bluuebunny/crossref_metadata_2025 huggingface dataset:
The effect of lithium therapy on parameters thought to be involved in the development of autoimmune thyroid disease
Authors: Wilson R. , McKlllop J. H. , Crocket G. T. , Pearson C. , Jenkins C. , Burns F. , Burnett A. K. , Thomson J. A.
Published: March 2008

This study has considered the effects of primary affective disorders and lithium therapy on a number of factors thought to be Important In the development of autoimmune thyroid disease. These factors were examined In (a) controls with no history of any such disorders; (b) patients with primary affective disorders treated with drugs other than lithium and (c) patients with primary affective disorders treated with lithium alone.

Eight of 40 patients who were receiving lithium therapy were found to be positive for thyroid microsomal and/or thyroglobulin antibodies, compared to only 3/40 patients who were receiving some other form of treatment for their depression. Peripheral blood mononuclear ceils from patients receiving lithium were found to have significantly reduced numbers of suppressor/cytotoxlc T cells (p>0.05). In addition, suppressor T cells from these patients showed a significantly reduced response to stimulation with concanavalin A (p>0.01). These effects were greatest In patients found to be antibody positive. Increased B cell activity, as measured by Increased IgG and IgM release following mltogen stimulation, was seen in patients receiving lithium and in those patients receiving other forms of treatment for their depression. This would suggest that the Increase Is a feature of primary affective disorders and is not due specifically to lithium treatment. It would appear from this study that lithium therapy induces antibody formation In susceptible Individuals and this may ultimately lead to the development of thyroid disease.
Histological and biochemical distinctiveness of atypical aldosterone‐producing adenomas responsive to upright posture and angiotensin
Authors: Tunny Terry J. , Gordon Richard D. , Klemm Shelley A. , Cohn David
Published: March 2008

Fifteen patients with primary aldosteronism were classified as anglotensin II‐unresponsive aldosterone‐producing adenoma (All‐U APA, n = 9), or anglotensin II‐responsive aldosterone‐producing adenoma (All‐R APA, n= 6), based on the responsiveness of aldosterone to upright posture and to anglotensin II infusion. Lack of aldosterone response to anglotensin II Infusion immediately post‐operatively In the All‐R APA subtype was consistent with previous responsiveness residing solely within the adenoma. Cortisol levels In five of the six patients with All‐R APA failed to suppress normally with dexamethasone consistent with some autonomous production of cortisol by the adenoma. In contrast, cortisol levels suppressed normally during dexamethasone administration In all patients with All‐U APA. This biochemical distinction can be added to the previously described overproduction of 18‐oxo cortisol in All‐U APA but not in All‐R APA. Histological examination of adenoma sections revealed predominantly (±‐50%) zone fascicuiata type cells in All‐U APA. In contrast, All‐R APA contained less than 20% zona fasciculata type. Thus, biochemical differences between All‐U APA and All‐R APA subtypes of primary aldosteronism may be due to underlying differences In cellular composition of the aldosterone‐producing adenomas.
Physiological growth hormone secretion in adult growth hormone deficiency: comparison with normal controls
Authors: Whitehead Helen M. , Aikent Brenda , Lewis Stuart , Sheridan Brian , Haddon David R.
Published: March 2008

A comparison was made between the pulsatile pattern of growth hormone secretion In 14 growth hormone deficient adults (serum growth hormone less than 7 mU/l following insulin‐stimulated hypoglycaemia) and 14 age and sex matched controls. The 24‐h secretory profile was generated by 2‐hourly sampling from 0800 to 2200 h, and 30‐min sampling from 2200 to 0600 h. Plasma GH in each sample was measured using a double antibody radloimmunoassay. The profiles were analysed using a computer program (Pulsar). Sleep‐electroencephalography was recorded In all subjects. The total amount of GH secreted In a 24‐h period (area under the curve over baseline) was significantly less In the growth hormone deficient group (P > 0·002). The pulse frequency, amplitude, height and percentage GH secreted in peaks were also significantly less in the growth hormone deficient group (P > 0± 002 respectively). We conclude that adults deficient In GH, as defined by conventional pharmacological stimuli, are in addition physiologically deficient of pulsatile GH secretion.
HLA Associations with Hashimoto's thyroiditis
Authors: Tendon N. , Zhang L. , Weetman A. P.
Published: March 2008

There Is disagreement over the HLA‐DR associations of Hashimoto's (goitrous) thyroiditis. We have studied 86 English Caucasian patients with this condition whose DR types were determined by restriction fragment polymorphism analysis. HLA‐DR3 was significantly more frequent In these patients than in 100 controls (χ2= 7·09; P > 0·01). The relative risk was 2·23 and aetiological fraction 0·29. HLA‐DPB and DOB alleles were analysed in a proportion of these subjects by enzymatic DNA amplification and oligonucleotide probing. The only significant finding was an excess of HLA‐DQw2 (In linkage disequllibrium with DR3) In the Hashimoto group (χ2=7·43, P > 0·007). These results do not support a difference between goitrous and atrophic thyroiditis based on respective associations with HLA‐DR5 and DR3, but confirm a recent study in which HLA‐DR3 was associated with Hashimoto's thyroiditis. However, It Is possible that genes telomeric to DR3 may be Involved in determining which type of thyroiditis a patient with autoimmune hypothyroidism develops.
Production of calcitonin gene related peptide, calcitonin and PTH‐related protein by a prostatic adenocarcinoma
Authors: Shulkes A. , Fletcher D. R. , Rubinstein C. , Ebelingt P. R. , Martint T. J.
Published: March 2008

