bluuebunny/crossref_metadata_2025 huggingface dataset:
Circadian rhythm and pulsatility of parathyroid hormone secretion in man
Authors: Herfarth Klaus , Schmidt‐Gayk Heinrich , Graf Stefanie , Maier Andreas
Published: March 2008

OBJECTIVE We wished to investigate the circadian rhythm and pulsatility of parathyroid hormone (PTH) secretion in man, as conflicting results have been published.

DESIGN and PATIENTS To investigate the circadian rhythm during daytime, we sampled (a) peripheral blood at hourly intervals in 12 healthy young men from 0900 h until 1700 h. For observation of pulsatility, we sampled (b) peripheral blood at 1‐minute intervals for 1 hour in three healthy men and three healthy women (mean 27 7 years, range 21– 56 years) and (c) at 1‐minute intervals for 30 minutes in 21 patients with surgically confirmed primary hyperparathyroidism (pHPT).

MEASUREMENTS The serum levels of intact PTH were measured by two‐site immunoradiometric assay and special care was taken to reduce intra‐assay variability, especially at the normal PTH concentration. In series (a), ionized calcium, total calcium and phosphate were also determined.

RESULTS A circadian rhythm during daytime was found for intact PTH in healthy men and women with a nadir at 0930 h and a peak in the afternoon. Ionized calcium and total calcium (protein‐adjusted) decreased and phosphate increased in the afternoon. These changes were all statistically significant (P < 0– 02).

Pulsatility of PTH: Statistical cluster analysis of the data showed no pulsatility either in healthy persons or in patients with primary hyperparathyroidism. In two healthy women and one healthy man slight changes of longer duration were discovered, but no complete pulses. In five patients with primary hyperparathyroidism, larger differences between the highest and lowest concentrations of intact PTH were found, but no complete pulses.

CONCLUSIONS Our data show a significant circadian rhythm during daytime of intact PTH and only minor changes from minute to minute. The alterations in PTH‐levels occurred at longer time intervals in healthy persons. In some patients with primary hyperparathyroidism, decreases of PTH‐levels were found. The circadian rhythm of PTH may be due to slight changes in calcium or phosphate concentration.
The empty sella: results of treatment in 76 successive cases and high frequency of endocrine and neurological disturbances
Authors: Gallardo Enrique , Schächter Dina , Caceres Edith , Becker Pedro , Colin Enrique , Martinez Carlos , Henriquez Camilo
Published: March 2008

OBJECTIVE We assessed the frequency of endocrine or neurological disturbances and the results of surgery in patients with empty sella, diagnosed with cisternography and/or computerized tomography scanning.

DESIGN AND PATIENTS Analysis of hospital records of 76 successive patients (73 primary, three secondary empty sella) from a single institution.

MEASUREMENTS Clinical and neuro‐ophthalmological evaluation. Serum PRL, GH, TSH, LH, FSH, T4, T3 by radioimmunoassay. Diagnosis of empty sella with cisternography and/or computerized tomography scanning (n = 69), or discovered at surgery (n = 7).

RESULTS Patients with empty sella had: headache (69 7%), visual disturbances (34 2%), cerebrospinal fluid rhinorrhoea (11 8%), endocrine disturbances (51 4%, including hyperprolactinaemia, acromegaly, Cushing's syndrome). A pituitary tumour was discovered in two patients, in seven other ones it was suspected but not found at surgery. Transsphenoidal packing of empty sellas was done in 56 cases, with 71% post‐operative complications. With surgery there was improvement of headache in 71%, of visual disturbances in 46%. Cerebrospinal fluid rhinorrhoea (discovered at surgery in four other patients) was not resolved by the first operation in six out of 13 patients. In 20 patients without surgery, headache improved in 64 6%.

CONCLUSIONS The empty sella is frequently associated with a variety of neurological and endocrine disturbances, which is contrary to conventional belief. Cerebrospinal fluid rhinorrhoea is not a rare complication and it may be difficult to treat. Some cases of empty sella may be due to partial pituitary apoplexy. Autoimmunity may have existed in other cases. Surgery may be useful in many patients, but a judicious selection is needed because it entails complications and non‐operated patients may improve spontaneously.
Non‐autonomy of parathyroid hormone secretion in acute primary hyperparathyroidism
Authors: Schachter Pinhas P. , Christy Mark D. , Avigad Itamar S. , Shabtay Moshe , Leight George S.
Published: March 2008

A patient with acute primary hyperparathyroidism treated with mithramycin preoperatively, underwent neck exploration and two enlarged parathyroid glands were excised: one huge adenoma (6g) and another smaller gland. Mithramycin was administered preoperatively to lower life‐threatening hypercalcaemia, and parathyroid slices from the huge adenoma removed at surgery were submitted in vitro to various calcium concentrations in the media to determine the influence of calcium on parathyroid adenoma secretory pattern in acute primary hyperparathyroidism. Mithramycin induced a significant decline in calcium levels and significant elevations of calciotrophic hormones (intact PTH, mid‐region specific PTH, calcitonin and calcitriol). Significant suppression in PTH output in vitro was achieved by increasing calcium levels in the media. These results exclude autonomous PTH secretion (non‐calcium dependent) as a possible aetiology of acute primary hyperparathyroidism. We suggest that a sudden increase in the set‐point of the diseased parathyroid cells in the presence of a huge cell mass accounts, in large part, for both the marked hypercalcaemia and elevated PTH levels in this patient.
Thyroid abscess complicating subacute thyroiditis: A consequence of steroid therapy?
Authors: Quin J. D. , Gray H. W. , Baxter J. N. , Thomson J. A.
Published: March 2008

A patient with subacute thyroiditis developed a thyroid abscess after drainage of a pilonidal abscess. An infective focus in a patient with subacute thyroiditis on steroids should be treated aggressively with adequate antibiotic cover

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Hypothalamic abnormalities in patients with pituitary‐dependent Cushing's syndrome
Authors: Stewart P. M. , Penn R. , Gibson R. , Holder R. , Parton A. , Ratcliffe J. G. , London D. R.
Published: March 2008

OBJECTIVE We aimed to investigate the pattern of 24‐hour ACTH and cortisol secretion in pitultary‐dependent Cushing's syndrome and to evaluate the pituitary and hypothalamic contributions to the disease.

