"All change ...".
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History, 20th Century↗
Biomedical subjects
D R Hadden
Publications and source records attributed to D R Hadden.
What is the gold standard for glycosylated haemoglobin?
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Diabetes Mellitus↗
Assessment of endocrine function after transsphenoidal surgery for Cushing's disease.
OBJECTIVE: We assessed the endocrine outcome after transsphenoidal surgery for Cushing's disease. DESIGN: Five-year (mean) follow-up (range 1 month-12 years) of patients undergoing transsphenoidal surgery for Cushing's disease between 1977 and 1990; review of case notes, current clinical and biochemical assessment including 24-hour urinary free cortisol. SETTING: Northern Ireland. SUBJECTS: Forty-one patients (33F: 8M); mean age at diagnosis 39.1 years (9-72 years). MAIN OUTCOME MEASURES: Measurements of early post-operative 0800 h serum cortisol and 24-hour urinary free cortisol at least 24 hours after withdrawal of oral hydrocortisone therapy. This was followed by low dose dexamethasone testing. Current 24-hour urinary free cortisol measurements. Retrospective definition of cure. RESULTS: Twenty-seven patients were either cured or improved by surgery, 14 were considered definite failures. Of 19 patients cured, eight had unmeasurable early post-operative 0800 h serum cortisol levels while of 15 tested, 13 had complete suppression with dexamethasone and two suppressed normally but to still measurable levels (39 and 60 nmol/l respectively). Seventeen patients in total have subsequently had bilateral adrenalectomy of whom two have developed Nelson's syndrome. Seven of the 41 patients were shown to have definite cyclical cortisol secretion first diagnosed post-operatively in three patients. Hormone deficiency included TSH (5), LH/FSH (1), cortisol (1) and ADH (temporary in 7, permanent in 1). In all, seven patients had some type of permanent hormonal deficiency post-operatively. CONCLUSIONS: Transsphenoidal surgery offers a worthwhile cure rate without the necessity of life-long endocrine therapy. Post-operative endocrine assessment must be rigorous so that early further management can be planned in the significant percentage of patients in whom cure is not achieved. Early complete suppression on low dose dexamethasone testing is very suggestive of cure but repeated and long-term monitoring of 24-hour urinary free cortisol is advisable.
Adenoma↗
Bilateral adrenalectomy: low mortality and morbidity in Cushing's disease.
OBJECTIVE: We assessed the current role of bilateral adrenalectomy in the overall management strategy of hypercortisolism. DESIGN: Retrospective review of case notes. PATIENTS: Twenty-six patients (20F/6M); mean age 46 years (range 15-70 years), median duration of follow-up 5.25 years (0.6-19.1 years) who had undergone bilateral adrenalectomy at the Royal Victoria Hospital since 1972. Eighteen had had prior transsphenoidal surgery which did not control the hypercortisolism. MEASUREMENTS: Morbidity, mortality, incidence of Nelson's syndrome. RESULTS: Surgery was performed through bilateral postero-lateral incisions (20 patients) or a long epigastric incision (six patients). The mean combined weight of the adrenals at surgery was 11.2 g. Twenty patients received subcutaneous heparin and 18 antibiotic prophylaxis peri and post-operatively. There was no operative mortality. Minor complications included one post-operative wound infection and a small pneumothorax requiring drainage. Major complications occurred in two other patients, both with pre-existing invasive pituitary tumours and considered at high risk because of age and general debility. One patient had a massive pulmonary embolus and the other a subphrenic abscess post-operatively. This latter patient, the only mortality, died from an unrelated cause three years post-operatively. Six patients have subsequently undergone pituitary surgery and three have received external pituitary irradiation therapy for expanding tumours. CONCLUSIONS: Bilateral adrenalectomy, in experienced hands, is a relatively safe and useful management option in patients with hypercortisolism. Growth of a pituitary adenoma post-operatively is now the most worrying complication.
Adolescent↗
Fetal outcome in mothers with impaired glucose tolerance in pregnancy.
