Familial partial lipodystrophy associated with compound heterozygosity for novel mutations in the LMNA gene.
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Adult↗
Biomedical subjects
P E Belchetz
Publications and source records attributed to P E Belchetz.
Lesson of the week: unsuspected central hypothyroidism.
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Adult↗
Effect of photodynamic therapy on recurrent pituitary adenomas: clinical phase I/II trial--an early report.
Pituitary adenomas, although histologically benign, are not always curable by surgery alone, principally because of dural infiltration, as well as their peculiar anatomical location. Radiotherapy has been employed as an adjuvant therapy to address residual disease with favourable results. This approach is, however, not without side effects, and it cannot be repeated. We are therefore investigating the effectiveness of photodynamic therapy (PDT) on recurrent pituitary adenomas in humans. This study details the protocol applied to 12 patients with recurrent pituitary adenomas, which involved systemic administration of photosensitizer (Photofrin) followed, after a period of 24-48 h, by intraoperative illumination of the tumour bed using 630 nm laser light. The primary end points were visual, endocrine and radiological improvement. The incidence of side effects was also monitored. The longest follow-up is 2 years. Most patients suffering from visual acuity or field defects have shown improvement when followed for 12 months or more. Three patients showed complete recovery of their visual fields. All those who presented with functional adenomas have shown reduction in their hormone levels. Tumour volume, relative to the preoperative size, was 122, 87, 66, 60 and 46% at 4 days, and 3, 6, 18 and 24 months, respectively. One patient developed severe skin photosensitization due to early exposure to direct sunlight and three others displayed minor skin reactions. There was no treatment-related mortality or morbidity. One patient (operated transcranially) developed hemiparesis postoperatively, which recovered completely. We think this is unrelated to the treatment. This prospective study demonstrates that PDT may be safely applied to the pituitary fossa by the trans-sphenoidal route and indicates the need for a randomized, controlled trial in order to establish its therapeutic potential.
Adenoma↗
Commentary: hypoadrenalism should also be considered in cases of persistent hyponatraemia.
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Adrenal Cortex Diseases↗
Cognitive dysfunction in patients with pituitary tumour who have been treated with transfrontal or transsphenoidal surgery or medication.
OBJECTIVE: This study was carried out to examine the neuropsychological status of patients treated for pituitary tumour by transfrontal surgery, transphenoidal surgery or medical treatment only, with or without radiotherapy. DESIGN AND MEASUREMENTS: Three groups of 23 patients who had been treated for pituitary tumour were compared with 23 healthy controls on a range of neuropsychological measures. The surgical patients were also subdivided into two groups and compared. The neuropsychological measures were standardized psychological tests designed to assess aspects of attention, memory and executive function. PATIENTS: The patients were those who had been treated with transfrontal surgery (n = 23), transsphenoidal surgery (n = 23) and medication only (n = 23). The groups did not differ with respect to age, education or premorbid ability level as assessed by the National Adult Reading Test. All participants were free of known sources of cognitive impairment other than pituitary tumour. RESULTS: Comparison of the four groups revealed that nearly half of the transfrontal, one-third of the transsphenoidal and one-quarter of the non-surgical group had three or more neuropsychological tests scores below the 10th percentile compared to less than 5% of the controls. Impairments in memory and executive function were found in both surgical groups. The non-surgical patients appeared to have problems only on tasks requiring high levels of cognitive processing. Differences were found between the two surgical groups with respect to the severity of the cognitive impairment, the transfrontal patients having more severe impairment than the transsphenoidal. No significant negative effects on cognitive functioning were associated with radiotherapy; however, transfrontal surgery patients who had not been treated with radiotherapy were found to be more impaired than other patients. This was thought to be related to radical surgery. CONCLUSIONS: Many patients with treated pituitary tumour suffer significant cognitive impairment. The severity and nature of impairment differs between treatment groups, although the cause of this could not be addressed by this study. Recommendations are made for future research and clinical practice.
Adult↗
Mortality and cancer incidence in acromegaly: a retrospective cohort study. United Kingdom Acromegaly Study Group.
