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Biomedical subjects

I A MacFarlane

Publications and source records attributed to I A MacFarlane.

At least 19 recordsLinked to original sources

Ablative thyroid treatment for thyrotoxicosis due to thyrotropin-producing pituitary tumours.

BACKGROUND: Thyrotropin (TSH)-secreting pituitary adenomas (TSHomas) are rare tumours that can be invasive. It has been suggested that thyroid surgery or radioiodine treatment should not be considered in patients with such tumours as these treatments may facilitate rapid and aggressive tumour expansion. AIM: To study the effects of thyroid ablative treatment on tumour size and thyroid status in two patients with TSHomas in whom the size of the adenoma was clearly documented before treatment was started. METHODS: Patients studied were: (1) a female patient with a TSHoma who declined to undergo pituitary surgery and underwent a total thyroidectomy instead and (2) a male patient who opted for radioiodine treatment for his recurrent TSHoma. Changes in tumour size on serial magnetic resonance imaging scans, and restoration of euthyroidism were studied. RESULTS: No marked changes in tumour size or features of aggressiveness occurred in these patients over periods of 8 and 12 years. Euthyroidism was restored and maintained in both patients. CONCLUSIONS: Ablative thyroid treatment can be a safe and successful option to treat TSHomas, but long-term and close follow-up of these patients is mandatory to ensure that the size and behaviour of the tumours do not change markedly.

Adult↗

The natural history of chronic painful peripheral neuropathy in a community diabetes population.

AIMS: To examine the natural history of chronic painful diabetic neuropathy (CPDN). METHODS: A cross-sectional study of 350 people with diabetes was performed during 1998-1999 to assess the prevalence of CPDN in the community. Fifty-six patients with CPDN were identified and were followed up an average of 5 years later. RESULTS: From the original cohort, 12 patients had died and 14 had moved away or were unable to participate in the follow-up study. Thus 30 patients with CPDN [21 male, mean (SD) age 68.6 years (9.4), mean (SD) duration of diabetes 15.4 years (8.7)] were re-assessed. Seven (23%) had been pain free for at least 12 months and 23 continued to report neuropathic pain of similar quality and severity [total McGill Pain Questionnaire Score median (interquartile range) at follow-up 22 (16-39) vs. 20 (16-33) at baseline, P = 0.3; mean (SD) visual analogue scale (VAS) score for pain over the preceding 24 h 5.3 cm (2.9) vs. 4.6 cm (2.5) at baseline, P = 0.1]. Only 65% had ever received treatment for CPDN despite 96% (22/23) reporting pain to their physician; 43.5% had received antidepressants, 17.4% anticonvulsants, 39% opiates and 30% had tried complementary therapies. CONCLUSIONS: The neuropathic pain of CPDN can resolve completely over time in a minority (23%). In those in whom painful neuropathic symptoms had persisted over 5 years, no significant improvement in pain intensity was observed. Despite the improvement in treatment modalities for chronic pain in recent years, patients with CPDN continue to be inadequately treated.

Aged↗

Prevalence of obesity in type 2 diabetes in secondary care: association with cardiovascular risk factors.

AIMS: To determine the prevalence of overweight and obesity among patients with type 1 and type 2 diabetes mellitus attending a secondary care diabetes clinic in the United Kingdom, and to assess the impact of overweight and obesity on glycaemic control and cardiovascular risk factors in patients with type 2 diabetes. METHODS: 3637 patients with diabetes were identified from the hospital electronic diabetes register, 916 with type 1 diabetes (mean (SD) age 40.4 (15.1) years, 496 male) and 2721 with type 2 diabetes (mean (SD) age 62.5 (11.8) years, 1436 male). Data on body mass index (BMI), glycaemic control, lipid profiles, and blood pressure were extracted. RESULTS: Of patients with type 1 diabetes, 55.3% were overweight (BMI >or=25 kg/m(2)), 16.6% were obese (BMI >or=30 kg/m(2)), and 0.4% had morbid obesity (BMI >or=40 kg/m(2)). In contrast, 86% of patients with type 2 diabetes were overweight or obese, 52% were obese, and 8.1% had morbid obesity. Obese patients with type 2 diabetes were younger, had poorer glycaemic control, higher blood pressures, worse lipid profiles, and were more likely to be receiving antihypertensive and lipid lowering drugs compared with patients with BMI <30 kg/m(2). CONCLUSIONS: Obesity is the rule among patients attending this hospital diabetes clinic, with 86% of those with type 2 diabetes overweight or obese. Obesity is associated with significantly worse cardiovascular risk factors in this patient group, suggesting that more active interventions to control weight gain would be appropriate.