PTH and calcitonln are the two major hormones controlling calcium metabolism. Recently two new substances related to these hormones have been Isolated: calcitonln gene related peptide (CGRP) and PTH‐related protein (PTHrP). CGRP Is a potent vasodilator and stimulant of intestinal secretion while PTHrP Is probably the agent responsible for humoral hypercalcaemla of malignancy. We report here a patient with a prostatlc tumour presenting with vasodilatlon, diarrhoea and hypercalcaemia. Our investigations revealed that the primary prostatic and liver secondary tumour contained CGRP, calcitonln and PTHrP. Most of the immunoreactive CGRP in the tumour and plasma co‐eluted with the biologically active form of CGRP. The circulating levels of CGRP correlated with the presence of the diarrhoea. PTHrP concentration In the tumours was one of the highest reported for any tumour although previous studies may have utilized less than optimal extraction procedures. The somatostatin analogue, octreotide (SMS 201–995), did not reduce the plasma CGRP or the diarrhoea, a finding similar to that seen in patients with medullary thyroid carcinoma and high plasma CGRP. The hypercalcaemla was also unaffected by octreotide administration. This is the first report of a prostatic tumour associated with over‐production of calcltonin, PTHrP and CGRP. The major life‐threatening effects of this unusual case of prostatic carcinoma were diarrhoea and hypercalcaemia. Both these effects could be tentatively ascribed to newly discovered substances, CGRP and PTHrP. With the greater availability of assays to measure CGRP and PTHrP in plasma, a detailed examination of the incidence of over‐production of these substances In various cancers will be possible.
Megavoltage pituitary irradiation in the management of prolactinomas: long‐term follow‐up
Authors: Tsagarakis S. , Grossman A. , Plowman P. N. , Jones A. E. , Touzel R. , Rees L. H. , Wass J. A. H. , Besser G. M.
Published: March 2008

objective To determine the long‐term effects of external beam megavoltage radiotherapy (RT: 4500 cGy via three portals at 180 cGy or less total daily dose) on endocrine function in prolactinomas.

design Longitudinal study following radiotherapy with periodic re‐assessment at regular Intervals, at least 2 months off dopamine agonist therapy.

patients Thirty‐six female patients, age range 19–50 years, with either macroprolactlnomas (12 patients) or macroprolactinomas (24 patients), but without significant suprasellar extensions.

measurements Clinical appraisal, and anterior and posterior pituitary assessment: basal levels at yearly intervals or less, with dynamic screening with TRH, LHRH and hypoglycaemic stimulation every 2–3 years.

results Before RT, serum prolactin (PRL) levels ranged from 1150 to 34 000 mU/l; after RT (mean 8·5 years, range 3–14), serum PRL fell to normal (l.e. >360 mU/l) in 18 of the 36 patients (50%), and to just above the normal range (378–780 mU/l) in a further 10 (28%). Two patients had PRL levels at their last follow‐up higher than those at presentation, with one patient showing evidence of tumour recurrence on CT scan. A total of eight of the 36 patients (23%) developed post‐RT gonadal deficiency by the end of follow‐up at 8 ± 3·1 years (± SD, range 3–11), but six were aged over 40 years at that time. GH deficiency was frequent, occurring in 94% of patients, usually from 2 to 3 years post‐RT, while TSH deficiency and reduced ACTH reserve was uncommon (each 14%), and occurred later. In the subgroup of 12 patients with macroprolactinomas, results were broadly comparable.

conclusions Megavoltage RT produces a progres‐sive fail in serum prolactin in the great majority of patients with prolactinomas, with a relatively low incidence of TSH or ACTH deficiency. As it Is now clear that dopamine agonist therapy alone provides suff iclent management for microprolactinomas, RT may be used for the long‐term control of macroprolactlnomas, together with interim dopamine agonist therapy. It allows pregnancy to be safely undertaken but, in view of the delayed onset of gonadal deficiency, Its administration should be tlmed with respect to the desired onset of conception In women.
Primary localized cutaneous amyloidosis and familial medullary thyroid carcinoma
Authors: Ferrer Jorge P. , Halperin Irene , Conget J. Ignacio , Alsina Mercé , Martinez‐Osaba Maria J. , Palou Josep , Bombs Josep A. , Vilardell Enric
Published: March 2008

We have studied a family with an autosomai dominant Inheritance of primary localized cutaneous amyloidosis (PLCA) and familial medullary thyroid carcinoma (MTC). Ten family members were screened for multiple endocrine neoplasia (MEN) 2; five were found to have MTC and two had C‐cell hyperplasia. None had evidence of phaeochromocytoma or parathyroid abnormalities. Five of these seven patients presented characteristic inter‐scapular hyperpigmented lesions, showing dermal amylold deposits In two of the four patients In which a biopsy was performed. The data are analysed In the light of two recent reports of MEN 2A associated with Identical lesions. We conclude that PLCA should be sought in MTC patients, even If no other endocrinopathies are present. This may be Informative of the familial character of MTC in Index cases and also of the tumour gene status in family members who are being screened
Plasma growth hormone (GH)‐releasing hormone levels in patients with lung carcinoma
Authors: Schopohl Jochen , Lose Marco , Frey Chris , Wolfram Gernot , Huber Rudolf , Permanetter Willibald , von Pawel Joachim , Müller O. Albrecht , von Werder Klaus
Published: March 2008

objective The aim was to investigate the serum levels of growth hormone releasing hormone and GH in patients with lung carcinoma

design After an overnight fast a plasma sample was collected for determination of growth hormone releasing hormone and GH

patients The investigation was performed in 28 patients with non small cell lung carcinoma, in 44 patients with small cell lung carcinoma, and 10 patients with non malignant lung disease. A group of 37 normal subjects served as control

measurements Growth hormone releasing hormone and GH were determined by radloimmunoassay

results Patients with small cell lung carcinoma showed higher plasma growth hormone releasing hormone levels (49·9±4 ng/l) than control subjects (16·3±2·1 ng/l; p>0·05), patients with non small cell lung carcinoma (23·9± 8·8 ng/l; p>0·05), and patients with non malignant lung disease (12·7±5·5; P > 0·05). Basal GH level was lower than 5 μ g/l In all patients except five patients with small cell lung carcinoma and one patient with non small cell lung carcinoma.