Patients with acromegaly have a reduced life expectancy, with the accepted causes for premature death being vascular and respiratory disease. Increased mortality from malignant disease has also been reported. We, therefore, performed a multicenter retrospective cohort study of 1362 patients with acromegaly and investigated the relationships of mortality and cancer incidence with GH levels, duration of disease, and age at diagnosis. The overall cancer incidence rate [standardized incidence ratio, 0.76; 95% confidence interval (CI), 0.60-0.95] was lower than that in the general population of the United Kingdom, and there was no significant increase in site-specific cancer incidence rates. The overall cancer mortality rate was not increased, but the colon cancer mortality rate (standardized mortality ratio, 2.47; 95% CI, 1.31-4.22) was higher than expected. Mortality rates due to colon cancer, all malignant disease, cardiovascular disease and overall mortality were increased with higher posttreatment GH levels (P for trends, <0.02, <0.05, <0.02, and <0.0001). The overall mortality rate in patients with acromegaly with posttreatment GH levels less than 2.5 ng/mL (5 mU/L) was comparable to that in the general population of the United Kingdom (standardized mortality ratio, 1.10; 95% CI, 0.89-1.35). We conclude that high posttreatment GH levels are associated with an increased overall mortality rate and increased mortality rates due to colon cancer, cardiovascular disease, and all malignant disease. Posttreatment GH levels less than 2.5 ng/mL (5 mU/L) result in an overall mortality rate similar to that in the general population.
Acromegaly↗
Bilateral sequential inferior petrosal sinus sampling with corticotrophin-releasing hormone stimulation in the diagnosis of Cushing's disease.
OBJECTIVE: The demonstration of a central to peripheral ACTH gradient in a hypercortisolaemic patient is diagnostic of Cushing's disease. We tried to determine whether single blood samples for ACTH obtained sequentially from each of the inferior petrosal sinuses following human corticotrophin-releasing hormone (hCRH) stimulation can reliably establish such a gradient. DESIGN: Prospective study. PATIENTS: Seventeen patients with clinical and biochemical features of Cushing's syndrome. METHODS: After the administration of hCRH, the patients underwent bilateral sequential inferior petrosal sinus sampling, with a single blood sample obtained from each of the inferior petrosal sinuses sequentially, along with a peripheral venous sample. The petrosal sinus catheter was withdrawn immediately after obtaining a blood sample. Patients did not require indwelling catheters in the petrosal sinuses, nor heparinisation. RESULTS: Bilateral sequential inferior petrosal sinus sampling correctly identified a pituitary source of ACTH, as shown by a central to peripheral ACTH ratio >2, in all patients in whom the procedure was successfully carried out. All patients underwent transsphenoidal pituitary surgery resulting in remission. CONCLUSIONS: The simplified method of inferior petrosal sinus sampling, using a single sequential sample from each of the inferior petrosal sinuses, following initial hCRH stimulation, is as accurate as the more complex test using multiple bilateral simultaneous inferior petrosal sinus samples. It avoids the use of indwelling cerebral venous catheters and is therefore unlikely to cause brain stem damage.
Adult↗
Ovarian hyperthecosis, diabetes and hirsuties in post-menopausal women.
OBJECTIVE: We describe four patients with ovarian hyperthecosis and the effects of gonadotrophin releasing hormone on clinical and metabolic variables. DESIGN: Open out-patient study. PATIENTS: Four women presented with post-menopausal hirsuties. They had significant hair growth across the chest, upper back and shoulders. Three had histologically proven ovarian hyperthecosis and a fourth had large ovaries visualized on ultrasound. All four women had pronounced risk factors for vascular disease; hypertension, hyperlipidaemia and glucose intolerance, and three had already developed symptomatic vascular disease. RESULTS: Gonadotrophin releasing hormone agonist therapy resulted in significant reduction in plasma androgens and cosmetic reduction in hair growth but had no effect on hyperlipidaemia. CONCLUSION: The post-menopausal women described in this report were clinically considered to have hyperandrogenism due to the pathological pattern of marked body hair over the upper trunk. Treatment with GnRH was very effective at reducing the severity of the hirsuties. The post-menopausal women with hyperthecosis in this report had a high prevalence of cardiovascular disease. Since hyperandrogenism and insulin are considered risk factors for cardiovascular disease in premenopausal women with polycystic ovaries, we discuss the possible relationship between insulin and the post-menopausal ovary.
Aged↗
The effect of treatment variables on mood and social adjustment in adult patients with pituitary disease.