Adult↗

Hospital in-patients with diabetes: increasing prevalence and management problems.

AIMS: To re-assess the prevalence, management problems, clinical outcomes and discharge summaries of hospital in-patients with diabetes. METHODS: Case records of all patients occupying in-patient beds were audited on a single weekday in 2003 in a large urban hospital and repeated after 3 months. Data was compared with an identical audit 12 years previously. RESULTS: Over 12 years the number of beds available for admission (1191) had reduced by 25% with a bed occupancy of 97%. Diabetes prevalence had increased from 7.0% to 11.1% (P < 0.01) (97% Type 2). Diabetes management was considered inappropriate in 29%, more than in 1991 (20%). After 3 months, discharge summaries had been completed on 75% of patients but diabetes was mentioned in only 53%. CONCLUSION: The prevalence of in-patient diabetes (11.1%) was over 50% greater and diabetes management was suboptimal in more patients than in 1991. In many length of stay was prolonged and almost half of the discharge summaries did not mention diabetes. These findings have major implications for service delivery and resource planning.

Adult↗

Electrical spinal cord stimulation in the long-term treatment of chronic painful diabetic neuropathy.

AIMS: Electrical spinal cord stimulation (ESCS) is a technique for the management of chronic painful diabetic neuropathy (CPDN) affecting the lower limbs. We assessed the efficacy and complication rate of ESCS implanted at least 7 years previously in eight patients. METHODS: After a trial period of percutaneous stimulation, eight male patients had been implanted with a permanent system. Mean age at implantation was 53.5 years and all patients were insulin treated with stage 3 severe disabling CPDN of at least 1 year's duration. The ESCS was removed from one patient at 4 months because of system failure and one patient died 2 months after implantation from a myocardial infarction. RESULTS: Six patients were reviewed a mean of 3.3 years post-implantation. With the stimulator off, McGill pain questionnaire (MPQ) scores (a measure of the quality and severity of pain) were similar to MPQ scores prior to ESCS insertion. Pain scores (visual analogue scale) were measured with the stimulator off and on, respectively: background pain [74.5 (63-79) mm vs. 25 (17-33) mm, median (interquartile range), P = 0.03), peak pain (85 (80-92) mm vs. 19 (11-47) mm, P = 0.03]. There were two further cardiovascular deaths (these patients had continued pain relief) and the four surviving patients were reassessed at 7.5 (range 7-8.5) years: background pain [73 (65-77) mm vs. 33 (28-36) mm, median (interquartile range)], peak pain [86 (81-94) mm vs. 42 (31-53) mm]. Late complications (> 6 months post-insertion) occurred in two patients; electrode damage secondary to trauma requiring replacement (n = 1), and skin peeling under the transmitter site (n = 1). One patient had a second electrode implanted in the cervical region which relieved typical neuropathic hand pains. CONCLUSIONS: ESCS can continue to provide significant pain relief over a prolonged period of time with little associated morbidity.

Activities of Daily Living↗

Awareness and use of smoking cessation treatments among diabetic patients.

AIMS: To investigate awareness of pharmacotherapeutic aids to smoking cessation in diabetic cigarette smokers. METHODS: A structured questionnaire-based interview was held by a research nurse individually with consecutively attending cigarette smokers. RESULTS: Of 597 diabetic patients attending a routine clinic, 100 (17%) were current cigarette smokers. Mean (+/-sd) age was 58+/-11 years, 58% were male, and 96% Type 2 diabetic patients. Mean daily cigarette consumption was 16/day, for a mean duration of 35 years. There were 34% who had never heard of nicotine replacement therapy (NRT), and of those who had, only 49% considered it safe with diabetes. Bupropion (Zyban) was unknown to 46%, and of those who knew of it, 39% thought it unsafe in diabetic patients. Only 31% of the group had been previously offered NRT, and 14% bupropion. The NHS Quitline was known of by 84%, but only 8% had used it. CONCLUSIONS: Cigarette smokers with diabetes have poor uptake, awareness and knowledge of NRT and bupropion as aids to smoking cessation. They comprise a high-risk group, for large and small vessel disease, and these findings are therefore of concern. More active education and support for these patients by medical and nursing staff is needed.