conclusions The higher plasma growth hormone releasing hormone levels in patients with small cell lung carcinoma compared to normal controls and patients with non small cell lung carcinoma and patients with non malignant lung disease, confirm the frequent neuroendocrine activity of this particular tumour
Changes in skeletal muscle and body composition after discontinuation of growth hormone treatment in growth hormone deficient young adults*
Authors: Rutherford O. M. , Jones D. A. , Round J. M. , Buchanan C. R. , Preece M. A.
Published: March 2008

objectives The aim of this study was to determine whether there are any changes in skeletal muscle strength and size and body composition following growth hormone (GH) withdrawal in GH deficient young adults

design A longitudinal, 1‐year, open, uncontrolled study of the changes in skeletal muscle and body composition following GH withdrawal was performed. Endocrine status was reassessed at the end of the study period during an insulin tolerance test. Some measurements were repeated after 2 years off treatment

patients Twelve (11 male, one female; age range 14–21) patients who had been diagnosed during childhood as growth hormone deficient took part in the study. Four of the 12 patients were found to have a normal GH response on retesting at the end of the study and their results were analysed as a separate group

measurements Quadriceps and forearm flexor maximum voluntary isometric strength, body fat content and serum IGF‐1 were measured at 3‐monthly intervals over 1 year. Every 6 months muscle size was measured from computerized tomography scans and fibre area from quadriceps needle biopsy samples

results For the growth hormone deficient group the 12 month quadriceps strength, size and fibre areas were 94·0%±8·5 (mean±SD), 94·5%±6·3 and 85·6%±17·7 respectively of control (baseline) values. Forearm flexor strength and size were 101·4%±7·9 and 92·0%±9·2 of control. Body fat percentage had Increased from 19·5%±8·6 to 24·1%±9·5. No change was seen In the non‐growth hormone deficient group

conclusions Although the changes measured were relatively small they suggest a role for GH In the maintenance of muscle integrity and body composition in the young adult with growth hormone deficiency
Effects of gonadotrophin releasing hormone antagonist and agonist on the pulsatile release of gonadotrophins and α‐subunit in postmenopausal women*
Authors: Couzinet B. , Lahlou N. , Thomas G. , Thalabard J. C. , Bouchard P. , Roger M. , Schalson G.
Published: March 2008

objective The present study was designed to further assess the mechanism of action of GnRH and GnRH analogues

design AND PATIENTS Both the Nal‐Glu GnRH antagonist and the D‐Trp6 GnRH agonist were administered sequentially to nine normal, post‐menopausal women. MEASUREMENTS A baseline study of pulsatile LH, FSH and free α‐subunit secretion was performed, with sampling every 10 min for 8 h, and then repeated 8 h after a single subcutaneous injection of Nal‐Glu GnRH antagonist (5 mg). Sampling was repeated 21 days after the intramuscular injection of a depot preparation of D‐Trp6 GnRH (3·75 mg) in the same women.

results The baseline sampling period showed synchronous pulses of LH and free α‐subunit. The antagonist Nal‐Glu decreased plasma LH (71%) and free α‐subunit (43%). However, with the single dose of 5 mg, pulsatile LH and free α‐subunit release were not completely suppressed and remained temporally correlated. The GnRH agonist had a potent inhibitory action on plasma immunoreactive LH (IRMA) (93%). In contrast, it increased the mean plasma levels of free α‐subunit from 1·66·0±01 to 5·06·0±02 μ g/l (205%). The pulsatile secretory patterns of both LH and free α‐subunit were abolished by the agonist. Immunoreactive FSH levels were decreased by the antagonist (24%) and suppressed by the agonist (93%).

conclusions The pulsatile study confirms the different mechanism of action of GnRH analogues. Following antagonist administration, low amplitude free α‐subunit pulses persist and are synchronous with residual LH pulses. In contrast, LH and free α‐subunit are not maintained under agonist treatment. These data provide evidence for the differential regulation of LH and free α‐subunit by GnRH.
Corticosteroid‐induced growth hormone secretion in normal and obese subjects
Authors: Muruals Covadonga , Cordidot Fernando , Moralesf Maria J. , Casanueva Felipe F. , Dléguez Carlos
Published: March 2008

objective In normal subjects, cortlcosterolds stimulate growth hormone (GH) secretion at 3 hours. Obesity is associated with blunted GH secretion. In order to clarify both the deranged mechanism of GH secretion In obesity and the corticosterold mechanism of action we have assessed In normal and obese subjects the effects of dexamethasone, pyridostigmine (a drug capable of suppressing somatostatln release) and GHRH. We also compared in normal subjects the stimulatory effect of three different cortlcosterolds on plasma GH levels

design In both normal and obese subjects the following tests were carried out: placebo; dexamethasone alone (4 mg l.v. at 0 minutes); and dexamethasone plus pyridostigmine (120 mg p.o. at 60 minutes)

