Chronic fatigue syndrome and functional hypoadrenia--fighting vainly the old ennui.
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Adrenal Insufficiency↗
Biomedical subjects
W J Jeffcoate
Publications and source records attributed to W J Jeffcoate.
An assessment of blood pressure measurement in a diabetic clinic using random-zero, semi-automated, and 24-hour monitoring.
We have undertaken a randomized, observer-blinded comparison of three different methods of assessing blood pressure in 40 outpatients with hypertension complicating diabetes mellitus: the Hawksley random zero sphygmomanometer (RZS) by two observers using a dual headed stethoscope; the semi-automated Dinamap monitor, and 24-h ambulatory blood pressure monitoring (ABPM) using a Spacelabs 90207. The techniques were compared by plotting the difference against average of readings obtained by combinations of two techniques (RZS observer 1 vs 2; RZS (mean observer 1 and 2) vs Dinamap; RZS (mean observer 1 and 2) vs daytime ABPM; and Dinamap vs daytime ABPM). There was good agreement of readings with RZS, observers 1 and 2 and RZS with Dinamap and daytime ABPM. When the three methods were used to classify blood pressure control according to BDA criteria, it was found that they produced equivalent results and although mean systolic pressures appeared lower with ABPM this did not reach statistical significance. Overall control of systolic blood pressure was classified as unsatisfactory in 82% of patients, diastolic blood pressure was unsatisfactory in 55%. Fifty-five percent were determined to be nocturnal 'non-dippers' by ABPM. They were older: median age 62.9 (range 35.9-83.5) years compared to 48.2 (32.4-70.0) years for 'dippers' (p<0.05). Thirteen of the 18 patients who did dip overnight had creatinines within the normal laboratory range, whereas only 6 of 22 'non-dippers' had normal creatinines (median 91 (56-768) micromol l(-1) for 'dippers' vs 166 (76-479) micromol l(-1) for 'non-dippers', p < 0.001). Nineteen of the 29 males studied were 'non-dippers' compared with only 4 out of 11 females (p < 0.001). There was no association between dipper status, duration or type of diabetes or presence of proteinuria.
Adult↗
Conservative management of osteomyelitis in the feet of diabetic patients.
Experience of conservative management of osteomyelitis in a specialized, multidisciplinary, diabetic foot clinic was reviewed. The records of all patients attending the clinic over a 10-year period were examined retrospectively, and 22 patients with overt osteomyelitis were identified. Median age was 66 (31-87) years. In 12 cases the bone infection was a complication of a pre-existing ulcer; the most prevalent organism cultured from swabs was Staphylococcus aureus. The main site of infection was the first toe. The total duration of antibiotic treatment was 12 weeks (median, range 5-72), and clindamycin was the most commonly used oral agent. Four patients did not respond to initial conservative therapy and proceeded to amputation, while 1 patient responded clinically but had a recurrence of osteomyelitis at the same site 6 years later. In the remaining 17 patients resolution of osteomyelitis was achieved with conservative management over a median period of follow-up of 27 (range 5-73) months. The success of conservative therapy with prolonged courses of oral antibiotics challenges conventional advice that excision of infected bone is essential in the management of osteomyelitis affecting the foot in diabetes.
Administration, Oral↗
Factors contributing to the presentation of diabetic foot ulcers.
We have undertaken a prospective study of the presentation of all 669 ulcers seen in a specialist multidisciplinary foot clinic between 1 January 1993 and 1 August 1996, with particular reference to the factors which precipitated ulceration as well as to any delays in referral. Nearly two-thirds (61.3%) of all lesions were first detected by the patient or a relative, and the remainder by a healthcare professional. The median (range) time which elapsed between ulcer onset and first professional review was 4 (0-247) days, and the median time between first review and first referral to the specialist clinic was 15 (0-608) days. Significant delays were judged to have occurred in 39 instances. The most common precipitant of ulceration was rubbing from footwear, which was responsible for 138 (20.6%). Fifty-eight (8.7%) were the result of immobilization from other illness, and a further 24 were the consequence of surgery. Overall, professional factors contributed to the development or deterioration of 106 lesions (15.8% total). These results should form the basis of strategies designed to minimize the onset of ulceration in those known to be at risk: educational strategies need to be directed at professionals as much as at patients.
Diabetic Foot↗
Corticotrophic macroadenoma of the pituitary associated with hypoadrenalism.
