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Biomedical subjects

A B Atkinson

Publications and source records attributed to A B Atkinson.

At least 109 records · Page 6Linked to original sources
PubMed1990

The effect of cyproheptadine and/or bromocriptine on plasma ACTH levels in patients cured of Cushing's disease by bilateral adrenalectomy.

Cyproheptadine and bromocriptine have been reported to be therapeutic in suppressing ACTH levels in Cushing's disease and Nelson's syndrome. However, there have been only scattered reports of their effect in suppressing raised ACTH levels found in patients cured of Cushing's disease by bilateral adrenalectomy. In order to assess whether these agents could prove beneficial in such patients we studied 12 patients previously treated with bilateral adrenalectomy alone for Cushing's disease before and after 3 weeks of cyproheptadine and/or bromocroptine therapy. All had raised plasma ACTH values but no patient had evidence of a pituitary macroadenoma. Plasma ACTH and cortisol were sampled 2-hourly for 24 h. Neither drug regime led to any change in plasma levels of cortisol for 24 h after a 20 mg dose of oral hydrocortisone. Plasma ACTH (mean +/- SEM) showed a small but significant overall reduction (523 +/- 45 vs 392 +/- 34 ng/l; P less than 0.05) while on bromocriptine alone (5 mg given at 0800 and 1800 h, n = 5). When each time point was analysed individually this reduction was significant at only five out of 13 time points. At 0400 h plasma ACTH (mean +/- SEM) was 758.4 +/- 298.1 vs 380.2 +/- 166.6; 0600 h, 795 +/- 288.7 vs 477.8 +/- 191.7; 1200 h, 266.8 +/- 106.2 vs 187.0 +/- 80.3; 1400 h, 470.0 +/- 239.0 vs 302.0 +/- 135.9; 1600 h, 548.6 +/- 262.5 vs 394.2 +/- 178.5 ng/l (P less than 0.05). There was no significant change in plasma ACTH during treatment with the combination of bromocriptine and cyproheptadine.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenalectomy↗
PubMed1990

Somatostatin analogue (SMS 201-995) in resistant acromegaly: a preliminary report.

The results of treating 10 acromegalic patients with octreotide are compared with those of bromocriptine. Bromocriptine (5 mg 4 times daily for 5 weeks) reduced mean growth hormone (GH) concentrations from 60 to 35 mU/l in 8 patients; a further 2 patients were unable to tolerate this dose. Ten patients (8 unresponsive to bromocriptine) received octreotide 100 micrograms 3 times daily, rising to 500 micrograms 3 times daily according to monthly 24-hour GH profiles. Two patients were withdrawn from octreotide therapy; in the remaining 8, mean GH fell from 36 to 11 mU/l after 6 months' therapy (a reduction to 22% of basal concentrations, compared to a reduction to 58% on bromocriptine). Asymptomatic changes of glucose tolerance and the development of gallstones were noted; further information on the latter is urgently required. In summary, the smallest effective dose of octreotide should be used and each patient should be monitored biochemically.

Acromegaly↗
PubMed1990

Plasma atrial natriuretic factor levels during normal pregnancy and pregnancy complicated by diabetes mellitus and hypertension.

Atrial natriuretic factor (ANF) may play a role in the regulation of the changes of blood volume and vascular reactivity during pregnancy and when pregnancy is complicated by hypertension. Reports of plasma ANF levels during pregnancy are conflicting. We have prospectively studied plasma ANF levels during pregnancy in 25 women, and compared these with 20 age-matched non-pregnant women. Five women developed hypertension during pregnancy and a further five who remained normotensive had insulin-dependent diabetes mellitus. Plasma ANF was 6.8 +/- 1.2 (mean +/- SEM) and 6.3 +/- 0.9 pmol/l during weeks 8-15 and 24-31 of normal pregnancy (n = 15; vs non-pregnant levels (4.0 +/- 0.6 pmol/l) P less than 0.05, n = 20). Levels were 4.3 +/- 0.8 and 3.9 +/- 0.4 pmol/l during weeks 16-23 and 32-39. In the diabetic patients and in the group who developed hypertension levels were at no time different from the uncomplicated pregnancy group. Serum aldosterone increased as pregnancy progressed, but plasma renin activity remained unchanged. As plasma ANF was not different between those who did, and those who did not develop hypertension, early measurement of it will not predict who will and who will not develop hypertension during pregnancy.