PATIENTS Five women with Cushing's disease (mean age 35±5 (SEM) years) and five normal female controls (mean age 25±2 years) were studied.

DESIGN AND MEASUREMENTS Plasma ACTH and cortisol levels were measured every 15 minutes for 24 hours using established IRMA and RIA respectively. ACTH and cortisol mean and trough levels, pulse number and amplitude were calculated using established computer software, programmed to identify ACTH and cortisol peaks.

RESULTS Patients with Cushing's disease had a twofold increase in 24‐hour mean cortisol levels and a threefold increase in 24‐hour mean ACTH levels (Cushing's 5.9±1.0, controls 1.9±0.2 pmol/l, P<0.01). This was predominantly mediated by an increase in ACTH pulse amplitude. However, 24‐hour ACTH pulse number was also increased (Cushing's 15±2±2±6, controls 10±6±1±7, P<0±05) due to an increase in pulse number between 1800 and 2400 h. ACTH trough levels were also higher in patients with Cushing's disease (Cushing's 5±3±1±3, controls 2±3±0±2 pmol/I, P<0±05).

CONCLUSION Twenty‐four‐hour mean plasma cortisol and ACTH levels are elevated two to three‐fold in patients with Cushing's disease. The Increase in ACTH pulse amplitude suggests a pituitary abnormality in patients with Cushing's disease. However, the increased ACTH pulse frequency together with elevated trough levels is interpreted as Indicating coexisting hypothalamic stimulation (or loss of inhibition).
Percutaneous ethanol injection treatment of autonomous thyroid adenoma: hormonal and clinical evaluation
Authors: Monzanl Fablo , Golettl Orlando , Caracclo Nadla , Del Guerra Paolo , Ferdeghinl Marco , Puccl Enrico , Baschieri Lldlo
Published: March 2008

OBJECTIVE We have evaluated the efficacy of percutaneous ethanol Injection as an alternative to surgery and iodlne‐131 treatment in solitary autonomous thyroid adenoma.

DESIGN Percutaneous ethanol Injection (0.5–2.8 ml ethanol/ml nodular tissue) was performed under sonographic guidance in 3–5 (1–2 weekly) sessions; a 7.5 MHz linear real‐time scanner (Toshiba, mod. 32B) was used for sonographic studies. The thyroid hormone profile was assessed during treatment and for the next 6 months.

PATIENTS Fifty‐six patients (40 females, 16 males, mean age 46.SD 9 years; 30 pretoxic, 26 toxic) were included in the study: their pretreatment technetlum‐99 m thyroid scan showed a single hot nodule with total suppression of extranodular tissue in 45 and near‐total suppression in 11.

MEASUREMENTS Thyroid hormones, antithyroglobulin and antiperoxidase antibodies were measured by specific radloimmunoassay, while thyrotrophin was evaluated by ultrasensitive Immunoradiometric assay.

RESULTS Apart from a case of transient pyrexia, no relevant adverse effects were observed. A slight thyrold hormone increase was seen in both groups immediately following a treatment. Six months after therapy a biochemical and clinical remission of hyperthyroldism was observed in 18 out of 22 toxic patients (81.8%); a significant increase of TSH levels was seen in both groups (P<0.01). With follow‐up, significant volume shrinkage (P< 0.001) as well as structural alterations of the nodule were consistently recorded at sonography; a linear relationship (r= 0.98; P<0.0001) between pretreatment volume and volume reduction was found. At scintiscan, functional activity of extranodular parenchyma was found In 40 out of 56 patients (71.4%), 16/26 (61.5%) In the hyperthyrold group, 24/30 (80.0%) In the pretoxic group.

CONCLUSIONS These data confirm that percutaneous ethanol Injection is effective in obtaining functional ablation and in Inducing remission of hyperthyroldism, when present; adverse effects seem infrequent.
The role of 1,25‐dihydroxyvitamin D in the mechanism of acquired vitamin D deficiency
Authors: Clements M. R. , Davies M. , Hayes M. E. , Hlckey Claire D. , Lumb G. A. , Mawer E. Barbara , Adams P. H.
Published: March 2008

OBJECTIVE We wished to assess the effect of changes In the plasma concentration of 1,25‐dihydroxyvitamin D on the plasma elimination half‐time for 25‐hydroxyvitamin D In man.

DESIGN The turnover of 25‐hydroxyvltamin D in plasma was Investigated after intravenous doses of the radioac‐tively labelled metabolite had been given to a group of patients (n= 17) with disorders of bone and mineral metabolism before and after oral treatment with calcium or 1,25‐dihydroxyvitamin D.

PATIENTS Seven patients with post‐menopausal osteoporosis, five with hypoparathyroidlsm, three with hypo‐phosphataemic osteomalacia, one with renal osteodystro‐phy and one patient with coeliac disease were studied.

MEASUREMENTS Intravenous injections of 3H‐labelled 25‐hydroxyvitamin D were given and plasma elimination half‐time assessed over periods of 4–14 days during which frequent measurements of plasma calcium, phosphate, parathyroid hormone, 25‐hydroxyvltamln D and 1,25‐dihydroxyvitamin D were made. Changes in the plasma elimination half‐time for 3H‐25‐hydroxyvltamin D before and after treatment with calcium and 1,25‐dlhydroxyvitamin D were evaluated by non‐parametric statistical analysis.