In normal subjects we also studied the effects of hydrocortisone (100 mg l.v. at 0 minutes) and deflazacort (a corticosteroid that does not cross the blood‐brain barrier) (60 mg l.v. at 0 minutes). In obese subjects we also assessed the effect of dexamethasone plus GHRH (100 μ g l.v. at 150 minutes) on plasma GH levels.

patients Ten normal subjects and 22 obese subjects were studied. Normal controls were within 10% of their ideal body weight. Obese subjects had a body mass Index of 37·1±1·1 (mean ± SEM)

measurements Plasma GH levels were measured by radioimmunoassay

.

results Dexamethasone‐induced GH secretion In normal subjects (28·6±7·8 mμ/l, P > 0·05). Cortlcosterolds did not alter GH levels In obese subjects. Pretreatment with pyridostigmine increased dexamethasone‐induced GH release in normal subjects (40·8±6·8 mμ/l) but this did not achieve statistical significance. Dexamethasone plus pyridostigmine did not alter GH levels In obese subjects (8·0±1·6 mU/l). In some subjects, dexamethasone protreatment potentiated GHRH‐stimulated GH secretion, while In half the subjects the basal GH levels were not altered.

In control subjects, hydrocortisone and deflazacort caused GH release similar to dexamethasone

conclusions Corticosteroids are a new and selective stimulus of GH secretion. They do not cause GH release in obese subjects. Their relative independence from chollnergic control suggest that they act by reducing somatostatin secretion
Effects of pyridostigmine on spontaneous and growth hormone‐releasing hormone stimulated growth hormone secretion in children on daily glucocorticoid therapy after liver transplantation
Authors: Giustina Andrea , Girelli Angela , Albert Danlele , Bossonl Simonetta , Buzl Fabio , Doga Mauro , Schettino Maurlzlo , Wehrenberg William B.
Published: March 2008

objectives We aimed to investigate both nocturnal spontaneous and morning growth hormone (GH)‐releasing hormone (GHRH)‐induced GH secretion in children on daily glucocorticoid treatment after liver transplantation and to evaluate the effect of pyridostigmine (an acetylcholinesterase inhibitor thought to reduce hypothalamic somatostatin tone) on GH secretion in these patients

design We performed a randomized, single‐blind, crossover study

patients We studied three male and three female Juvenile patients, within a year of orthotopic liver transplantation and under immunosuppressive glucocorticoid therapy (mean dose ± SEM, 5·92·0±63 mg/day) and five normal children (four males, one female)

measurements Both nocturnal spontaneous and morning GHRH‐induced GH secretion were evaluated after administration of placebo, 1 tablet P.O., or pyridostigmine, 2 mg/kg p.o

results Spontaneous GH. Placebo: in liver transplanted children nocturnal GH secretion (mean GH level 10·8±2·0 mU/l) was not significantly different with respect to normal children (mean GH level 12·8±1·2 mU/l); pyridostigmine: nocturnal GH secretion was significantly Increased as compared to placebo In subjects with liver transplantation but not In normal children. GHRH test. Placebo: liver transplanted patients showed a blunted GH response to GHRH with respect to normal children; pyridostigmine: the GH responses to GHRH (P > 0·05) Increased as compared to placebo and did not differ sign If Icantly In the two groups.

conclusions Our data suggest a steroid‐mediated increase in hypothalamic somatostatin tone in liver transplanted children
Effects of ambient glycaemic state on growth hormone responsiveness in insulin‐dependent diabetes
Authors: Ismail I. S. , Scanlon M. F. , Peters J. R.
Published: March 2008

objective We wished to examine the effects of ambient glycaemla on hypothalamic somatostatlnerglc tone In Insulin‐dependent diabetes mellitus

design After 6‐hour periods of either euglycaemla (15 mmol/l) or hyperglycaemia (15 mmol/l), exercise‐induced GH secretion was measured

patients Seven insulin dependent diabetics with no evidence of complications were recruited

results There was no significant difference between basal GH levels during euglycaemla and hyperglycaemia (5·50 vs 5·53 mU/l). Nor was there a significant difference when mean Δ GH levels (33·9 vs 27·4 mU/l) or mean area under GH curve (2331 vs 4038 mU min/l) during euglycaemia or hyperglycaemia were compared.

conclusions We find no evidence therefore to support short‐term effects of ambient glucose concentration on GH responsiveness, and by inference no direct effect of short‐term changes in glycaemic control on hypothalamic release of somatostatln in the aetiology of GH hypersecretion In insulin‐dependent diabetes mellitus
Circulating levels of inhibin in pregnant women at term: simultaneous disappearance with oestradiol and progesterone after delivery
Authors: Kettel L. M. , Rosati S. J. , Bangah M. L. , Burger H. G. , Yen S. S. C.
Published: March 2008

Circulating levels of immunoreactive inhibin (ir‐inhibin) and its disappearance after delivery of the placenta were determined in seven pregnant women at term. Serum cestradiol (E2) and progesterone (P4) levels were measured simultaneously and served as comparisons. Fetal contributions of ir‐inhibin were asessed by determining concentrations in the umbilical artery (UA) and vein (UV). Relative changes in circulating levels of ir‐inhibin, E2, and P4 were compared to levels found in nonpregnant women during the early follicular phase (EFP) and mid‐luteal phase (MLP) of the normal menstrual cycle. In pregnant women, ir‐inhibin levels at delivery were 15‐ and 3‐fold higher than EFP and MLP values respectively. The disappearance of all three hormones after removal of the placenta followed a bi‐exponential curve with an initial, rapid component and a second, slower component. There was a highly signifiant positive correlation between the disappearance curves of all three placental hormones (r = 0–97, P > 013001). Concentrations of ir‐inhibin in the cord blood were about half that in maternal serum and without significant difference between levels in UA and UV.
The pathogenesis of the ovarian hyperstimulation syndrome (OHS): a possible role for ovarian renin
Authors: Ong A. C. M. , Eisen V. , Rennie D. P. , Homburg R. , Lachelin G. C. L. , Jacobs H. S. , Slater J. D. H.
Published: March 2008