Aged↗

Glycaemic control in a type 1 diabetes clinic for younger adults.

BACKGROUND: In the Diabetes Control and Complications Trial (DCCT, 1993) tight diabetes control (HbA1c <7%) was associated with significantly less microvascular complications compared to 'conventionally' treated type 1 patients. AIM: To assess the effectiveness of a dedicated young-adult type 1 diabetes clinic in achieving HbA1c levels <7% between 1991 and 2001. DESIGN: Retrospective review of case-notes. METHODS: All patients who attended the clinic in the first six years (1991 to 1996) were studied. All were offered at least two appointments per year. Case-notes were reviewed up to December 2001. RESULTS: We treated 386 type 1 patients (59.8% male, mean age 28.7 years, mean duration diabetes 9.5 years). After a mean follow-up of 7.7 years, 261 (67.6%) had attended in the past 2 years, 22 (5.8%) were known to have died, 11 (2.8%) had transferred to another clinic and 92 (23.8%) had repeatedly failed to attend appointments for 2 years. Over 11 years, the total mean (SD) HbA1c was 9.19% (1.3). Only 3.4% of patients achieved an average HbA1c of <7% during the study period, and 80% of patients had average HbA1c levels of >8%. DISCUSSION: Despite regular specialist physician, specialist diabetes nurse and dietician input, encouragement of multiple daily insulin injections and repeatedly following-up failed appointments (including home visits), fewer than 1:20 patients achieved the DCCT target of mean HbA1c <7%. Tight diabetes control is rare in a routine clinic setting.

Adult↗

Chronic painful peripheral neuropathy in an urban community: a controlled comparison of people with and without diabetes.

AIMS: A cross-sectional study has been performed in order to estimate the prevalence, severity, and current treatment of chronic painful peripheral neuropathy (CPPN) in people with diabetes in the community. METHODS: Using a structured questionnaire and examination we have assessed these factors in a community sample of people with diabetes (n=350) and compared them with 344 age- and sex-matched people without diabetes from the same locality. RESULTS: The prevalence of CPPN was estimated to be 16.2%[95% confidence interval (CI): 6.8-16%] in people with diabetes compared with 4.9% (95% CI: 2.6-7.2%) in the control sample (P < 0.0001). Diabetic subjects with and without CPPN did not differ in age, sex, type and duration of diabetes, body mass index, smoking status and glycaemic control. However, CPPN diabetic subjects had significantly higher Visual Analogue Scale (VAS) scores for pain over the preceding 24 h [median (interquartile range) 3.5 (1.5-6.7) cm vs. 0.7 (0-3.9) cm, P < 0.0001]. Also, the total McGill Pain Questionnaire Score (a measure of pain quality and severity) was 18 (13-31.5) vs. 10 (4-16) (P < 0.0001). Of patients with diabetes and CPPN, 12.5% (7/56) had never reported their symptoms to their treating physician and 39.3% (22/56) had never received any treatment for their painful symptoms. CONCLUSIONS: CPPN is common, often severe but frequently unreported and inadequately treated.

Adult↗

Diabetes in a high secure hospital.

AIMS: To determine the prevalence of diabetes mellitus and its possible causes and to assess its control in a high secure hospital. METHODS: A cross sectional survey and a prospective cohort study were conducted. The cross sectional survey included 408 patients admitted under the Mental Health Act, and the prospective study included 22 patients with known diabetes followed up for 24 months. The outcome measures evaluated were drug treatment, status of microvascular and macrovascular complications, glycated haemoglobin, and body mass index. RESULTS: In the cross sectional survey, 35 out of 408 patients (8.6%; 95% confidence interval 5.9% to 11.3%) had known diabetes, and all of these had type 2 diabetes. Obesity, cigarette smoking, schizophrenia, and antipsychotic drug use were frequent, and weight gain was common after hospital admission. Glycaemic control was variable, and, although a majority of patients were above recommended treatment targets, control remained stable over the follow up period. CONCLUSIONS: Type 2 diabetes was common in this hospital. Both its prevalence and the suboptimal glycaemic control in some patients probably relate to sedentary life, dietary factors, smoking, and perhaps widespread use of antipsychotic drugs. However, regular multidisciplinary input enabled most patients to maintain relatively stable glycaemic control, with good control of blood pressure and lipids, at levels similar to those seen in community and hospital diabetic clinics. Further modification of lifestyle risk factors is probably needed to reduce the prevalence and impact of diabetes in this patient group.