RESULTS The elimination half‐time for 3H‐25‐hydroxyvita‐min D in plasma was significantly shortened by raising the circulating concentration of 1,25‐dihydroxyvitamin D. Conversely, in a patient with intestinal malabsorption of calcium, the metabolic clearance of 3H‐25‐hydroxyvitamln D was prolonged when the concentration of 1,25‐dlhydroxy‐vitamln D In plasma was decreased by suppressing secondary hyperparathyroldism with large calcium supplements. In the longer‐term studies (n= 10) there was a highly significant Inverse relation (r= 0.88, P <0.001) between the change in the plasma concentration of 1,25‐dlhydroxyvitamin D and the Induced change in the elimination half‐time of 3H‐25‐hydroxyvitamin D. There was also a significant correlation (r= 0.66, p < 0.0025) between the observed fall in the plasma concentration of unlabelled 25‐hydroxyvitamin D and the predicted fall calculated from the measured value for the half‐time of the 3H‐labelled metabolite. In acute studies in patients with post‐menopausal osteoporosis (n= 7), enhanced metabolic Inactlvatlon of 3H‐25‐hydroxyvitamln D was detectable within 24 hours of oral administration of 1,25‐dihydroxyvitamin D.

CONCLUSIONS The effect of 1,25‐dlhydrhyvltamln D on the catabolism of 25‐hydroxyvltamin D can contribute to the development of vitamin D deficiency in many clinical disorders. When the natural supply of vitamin D is limited by sunlight deprivation, a sustained Increase in the plasma concentration of 1,25‐dihydroxyvitamin D due to primary or secondary hyperparathyroidlsm will lead to accelerated depletion of vitamin D stores.
Peripheral bone density in women with untreated multinodular goitre
Authors: Mudde A. H. , Reijnders F. J. L. , Kruseman A. C. Nieuwenhuijzen
Published: March 2008

OBJECTIVES We wished to determine whether women with multinodular goitre and spontaneous subclinical hyperthyroidism have decreased bone density.

DESIGN AND SUBJECTS Bone density was measured at the distal and proximal forearm. Data were expressed as Z‐scores relative to the mean values out of 125 control subjects matched for age and menopause. The Z‐scores of 23 women with subclinical hyperthyroid goitre (TSH<0.1 mU/l and normal values for FT4 and total T3) and of 54 women with euthyroid goitre were compared.

MEASUREMENTS Bone density was measured by single photon absorptiometry. TSH was measured by IRMA, FT4 by RIA.

RESULTS Relative to the euthyroid goitre subjects the mean±SEM Z‐scores of both the distal and proximal forearm density were lower (‐ 0.69±0.17 vs ‐ 0.1 ± 0.18, P <0.05 and ‐0.5±0.18 vs 0.07±0.18, P <0.05, respectively). Median (range) FT4 in the subclinical hyperthyroid goitre subjects was significantly higher than euthyroid goitre subjects (15.6 (11–23.2) pmol/l vs 11.9 (8.3–18.3) pmol/l, P <0.001) although still within the normal range. FT4 correlated inversely with Z‐scores of both distal and proximal forearm bone density in the subjects with subclinical hyperthyroidism (r= ‐0.42, P <0.05 and r= ‐0.43, P <0.05, respectively), but not in the euthyroid goitre subjects.

CONCLUSION These findings indicate that women with untreated multinodular goitre and subclinical hyperthyroidism have reduced bone density in the forearm.
Frequency of prolactin pulsatile release in normal men and in agonadal patients is neither coupled to LH release nor influenced by androgen modulation
Authors: Genazzani A. D. , Forti G. , Guardabasso V. , Maggi M. , Milloni M. , Clanfanelli F. , Serio M.
Published: March 2008

OBJECTIVE We wished to examine and characterize the prolactin pulsatile secretory pattern In both normal and agonadal males in order to assess whether there was any concordance with LH secretion.

DESIGN Patients were sampled every 5 minutes for 12 hours.

PATIENTS We studied five normal and four agonadal men, the latter group before and on testosterone enanthate (TE) (200 mg l.m. every 15 days) treatment.

MEASUREMENTS Prolactin and luteinizing hormone plasma levels were determined using commercial RIA systems. Pulse detection was performed using the DETECT program and the degree of concordance between luteinizing hormone and prolactin was established computing the specific concordance Index.

RESULTS We demonstrated the presence of a frequent PRL secretory pattern in normal men (22.8±1.8 peaks/12h; mean±SEM) and in agonadal patients, both in basal conditions and during testosterone treatment (20.5±2.8 and 18±1.6 peaks/12h, respectively). The testosterone treatment in agonadal men significantly reduced luteinlzing hormone pulse frequency (baseline: 27.5±2, testosterone administration: 18.1±3 peaks/12h, P <0.01) but did not affect pulsatile prolactin release. Using a 10 and 15 minute sampling protocol, we observed that prolactin pulse frequency significantly decreased (P <0.01) and was similar to the frequencies estimated In previous reports. When lutelnizing hormone and prolactin time series were studied to evaluate the possible presence of a specific concordance (SC) between the secretory events of the two hormones, no significant degree of concomitancy was observed neither using the specific concordance index or the cross‐correlation analysis.