Adult↗
PubMed1990

Studies on the pathogenesis of hypertension in Cushing's disease and acromegaly.

The pathogenesis of the hypertension associated with Cushing's syndrome and with acromegaly is poorly understood. We have investigated the possible roles of sodium retention, activation of the renin-angiotensin system and increased sympathetic nervous system activity in untreated patients. In 11 patients with Cushing's disease, seven of whom were hypertensive, total exchangeable sodium was normal despite increased levels of the mineralocorticoid hormones, 11-deoxy-corticosterone and corticosterone. The renin-angiotensin system was also normal. Cardiac sensitivity to the beta-receptor agonist isoprenaline was increased, but this was not due to an increase in beta-adrenoceptor density. Hypertension in Cushing's disease is neither sodium-dependent nor angiotensin II-mediated, but increased cardiac sensitivity to catecholamines, by increasing cardiac output, may contribute to the pathogenesis of hypertension. In nine patients with acromegaly (three of whom were hypertensive) total exchangeable sodium was elevated. Although no correlation between blood pressure and exchangeable sodium was found, hypertension in acromegaly is probably sodium dependent. No evidence was found for a pathogenetic role for either the renin-angiotensin-aldosterone or the sympathetic nervous system.

Acromegaly↗
PubMed1990

Ascertainment and natural history of treated acromegaly in Northern Ireland.

The prevalence of known cases of acromegaly in Northern Ireland in 1984 was 6.3 per 100,000 population. The incidence of newly-diagnosed cases over the preceding 25 years was 5.5 patients per year, or 0.4 patients per 100,000 population per year. This rate would be equivalent to about 200 new cases per year in the United Kingdom. Four options have been available to most of these patients--surgical hypophysectomy (transfrontal or transsphenoidal), pituitary radiotherapy (usually external cobalt beam), drug treatment with bromocriptine, or no treatment. Choice of treatment has been mainly influenced by tumour size, with the larger pituitary adenomas having surgery initially. No single form of treatment has been successful in achieving a clinical remission or cure in more than a minority of cases. The most successful outcome has been where total pituitary ablation has been achieved. Life-table analysis for the whole group shows life expectancy which is not markedly different for that of an age-matched population from Northern Ireland. Morbidity related to long term osteoarthritis and treatment complications remain a major problem. The incidence of malignant tumours is higher than would be expected.

Acromegaly↗
PubMed1989

Long-term glycaemic control and diabetic retinopathy.

216 patients with insulin-dependent diabetes mellitus were studied by retinal photography, and the absence or presence of retinopathy was related to the mean of serial glycosylated haemoglobin measurements (mean HbA1) carried out every 3 months during the previous 6 years. 122 patients had no diabetic retinopathy, 86 had background retinopathy, and 8 proliferative retinopathy. Mean HbA1 levels showed a strong correlation with increasingly severe grades of retinopathy, even when differences in duration of diabetes were taken into account. Proliferative retinopathy was seen only in patients with mean HbA1 above 10%. These results support the view that the development of diabetic retinopathy is related to long-term glycaemic control and emphasise the desirability, and possible benefit, of achieving control as close to normal as is possible for each individual patient.

Adolescent↗
PubMed1989

Motor vehicle driving among diabetics taking insulin and non-diabetics.

