bluuebunny/crossref_metadata_2025 huggingface dataset:
Responses of plasma adrenocortical steroids to low dose ACTH in normal subjects
Authors: Daidoh H. , Morita H. , Mune T. , Murayama M. , Hanafusa J. , NI H. , Shibata H. , Yasuda K.
Published: March 2008

OBJECTIVE The standard ACTH test in clinical use employs a pharmacological dose of ACTH which assesses the maximum secretory capacity of the adrenal cortex. We have investigated the responses of plasma adrenocortical steroids including cortisol, aldosterone and dehydroepiandrosterone (DHEA) to physiological doses of ACTH (ACTH 1–24, tetracosactide, Cortrosyn) and determined the minimal dose which induces a response equivalent to that induced by a pharmacological dose of ACTH.

DESIGN Rapid ACTH tests at various physiological (0.1, 0.5, 1 and 5μg) and standard pharmacological (250μg) intravenous doses.

SUBJECTS Seven healthy normal volunteers.

MEASUREMENTS Plasma cortisol, aldosterone and DHEA were measured. Peak value and the increment from basal value were used as indices of responses.

RESULTS Each steroid responded to physiological doses of ACTH in a dose dependent manner. The minimum dose inducing an equivalent response to 250μg ACTH was 0.5μg for peak and incremental values in cortisol and DHEA, while that for aldosterone was 0.1μg. The time to peak for each steroid was delayed as the dose increased. Plasma aldosterone and DHEA peaked significantly earlier than plasma cortisol in 1–5μg and 0.5–5‐μg ACTH tests, respectively.

CONCLUSIONS These results suggest that the sensitivity of secretion to physiological doses of ACTH in descending order is aldosterone > DHEA = cortisol. When peak and incremental values are used, sufficient doses of ACTH are 0.1μg for plasma aldosterone and 0.5μg for plasma cortisol and DHEA in the rapid ACTH test.
Combined treatment of growth hormone and the bisphosphonate pamidronate, versus treatment with GH alone, in GH‐deficient adults: the effects on renal phosphate handling, bone turnover and bone mineral mass
Authors: Valk N. K. , Erdtsieck R. J. , Algra D. , Lamberts S. W. J. , Pols H. A. P.
Published: March 2008

OBJECTIVE A potential drawback of GH replacement therapy In GH deficient (GHD) patients is the Initial decrease in bone mass. The present study Investigates the effects of the addition of pamidronate to GH replacement therapy in adult GHD subjects, on serum PTH and 1,25‐dihydroxyvitamin D3 (1,25‐(OH)2D3) levels, renal phosphate handling, bone turnover and bone mineral content (BMC).

DESIGN Six GHD adult patfents were studied for two periods of 6 months with a wash‐out period of 3 years. In the first period they were treated with conventional replacement therapy and GH. In the second study period GH treatment was Identical, whlle after 2 weeks 150 mg pamidronate per day was added.

RESULTS In the first study period (GH only) there was a slgniflcant increase of phosphate reabsorption, without a change In serum PTH and 1,25‐(OH)2D3 levels. Thls suggests a specific effect of GH or IGF‐l on renal phosphate handling. This was supported by the close correlatlon between serum IGF‐I levels and TmPlGFR (r=0·75, P < 0.0001). When GH was administered together with pamldronate, this correlation was less, but remained signiflcant (r=0·44, P < 0001). The Increase In bone turnover and decrease in BMC, as Initially observed during GH replacement therapy alone, were attenuated by simultaneous pamidronate administration. The decline in lumbar spine BMC (measured with dual‐photon absorptiometry) at 6 months was −3.1 ± 1.5% during GH replacement therapy alone vs an increase of +3.8 ± 2.0% during the admlnistratlon of the comblnatlon of GH and pamldronate (measured with dual‐energy X‐ray absorptlometry). At the distal and proximal forearm the changes amounted to −0.5 ± 3.4% vs +4.5 ± 1.8% and −1 ± 1.2% vs +1.2 ± 1.1 % respectively.

CONCLUSIONS This study shows that the addition of a bisphosphonate to GH replacement therapy in GHD adults counteracts the GH (or IGF‐I) Induced Increase In renal phosphate reabsorptlon. Furthermore, It reduces OH induced bone turnover and prevents the lnitlal decrease in bone mineral content seen during GH treatment alone, resultlng In a beneflclal effect on bone mlneral mass. Pamidronate might therefore be an important adjunct to GH replacement therapy in adults with GHD and severe osteopenia during the early phase of GH Induced stlmulation of bone turnover.
Is calculation of the dose in radioiodine therapy of hyperthyroidism worth while?
Authors: Jarløv Anne E. , Hegedüst Laszio , Kristensen Lars Ø. , Nygaard Birte , Hansen Jens M.
Published: March 2008

OBJECTIVE The persistent controversy as to the best approach to radioiodine dose selection in the treatment of hyperthyroldism led us to perform a study in order to compare a fixed dose regime comprising doses of 185, 370 or 555 MBq based on gland size assessment by palpation only, with a calculated 131I dose based on type of thyroid gland (diffuse, multinodular, solitary adenoma), an accurate thyroid volume measurement, and a 24‐hour 131I uptake determination.

DESIGN Prospective randomized study.

PATIENTS Two hundred and twenty‐one consecutive hyperthyroid patients referred for 131I treatment. Four patlents who dled for reasons unrelated to hyperthyroidism, 7 lost to follow‐up and 47 who did not receive antithyroid drugs after treatment, were excluded. The remalnlng 163 patlents (143 women) were studied, dlvlded into subgroups accordlng to the type of gland. They all recelved antithyroid drugs prior to 131I treatment and this was resumed 7 days after treatment for a period of 3 weeks.

