bluuebunny/crossref_metadata_2025 huggingface dataset:
PERSISTENT TRH‐INDUCED GROWTH HORMONE RELEASE AFTER SHORT‐TERM AND LONG‐TERM L‐THYROXINE REPLACEMENT THERAPY IN PRIMARY CONGENITAL HYPOTHYROIDISM
Authors: FAGGIANO M. , CRISCUOLO T. , GRAZIANI M. , IORIO S. , PISANO G. , SINISI A. A. , SINISI A. M. , BELLASTELLA A.
Published: March 2008

No appreciable changes in plasma GH levels after TRH stimulation have been observed in normal subjects, whereas acute GH release has been reported in primary hypothyroidism and other pathophysiological states. To evaluate the effect of the T4 replacement therapy on TRH‐induced GH release, 28 patient volunteers with primary congenital hypothyroidism (PCH), were studied before (11 subjects), after 1 month (nine subjects) and after long‐term T4 replacement therapy (eight subjects). All patients underwent a TRH test with measurement of TSH, PRL and GH levels, and were compared to 28 age‐matched normal subjects. An increase of plasma GH after TRH was found in 46% of patients without any therapy, in 67% of patients after one month of T4 administration and in 75% of patients after long‐term therapy. No changes were observed in plasma GH levels in controls. The TSH response to TRH was inhibited and the response of PRL was reduced step by step by T4 replacement therapy in our patients with PCH. Our results suggest that: (i) Replacement T4 therapy in PCH does not abolish the paradoxical GH response to TRH, in spite of inhibiting the TSH response and reducing the exaggerated PRL response; (ii) the GH response to TRH in PCH seems to be unrelated to low thyroid hormone levels and/or to high TSH levels, but it could be due to changes in hypothalamic‐pituitary regulation which are not improved by T4 replacement therapy.
GROWTH HORMONE RELEASING FACTOR‐TEST IN ACROMEGALY: COMPARISON WITH OTHER DYNAMIC TESTS
Authors: LOSA M. , SCHOPOHL J. , STALLA G. K. , MÜLLER O. A. , VON WERDER K.
Published: March 2008

Human pancreatic growth hormone releasing factor (hpGRF1–44) was given intravenously as a 100 μg bolus to 20 patients with active acromegaly. The GH‐responses were variable, ranging from an increase of 8 to 2813% from the basal level (mean ± SE, 428·136%). Sixteen GRF‐responders (Δ%± 100%) were arbitrarily distinguished from four GRF non‐responders, whose GH‐levels increased less than 100% from basal level after GRF‐administration. The outcome of the GRF‐test did not correlate with the results of other dynamic tests of GH‐secretion in acromegaly (oral glucose tolerance test, insulin hypoglycaemia, TRH‐, LHRH‐, CRF‐stimulation). In 10 patients who had not been treated before, the GH‐increments after GRF were higher than those in seven patients who had previously been subjected to transsphenoidal surgery, though they still had clinically and biochemically active acromegaly. Ten acromegalics, who were tested with GRF, were later treated surgically by the transsphenoidal route and were reevaluated with GRF‐stimulation 2 months after surgery. Eight patients appeared clinically cured of whom four had complete normalization and four had significantly lower basal and conventionally stimulated GH‐levels postoperatively. These patients also had normal postoperative GH‐responses to GRF, which had been significantly higher before surgery compared with normal controls. It is concluded that the GRF‐test in acromegaly does not help in establishing the diagnosis. The normalization of the GH‐response to GRF after transsphenoidal surgery seems to represent additional evidence for normalization of GH‐secretion, though the latter is not proven by the normal outcome of this test.
THE INFLUENCE OF OESTROGENS ON THE SENSITIVITY OF PRL, TSH AND LH TO THE INHIBITORY ACTIONS OF DOPAMINE IN HYPERPROLACTINAEMIC PATIENTS
Authors: VALCAVI R. , HARRIS P. E. , FOORD S. M. , DIEGUEZ C. , EVANS P. J. , PETERS J. R. , HALL R. , SCANLON M. F.
Published: March 2008

The effects of oestrogen priming on the response of serum PRL, LH and TSH to dopamine (DA) infusion have been studied in hyperprolactinaemia. Seven hyperprolactinaemic females (aged 22–57 years; basal PRL 911–5130 mU/1, normal >420 mU/1), had submaximal DA infusions (0·06 μg/kg/min) over 3 h. The DA was repeated at the same dose after pretreatment with ethinyl oestradiol (E2) 100 μg daily by mouth for 3 d, and after a further 2 week interval, following pretreatment with tamoxifen (TAM) 20 mg twice a day by mouth for 3 d. Ethinyl oestradiol pretreatment stimulated a rise in basal PRL levels in all subjects (mean ± SE, mU/1; 2903 ± 761 vs 2293 ± 684, P>0·05) while TAM produced a higher but more variable increase in basal PRL levels (mean ± SE, mU/1; 3402 ± 757, P= n.s.). The individual increments in basal PRL levels after both E2 and TAM pretreatment showed a significant positive correlation with the greater decrement in PRL levels during E2 and TAM primed DA infusions (E2, r= 0·93, P > 0·01, TAM, r= 0·83, P > 0·05). E2 pretreatment produced a rise in basal LH levels in 5/7 patients, and there was a significant positive correlation between the rise in basal LH levels after E2 and the decremental change in LH levels in E2 primed DA infusions (r= 0·94, P>0·01). Basal TSH levels were unaffected by E2 and TAM pretreatment, but during DA infusion there was a significantly greater decremental change following E2 pretreatment (sum of decrements, mean ± SE mU/1; 8·1 ± 1·58 vs 4·65 ± 1·23, P > 0·02). In conclusion, E2 and TAM increased PRL sensitivity to the inhibitory actions of DA treatment. In contrast, E2 but not TAM, exerted similar effects on the dopaminergic inhibition of LH and TSH.
SERUM SEX HORMONE CONCENTRATIONS IN INSULIN DEPENDENT DIABETIC WOMEN WITH AND WITHOUT AMENORRHOEA
Authors: DJURSING H. , HAGEN C. , ANDERSEN A. NYBOE , SVENSTRUP B. , BENNETT P. , PEDERSEN L. MØLSTED
Published: March 2008

