bluuebunny/crossref_metadata_2025 huggingface dataset:
COMPARISON OF THE ACTH AND CORTISOL RESPONSES TO PROVOCATIVE TESTING WITH GLUCAGON AND INSULIN HYPOGLYCAEMIA IN NORMAL SUBJECTS
Authors: LITTLEY M. D. , GIBSON S. , WHITES A. , SHALET M.
Published: March 2008

The glucagon stimulation test (GST) is often used to assess pituitary ACTH reserve, particularly when other tests are contra‐indicated. In a preliminary investigation, in patients with pituitary disease, we failed to demonstrate the ACTH dependence of the cortisol response. We have therefore compared the ACTH, cortisol and glucose responses to glucagon (1 mg s. c.), insulin (0.2 U/kg i. v., ITT) and placebo in six healthy male volunteers, sampling every 10 min for 6 h. During the GST, mean |Mp SD serum cortisol rose from 256 ± 80 nmol/1 to a peak of 481 ± 164 nmol/1 (range 289–717 nmol/1, P < 0.01) in comparison with 280 ± 81 nmol/1 to 602 ± 110 nmol/1 (range 493‐742 nmol/1) during the ITT (P < 0.002). The mean peak cortisol levels achieved in the two tests did not differ significantly. In the GST, plasma ACTH rose from a mean basal value of 10.9 ± 16.6 ng/1 to a mean peak level of 123 ± 76 ng/1 (P < 0.02) (ACTH ng/ 1 × 0.225 = pmol/1). The corresponding values in the ITT were 7.1 ± 16.2 ng/l and 263 ± 91 ng/1(P < 0.001). The mean peak ACTH level was significantly greater during the ITT (P < 0.05). Thus the cortisol response was ACTH dependent in both the GST and the ITT in normal subjects. Furthermore, the ACTH response was of sufficient duration to be detected by the usual procedure of sampling every 30 min. However, in clinical practice, more prolonged sampling should be undertaken during the GST, as two subjects showed their peak cortisol response after 3 h. In addition, this study suggests that the ‘normal’response to GST requires redefinition in view of four subjects in whom the peak cortisol response was less than 500 nmol/1.
DIFFUSE SCLEROSING PAPILLARY CARCINOMA OF THYROID: A WOLF IN SHEEP'S CLOTHING
Authors: WU PATRICIA S‐C. , LESLIE PETER J. , McLAREN KATHRYN M. , TOFT ANTHONY D.
Published: March 2008

We describe three patients with a rare, and only recently reported, variant of papillary carcinoma of the thyroid. In each case the clinical presentation and biochemical or serological findings were indicative of benign disease.
INFLUENCE OF OESTRADIOL AND PROGESTERONE ON PULSATILE LH SECRETION IN POSTMENOPAUSAL WOMEN
Authors: CAGNACCI ANGELO , MELIS GIAN BENEDETTO , PAOLETTI ANNA MARIA , GAMBACCIANI MARCO , SOLDANI RENZA , SPINETTI ADRIANA , FIORETTI PIERO
Published: March 2008

Pulsatile LH secretion was studied in six healthy postmenopausal women. Blood samples were obtained every 10 min during an 8‐h saline infusion performed before and during the administration of transdermal oestradiol alone (E2; 50 μg/day) and in combination with vaginal progesterone (P; 100 mg twice daily). Plasma E2 and P levels reached values similar to those found in the early follicular phase and in the luteal phase of the menstrual cycle, respectively. The mean plasma LH levels significantly decreased (P < 0.01) during trans‐dermal E2 with and without vaginal P. A significant increase in the frequency (P < 0.025) and the amplitude (P <0.05) of LH pulses was observed during transdermal E2. The administration of vaginal P to oestrongenized women significantly blunted the frequency (P < 0.05) and enhanced the amplitude (P<0.05) of LH pulses. In all experimental conditions, the mean plasma LH levels showed a positive linear correlation with the amplitude of LH pulses. The present results show that peripheral levels of E2, similar to those of the early follicular phase of the menstrual cycle, can influence the pulsatile pattern of LH secretion, enhancing the frequency and the amplitude of LH pulses. In oestrogenized patients, the increase of peripheral P plasma levels to postovulatory values restored a pulsatile pattern of LH secretion similar to that of the early luteal phase of menstrual cycle.
CELL POPULATION KINETICS IN DOG AND HUMAN ADULT THYROID
Authors: COCLET J. , FOUREAU F. , KETELBANT P. , GALAND P. , DUMONT J. E.
Published: March 2008

Cell population kinetics was studied by bromodeoxyuridine (BrdU) histochemical and 3H thymidine radioautographic labelling in dog thyroids. In‐vivo labelling with BrdU and in‐vitro labelling of incubated slices with 3H thymidine gave similar results. This validates the use of in‐vitro labelling of slices for the study of cell kinetics in the thyroid. In‐vitro labelling of human thyroid slices demonstrated a labelling index of 13.4 ± 10−5 for follicular cells; assuming an S phase of 10 h, this corresponds to a turnover time of the order of 8.5 years for the follicular cells. Stromal cells appear to turn over faster. These results show for the first time that human thyroid cells divide about five times during adulthood and therefore that the steady state level of thyroid cell mass results from a balance between cell division and cell loss. A shorter turnover time was found as expected in the thyroid of an adolescent and in follicular colloid nodules.
HORMONES AND HYPERTENSION
Authors: FRASER ROBERT , DAVIES DAVID L. , CONNELL JOHN M. C.
Published: March 2008

It seems clear that hypertension may be a common feature of growth hormone excess, but precise frequency figures cannot be derived from current data due to bias and inadequate epidemiological study techniques. The mechanism of increased blood pressure is also unclear. There is clear evidence of gross sodium retention and hypertrophy of the heart and blood vessels but these occur in both normotensive and hypertensive acromegaly. This is also true of changes in body fluid volumes. Studies of changes in the levels of, and blood pressure sensitivity to, hormones such as ANF, angiotensin II and catecholamines are frequently contradictory and also difficult to interpret at present. The interrelationships between growth hormone, renal function and blood pressure require further careful study.
BROMOCRIPTINE THERAPY FOR NON‐FUNCTIONING PITUITARY ADENOMA
Authors: VAN SCHAARDENBURG D. , ROELFSEMA F. , VAN SETERS A. P. , VIELVOYE G. J.
Published: March 2008