MEASUREMENTS Thyroid function variables were determined approximately 2 weeks before 131I treatment, and again 1, 2, 3, 6, 9 and 12 months after treatment. Prior to 131I therapy the size of the thyroid gland was determined by ultrasound and a 24‐hour uptake of 131I was carried out. Thyroid in 78 of the 163 patients. Twelve months after the initial 131I dose patients could be classified as euthyroid, hyperthyrold or hypothyroid.

RESULT Neither in the group of 163 patients nor within the three subgroups of hyperthyroidism could any significant difference in outcome between the two treatment regimes be demonstrated. Thirty‐two of 78 patients (41%) in the calculated dose group and 30 of 85 patients (35%, NS) in the fixed group were classified as hyperthroid. Seven of 78(9%) in the calculated dose group were classified as permanently hypothyroid. Finally, 39 of 78(50%) In the calculated dose group and 49 of 85(58%, NS) in the fixed group were enthyroid at 12 months after 131I treatment. One year after 131I therapy thyroid volume was deduced from 59.3 ± 9.2 (mean ± SEM) to 36.2 ± 6.6 ml (average reduction 39%) In the calculated dose group (P < 0.001). This reduction did not differ significantly from the fixed dose group where thyroid volume declined from 61.6 ± 6.1 to 41.17 ± 4.7 ml (average reduction 32%) (P < 0.001).

CONCLUSIONS A semiquantitative approach is probably as good as the more elaborately calculated radiolodine dose for treatment of hyperthyroidism. It is clearly more cost effective and allows the use of predetermined standard doses.
Is previous hyperthyroidism still a risk factor for osteoporosis in post‐menopausal women?
Authors: Grant David J. , McMurdo Marion E. T. , Mole Patricia A. , Paterson Colin R.
Published: March 2008

OBJECTIVE Hyperthyroidism is a risk factor for osteoporosis, but the relative contributions of the episode of hyperthroidism and thyroxine replacement for subsequent hypothroidism remain uncertain. In this study we have measured bone mineral density (BMD) in post‐menopausal women with a previous history of hyperthyroidism, comparing those requiring thyroxine therapy with those remaining euthyroid and with an historical local control population.

DESIGN Cross‐sectional study.

PATIENTS One hundred and SIX post‐menopausal women with a previous history of hyperthyroldism. These were divided Into four groups: treated with radiolodine, remaining euthyroid (group RU, n = 15); treated with radiolodine, receiving thyroxine for at least 5 years (group RT, n = 46); treated with surgery, remaining euthyrold (group SU, n = 21); treated with surgery, receiving thyroxine for at least 5 years (group ST, n = 24). There were 102 control subjects.

MEASUREMENT Forearm bone mineral density at distal and ultradistal sites as measured by single‐photon absorptlometry.

RESULTS Results were expressed as ‘2‐scores’ i.e. number of standard deviatlons from the mean of a 5‐year age‐band from the local control population. Mean Z‐scores at distal and ultradistal sites were as follows: −0.61 and −0.81 in group RU; −0.58 and −0.56 In group RT; −0.27 and −0.30 in group SU; −0.81 and −0.57 In group ST. Patients in groups RU, RT and ST but not SU had significantly lower BMD than controls.

CONCLUSION Post‐menopausal women with previous hyperthyroidism treated with radioladine have reduced BMD, whether or not receiving thyroxine. They should be targeted for densitometry and protective therapy with oestrogen should be considered. Those treated with surgery appear to be at less risk; this may be because most are diagnosed and treated whilst premenopausal. Thyroxine may have a deleterious effect in this group; longitudinal studies would provide further clarification.
Vitamin D status in primary hyperparathyroidism in India
Authors: Harinarayan C. V. , Gupta N. , Kochupillai N.
Published: March 2008

OBJECTIVES Primary hyperparathyroidism is a syndrome with variable clinical expression, presenting as asymptomatic hypercalcaemia in Western countries and with predominant bone disease in developing countries. Vitamin D deficiency has been implicated as the cause of bone disease. There is a paucity of information on the vitamin D (25‐OHD3) status of patients with primary hyperparathyroidism presenting with bone disease. The present study aims to evaluate the vitamin D status in patients with primary hyperparathyroidism and to correlate it with the bone disease.

DESIGN Twenty consecutive patients with primary hyperparathyroidism admitted to the endocrinology and metabolism wards of the All India Institute of Medical Sciences were analysed to assess their clinical, radiological and biochemical features, as well as parathyroid hormone (mid‐molecular, PTH‐MM) and 25‐OHD3 levels.

MEASUREMENTS PTH‐MM levels and 25‐OHD3 levels were measured using RIA kits.

RESULTS Bone disease (osteitis fibrosa cystica) was the mode of presentation in 90%. Radiologically, sub‐periosteal resorption was present in 90% of the total group of patients, brown tumours in 60%, and pathological fractures in 40%. Renal stones and/or nephrocalcinosis was present in 50% of patients. Mean serum calcium, phosphate and alkaline phosphatase concentrations (mean of 3 days values) were 2.72 ± 0.24 mmol/l; 1.01 ± 0.28 mmol/l and 425 ± 249 IU/l respectively. The 24‐hour (mean of 3 days values) urine calcium and phosphate excretions were 8.0 ± 4.2 mmol and 19.0 ± 13mmol. Only 50% of the patients had hypercalcaemia (> 2.7 mmol/l). However, 90% of the whole group of patients had hypercalciurla. The mean serum creatinine concentration of patients with hypercalcaemia was 108 ± 38 μmol/l and of those with normocalcaemia 89 ± 33 pmol/l. The mean serum PTH‐MM was 438 ± 350 pmol/l (the detection limit for the kit was 34 pmol/l). Ultrasound examination detected adenomas in 72% of the cases and computerized tomography of the neck localized adenomas in 71 % of the cases. The median weight of the adenoma was 4.6 g (range 0.125–25 g). Two patients had coexistent hyperplasia of the other parathyroid glands and two had recurrent adenomas. 25‐OHD3 levels were assessed in all 20 patients under fasting conditions. The mean value of 25‐OHD3 observed (8.4 ± 51 μg/l) was comparable to the mean value measured in 14 healthy age and sex matched controls (83 ± 25 μg/l).