Abnormal steroid secretion may contribute to anovulation in insulin dependent diabetic patients with amenorrhoea. We have measured serum sex hormonebinding globulin (SHBG) and free and bound oestrogen and androgen levels in 17 such patients. As controls we included 17 patients with insulin dependent diabetes mellitus and normal menstrual cycles, 21 regularly menstruating normal women (both sampled during early follicular phase), and 23 non‐diabetic patients with amenorrhoea. The diabetic patients with normal cycles had significantly higher serum concentrations of Δ4‐androstenedione and testosterone than the normal women (P>0·01). The amenorrhoeic diabetics in contrast had significantly lower serum concentrations of SHBG, 5 α‐dihydrotestosterone and free and total oestradiol‐17β than either group of menstruating women (P>0·05), and significantly lower concentrations of Δ4‐androstenedione (P > 0·01), dehydroepiandrosterone sulphate (P > 0·01), testosterone (P > 0·01), and oestrone (P > 0·05), than the cycling diabetics. The two amenorrhoeic groups had similar free and bound sex hormone concentrations except that Δ4‐androstenedione levels were significantly lower in the diabetics (P>0·01). We conclude that the low sex hormone levels in diabetic women with amenorrhoea may be due to suppression of the hypothalamic‐pituitary axis in view of the impaired LH secretion found in these patients and that excess androgen secretion seems not to be of aetiological importance in amenorrhoea related to diabetes mellitus. The decreased steroid levels in amenorrhoeic diabetics is due to their suppressed ovarian function while the increased androgen levels in diabetics with regular cycles are probably of ovarian origin.
EFFECTS OF EXOGENOUS CATECHOLAMINES AND EXERCISE ON PLASMA MAGNESIUM CONCENTRATIONS
Authors: JOBORN H. , ÅKERSTRÖM G. , LJUNGHALL S.
Published: March 2008

Catecholamines and physical exercise are known to influence the metabolism of several minerals in man, but the effects on magnesium (Mg) have been scarcely investigated. In the present study, infusion of adrenaline (5 μg/min for 30 min followed by 10 μg/min for 30 minutes) significantly reduced the plasma Mg levels in healthy males. This effect was abolished by simultaneous infusion of propranolol. Noradrenaline had no such effect. In order to stimulate endogenous catecholamine release healthy males carried out physical exercise in four different ways: (1) ergometer bicycling at maximum load until exhaustion with and without oral beta‐blockade, (2) ergometer bicycling with stepwise increasing load until exhaustion, (3) isokinetic maximal exercise with one leg, with blood sampling both from the venous effluent of the exercising leg and the opposite resting arm and (4) long‐term (60 min) steady state ergometer bicycling at approximately 65% of estimated maximum capacity. During short‐term (less than 20 min) intense exercise (i.e. experiments 1–3) the plasma Mg concentrations were increased. This was probably due to a reduction of plasma volume and to an influx of Mg to the vascular pool. During long‐term steady state exercise (experiment 4) the Mg levels were not significantly affected but decreased during the first hour of recovery. These results suggest that both the beta‐adrenergic system and muscular activity by itself affect Mg homeostasis.
THE RELATIONSHIP BETWEEN SERUM PROLACTIN AND IMMUNOCYTOCHEMICAL STAINING FOR PROLACTIN IN PATIENTS WITH PITUITARY MACROADENOMAS
Authors: ROSS R. J. M. , GROSSMAN A. , BOULOUX P. , REES LESLEY H. , DONIACH I. , BESSER G. M.
Published: March 2008

We have studied the relationship between mean pretreatment levels of serum prolactin and the presence of positive immunohistochemical staining for prolactin in the pituitary tumours of 55 patients. Pretreatment serum prolactin was significantly higher in patients with tumours showing many prolactin immunostaining cells than in those with none (P>0·001). When the pretreatment serum prolactin exceeded 6000 mU/1, the tumours contained over 90% of prolactin positive cells; one patient was an exception who had received longterm high dose bromocriptine therapy, and her tumour showed only occasional cells with positive staining. When the pretreatment serum prolactin level was under 2500 mU/1, a tumour was found which showed either no cells or fewer than 1% of cells which stained for prolactin. There was no significant difference in pretreatment serum prolactin levels between 11 patients with craniopharyn‐giomas and 34 patients with pituitary macroadenomas showing no prolactin immunostaining. Seventy‐one percent (32) of the 45 patients with craniophar‐yngiomas or tumours with negative immunostaining for prolactin, had raised pretreatment serum prolactin levels (above 360 mU/1) although this was usually only slightly elevated; the levels exceeded 2500 mU/1 in six (13%) of them (two craniopharyngiomas, four pituitary tumours) but in none did the levels exceed 6000 mU/1. Four of the 55 pituitary tumours showed occasional cells (less than 1%) that stained positively for growth hormone. In none of the patients with these tumours was there evidence of acromegaly or pathologically elevated circulating growth hormone levels.
ON THE STABILITY IN VITRO OF BIOACTIVE HUMAN ADRENOCORTICOTROPHIN IN BLOOD AND PLASMA
Authors: LAMBERT A. , FROST J. , RATCLIFFE W. A. , ROBERTSON W. R.
Published: March 2008