CONCLUSONS This report demonstrates (a) the presence of frequent pulsatile release of prolactin in both controls and agonadal patients (baseline and on testosterone enanthate), (b) the use of an appropriate sampling Interval (5 minutes) to unmask the prolactin pulsatile release, (c) that in men, lutelnizing hormone secretory events are not temporally linked to prolactin secretion, and (d) that androgens, even if reducing luteinlzing hormone pulse frequency in agonadal patients, do not significantly affect prolactin pulsatile secretion, suggesting that testosterone and its metabolites do not affect lactotroph activity.
Effectiveness of computer‐assisted perimetry in the follow‐up of patients with pituitary microadenoma responsive to medical treatment
Authors: Cannavó S. , Natale R. De , Curtó L. , Calzi L. Li , Trimarchl F.
Published: March 2008

DESIGN Patients were studied before and after 1 year of bromocriptine or 6 months of SMS 201–995 treatment, for prolactinomas or GH‐secreting adenomas, respectively. PATIENTS Seventeen patients with intrasellar pituitary tumour (ten prolactinomas, all females; seven GH‐secreting adenomas, four males and three females) and the presence of relative or absolute scotomas, were examined.

MEASUREMENTS We used computed tomodensitometry, Goldman perimeter and computer‐assisted perimetry.

RESULTS The patients were divided into three groups according to their response to medical treatment as proved by computed tomodensitometry which revealed the disappearance of the tumour in four prolactinomas (group 1), a reduction < 40% in three prolactinomas and in three acromegalics (group 2) and no significant variation in the diameter of the adenoma in three prolactinomas and in four acromegalics (group 3).

Comparison by the paired t‐test of the visual fields before and after treatment revealed a significant positive change (P < 0.01) for all patients in groups 1 and 2 and for one patient in group 3, with disappearance of the scotomas in all cases in group 1 and in two cases in group 2.

Visual field defects were detected by means of the Goldman perimeter in only one patient with prolactinoma and in two acromegalics, although the computer‐assisted perimetry showed that, in 15 out of 17 patients, visual impairment was unilateral and in all cases the presence of relative scotomas was concentrated in the upper temporal quadrant.

The visual defects observed with computer‐assisted perimetry and the pituitary tumour dimension evaluated with computed tomodensitometry did not show significative correlations (r= 0.059, P NS).

CONCLUSIONS Computer‐assisted perimetry was most useful in the diagnosis and follow‐up of patients with pituitary adenoma, especially in the evaluation of small masses without subjective symptoms of visual loss, when the Goldman perimeter does not usually allow us to recognize minimal chiasmatic involvements or the improvement of visual field as a result of the medical therapy.
Serum levels of growth hormone‐binding protein and insulin‐like growth factor‐I during puberty*
Authors: Massa Guy , Bouillon Roger , Vanderschueren‐Lodeweyckx Magda
Published: March 2008

OBJECTIVE The aim was to investigate the effect of pubertal development on serum levels of growth hormone binding protein (GHBP) and IGF‐I, and to study the relationship between GHBP levels and height standard deviation score (SDS), nutritional state and IGF‐I levels. DESIGN AND PATIENTS The investigation was performed on serum samples from 72 healthy adolescents of different pubertal stage. Results were compared to those obtained in 46 prepubertal children.

MEASUREMENTS Serum levels of GHBP were measured by HPLC gel filtration and IGF‐I levels were measured by RIA after acid‐ethanol extraction.

RESULTS No effect of pubertal stage on serum levels of GHBP was found. A positive relationship was found between serum levels of GHBP and height SDS (r= 0.38; P < 0.005) and weight expressed as percentage of median weight for height age (r= 0.46; P < 0.0005). Serum levels of IGF‐I increased during puberty and were not correlated with height SDS or weight for height age. In pubertal subjects, no relationship existed between serum levels of GHBP and IGF‐I. In prepubertal subjects, however, a significantly positive relationship between GHBP and IGF‐I levels (r= 0.66; P < 0.0005) was found.

CONCLUSIONS Pubertal development does not seem to influence serum levels of GHBP. Height SDS and nutritional state are related to the concentration of GHBP. Before puberty, the level of GHBP is positively related to IGF‐I levels; during puberty, however, the increase in serum IGF‐I levels is not accompanied by changes in the amount of circulating GHBP.
Growth hormone secreting pituitary carcinoma: a case report and literature review
Authors: Stewart P. M. , Carey M. P. , Graham C. T. , Wright A. D. , London D. R.
Published: March 2008

Only five cases of growth hormone secreting pituitary carcinoma have been documented. We present a 49‐year‐old West Indian male with grossly elevated plasma growth hormone (760–10 400 mU/l), and a large aggressive pituitary tumour that continued to grow despite repeated pituitary surgery, radiotherapy and medical therapy (bromocriptine and somatostatin analogue). Thirteen years after diagnosis the patient died secondary to left ventricular failure. A post‐mortem revealed a large locally invasive pituitary tumour, but in addition numerous tumour seedlings within the cerebrospinal fluid space, and a solitary intraparenchymal tumour deposit within the right temporal lobe, clearly separate from the primary tumour.

Pituitary carcinoma should be considered in any acromegalic with grossly elevated plasma growth hormone levels who falls to respond to conventional therapy.
Prevalence of gastritis in patients with acromegaly: untreated and during treatment with octreotide
Authors: Anderson J. V. , Catnach S. , Lowe D. G. , Fairclough P. D. , Besser G. M. , Wass J. A. H.
Published: March 2008

OBJECTIVE It has previously been suggested that acromegalic patients treated with the somatostatin analogue octreotide invariably have chronic gastritis. We have examined the prevalence of gastritis in a large group of acromegalic patients, untreated and during treatment with octreotide.

DESIGN We studied three groups of acromegalic patients: (A) untreated; (B) octreotide‐treated; (C) a subgroup of these studied both before and during octreotide therapy. PATIENTS Forty‐eight patients, grouped as above, with active acromegaly were examined for the presence of gastritis.

MEASUREMENTS Gastroscopy and histological examination of gastric biopsies for the presence of gastritis and Helicobacter organisms were undertaken. The principal outcome was quantification of the prevalence of gastritis in the various study groups.