CONCLUSION Patients with primary hyperparathyroidism in India presented with bone and renal diseases; half were normocalcaemic. All the patients had hypercalcuria despite the bone disease. The PTH‐MM levels were increased and 25‐OHD3 levels were low. The predominant bone disease is probably due to prolonged primary hyperparathyroidism coexisting with low calcium intake and/or 25‐OHD3 deficiency. The mean weight of the adenoma was higher than that reported for patients in the Western literature.
High prevalence of nodular thyroid disease in patients with Cushing's disease
Authors: Invitti C. , Manfrini R. , Romanini B. M. , Cavagnini F.
Published: March 2008

OBJECTIVES In the recent past, we have noted a frequent Occurrence of thyroid nodules in our patients with Cushing's disease. We therefore elected to evaluate thyroid structure and function in these patients and also In patients with Cushing's syndrome of primary adrenal origin.

PATIENTS AND METHODS In 33 of the 37 patients (30 women and 3 men aged 19–66 years) with endogenous hypercortisolism referred to our Institution during the last five years, measurement of T4, T3, FT4, FT3, TSH serum levels and thyroid ultrasonography were performed, at first admission in 15 cases and subsequently in the course of follow‐up in 18 cases. At the time of the study, 16 of the 33 patients had active Cushing's disease while 9 were in remission after successful surgery, 6 patients had an adrenal tumour and 2 patients had previously undergone unilateral adrenalectomy for an adrenal adenoma. Thyroid function and ultrasonography were also evaluated in 55 normal subjects, 40 women and 15 men aged 20–73 years.

RESULTS In 25 patients with Cushing's disease, we found a significantly higher prevalence of thyroid nodular disease than that recorded in 55 control subjects (60.0 vs 20.0%, χ2= 10.779, P < 0.005) and comparable to that in patients with active disease (56.2%) and those in remission (66.6%). Multiple nodules were present in 8 Cushing's patients and in 4 normal subjects while a single nodule was detected in 7 patients and in 7 controls. A markedly lower Occurrence of thyroid abnormality was found in the 8 patients with adrenal tumours (25.0%, NS vs controls). In 9/17 (52.9%) patients with ultrasonographic evidence of thyroid nodules, these were palpable. As expected, serum thyroid hormone and TSH levels were reduced in patients with active Cushing's syndrome compared to normal controls.

CONCLUSIONS We found a significantly higher prevalence of nodular thyroid disease in patients with Cushing's disease with respect to a group of controls in whom the prevalence of thyroid nodules was comparable to that reported for the general population in Europe. The possibility that glucocorticoid excess is responsible for the development of thyroid changes does not seem likely since in our small series of patients with adrenal tumours the prevalence was only slightly higher than that observed in control subjects. Other factors related to hyperactivity of the corticotrophic cell, or a growth factor stimulating both corticotroph and thyrocyte proliferation might be involved. Evaluation of a larger series of patients with adrenal tumours may help to distinguish between these possibilities.
The effect of an opiate antagonist on the hormonal changes induced by hexarelin
Authors: Korbonits Márta , Trainer Peter J. , Besser G. Michael
Published: March 2008

OBJECTIVE Growth hormone‐releasing peptides (GHRPs) stimulate growth hormone (GH) release in vitro and in vivo in animals and in humans. GHRPs were developed by modification of the structure of met‐enkephalln but GHRP‐6 does not activate opioid receptors in animal studies. These agents may well have diagnostic and/or long‐term therapeutic potential in the future so their effects on opioid receptors need to be clarified in humans as well. Hexarelin is a recently developed six amino acid residue GHRP.

DESIGN We have Investigated the effects of 100 μ g/kg I.v. dose of the opiate antagonist naloxone and 2 μ g/kg I.v. hexarelin or placebo on serum GH, prolactin, TSH, cortisol and plasma ACTH in 12 healthy volunteers in a double‐blind, randomized trial.

RESULTS Hexarelin signiflcantly stimulated the peak serum levels and area under the curve for clrculating GH and this effect was not modulated by naloxone. Hexarelin also caused significant elevation of circulating prolactin, cortisol and ACTH but did not Influence circulating TSH levels. The effect of naloxone on cortisol and ACTH was stimulatory, while it did not influence prolactin, GH and TSH levels. The effect of the two drugs together on cortisol and ACTH was less than additive.