A 75 g oral glucose tolerance test was carried out on 953 pregnant women who were identified on the basis of clinical risk factors. The tests were analysed by the WHO criteria: 826 were normal, 120 showed impaired glucose tolerance, and 7 identified diabetes. A number of obstetric and perinatal outcome measures were compared between the groups with normal and impaired glucose tolerance, and also with 135 women who had pre-existing Type 1 diabetes and delivered during the study period. There was no significant difference in the incidence of antenatal complications between mothers with normal and impaired glucose tolerance. There was a higher rate of induced labour (p < 0.05) and caesarean section (p < 0.01) in the impaired glucose tolerance group compared to the normal group, but no difference in fetal outcome or neonatal morbidity. All of these outcome measures were increased in the Type 1 diabetic pregnancies.
Adult↗
Long-term glycemic control and neurological function in IDDM patients.
OBJECTIVE: To examine the relationship between sensory modalities of neurological function and antecedent glycemic control in IDDM patients. RESEARCH DESIGN AND METHODS: Examinations were conducted on 220 IDDM patients (age at onset < 25 yr, duration < 18 yr) for the presence or absence of the right or left ankle reflex and determination of vibration perception threshold at each medial malleolus and great toe using biothesiometry. These parameters were related to the concurrent HbA1 and to a mean of serial measurements (mean HbA1) over the previous 6 yr. RESULTS: Ankle reflexes were absent in 39 (right ankle) and 41 (left ankle) patients, respectively. Mean (right + left) ankle and toe VPTs were 8.7 +/- 3.6 and 6.3 +/- 4.2 (mean +/- SD) (arbitrary units), respectively. Both the mean and concurrent HbA1 were significantly different in patients with absent ankle reflexes (11.6 +/- 1.9 and 12.2 +/- 2.8%, respectively) compared with present ankle reflexes (10.3 +/- 1.7, 10.3 +/- 2.1%) (P < 0.0001). Similarly, a present ankle reflex was related to mean HbA1 arbitrarily divided into groups < 10, 10-12, > 12% (P = 0.0009). In contrast, mean ankle VPT (8.0 +/- 2.2, 8.8 +/- 3.1, and 10.3 +/- 6.2) and toe VPT (5.5 +/- 2.2, 6.1 +/- 2.9, and 8.5 +/- 8.2) did not increase significantly with poor glycemic control (P > 0.05). Age, right ankle reflex, retinopathy, 24-h urinary albumin excretion rate, and erect systolic blood pressure were the only independent variables predicting the toe VPT using linear regression analysis. CONCLUSIONS: These findings support a role for glycemic control in neurological dysfunction in IDDM patients, but also suggest that other unknown factors may be involved.
Adult↗
Hyperinsulinaemia and syndrome X.
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Adult↗
Growth hormone treatment of adults with growth hormone deficiency: results of a 13-month placebo controlled cross-over study.