The disappearance in vitro of ACTH from whole human blood and plasma held at 22°C has been monitored using a dispersed adrenal cell bioassay and an unextracted radioimmunoassay. In three normal subjects after a metyrapone test and two patients with Addison's disease, endogenous bioactive ACTH levels were unchanged for at least 1 h in blood and 2 h in plasma. Moreover < 50% of the bioactive plasma ACTH was still present in the plasma samples from the patients with Addison's disease after 24 h incubation at ambient temperatures. Human pituitary ACTH (1–39), spiked into plasma from dexamethasone suppressed subjects to give a concentration of 250 ng/1, was stable by bioassay for at least 2 h. No loss of biological activity was observed on subjecting plasma from a patient with Addison's disease or spiked plasma to two cycles of thawing at 37°C and freezing at — 70°C or thawing at 20°C and freezing at — 20°C. Some loss of bioactivity (20%) occurred on subjecting the patient's, but not ACTH‐spiked plasma to four cycles of thawing at 20°C/freezing at — 20°C. We conclude that bioactive ACTH (endogenous or exogenous) may be more stable in vitro in human blood and plasma than has been previously thought. If our studies can be confirmed in a larger series then it may be that conditions for handling blood specimens for ACTH assays could be reappraised.
THE GEOGRAPHICAL DISTRIBUTION OF THYROTOXICOSIS IN ENGLAND ACCORDING TO THE PRESENCE OR ABSENCE OF TSH‐RECEPTOR ANTIBODIES
Authors: PHILLIPS D. I. W. , BARKER D. J. P. , SMITH B. REES , DIDCOTE S. , MORGAN D.
Published: March 2008

In a prospective study of the incidence of thyrotoxicosis sera from 216 thyrotoxic patients in seven English towns were assayed for TSH‐receptor antibodies. The incidence of antibody negative thyrotoxicosis correlated closely with the previous prevalence of endemic goitre in the towns (r= 0·9) indicating a high current incidence of toxic nodular goitre in previously goitrous towns. Antibody positive thyrotoxicosis, an indicator of Graves’ disease, showed no correlation with goitre although there was statistically significant geographical variation in incidence. The percentage of all thyrotoxic patients who were antibody positive varied between towns, from 35% to 92%.
PITUITARY ACTH DEPENDENT CUSHING'S SYNDROME DUE TO ECTOPIC PRODUCTION OF A BOMBESIN‐LIKE PEPTIDE BY A MEDULLARY CARCINOMA OF THE THYROID
Authors: HOWLETT T. A. , PRICE JANET , HALE ANN C. , DONIACH I. , REES LESLEY H. , WASS J. A. H. , BESSER G. M.
Published: March 2008

A 41‐year‐old man presented with Cushing's syndrome and the biochemical features of ectopic ACTH production. Investigation revealed mediastinal metastases from a medullary carcinoma of the thyroid. The peripheral plasma contained grossly elevated levels of bombesin‐like immunoreactivity (irBombesin) as well as calcitonin; blood sampling via a venous catheter confirmed a gradient of irBombesin, but not of ACTH, in the mediastinal vein draining the tumour. On extraction the tumour contained a bombesin‐like peptide, but not vasopressin or corticotrophin releasing factor and only very low levels of ACTH; immunohistochemical studies showed positive immunostaining for bombesin and calcitonin but none for ACTH or CRF. No ACTH was released from dispersed tumour cells in vitro. However an extract of the tumour stimulated ACTH release in vitro from perifused dispersed rat anterior pituitary cells. This is the first reported case of Cushing's syndrome due to ectopic production of a bombesin‐like peptide, causing excessive pituitary ACTH secretion.
FAMILIAL HYPOCALCIURIC HYPERCALCAEMIA I: RENAL HANDLING OF CALCIUM, MAGNESIUM AND PHOSPHATE
Authors: KRISTIANSEN J. H. , MORTENSEN J. BROCHNER , PEDERSEN K. O.
Published: March 2008

Ten hypercalcaemic members from three generations of a family with familial hypocalciuric hypercalcaemia (FHH) were compared with age and sex matched healthy subjects. Two of the former had undergone unsuccessful subtotal parathyroidectomy. Our results showed that the hypercalcaemia was mainly attributable to an increased capacity for tubular reabsorption of calcium, but in part also to an increased release of calcium from bone. The relative hypermagnesaemia had a similar dual origin. The serum phosphate concentration was low and this could be accounted for in full by a decrease in renal tubular reabsorption of phosphate, as assessed by the renal threshold phosphate concentration (TmPO4/GFR). The results of PHT measurements with two radioimmuneassays were equivocal. Most patients had normal serum PTH values, but with one assay mean serum PTH was significantly higher in the hypercalcaemic group. We conclude that the abnormalities of the divalent cation and phosphate metabolism cannot be accounted for in full by increased circulating PTH activity, and are predominantly due to an intrinsic renal abnormality.
CLINICAL SIGNIFICANCE OF UNCONJUGATED 3α,5β‐TETRAHYDROALDOSTERONE AND 5β‐DIHYDROALDOSTERONE MEASURED BY RADIOIMMUNOASSAY
Authors: LEWICKA SABINA , VECSEI P.
Published: March 2008

Radioimmunoassays of two unconjugated reduced metabolites of aldosterone were developed. Excretion rates of unconjugated 5β‐dihydroaldosterone (5β‐DHAld) and 3α,5β‐tetrahydroaldosterone (3α,5β‐THAld) were measured in 192 hypertensive patients and 16 normal subjects and results were compared with urinary tetrahydroaldosterone‐glucuronide(TH‐Aldo‐glu), aldosterone‐18‐glucuronide (Aldo‐18‐glu) and ‘free’ aldosterone. Generally, values of unconjugated reduced metabolites correlated with one another but in some cases were exceptionally elevated indicating alteration of urinary bacterial flora or impairment of the enzymatic system regulating the conjugation reaction. We suggest that in those cases of hypertension and suspected primary aldosteronism when aldosterone‐18‐glucuronide and tetrahydroaldosterone glucuronide values remain within normal range, determination of the free metabolite fraction may be diagnostically helpful.
PLASMA CONCENTRATIONS OF SEX HORMONES IN POSTMENOPAUSAL WOMEN IN NON‐ALCOHOLIC CIRRHOSIS
Authors: BANNISTER P. , SHERIDAN P. , LOSOWSKY M. S.
Published: March 2008