CONCLUSIONS This study confirms that the activation of opiate receptors does not play a role in the GH‐releasing effect of growth hormone‐releasing peptides in humans.
Transient osteoporosis of the hip in pregnancy: natural history of changes in bone mineral density
Authors: Funk Janet L. , Shoback Dolores M. , Genant Harry K.
Published: March 2008

A 31‐year‐old white female developed severe bilateral hip pain during the third trimester of pregnancy that persisted after parturition. Laboratory abnormalities (elevated alkaline phosphatase and erythrocyte sedimentation rate) and radiographic changes (faint demineralization of the femur in the more symptomatic hip on plain films with evidence of bone marrow oedema and small joint effusions bilaterally on MRI) in the absence of other causes of focal osteoporosis were consistent with the diagnosis of transient osteoporosis of the hip in pregnancy. Although loss of bone mineral density (BMD) characterizes this syndrome, serial BMD measurements in symptomatic transient osteoporosis of the hip in pregnancy have not previously been reported. In the case reported here, serial bone density measurements were obtained over a 4‐year period following the onset of symptoms. BMD in both femoral necks, which Initially was approximately 20% lower than the average for age matched controls, increased markedly during the first year, plateaued during the following year, and then rapidly increased again following cessation of lactation. Unexpectedly, BMD in the lumbar spine, an asymptomatic site, was also markedly decreased at the time of presentation (31% lower than the mean of age‐matched controls). Recovery of spinal density did not occur during the first year. However, spinal BMD did begin to increase during the second year and continued to rise after the cessation of lactation. In contrast to the marked reduction in bone density at these sites of trabecular bone, cortical bone density in the forearm was normal. Possible aetiologies of pregnancy associated osteoporosis are discussed.
Cushing's disease due to female gonadotroph adenoma of the pituitary
Authors: Ikeda Hidetoshi , Yoshimoto Takashi , Kovacs Kalman , Horvath Eva
Published: March 2008

A 39‐year‐old woman presented with amenorrhoea, hyperprolactinaemia and sellar mass. Bromocrlptine normalized PRL levels but failed to suppress tumour growth. Subsequently, she developed clinical signs and elevated blood cortisol levels consistent with a diagnosis of Cushing's disease. A pituitary tumour was removed which was immunoreactive for ACTH. Electron microscopic examination, however, revealed a female gonadotroph adenoma indicating that adenoma cells regarded as gonadotrophs by ultrastructural analysis may occasionally secrete ACTH and cause Cushing's disease.
Further increase in forearm cortical bone mineral content after discontinuation of growth hormone replacement
Authors: Holmes Sarah J. , Whltehouse Richard W. , Economou Georgla , O'Halloran Domhnall J. , Adams Judith E. , Shalet Stephen M.
Published: March 2008

OBJECTIVE Growth hormone replacement of adults with childhood onset GH deficiency results In an Increase In bone mineral density (BMD) after 6‐12 months of OH replacement. By measuring BMD 12 months after discontinuation of GH replacement we aimed to Investigate whether there is an effect of GH replacement on BMD persisting after GH has been withdrawn.

DESIGN BMD was measured 13 ± 1 (mean ± SE, range 11‐16) months after discontinuation of OH replacement. PATIENTS Ten adults, age 23·;2 ±1·;4 (range 18·8‐32·4) years, with childhood onset isolated GH deficiency (2 idiopathic, 8 irradiation induced) who had previously completed a study of the effect of 12 months of OH replacement on BMD.

MEASUREMENTS Forearm cortical bone mineral content (BMC) was measured using single‐photon absorptlometry at the proximal site of the distal forearm. Forearm integral BMC at the ultradistal site of the forearm and bone width at both proximal and ultradistal rites of the distal forearm were measured by the same technique. Vertebral trabecular BMD was measured using quantitative computed tomography.

RESULTS Forearm cortical BMC was significantly greater than that measured at the time of discontinuation of OH (1·48 ±0·04 vs 1·44 ± 0·05 g/cm). There was no significant change in forearm integral BMC or in vertebral trabecular BMD after discontinuation of OH. There was no significant change in bone width at proximal and ultradistal sites of the distal forearm after discontinuation of GH.

CONCLUSION After discontinuation of OH replacement the further increase In forearm cortical bone mineral content without a significant Increase In forearm bone width suggests that the Increase In cortical bone mineral content Is due to a persisting effect of previous GH replacement, and not to further spontaneous attainment of bone mass before peak bone mass lo reached. These findings emphasize the importance of continuing to monitor bone mass after the stimulus to Increase bone turnover has been withdrawn.
Somatostatin receptor imaging in persistent medullary thyroid carcinoma
Authors: Frank‐Raue K. , Bihl H. , Dörr U. , Buhr H. , Zlegler R. , Raue F.
Published: March 2008

OBJECTIVE Somatostatin is secreted from thyroid C‐cells and seems to play an Important part In the regulation of calcitonin secretion. We therefore evaluated the usefulness of somatostatin receptor scintigraphy in the localization of tumour tissue in patients with persistent medullary thyroid carcinoma.

DESIGN A prospective clinical study.

PATIENTS The series consisted Of 26 patients with elevated calcitonin levels after total thyroldectomy for histologically proven medullary thyroid carcinoma.

METHODS Somatostatin receptor scintigraphy using 111 In‐pentetreotide (Octreoscan) was performed in all patients and the results correlated with histology, ultrasonography, computerized tomography, magnetic resonance Imaging, plain radiography, bone scintigraphy and selective venous Catheterization. calcitonin and carcinoembryonic antigen levels were measured.

RESULTS The sensitivity of somatostatin receptor scintigraphy for localization of persistent medullary thyroid carcinoma was 57% in patients with histologically proven disease. The results depended on tumour mass (low sensitivity (33%) in minimal residual disease) and on the location of metastases (Insensitive in detecting liver metastases).