Adult↗

Assessment of quality of life in adults receiving long-term growth hormone replacement compared to control subjects.

OBJECTIVE: There are few studies of quality of life (QOL) in adults with growth hormone deficiency (GHD) compared to matched control populations without GHD. These have shown impairments in a variety of QOL measures, which improve but do not normalize after short-term replacement with GH. There is little information on QOL in long-term treated GHD patients compared with controls without GHD. PATIENTS AND METHODS: A total of 120 adults with GHD who had received GH replacement for at least 1 year were identified from the neuroendocrine clinic. Patients were asked to complete eight QOL questionnaires and an Energy Visual Analogue Scale (VAS). Results were compared with 83 control subjects without GHD from the local population who agreed to complete seven of the QOL questionnaires (excluding Disease Impact scale) and the energy VAS. The eight questionnaires were a combination of generic and disease-specific questionnaires used to assess health related QOL, namely: Short Form-36 (SF-36), Nottingham Health Profile (NHP), Disease Impact, Life Fulfilment and Satisfaction scales, Mental Fatigue Questionnaire (MFQ) and Self Esteem scale, Hospital Anxiety Depression (HAD) scale and QOL-AGHDA (assessment of GHD in adults). RESULTS: Eighty-nine patients returned questionnaires and 85 (71%) had complete data for analysis. The mean (SD) duration of GH replacement was 36.0 +/- 26.4 (range 13-159) months. Mean age was 43.9 +/- 15.8 years (37 males) in treated GHD patients compared to a mean age 41.7 +/- 10.5 years (32 males) in the controls. Mean IGF-1 levels were 22.5 +/- 13.6 nmol/l in the GHD patients and the mean dose of GH replacement was 1.2 +/- 0.4 IU daily. Analysis of the QOL questionnaires from the GH treated patients revealed highly significant impairments in all measures (most P </= 0.0001, except life fulfilment-material, P = 0.33) compared to the control population. CONCLUSIONS: This large population with treated GH deficiency have significant impairments in multiple aspects of QOL despite replacement with GH and other pituitary hormones for at least 1 year (mean 3 years). It is likely therefore that other factors in addition to GH deficiency must influence QOL in these patients. Further strategies to improve QOL in these individuals should therefore be considered, e.g. psychological support and treatments and physical treatments (such as exercise programmes).

Adult↗

Elderly people with hypothalamic-pituitary disease and untreated GH deficiency: clinical outcome, body composition, lipid profiles and quality of life after 2 years compared to controls.

