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J S Bevan

Publications and source records attributed to J S Bevan.

At least 19 recordsLinked to original sources
PubMed2005

Antithyroid drug regimen for treating Graves' hyperthyroidism.

BACKGROUND: Antithyroid drugs are widely used in the therapy of hyperthyroidism. There are wide variations in the dose, regimen or duration of treatment used by health professionals. OBJECTIVES: To assess the effects of dose, regimen and duration of antithyroid drug therapy for Graves' hyperthyroidism. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (Central), MEDLINE, EMBASE, BIOSIS, CINAHL, HEALTHSTAR, Current Controlled Trials and reference lists. We contacted investigators and hand searched conference abstracts. Most recent search: July 2004. SELECTION CRITERIA: Randomised and quasi-randomised trials of antithyroid medication for Graves' hyperthyroidism were used. DATA COLLECTION AND ANALYSIS: Trial allocation to included, excluded and awaiting assessment categories was made by consensus. Two reviewers independently extracted data and assessed trial quality. Pooling of data for primary outcomes, and select exploratory analyses were undertaken. MAIN RESULTS: Twenty-three randomised trials involving 3115 participants were included. Overall the quality of trials as reported was poor; specifically in terms of allocation concealment, assessor blinding and loss to follow-up. Four trials examined the effect of duration of therapy on relapse rates of Graves' hyperthyroidism. In one trial using the Titration regimen, longer duration therapy (18 months) had significantly fewer relapses (37% versus 58%) than six month therapy (Odds ratio (OR) 0.42, 95% confidence interval (CI) 0.18 to 0.96). In one quasi-randomised trial using the Block-Replace regimen, there was no significant difference between the six and 12 month (relapses rates 41% versus 35%) arms of the study. Extending the duration of therapy to over 18 months was not associated with improved relapse rates (Peto OR 0.75, 95% CI 0.39 to 1.43). Twelve trials examined the effect of Block-Replace versus Titration regimen. The relapse rates were similar in both groups at 51% in the Block-Replace group and 54% in the Titration group (Peto OR 0.86, 95% CI 0.68 to 1.08). Participants reporting rashes (10% versus 5%) and withdrawing due to side effects (16% versus 9%) were significantly higher in the Block-Replace group compared to the Titration group respectively. Three studies considered the addition of thyroxine with continued low dose antithyroid therapy after initial therapy with antithyroid drugs. There was significant heterogeneity between the studies and the difference between the two groups were not significant (Odds ratio 0.58, 95% CI 0.05 to 6.21). Four studies considered the addition of thyroxine alone after initial therapy with antithyroid drugs. There was no significant difference in the relapse rates between the groups after 12 months follow-up with relapse rates being 31% (88/282) with thyroxine and 29% (82/284) with placebo (Peto OR 1.15, 95% CI 0.79 to 1.67). AUTHORS' CONCLUSIONS: The evidence (based on four studies) suggests that the optimal duration of antithyroid drug therapy for the Titration regimen is 12 to 18 months. The six month Block-Replace regimen was found to be as effective as the 12 month treatment in one quasi-randomised study. The Titration (low dose) regimen had fewer adverse effects than the Block-Replace (high dose) regimen and was no less effective in trials (based on 12 trials) of equal duration. Continued thyroxine treatment following initial antithyroid therapy does not appear to provide any benefit in terms of recurrence of hyperthyroidism. The incidence of hypothyroidism was not reported and there were no deaths reported in the study populations.

Antithyroid Agents↗
PubMed2004

Antithyroid drug regimen for treating Graves' hyperthyroidism.