Over a 6‐year period, 25 patients with non‐functioning pituitary adenomas were treated with bromocriptine, while 18 other patients with this condition underwent surgery as the first therapeutic modality. The medically treated group, consisting of those patients without alarming eye symptoms, was analysed in retrospect. Eight of these patients had previously undergone surgery and radiotherapy. Bromocriptine was used in a dose of 5 to 22.5 mg per day; the mean duration of treatment was 18 months. For 11 patients, radiological findings obtained during the year before treatment with bromocriptine revealed progression in five cases and stable tumour size in the others. Three of the five patients with progression showed tumour size reduction during bromocriptine therapy while no further growth occurred in the other two. When medication was stopped in one responding patient, the tumour grew again. One other patient, without pretreatment radiological investigation, exhibited tumour size reduction during bromocriptine therapy, and one patient exhibited radiological progression during the study period. In one case visual fields improved and in one other deteriorated without parallel changes in tumour size on computerized tomography. The favourable reactions were equally divided between the groups with and without previous radiotherapy. We conclude that bromocriptine is rarely capable of reducing the size of non‐functioning pituitary adenomas (16% in this series). However, pituitary adenomas exhibiting recent growth may be sensitive to this drug, leading to size reduction or growth arrest.
INTERACTION OF CLONIDINE AND GHRH ON GH SECRETION IN VIVO AND IN VITRO
Authors: ALBA‐ROTH JULIA , LOSA MARCO , SPIESS YURIKO , SCHOPOHL JOCHEN , MÜLLER O. ALBRECHT , VON WERDER KLAUS
Published: March 2008

To investigate the mechanism by which clonidine stimulates GH‐secretion in vivo and in vitro, we studied its interaction with GHRH. In vivo: eight or six normal male subjects were submitted to five protocols: (1) 150 μg clonidine orally followed by 50 μg GHRH 1–44 i.v. 2 h later, (2) 50 μg GHRH 1–44 i.v. followed by 150 μg clonidine orally 2 h later, (3) 150 μg clonidine orally followed by GHRH i.v. 30 min later, (4) 300 μg clonidine orally followed by 50 μg GHRH i.v. 3 h later and (5) 50 μg GHRH i.v. followed by 300 μg clonidine orally 90 min later. In vitro: Rat anterior pituitary cells were coincubated with clonidine (10‐11, 10‐9, 10‐7 and 10‐5 m) and GHRH (0.005, 0.05, 10 nM) for 4h. Results: 150 μg clonidine alone does not stimulate GH‐secretion. Furthermore, the GH‐increase was not significantly different when GHRH bolus was given before, after or together with clonidine. When 300 μg clonidine was given before GHRH GH‐levels were significantly higher (max 28.6 ± 8.0 mU/1) at 90 min, compared to when clonidine was given after GHRH (max 7.8 ± 3.6 mU/1). The GHRH bolus after clonidine led to a significantly lower GH‐increase (max 31.6 μg 17.0 mU/1) compared to the GHRH‐induced GH‐increase (max 47.2 μg 13.0 mU/1) before clonidine. In vitro, clonidine had no stimulatory effect on GHRH‐stimulated GH secretion. These findings are compatible with clonidine leading to stimulation of GH by inducing endogenous GHRH release.
METHIMAZOLE‐INDUCED AGRANULOCYTOSIS IN JAPANESE PATIENTS WITH GRAVES’ DISEASE
Authors: TAMAI HAJIME , TAKAICHI YUKIHIKO , MORITA TETSUYA , KOMAKI GEN , MATSUBAYASHI SUNAO , KUMA KANJI , WALTER ROBERT M. , KUMAGAI LINDY F. , NAGATAKI SHIGENOBU
Published: March 2008

We reviewed the records of approximately 7000 Japanese patients whose hyperthyroidism was treated with methimazole (MMI) alone. Four patients (Group I) developed agranulocytosis during a second course of MMI therapy and eight patients (Group II) during an initial course. Six patients (three in each group) received less than 30 mg MMI daily. Agranulocytosis occurred after more than 2 months of therapy (12 weeks‐1 year) in five patients. Seven patients were less than 40 years of age. One patient displayed a gradual protracted development of agranulocytosis. These results indicate that agranulocytosis after MMI may occur irrespective of dose, age, duration of treatment, and with a second exposure.
ANTIGENICITY AND EFFICACY OF AUTHENTIC SEQUENCE RECOMBINANT HUMAN GROWTH HORMONE (SOMATROPIN): FIRST‐YEAR EXPERIENCE IN THE UNITED KINGDOM
Authors: BUZI F. , BUCHANAN C. R. , MORRELL D. J. , PREECE M. A.
Published: March 2008

Twenty‐one children were treated for GH deficiency with authentic sequence biosynthetic human GH (somatropin), 60 μg/kg body weight, subcutaneously, three times weekly for 1 year or longer. The magnitude of growth response and rise in serum insulin‐like growth factor I levels were similar to those expected from experience with pituitary GH and somatrem. Three patients developed serum antibodies to GH with a binding capacity < 0.02 μg/l, but in only one patient was the GH binding capacity < 10 μg/l and he showed no attenuation of growth response. Eschericliia coli polypeptide antibodies did not rise significantly and no clinically important side‐effects occurred. Somatropin is safe, effective and of low immunogenicity in the treatment of GH deficiency.
USE OF COMBINED ORAL CONTRACEPTIVE PREPARATIONS ALTERS THE INSULIN SENSITIVITY OF FATTY ACID AND KETONE METABOLISM
Authors: SINGH B. M. , NATTRASS M.
Published: March 2008

Eight women taking low‐dose‐oestrogen combined oral contraceptive preparations were compared to eight women in the luteal phase of the menstrual cycle during hourly incremental insulin infusions of 0 (basal), 0.005, 0.01 and 0.05 U/kg/h short‐acting insulin.

Dose‐response relationships between insulin and intermediary metabolites were sought by analysis of variance applied to regression. For insulin (log) and glucose the slope of the relationship was significantly shallower in the oral contraceptive group.