RESULTS Group A: 10 of the 33 patients (30%) had gastritis before any therapy with octreotide. Group B: 17 of 36 patients (47%) on octreotide treatment for 6–59 months (mean 20.5) had gastritis, and this was present in five out of the sub‐group of eight patients (62%) treated for over 3 years. Group C: three of 21 patients (14%) developed gastritis during treatment with octreotide for between 6 and 23 months (mean 12.4). There was a highly significant association between the presence of gastritis and the presence of Helicobacter pylori organisms.

CONCLUSIONS Octreotide therapy of acromegaly may predispose to the development of gastritis, but this remains statistically unproven. Certainly, gastritis is not an invariable consequence of octreotide therapy, even after prolonged periods of treatment. The presence of gastritis is associated with H. pylori infection.
The pulsatile GH secretion in acromegaly: Hypothalamic or pituitary origin?*
Authors: Riedel M. , Günther T. , von zur Mühlen A. , Brabant G.
Published: March 2008

OBJECTIVE We studied the effects of different modes of octreotide therapy on the pulsatile pattern of GH release in an attempt to define better its regulation by growth hormone‐releasing hormone (GHRH) and somatostatin and its effects on IGF‐I plasma levels in acromegaly.

DESIGN In six acromegalic patients not cured by previous treatment we compared the 24‐hour GH secretion profiles under basal conditions with subcutaneous (s.c.) bolus injections of 100 μg octreotide every 8 hours and with continuous s.c. Infusions of the same daily dose. Blood samples were taken every 10 minutes over 24 hours followed by a GHRH test (100 μg GHRH i.v.) with blood sampling every 15 minutes for another 2 hours. After a 4‐week interval all patients were treated either by the bolus or continuous mode of octreotide application in a randomized cross‐over design. On day 4 of treatment blood sampling and GHRH test were repeated. Octreotide treatment was withdrawn for another 4 weeks; all patients then received the alternate application mode and were measured under similar conditions.

MEASUREMENTS Serum GH and plasma IGF‐I concentrations were analysed by serial array averaging. IGF‐I levels were measured in two different assays with and without previous protein extraction. For GH pulse detection three different algorithms (Cluster, Pulsar, Desade) were applied.

RESULTS With both treatments, the initially elevated basal 24‐hour mean serum GH concentrations (58.0 ± 9.7 mU/l mean.SEM) decreased significantly (bolus: 11.5 ± 4.9 mU/l, P < 0.001 vs basal; continuous Infusion: 7.6 ± 1.9 mU/l, P < 0.001 vs basal) after 4 days. GH suppression was significantly more pronounced following continuous infusion than bolus (P < 0.05). IGF‐I plasma concentrations were lowered significantly (P < 0.05) with both forms of treatment which did not differ between themselves. Bolus and continuous infusion treatment significantly inhibited (P < 0.05) the amplitudes of pulsatile GH release, but did not change the pulse frequency. In two of the patients, GHRH stimulation did not increase GH serum levels suggesting a constitutive activation of adenylyl cyclase.

CONCLUSION Continuous subcutaneous octreotide treatment in acromegaly suppresses mean GH levels better than bolus injection. The number of GH pulses remains unaffected by both modes of treatment providing evidence against a somatostatinergic mechanism of pulsatile GH secretion in these patients. The unchanged frequency of pulsatile GH release in the patients unresponsive to exogenous GHRH indicates that this pattern might be independent of hypothalamic GHRH and somatostatin and suggests a pituitary‐derived mechanism for GH pulse generation in acromegaly.
Effect of growth hormone on the low level of growth hormone binding protein in idiopathic short stature
Authors: Fontoura Manuel , Mugnier Elizabeth , Brauner Raja , Rappaport Raphael , Postel‐Vlnay Marie‐Catherine
Published: March 2008

OBJECTIVE Growth hormone receptor status was assessed in children with idiopathic short stature by evaluating plasma growth hormone‐binding protein before and under GH therapy.

DESIGN Among 22 children presenting idiopathic short stature, 15 were randomly selected to be treated with GH (1.2 IU/kg/week); they were studied before and under GH therapy. Untreated patients served as a control group for age and GH effect.

PATIENTS Twenty‐two prepubertal children, aged 5–11 years, were studied. They presented growth retardation of ‐2.8±0.1 SDS (mean . SEM). All had normal GH secretion and their mean IGF‐I plasma level was normal.

MEASUREMENT Growth hormone‐binding protein was measured using high pressure liquid chromatography gel filtration. The specific binding of 125I‐hGH to the growth hormone‐binding protein was expressed as a percentage of the total radioactivity.

RESULTS Specific binding of 125I‐hGH to the high affinity growth hormone‐binding protein was low with a mean . SEM value of 11.1 . 0.9% of radioactivity. In the treated group, growth hormone‐binding protein increased significantly after 3 months of treatment; It reached 21.1 . 1.0% of radioactivity (mean . SEM) in the eight children who have been treated for 18 months. In the seven untreated children, the growth hormone‐binding protein value Increased to 16.2.1.1% after 18 months; this value is significantly lower than that found in the GH‐treated children, demonstrating that the GH effect Is greater than the age‐related increase in the growth hormone‐binding protein. A positive correlation was found between IGF‐I plasma levels and growth hormone‐binding protein and also between growth velocity and growth hormone‐binding protein.