BACKGROUND: Antithyroid drugs are widely used in the therapy of hyperthyroidism. There are wide variations in the dose, regimen or duration of treatment used by health professionals. OBJECTIVES: To assess the effects of dose, regimen and duration of antithyroid drug therapy for Graves' hyperthyroidism. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (Central), MEDLINE, EMBASE, BIOSIS, CINAHL, HEALTHSTAR, Current Controlled Trials and reference lists. We contacted investigators and hand searched conference abstracts. Most recent search: June 2002. SELECTION CRITERIA: Randomised and quasi-randomised trials of antithyroid medication for Graves' hyperthyroidism were used. DATA COLLECTION AND ANALYSIS: Trial allocation to included, excluded and awaiting assessment categories was made by consensus. Two reviewers independently extracted data and assessed trial quality. Pooling of data for primary outcomes, and select exploratory analyses were undertaken. MAIN RESULTS: Nineteen randomised trials involving 2233 participants were included. Overall the quality of trials as reported was poor; specifically in terms of allocation concealment, assessor blinding and loss to follow-up. Four trials examined the effect of duration of therapy on relapse rates of Graves' hyperthyroidism. In one trial using the Titration regimen, longer duration therapy (18 months) had significantly fewer relapses (37% vs 58%) than six month therapy (Odds ratio (OR) = 0.42, 95% confidence interval (CI) 0.18 to 0.96). In one quasi-randomised trial using the Block-Replace regimen, there was no significant difference between the six and 12 month (relapses rates 41% versus 35%) arms of the study. Extending the duration of therapy to over 18 months was not associated with improved relapse rates (Peto OR = 0.75, 95% CI 0.39 to 1.43). Ten trials examined the effect of Block-Replace versus Titration regime. Relapse rates were similar in both groups at 54% in the Block-Replace group and 58% in the Titration group (Peto OR = 0.83, 95% CI 0.63 to 1.10). Participants reporting rashes (11% versus 5%) and withdrawing due to side effects (16% versus 9%) were significantly higher in the Block-Replace group compared to the Titration group respectively. Three studies considered the addition of thyroxine after initial therapy with antithyroid drugs. There was significant heterogeneity between the studies and the difference between the two groups were not significant (Odds ratio = 0.58, 95% CI 0.05 to 6.21). REVIEWERS' CONCLUSIONS: The evidence (based on three studies) suggests that the optimal duration of antithyroid drug therapy for the Titration regimen is 12 to 18 months. The six month Block-Replace regimen was found to be as effective as the 12 month treatment in one quasi-randomised study. The Titration (low dose) regimen had fewer adverse effects than the Block-Replace (high dose) regimen and was no less effective in trials (based on 10 trials) of equal duration. The incidence of hypothyroidism was not reported and there were no deaths in the study populations.

Antithyroid Agents↗
PubMed2004

The efficacy and safety of lanreotide Autogel in patients with acromegaly previously treated with octreotide LAR.

OBJECTIVE: Lanreotide Autogel is a sustained-release aqueous gel formulation supplied in a prefilled syringe, with injection volume <0.5 ml. The aim of this study was to establish the efficacy and safety of Autogel in patients with acromegaly previously treated with octreotide LAR. DESIGN: A 28-week, open, multicentre study. PATIENTS: Twelve patients with acromegaly, treated with 20 mg octreotide LAR for >4 months, with serum GH levels <10.0 mU/l. METHODS: Autogel (90 mg) was given every 28 days during weeks 0-12. At week 16 the dose was titrated based on GH levels at weeks 8 and 12. If GH levels were <2.0, 2.0-5.0, or >5.0 mU/l, Autogel was reduced to 60 mg, maintained at 90 mg, or increased to 120 mg respectively, for the next three injections. GH and IGF-I levels were reassessed at weeks 24 and 28. RESULTS: Ten patients completed the study. Five remained on 90 mg Autogel throughout the study; in two patients the dose was reduced to 60 mg from week 16; in three patients it was increased to 120 mg. Mean GH levels were: baseline, 3.0+/-1.7 mU/l; week 12, 3.5+/-1.8 mU/l; week 28, 3.3+/-1.6 mU/l (NS). Mean IGF-I levels were: baseline, 212+/-70 microg/l; week 12, 185+/-91 microg/l; week 28: 154+/-61 microg/l (P=0.027). Six patients at baseline and eight at week 28 had normalised GH and IGF-I levels. Three patients reported adverse events: musculoskeletal pain (n=2) and injection-site symptoms (n=1). CONCLUSIONS: Lanreotide Autogel is effective and well tolerated in patients with acromegaly. This study in a small group of patients with well-controlled acromegaly suggests that the majority of patients switched from 20 mg LAR to 90 mg Autogel will have equivalent or better disease control.