CONCLUSIONS Somatostatin receptor scintigraphy is of value as an additional diagnostic tool in localizing medullary thyroid carcinoma, especially pulmonary metastases. It is of minor importance in detecting minimal residual disease.
Loss of biological activity of arginine vasopressin during its degradation by vasopressinase from pregnancy serum
Authors: Gordge M. P. , Williams D. J. , Huggett N. J. , Payne N. N. , Nelld G. H.
Published: March 2008

BACKGROUND AND OBJECTIVE Degradation of AVP by placental vasopressinase may precipitate gestational diabetes insipidus, which in some cases is accompanied by pre‐eciampsia. Abnormally elevated vasopressinase has also been reported in pre‐eciampsia without diabetes Insipidus. This association between excessive vasopressinase production and pre‐eciampsia might be explained if the products of AVP degradation by vasopressinase retained pressor activity even after anti‐diuretic activity had been destroyed. Recent evidence indicates that such products may raise blood pressure in rats. The objective of this study was, therefore, to purify vasopressinase and investigate its action on both the V1 and V2 receptor‐stimulating activity of AVP.

DESIGN Vasopressinase was purified from pooled pregnancy serum by ammonium sulphate precipitation, followed by sequential Ion exchange, lentil lectin affinity and gel filtration chromatography. Purified enzyme was then used to degrade AVP and the loss of both immunoreactivity and biological activity monitored. Loss of V1 receptor‐stimulating activity and V2 receptor‐stimulating activity was compared by two‐way ANOVA.

PATIENTS Blood was obtained from healthy women between week 34 and the end of pregnancy. Pooled serum from 20–30 patients was used as starting material for the purification of vasopressinase.

MEASUREMENTS AVP immunoreactivity was measured by radioimmunoassay, V1 receptor‐stimulating activity by a platelet aggregation bioassay, and V2 receptor‐stimulating activity by adenylate cyclase stimulation in LLC‐PK1 target cells.

RESULTS Purified vasopressinase was a dimeric protein of molecular weight 330 kDa, which cleaved the synthetic substrate S‐benzyl‐l‐cystelne‐4‐nitroanilide with a Km of 0·33 mM. Incubation of AVP (0·1 mm) with vasopressinase (0·66 g/I) at 37°C led to a parallel loss of both AVP immunoreactivity and biological activity. The rates of loss of V1 and V2 receptor mediated activities were not significantly different.

CONCLUSIONS We report the first direct comparison between the loss of V1 and V2 receptor mediated activities of vasopresrinase degraded AVP. There was no significant retention of V1, relative to V2, receptor mediated activity. AVP degradation products are unlikely to be pathogenic in hypertensive pregnancy.
Megestrol‐induced Cushing's syndrome
Authors: Steer K. A. , Kurtz A. B. , Honour J. W.
Published: March 2008

This case describes the first report of a patient developing Cushing's syndrome whilst being treated with the synthetic progestogen, megestrol acetate (Megace).

Drugs are the commonest cause of Cushing's syndrome. Some synthetic progestogens are known to have glucocorticoid activity at high doses. On structural grounds neither megestrol nor its major metaboiltes would be expected to interact with the glucocorticoid receptor, though the manufacturers report that it may have ‘weak glucocorticoid activity'.
Pseudo‐phaeochromocytoma after multiple drug interactions involving the selective monoamine oxidase inhibitor selegiline
Authors: Lefebvre H. , Noblet C. , Moore N. , Wolf L. M.
Published: March 2008

A patient presented with paroxysmal hypertension and typical clinical features of phaeochromocytoma, but with a normal adrenal computed tomographic scan and much higher plasma noradrenaline than adrenaline concentrations. Urinary vanillyimandelic acid concentrations were only moderately elevated. This syndrome probably arose as a consequence of an interaction between the monoamine oxidase inhibitor selegiline, the sympathomimetic agent ephedrine, and a tricyclic antidepressant The mechanism of the interaction is thought to be related to increased sympathetic release of noradrenaline by ephedrine, inhibition of catabolism by selegiline, and inhibition of reuptake of noradrenaline by the tricyclic. Although newer selective monoamine oxidase inhibitors are considered to be safer than earlier non‐selective inhibitors, they can also contribute to drug intersections mimicking phaeochromocytoma.
Ovarian morphology and insulin sensitivity in women with bulimia nervosa
Authors: Raphael F. J. , Rodin D. A. , Peattle A. , Bano G. , Kent A. , Nussey S. S. , Lacey J. H.
Published: March 2008

OBJECTIVE Hyperinsulinaemia has a role in the development of hyperandrogenism and polycystic ovary syndrome in women of normal weight. Polycystic ovaries are common in women with bulimia nervosa and this study aimed to determine whether women with bulimia nervosa are insulin resistant and to examine the relation between Insulin sensitivity and ovarian morphology.

DESIGN A short intravenous insulin tolerance test was used as a direct measure of insulin sensitivity In a group of women with bulimia nervosa and 8 control group.

PATIENTS A series of 12 women with bulimia nervosa and normal weight was compared with a control group of 9 healthy women who had no clinical signs of eating disorder or hyperandrogenism and did not have polycystic ovaries.

MEASUREMENTS Bulimic behaviour was assessed using the BITE (Bulimia Investigation Test, Edinburgh) questionnaire and clinical interviews. Ovarian morphology was assessed using transabdominal ultrasonography. Insulin sensitivity and serum Insulin, fasting glucose, LH, FSH, prolactin, testosterone, androstenedione and sex hormone binding globulin (SHBG) were measured and compared between the two groups.

RESULTS Ten of the 12 women with bulimia nervosa underwent ovarian ultrasound examination and they all had polycystic ovaries. There was no difference in serum LH, FSH, testosterone, androstenedione or SHBG concentrations between the women with bulimia nervosa and the non‐bulimic control group. Fasting blood glucose concentrations were normal in all the women studied and did not differ between the women with bulimia nervosa and the control women. There was also no difference In fasting serum Insulin or Insulin sensitivity between the women with bulimia nervosa and the non‐bulimic women.