Two patients with severe ovarian hyperstimulation syndrome are described. Increased plasma concentrations of immunoradlometrically determined total renin are shown, together with greatly increased plasma levels of active renin and aldosterone. These very high values for total renin, renin activity and aldosterone were not suppressed when extracellular compartments were greatly expanded; the values subsequently declined to normal levels, despite the use of diuretics. This suggested that the renin was of non‐renal origin since its production was apparently unaffected by influences which control juxtaglomerular secretion. The high concentrations of the rennin—angiotensin—aldosterone system suggest that it contributes to the genesis of the ovarian hyperstimulation syndrome
Use of ketoconazole in the treatment of Cushing's disease and ectopic ACTH syndrome
Authors: Tabarin A. , Navarranne A. , Guérin J. , Corcuff J. ‐B. , Parneix M. , Roger P.
Published: March 2008

Ketoconazole, an imidazole derivative which Inhibits adrenal steroidogenesis, has been used with success for the metabolic control of Cushing's disease. Few data are available about the use of ketoconazole in the management of the ectopic ACTH syndrome. We have used ketoconazole in eight patients: four patients with Cushing's disease, two patients with overt and two with occult ectopic ACTH syndrome. Among patients with Cushing's disease, reversible hypoadrenalism occurred once. All had full clinical and biochemical regression of the disease for more than 6 months with 400–1200 mg ketoconazole per day. Patients with ectopic ACTH syndrome received 1200 mg ketoconazole per day for at least 2 months. Partial biochemical regression was observed in two and a secondary escape to adrenal blockade in two others. These findings further indicate that ketoconazole is a valuable tool for the metabolic control of Cushing's disease. On the contrary, in ectopic ACTH syndrome, this aim can be impossible to reach with ketoconazole although the reasons for its ineffectiveness remain to be determined.
Long‐term follow‐up of treatment of thyrotoxicosis by three different methods
Authors: Franklyn Jayne A. , Daykin Jackie , Drolc Zorka , Farmer Malcolm , Sheppard Michael C.
Published: March 2008

In view of continuing debate regarding the best definitive therapy for thyrotoxicosis, we examined the long‐term outcome of radiolodine (131I) or surgical treatment of 1918 thyrotoxic patients divided into three groups: those given 131I at a dose calculated from thyroid size, 131I uptake and effective half‐life to administer a fixed radioactivity dose to the thyroid; those treated with a dose of 131I (110,185 or 370 MBq) chosen empirically; and those treated by partial thyroidectomy. A minimum 10‐year follow‐up was achieved for 1119 patients treated with a calculated 131I dose; a single dose resulted in control of disease in 90.5|X%. At 5 years, 18|X% were hypothyroid, the prevalence rising to 42|X% at 20 years. Of 504 patients treated with an empirical 131I dose and followed for at least 5 years, thyrotoxicosis was controlled by a single dose in 89.7|X%. The rate of hypothyroidism at 5 years (38.5|X%) was higher than that found in the calculated dose group. A minimum 10‐year follow‐up was achieved for 295 surgically treated patients; thyrotoxicosis was controlled in 89.2|X%. The prevalence of hypothyroidism (2|X% at 5 years, 27.5|X% at 20 years) was lower than that found after 131I, whether given by calculated or empirical dose. Each of the treatments employed resulted in an acceptable rate of cure of thyrotoxicosis. If maintenance of euthyroidism is the major objective, our findings suggest that surgery represents the treatment of choice. Furthermore, calculated dose 131I administration has advantages in terms of risk of hypothyroidism over empirical dose treatment. In choosing treatment, these apparent advantages of partial thyroidectomy and calculated 131I doses over empirical doses of 131I must be weighed against surgical morbidity, cost and patient inconvenience.
Increased growth hormone response to growth hormone releasing hormone induced by erythropoietin in uraemic patients
Authors: Cantalamessa L. , Cremagnani L. , Orsatti A. , Vigna L. , Buccianti G.
Published: March 2008

This study was designed to assess the response of growth hormone (GH) to growth hormone releasing hormone (GHRH) and the possible interaction of acutely administered recombinant human erythropoietin (rhEPO) on GH response to GHRH in a group of uraemic patients. Eight patients on maintenance haemodialysis, not previously treated with rhEPO, and six healthy controls were tested with GHRH (100 μg i.v. in bolus), and with GHRH (100 μg i.v. in bolus) plus rhEPO (40 U/kg in constant infusion for 30 min) on different days. GHRH injection provoked a GH release in five out of eight uraemic patients; the overall mean response did not differ significantly from the GH response obtained in controls (P = 0.30). Erythropoletin infusion significantly increased GH release after GHRH (P > 0.01 at 15, 30, 45, 60 min after GHRH injection) in uraemic patients; in controls, on the contrary, stimulation with GHRH plus rhEPO did not induce a greater increase of OH release compared with that observed after GHRH alone (mean GH peak 37.66 |Mp 7.68 mU/I after GHRH; and 38.0 |Mp 9.18 mU/I after GHRH plus rhEPO; P < 0.5). In this study acutely administered rhEPO significantly potentiated the GH response to GHRH in uraemic patients whereas the same effect was not demonstrable in subjects with normal renal function.
Cyproterone acetate for severe hirsutism:results of a double‐blind dose‐ranging study*
Authors: Barth J. H. , Cherry C. A. , Wojnarowska F. , Dawber R. P. R.
Published: March 2008