OBJECTIVE: Studies of mood in hypopituitary adults have yielded inconsistent results. This investigation was carried out to investigate whether treatment characteristics may be responsible for the inconsistent results. DESIGN AND MEASUREMENTS: We compared three groups of patients with a group of matched healthy controls on self-report measures of mood and social adjustment (Beck depression inventory, State-trait anxiety inventory, Social adjustment scale (modified)) and a measure of quality of life (Nottingham health profile, NHP). PATIENTS: The patient groups were those treated with transfrontal surgery (n = 23), transsphenoidal surgery (n = 23) or medication only (n = 23). In addition, a close informant of each subject was asked to complete a social adjustment measure about the subject's level of adjustment. RESULTS: On the self-report mood and social adjustment measures and the emotion sub-scale of the NHP, the transsphenoidal and medication patient groups rated themselves as being more depressed, anxious and having poorer social adjustment than the transfrontal or control groups. The close informants, however, rated all three patient groups as having poorer social adjustment than the controls. Patients treated with surgery and without radiotherapy reported fewer symptoms of depression than those treated with radiotherapy. Realistic self-appraisal of social adjustment in surgical patients was found only in those treated with transsphenoidal surgery without radiotherapy. CONCLUSIONS: Patients treated for pituitary tumour, excepting those treated with transfrontal surgery and to a lesser extent those treated with radiotherapy, suffer from mild mood disturbance and self-perceived decreased social adjustment. All patient groups are seen by others as having decreased social adjustment, raising the possibility that the transfrontal patients and possibly those who have had radiotherapy, lack insight. This may explain some of the discrepancies in the previous literature and needs to be taken into account when using self-report measures with these patients.
Adenoma↗
Cognitive dysfunction in patients treated for pituitary tumours.
Assessment of neuropsychological status and mood was carried out on 36 patients who had been treated for pituitary tumour and on 36 healthy controls. Impairments in memory and executive function were exhibited by the patients even when other known causes of cognitive dysfunction had been excluded. There was no difference in mood between the two groups, and the deficits in cognitive dysfunction were not related to mood disturbance or to the effects of radiotherapy. The defects were however, related to the presence of surgery, although not to the type of surgery. Reasons for the cognitive dysfunction are unclear but are likely to be multifactorial possibly including the effects of neurosurgery and/or hormone imbalance resulting from pituitary surgery.
Adult↗
Comparison of tests of stress-released cortisol secretion in pituitary disease.
OBJECTIVES: We wished to compare peak and incremental rise in plasma cortisol in response to insulin induced hypoglycaemia (IIH) stress test, i.m. glucagon stimulation test (IMGST) and short Synacthen test (SST) in patients with pituitary disease, using a modern radioimmunoassay for cortisol. We compared the three stimulants using receiver operator characteristic (ROC) plots, assuming a cortisol threshold of 500 nmol/l or 580 nmol/l for the IIH stress test which we used as the standard from which to evaluate the SST and the IMGST. PATIENTS AND DESIGN: We prospectively studied 16 patients (8F, 8M mean age 43.69 +/- 3.72 years) admitted to the investigation ward for IIH stress test and who were asked to undergo two additional tests (IMGST and SST) on consecutive days. MEASUREMENTS: We measured serum cortisol at baseline, 30, 45, 60, 90 and 120 minutes during the IIH stress test; baseline, 150 and 180 minutes during GST, and baseline and 30 minutes during the SST. RESULTS: There was a significant rise in cortisol from baseline in all tests (P < 0.001). There was no significant difference among the peak plasma cortisol responses or the incremental rises in plasma cortisol following IMGST, SST and IIH stress test (repeated measures ANOVA F = 0.704, P = 0.503; F = 0.238, P = 0.79). The ROC plots clearly showed that the SST has poor diagnostic utility at both IIH thresholds, compared with the IMGST. CONCLUSION: The peaks and incremental rises in cortisol following all three tests are comparable. Using the insulin induced hypoglycaemia stress test as a reference and peak cortisol thresholds of 500 and 580 nmol/l as discriminating variables, the short Synacthen displayed poor diagnostic utility when compared to the i.m. glucagon stimulation test. The short Synacthen may be misleading if used as a screening test as advocated by a number of authors.