CONCLUSIONS Bulimia nervosa is not associated with Insulin resistance and chronic hyperinsulinaemia.
Osteomalacia associated with adult Fanconi's syndrome: clinical and diagnostic features*
Authors: Clarke Bart L. , Wynne Alan G. , Wilson David M. , Fitzpatrick Lorraine A.
Published: March 2008

OBJECTIVE Osteomalacia associated with adult acquired Fanconi's syndrome is thought to result from hypophosphataemia and relative 1,25‐dihydroxy vitamin D deficiency. We have followed the clinical and diagnostic features of patients with osteomalacia associated with adult Fanconi's syndrome, with particular emphasis on their responses to treatment with calcium, phosphate and vitamin D.

DESIGN Retrospective Mayo Clinic case‐note review from 1975 to 1994 and prospective follow‐up study, combined with literature review.

PATIENTS Eleven patients (7 male, 4 female) were identified who satisfied criteria for diagnosis of osteomaiacia and adult Fanconi's syndrome. Twenty‐five additional patients were identified in a literature review from 1954 to the present.

METHODS Clinical history and physical examination, serum and urine bone and mineral parameters, X‐ray radiography and iliac crest bone histomorphometry.

RESULTS All patients presented with typical symptoms of osteomalacia, including lower extremity or low back bone pain, and ail had fractures, pseudofractures, and/or bone demineralization on X‐ray radiography. Osteomalacia and Fanconi's syndrome were diagnosed concurrently in 10 patients, whereas osteomalacia preceded diagnosis of Fanconi's syndrome by 5 years in one patient. Pre‐treatment bone biopsies in 9 of the 11 patients demonstrated increased osteoid surface, volume and width. In the one patient labelled with tetracycline prior to biopsy, mlnerallzation lag time was prolonged at 111 days (normal 19.2±1.0 days). Hypophosphataemia, inappropriately low 1,25‐dihydroxyvltamin D levels, renal insufficiency, and chronic acidosis due to bicarbonate leak and uraemia, contributed to the osteomalacia in these patients. Secondary hyperparathyroidism was present In two patients. Eight of the 11 patients with osteomalacia associated with Fanconi's syndrome had monoclonal disorders, including multiple myeloma or lymphoma, many of them manifest by light‐chain proteinuria. Over a mean patient follow‐up period of 46 months (range 1–239 months), patients responded symptomatically to calcium, phosphate, and vitamin D replacement typically within 1–6 months. In 8 patients in whom follow‐up data were available, post‐treatment serum phosphate and 1,25‐dihydroxyvitamin D levels Improved in the setting of stable mild renal insufficiency; only one patient developed end‐stage renal failure after 20 years, suggesting that these patients do not invariably progress rapidly to renal failure.

CONCLUSIONS Regardless of the underlying cause, osteomalacia associated with adult acquired Fanconi's syndrome appears to respond well to calcium, phosphate, and vitamin D replacement. These patients do not appear to necessarily require 1,25‐dihydroxyvitamin D replacement.
Effect of acute desmopressin and of long‐term thyroxine replacement on haemostasis in hypothyroidism
Authors: Erfurth Eva Marie T. , Ericsson Ulla‐Brltt C. , Egervall Karln , Lethagen Stefan R.
Published: March 2008

OBJECTIVE Hypothyroidism can be complicated by bleeding symptoms such as easy bruising, menorrhagla and sometimes even a severe bleeding tendency with fatal outcome. Usually there is a prolonged bleeding time, or a low plasma concentration of coagulation factor VIII (FVIII) or von Willebrand factor (vWF). The aim of the present study was to investigate the acute haemostatic effect of desmopressin in hypothyroid patients. Another aim was to study the long‐term effect of thyroxine replacement on the plasma concentrations of coagulation factors and to ascertain the duration of thyroxine treatment needed to restore haemostatic function.

DESIGN AND PATIENTS The effects of desmopressin, given intravenously over 10 minutes at a dosage of 0.3 μg/kg, and thyroxine treatment on haemostatic function were studied prospectively In 10 patients with hypothyroidism.

RESULTS Before treatment only five of the patients manifested bleeding symptoms; one had prolonged bleeding time, and one had low plasma concentrations of vWF: Ag. Desmopressin virtually immediately reduced bleeding time, enhanced platelet adhesiveness, and significantly increased plasma concentrations of FVIII and vWF.

The plasma concentrations of FVIII and vWF showed a significant increase after 4 months, whereas 7 months treatment with thyroxine was needed to reduce bleeding time significantly.

CONCLUSION Our results suggest that in hypothyroid patients desmopressin may be of value for the acute treatment of bleeding or as cover for surgery.
Adrenarche does not occur in treated patients with congenital adrenal hyperplasia resulting from 21‐hydroxylase deficiency
Authors: Brunelli Valeria L. , Chlumello Giuseppe , David Michel , Forest Maguelone G.
Published: March 2008

OBJECTIVE There have been few studies of adrenarche In patients with congenital adrenal hyperplasia (CAH). We have therefore sought to detect the onset of adrenarche In CAH patients and to investigate whether its evolution was influenced by the severity of the disease, the age at the onset of substitution therapy, or both.

DESIGN AND PATIENTS Sixteen female CAH patients were studied longitudinally for 4–11 years. They were all given substitution therapy and treatments were well controlled as judged by repeated hormonal evaluations. The patients were divided into two groups: group A consisted of 10 girls with a severe classic (congenital) form, while group B included 6 girls presenting with a non‐classic form.

MEASUREMENTS Circulating levels of dehydroepiandrosterone sulphate (DHEAS), were determined as an indicator of adrenarche. Hormonal assessments Included measurements of 17‐hydroxyprogesterone (17‐OHP), testosterone, ACTH and plasma renin activity. All were estimated by conventional specific assays.