OBJECTIVE: To determine whether rates of road traffic accidents were higher in diabetics treated with insulin than in non-diabetic subjects. DESIGN: Controlled, five year retrospective survey. SETTING: Diabetic, dermatology, and gastroenterology outpatient clinics. PATIENTS: 596 Diabetics treated with insulin (354 drivers) aged 18-65 attending two clinics and 476 non-diabetic outpatients (302 drivers). MAIN OUTCOME MEASURES: Rates of accidents in diabetic and non-diabetic subjects. RESULTS: A self completed questionnaire was used to record age, sex, driving state, and rates of accidents and convictions for motoring offences among diabetic and non-diabetic volunteers. For the diabetic volunteers further information was obtained on treatment, experience of hypoglycaemia, and declaration of disability to the Driving and Vehicle Licensing Centre and their insurance company. Accident rates were similar (81 (23%) diabetic and 76 (25%) non-diabetic drivers had had accidents in the previous five years). A total of 103 diabetic drivers had recognised hypoglycaemic symptoms while driving during the previous year. Only 12 reported that hypoglycaemia had ever caused an accident. Overall, 249 had declared their diabetes to an insurance company. Of these, 107 had been required to pay an increased premium, but there was no excess of accidents in this group. CONCLUSIONS: Diabetic drivers treated with insulin and attending clinics have no more accidents than non-diabetic subjects and may be penalised unfairly by insurance companies.

Accidents, Traffic↗
PubMed1989

Partially compensated hypoadrenalism presenting with persistent skin pigmentation.

A 33-year-old female presented in 1966 with striking pigmentation, typical of Addison's disease, and amenorrhea. Endocrine assessment then showed normal basal serum cortisol and urinary hydroxysteroid levels, but serum cortisol did not respond to stimulation with either exogenous ACTH or lysine vasopressin. Steroid replacement treatment was started. Treatment was discontinued by the patient on her own initiative and after some yr she was lost to follow-up. Reassessment in 1986 showed a pigmented patient who had continued in good health. She had a normal basal serum cortisol level with circadian variation. Plasma ACTH levels were high but showed diurnal rhythmicity and suppressed incompletely with 2 mg or 8 mg of dexamethasone/24 h. Plasma aldosterone levels were normal and showed appropriate postural changes, but plasma renin levels were high. This patient has an immunological profile of autoimmune disease with positive adrenal, thyroid microsomal and gastric parietal cell antibodies with a history of a premature menopause which may also be of autoimmune origin. She has been seen over a 20-yr period and despite her appearance still has no biochemical evidence of glucocorticoid or mineralocorticoid deficiency. It is suggested that the patient had compensated hypoadrenalism, with serum cortisol levels maintained in the normal range by high plasma ACTH levels and serum aldosterone levels maintained by high renin levels. The long term result of the high ACTH levels was increased skin pigmentation.

Adrenal Insufficiency↗
PubMed1989

Basal and saline-stimulated levels of plasma atrial natriuretic factor in acromegaly.

We have studied plasma ANF before and after a 4-h intravenous infusion of normal saline in eight subjects with active acromegaly and in eight age and sex-matched control subjects. Plasma ANF, serum aldosterone and blood pressure were measured basally and after 2 and 4 h and plasma renin activity basally and after 4 h. Basal plasma ANF was similar in each group (4.4 +/- 1.5 pmol/l (mean +/- SEM) in acromegalic subjects and 5.3 +/- 0.7 pmol/l in controls NS). Plasma ANF did not rise significantly after saline in the acromegalic group (2-h value, 5.9 +/- 0.9; 4-h value, 5.1 +/- 0.9 pmol/l) but did rise significantly in the control group (2-h value, 8.9 +/- 1.9; 4-h value 9.5 +/- 1.3 pmol/l, both values P less than 0.05 vs basal level). The 4-h ANF value was significantly higher in the control group than in the acromegalic group (P less than 0.05). Basal and stimulated serum aldosterone values were similar in the two groups. Plasma renin activity suppressed to a lesser extent in the acromegalic group after 4 h. The facts that basal plasma ANF was not raised in acromegalic subjects and did not respond to saline stimulation demonstrate that an abnormality of ANF control may be an important factor in the aetiology of the expanded sodium status of patients with acromegaly and hence may contribute to the hypertension seen in patients with growth hormone excess.

Acromegaly↗
PubMed1989

Plasma ACTH responses to cortisol infusion are similar in patients with primary hypoadrenalism and patients studied some years after bilateral adrenalectomy for Cushing's syndrome.