Sex hormone and sex hormone binding globulin (SHBG) levels were measured in the plasma of postmenopausal women with non‐alcoholic liver cirrhosis (n= 24) and compared with levels in matched controls (n= 21). Plasma oestradiol was elevated: 80 vs 30 pmol/l, P < 0·005 (median values). Plasma SHBG was elevated, 15 vs 10 mg/dl, P < 0·001. Plasma dehydroepiandrosterone sulphate levels were low, 0·35 vs 2·0 μmol/l, P < 0·0005, as were plasma androstenedione levels, 2·5 vs 4·5 nmol/l, P < 0·05. There was no significant difference in plasma testosterone. These data suggest that liver disease per se alters sex hormone and sex hormone binding globulin levels in postmenopausal women.
EFFECT OF PINEALECTOMY ON SERUM MELATONIN, LUTEINIZING HORMONE AND PROLACTIN: A CASE REPORT
Authors: CHIK C. L. , TALALLA A. , BROWN G. M.
Published: March 2008

A patient, aged 47 is described in whom changes in hormonal profiles were observed following surgical excision of the pineal. She presented with a clinical syndrome of increased intracranial pressure and postmenopausal symptoms. Computerized tomographic scans showed obstructive hydrocephalus from a cystic lesion in the pineal region. Surgical removal of the cystic mass revealed a benign ependymal cyst and normal pineal tissue. After the operation, she had no nocturnal increase in serum melatonin. The morning basal LH was further elevated and night‐time PRL showed little fluctuation from the basal levels.
ABNORMAL ANDROGEN AND OESTROGEN METABOLISM IN MEN WITH STEROID SULPHATASE DEFICIENCY AND RECESSIVE X‐LINKED ICHTHYOSIS
Authors: LYKKESFELDT G. , BENNETT P. , LYKKESFELDT A. E. , MICIC S. , MØLLER S. , SVENSTRUP B.
Published: March 2008

Serum levels of sex hormone binding globulin (SHBG), testosterone, free testosterone, dihydrotestosterone, androstenedione, dehydroepiandrosterone sulphate, oestradiol, oestrone, oestrone sulphate, FSH, and LH were measured in 20 steroid sulphatase‐deficient men with recessive X‐linked ichthyosis and in normal men. The serum oestrone sulphate level was significantly higher than normal in the patients (P< 0·0001). In affected men, there was a tendency towards higher dehydroepiandrosterone sulphate levels and no decline with age was seen in the patients as opposed to normal men (interaction:P< 0·025). Serum androstenedione, and oestradiol levels were lower than normal in the patients (P< 0·0005 andP= 0·055, respectively), while their LH level was higher than normal (P< 0·0005). The serum levels of SHBG, total and free testoster‐one, dihydrotestosterone, oestrone, and FSH were not significantly different from normal in the icthyotic patients. We suggest that the observed abnormalities in these patients are a consequence of the enzyme deficiency which severely impairs the ability of tissues to hydrolyse steroid sulphates.
DIAGNOSTIC VALUE OF A SINGLE SERUM THYROGLOBULIN DETERMINATION ON AND OFF THYROID SUPPRESSIVE THERAPY IN THE FOLLOW‐UP OF PATIENTS WITH DIFFERENTIATED THYROID CANCER
Authors: PACINI F. , LARI R. , MAZZEO S. , GRASSO L. , TADDEI D. , PINCHERA A.
Published: March 2008

To assess the significance of a single serum thyroglobulin (Tg) determination on and off thyroid suppressive therapy, serum Tg measurements have been performed in 349 serum samples from 82 patients with differentiated thyroid cancer. All samples were collected after total thyroidectomy with or without subsequent ablation of residual thyroid tissue by radioiodine. One hundred and fifty‐three samples were obtained while the patients were on thyroid suppressive therapy and 196 after withdrawal of medication. The results of serum Tg assays were analysed in relation to the presence or absence of residual or metastatic thyroid tissue, as assessed by clinical and laboratory evaluation, including 131I whole body scan. In patients with thyroid residue but no metastases, undetectable serum Tg (false negative results) occurred in 45% of cases off therapy and in 92·9% of cases during therapy. In the presence of metastases no undetectable serum Tg result was found in patients off therapy, while four (6·9%) out of 58 samples from patients with bone and/or lung metastases and seven (31·8%) out of 22 samples from patients with lymph node metastases alone were undetectable (falsely negative) during suppressive therapy. Serum Tg was undetectable in sera from patients with no evidence of thyroid residue or metastatic disease in all but one (1·7%) of 59 samples on and three (5·4%) of 56 samples off suppressive therapy. These Tg results were confirmed to be truly rather than falsely positive, since evidence of metastatic disease was obtained by whole body scan after the administration of therapeutic doses of 131I. These data indicate that the finding of detectable serum Tg during suppressive therapy is a reliable indicator of metastatic disease, while a negative result does not exclude the presence of metastases especially in the case of lymph node involvement. In this regard assays performed off therapy have greater diagnostic value.
FAMILIAL MALE PSEUDOHERMAPHRODITISM WITH GYNAECOMASTIA DUE TO 17β‐HYDROXYSTEROID DEHYDROGENASE DEFICIENCY. A REPORT OF 3 CASES
Authors: BALDUCCI R. , TOSCANO V. , WRIGHT F. , BOZZOLAN F. , DI PIERO G. , MARODER M. , PANEI P. , SCIARRA F. , BOSCHERINI B.
Published: March 2008

Three sisters with male pseudohermaphroditism due to 17β‐hydroxysteroid dehydrogenase deficiency are described. On the basis of a 46 XY karyotype and female phenotype all subjects were thought to have the testicular feminization syndrome. At puberty the two older patients developed signs of virilization and gynaecomastia. In these patients the plasma androstenedione level was 4‐5 times higher than normal, whilst the plasma testosterone level was low compared to the normal range and, under basal conditions, their plasma and rostenedione to testosterone ratio was 20–25 times higher than normal. Interestingly, in the third, prepubertal case, the basal androstenedione to testosterone ratio was normal but became six times higher than normal after hCG stimulation. These data support the diagnosis of male pseudohermaphroditism due to 17β‐hydroxysteroid dehydrogenase deficiency and underline the diagnostic value of the hCG stimulation test prepubertally.
SHORT‐ AND LONG‐TERM EVALUATION OF NORMAL AND ABNORMAL HUMAN THYROID CELLS IN MONOLAYER CULTURE
Authors: DAVIES T. F. , PLATZER M. , SCHWARTZ A. E. , FRIEDMAN E. W.
Published: March 2008