RESULTS Mean levels were analysed in consecutive two‐year age periods. In group A, DHEAS levels were significantly lower at any age than in control subjects, and lower than In patients with non‐classic CAH. DHEAS levels showed no increment with age. In group B, plasma DHEAS levels were surprisingly high for the age at the time of diagnosis, declining gradually on substitution therapy, although they remained somewhat higher than in group A.

CONCLUSIONS The high DHEAS levels observed In untreated girls of group B are probably the result of chronic hypersecretion of ACTH. Under well controlled, non‐suppressive substitution therapy, patients with congenital adrenal hyperplasia showed no rise in DHEAS levels at the physiological age of adrenarche whatever the degree of the enyzme defect and whatever the age at onset of therapy.
Hypothalamic‐pituitary dysfunction in patients with craniopharyngioma
Authors: Paja M. , Lucas T. , García‐Uria J. , Salamé F. , Barceió B. , Estrada J.
Published: March 2008

OBJECTIVE Previous studies of preoperative pituitary function in patients with craniopharyngioma have been limited in scope and have focused on children. We have evaluated the impact of craniopharyngiomas and their surgical treatment on pituitary function In a large group of mostly adult patients.

DESIGN We performed a retrospective study of patients treated at our centre between 1980 and 1992.

PATIENTS Twenty‐two men and 13 women, most of them adults, treated surgically for craniopharyngioma during the above period.

MEASUREMENTS Serum glucose, GH, LH, FSH, TSH and Cortisol were measured both before and after a combined insulin induced hypoglycaemia, GnRH and TRH test. Basal concentrations of thyroid hormones, PRL and gonadal steroids were also measured. Preoperative computed tomographic scan was performed in all patients, and a detailed study of visual function before and after surgery was available for 32 of them. Endocrine function was reevaluated post‐operatively.

RESULTS In preoperative studies, 29 patients had some anterior pituitary deficit and 13 had diabetes insipidus. The most common abnormality was gonadotrophin deficiency, followed by GH deficiency. Dynamic studies suggested a hypothalamic origin for these deficits. In post‐surgical evaluation, Impaired pituitary function was observed in most patients. Panhypopituitarism was present in 28 cases and diabetes insipidus in 24.

CONCLUSIONS Our report illustrates the high Incidence of endocrine deficits in patients with craniopharyngioma. Additional hypothalamic‐pituitary dysfunction usually occurs following surgical treatment of these tumours.
Familial prolactinoma
Authors: Berezin Meir , Karasik Avraham
Published: March 2008

BACKGROUND Apart from the rare association with type I multiple endocrine neoplasia (MEN‐1), familial types of prolactinoma have not been reported.

PATIENTS AND MEASUREMENTS Eight hyperprolacti‐naemic patients in four families and 18 of their first and second‐degree relatives (parents, children and grandchildren) were examined. Hormone levels were measured, as well as other biochemical parameters.

RESULTS Prolactinoma was diagnosed In more than one member of each of the four families.

CONCLUSION Familial prolactinoma Is a distinct entity which Is probably due to a genetic mutation promoting lactotroph proliferation.
Measurement of thyroglobulin in newborn screening specimens from normal and hypothyroid infants
Authors: Mitchell M. L. , Hermos R. J.
Published: March 2008

BACKGROUND AND OBJECTIVE Thyroglobulin (Tg) has been found In varying concentrations In Infants and children with congenital hypothyroidism. Our primary goal was to ascertain whether Tg In filter paper blood specimens used for routine newborn screening would be a useful adjunct In the early diagnosis of newborn children with congenital hypothyroidism. Our secondary objective was to correlate the results of the Tg determinations with the results of thyroid scintigraphy in the same cohort of Infants with congenital hypothyroidism.

DESIGN An RIA kit with high sensitivity for the measurement of Tg in serum was modified for use with filter paper blood specimens. Results of thyroid scintigraphy were obtained from the family physicians on 10 Infants with ectopic thyroid glands and 18 who were considered to be athyreotic.

MEASUREMENTS Determinations of Tg were carried out retrospectively on newborn screening filter paper blood specimens from 61 full‐term normal Infants and 42 newborns with confirmed congenital hypothyroidism.

RESULTS Thyroglobulin concentrations during the first week of life in the normal controls ranged between 17 and 160 μg/l, with a median of 66 μg/l. Tg values for Infants with ectopic thyroid glands ranged between 38 and 282 μg/l, with a median of 116 μg/l. In contrast, newborns who were considered athyreotic had Tg values ranging between undetectable and 104 μg/l with a median of 15/ig/l. Fifty per cent of the athyreotic patients and 50% of patients with ectopic thyroid glands had Tg values above or below the normal range and thus fell within the diagnostic category of hypothyroidism on the basis of Tg alone. Fifty per cent of patients who were considered athyreotic by scintigraphy had Tg concentrations ranging from 20 to 104 μg/l.