CONCLUSIONS The low growth hormone‐binding protein and the response to high doses of GH suggest partial GH resistance at the receptor level, in this group of children with idiopathic short stature.
The early mineralocorticoid effector mechanism, the sodium—proton exchanger, is sensitized in lymphocytes from patients with Cushing's syndrome
Authors: Wehling M. , Käsmayr J. , Christ M. , Sippell W. , Thelsen K. , Müller O.‐A.
Published: March 2008

OBJECTIVE In‐vitro binding of aldosterone to mineralocorticoid receptors on human mononuclear leucocytes and its effects on the intracellular sodium and potassium concentrations, the sodium‐proton exchanger and cell volume of human mononuclear leucocytes have been described for normals. In the present paper this easily accessible human cell model was studied in Cushing's syndrome to detect abnormalities of the mineralocorticoid effector mechanism.

DESIGN The rate of cell swelling in isotonic sodium propionate reflecting the activity of the sodium‐proton exchanger and the stimulatory activity of 1.4 nM aldosterone were determined in a Coulter Channelyzer.

PATIENTS Nine female patients with pituitary‐dependent (7) and adrenal hypercortlsollsm (2) were included in the study.

MEASUREMENTS Compared with controls from matched normals, the cell volume of human mononuclear leucocytes in a physiological buffer was significantly increased in the patients. The increment of cell size in isotonlc sodium propionate was elevated in the presence of 1.4 nM aldosterone only.

RESULTS These findings are equivalent to an excess stimulation of the sodium‐proton exchanger by aldosterone in these patients. Plasma cortlsol was inversely correlated with the cell swelling In propionate.

CONCLUSIONS These data indicate that the early mineralocorticoid effector mechanism in human mono‐nuclear leucocytes from patients with Cushing's syndrome has an increased sensitivity to aldosterone compared with that from normals. This could reflect an adaptation of the cellular electrolyte metabolism to the decreased mineralocorticoid activity balancing the increased glucocorticold activity. If representative of other cell systems, e. g. renal tubular cells, these findings would identify accompanying electrolyte disorders in these patients not as a side‐effect of glucocortlcolds, but as a result of an increased sensitivity to endogenous mlneralo‐corticolds.
The effect of endurance training on serum triiodothyronine kinetics in man: physical conditioning marked by enhanced thyroid hormone metabolism*
Authors: Rone James K. , Dons Robert F. , Reed H. Lester
Published: March 2008

OBJECTIVE We studied the relationship between endurance training, aerobic capacity, and T3 metabolism in healthy euthyroid men.

DESIGN T3 kinetic studies performed on two groups of subjects differentiated on the basis of physical activity status and aerobic capacity.

SUBJECTS Five endurance‐trained athletes and five sedentary controls (mean±SD Vo2 max = 48.2 ± 7.1 vs 23.2±4.5 ml/kg/min, respectively) matched for age, body surface area, lean body mass, and baseline thyroid function.

MEASUREMENTS Kinetic analysis performed using serial serum T3 levels measured following oral T3 administration. Metabolic clearance rate, total volume of distribution, disposal rate, and total body pool calculated using non‐compartmental analysis.

RESULTS When normalized for lean body mass, all kinetic parameters were 25–38% greater in the athletic group compared to controls (P <0.05). Total volume of distribution, disposal rate, and total body pool were positively correlated with aerobic capacity (r=+0.69 to +0.79; P <0.05). Metabolic clearance rate was positively correlated to a non‐significant degree.

CONCLUSIONS These results confirm the findings of prior studies that thyroid hormone metabolism is altered by physical conditioning. In addition, we demonstrated a positive correlation between aerobic capacity and several parameters of T3 kinetics. Differences in absolute lean body mass cannot explain these findings; rather it appears that there is something qualitatively different in the way endurance‐trained tissue processes thyroid hormone, compared to untrained tissue. The study was not designed to elucidate these differences at the cellular level; however, it does support a link between muscle physiology and T3 activity and may suggest a physiological role for thyroid hormone in physical conditioning.
High affinity growth hormone binding protein in plasma of patients with acromegaly and the effect of octreotide treatment
Authors: Roelen C. A. M. , Donker G. H. , Thijssen J. H. H. , Koppeschaar H. P. F. , Blankenstein M. A.
Published: March 2008

OBJECTIVE The objective of this study was to investigate the effect of plasma GH‐levels on the high affinity growth hormone bindng protein (GHBP).

PATIENTS We studied plasma samples of eight patients with acromegaly and eight age and sex matched healthy subjects.

DESIGN Patients with acromegaly were treated with octreotide administered by continuous subcutaneous infusion. Levels of growth hormone binding protein (GHBP) were measured in plasma samples before therapy and 3, 6 and 12 months after starting treatment. During this period, octreotide was administered in doses of 300–800 μg/day. The mean dose per patient over the study period ranged from 300 to 575 μg/24 h. The GHBP levels of patients with acromegaly were compared with those in the healthy subjects.

MEASUREMENTS Bound and free 125I‐GH in plasma were measured using FPLC gel chromatography on a Superose 12 column, after an overnight incubation period. The binding data were used for a Scatchard plot analysis. Wilcoxon's signed rank test was used for statistical analysis.

RESULTS We found lower GHBP levels in acromegalic patients (P= 0.01) than in the control subjects. Octreotide treatment resulted in IGF‐I levels <300 μg/l in four patients. In these patients GHBP levels increased.

CONCLUSIONS We conclude that growth hormone binding protein levels are down regulated in acromegaly, indicating an important role for GH in the regulation of this protein.
Thyroid function and thyroid autoimmunity independently modulate serum concentration of soluble interleukin 2 (IL‐2) receptor (sIL‐2R) in thyroid diseases
Authors: Marlottl S. , Caturegll P. , Barbesino G. , Marinò M. , Del Prete G. F. , Chlovato L. , Tonacchera M. , De Carll M. , Pinchers A.
Published: March 2008

The serum concentration of soluble interleukin‐2 receptor (sIL‐2R) is a marker of T‐lymphocyte activation. Increased circulating sIL‐2R has been reported in untreated Graves' disease. This finding has been interpreted as the consequence of the autoimmune activation, but recent data suggest that sIL‐2R is directly correlated to thyroid state. The aim of this study was to elucidate the respective roles of autoimmunity and thyroid function in modulating serum sIL‐2R.