OBJECTIVE: Elderly patients with GH deficiency (GHD) have significant impairments in multiple aspects of quality of life (QOL) but similar lipid profiles compared to age-matched control subjects. There are, however, no data on changes in these parameters with time. This study assessed the impact of untreated GHD over a period of 2 years in a group of elderly patients with hypothalamic-pituitary disease in relation to new illnesses and differences in body composition, circulating lipid profile levels and QOL. Control subjects were also followed for 2 years. SUBJECTS: Twenty-seven elderly patients (> 65 years) with hypothalamic-pituitary disorders and GHD (mean peak stimulated GH response 1.6 mIU/l, range 0.6--5.0) were studied initially. Two years later 21 (13 males) agreed to attend for reassessment. Mean age was then 72.7 +/- 5.04 years (range 67--85). Eighteen patients had pituitary tumours, three had craniopharyngiomas. Twenty-seven control subjects were studied at baseline and 17 (7 males) agreed to attend for reassessment. Mean age was then 75.9 +/- 6.97 years (range 67--88). METHODS: Weight, body mass index (BMI), total fat mass (FM) (bioelectrical impedance), serum IGF-1 and fasting lipid profile (total cholesterol, triglyceride, HDL cholesterol, LDL cholesterol) were measured. QOL was assessed in both groups using five interviewer-administered self-rating questionnaires: the Nottingham Health Profile, Short Form-36, Hospital Anxiety and Depression Scale, Mental Fatigue Questionnaire and Life Fulfillment Scale. The GHD group also completed the Disease Impact Scale. RESULTS: Two of the 27 patients with GHD died during the 2-year follow-up (myocardial infarction and probable cerebrovascular accident). Four controls could not be traced but there were no deaths in the other 23. In the 21 GHD patients after 2 years, mean serum IGF-1 and BMI were unchanged (12.6 +/- 5.8 vs. 13.3 +/- 5.1 nmol/l, P = 0.5 and 28.3 +/- 4.3 vs. 29.1 +/- 4.2, P = 0.5, respectively) at the 2-year follow-up and there were no significant changes in the lipid profiles. However, there was a significant reduction in fat mass (31.7 +/- 11.2 vs. 28.5 +/- 10.9%, P = 0.04). In the 17 control subjects after 2 years, serum IGF-1 levels (17.2 +/- 4.0 vs. 15.7 +/- 5.6 nmol/l, P = 0.4), BMI and fat mass were unchanged. However, there was a significant fall in total cholesterol levels over the 2-year follow-up (6.3 +/- 0.9 vs. 5.7 +/- 0.9 mmol/l, P < 0.0001), although LDL cholesterol, triglycerides and HDL cholesterol were unchanged. Analysing the QOL data, the GHD patients had less energy (P < 0.05), more depression (P < 0.05), more pain (P < 0.05) and lower life fulfillment scores (P < 0.01) after 2 years. However, the control subjects also had less energy (P < 0.05), less vitality (P < 0.05) and lower self-esteem (P < 0.05), more depression (P < 0.05), worse mental health (P < 0.05), life fulfillment personal (P < 0.01), life fulfillment material (P < 0.02), physical functioning and role physical functioning (P < 0.05) after 2 years. Comparing the patients and controls at baseline, there were significant differences in IGF-1, BMI, FM, LDL cholesterol, personal life fulfillment, mental fatigue, general health and mental health. However, after 2 years, only BMI and depression scores were significantly different. CONCLUSION: These patients with untreated GHD did not have deterioration of body composition or lipid profiles when reassessed after a period of 2 years. In fact, fat mass fell. The control subjects did have a significant decrease in total cholesterol but no change in other lipids or body composition. Some quality of life domains did deteriorate in the patients with GHD. However, the control subjects also had worse quality of life scores after 2 years which were then little different from the GHD patients. These results raise doubts about the benefits of GH replacement in elderly people with GHD.

Adenoma↗

Is coeliac disease more prevalent in young adults with coexisting Type 1 diabetes mellitus and autoimmune thyroid disease compared with those with Type 1 diabetes mellitus alone?

AIM: It is known that patients with Type 1 diabetes mellitus are more prone to develop coeliac disease and that autoimmune thyroid disease occurs more frequently in patients with coeliac disease. We therefore assessed whether coeliac disease, either known or occult, occurs more frequently in young/middle aged adults with Type 1 diabetes and coexisting autoimmune thyroid dysfunction than in adults with Type 1 diabetes alone. METHODS: The prevalence of known coeliac disease was assessed in 509 (301 males, aged 16-55 years) patients with Type 1 diabetes, 28 (5.5%) of whom had treated autoimmune thyroid disease. In a second study 38 patients with Type 1 diabetes and coexisting autoimmune thyroid disease along with 112 patients with Type 1 diabetes alone were then screened for coeliac disease using serum IgA endomysial antibodies and IgA gliadin antibodies. RESULTS: Seven of the 509 patients (1.4%) had been diagnosed with coeliac disease and two of these had later developed autoimmune thyroid disease (both hypothyroid). The subsequent screening exercise found that one of the 38 patients with both Type 1 diabetes and thyroid disease had positive endomysial antibodies on screening. However, duodenal biopsy was negative for coeliac disease. There were two patients with positive endomysial antibodies in the group of 112 patients with diabetes only. Both had duodenal biopsy but only one was consistent with coeliac disease. CONCLUSION: The prevalence of known coeliac disease in this young adult Type 1 diabetes clinic in North-west England was 7/509 (1.4%). Two of these seven patients with coeliac disease were from the group of 28 who had autoimmune thyroid disease as well. Therefore we suggest that patients with known coeliac disease and Type 1 diabetes should be screened for autoimmune thyroid disease. The second screening study then found 3/150 (2%) to have a serological marker for coeliac disease. However, patients with both Type 1 diabetes and autoimmune thyroid disease were not more likely to have occult coeliac disease compared with those with Type 1 diabetes only.