Adult↗
Development of acromegaly during treatment of hyperprolactinemia with bromocriptine: an unusual acidophil stem cell adenoma.
We present clinical details of a patient with a 20-yr history of amennorhea, a pituitary tumor, elevated PRL levels, and initially undetectable GH. Bromocriptine failed to fully suppress PRL, and there was no tumor shrinkage. Within 7 months of starting bromocriptine treatment, the patient developed clinical and biochemical signs of acromegaly. At surgery, a stem cell adenoma was excised. The mechanisms by which bromocriptine may have resulted in the development of acromegaly in this patient are discussed.
Acromegaly↗
Octreotide treatment increases exercise capacity in patients with acromegaly.
This prospective study was conducted to determine the effect of Octreotide treatment on cardiovascular function in patients with active acromegaly. Ten acromegalic patients who failed to suppress growth hormone (GH) to < 5 mU/l during a 2 h oral glucose tolerance test were treated with 100 micrograms of Octreotide subcutaneously three times daily for 2 months, followed by 200 micrograms three times daily if the mean GH level was > 5 mU/l, for a total of 1 year. All patients had GH and insulin-like growth factor I (IGF-I) estimation, ejection fraction determined by Echocardiogram and multigated image acquisition scan, electrocardiogram (ECG), exercise ECG, 24-h ECG and chest x-ray. At 6 and 12 months, both GH and IGF-I were reduced but ECG, heart size and ejection fraction were unchanged. The patients improved symptomatically and had significant reduction in resting heart rate and increase in weight. Exercise time (mean +/- SD) increased from 637 +/- 137s at baseline to 787 +/- 101s at 1 year (p < 0.01) and work done increased from 9 +/- 3.3 to 11.9 +/- 2.7 metabolic equivalents (p < 0.001). We conclude that the decrease in GH and IGF-I following Octreotide treatment of acromegaly is accompanied by decreased heart rate and increased exercise capacity despite an unchanged ejection fraction.
Acromegaly↗
Hormonal treatment of postmenopausal women.
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Breast Neoplasms↗
Gynaecomastia caused by a primary mediastinal seminoma.
The case of a young man aged 26 is reported. He presented with a short history of painful gynaecomastia, and no other associated symptoms. Radiological investigations showed a mass in the anterior mediastinum. Endocrine investigations showed high circulating oestradiol and high hCG-beta levels. There was no evidence of primary testicular tumour or metastases. Surgical removal of the mediastinal mass led to normalization of oestradiol and hCG-beta levels and regression of gynaecomastia. Histology showed the tumour to be a primary mediastinal seminoma staining positively for hCG-beta. Further treatment consisted of chemotherapy with etoposide and cis-platinum. The patient has remained well with no evidence of disease recurrence. The tumour markers remain normal.
Adult↗
Comparison of changes in bone mineral in idiopathic and secondary osteoporosis following therapy with cyclical disodium etidronate and high dose calcium supplementation.
OBJECTIVE: Our clinical practice has been to offer treatment with cyclical disodium etidronate and high dose calcium supplements (1500-1600 mg/day) to all female patients with osteoporosis who are unable or unwilling to take hormone replacement therapy (HRT), and male osteoporotics. In a retrospective study we compared the effect of this treatment on measures of bone mineral over a 12-month period in women with post-menopausal and secondary osteoporosis. We also assessed its effects in 10 male osteoporotics. DESIGN: A retrospective analysis of 83 consecutive patients with osteoporosis who completed 12 months of treatment with disodium etidronate and calcium and who had a dual energy X-ray absorptiometry (DEXA) scan at baseline and following 12 months of therapy. PATIENTS: The study included 73 women (45 post-menopausal and 28 secondary osteoporotics) and 10 men with established osteoporosis as shown by spinal and femoral bone mineral densities (BMD) > 2 standard deviations (SD) below young normals, and radiological evidence of osteoporosis. MEASUREMENTS: Each patient had routine biochemistry at baseline, an X-ray of thoracic and lumbar spine and a DEXA scan of lumbar spine (L2-L4) and femoral neck. The DEXA scan was repeated following 12 months of therapy. RESULTS: There was no difference between increase in spinal BMD in the post-menopausal (5.7%) versus secondary osteoporotic group (6.7%). There was a significant increase in spinal BMD at 12 months in the 10 male osteoporotics (9.0%, P < 0.01). No overall change in femoral neck BMD was noted. CONCLUSIONS: Cyclical disodium etidronate given with high dose calcium supplements is equally effective in increasing spinal bone mineral density in post-menopausal and secondary osteoporosis. It also results in a significant rise in spinal bone mineral density in male osteoporotics. Whether this produces a reduction in fracture rates is unknown.