It has been suggested that the first-phase feedback of steroid feedback on ACTH secretion is abnormal in Cushing's disease patients studied after adrenalectomies. We have performed hydrocortisone infusions (100 mg over 2 h) in 15 patients who had previously undergone bilateral adrenalectomy for Cushing's disease. None had had any pituitary-directed therapy and none had a pituitary macroadenoma. Their responses were compared with a group of seven hypoadrenal patients. A significant rise in serum cortisol was observed between 5 and 10 min in both groups. The first significant fall in ACTH occurred between 30 and 45 min in both groups. There was no abnormality of first-phase feedback in the Cushing's group and our results do not therefore support previous speculation that such an abnormality provides evidence for a higher central nervous system (CNS) aetiology of Cushing's disease.

Adrenal Insufficiency↗
PubMed1989

Bilateral inferior petrosal sinus sampling as a routine procedure in ACTH-dependent Cushing's syndrome.

Bilateral inferior petrosal sinus sampling was successfully performed in 12 of 13 consecutive patients with ACTH-dependent Cushing's syndrome. Ten of the patients subsequently had transsphenoidal pituitary microsurgery. Eight patients in whom the inferior petrosal sinus to peripheral vein ACTH level ratio was 1.5 or greater were found to have a pituitary adenoma. One of the remaining two patients who had ratios less than 1.5 had pituitary hyperplasia while the other had no identified abnormality. In five of the patients with pituitary tumour a ratio above 1.5 was present on only one side. Bilateral petrosal sampling is therefore always necessary. Tumour localization within the pituitary was only poorly predicted by either petrosal sinus sampling (four of eight) or computed tomography scanning (three of eight). If petrosal sinus sampling is used early in the differential diagnosis of ACTH-dependent hypercortisolism, then the use of other differential diagnostic tests may not always be necessary.

Adenoma↗
PubMed1989

Phaeochromocytoma in pregnancy. Five cases and a review of the literature.

We report five patients with phaeochromocytoma associated with pregnancy and review the 42 other cases reported in the literature from 1980 to 1987. The overall maternal mortality was 17% and the fetal loss 26%; antenatal diagnosis of phaeochromocytoma reduced the maternal mortality to zero and the fetal loss to 15%, but was made in only 53% of the patients. Although phaeochromocytoma is rare, a high index of clinical suspicion must be maintained and all those at risk investigated if earlier diagnosis and improved outcome are to be achieved. Once the diagnosis is confirmed, alpha-blockade is essential and beta-blockade may be required. CT scan or magnetic resonance imaging may be used to localize the tumour during the antenatal period. In the first and second trimesters, tumour resection has a good fetal outcome; in later pregnancy, delivery by elective caesarean section followed by tumour resection is recommended.

Adrenal Gland Neoplasms↗
PubMed1989

Variations in the plasma concentration of atrial natriuretic factor across 24 hours.

There is little information available concerning the presence or absence of a normal variation in the circulating concentration of atrial natriuretic hormone throughout a 24 h period. We have examined this in 8 normal subjects (aged 23-35 years) on a fixed 120 mmol Na+ diet. Circulating levels of ANH, plasma renin activity, serum aldosterone and serum cortisol were determined two-hourly during 24 h in a supine position. There was a significant change in the concentration of each of these four hormones during the study period (P less than 0.05). ANH: peak 8.5 (22.00 h), nadir 4.0 (12.00 h) (pmol/l); PRA: peak 1.7 (04.00 h), nadir 0.8 (22.00 h) (microgram.l-1.h-1); aldosterone: peak 350 (14.00 h), nadir 143 (22.00 h) (pmol/l); cortisol: peak 346 (08.00 h), nadir 51 (22.00 h) (nmol/l). Peak plasma ANH occurred at 22.00 h and with the exception of times 20.00 h and 10.00 h this value was significantly higher than all the other time means (P less than 0.05). The only other significant differences were between plasma ANH at 20.00 h and 06.00 h, 08.00 h, 12.00 h and 14.00 h, respectively (P less than 0.05). From midnight until 18.00 h, there was no significant difference between any of the time means. There was a peak in PRA at 04.00 h, while peak serum aldosterone and serum cortisol occurred at 14.00 h and 08.00 h, respectively. This study suggests that ANH may display a diurnal rhythm. Our findings provide further physiological evidence that plasma ANH and PRA may have a reciprocal relationship.

Adult↗
PubMed1989

A weight-related intravenous dexamethasone suppression test distinguishes obese controls from patients with Cushing's syndrome.