Summary. objective The objective was to determine If cyproterone acetate (CPA) therapy lor hirsute women demonstrated a dose response.

design A double‐blind dose‐ranging study of the effect of 3 doses of cyproterone acetate for a period of 12 months.

patients Twenty‐one hirsute women received the Dlanette contraceptive pill (35μ ethinyl oestradlol+2 mg CPA, Sobering Healthcare, UK, 20 received Dlanette plus 20 mg CPA and 19 received Dlanette plus 100 mg CPA: supplementary CPA was administered on days 1–10 of the birth control pill cycle as described by Hammersteln.

measurements

Hair growth was measured using the clinical scale of Ferrlman and Gallwey and by direct measurement of hair shaft diameter and linear growth of hair on the face, forearm, abdomen and thigh.

results Thirty‐eight women completed 12 months therapy, eight withdrew due to side‐effects and 14 were lost to follow‐up. All three dose schedules produced significant reductions In clinical hair growth scores. This reduction was seen after 6 months with Dlanette alone (P< 0.005) and after 3 months with both the higher doses (P< 0.01). There were no significant differences between the effect of different doses at any of the three‐monthly time points. Hair diameter measurements were reduced by all doses after 12 months:face by 27*, 37, 37%*, forearm 5, 10, 8%*, abdomen 22*, 39*, 33%*, thigh 12, 24*, 30%* (median reductions (*P< 0.01) for Dianette, D + 20 mg CPA and D + 100 mg CPA respectively. There were no significant reductions in daily linear growth rates. A comparison of the percentage reduction In hair shaft diameter at each site demonstrated no significant difference between doses, although the reductions by the three doses on the forearm, abdomen and thigh suggested a trend towards a dose response.

conclusions We conclude that cyproterone acetate 2 mg daily appears to be as effective as higher doses in the therapy of hirsute women.
Critically ill patients have high basal growth hormone levels with attenuated oscillatory activity associated with low levels of insulin–like growth factor‐I
Authors: Ross Richard , Miell John , Freeman Emma , Jones Jennifer , Matthews David , Preece Michael , Buchanan Charles
Published: March 2008

Summary. objective The aim was to study the relationship between growth hormone (GH) and insulin‐like growth factor‐I (IGF‐I) in critically ill patients.

design Case‐control study of critically ill patients admitted to the intensive care unit was carried out.

patients Six critically ill patients (51–78 years) who required ventilation and parenteral nutrition and six age, weight, height, and sex‐matched healthy adults were studied.

measurements The patients and controls were studied for two 24‐hour periods; the patients before and after starting parenteral feeding, and the controls during a 36‐hour fast and when taking meals equivalent in calories and protein to the patients' parenteral feed. Serum GH was measured at 20‐minute intervals and analysed by a pulse detection algorithm (Pulsar) and Fourier transformation. IGF‐I was measured at 0, 12, and 24 hours.

results Patients had low serum IGF‐I levels compared with controls, whether fasted or fed, despite having mean GH levels similar to fasted controls. For fasted patients va fasted controls the mean (1 SD) GH levels were 4.5 . 2.0 vs 4.0 × 2.4 mU/l respectively, and IGF‐I levels at the end of the fast were 0.17 × 0.11 vs 0.78 × 0.29 U/ml (P=0.003). Patients showed elevated baseline GH levels compared with controls when fasted and during parenteral feeding (patients vs controls fasted 3.1 × 1.9 vs 0.8 × 0.5 mU/l, P= 0.01; patients vs controls fed 4.2 × 4.5 vs 0.5 × 0.04 mU/l, P= 0.028). Fourier transformation confirmed oscillatory GH levels in the controls, fasted or fed, but this activity was attenuated in the patients. Parenteral feeding had no effect on the GH profiles or IGF‐I levels of patients, but controls showed greater mean GH levels during their fast than when fed.

conclusions We have demonstrated that critically ill patients have low IGF‐I levels associated with augmented baseline GH levels which show reduced oscillatory activity. The results would be compatible with the hypothesis that there is an adaptive change in critically ill patients away from the indirect effects of GH (stimulation of IGF‐I production and anabollsm) and toward the direct effects (lipolysis and Insulin antagonism) which increase the availability of energy substrates. The pattern of GH levels seen In our patients may be important in this adaptation.
Cell kinetics in parathyroid adenomas: evidence for decline in rates of cell birth and tumour growth, assuming clonal origin
Authors: Parfitt A. M. , Wlllgoss D. , Jacobi J. , Lloyd H. M.
Published: March 2008

Summary. objective We aimed to provide a cell kinetic explanation for the demonstrated lack of disease progression in most patients with mild, asymptomatic primary hyperparathyroldism.

design We compared cell birth rates, estimated at the time of adenoma excision, with the lowest birth rates needed to grow tumours of the observed size.

patients Sixty‐three patients with primary hyperparathyroldism due to a single chief cell adenoma who had normal renal function were followed up for long enough to demonstrate cure after surgical excision.