Bone Density↗
Is a low skinfold thickness an indicator of osteoporosis?
OBJECTIVE: The association between thin skin and osteoporosis has been known for some years. We wished to assess a simple measure of skinfold thickness (SFT) as a screening test for osteoporosis and to study the effect of chronological and menopausal age on SFT in a group of osteoporotic women and normal controls. DESIGN: A case control study of 225 consecutive women who attended an osteoporosis clinic. PATIENTS: We studied 225 women, 141 with osteoporosis (mean age 61.8 +/- 10.5 years) and 65 normal controls (mean age 59.9 +/- 8.8 years), with 19 exclusions. METHODS: Each patient had routine biochemistry, spinal X-rays and a dual-energy X-ray absorptiometry (DEXA) scan of lumbar spine and femoral neck. In addition they had skinfold thickness measured by a single observer using Holtain Tanner Whitehouse callipers over the 4th metacarpal of the right hand. RESULTS: Mean skinfold thickness was lower in the osteoporotic group, 1.6 +/- 0.4 mm compared to normals 1.8 +/- 0.3 mm (P < 0.0001). SFT did not decline significantly with chronological or menopausal age in the normals (correlation coefficients r = -0.06, r = -0.09) in contrast to the osteoporotic group (correlation coefficients r = -0.52, P < 0.001; r = -0.27, P < 0.0001). Subjects with a SFT of < or = 1.5 mm had a higher probability of osteoporosis (odds ratio 3.12, 95% confidence interval 1.58-6.14). Subjects with a SFT of > or = 2.1 mm had a lower probability of osteoporosis (odds ratio 0.305, 95% confidence interval 0.126-0.740). CONCLUSION: Our results demonstrate a lower mean SFT in osteoporotic compared with normal women, with a negative correlation between SFT and chronological and menopausal age in osteoporotics, but not in normal controls. A low skinfold thickness appears to be an indicator of developing osteoporosis and a high SFT may indicate a normal bone mass.
Aged↗
The effects of insulin-like growth factor-1 on plasminogen activator inhibitor-1 synthesis and secretion: results from in vitro and in vivo studies.
In vitro studies have shown that insulin and IGF-1 releases the fibrinolytic inhibitor plasminogen activator inhibitor-1 (PAI-1) from cells of hepatic origin. To investigate the effects of IGF-1 on fibrinolysis: 1) cultured hepatoma cells were grown in the presence of IGF-1 and media collected for secreted PAI-1 and cells probed for PAI-1 mRNA, 2) 8 hypopituitary patients were treated with recombinant human growth hormone (rhGH) and 3) 5 type 2 diabetic patients were treated with recombinant human IGF-1 (rhIGF-1). Treatment of Hep G2 cells with IGF-1 (1000 ng/ml) increased secretion of PAI-1 from a median value of 80 ng/10(6) cells (range 21-91) to 144 ng/10(6) cells (range 128-169) after 24 h (p < 0.01). Synthesis of PAI-1 mRNA increased in a similar fashion. Treatment of hypopituitary patients with rhGH led to an increase in circulating IGF-1 from a mean value of 166 (range 41-324) ng/ml at baseline to 322 (77-575) ng/ml at 4 weeks and 259 (104-533) ng/ml after 8 weeks (p < 0.02). Despite this, no changes in circulating PAI-1 or fibrinolysis occurred. Type II diabetic patients treated with rhIGF-1 showed an increase in circulating IGF-1 from a mean value of 120 ng/ml (range 109-196), at baseline to 823 ng/ml (585-894) after 5 days. This also was not associated with changes in circulating PAI-1 or in fibrinolysis. The results confirm that IGF-1 induces the synthesis of PAI-1 in Hep G2 cells.(ABSTRACT TRUNCATED AT 250 WORDS)
Diabetes Mellitus, Type 2↗