A 60-year-old man underwent transfrontal surgery for a macroadenoma of the pituitary which presented with chiasmal compression, and immunohistochemical examination of the resected specimen revealed a corticotrophic tumour. Despite subsequent external irradiation, he was left with a large tumour remnant, which continued to grow. There were no clinical signs of Cushing's syndrome either before or after surgery and 24 h urine excretion of cortisol was not elevated. Plasma ACTH concentrations were marginally raised. However, there was loss of circadian variation in serum cortisol concentrations and administration of high-dose oral dexamethasone was followed by a marked and reproducible rise in both ACTH and cortisol. Two years later he developed symptoms and signs of hypoadrenalism and urine cortisol excretion was low, even though the paradoxical response to dexamethasone was preserved. Treatment with 0.5 mg dexamethasone each day was associated with partial resolution of his symptoms and urine cortisol concentration rose into the normal range. This treatment was maintained until his death in hospital in April 1988. The possible mechanism underlying the association between a corticotrophic tumour and hypoadrenalism are discussed.
Adenoma↗
A neurological complication of inferior petrosal sinus sampling during investigation for Cushing's disease: a case report.
A 45 year old woman with hirsutism was found to have classic biochemical features of ACTH dependent Cushing's disease, with partial cortisol suppression in response to dexamethasone. As no pituitary adenoma could be visualised by CT or MRI, she proceeded to bilateral simultaneous inferior petrosal sinus sampling before possible surgery. During the course of this procedure she had a stroke affecting the brainstem at the level of the pontocerebellar junction. This complication of petrosal sinus sampling has been previously described but is not widely recognised; the procedure should only be undertaken when results of less invasive tests are equivocal.
Adrenocorticotropic Hormone↗
Is macrosomia associated with poor glycaemic control in diabetic pregnancy?
The study aimed to determine the influence of glucose control during pregnancy on the incidence of macrosomia in the infants of mothers with insulin-dependent diabetes. The prevalence of macrosomia was determined in pregnancies of all such women attending the City Hospital Nottingham, between July 1987 and July 1993, where it is policy for diabetic patients to aim during pregnancy for preprandial capillary glucose levels of less than 6.0 mmol I-1, and postprandial glucose levels of less than 8.0 mmol I-1. Macrosomia was defined as a birthweight greater than 90th centile using a computer model which takes into account all the major determinants of birthweight. Twelve of 29 infants were macrosomic, which is greater than expected (p < 0.01). During pregnancy there was no difference in mean seven point glucose profiles between those mothers with normal weight babies and those with macrosomia, but fructosamine levels at booking were significantly higher in the latter 2.5 (1.9-2.9) vs 2.2 (1.2-3.0); p < 0.05. These data confirm other studies and suggest that the incidence of macrosomia may be reduced by tighter control of diabetes at conception and in the first trimester, but to a lesser extent during later pregnancy.
Blood Glucose↗
Age related changes in glycated haemoglobin in patients with insulin-dependent diabetes mellitus.
A computerized diabetes register was used retrospectively to define trends in HbA1 and blood glucose with increasing age, using a population of patients with insulin-dependent diabetes. A total of 1874 patients provided 11,776 results for analysis between 1982 and 1993. Mean HbA1 rose progressively between ages 10 and 16 years from 9.8% +/- 2.4 (SD) to 10.6% +/- 2.7 at 12, 11.7% +/- 3.1 at 14 and 12.2% +/- 3.2 at 16 years. Mean HbA1 then fell steadily until it reached a nadir of 10.2% +/- 2.8 at 27 years. There followed a gradual deterioration in control each decade: 10.2% +/- 2.9 at 30 years, 10.4% +/- 2.8 at 40, 10.9% +/- 2.6 at 50 and 10.8% +/- 2.7 at 60 years (r2 = 0.56). Glycaemic control was worse in females than in males: HbA1 area under curve between the ages of 10 and 70 years being 6.1% higher (p < 0.0001). This study confirms the clinical impression of worsening control during teenage years but provides evidence of previously unrecognized trends in later life. Nevertheless, a continuing improvement in glycaemic control between 1982 and 1993 was evident in all age groups.
Adolescent↗
Glycated proteins as indices of glycaemic control in diabetic patients with chronic renal failure.