We have investigated the TSH responsiveness of normal and abnormal human thyroid cells cultured in the short term with high serum concentrations and for up to 6 months in a low serum, chemically‐defined, medium. Cells from normal human thyroid tissue (n= 9), multinodular goitre (n= 6), benign follicular adenomata (n= 6), and differentiated thyroid carcinoma (n= 3) formed confluent monolayers which were sensitive to bovine TSH (bTSH) in concentrations greater than 25 μU/ml when assessed by the intracellular response of cyclic AMP at 7 d of culture. Such sensitivity was less than that observed with a continuously proliferating thyroid cell line (FRTL‐5) derived from Fisher rat thyroid and which responded to concentrations of bTSH as low as 5–10 μU/ml. Human cells derived from iodine/antithyroid drug treated Graves' thyroid tissue (n= 6) were less sensitive than normal cells requiring up to 500 μU/ml bTSH to increase intracellular cyclic AMP and poorly differentiated thyroid cancer cells (n= 3) failed to respond to bTSH. Long‐term human thyroid cultures of normal and follicular adenoma cells in the chemically‐defined medium used for the FRTL‐5 cells had absent fibroblast growth and continued in monolayer form without significant follicle formation. These cells remained highly sensitive to bTSH stimulation when tested after 4, 13, and 26 weeks of continuous culture. All such cell preparations failed to proliferate under conditions which favoured the rapid growth of the rat thyroid cells. These data demonstrated that while thyroid cell culture conditions described in the literature do not permit proliferation of human thyroid cells, they do allow an assessment of their functional state in vitro which may lead to a further understanding of thyroid cell pathophysiology.
ANDROGENS, BEHAVIOUR AND NOCTURNAL ERECTION IN HYPOGONADAL MEN: THE EFFECTS OF VARYING THE REPLACEMENT DOSE
Authors: O'CARROLL R. , SHAPIRO C. , BANCROFT J.
Published: March 2008

The behavioural effects of varying the replacement dose of the oral androgen testosterone undecanoate (TU, Restandol) were investigated in eight hypogonadal men. Each man was withdrawn from his previous androgen replacement regimen and after a period of no treatment was administered four doses of TU (40, 80, 120 and 160 mg/d) in four successive one‐month treatment periods using a double‐blind design. Throughout the study each man recorded his sexual interest, behaviour and mood state using a daily diary form. In addition, four hypogonadal subjects had sleep erections and sleep quality assessed in the laboratory during a state of androgen withdrawal and again after a minimum of 5 months of androgen treatment. A dose response relationship was demonstrated for frequency of sexual thoughts, arousal accompanying sexual thoughts and well‐being. Sleep erections improved significantly during testosterone administration. In men, sexual interest and sleep erections are androgen‐dependent.
LONG‐TERM RESULTS OF TRANSSPHENOIDAL PITUITARY MICROSURGERY IN 60 ACROMEGALIC PATIENTS
Authors: ROELFSEMA F. , VAN DULKEN H. , FRÖLICH M.
Published: March 2008

Sixty patients with clinically and biochemically active acromegaly were treated by transsphenoidal surgery. All patients underwent a full assessment of pituitary function both preoperatively and postoperatively; these studies were repeated 6 months after surgery and every year, when possible. The mean follow‐up period was 3.3 years (range 0.5‐7 years). The GH level normalized in 62% of patients after surgery. A paradoxical reaction of GH to TRH was present in 35 patients before surgery and had normalized in 17 after surgery. Large tumours were associated with higher GH levels than smaller tumours. A prognostic factor in terms of normalization of both the GH level and an eventual paradoxical reaction to TRH or a glucose challenge was a low preoperative GH level. Three out of seven patients with either a positive postoperative TRH test but a normal GH level, or a slightly elevated GH level suffered a biochemical and clinical recurrence and two of them underwent reoperation. In contrast, when the TRH test had normalized (always in association with normal GH levels) no recurrence was found. The impact of surgery on the other pituitary functions was generally slight and the numbers of patients with preoperative and postoperative impairment were about equal. Postsurgical radiation therapy was administered to patients with an elevated GH level, a non‐normalized TRH test irrespective of whether the GH level had normalized, or local invasion of the tumour. In 11 out of 17 patients with elevated GH levels after surgery, normalization was achieved by radiation therapy after a mean period of 2.7 years. The incidence of pituitary failure after irradiation appeared to be high; gonadal function in men and the GH reserve function were especially vulnerable. From this study we conclude that in many cases the adenoma can be removed effectively, without compromising the other pituitary functions. However, a substantial number of the patients require additional radiation therapy, leading to an inevitable loss of other pituitary functions.
AUTOIMMUNITY AND THE PATHOGENESIS OF LOCALIZED THYROID AUTONOMY (PLUMMER'S DISEASE)
Authors: WIENER J. D. , VAN DER GAAG R. D.
Published: March 2008