Acromegaly↗
PubMed2003

Antithyroid drug regimen for treating Graves' hyperthyroidism.

BACKGROUND: Antithyroid drugs are widely used in the therapy of hyperthyroidism. There are wide variations in the dose, regimen or duration of treatment used by health professionals. OBJECTIVES: To assess the effects of dose, regimen and duration of antithyroid drug therapy for Graves' hyperthyroidism. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (Central), MEDLINE, EMBASE, BIOSIS, CINAHL, HEALTHSTAR, Current Controlled Trials and reference lists. We contacted investigators and hand searched conference abstracts. Most recent search: June 2002. SELECTION CRITERIA: Randomised and quasi-randomised trials of antithyroid medication for Graves' hyperthyroidism were used. DATA COLLECTION AND ANALYSIS: Trial allocation to included, excluded and awaiting assessment categories was made by consensus. Two reviewers independently extracted data and assessed trial quality. Pooling of data for primary outcomes, and select exploratory analyses were undertaken. MAIN RESULTS: Nineteen randomised trials involving 2233 participants were included. Overall the quality of trials as reported was poor; specifically in terms of allocation concealment, assessor blinding and loss to follow-up. Four trials examined the effect of duration of therapy on relapse rates of Graves' hyperthyroidism. In one trial using the Titration regimen, longer duration therapy (18 months) had significantly fewer relapses (37% vs 58%) than six month therapy (Odds ratio (OR) = 0.42, 95% confidence interval (CI) 0.18 to 0.96). In one quasi-randomised trial using the Block-Replace regimen, there was no significant difference between the six and 12 month (relapses rates 41% versus 35%) arms of the study. Extending the duration of therapy to over 18 months was not associated with improved relapse rates (Peto OR = 0.75, 95% CI 0.39 to 1.43). Ten trials examined the effect of Block-Replace versus Titration regime. Relapse rates were similar in both groups at 54% in the Block-Replace group and 58% in the Titration group (Peto OR = 0.83, 95% CI 0.63 to 1.10). Participants reporting rashes (11% versus 5%) and withdrawing due to side effects (16% versus 9%) were significantly higher in the Block-Replace group compared to the Titration group respectively. Three studies considered the addition of thyroxine after initial therapy with antithyroid drugs. There was significant heterogeneity between the studies and the difference between the two groups were not significant (Odds ratio = 0.58, 95% CI 0.05 to 6.21). REVIEWER'S CONCLUSIONS: The evidence (based on three studies) suggests that the optimal duration of antithyroid drug therapy for the Titration regimen is 12 to 18 months. The six month Block-Replace regimen was found to be as effective as the 12 month treatment in one quasi-randomised study. The Titration (low dose) regimen had fewer adverse effects than the Block-Replace (high dose) regimen and was no less effective in trials (based on 10 trials) of equal duration. The incidence of hypothyroidism was not reported and there were no deaths in the study populations.

Antithyroid Agents↗
PubMed2002

Presentation of a PTHrP-secreting pancreatic neuroendocrine tumour, with hypercalcaemic crisis, pre-eclampsia, and renal failure.

Severe hypercalcaemia during pregnancy is rare and most cases are secondary to hyperparathyroidism. This is the first report of a parathyroid hormone related protein (PTHrP) secreting neuroendocrine tumour of the pancreas manifesting with severe hypercalcaemia during pregnancy. Measurement of PTHrP was useful in both the diagnosis and follow up of our patient and should be considered in the diagnostic workup of patients with unexplained hypercalcaemia. A raised PTHrP concentration is a strong indicator of malignancy.

Acute Kidney Injury↗
PubMed2002

Primary medical therapy for acromegaly: an open, prospective, multicenter study of the effects of subcutaneous and intramuscular slow-release octreotide on growth hormone, insulin-like growth factor-I, and tumor size.