CONCLUSION These studies have shown that thyroglobulin can be measured In the same filter paper blood specimens used for routine newborn screening. Estimation of thyroglobulin In screening specimens from hypothyroid and normal infants indicated that some Infants with congenital hypothyroidism could be Identified solely on the basis of the thyroglobulin concentration. Comparison of the results of scintigraphy with thyroglobulin levels In the same hypothyroid patients suggested that thryoglobulin provided a more reliable marker for the presence or absence of the thyroid gland than did scintigraphy.
Fetal osteocalcin levels are related to placental 11β‐hydroxysteroid dehydrogenase activity in humans
Authors: Benediktsson Rafn , Brennand Janet , Tibi Laila , Calder Andrew A. , Seckl Jonathan R. , Edwards Christopher R. W.
Published: March 2008

OBJECTIVE Overexposure to glucocorticoids in utero reduces birth weight and, In animals, leads to persistent hypertension in the offspring. The fetus is normally protected from maternal glucocorticoids by placental 11β‐hydroxysteroid dehydrogenase (11β‐HSD) which catalyses the conversion of Cortisol to Inert cortisone. In adult humans, osteocalcin is a sensitive marker of glucocorticoid exposure. The aim of this study was to determine whether cord blood osteocalcin levels were related to the ability of placental 11β‐HSD to inactivate maternal Cortisol.

DESIGN Cross‐sectional study examining the relation between cord blood levels of osteocalcin and placental glucocorticoid metabolism at term.

PATIENTS Twenty‐one women attending for delivery at the Simpson Memorial Maternity Pavilion in Edinburgh had cord venous and arterial blood samples collected at delivery.

MEASUREMENTS Cord plasma levels of osteocalcin, Cortisol and cortisone were measured by radioimmunoassay and indices of placental 11β‐HSD activity were calculated.

RESULTS All indices of placental 11β‐hydroxysteroid dehydrogenase activity correlated directly and significantly with cord blood osteocalcin levels. For cord blood osteocalcin and the placental 11β‐HSD Activity Index, Pearson's r was + 0.58, r2=0.33 and P<0.02.

CONCLUSION We conclude that term cord blood osteocalcin level reflects the effectiveness of placental glucocorticoid Inactlvation, and may be a marker for the development of adult hypertension.
Somatostatin receptor scintigraphy and octreotide treatment in patients with thyroid eye disease
Authors: Krassas G. E. , Dumas A. , Pontikldes N. , Kaltsas Th.
Published: March 2008

OBJECTIVE Octreotide, a potent long‐acting synthetic somatostatin analogue, has been reported to have a beneficial effect in thyroid eye disease (TED), but the precise mechanism of action remains unexplained. 111 In‐DTPA‐D‐Phe1 ‐octreotide (Octreoscan‐111) has been used to localize a number of endocrine tumours and visualize somatostatin receptors in the retrobulbar tissue of patients with TED. Furthermore, this technique can predict the inhibitory effect of octreotide on hormone secretion by endocrine tumours, as there is a close relation between the clinically observed Inhibition and visualization of the tumour using Octreoscan‐111. The alms of the present study were to confirm the beneficial effect of octreotide in patients with TED, to investigate the presence of somatostatin receptors In the orbital area and also, if possible, to ascertain whether this technique could select those patients with TED who might benefit from treatment with octreotide.

DESIGN A prospective study.

SETTING An endocrine clinic of a national hospital.

PATIENTS Twenty treated thyrotoxic patients with TED, 5 treated thyrotoxic patients without TED and 5 normal Individuals were studied. In 12 patients with TED, 5 without TED and 5 normal individuals, Octreoscan‐111 scintigraphy of the orbits was performed. The remaining 8 patients with ophthalmopathy served as controls. In patients with TED who were Investigated with Octreoscan‐111, 300 μg octreotide dally was given for 12 weeks.

RESULTS Six patients In both eyes and one patient In one eye showed an improvement In ocular manifestations as assessed by clinical criteria and changes in the NOSPECS score, while the rest showed no Improvement. The patients who showed an Improvement had a high number of somatostatin receptors and positive orbital scans, while with one exception the patients who did not respond had a low number of receptors and negative orbital scans (P<0.02). None of the 5 patients without TED nor the normal individuals had a positive orbital scan. Seven out of 8 control patients with TED showed no change in the disease during the trial, while 1 deteriorated.

CONCLUSIONS We conclude that octreotide has a beneficial effect in thyroid eye disease and that Octreoscan‐111 could predict those patients with thyroid eye disease who might benefit from this treatment.
Urinary pyridinoline and deoxypyridinoline excretion in children
Authors: Shaw N. J. , Dutton J. , Fraser W. D. , Smith C. S.
Published: March 2008

OBJECTIVE There are few data on urinary markers of collagen breakdown In children. We have determined a normal range for urinary pyridinoline and deoxypyridinoline In children, assessed the variability in excretion in individual children and examined the effect of GH treatment on the excretion of these collagen cross‐links.

DESIGN A cross‐sectional study of a group of healthy children and sequential samples from children receiving GH treatment.

PATIENTS One hundred and nine healthy children aged 2–15 years, 8 healthy children aged 4–11 years and 4 children receiving GH treatment.

MEASUREMENTS Total pyridinoline and deoxypyridinoline excretion were measured by high performance liquid chromatography after initial acid hydrolysis and cellulose extraction steps. Serum parathyroid hormone was measured using a two‐site immunoradiometric assay and urinary hydroxyproline by Ehrlich's reaction using a colorlmetric assay. Pyridinoline and deoxypyridinoline excretion were expressed as a ratio against urine creatinine.

RESULTS High excretion of pyridinoline (Pyr) and deoxypyridinoline (DPyr) was seen at all ages with no apparent relation to age (mean Pyr/Cr 115 nmol/mmol and DPyr/Cr 31 nmol/mmol). No correlation was found with serum parathyroid hormone or urinary hydroxyproline excretion. Marked day to day variation was seen in individual children. A progressive rise in excretion was seen In children receiving GH treatment with no significant correlation to height velocity.

CONCLUSIONS There is a high excretion of the pyrldi‐nium cross‐linking amino acids in children of all ages compared to adults. However, a high variability exists In single morning urine samples which will limit the usefulness of these markers in growing children.