Adolescent↗

An audit of 500 subcutaneous glucagon stimulation tests to assess growth hormone and ACTH secretion in patients with hypothalamic-pituitary disease.

OBJECTIVE: The insulin tolerance test (ITT) is usually regarded as the 'gold standard' for the assessment of the hypothalamic-pituitary axis (growth hormone (GH) and ACTH) but must be used with caution and is contra-indicated in certain groups of patients. The glucagon stimulation test (GST) has previously been shown to be a good alternative when the ITT is contra-indicated and like the ITT stimulates both GH and ACTH secretion. There is however limited data on the use of the GST in patients with hypothalamic-pituitary disease. DESIGN AND PATIENTS: An audit of 500 GST was performed in 374 patients with hypothalamic-pituitary disease. Glucagon was administered via the subcutaneous route and bloods were taken at times 0 90 120 150 180 210 and 240 minutes. RESULTS: In the vast majority peak GH (84.4%) and cortisol (93%) responses occurred between 120 and 180 minutes Little information was obtained from the 240 minute sample. The medical supervision required was minimal and the side-effects encountered during this test were mild; 20% of the tests were associated with nausea occasionally with vomiting sweating or headaches. Four patients fainted but recovered quickly. CONCLUSIONS: This large audit has shown that the glucose stimulation test is well tolerated and can easily be performed in an out-patient setting with minimal medical supervision. The 240 minute sample added little additional information and could be omitted.

Acromegaly↗

Hydrocortisone replacement dosage influences intraocular pressure in patients with primary and secondary hypocortisolism.

BACKGROUND: It has been suggested that the variation of intraocular pressure (IOP) during the day follows the diurnal variation of serum cortisol. There is also a higher risk of ocular hypertension and glaucoma in patients taking excessive oral steroid treatment. We assessed whether different replacement doses of hydrocortisone (HC) influenced IOP. METHODS: Seventeen patients (six Addison's disease, 11 hypopituitarism; seven males) aged 24-58 years mean 42.7 years and 20 control subjects (nine males) aged 20--59 years mean 38.7 years were studied. On the first visit, the 17 patients had been taking HC replacement doses, 20 mg morning and 10 mg afternoon. Serum cortisol and IOP in both eyes (Goldmann applanation tonometer) were measured at 0900, 1100, 1300, 1500, 1700 hours with HC 20 mg taken after the 0900 h assessment. The dose of HC was then reduced to 10 mg morning and 10 mg afternoon for 1 week and the measurements were repeated in 16 patients, with HC 10 mg taken at 0900 h. RESULTS: In the patients the peak serum cortisol occurred at 1100 h after the 0900 h HC dose. Cortisol levels were significantly higher at 1100, 1300, 1500 and 1700 h after taking 20 mg compared to 10 mg HC. The mean (SEM) IOP (mmHg) was significantly higher after 20 mg HC compared with 10 mg HC at 1300 h: 14.7(0.6) v 13.1(0.6) (P = 0.004) and at 1500 h: 14.4(0.6) v 13.1(0.5) (P = 0.04). The total mean (SEM) daily IOP score was significantly higher after 20 mg HC compared with 10 mg HC: 14.5(0.3) v 13.5(0.3) (P = 0.0002). The total mean (SEM) daily IOP score after the 20 mg HC dose compared with the control subjects was: 14.5(0.3) v 13.7(0.3) (P = 0.08). CONCLUSION: Intraocular pressures during the day are influenced by the morning hydrocortisone replacement dosage with significantly higher intraocular pressure levels in the early afternoon following 20 mg compared with 10 mg. A morning hydrocortisone dose of 10 mg leads to a more physiological intraocular pressure profile during the day. These data support the view that a daily replacement dose of 30 mg hydrocortisone may be excessive.

Addison Disease↗

The influence of growth hormone replacement on heart rate variability in adults with growth hormone deficiency.