The pathogenesis of Plummer's disease (localized thyroid autonomy) is incompletely known. It has been shown that a normal thyroid follicle can harbour cells with widely different properties, and hyperactive follicles may arise from cells with both high replicating and hormonogenic potencies under the influence of chronic mild stimulation. We now find thyroid growth‐stimulating immunoglobulins (TGI) to be present in low or intermediate titre in the serum of 7 of 9 patients with Plummer's disease. Haemagglutinating antibodies against thyroid microsomal antigen were present in low titre in two of these as well as in three of 21 other patients with this disorder. Two of the patients had a suppressible goitre in addition to the autonomous nodule. One of these is described in more detail. The possibility is discussed that autoimmunity may play a pathogenic role in Plummer's disease. TGI, in relatively low litres as found here, could exert the chronic mild stimulation supposed to be the prime event in the generation of hyperactive follicles. Whether autonomy is intrinsically present in these follicles or triggered by stimulation, remains to be established. Hyperthyroidism supervenes only when the mass of autonomous cells surpasses a certain limit. It appears that these patients with Plummer's disease should be included in the multidimensional spectrum of autoimmune thyroid disease.
A PROGNOSTIC SCORE FOR Graves' DISEASE
Authors: PREUS M. , FRECKER M. F. , STENSZKY V. , BALAŠS CĈC. , FARID N. R.
Published: March 2008

We have reanalysed the clinical and laboratory data on 196 individuals with Graves' disease. The consensus of two clustering techniques and a new method of allocating patients to a cluster resulted in two groups of patients, those with a severe and others with a mild disease. The severe disorder is characterized by a high frequency of HLA‐B8 and‐Al, a low complement level, high titres of circulating immune complex and anti‐thyroglobulin antibody, a high lymphocyte transformation index and serum T3 level, a low level of active E‐rosettes, large goitres and a high value for the Crooks test. The mild disorder shows a higher frequency of HLA‐B12 and an abnormally low absolute lymphocyte number. A weight was calculated for each character according to the relative frequency in the two clusters. A total score could then be calculated for each patient based on their clinical and laboratory findings. There were two distinct distributions of scores corresponding to the two subgroups. This suggests different aetiological factors which may be more easily studied in these more homogeneous groups. Prognostic predictions can be made using the score. The risk of recurrence and the frequency and severity of ophthalmopathy increases dramatically as the score increases. The use of the score in making therapeutic decisions needs to be tested.
AUGMENTATION OF THE RESPONSE TO CRF IN MAN: RELATIVE CONTRIBUTIONS OF ENDOGENOUS ANGIOTENSIN AND VASOPRESSIN
Authors: MILSOM STELLA R. , CONAGLEN J. V. , DONALD R. A. , ESPINER E. A. , NICHOLLS M. G. , LIVESEY J. H.
Published: March 2008

The plasma ACTH response to corticotrophin releasing factor (CRF) was studied in seven normal individuals. Five subjects were restudied following 4 d of salt restriction which resulted in raised endogenous plasma angiotensin II secretion. In a third experiment six subjects were given CRF following pre‐infusion of hypertonic saline which significantly increased endogenous plasma vasopressin (AVP) levels. We were unable to demonstrate that high endogenous plasma AII levels were associated with a significant change in the plasma ACTH or cortisol responses to CRF. However there was an almost three‐fold increase in the ACTH response when endogenous plasma AVP was elevated by hypertonic saline. It is concluded that AVP is likely to be of physiological importance in potentiating the ACTH response to CRF and that AVP and CRF together may provide a better test of pituitary ACTH secretion than either peptide alone.
AMIODARONE AND THYROID HORMONE ACTION JAYNE A.
Authors: FRANKLYN JAYNE A. , DAVIS J. R. , GAMMAGE M. D. , LITTLER W. A. , RAMSDEN D. B. , SHEPPARD M. C.
Published: March 2008

In clinically euthyroid subjects on long‐term amiodarone therapy free thyroxine (T4) concentrations were increased and free triiodothyronine (T3) levels reduced. There was also a marked increase in reverse T3 in the treated group. These changes are consistent with inhibition of peripheral deiodination of T4 and reverse T3. Despite the rise in T4 serum thyrotrophin (TSH) levels were increased, suggesting an effect of amiodarone on the anterior pituitary. To investigate the interaction of amiodarone with the cellular actions of thyroid hormones we examined the influence of the drug in vitro on the binding of T3 to isolated nuclei prepared from rat anterior pituitary tissue. Amiodarone inhibited the nuclear binding of T3 in a dose dependent fashion. Addition of amiodarone in vitro also stimulated TSH release from cultured rat anterior pituitary cells, consistent with a T3 antagonistic effect. These studies provide evidence for a direct influence of amiodarone on the thyrotroph, mediated via nuclear T3 receptor binding.
STIMULATION BY FOOD OF PERIPHERAL PLASMA IMMUNOREACTIVE GROWTH HORMONE RELEASING FACTOR
Authors: SOPWITH A. M. , PENNY ELIZABETH S. , BESSER G. M. , REES LESLEY H.
Published: March 2008

A highly specific radioimmunoassay has been used to study changes in peripheral human plasma growth hormone releasing factor (GRF) following the ingestion of food. From a mean basal plasma concentration of 11.8 pg/ml (range <7–15.4 pg/ml) in six normal individuals following overnight fast, the circulating concentration of GRF‐like immunoreactivity increased to a mean maximum of 36.7 pg/ml (range 20.2–77.0 pg/ml) sampled 120 min after a mixed breakfast. This increase in GRF was accompanied by suppression rather than stimulation of circulating growth hormone. The predominant source of peripheral circulating GRF‐like immunoreactivity may therefore by extrahy‐pothalamic and responds to an oral food stimulus.
HUMAN SERUM THYROTROPHIN MEASUREMENT BY ULTRASENSITIVE IMMUNORADIOMETRIC ASSAY AS A FIRST‐LINE TEST IN THE EVALUATION OF THYROID FUNCTION
Authors: MARTINO E. , BAMBINI G. , BARTALENA L. , MAMMOLI CLAUDIA , AGHINI‐LOMBARDI F. , BASCHIERI L. , PINCHERA A.
Published: March 2008