Conventional surgery and radiotherapy for acromegaly have limitations. There are few data on the use of the somatostatin analog octreotide (Oct) as primary medical therapy. An open prospective study of 27 patients with newly diagnosed acromegaly was conducted in nine endocrine centers in the United Kingdom. Twenty patients had macroadenomas, and 7 had microadenomas. For the first 24 wk (phase 1), patients received sc Oct in an initial dose of 100 microg, 3 times daily, increased to 200 micro g three times daily after 4 wk in the 13 patients whose mean serum GH remained greater than 5 mU/liter (2 microg/liter). Five-point GH profiles were performed at 0, 4, 12, and 24 wk, and high resolution pituitary imaging using a standard protocol was performed at 0, 12, and 24 wk (magnetic resonance imaging in 25 patients and computed tomography in 2). Tumor dimensions and volumes were calculated by a central, reporting neuroradiologist, and the results were audited by a second, independent neuroradiologist. After 24 wk, 15 patients proceeded to phase 2 of the study with a direct switch to monthly injections of the depot formulation of Oct, Sandostatin long-acting release (Oct-LAR). Further GH profiles were performed at 36 and 48 wk, and pituitary imaging was performed at 48 wk. The median pretreatment serum GH concentration was 30.7 mU/liter (range, 6.7-141.4). During sc Oct, serum GH fell to less than 5 mU/liter in 9 patients (38%), and IGF-I fell to normal in 8 patients (33%). All 27 tumors shrank during sc Oct; for microadenomas the median tumor volume reduction was 49% (range, 12-73), and for macroadenomas it was 43% (range, 6-92). After 24 wk of Oct-LAR (end of phase 2), the GH level was less than 5 mU/liter in 11 of 14 patients (79%), and IGF-I was normal in 8 of 15 patients (53%). In the 15 patients given Oct-LAR (10 macroadenomas), wk 48 scans showed a further overall median tumor volume reduction of 24%. At the end of the study 79% of patients had mean serum GH levels below 5 mU/liter, 53% had normal IGF-I levels, and 73% showed greater than 30% tumor shrinkage. Twenty-nine percent of patients achieved all 3 targets, but no patient with pretreatment GH levels above 50 mU/liter did so at any stage of the study. Primary medical therapy with Oct offers the prospect of normalization of GH/IGF-I levels together with substantial tumor shrinkage in a significant subset of acromegalic patients. This is most likely to occur in patients with pretreatment GH levels less than 50 mU/liter (20 microg/liter).

Acromegaly↗
PubMed2000

Cushing's syndrome due to phaeochromocytoma secreting the precursors of adrenocorticotropin.

Adrenal phaeochromocytoma rarely causes ectopic ACTH syndrome. We describe a 44-yr-old hypertensive woman who was Cushingoid and markedly pigmented. Laboratory studies indicated severe hypokalaemia, abnormal liver function tests, and random serum cortisols greater than 1660 nmol/L. Urinary catecholamines were markedly increased. An abdominal computed tomography scan showed a 4-cm left adrenal mass and an hypertrophied right adrenal. ACTH levels were elevated at 200 pmol/L, but ACTH precursors, which cross-react in the ACTH assay, were more highly elevated at 1625 pmol/L. The tumor cells cultured in vitro also secreted ACTH precursors, whereas ACTH levels were undetectable. Because the patient was highly pigmented, we measured circulating concentrations of alpha-MSH, which were undetectable and certainly insufficient to stimulate melanogenesis, suggesting that tumorderived ACTH precursors or ACTH were responsible for the pigmentation. A laparoscopic adrenalectomy resulted in remission of the Cushing's syndrome and dramatic reduction in the pigmentation. Before operation, treatment of the patient with metyrapone and replacement dexamethasone decreased cortisol from more than 1660 to less than 20 nmol/L. Surprisingly, this resulted in a decrease in ACTH precursors to 100 pmol/L and ACTH to 9.0 pmol/L. In vitro treatment of the tumor cells with dexamethasone for 24 or 40 h increased ACTH precursor secretion. In summary, this phaeochromocytoma causing Cushing's syndrome secreted primarily ACTH precursors, which seemed to cause the marked pigmentation. In vivo and in vitro evidence suggests that glucocorticoids induced ACTH precursor secretion.