For insulin (log) and non‐esterified fatty acids the slopes of the regression lines were not different between groups but lines were significantly displaced. For insulin (log) and total ketone bodies (log) slopes of the regression lines were not different but significant displacement was observed. At identical insulin concentrations women taking an oral contraceptive had higher non‐esterified fatty acids (NEFA) (difference between groups +0.15 mmol/l, P > 0.001) and total ketone bodies (log; −0.26 mmol/l, P > 0.001). The potency of insulin action in oral contraceptive users versus the luteal group was 0.47 (P > 0.01) for NEFA and 0.38 (P > 0.001) for total ketone bodies.

The results demonstrate, for the first time, in‐vivo insulin resistance of NEFA and ketone bodies’ metabolism induced by oral contraceptive use.
ACUTE CHANGES IN SERUM THYROTROPHIN IN TREATED ADDISON'S DISEASE
Authors: ISMAIL A. A. A. , BURR W. A. , WALKER P. L.
Published: March 2008

Serum and salivary cortisol, plasma ACTH and serum TSH, free T4, free T3, PRL, LH and FSH were measured before and hourly after the morning steroid replacement therapy of five patients with Addison's disease. In the 4 h after hydrocortisone the levels of TSH fell in all five patients, the levels (mIU/l) decreasing from 6·8 to 3·8; 0·9 to 0·6; 24·3 to 13·2; 28·1 to 7·4 and 17·2 to 11·6. No such change was seen when the procedure was repeated with the morning steroid dose withheld. In two patients, dexamethasone produced similar changes in serum TSH to those observed with hydrocortisone. Steroid therapy had no consistent effect on LH, FSH and PRL levels. Our results show that the time interval between taking medication and withdrawing blood samples should be considered when interpreting TSH levels in treated Addison's disease.
EFFECT OF FENOLDOPAM, A DOPAMINE D‐1 RECEPTOR AGONIST, ON PITUITARY, GONADAL AND THYROID HORMONE SECRETION
Authors: BOESGAARD S. , HAGEN C. , ANDERSEN A. N. , ELDRUP E. , LANGE P.
Published: March 2008

The influence of fenoldopam, a dopamine (DA) D‐1 receptor agonist, on basal and GnRH/TRH stimulated PRL, GH, LH, TSH, testosterone and thyroid hormone secretion was studied in nine normal men. All men received 4‐h infusions of either 0.9% saline or fenoldopam at an infusion rate of 0.5 μg/kg min, 12–16 ml/h, adjusted according to weight. After 3 h of infusion, 50 μg GnRH and 100 μg TRH was given i. v. Blood samples were collected every 15 min from 1 h before to 1 h after the infusion for a total of 6 h for measurements of PRL, LH, FSH, GH, TSH, testosterone, T4and T3. The median PRL concentration increased significantly (P< 0.01) to 128%, range 87–287, of preinfusion levels, compared to the decline during control infusion (85%, 78–114). Basal TSH levels declined significantly to 71% (60–91) during fenoldopam compared with 82% (65–115) during control infusion (P< 0.05). Basal LH, FSH, GH and thyroid hormones were similar during fenoldopam and control infusions (P> 0.05). The LH response to GnRH/TRH was significantly (P< 0.02) increased by fenoldopam infusion. Basal and stimulated testosterone concentration was lower during fenoldopam (P> 0.01) infusion compared with control. Other hormones were similar after GnRH/TRH stimulation during fenoldopam and saline infusions. These results suggest that DA D‐1 receptors are involved in the modulation of pituitary hormone secretion. We suggest that the effect of fenoldopam on PRL and TSH is mainly at the hypothalamic level. Regarding the effect on LH concentrations, an additional direct effect of fenoldopam on testosterone regulation can not be excluded.
COMPARISON OF THE EFFECTS OF ORAL AND TRANSDERMAL OESTRADIOL ADMINISTRATION ON OESTROGEN METABOLISM, PROTEIN SYNTHESIS, GONADOTROPHIN RELEASE, BONE TURNOVER AND CLIMACTERIC SYMPTOMS IN POSTMENOPAUSAL WOMEN
Authors: SELBY PETER L. , MCGARRIGLE H. H. G. , PEACOCK MUNRO
Published: March 2008

We compared the effect of administering oestradiol via the transdermal or oral routes in six and eight postmenopausal women respectively. Although both treatments achieved similar plasma levels of oestradiol, oral administration led to much greater increases in plasma levels of oestrone and the sulphates and glucuronides of oestradiol, oestrone and oestriol than transdermal treatment (P < 0.001).

Both treatments reduced plasma FSH; from 42 ± 10 (SE) IU/1 to 30 ± 2 IU/1 with oral and from 46 ± 7 IU/1 to 28 ± 6 IU/1 with transdermal treatment. Urine calcium excretion fell from 0.41 ± 0.06 (molar ratio to creatinine) to 0.17 ± 0.02 with oral and from 0.25 ± 0.06 to 0.13 ± 0.02 with transdermal treatment. Patients' symptoms were improved by both treatments. These changes were related to the plasma oestradiol concentration but not to that of oestrone.

Oral, but not transdermal, treatment stimulated hepatic protein synthesis as shown by increased plasma levels of both vitamin‐D‐binding globulin and sex‐hormone‐binding globulin.