An ultrasensitive immunoradiometric assay (IRMA) using two monoclonal anti‐TSH antibodies has been used for TSH measurements in basal conditions and after TRH stimulation. The results have been compared with those obtained by conventional radioimmunoassay (RIA). The IRMA method had very high sensitivity (0·07 μU/ml). Detectable serum TSH concentrations were found in all normal subjects by IRMA, but in only 76% by RIA. No overlap was observed with the results obtained by IRMA in untreated overtly hyperthyroid patients, in whom serum TSH was below the limit of detection. The relationship between basal and TRH‐stimulated serum TSH concentrations by IRMA and RIA was evaluated in 176 subjects including normals and patients with untreated and treated hyperthyroidism, functioning thyroid adenoma, non‐toxic goitre and patients on l‐thyroxine therapy. A normal TSH response to TRH was observed in virtually all patients with detectable basal serum TSH by both methods. When patients with undetectable basal serum TSH levels were considered, all but one (98%) had no TSH response to TRH by IRMA. On the contrary using RIA, an absent response was found only in 47% of subjects, a blunted responses in 10% and a normal response in 42%. These data indicate that basal serum TSH measurements by IRMA allows a complete discrimination of normal from hyperthyroid patients and can avoid the need for TRH stimulation tests.
ENDOGENOUS LUTEINIZING HORMONE SURGE IN WOMEN DURING INDUCTION OF MULTIPLE FOLLICULAR DEVELOPMENT WITH PULSATILE FOLLICLE STIMULATING HORMONE
Authors: MESSINIS I. E. , TEMPLETON A. , BAIRD D. T.
Published: March 2008

In this study nine consecutive normally cycling women undergoing in‐vitro fertilization (IVF) were superovulated with clomiphene citrate followed by pulsatile ‘pure’FSH injected s.c. via a pump (28 IU every 3 h). All women displayed an endogenous LH surge, which was markedly attenuated in most of the cases (peak value 44·5 ± 5·9 U/l, duration 29·2 ± 1·2 h, mean ± SEM) as compared to spontaneous cycles. An increase in serum progesterone levels before the onset of the LH surge was seen in only one woman at a time when the LH values were low. During the LH surge serum progesterone levels increased significantly in all patients (12·7 ± 1·90 nmol/l vs 4·74 ± 1·57 nmol/l at the onset of the surge, mean ± SEM, P < 0·05) indicating follicular luteinization. Very high oestradiol levels in serum were found at the onset of the LH surge (7504 ± 898 pmol/1, mean ± SEM). Preovulatory oocytes were recovered from all women through a laparoscope 34–36 h after the beginning of the LH surge and embryos were replaced to them after IVF. One ongoing clinical pregnancy occurred. In contrast to results in monkeys, these results demonstrate for the first time that normally cycling women superovulated with clomiphene pulsatile ‘pure’FSH will display an endogenous LH surge. Although the surge is attenuated implantation can occur.
EFFECT OF FENOLDOPAM ON THE ALDOSTERONE RESPONSE TO METOCLOPRAMIDE IN MAN
Authors: DUPONT A. G. , VANDERNIEPEN P. , VOLCKAERT A. , SMITZ J. , VANSTEIRTEGHEM A. C. , SIX R. O.
Published: March 2008

The effect of fenoldopam, a selective DA1‐agonist, on the plasma aldosterone response to metoclopramide was studied in six hypertensive patients included in a multicentre double‐blind placebo controlled cross‐over study of the antihypertensive effects of fenoldopam. Fenoldopam significantly increased baseline plasma renin activity (PRA); baseline plasma aldosterone levels rose slightly. Baseline PRL and the PRL response to metoclopramide were not altered by fenoldopam. After metoclopramide, a significant increase of plasma aldosterone was observed during treatment with fenoldopam, as well as in the placeboperiod. The peak values were not significantly different and occurred at 15 min during both treatment periods. These results indicate that fenoldopam does not reduce metoclopramide‐induced aldosterone secretion and therefore suggest that the adrenal dopamine receptor is not identical to the vascular DA1 receptor.
TSH RECEPTOR ANTIBODY SYNTHESIS BY THYROID LYMPHOCYTES
Authors: MCLACHLAN S. M. , PEGG C. A. S. , ATHERTON M. C. , MIDDLETON S. L. , CLARK F. , SMITH B. REES
Published: March 2008

Several indirect observations have indicated that lymphocyte in the thyroid may be an important site of TSH receptor antibody synthesis in Graves’disease and we now describe an investigation of this possibility using improved lymphocyte isolation and TSH receptor antibody assay procedures. Our studies demonstrate that thyroid Iymphocytes spontaneously produce TSH receptor antibody in culture. Furthermore, experiments with mitogen tend to suggest that these cells, in contrast to lymphocytes from lymph nodes draining the thyroid, are part of an active immune response to the TSH receptor.
THE CIRCADIAN VARIATION OF THYROTROPHIN IN PATIENTS WITH PRIMARY THYROIDAL DISEASE
Authors: EVANS P. J. , WEEKS I. , JONES M. K. , WOODHEAD J. S. , SCANLON M. F.
Published: March 2008

We have used a highly sensitive immunochemiluminometric assay (ICMA) for human TSH to study the effect of thyroid status on the circadian variation in TSH levels. Three subjects with Graves' disease, three with toxic multinodular goitre and three with euthyroid multinodular goitre were sampled every hour for 24 h. The results obtained were compared to those from five euthyroid control subjects. It was found that some patients with hyperthyroidism and suppressed basal TSH levels exhibited a 24 h secretory pattern similar to that seen in normal subjects with peak TSH levels occurring at night. In addition two subjects with a euthyroid multinodular goitre demonstrated levels of TSH below the normal range despite being clinically and biochemically euthyroid. TSH suppression in these subjects is probably related to some degree of thyroid autonomy and possible development of hyperthyroidism in the future.
NORMAL CIRCULATING IMMUNOREACTIVE GROWTH HORMONE RELEASING FACTOR (hGRF) CONCENTRATIONS IN PATIENTS WITH FUNCTIONAL HYPOTHALAMIC hGRF DEFICIENCY
Authors: SOPWITH A. M. , PENNY ELIZABETH S. , GROSSMAN A. , SAVAGE M. O. , BESSER G. M. , REES LESLEY H.
Published: March 2008