Adrenal Gland Neoplasms↗
PubMed1999

The therapeutic value of somatostatin and its analogues.

In this review we discuss the physiological effects of somatostatin, which are mediated by specific receptor subtypes on different tissues. These observations have suggested new therapeutic possibilities for the use of the synthetic somatostatin analogues in the treatment of acromegaly as well as a number of other endocrine and non-endocrine disorders.

Acromegaly↗
PubMed1999

Comparison of monthly intramuscular injections of Sandostatin LAR with multiple subcutaneous injections of octreotide in the treatment of acromegaly; effects on growth hormone and other markers of growth hormone secretion.

OBJECTIVE: To compare the effects of monthly intra-muscular injections of a long acting preparation of octreotide, Sandostatin LAR, with multiple daily subcutaneous injections of octreotide and to study the interrelationships between mean 24 h growth hormone profile, serum total and free IGF-1 levels, 24 h urinary growth hormone levels and serum IGFBP-3. DESIGN: Patients were assessed by 24 h GH profile off octreotide or any other GH modifying drug therapy; on subcutaneous octreotide (200-600 micrograms daily in divided doses for six weeks); and 28 days after the second of two injections of Sandostatin LAR (20 mg by intra-muscular injection) administered 28 days apart. Serum total and free IGF-1, serum IGFBP-3 and 24 h urinary GH were also measured on each occasion. RESULTS: Sandostatin LAR was well tolerated. None of the patients reported any adverse effect and all completed the study uneventfully. Mean GH off treatment was 10.1 +/- 3.0 micrograms/l falling equally significantly (P < 0.05) during therapy with subcutaneous octreotide to 3.0 +/- 0.7 micrograms/l and Sandostatin LAR to 2.8 +/- 0.7 micrograms/l. Fasting 0900 h GH was significantly reduced (P < 0.05) on Sandostatin LAR (3.0 +/- 0.7 micrograms/l) compared with subcutaneous octreotide (5.1 +/- 1.2 micrograms/l). Mean total IGF-1 off treatment was 658.6 +/- 56.1 micrograms/l and was reduced to a comparable extent with subcutaneous octreotide and Sandostatin LAR (466.0 +/- 59.7 and 448.6 +/- 59.5 micrograms/l respectively; both P < 0.05). Free IGF-1 off treatment was 3.1 +/- 0.6 micrograms/l and was reduced equally by subcutaneous octreotide and Sandostatin LAR (1.2 +/- 0.2 and 1.2 +/- 0.2 micrograms/l; both P < 0.05). IGFBP-3 was reduced to a greater extent during Sandostatin LAR than during subcutaneous octreotide (4518.2 +/- 247.3 vs 5132.8 +/- 280.7 micrograms/l; P < 0.05). Twenty-four hour urinary GH excretion was reduced to a comparable extent with both therapies. Highly significant positive correlations were found between mean 24 h GH levels and free IGF-1 (r = 0.66, P < 0.0001) and 24 h urinary GH excretion (r = 0.94, P < 0.0001). The relationships between mean 24 h GH levels and total IGF-1 and IGFBP-3 although significant showed less powerful correlations. CONCLUSIONS: These results suggest that Sandostatin LAR is well tolerated and as effective as subcutaneous octreotide. In addition, urinary growth hormone and serum free IGF-1 may prove valuable for outpatient follow-up of acromegalic patients, as both correlate well with mean 24 h serum growth hormone levels.

Acromegaly↗
PubMed1998

Radioiodine treatment in unsuspected pregnancy.

OBJECTIVE: Radioiodine is being used increasingly as first line therapy for hyperthyroidism. Our aim is to highlight some of the difficulties which can occur following the use of 131I to treat hyperthyroidism in fertile women. PATIENTS: We present 3 cases of young women to whom radioiodine was given, only to find some weeks later that they had been pregnant at the time of treatment. CONCLUSIONS: These cases serve as a reminder of the importance of obtaining an accurate and full menstrual and contraceptive history. Guidelines advocate the application of the ten day rule with the further recommendation that pregnancy testing may be undertaken as an alternative.

Adult↗
PubMed1997

Treatment of macroprolactinoma with cabergoline: a study of 85 patients.