We conclude that although both oral and transdermal oestradiol reduce postmenopausal bone loss, gonadotrophin secretion and symptoms, oral treatment also leads to hepatic stimulation and extensive metabolism of oestradiol, both of which may increase side‐effects without conferring additional benefit.
CALCITONIN GENE‐RELATED PEPTIDE AND CALCITONIN AS TUMOUR MARKERS IN MEN 2 FAMILY SCREENING
Authors: SCHIFTER SØREN
Published: March 2008

This investigation deals with the potential additional value of serum CGRP measurements as compared to calcitonin in screening for medullary carcinoma of the thyroid (MTC) in families with multiple endocrine neoplasia type 2 (MEN 2). Basal as well as pentagastrin‐stimulated values for CGRP are evaluated in relation to the corresponding levels for calcitonin. Serum CGRP is within normal range in most family members with pathological calcitonin response to the pentagastrin stimulation test. Furthermore, these potentially affected family members do not respond to the pentagastrin stimulation test with an increase in CGRP. Pentagastrin stimulation tests performed in patients with manifest MTC affect the serum CGRP levels inconstantly and in two patients, with elevated basal level of CGRP, stimulation caused a release of calcitonin while concentrations of CGRP remained unaffected. We conclude that determination of serum CGRP adds no information to that of serum calcitonin in MEN 2 family screening for MTC.
BONE MASS IN HIRSUTE WOMEN WITH ANDROGEN EXCESS
Authors: DIXON JILL E. , RODIN ADAM , MURBY BRIAN , CHAPMAN MICHAEL G. , FOGELMAN IGNAC
Published: March 2008

The spinal and femoral bone mass of 32 hirsute women with oligomenorrhoea and androgen excess was measured using dual photon absorptiometry and compared with the bone mass of 32 control women with regular menstrual cycles. Despite significantly lower oestradiol levels in the hirsute population there was no significant difference in the bone mass. Furthermore there was no significant difference in bone mass in five hirsute women with undetectable levels of oestradiol. It is concluded that androgen excess can maintain normal bone mass in the face of low or undetectable oestradiol levels.
DIHYDROTESTOSTERONE REGULATES PLASMA SEX‐HORMONE‐BINDING GLOBULIN IN PREPUBERTAL MALES
Authors: EL‐AWADY MOSTAFA K. , SALAM M. A. , GAD Y. Z. , EL‐SABAN J.
Published: March 2008

Plasma levels of sex‐hormone‐binding globulin (SHBG) in man are known to be regulated up and down by oestradiol and testosterone, respectively. To determine whether testosterone reduces SHBG level directly or via its conversion into dihydrotestosterone before puberty, the changes of plasma SHBG, testosterone, oestradiol and dihydrotestosterone following human chorionic gonadotrophin stimulation are studied in ten 5α‐reductase‐deficient and in six normal prepubertal boys. Three main observations provide evidence that dihydrotestosterone plays a major role in SHBG regulation. (1) Basal plasma SHBG in 5α‐reductase‐deficient is higher than in normal boys (P < 0.1). (2) Circulating SHBG fails to decrease (P > 0.1) after human chorionic gonadotrophin stimulation despite striking elevation of plasma testosterone in 5α‐reductase deficiency where negligible dihydrotestosterone response occurs. This is in contrast to normal boys where SHBG is significantly reduced (P < 0.01) after stimulation. (3). In normal boys the magnitude of plasma dihydrotestosterone response to human chorionic gonadotrophin correlates with that of SHBG (r= 0.72) more than testosterone does versus SHBG (r= 0.36). It is concluded that dihydrotestosterone decreases SHBG concentration in plasma of prepubertal boys. At least part of the observed decrease in SHBG following testosterone administration in earlier reports must have occurred after its conversion to dihydrotestosterone.
RENAL FUNCTION AND ELECTROLYTE LEVELS IN HYPERTHYROIDISM: URINARY PROTEIN EXCRETION AND THE PLASMA CONCENTRATIONS OF UREA, CREATININE, URIC ACID, HYDROGEN ION AND ELECTROLYTES
Authors: FORD H. C. , LIM W. C. , CHISNALL W. N. , PEARCE J. M.
Published: March 2008

In order to help clarify the effects of hyperthyroidism on renal function and electrolyte metabolism, we measured the venous plasma concentrations of urea, creatinine, urate, hydrogen ion and electrolytes, and the urinary concentrations of total protein, albumin, retinol‐binding protein, N‐acetyl‐β‐D‐glucosaminidase activity, and creatinine in patients when hyperthyroid and again after they had been euthyroid for at least 4 months. Significant (P < 0.05) decreases in the mean plasma concentrations of urate and chloride and significant increases in creatinine, total CO2 and hydrogen ion mean concentrations were observed when the patients became euthyroid. The mean concentrations of sodium, potassium and urea did not change significantly. The values of the ratios total protein/creatinine, albumin/creatinine, N‐acetylglucosaminidase/creatinine and retinol‐binding protein/creatinine were all significantly (P < 0.05) elevated in random urine specimens obtained from hyperthyroid patients as compared to the values when euthyroid. Mild proteinuria occurs in most thyrotoxic patients which does not appear to be due predominantly to either glomerular or tubular renal injury. The changes in plasma analytes that were observed may be attributed to increases in glomerular filtration rate and tissue nucleic acid turnover and a tendency to respiratory alkalosis in the hyperthyroid patients.
TSH BINDING‐INHIBITING ANTIBODIES IN HYPERTHYROIDISM: RELATIONSHIP TO CLINICAL SIGNS AND HORMONE LEVELS
Authors: BENKER G. , KOTULLA P. , KENDALL‐TAYLOR P. , EMRICH D. , REINWEIN D.
Published: March 2008

TSH binding‐inhibiting antibody (TBIAb) activity was measured in 809 European patients with different forms of hyperthyroidism. Distribution of these TBIAb was skewed, with a peak in the range of normal controls, and an ill defined, not clearly separated peak at higher levels of TSH displacement. There was no unequivocal separation of two possible subgroups of hyperthyroidism (immunogenic and non‐immunogenic). TBIAb distributions of patients with and without endocrine ophthalmopathy (EO) overlapped considerably. Although patients with Graves' disease, arbitrarily defined by the presence of endocrine ophthalmopathy or diffuse nuclide uptake by thyroid scanning, had mostly elevated TBIAb activity, 24.3% had values within the range of normal controls (mean + 2SD). Patients with diffuse thyroid uptake had significantly higher TBIAb levels than patients with nodular scan findings. In Graves' disease, TBIAb activity was positively correlated with the severity of endocrine ophthalmopathy, the size of the thyroid, and the serum levels of total and free triiodothyronine. There was no influence of age, sex, pretreatment, or regional iodine supply. These results suggest (1) that the clinical manifestations of Graves' disease are statistically related to TBIAb activity and (2) that separation of immunogenic and non‐immunogenic forms of hyperthyroidism by means of TBIAb determination is unsatisfactory. The almost continuous distribution of TBIAb points to insufficient sensitivity of the present technique and raises doubts as to whether TBIAb values can be reliably classified as ‘positive’ or ‘negative’.
METABOLIC PROFILES IN PATIENTS WITH INSULINOMA
Authors: HALE PETER J. , NATTRASS MALCOLM
Published: March 2008