measurements

Fresh adenoma tissue was incubated with trltlated thymldine. The proportion of cells synthesizing DNA was determined directly by radloautography in 18 cases, and indirectly from the regression of label index on rate of DNA synthesis in 45 cases. The birth rate of new cells was calculated assuming the duration of S phase to be 12 hours. The number o° cells In each adenoma was estimated both from parenchymal weight and from total DNA content, and the minimum birth rate needed to produce this number of cells from a single cell, beginning in utero, was calculated on an exponential model.

results The mean observed birth rate of new cells (mean (SD)) was 17.3 (11.1)%/year, and the minimum needed birth rate was 4.28 (21.6)%/year, significantly, (P < 0.001) higher than the observed birth rate.

conclusions The rate of mitosis had fallen substantially during the life span of most parathyroid adenomas. To account for this, we propose that the mutation impiled by a clonal origin increases the secretory setpolnt. Because proliferation, as well as hormone secretion, is influenced by calcium In parathyroid cells, the expected result would be rapid initial growth, slowing down as tumour size reached an asymptotic value corresponding to the total rate of hormone secretion needed to raise the plasma calcium to the new setpolnt.
Osmotic and non‐osmotic regulation of thirst and vasopressin secretion in patients with compulsive water drinking
Authors: Thompson C. J. , Edwards C. R. W. , Baylis P. H.
Published: March 2008

Summary. objective To examine the osmotic and non‐osmotic regulation of thirst and AVP release In patients with compulsive water drinking.

design A 2‐hour Intravenous Infusion of hypertonic (855 mmol/l) sodium chloride solution, followed by a 2‐hour drinking period.

patients Seven patients with compulsive water drinking, seven patients with diabetes insipidus and seven healthy controls.

measurements Plasma AVP, osmolality, sodium and haematocrit, thirst ratings on a visual analogue scale and the volume of water drunk in 2 hours following Infusion. RESULTS Plasma AVP responses to osmotic stimulation, and non‐osmotic inhibition by drinking, were normal In patients with compulsive water drinking. Basal thirst ratings were higher in compulsive water drinking than in either diabetes (P < 0.001) or controls (P < 0.001), despite lower basal plasma osmoialities. There was a significant rise In thirst ratings during saline infusion, which correlated closely with plasma osmolality, in all three groups, but the final thirst ratings were higher in compulsive water drinkers, who subsequently drank more water than In either diabetes insipidus (P < ‐0.01) or controls (P < 0.001). Drinking rapidly lowered thirst ratings in controls and diabetes insipidus before changes occurred in plasma osmolality, but remained elevated in patients with compulsive water drinking. Linear regression analysis defined a lower osmotic threshold for thirst in compulsive water drinking compared with controls or diabetes insipidus.

conclusions

There are abnormalities of the osmotic stimulation and non‐osmotic inhibition of thirst in compulsive water drinking, suggesting that the underlying defect is one of interpretation of osmotic and non‐osmotic inputs. Measurement of thirst responses during hypertonic saline infusion and subsequent water drinking may provide useful diagnostic Information in the differentiation of polyuric states.
Pituitary macroadenomas associated with hyperprolactinaemia: immunocytochemical and in‐situ hybridization studies
Authors: McNicol A. M. , Walker E. , Farquharson M. A. , Teesdale G. M.
Published: March 2008

Summary. objective We have assessed whether in‐situ hybridization for prolactin messenger RNA (mRNA) provides additional Information for the classification of pituitary macroadenomas associated with hyperproiactinaemla.

design in‐situ hybridization for PRL mRNA was performed on surgical biopsies of pituitary adenomas and the results correlated with serum PRL levels and PRL immunoreactivity.

patients Twenty‐one patients (11 men, 10 women) were included; five had normal serum PRL levels, 11 mild hyperprolactinaemia (< 3000 mU/I) and five marked hyperprolactinaemia (> 3000 mU/I).

measurements

Immunocytochemistry for PRL and in‐situ hybridization for PRL mRNA were performed on surgical biopsies.

results Immunoreactivity for PRL was detected In tumours from all patients with serum PRL > 3000 mU/I and in one of 11 patients with mild hyperprolactinaemla. Positive signal for PRL mRNA was detected in four of five immunopositive cases studied, in a further two cases with mild hyperprolactinaemia, and in one tumour associated with normal serum PRL level.

conclusions

In‐situ hybridization provides evidence of PRL gene activation in the absence of immunoreactivity for prolactin. This may reflect low levels of hormone storage or defective translation of the mRNA.
Correlation of plasma insulin and insulin‐like growth factor‐I with indices of androgen transport and metabolism in women with polycystic ovary syndrome
Authors: Sharp P. S. , Kiddy D. S. , Reed M. J. , Anyaoku V. , Johnston D. G. , Franks S.
Published: March 2008

Summary. objective Polycystic ovary syndrome (PCOS) Is said to be associated with hyperinsulinaemia. Insulin stimulates androgen production by ovarian tissue in vitro and previous studies have identified a positive correlation of Insulin with androstenedione. The aim of the present study was to discover whether insulin levels correlate with clinical presentation and with markers of androgen trans‐port and metabolism In women with PCOS.

design

Within‐group analysis of clinical and biochemical characteristics of a consecutive series of women with PCOS, focusing on correlations of plasma insulin with clinical presentation and androgens. Insulin levels were also compared with a control group of normal women.

patients Forty‐seven women who presented with hirsutlsm, cycle abnormalities or both, with ultrasound proven PCOS, were recruited. Mean age was 26.6±0.7 years (mean±SEM), BMI 27.3±1.2 kgtm2.