This study investigates the reliability of glycated haemoglobin, measured by electroendosmosis or by affinity chromatography, fructosamine, and albumin adjusted fructosamine, as indices of glycaemic control in Type 1 diabetes complicated by chronic renal failure. Twenty uraemic diabetic patients took part in the study, including 5 patients managed conservatively, 6 on CAPD, 3 on haemodialysis, and 6 renal transplant recipients. Results were compared with those from 15 diabetic subjects with normal renal function. In renal patients, there was significant correlation between glycated haemoglobin measured by electroendosmosis (r = 0.45; p = 0.04) or by affinity chromatography (r = 0.57; p = 0.01) and mean capillary blood glucose concentrations over the previous 6 weeks. The regression equations did not differ significantly between subjects with renal failure and those with normal renal function, suggesting that similar ranges can be used in interpreting glycated haemoglobin results from each group of patients. Patients on haemodialysis may be an exception; there was evidence that glycated haemoglobin may be misleadingly low in such subjects. Fructosamine correlated significantly with mean blood glucose concentrations measured over the previous week in patients with normal renal function (r = 0.75; p = 0.001), but not in patients with chronic renal failure (r = -0.1; p = 0.71). Calculation of an albumin adjusted fructosamine result failed to improve the correlation with blood glucose concentrations. The use of fructosamine cannot be recommended as an index of glycaemic control in uraemic patients.
Blood Glucose↗
A comparison of 20 or 40 mg per day of carbimazole in the initial treatment of hyperthyroidism.
OBJECTIVE: The optimal dosage regimen for carbimazole (CBZ) in the treatment of hyperthyroidism remains uncertain, despite clinical use of the drug for approximately fifty years. We have compared the early clinical and biochemical responses to 20 or 40 mg/day of CBZ given as initial treatment for hyperthyroidism. DESIGN: Prospective open multicentre trial. PATIENTS: Sixty-three patients presenting with hyperthyroidism. MEASUREMENTS: Serum total and free thyroid hormones, serum TSH and SHBG were measured at baseline and at 4 and 10 weeks after start of therapy. Weight, pulse and a symptom questionnaire were also monitored at 6 and 12 weeks. RESULTS: Patients randomized to a starting dose of 40 mg/day CBZ had lower total (98 +/- 10 vs 158 +/- 11 nmol/l, P < 0.001) and free T4 (19.4 +/- 2.6 vs 35.2 +/- 3.7 pmol/l, P < 0.001) and total (2.6 +/- 0.3 vs 4.3 +/- 0.4 nmol/l, P < 0.001) and free T3 (8.3 +/- 1.0 vs 13.7 +/- 1.2 pmol/l, P < 0.01) at 4 weeks than those receiving 20 mg/day. Clinical responses at 6 and 12 weeks (weight, pulse, symptom score) and SHBG concentrations were similar. Drug-related hypothyroidism was less likely to occur at 4 and 10 weeks in those patient who initially received 20 mg CBZ/day, but this dose was less effective at controlling hyperthyroidism in those with more severe hyperthyroidism with baseline TT4 > 260 nmol/l. CONCLUSIONS: In treating hyperthyroidism, 20 mg/day carbimazole is effective, convenient and has a lower risk than 40 mg/day of iatrogenic hypothyroidism in patients with mild or moderate hyperthyroidism. Higher doses are required for those with severe hyperthyroidism.
Adolescent↗
Long-term follow-up of patients with hyperprolactinaemia.
AIM: To determine the frequency with which hyperprolactinaemic illness tends to resolve with time. STUDY DESIGN: A retrospective case-notes review from a specialist endocrine unit in a provincial teaching hospital and tertiary referral centre. PATIENTS: Seventy women with hyperprolactinaemia referred to the unit in the 15 year period between May 1979 and May 1994. All those with a non-pituitary cause or with macroadenoma had been excluded, as were those who did not have high-resolution imaging, or who were on treatment at the time of referral. INTERVENTION: Intermittent course of treatment with dopamine receptor agonists according to individual need. ENDPOINTS: Latest serum PRL concentration in those who had discontinued treatment, and whether serum PRL tended to be lower in any particular group. RESULTS: There was a significant fall in median PRL concentration from 2000 (714-8000) to 1000 mU/l (220-5600) in the 31 women who had discontinued therapy (P < 0.0005), and serum PRL was normal (< 700 mU/l) in 11 of them. Serum PRL also fell to normal in three of ten women who had no treatment at all. Final PRL concentration was normal in 35% of women who had had at least one pregnancy during the period of follow-up compared to 14% who had not (P < 0.05). CONCLUSIONS: These data confirm the findings of others that hyperprolactinaemia will prove self-limiting in up to one-third of women, and that pregnancy may be one factor which triggers a return to normal function.
Adolescent↗
Effect of long-term glycemic control on cognitive function.