Twelve‐hour metabolic profiles have been measured in six patients with insulinoma and results compared with normal subjects of similar age and weight. Fasting blood glucose was lower (mean ± SEM 2.9 ± 0.3 mmol/l vs 50 ± 0.2 mmol/l) and plasma insulin higher (20.0 ± 3.9 mU/l vs 7.2 ± 1.6 mU/l) in insulinoma patients. Over the 12‐h period blood glucose, pyruvate and glycerol were significantly lower, and plasma insulin, blood lactate, alanine and plasma non‐esterified fatty acids (NEFA) significantly higher in insulinoma patients. Overall the concentration of blood total ketone bodies was significantly higher in insulinoma patients. Values were higher in the early part of the day but lower later in the day and did not show the marked pre‐meal rise observed in the normal subjects. The raised NEFA and ketone bodies are of particular interest as they may be a source of fuel supply in the presence of relative glucose deficiency.
RHYTHMS OF SERUM MELATONIN IN PATIENTS WITH SPINAL LESIONS AT THE CERVICAL, THORACIC OR LUMBAR REGION
Authors: LI Y. , JIANG D. H. , WANG M. L. , JIAO D. R. , PANG S. F.
Published: March 2008

The neural pathway essential for the diurnal rhythm of serum melatonin was studied in humans. Blood samples from 17 patients with chronic lesions of cervical (n= 8), low thoracic or lumbar (n= 9) spinal cord were collected at 0200, 0400,1000 and 1400 h of their normal light‐dark cycle. Blood samples were also collected from eight control subjects at 0200 and 1400 h. No special treatment of food, drug or photoperiod was implemented. Serum melatonin was extracted by dichloromethane and determined by radioimmunoassay. In patients with cervical spinal lesions (C3‐C7), it was found that serum melatonin levels were low and no diurnal rhythm was observed. Conversely, diurnal rhythm of circulating melatonin with significantly higher levels (P< 0.01) in the dark period were observed in individuals with injuries at the low thoracic or lumbar regions (T9‐L2). In the second experiment, blood samples from two other patients were collected for three consecutive days during acute period of spinal injuries (cervical or upper thoracic region) and serum melatonin concentrations were determined. Again, there were low levels of serum melatonin with no observable diurnal rhythm in the patient with cervical lesion (C4–5). However, diurnal rhythms were maintained with high levels in the dark period in the patient with upper thoracic spinal (T2–3) transection. Our data suggest that the cervical region of the spinal cord is part of the neural pathway essential for the diurnal rhythm of pineal melatonin secretion in human beings.
SIMULTANEOUS ASSAY OF THYROID ADENYLATE CYCLASE‐ AND GROWTH‐STIMULATING ANTIBODIES USING FRTL‐5 CELLS. EVIDENCE SUGGESTING THEIR IDENTITY IN PATIENTS WITH GRAVES' DISEASE
Authors: MARCOCCI C. , VITTI P. , LOPEZ G. , SANTINI F. , MAMMOLI C. , FENZI G. F. , PINCHERA A.
Published: March 2008

The relationship between thyroid growth‐stimulating antibodies (TGSAb) and thyroid adenylate cyclase‐stimulating antibodies (TSAb) in patients with Graves' disease is still a matter of controversy. To investigate this problem, we have developed an assay for the simultaneous measurement of TSAb and TGSAb using FRTL‐5 cells. TSAb was detected by its ability to stimulate iodide (I−) uptake and TGSAb by the 3H‐thymidine ([3H]‐Tdr) incorporation assay. Thirty‐four immunoglobulin G (IgG) preparations from patients with active Graves' disease were selected from a previous series in order to include both TSAb‐negative IgGs (n = 9) and TSAb‐positive IgGs (n= 25) by the cAMP stimulation assay, with a wide range of stimulatory activity. With one exception, the TSAb‐positive IgGs produced a significant stimulation of I− uptake; 20 of them were also TGSAb‐positive. The nine IgGs negative in the cAMP assay, were also negative in the I− uptake and the [3H]‐Tdr incorporation assays. The majority of samples had a similar potency in the two assays and a significant positive correlation was found (r=0.76; P < 0.001). Two IgGs previously shown to inhibit TSH‐stimulated adenylate cyclase in FRTL‐5 cells produced an almost complete inhibition (80–90%) of both TSH‐ and Graves' IgG‐stimulated I‐ uptake and [3H]‐Tdr incorporation. In conclusion, using a simultaneous assay for thyroid growth and adenylate cyclase stimulation, TGSAb in Graves' patients were found only in TSAb‐positive IgGs; both Graves' IgG‐stimulated activities were inhibited by antibodies blocking the TSH‐dependent adenylate
BILATERAL TESTICULAR TUMOURS IN CONGENITAL ADRENAL HYPERPLASIA: A CONTINUING DIAGNOSTIC AND THERAPEUTIC DILEMMA
Authors: CUNNAH D. , PERRY L. , DACIE J. A. , GRANT D. B. , LOWE D. G. , SAVAGE M. O. , BESSER G. M.
Published: March 2008

Bilateral testicular tumours are a rare but well described complication of congenital adrenal hyperplasia (CAH). It can be extremely difficult to distinguish histologically between Leydig cell tumours and adrenocortical rest hyperplasia which may lead in some cases to unnecessary orchidectomy in young men. A 26‐year‐old male in whom CAH had been diagnosed neonatally, was referred for further investigation of a craggy mass in the left testis. Six months earlier, right orchidectomy had been performed after presentation with bilateral enlarged, hard testes and azoospermia. The tumour was interpreted to be a malignant interstitial cell tumour of the testis. Our investigations revealed that his CAH was inadequately controlled and that the hormonal secretion from the remaining left testicular mass was ACTH dependent. Percutaneous venous sampling revealed high concentrations of Cortisol and other adrenocortical hormones coming from the gonadal vein. Dexamethasone suppressed these adrenal hormones and reduced the size and softened the consistency of the testicular mass. Total disappearance of the mass was achieved by using dexamethasone, given in a reverse circadian rhythm regimen. Spermatogenesis returned and the patient's wife became pregnant after 6 months; she gave birth to a normal male infant. To our knowledge, this is the first time in this clinical setting that fertility has been achieved. This case highlights the need for both a functional and histological assesement of such ‘tumours’ in CAH prior to orchidectomy.
BILATERAL INFERIOR PETROSAL SINUS SAMPLING AS A ROUTINE PROCEDURE IN ACTH‐DEPENDENT CUSHING'S SYNDROME
Authors: McCANCE DAVID R. , McILRATH EDWARD , McNEILL AVRIL , GORDON DEREK S. , HADDEN DAVID R. , KENNEDY LAURENCE , SHERIDAN BRIAN , ATKINSON A. BREW
Published: March 2008