measurements Plasma Insulin levels were measured at 30‐minute intervals for 3 hours following a 75 g glucose load. Blood was also taken for measurement of testosterone (T), androstenedione (A), free testosterone (f T), sex hormone binding globulin (SHBG) and Insulin‐like growth factor‐i (IGF‐I). Androsterone glucoronide (AG), a marker of peripheral androgen metabolism, was also measured. RESULTS Neither basal Insulin nor the sum of Insulin measurements during the glucose tolerance test (sumINS) in women with PCOS were significantly different from a control group with normal ovaries. Within the PCOS group, basal insulin was greater in women with Irregular cycles or amenorrhoea than In those with regular ovule‐tory menses (8.0± 1.1 vs 3.1 ± 1.5 mU/I, P < 0.01) despite similarly raised androgen levels. Both basal Insulin and sumINS correlated with BMI In women with PCO (r=0.37, P < 0.05 and r= 0.64, P < 0.01 respectively) but not in controls. There was no significant correlation between insulin or IGF‐I levels and T, A or AG despite a positive correlation of AG (but no other androgen) with BMI. SHBG showed an Inverse correlation and I T correlated positively with sumINS (r= ‐0.51, P < 0.01; r=0.39, P < 0.05). Regression analysis of each of the androgens on the other variables demonstrated no significant relationship between insulin and androgens.

conclusions These data suggest that, in vivo, the major effect of insulin on androgen secretion is mediated by changes In SHBG rather than by direct stimulation of ovarian androgen production. Higher Insulin concentrations In anovulatory compared with ovulatory women with hyperandrogenaemia may indicate that Insulin resistance In the ovary contributes to the mechanism of anovulatio in PCOS.
Plasma corticotrophin releasing factor and vasopressin responses to exercise in normal man
Authors: Witten G. A. , Stewart D. E. , Graves M. P. , Ellis M. J. , Evans M. J. , Wells J. E. , Donald R. A. , Espiner E. A.
Published: March 2008

Summary. objective To evaluate the hypothalamo‐pitultary‐adrenal (HPA) response to both mild and Intense exercise.

design Maximum oxygen consumption (Vo2max.) was Initially determined. Exercise to 20% (mild) and 90% (Intense) Vo2max. was undertaken in random order. Subjects were exercised over a 5‐minute period to the required level of Intensity, which was maintained for a further 10 minutes.

subjects Six trained male athletes.

measurements Brachial vein blood was sampled before and at 5‐minute intervals during and after exercise and assayed for plasma cortisol, ACTH, arginine vasopressin (AVP), corticotrophin releasing factor (CRF), sodium and lactate levels. Haemoglobin and haematocrit were measured before and at the end of exercise. Heart rate was monitored continuously and blood pressure measured whenever blood was sampled before and after exercise.

results Maximum heart rate was 184.2 and 82.5 (mean ± SEM) beats per minute at 90 and 20% Vo2max. respectively. Plasma volume fell by 8.7 ± 2.4% with intense exercise. Significant increases in plasma concentrations of AVP, ACTH and conisol, but not CRF, occurred during intense exercise. Plasma sodium concentration, which Increased during intense but not mild exercise, peaked at 10 minutes after the onset of exercise and preceded the rise in plasma AVP. The AVP peak clearly preceded the ACTH peak in two subjects and occurred synchronously with it in three subjects.

conclusion These results Indicate that although significant HPA activation occurs during Intense exercise, CRF does not appear to play a major role In mediating the ACTH response to an acute episode of vigorous exercise in man. AVP may be more important In this regard.
Ketoconazole treatment in Cushing's syndrome: experience in 34 patients
Authors: Sonino Nicoletta , Boscaro Marco , Paoletta Agostino , Mantero Franco , Zillotto Donato
Published: March 2008

Summary. objective Ketoconazole treatment of Cushing's syndrome has been reported in single cases and a few small groups of 5–8 patients. We report our experience in 34 patients.

design Clinical study, with pretreatment and post‐treatment evaluations.

patients Out of 67 patients with Cushing's syndrome admitted during the last 6 years, 34 (28 females/six males; age range 14–67 years) received ketoconazole as a palliative treatment due to severe clinical conditions or management of the disease while awaiting results of definitive therapy.

measurements Urinary cortisol, plasma cortisol and ACTH, and routine chemistry were measured every week for 4 weeks, and then once a month.

results Comparing the last values (mean±SEM) during treatment with baseline, urinary cortisol decreased from 1296.176 to 270.69 nmol/d (n=34; p=<.001); plasma cortisol decreased from 672 . 31 to 549 ± 35 nmol/1 (n= 34; p < 0.001). For patients with pituitary‐dependent Cushing's syndrome, urinary cortisol decreased from 1073.126 to 200.21 nmol/d (n=28; p<0.001) while plasma ACTH changed from 12.5±1.3 to 11.3±0.8 pmol/1 (n=26; not significant). Twelve patients were treated for more than 6 months, and those with pituitary‐dependent disease all received pituitary radiation therapy, except the two who eventually escaped pharmacological control. One additional patient with adrenal carcinoma and one with ectopic ACTH syndrome showed lack of control of urinary cortisol levels. Ketoconazole was withdrawn within the first week In two patients for allergic reaction and acute liver toxicity. Other side‐effects Included: asymptomatic liver function abnormalities In three patients; gastrointestinal symptoms in four; worsening of gynaecomastia In one. Rapid clinical Improvement was observed together with the normalization of urinary cortisol levels, with regression of symptoms such as diabetes mellitus, hypertension, hypokalaemia, and restoration of well being.

conclusions These data confirm that ketoconazole is valuable In the management of hypercortlsolism, provided that patients are closely watched to exclude those who may develop liver toxicity and to prevent the occurrence of adrenal Insufficiency.