OBJECTIVE: Cabergoline is now established as an effective and well-tolerated treatment for prolactinoma. However, there are relatively few published data on the treatment of macro-, as opposed to micro-, prolactinoma. We have therefore reviewed the efficiency and safety of cabergoline in the treatment of patients with prolactin-secreting macroadenomas treated on a compassionate basis. STUDY DESIGN AND PATIENTS: Eighty-five patients with prolactin-secreting macroadenomas were treated with cabergoline 0.25 to 10.5 mg per week (median 1 mg) given to one to seven doses. Treatment durations ranged between 3 months and 8 years. Sixty-five patients (32 intolerant, 16 resistant) had been treated previously with other dopamine agonists. Pretreatment prolactin levels ranged between 80 and 8300 micrograms/I and tumour maximum diameters were between 11 and 42 mm. MEASUREMENTS: Serum prolactin, visual fields if initially abnormal, occurrence of menses or return of libido and potency, blood chemistry and adverse events were assessed at 1 month and then at 3-month intervals during treatment. Pituitary computed tomography or magnetic resonance imaging was usually repeated at 3 months and 1 year, then yearly, in most patients (n = 62). RESULTS: Normalization of prolactin levels was achieved in 52 patients (61.2%) and a prolactin decrease of at least 75% of pretreatment values occurred in 24 others (28.2%). Of the 20 de novo patients, 17 had prolactin normalized and the remainder had at least 75% reduction. Disappearance of tumour image was found in eight of 62 evaluable patients (12.9%) and reduction of the largest diameter by at least 25% in another 33 (53.2%), with an overall success rate of 66.1%; among the 17 evaluable de novo patients the success rate was 82.3%. Fifteen of 21 patients who failed to show tumour shrinkage had previously demonstrated resistance/intolerance to other prolactin-lowering treatments. Of the 12 patients with visual field defects at baseline, six normalized and two showed an improvement. Menses resumed during cabergoline treatment in 79.5% of premenopausal women. Restoration of potency was reported by seven of eight evaluable men. Adverse events were recorded in 24.7% of cases, four of whom (4.7%) discontinued treatment. CONCLUSIONS: Although the present data were not obtained in a formal study we conclude that cabergoline is an effective and well-tolerated treatment for macroprolactinoma patients.

Adolescent↗
PubMed1997

An audit of the diagnostic usefulness of PRL and TSH responses to domperidone and high resolution magnetic resonance imaging of the pituitary in the evaluation of hyperprolactinaemia.

BACKGROUND AND OBJECTIVE: The usefulness of dynamic tests of PRL release in determining underlying pathology in hyperprolactinaemic patients is not well recognized by endocrinologists, only 15% of whom routinely perform such tests. High resolution pituitary magnetic resonance imaging (MRI) has become more widely available during the past 5 years and is now generally regarded as the pituitary imaging method of choice. Since few prolactinoma patients are now submitted to surgery, it is important to ascertain the usefulness of these techniques in suggesting a pathological diagnosis. DESIGN: A 3 year retrospective audit of the information derived from measurement of PRL and TSH responses to the dopamine antagonist domperidone and from high resolution pituitary MRI in patients being investigated for hyperprolactinemia in regional endocrine unit. PATIENTS: Eighty-four patients (10 male, 74 female) whose investigation of hyperprolactinaemia included a domperidone test and high resolution pituitary MRI. Patients who had domperidone tests performed after pituitary surgery or who did not have pituitary MRI were excluded from the analysis. MEASUREMENTS: PRL and TSH were measured basally and at 30 and 60 minutes following domperidone (10 mg i.v.) and gadolinium-enhanced pituitary MRI was performed in all patients. RESULTS: 20 patients had a normal PRL response to domperidone (defined as PRL30/PRL0 > 3) and this group included five patients in whom hyperprolactinaemia was not sustained. Pituitary MRI showed evidence of a microadenoma in only two patients, imaging being unequivocally normal in the majority. Sixty-four patients had an abnormal PRL response to domperidone and 18 of these had a macrolesion (nine prolactinomas, nine other tumours). Pituitary MRI was performed in the remaining 46 patients with abnormal PRL response to domperidone and suggested microadenoma in 29 (63%), identified other structural abnormalities in six cases but was entirely normal in 11 cases. Neither the basal PRL level nor the TSH response could refine the diagnosis further because of overlap between the various subgroups. CONCLUSIONS: The majority of patients with a normal dynamic response of PRL to domperidone had a normal or near normal pituitary MRI scan. In the two cases where an abnormality was detected it could have been an incidental microadenoma or cyst, thus suggesting that pituitary scanning could normally be omitted in patients whose PRL response to domperidone is normal (24% of our total). The group of patients with an abnormal dynamic response of PRL to domperidone was not generally amenable to further diagnostic refinement by considering the degree of hyperprolactinaemia or the TSH response to domperidone because of overlap of these parameters between the diagnostic subgroups. Therefore any degree of hyperprolactinaemia associated with a blunted PRL response to domperidone warrants pituitary imaging.