DESIGN AND PATIENTS sIL‐2R was evaluated in 20 normal euthyroid subjects and in a large series of patients with autoimmune and non‐autoimmune thyroid disorders in different functional state.

MEASUREMENTS sIL‐2R was assayed by a solid‐phase monoclonal antibody assisted ELISA method.

RESULTS Serum sIL‐2R in normals was 461 ± 186 U/ml (mean ± SD). Increased sIL‐2R was found in 61 hyperthyroid patients with Graves' disease (1610 ± 962 U/ml, P <0.0001) and in 23 with toxic adenoma (1121 ± 598 U/ml, P <0.0001). Restoration of euthyroidism lowered to normal sIL‐2R in both groups. Serum sIL‐2R was higher in euthyroid Graves' disease patients with active than in those with non‐active ophthalmopathy. Decreased serum sIL‐2R (228 ± 93 U/ml, P <0.0001) was found in 30 patients hypothyroid after total thyroidectomy. Highly variable circulating sIL‐2R (range 100–1456 U/ml, mean ± SD: 379 ± 301 U/ml) was found in 49 patients with hypothyroid Hashimoto's thyroiditis (P= NS vs normals; P <0.02 vs post‐thyroldectomy hypothyroid patients). Treatment with L‐thyroxine increased sIL‐2R in all thyroldectomized and in the majority of Hashimoto's thyroidltis patients. In individual Hashimoto's thyroiditis patients (mostly with increased serum sIL‐2R), L‐thyroxine caused a decrease of circulating sIL‐2R. sIL‐2R was normal in 29 patients with euthyroid Hashimoto's thyroiditis. Both in Graves' disease and in Hashimoto's thyroiditis, no correlation was found between sIL‐2R and anti‐thyroglobulin, anti‐thyroid peroxidase and anti‐thyrotrophin‐receptor autoantibodies. Highly significant positive correlation between serum thyroid hormones and sIL‐2R was found in all study groups.

CONCLUSIONS In thyroid disorders thyroid hormones are the main regulator of serum sIL‐2R concentration. The contribution of autoimmune activation may be detected only in some patients with autoimmune hypothyroidism, while in Graves' disease the role of the immune system is masked by the hyperthyroid state.
Body composition and bone mass in post‐menopausal women
Authors: Compston J. E. , Bhambhanl M. , Laskey M. A. , Murphy S. , Khaw K. T.
Published: March 2008

OBJECTIVE We aimed to assess total body composition and to study the Interrelationships between fat and lean tissue mass with total and regional bone mass in healthy British post‐menopausal women.

DESIGN AND PATIENTS Total body composition and regional bone mass were measured in 97 healthy post‐menopausal women recruited from the general community. The mean age was 57.9 years, range 49–65.

MEASUREMENTS Total body composition (fat, lean tissue and bone mineral) and regional bone density in the lumbar spine and femur were measured by dual energy X‐ray absorptiometry on a Lunar DPX.

RESULTS Significant negative correlations with age were found for total body bone mineral density (r= ‐0.200, P= 0.049), and lumbar spine bone mineral density (r= ‐ 0.28, P= 0.006); the calculated rate of bone loss from these two sites was 0.33 and 0.7% per annum respectively. Fat tissue mass showed a positive correlation with age (r= 0.22, P= 0.03). High correlations were observed between total body and regional bone mineral density (r= 0.755–0.829, P <0.001). After adjustment for age and lean mass, statistically significant correlations were seen between fat tissue mass and all bone mass measurements (P < 0.01–0.001), the strongest correlations being found for total body bone mineral content and density (r=0.477 and 0.488 respectively). Lean tissue mass showed a strong correlation with total body bone mineral content (r= 0.580, P <0.001), after adjustment for age and fat mass; It was less strongly correlated with other bone mass measurements than fat mass, showing only weak correlations with total body, trochanterlc and lumbar spine bone mineral density (r= 0.228–0.246, P <0.05). Age‐adjusted body weight showed stronger correlations with total and regional bone mass than did either body mass index or height.

CONCLUSIONS Both fat and lean tissue mass are related to total and regional bone mass in post‐menopausal women, the relationship being strongest for fat mass. Body weight shows stronger correlations with bone mass than either height or body mass index. In view of the direction and magnitude of changes in fat, lean tissue and bone mineral after the menopause, adiposity and muscularity are more likely to be determinants of peak bone mass than of the rate of post‐menopausal bone loss.
Growth hormone treatment of adults withgrowth hormone deficiency: results of a 13‐month placebo controlled cross‐over study
Authors: Whitehead Helen M. , Boreham Colin , Mcllrath Edwin M. , Sheridan Brian , Kennedy Laurence , Atkinson A. Brew , Madden David R.
Published: March 2008

objective We aimed to study the effect of biosynthetlc growth hormone (GH) replacement In growth hormone deficient adults.

design We performed a double‐blind placebo‐controlledcross‐over study of 6 months biosynthetic GH, replacement and 6 months placebo separated by a 1‐month'swashout period.

patients Fourteen growth hormone deficient adults were studied.

measurements We measured total body weight, percentage fat mass, lean body mass, muscle volume, exercise capacity, maximum oxygen consumption, muscle strength, bone mineral content, a number of biochemical parameters, IGF‐I, GH antibodies andpsychological well‐being.