OBJECTIVE: We aimed to study the effect of biosynthetic growth hormone (GH) replacement in growth hormone deficient adults. DESIGN: We performed a double-blind placebo-controlled cross-over study of 6 months biosynthetic GH, replacement and 6 months placebo separated by a 1-month's washout period. PATIENTS: Fourteen growth hormone deficient adults were studied. MEASUREMENTS: We measured total body weight, percentage fat mass, lean body mass, muscle volume, exercise capacity, maximum oxygen consumption, muscle strength, bone mineral content, a number of biochemical parameters, IGF-I, GH antibodies and psychological well-being. RESULTS: Total body weight remained unchanged, but lean body mass increased (before GH mean +/- SEM 49.8 +/- 5.5, after 53.4 +/- 5.6 kg; placebo before 51.2 +/- 5.4, after 50.4 +/- 5.1 kg; P less than 0.05 and fat mass decreased (before GH 21.5 +/- 4.1, after 19.3 +/- 4.3; placebo before 19.3 +/- 4.0, after 22.5 +/- 4.5 kg; P less than 0.05). Thigh muscle volume increased: (before GH 94.1 +/- 7.7, after 99.5 +/- 8.4 ml; placebo before 99.3 +/- 8.6, after 95.4 +/- 7.8 ml/0.8 mm computerized tomographic slice; P less than 0.05). Exercise capacity increased (before GH 174 +/- 15, after 199 +/- 18.9 watts; placebo before 162.5 +/- 2.3, after 154 +/- 19.8 watts; P less than 0.05), as did maximum oxygen consumption (before GH 1.93 +/- 0.2, after 2.17 +/- 0.2 l/m; placebo before 1.92 +/- 0.3, after 1.98 +/- 0.2 l/m; P less than 0.05). There was no change in quadriceps muscle strength. Alkaline phosphatase increased (before GH 87.5 (32-158), after 106.0 (49-179) U/I, placebo 99.5 (50-145), after 72.0 (40-111) U/I; P less than 0.05) without a change in the spinal bone density. IGF-I increased (before GH 62 (36-97), after 216 (62-362) micrograms/l; placebo before 59 (52-112), after 60.5 (38-94) micrograms/l; P less than 0.05). Carbohydrate tolerance remained unchanged as did fasting lipids, serum sodium, potassium, urea, calcium, phosphate and liver transaminases. Psychological well-being remained unchanged. No growth hormone antibodies were detected before or after GH treatment. CONCLUSIONS: GH alters the body composition of growth hormone deficient adults and leads to improved exercise capacity; alkaline phosphatase activity increases but without a change in spinal bone density, and carbohydrate tolerance remains unaltered.
Adult↗
Insulin, glibenclamide or metformin treatment for non insulin dependent diabetes: heterogenous responses of standard measures of insulin action and insulin secretion before and after differing hypoglycaemic therapy.
Using carefully selected relatively non-obese non insulin dependent diabetic patients, we were not able to show differences in standard measures of insulin production or insulin action between patients treated with a long acting crystalline zinc insulin, with glibenclamide, or with metformin for a six week period. All three drugs were hypoglycaemic, but a fall in basal hepatic glucose output measured by the 3H3 glucose technique was only seen in those patients who had an initial fasting plasma glucose above 12.0 mmol/l, irrespective of treatment.
Blood Glucose↗
The relationship between long-term glycaemic control and diabetic nephropathy.
Urine albumin excretion was studied by two widely accepted methods in 210 patients with insulin-dependent diabetes mellitus and related to the mean of serial glycosylated haemoglobin (HbA1) measurements made every 3 months during the previous 6 years. Microalbuminuria (albumin excretion rate > 20 micrograms/min) was present in 9.5 per cent of patients when defined by a 24-hour collection and 8.1 per cent of patients when defined by a timed overnight urine sample. Those with microalbuminuria, as estimated from a timed overnight urine sample, had a longer duration of diabetes but otherwise did not differ in age, duration of diabetes or arterial blood pressure from patients whose albumin excretion rate was 20 micrograms/min or less irrespective of the method of urine collection. The mean and the most recent HbA1 levels differed significantly between the normal and the microalbuminuric groups when defined by the 24-hour albumin excretion rate (p < 0.001, p < 0.01), but no significant difference between these groups was found when albumin excretion rates were calculated from the timed overnight urine sample. Albumin excretion rate, examined in relation to mean HbA1, increased significantly with worsening glycaemic control whether measured over 24 hours or overnight (p < 0.05, p < 0.01). These findings support an association between glycaemic control and microalbuminuria, but the correlation is weak, dependent on the method of urine collection and is just as good for a relatively short-term as for a long-term measure of average blood glucose.
Adolescent↗
Incidence of insulin dependent diabetes in children aged under 15.
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Adolescent↗
Presymptomatic screening for MEN-2A.
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Chromosomes, Human, Pair 10↗
Accelerated retinopathy and nephropathy in diabetic pregnancy.
We report a case of severe deterioration in sight despite good metabolic control in a pregnant diabetic patient which has not recovered at two years post-delivery. This was accompanied by a deterioration in renal function which similarly has not improved.
