G. , HINTNER H.
Published: March 2008

Five patients with hereditary angiooedema were treated with Danazol for periods up to 10 months. This therapy resulted in normalization of serum levels of the inhibitor of the first complement component and disappearance of clinical disease symptoms in all patients. Although a variety of hormones were measured, only those of the pituitary‐gonadal axis altered during treatment: a moderate decrease in leuteinizing hormone levels and a sharp fall of testosterone in adult men were observed. In all patients, however, both sex hormone binding globulin and thyroxine binding globulin concentrations were considerably suppressed during Danazol therapy. However, levels of corticosterone binding globulin remained unchanged. The fraction of endogenous testosterone not bound to sex hormone binding globulin invariably increased. The possible relevance of these findings to the understanding of the mode of action of Danazol both in these patients and in general, are discussed.
THE EFFECT OF PROPRANOLOL ON THYROID HORMONES IN T3 TOXICOSIS
Authors: JONES M. K. , OWENS D. R. , JONES G. R. , BIRTWELL J.
Published: March 2008

Serum thyroid hormone concentrations were measured before and during 6 months treatment with propranolol (160 mg/day) in eight patients with T3 (triiodothyronine) toxicosis. Serum total T3 concentrations showed a significant (P < 0·01) and sustained fall to approximately 80% of pre‐treatment values. Six of the patients, however, remained clinically and biochemically hyper‐ thyroid and our data do not support the use of propranolol as sole therapy in T3 toxicosis.