results Total body weight remained unchanged, but lean body mass increased (before GH mean ± SEM 49·8±5·5, after 53·4±5·6 kg; placebo before 51·2±5·4, after 50·4±5·1 kg; P < 0·05 and fat mass decreased (before GH 21·5±4·1, after 19·3±4·3, placebo before 19·3±4·0, after 22·5±4·5 kg; p < 0·05). Thigh muscle volume increased: (before GH 94·1±7·7, after 99·5±8·4 ml; placebo before 99·3±8·6, after 95·4±7·8 ml/0·8 mm computerized tomographic slice; P < 0·05). Exercise capacity increased (before GH 174·15, after 199·18·9 watts; placebo before 162·5±2·3, after 154·19·8 watts; P < 0·05), as did maximum oxygen consumption (before GH 1·93±0·2, after 2·17±0·2 I/m; placebo before 1·92±0·3, after 1·98±0·2 I/m; P < 0·05). There was no change in quadriceps muscle strength. Alkaline phosphatase increased (before GH 87·5 (32–158), after 106·0 (49–179) U/l; placebo 98·5 (50–145), after 72·0 (40–111) U/l; P < 0·05) without a change in the spinal bone density. IGF‐I increased (before GH 62 (36–97), after 216 (62–362) μg/l; placebo before 59 (52–112), after 60·5 (38–94) μg/l; P < 0·05). Carbohydrate tolerance remained unchanged as did fasting lipids, serum sodium, potassium, urea, calcium, phosphate and liver transaminases. Psychological well‐being remained unchanged. No growth hormone antibodies were detected before or after GH treatment.

conclusions GH alters the body composition of growthhormone deficient adults and leads to improved exercisecapacity; alkaline phosphatase activity increases butwithout a change in spinal bone density, and carbohydratetolerance remains unaltered.
Physiological oestradiol administration does not change the biological to immunological ratio of LH in serum from post‐menopausal women
Authors: Buckler H. M. , Rothwell C. , Holds S. , Robertson W. R.
Published: March 2008

OBJECTIVE We Investigated the effect of chronic physiological concentrations of oestradiol on the bioactivity (B) and immunoactivity (I) of LH in serum using radioimmunoassay (RIA) and a sensitive Immunoradlometrlc (IRMA) assay.

DESIGN Twelve post‐menopausal, hysterectomized women received a 50‐mg subcutaneous E2 Implant, in the absence of progestogen treatment. Pretreatment serum samples were obtained on two occasions for measurement of E2and FSH by radioimmunoassay and for measurement of LH by bioassay (BIO), immunoradio‐metric assay and radioimmunoassay. Further serum samples were obtained monthly for 6 months for assay as above.

RESULTS The serum E2level (basal levels< 70 pmol/l) rose following implant (P<0.01) peaking at 1 month (mean 454, range 356–580 pmol/l) and remaining within premenopausal physiological levels for 6 months. There were falls in FSH, LH‐RIA, LH‐IRMA and LH‐BIO (P< 0.001). There was no change in the B:I ratio for B:I‐RIA or B:I‐IRMA for LH which were 1.8 and 3.3, respectively pretreatment and 1.7 and 2.9 after 1 month's treatment.

CONCLUSION The treatment of post‐menopausal women with 50‐mg E2subcutaneous implants produces physiological premenopausal E2levels for at least 6 months. There is no change In the B:I ratio of LH using either the RIA or IRMA during chronic E2 treatment.
Phaeochromocytoma in multiple endocrine neoplasia type 2 A: survey of 100 cases
Authors: Casanova S. , Rosenberg‐Bourgin M. , Farkast D. , Calmettes C. , Feingold N. , Heshmatl H. M. , Cohen R. , Conte‐Devolx B. , Guillausseau P. J. , Houdent C. , Bigorgne J. C. , Boiteau V. , Caron J. , Modigliani E.
Published: March 2008

OBJECTIVE We report clinical, biochemical, morphological and histological data of phaeochromocytoma in 40 French families and in apparently sporadic cases of multiple endocrine neoplasia (MEN) type 2 A (medullary thyroid carcinoma, phaeochromocytoma, with or without hyperparathyroidism).

DESIGN This retrospective study was obtained from cases registered by the‘Groupe d'Etudes des Tumeurs a Calcitonine’ from 1968 to 1990. We analysed the cases having sufficiently precise data on phaeochromocytoma with Pigas Software.

PATIENTS Characteristics of phaeochromocytoma In 100 patients with MEN 2 A were reviewed. Phaeochromocytoma was bilateral in 51 %. The disease was inherited in 94 patients from 40 families (40 probands, 54 relatives), and was apparently sporadic In six.

RESULTS In this series, diagnostic circumstances were highly suggestive of phaeochromocytoma in 39.8% of the cases, whereas in 43.2%, diagnosis was made through systematic investigations of patients, either before (27.3%) or after (13.6%) thyroidectomy, or after discovery of hyperparathyroidism (2.3%). Fifteen per cent of patients were detected by family screening. Sudden death occurred in 8.9%, malignant phaeochromocytoma In 3%, and ectopic tissue in 4% of the cases. Urinary metanephrines appeared to be the most sensitive screening test. The extent of clinical symptoms was not associated with a particular hormonal pattern. Bilateral adrenalectomy was performed in 60% (in one step in 50%, in two steps in 10%). In these patients, bilateral histological lesions were observed in 92.5%. Simultaneous diagnosis for adrenal and thyroid disease was made in 73.4%, but phaeochromocytoma may be diagnosed before (9.6%) or after (17%) medullary thyroid carcinoma, with an interval greater than 2 years in 25 cases.

CONCLUSION Owing to variable clinical symptoms of phaeochromocytoma in these 100 cases of MEN 2 A, systemic biological adrenal assay is required. The search for phaeochromocytoma in medullary thyroid carcinoma (and vice versa) has to be systematically performed, even in apparently sporadic cases. Screening for phaeochromocytoma must be repeated for years, owing to the frequency of bilateral adrenal disease.