OBJECTIVE: To investigate the relationship between recurrent hypoglycemia and cognitive impairment in insulin-dependent diabetic patients. RESEARCH DESIGN AND METHODS: Seventy patients who were diagnosed as diabetic at age 18 years or older, were under 55 years old, and had no condition likely to affect cognitive abilities were recruited from a diabetic register. Patients were interviewed to obtain information on the frequency of major and minor hypoglycemia. Their cognitive abilities were assessed on tests of premorbid intelligence, current intelligence, reaction time, concentration, memory, and information processing. RESULTS: There was a significant correlation between the apparent decline in intelligence, expressed as the discrepancy between the estimated premorbid and the actual performance intelligence quotient, and the frequency of major hypoglycemic attacks (rs = -0.30; P < 0.01). Comparison of patients with and without recurrent hypoglycemia showed few significant differences in cognitive ability. CONCLUSIONS: Results support previous work that suggests that major hypoglycemic attacks have a significant effect on some aspects of cognitive function, but the clinical importance of this finding remains to be determined.
Adult↗
Autonomous nodular hyperplasia of the adrenal cortex: tertiary hypercortisolism?
Two cases of Cushing's syndrome are reported in which apparently autonomous adrenal adenomata were associated with the presence of pituitary tumours. In one case the patient was apparently cured by unilateral adrenalectomy, although she was noted to have radiological evidence of an intrasellar tumour; serum cortisol was not suppressed by dexamethasone and ACTH was undetectable. Serum ACTH in the second case was initially 31 ng/l but became undetectable during the course of investigation. Transsphenoidal removal of a corticotroph adenoma did not affect serum cortisol and she proceeded to unilateral adrenalectomy. The pathogenesis of autonomous macronodular hyperplasia is discussed, as well as the options for management.
Adenoma↗
Addisonian crisis presenting with a normal short tetracosactrin stimulation test.
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Addison Disease↗
Nesidioblastosis in adults.
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Adenoma, Islet Cell↗
The short Synacthen test in acute hospital admissions.
OBJECTIVE: We wished to define the cortisol response to 250 micrograms intramuscular tetracosactrin (Synacthen) in acute hospital admissions, using a modern immunoassay for cortisol. DESIGN: We performed a prospective study of, as near as possible, a consecutive series of 161 admissions to a single unit. PATIENTS: We studied 50 patients (age range 67-98, mean 80.3 years, 31-female, 19-male) admitted as an emergency, from whom it was possible to obtain informed consent, and whom it was possible to study within 24 hours of admission. MEASUREMENTS: We measured baseline, increment and peak serum cortisol following administration of 250 micrograms intramuscular tetracosactrin between 0800 and 0900 hours. RESULTS: Baseline cortisol concentrations ranged from 288 to 1585 nmol/l (mean 706; median 665). Peak cortisol concentrations ranged from 602 to 2265 nmol/l (mean 1076; median 999). Baseline and peak cortisol concentrations showed a significant correlation (P less than 0.001). Increment varied from 10 to 747 nmol/l (mean 374; median 336) and did not correlate with baseline. CONCLUSIONS: In acute hospital admissions, baseline serum cortisol between 0800 and 0900 hours should exceed 250 nmol/l. Peak serum cortisol after 250 micrograms intramuscular tetracosactrin should exceed 600 nmol/l. Calculation of the increment is of no value.
Acute Disease↗
The investigation of impotence.
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Alcoholism↗
Perceived needs of general practitioners and practice nurses for the care of diabetic patients.
This study compared the aims and needs of General Practitioners (GPs) and practice nurses who wished to improve the service they provided for non-insulin-treated diabetic patients. Contact was made with 242 GPs in 110 practices in Central and North Nottingham, and a questionnaire was sent to the 149 (62%) who requested one. Completed questionnaires were returned by 110 (74%) of these, and by 48 (80% of 60) of their practice nurses. Only 19 GPs ran a specific diabetic clinic, but nearly all (95%) wanted to improve the service they provided for diabetes care. In doing so, many wished for involvement of opticians, chiropodists, and dietitians, and all wished to involve the practice nurse. The need for involvement of hospital-based diabetes specialist nurses was perceived by only 37% GPs. More than two-thirds (69%) of practice nurses wanted more input into the care of diabetes. Both GPs and practice nurses felt that the role of the practice nurse should include screening for complications, although there was some disagreement about the extent of this involvement. GPs envisaged that patient education would be a major problem in establishing a diabetes service, but only 58% identified education as a task that could be accomplished by the practice nurse.
Attitude of Health Personnel↗