Using a highly specific radioimmunoassay we have measured the concentrations of human growth hormone releasing factor (ir‐hGRF) in the peripheral circulation of six individuals with acquired hypothalamic hGRF deficiency. Despite their hypothalamic dysfunction venous plasma ir‐hGRF increased normally in every patient after the stimulus of a mixed breakfast, from an average concentration basally of 13.6 ± 6.0pg/ml to a maximum of 29.0 ± 8.4 pg/ml (mean ± SEM) at 120 min. The findings indicate that circulating hGRF is at least in large part extrahypothalamic in origin, which in turn implies a physiological role for hGRF in the periphery.
RECURRENT PREGNANCY‐INDUCED POLYURIA AND THIRST DUE TO HYPOTHALAMIC DIABETES INSIPIDUS: AN INVESTIGATION INTO POSSIBLE MECHANISMS RESPONSIBLE FOR POLYURIA
Authors: BAYLIS P. H. , THOMPSON C. , BURD J. , TUNBRIDGE W. M. G. , SNODGRASS C. A.
Published: March 2008

A young patient developed hypothalamic diabetes insipidus due to histiocytosis in infancy and was satisfactorily treated with Pitressin. As a teenager she no longer had thirst or polyuria after treatment was stopped. These symptoms only returned during her two pregnancies. When non‐pregnant her urine output was 1·7–2·0 1/24 h, basal plasma osmolality 288–290 mOsm/kg, and during pregnancy 24 h urine volume was 4·5–5·21, plasma osmolality 278–280 mOsm/ kg. Studies on osmoregulation of thirst and AVP release, and on renal sensitivity to the V2 agonist desmopressin and endogenous vasopressin were performed in pregnant and non‐pregnant states. She had no circulating antibodies to AVP, and the effect of pregnancy‐associated vasopressinase was eliminated. Results showed lowered basal plasma osmolality and osmolar thirst threshold in pregnancy but no failure of the renal concentrating mechanism. Plasma AVP concentrations after osmotic stimulation were lower in pregnancy. We propose that she developed thirst and polyuria during pregnancy because of lowering of her osmolar thirst threshold to plasma osmolalities which caused her to drink sufficient quantities of fluid to further reduce AVP secretion. We cannot exclude, however, the possibility that there was increased clearance of circulating AVP.
PROLACTIN AND STRESS: SOME ENDOCRINE CORRELATES OF PRE‐OPERATIVE ANXIETY
Authors: BROOKS J. E. , HERBERT M. , WALDER C. P. , SELBY C. , JEFFCOATE W. J.
Published: March 2008

An attempt was made to correlate the serum concentration of PRL, GH and cortisol with anxiety experienced before elective surgery. A significant direct correlation was observed between cortisol and anxiety (P= 0·028), and between GH and anxiety (P= 0·001) although the latter correlation may have reflected the confounding effects of sex and age on GH levels. No correlation was observed between anxiety and PRL and we conclude that psychosocial stress cannot be invoked as an occasional cause of hyperprolactinaemia.
GROWTH HORMONE RESPONSES TO GRF 1–29 IN PATIENTS WITH PRIMARY HYPOTHYROIDISM BEFORE AND DURING REPLACEMENT THERAPY WITH THYROXINE
Authors: VALCAVI R. , JORDAN V. , DIEGUEZ C. , JOHN R. , MANTCARDI E. , PORTIOLI I. , RODRIGUEZ‐ARNAO M. D. , GOMEZ‐PAN A. , HALL R. , SCANLON M. F.
Published: March 2008

It is well known that hypothyroidism is frequently associated with impaired GH responses to different stimuli. In the present study we have evaluated GH responses to GH‐releasing factor (GRF) in patients with primary hypothyroidism before and during T4 replacement therapy. Fourteen patients (age range 26–60 years) underwent two GRF tests (1 μg/kg) before and during replacement therapy (150 μg/d). Administration of T4 increased peak GH responses to GRF in 9 patients and in the group as a whole (mean ± SEM, 17·0 ± 2·8 vs 32·6 ± 5·7 mU/l, P > 0·02). When the data are analysed by means of area under the curve (AUC), the GH response to GRF was increased by T4 in 10 patients and in the group as a whole (mean ± SEM, 51·7 ± 14·3 vs 101·5 ± 28·1, P > 0·02). These data indicate that thyroid hormone replacement therapy enhances the responsiveness of the somatotroph to GRF 1–29 in patients with primary hypothyroidism.
DIAGNOSIS AND MANAGEMENT OF ACTH‐DEPENDENT CUSHING'S SYNDROME: COMPARISON OF THE FEATURES IN ECTOPIC AND PITUITARY ACTH PRODUCTION
Authors: HOWLETT T. A. , DRURY P. L. , PERRY L. , DONIACH I. , REES LESLEY H. , BESSER G. M.
Published: March 2008

The clinical features, diagnosis and management of 16 consecutive patients with ectopic ACTH production are described and biochemical data are compared with those of 48 consecutive patients with pituitary‐dependent Cushing's disease. In 10 cases the ectopic ACTH secreting tumour was completely occult to routine clinical and radiological investigation, and no basal or dynamic investigation of adrenal‐pituitary function was able clearly to differentiate these patients from those with Cushing's disease. High dose dexamethasone suppression testing assessed by plasma cortisol was usually helpful but unexpected responses were seen in both diagnostic groups; the metyrapone test yielded no useful information and should now be abandoned. Hypokalaemia was seen in all patients with ectopic ACTH production but in only 10% of those with Cushing's disease who were not on diuretics at presentation. Successful diagnosis and tumour localization was most frequently achieved by a combination of CT scanning of the chest and abdomen and venous catheter sampling for ACTH. All patients in whom the ectopic ACTH‐secreting tumour was obvious at presentation died of their primary tumour within 8 months, whereas seven of the 10 patients with occult tumours at presentation are alive 1·5–16·5 years later, and appear cured. Occult ectopic ACTH secretion may be impossible to distinguish from pituitary Cushing's disease. Multiple and repeated investigations are often required to make this differential diagnosis, essential for appropriate therapy.