Adolescent↗
PubMed1997

The Australian Study of HIV and Injecting Drug Use. Part I: prevalence for HIV, hepatitis B and hepatitis C among injecting drug users in four Australian cities.

The objective of this study was to assess differences in HIV, hepatitis B and hepatitis C seroprevalence among injecting drug users (IDU) in four Australian cities. Eight hundred and seventh-two current IDU were recruited in approximately equal numbers from each of Adelaide, Melbourne, Perth and Sydney, and interviewed individually using a structured questionnaire. Fingerprick blood samples were taken from the majority of respondents, and tested for past exposure to the three viruses. HIV and hepatitis B and C raw seroprevalences were compared across cities, and comparisons were made of age-standardized seroprevalences for hepatitis B and C. Three percent of all respondents were HIV seropositive; 19% (23% age-standardized) were hepatitis B seropositive and 55% (60% age-standarized) were hepatitis C seropositive. There were general city differences and gender, sexual preference and treatment status group differences between the cities. Sydney respondents had the highest risk of infection for all three viruses in all comparisons. This was particularly striking for HIV among non-heterosexual men. Various explanations for the findings were considered, including city differences in demographic and drug use variables, underlying patterns of risk behaviour, and period/cohort effects. It was concluded that none of these explanations appeared to fit the pattern of findings, and that these probably represented true underlying differences in size of pools of infection. The reasons for this, however, cannot be ascertained from this study.

Journal Article↗
PubMed1997

The Australian study of HIV and injecting Drug Use. Part II: predicting exposure to hepatitis C and hepatitis B.

Researchers agree that while hepatitis B maybe in control, hepatitis C is present in epidemic proportions among injecting drug users and that current HIV prevention strategies have not been sufficient to halt the spread of this hepatitis virus, although there is some evidence to suggest that incidence rates are stabilizing. Since there is no effective cure and it is unlikely that a vaccine will become available in the foreseeable future all efforts to control the spread of hepatitis C must rely on education and prevention strategies. The Australian Study of HIV and Injecting Drug Use is a cross-sectional national study designed to investigate exposure to and risks for infection with bloodborne viruses. Of those volunteering a usable blood sample for hepatitis C antibody and hepatitis B core antibody testing 55% and 19%, respectively, returned reactive test results. Logistic regression statistical models were used to identify risk factors for hepatitis C and hepatitis B. Risk factors for hepatitis C were identified as duration of use, use of opiates on last injecting occasion, education level, treatment status and having a history of sexually transmissible diseases. Risk factors associated with hepatitis B were duration of use, and use of opiates on last injecting occasion. The lack of identifiable risk factors for hepatitis B suggest that past rather than current injecting and sexual behaviour patterns are required to predict accurately risk of exposure to hepatitis B. In addition to this, one-third of respondents reported being vaccinated against hepatitis B. Respondents perceived themselves to be at greater risk from hepatitis C than from hepatitis B or HIV. A discussion of strategies needed to prevent the spread of the hepatitis viruses will be presented along with recommendations for further research.

Journal Article↗
PubMed1996

Structure of the thyrotrophin-releasing hormone receptor in human pituitary adenomas.