Adult↗
Medical management of diabetes in pregnancy.
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Delivery, Obstetric↗
A long-term dose-response study of somatostatin analogue (SMS 201-995, octreotide) in resistant acromegaly.
Ten acromegalic subjects were studied in a trial designed to ascertain the optimum dosage of the somatostatin analogue SMS 201-995 (octreotide) in active acromegaly. Twenty-four-hour growth hormone (GH) profiles were assessed monthly for 6 months and again after 1 year of continuous therapy. After basal assessment octreotide was administered subcutaneously at a dose of 100 micrograms three times a day throughout the first month. The dose was increased by 300 micrograms/day at monthly intervals to a maximum of 1500 micrograms/day, unless serum GH fell to within set criteria. Eight patients completed the trial. One patient withdrew because of intractable diarrhoea while another died of causes related to his acromegaly and we have no evidence that octreotide played any part in his death. Mean 24-h GH fell from a basal level of 34.3 +/- SEM 7.6 mU/l to 8.0 +/- 1.3 mU/l (P less than 0.05) after 6 months. At 1 month (300 micrograms/day) mean GH was 13.6 +/- 2.2 mU/l and at 2 months (600 micrograms/day) 10.8 +/- 2.2 mU/l (P less than 0.05 vs 300 micrograms/day dose), and at 5 months (1500 micrograms/day) 11.3 +/- 2.0 mU/l (all P less than 0.05 vs basal). Analysis of group means revealed no significant difference between any dose schedules above 600 micrograms/day. After 1 year the mean GH of the group (n = 8) was 7.5 +/- 1.3 mU/l (P less than 0.05 vs basal). Three patients developed a deterioration and one an improvement in their glucose tolerance and three developed asymptomatic gallstones during the year of therapy. In conclusion, octreotide lowered GH levels in acromegaly over a 1-year period. We found no evidence that routinely increasing the dose beyond 600 micrograms/day was helpful.
Acromegaly↗
Physiological growth hormone secretion in adult growth hormone deficiency: comparison with normal controls.
A comparison was made between the pulsatile pattern of growth hormone secretion in 14 growth hormone deficient adults (serum growth hormone less than 7 mU/I following insulin-stimulated hypoglycaemia) and 14 age and sex matched controls. The 24-h secretory profile was generated by 2-hourly sampling from 0800 to 2200 h, and 30-min sampling from 2200 to 0600 h. Plasma GH in each sample was measured using a double antibody radioimmunoassay. The profiles were analysed using a computer program (Pulsar). Sleep-electroencephalography was recorded in all subjects. The total amount of GH secreted in a 24-h period (area under the curve over baseline) was significantly less in the growth hormone deficient group (P less than 0.002). The pulse frequency, amplitude, height and percentage GH secreted in peaks were also significantly less in the growth hormone deficient group (P less than 0.002 respectively). We conclude that adults deficient in GH, as defined by conventional pharmacological stimuli, are in addition physiologically deficient of pulsatile GH secretion.
Adult↗
Solvent abuse, toluene acidosis and diabetic ketoacidosis.
Solvent abuse in adolescents and young adults has been reported to cause a metabolic acidosis with a normal or increased anion gap (Streicher et al., 1981; Voights & Kaufman, 1983, Anonymous, 1988). We report a particularly severe clinical problem produced by the combination of toluene intoxication and diabetic ketoacidosis.
Acetone↗
Gene probe analysis in an informative family with multiple endocrine neoplasia syndrome type 2A (MEN 2A). Improvement in carrier risk estimation.
Gene probe analysis of the MEN 2A locus on chromosome 10 has been undertaken using the markers TB10.163, RBP 3 and TB14.34 in a large kindred with familial medullary thyroid carcinomas, with or without phaeochromocytomas or primary hyperparathyroidism. A maximum LOD score of 2.97 gave strong evidence of close linkage with zero recombination. For 12 members of the family so far not known to be affected by any form of the disease the estimated risk of carrying the gene has been considerably decreased in all but one, whose risk has been greatly increased.
Adolescent↗