Bilateral inferior petrosal sinus sampling was successfully performed in 12 of 13 consecutive patients with ACTH‐dependent Cushing's syndrome. Ten of the patients subsequently had transsphenoidal pituitary microsurgery. Eight patients in whom the inferior petrosal sinus to peripheral vein ACTH level ratio was 1.5 or greater were found to have a pituitary adenoma. One of the remaining two patients who had ratios < 1.5 had pituitary hyperplasia while the other had no identified abnormality. In five of the patients with pituitary tumour a ratio above 1.5 was present on only one side. Bilateral petrosal sampling is therefore always necessary. Tumour localization within the pituitary was only poorly predicted by either petrosal sinus sampling (four of eight) or computed tomography scanning (three of eight). If petrosal sinus sampling is used early in the differential diagnosis of ACTH‐dependent hypercortisolism, then the use of other differential diagnostic tests may not always be necessary.
QUANTITATIVE AND QUALITATIVE CHANGES IN LH SECRETION FOLLOWING PULSATILE GnRH THERAPY IN A MAN WITH IDIOPATHIC HYPOGONADOTROPHIC HYPOGONADISM
Authors: TSATSOULIS A. , SHALET S. M. , TALBOT A. , ROBERTSON W. R.
Published: March 2008

The pattern of bioactive and immunoreactive LH secretion before and during pulsatile GnRH therapy (18 μg/90 min) in a hypogonadotrophic hypogonadal male has been studied. Before treatment the patient was azoospermic and had low testosterone (1.2 nmol/1) with low and apulsatile immunoreactive LH (1.9 ± 0.2 IU/1) and FSH (1.4±1.9 IU/1) levels. There was no detectable LH bioactivity. During the first 24 h of GnRH therapy there was a small increase in immunoreactive (5.4±0.8 IU/1) and bioactive (6.7±1.3 IU/1) LH, with an irregular pattern and little effect on testosterone production (2.2 nmol/I). Within 1 week of treatment both bioactive (30.5±6.8 IU/1) and immunoreactive (13.6±1.5 IU/1) LH levels were above the normal range and the pattern of secretion was pulsatile. The bioactive to immunoreactive (B:I) LH ratios within the pulses (2.6±0.3) were higher (P < 0.01) than between pulses (1.97 ± 0.1) and the testosterone concentration (17.8 ± 2.1 nmol/1) was now normal. At one month LH secretion was similar and testosterone pulses of high amplitude were evident corresponding to high‐amplitude bioactive LH pulses. By 3 months mature spermatozoa (1.3 × 106/ml) were seen in the patient's semen. The pattern of LH secretion was pulsatile but the levels of bioactive (131 ± 36 IU/1) and immunoreactive (9.5±1.3 IU/1) LH decreased towards the normal range reflecting maturation of the testicular feedback control at the pituitary level. This effect was more pronounced on bioactive rather than immunoreactive LH secretion (57%vs 32% relative decrease). At 6 months LH levels were similar and the sperm count was normal (34 × 106/ml).
OPIOIDERGIC REGULATION OF LH PULSATILITY IN WOMEN WITH POLYCYSTIC OVARY SYNDROME
Authors: BERGA S. L. , YEN AND S. S. C.
Published: March 2008

Women with polycystic ovary syndrome (PCO) display disordered patterns of LH pulsatility and may have an impairment of opioidergic regulation of GnRH‐LH. In order to ascertain if these patterns reflect an inherent hypothalamic abnormality or a functional state consequent to the acyclicity of sex steroids, LH pulsatility and gonadotrophin responses to naloxone were examined in six PCO women before and after treatment with incremental daily doses of a progestogen, medroxyprogesterone acetate (MPA), for 10 days to determine (i) if progestogen treatment would alter the LH pulse pattern to resemble that of the luteal phase; and (ii) if the conversion to a luteal phase LH pulse pattern by MPA would involve the induction of opioidergic regulation.

LH pulsatility and FSH levels were determined by blood sampling at 10 min intervals for 8 h before and after MPA treatment during a saline infusion on the control day and during a naloxone infusion (1.6 mg/h) on the following day. Basal levels of oestradiol, oestrone. androstenedione, testosterone, and dehyd‐roepiandrosterone‐sulphate were measured before and after MPA. All six PCO women responded to MPA administration with a significant reduction in LH pulse frequency (P<0.005), an increase in LH pulse amplitude (P<0.0025), and an increase in LH pulse duration (P<0.025), without changes in mean LH, mean FSH, androgen, or oestrogen levels. Thus, a luteal phase LH pulse pattern was induced by MPA. Naloxone reversed the MPA‐induced changes in LH pulsatility, indicating that these responses involved the induction of central opioidergic activity. These results suggest that progestogen modulation of LH pulsatility in PCO women is similar to that of cycling women. The establishment by MPA treatment of opioidergic regulation of GnRH‐LH pulsatility implies that the opioidergic impairment seen in PCO women is a functional state
OBSERVER VARIATION IN THE SCINTIGRAPHIC DIAGNOSIS OF SOLITARY COLD THYROID LESIONS
Authors: JARLØV ANNE E. , GJØRUP THOMAS , HEGEDÜS LASZLO , HVID‐JACOBSEN KELD , MARVING JENS , HANSEN JENS M.
Published: March 2008