BACKGROUND AND OBJECTIVE: TRH acts on specific G-protein coupled receptors sited in cells of the anterior pituitary gland. Pituitary tumours expressing either TSH, PRL or GH may respond to TRH by enhanced, blunted or paradoxical hormone release. Non-functioning pituitary tumours may also show abnormal responses to TRH. Little is understood of the mechanisms regulating inappropriate hormone release in these tumours. Activating or inactivating mutations found in G-protein coupled receptors have been implicated in human pathological conditions. Mutations in the G-protein coupled TRH receptor might be involved in the aetiology of pituitary adenomas resulting in aberrant hormone secretion. We therefore screened samples of pituitary adenomas for the presence of somatic mutations in the TRH receptor gene. PATIENTS: Pituitary adenoma tissue samples were obtained at surgery from 50 patients with pituitary adenoma (17 acromegaly, 15 prolactinoma, 11 TSH-secreting and 7 non-functioning adenoma) along with blood samples to provide lymphocyte DNA as control sequence. METHODS: Genomic DNA was extracted from adenoma and lymphocyte samples and the entire coding region of the TRH receptor was amplified using 5 overlapping pairs of PCR primers. The PCR products were analysed for mutations by non-denaturing polyacrylamide gel electrophoresis which reveals single-strand conformational polymorphisms (SSCP) as a mobility shift in product migration. Wild-type and mutant TRH receptor cDNA were similarly analysed to confirm the sensitivity of the method. Additionally, PCR products were ligated into a PCR cloning vector and DNA sequencing carried out to confirm the findings of SSCP analysis. RESULTS: The human TRH receptor retained normal wild-type sequence in the large group of TSH secreting, PRL secreting, GH secreting and non-functioning pituitary adenomas investigated in this study. CONCLUSION: Our observations suggest that the TRH receptor structure is normal in TSH secreting, PRL secreting, GH secreting and non-functioning pituitary adenomas. It is therefore unlikely that the TRH receptor is involved in the pathology associated with the types of pituitary adenomas investigated in this study. It is possible that some other component of the pathway controlling TRH-signalling events may be implicated in pituitary tumorigenesis.

Acromegaly↗
PubMed1996

Laparoscopic trans-peritoneal adrenalectomy: a preliminary report of 14 adrenalectomies.

OBJECTIVES: Laparoscopic adrenalectomy offers the potential benefits of a smaller operation with more rapid hospital discharge, compared to open surgery. Only a few small series have been reported so far. We describe our preliminary experience of 14 adrenalectomies using this new technique. DESIGN: Review of all adrenalectomies (with the preoperative intention of laparoscopic removal) performed in an endocrine unit whose surgeon already had abdominal laparoscopic experience, particularly with cholecystectomy. PATIENTS AND MEASUREMENTS: Twelve patients (3 with Conn's syndrome, 3 Cushing's syndrome, 1 Cushing's disease, 2 phaeochromocytomas and 3 adrenal incidentalomas) were operated between September 1993 and February 1996. Operating times, operative technique, time from surgery to discharge, outcome and all complications were recorded prospectively. Comparative data were obtained from 14 consecutive open adrenalectomies performed by the same surgeon between February 1989 and February 1995. RESULTS: Fourteen glands were removed, two with a cholecystectomy, in 12 operations. Operating time (mean (range) 120 (60-225) min) was reduced with experience. Positioning the patient in the right lateral position facilitated left adrenalectomy. Time to discharge (mean (range)) was 5.3 (1-12) days. There were relatively minor complications in three patients, including two with Cushing's syndrome: a hernia at a port site, intra-peritoneal/wound haemorrhage and a pressure sore. Time to discharge for open adrenalectomy (mean (range)) was 6.5 (2-11) days and one case was complicated by wound infection. CONCLUSIONS: Laparoscopic adrenalectomy is a practical technique for appropriately trained surgeons who regularly undertake adrenalectomy. The smaller incisions offer potential advantages, particularly for patients with poor tissue quality due to Cushing's syndrome, but tissue haemorrhage may still be a problem in these patients. Time to hospital discharge was similar to that for open surgery.

Adenoma↗