To establish a rapid test for Cushing's syndrome we measured serum cortisol during and following iv dexamethasone infusion (5 micrograms.kg-1.h-1 for 5 h from 10.00 h) in simple obesity (N = 19) and in Cushing's syndrome (N = 12). We had first established that 5 micrograms.kg-1.h-1 was the lowest dose which consistently lowered serum cortisol in simple obesity. In obesity, serum cortisols ranged from undetectable (less than 30) to 48 nmol/l at 17.00, less than 30 to 37 at 19.00 and less than 30 to 38 at 08.00 h the following day. Serum cortisol at these three times did not show any overlap between simple obesity and Cushing's syndrome. Having established these findings we proceeded to study a group of patients with polycystic ovarian disease. These patients behaved differently. Their values at 17.00 and 19.00 h did not overlap those of Cushing's syndrome. However, at 08.00 h, 5 of the 7 had values within the range seen in Cushing's syndrome with a mean of 290 +/- 99 nmol/l. In conclusion, 17.00 and 19.00 h serum cortisol levels distinguish between Cushing's syndrome and both simple obesity and polycystic ovarian disease. However, in the latter, cortisol suppression is less prolonged than in simple obesity. This finding may be important for our understanding of the pathogenesis of the disease.

Adult↗
PubMed1989

Relationship between basal and sodium-stimulated plasma atrial natriuretic factor, age, sex and blood pressure in normal man.

The relationships between plasma atrial natriuretic factor (ANF), blood pressure (BP) and age have not been clearly defined. We measured plasma ANF levels and BP in 128 normal subjects (65 male; 63 female; mean age 48 years, range 20-87 years) on no medication. In subjects of 75 years or less (n = 120) plasma ANF was 5.7 +/- 0.3 pmol/l (mean +/- SEM). Plasma ANF did not differ between sexes (males 5.6 +/- 0.4 pmol/l, females 5.9 +/- 0.4 pmol/l). There was a positive correlation between plasma ANF and age, correlation coefficient (r) = 0.46, systolic BP (r = 0.44), diastolic BP (r = 0.22) and mean BP (r = 0.37) (all P less than 0.01), but after multiple linear regression analysis plasma ANF only related significantly (P less than 0.01) to age and systolic BP once other factors had been excluded. We also measured plasma ANF after erect and supine posture and during a 21IV normal saline infusion given over 4 hrs (n = 24; age range 21-62 years) after an overnight fast. Mean plasma ANF was 5.9 +/- 1.1 pmol/l erect, 7.4 +/- 1.6 pmol/l supine and rose to 10.1 +/- 1.4 pmol/l after saline (both P less than 0.05 vs basal). Response to saline was assessed as the area under the curve of hourly measurements. Neither this nor peak ANF during saline infusion correlated with age. We conclude that basal plasma ANF is influenced by age and systolic BP but plasma ANF response to acute saline stimulation is not.

Adult↗
PubMed1988

Cyclical Cushing's syndrome presenting as short stature in a boy with recurrent atrial myxomas and freckled skin pigmentation.

A young male patient demonstrated unusual features of Cushing's syndrome, atrial myxomas and freckled skin pigmentation. At 4.5 years of age he presented with intermittent swelling of his face and abdomen associated with weight gain and mild hypertension. A left atrial myxoma, suspected from routine physical examination, was surgically removed at 6.1 years of age. The initial mild symptoms clinically thought to be due to Cushing's syndrome, persisted intermittently without any consistent biochemical abnormality. At 10 years of age height velocity decreased and at 12 years early osteoporosis was observed radiologically. Repeated dexamethasone tests revealed a paradoxical increase in cortisol and corticotrophin from normal basal levels. Further investigation showed a cyclical pattern of hypercortisolism. The removal of a pituitary microadenoma failed to correct the features of Cushing's syndrome or prevent intermittent hypercortisolism. At 15.3 years a second left atrial myxoma was removed. This was followed by bilateral adrenalectomy. Histologically the features were consistent with primary pigmented nodular adrenocortical disease. This is the first patient described with cyclical Cushing's syndrome as part of this unusual complex of disorders.

Child, Preschool↗