In order to evaluate the reproducibility of the diagnosis of solitary cold thyroid lesions, two specialists in nuclear medicine and two specialists in endocrinology independently twice read 240 thyroid 99mTc pertechnetate scintigrams. No significant difference or interaction between the results obtained from the right and the left lobe was found. A solitary cold lesion was diagnosed in 100 of the 480 lobes; however, in only 30 did all four observers agree upon the diagnosis. Interobserver variation was determined by pairwise comparison of observers. The observed agreement was between 0.91 and 0.94. After adjusting for expected chance agreement, kappa values between 0.57 and 0.70 were found. Intraobserver variation was smaller than interobserver variation, revealing agreement rates of 0.93–0.96 and kappa values between 0.71 and 0.77. Agreement was related to large lesions, lesions located centrally in the lobe, and ovoid‐shaped lesions. Clinicians should be aware to what extent they can rely on the information they use in their decisions. The considerable inconsistency in the evaluation of cold lesions on thyroid scintigrams should be taken into consideration, and calls in question the value of using thyroid scintigrams for deciding whether a patient should be referred for operation or biopsy.
THE OVERNIGHT DEXAMETHASONE TEST IS A WORTHWHILE SCREENING PROCEDURE
Authors: CRONIN C. , IGOE D. , DUFFY M. J. , CUNNINGHAM S. K. , MCKENNA T. J.
Published: March 2008

The overnight low‐dose dexamethasone test is a convenient screening procedure for Cushing's syndrome. Claims that the test is associated with a high incidence of ‘false positives’, rendering it of little value particularly in obese and hospital in‐patients, have been investigated in the present study. The data from 100 consecutive subjects undergoing overnight low‐dose dexamethasone tests to examine for the possibility of Cushing's syndrome, were reviewed. Cushing's syndrome was identified in four patients, normal suppression of cortisol values occurred in 84 patients and 12 patients exhibited false positive results. Differences in body weights, body mass indices or in‐patient status did not distinguish between those subjects with normal suppression of plasma cortisol and those subjects who yielded false positive results. These data indicate that the simple overnight dexamethasone test substituted for the more cumbersome traditional 48‐h dexamethasone test in 84 of 96 patients who did not have Cushing's syndrome. Thus the overnight test provides a useful screening procedure but a small percentage of patients, approximately 12.5%, will require additional procedures to exclude Cushing's syndrome.
URINARY GLYCOSAMINOGLYCANS IN Graves'OPHTHALMOPATHY*
Authors: KAHALY G. , SCHULER M. , SEWELL A. C. , BERNHARD G. , BEYER J. , KRAUSE U.
Published: March 2008

An increased accumulation of glycosaminoglycans (GAG) in retrobulbar tissues has been reported in patients with thyroid eye disease. We examined the quantitative urinary GAG excretion in 101 patients with Graves'ophthalmopathy of different classes, 36 patients with Graves'hyperthyroidism without ophthalmopathy, 14 patients with toxic nodular goitre and 103 control subjects. Glycosaminoglycans were isolated from 24‐h urine collections by precipitation with cetylpyridinium chloride and ethanol followed by photometrical quantification of hexuronic acids after reaction with carbazole. In comparison with the control group (15.8, 10.4, 21.6 mg/24 h; median, 25th, 75th percentile) a significant (P < 0.005) elevation of urinary GAG excretion was found in patients with ophthalmopathy (192, 12.2, 28.7 mg/24 h), whereas patients with Graves'hyperthyroidism and no ophthalmopathy (16.2, 11.9, 21.7 mg/24 h) and patients with toxic nodular goitre (15.8, 11.5, 21.2 mg/24 h) exhibited no markedly increased values. Especially, patients with active, untreated ophthalmopathy showed on average a twofold increase (36.7, 28.1, 48.4 mg/24 h) in urinary GAG excretion. In contrast, high values were not found in patients with inactive ophthalmopathy and elevated values decreased under treatment, which correlated with clinical findings. Further, relapses were also accompanied by high GAG excretion. Thus, using a simple laboratory method, quantitative determination of urinary GAG excretion appears to present an effective parameter for the activity of Graves'ophthalmopathy.
REDUCED FOREARM BONE MINERAL CONTENT AND BIOCHEMICAL EVIDENCE OF INCREASED BONE TURNOVER IN WOMEN WITH EUTHYROID GOITRE TREATED WITH THYROID HORMONE
Authors: TAELMAN P. , KAUFMAN J. M. , JANSSENS X. , VANDECAUTER H. , VERMEULEN A.
Published: March 2008

We used single‐photon absorptiometry to assess forearm bone mineral content (BMC/BW) (arbitrary units normalized for bone width) at a proximal site (PBMC/BW) and at a more distal site (DBMC/BW) in 60 women treated with 25–50 μg T3 or 50–100 μg T4 for euthyroid goitre, in 13 untreated goitre patients, and in 2 controls matched for age and menopausal state for each goitre patient. BMC/BW was not significantly different between untreated goitre patients and controls. In 36 premenopausal patients, treated for 5.8 |Mp 5.4 years (mean |Mp SD) a slight decrease in PBMC/BW of about 5% compared to controls was observed (PBMC/BW 1.42 |Mp 0.19 vs 1.49 |Mp 013, P< 0.05). In 24 postmenopausal patients, treated for 10.0 |Mp 5.8 year, a 20% deficit in BMC/BW compared to controls was found (DBMC/BW 0.80 |Mp 0.18 vs 1.06 |Mp 0.20, P < 0.001 and PBMC/BW 1.14 |Mp 0–20 vs 1.42 |Mp 0.19, P < 0.001). Biochemical indices of bone metabolism in 43 pre and post‐menopausal patients and 43 controls showed in the patients a higher serum alkaline phosphatase activity (AP) (P < 0.01 and P < 0.05) and serum osteocalcin (NS and P < 0.05). AP was negatively correlated with TSH levels and, in postmenopausal patients, with DBMC/BW and PBMC/BW. Our results suggest that treatment of euthyroid women with moderate doses of thyroid hormone increases bone turnover with clear adverse effects on bone mineral status in postmenopausal patients.
DIURNAL SALIVARY CORTISOL PATTERNS DURING PREGNANCY AND AFTER DELIVERY: RELATIONSHIP TO PLASMA CORTICOTROPHIN‐RELEASING‐HORMONE
Authors: ALLOLIO BRUNO , HOFFMANN JOCHEN , LINTON E. A. , WINKELMANN WERNER , KUSCHE MARTIN , SCHULTE HEINRICH M.
Published: March 2008

The circadian rhythm of salivary cortisol was studied in 10 healthy women every 4 weeks throughout pregnancy. In addition, in 12 women the diurnal patterns of salivary cortisol, serum cortisol, plasma ACTH, plasma CRH and serum progesterone were analysed in late third trimester pregnancy and again 3–5 days after delivery. Salivary cortisol profiles exhibited a clear circadian rhythm during pregnancy with an increase in mean salivary cortisol from the 25th to 28th week onwards reaching concentrations in late pregnancy more than twice as high as in non‐pregnant controls, rapidly returning to normal concentrations after delivery. The coefficient of variation of salivary cortisol profiles decreased in third trimester pregnancy due to a parallel upward shift of cortisol concentrations (40.2 |Mp 3.4%vs 77.6 |Mp 6.6% after delivery, P > 0.01). A diurnal pattern was also found for plasma ACTH and serum cortisol before and after delivery with lower concentrations post‐partum (P > 0.01). In late pregnancy, progesterone concentrations were significantly higher in the evening (930 + 85 nmol/1 vs 813 |Mp 74 nmol/1 at 0900 h, P > 0.01) but showed no diurnal variation post‐partum. Plasma CRH was significantly elevated in late third trimester pregnancy (1.22 |Mp 0.23 μg/1 at 0900 h) but showed no diurnal change (1.30 |Mp 0.28 μg/1 at 1900 h). Moreover, no correlation between the free cortisol increase in late pregnancy and plasma CRH was noted despite a wide range of CRH levels (0‐13‐3.60 μg/1). In contrast, a significant correlation was observed between the serum progesterone increase and the salivary cortisol increase in late pregnancy (r = 0.70, P > 0‐05). These findings demonstrate that placental CRH is not the only regulator of maternal ACTH and cortisol release. Instead, our study suggests that placental CRH has little influence on baseline maternal adrenocortical function in pregnancy. The elevated salivary cortisol levels in pregnancy may be explained by glucocorticoid resistance owing to the antiglucocorticoid action of high progesterone concentrations.
SERUM SOLUBLE INTERLEUKIN 2 RECEPTOR IN HYPERTHYROID Graves'DISEASE AND EFFECT OF CARBIMAZOLE THERAPY
Authors: CHOW C. C. , LAI K. N. , LEUNG J. C. K. , CHAN J. C. N. , COCKRAM C. S.
Published: March 2008

To study the activation of T lymphocytes in hyperthyroid Graves'disease, the serum concentrations of soluble interleukin 2 receptors (sIL2R) were determined during active thyrotoxicosis and following the return to a euthyroid state with carbimazole therapy. Serum sIL2R was measured by an enzyme linked immunoassay. The mean |Mp SD serum sIL2R concentration during untreated hyperthyroidism was elevated as compared with controls (919.1 |Mp 523.4 vs 374.2|Mp 189‐4 U/ml, P<0.005). However, after carbimazole therapy the serum sIL2R in euthyroid patients fell to 377–9 |Mp 90.3 U/ml, which did not differ from healthy controls. Serum sIL2R correlated significantly with the serum free T3 only during hyperthyroidism (r= 0.678, P < 0.01). Our study suggests that in‐vivo measurement of serum sIL2R released from activated T lymphocytes is a useful immunological indicator of disease activity.
THE EFFECTS OF NAFARELIN AND DANAZOL ON VERTEBRAL TRABECULAR BONE MASS IN PATIENTS WITH ENDOMETRIOSIS
Authors: WHITEHOUSE R. W. , ADAMS J. E. , BANCROFT K. , VAUGHAN‐WILLIAMS C. A. , ELSTEIN M.
Published: March 2008

Single and dual‐energy quantitative computed tomography (QCT) were used to measure spinal trabecular bone mineral content in 24 women treated with either nafarelin (15 patients) or danazol (nine patients) for endometriosis. Significant loss of bone mineral (‐ 9.6 g/l; ‐ 5.9% P <0.001) was demonstrated after 6 months’treatment with nafarelin. This loss was reversible with no significant difference in the bone mineral measurement made before treatment and that made at 6 months after treatment was stopped (difference ‐ 1.95 g/l, NS). A small but statistically significant (+ 2.2 g/l, P<0.05) increase in bone mineral was measured in the group of patients treated with danazol for 6 months. The dual‐energy QCT gave similar results, indicating little change in trabecular fat content. A significant correlation was demonstrated between mean serum oestradiol levels during treatment with nafarelin and the change in bone mineral (r= 0.655, P < 0.005).
IN‐SITU ANALYSIS OF CALCITONIN AND CGRP EXPRESSION IN MEDULLARY THYROID CARCINOMA
Authors: BOULTWOOD J. , WYNFORD‐THOMAS D. , RICHARDS G. P. , CRAIG R. K. , WILLIAMS E. D.
Published: March 2008

A combination of immunocytochemistry (ICC) and in‐situ hybridization (ISH) applied to formalin‐fixed tissue sections was used to analyse the differential expression of calcitonin and CGRP genes, at both peptide and mRNA levels, in normal and neoplastic human thyroid C cells. Calcitonin peptide was readily detectable in normal C cells but its abundance in the neoplastic C cells of medullary thyroid carcinoma (MTC) was reduced in correlation with the degree of tumour differentiation. Conversely, the content of calcitonin mRNA was higher in MTC than in normal C cells and was not significantly related to tumour differentiation. Both the peptide and mRNA of CGRP were present at much lower levels than those of calcitonin in normal C cells but were increased in neoplastic C cells. We conclude that neoplasia of thyroid C cells is associated with (i) an increase in the content of CGRP mRNA and peptide relative to that of calcitonin, consistent with a defect in control of transcript processing, and (ii) a decrease in the ratio of calcitonin peptide to mRNA abundance relative to the normal, suggesting a defect in synthesis or storage of the peptide. ISH analysis of calcitonin mRNA may therefore be a very valuable addition to ICC analysis of the peptide as a diagnostic and prognostic marker for MTC.