OBJECTIVE: Growth hormone (GH) deficiency is associated with increased cardiovascular morbidity and mortality. Abnormalities in heart rate variability (HRV), a surrogate marker of cardiac autonomic tone, have also been found in untreated growth hormone deficient (GHD) patients. Similar abnormalities have been found in patients with complications postmyocardial infarction. DESIGN AND MEASUREMENTS: This study was designed to investigate whether GH treatment leads to normalization of cardiac autonomic tone. HRV measurements were obtained from 15 minute resting ECG recordings in 11 untreated adult GHD patients (7 females; mean age 39.2 years), 10 GHD patients (6 females; mean age 46.2 years) reCENving GH replacement (mean duration, 52.7 months) and 12 healthy controls (7 females; mean age 44.6 +/- 2.9 years) who were all of similar age, weight and BMI. The untreated GHD patients were then commenced on GH and HRV measurements repeated after 3 and 6 months of treatment. RESULTS: In accord with our previous findings, HRV analysis using Fast Fourier Transform (FFT) showed a distinct pattern of abnormality in GHD patients compared with controls. Specifically, there was an increase in nHF power (P = 0.04) and a reduction in nLF power (P = 0.04) (representing parasympathetic and sympathetic activity, respectively), a reduction in nVLF power (P = 0.03) and a 50% reduction in LF/HF ratio (P = 0.02) (a measure of sympathovagal balance) in GHD patients when compared with controls. HRV results in patients who have been on long-term GH replacement were indistinguishable from controls. After 3 months GH replacement in the untreated GHD patient group, nVLF power had increased by 28% (P = 0.03) at 3 months and this was sustained at 6 months. However, no significant changes in LF and HF power were seen. CONCLUSIONS: These results suggest that abnormalities of the cardiac autonomic system in GHD patients may be correctable. Longer duration of prospective follow-up will be required to determine at what time point improvements in the other frequency bands occur.

Adult↗

CSF rhinorrhoea following treatment with dopamine agonists for massive invasive prolactinomas.

OBJECTIVE: The management of CSF rhinorrhoea following dopamine agonist (DA) treatment for invasive prolactinomas is difficult and there is no clear consensus for its treatment. Our objective was therefore to investigate the different treatments for this condition. DESIGN AND PATIENTS: We examined the case notes of five patients with invasive prolactinomas and CSF rhinorrhoea following DA treatment. The different ways in which this complication had been managed is detailed along with a review of the literature. RESULTS: Five patients aged 24-67 years (3 male) with massive invasive prolactinomas (serum prolactin 95000-500000 mU/l) eroding the skull base were treated with dopamine agonists (3 bromocriptine, 1 cabergoline and 1 both). CSF rhinorrhoea developed in all patients between 1 week and 4 months after commencing dopamine agonist treatment. In two patients (cases 1 and 4), CSF rhinorrhoea ceased within a few days of stopping bromocriptine but restarted when treatment was resumed. One of these (case 4), a 67-year-old woman had no further treatment and CSF leakage stopped completely. She died of unrelated medical problems 3 years later. In one patient staphylococcus aureus meningitis and pneumocephalus developed as a complication of CSF rhinorrhoea. Three patients had endoscopic nasal surgery to repair the fistula using muscle grafts, and to decompress the pituitary tumour, with success in two. One patient had intracranial surgery and dural repair, which was successful in sealing the leak. CONCLUSIONS: We suggest that surgery as soon as is feasible is the treatment of choice for the repair of a CSF leak following dopamine agonist treatment. An additional strategy is the withdrawal of dopamine agonist to allow tumour re-growth to stop the leak.

Adult↗

Elderly people with hypothalamic-pituitary disease and growth hormone deficiency: lipid profiles, body composition and quality of life compared with control subjects.

OBJECTIVE: In healthy adults the secretion of growth hormone (GH) and insulin-like growth factor 1 (IGF-1) declines with ageing and body composition alters, particularly with an increase in total body fat. In elderly people, hypothalamic-pituitary disease can cause GH deficiency (GHD), compared with age matched controls. This study aimed to clarify whether GHD in the elderly is associated with differences in body composition, circulating lipid levels and quality of life (QOL) compared with control subjects. SUBJECTS: Twenty-seven elderly patients (14 males, mean age 71 years, range 65-83) with hypothalamic-pituitary disorders (23 pituitary tumours) and GHD (mean (SD) peak stimulated GH response 1.6 mIU/l (1.03) range 0.6-5) were studied. Twenty-five patients had been treated surgically (six cranial surgery, 19 transsphenoidal) and eight patients had received external cranial irradiation. Twenty-seven control subjects (14 males, mean age 72 years, range 65-86) were also studied. METHODS: Weight, body mass index (BMI), total fat mass (FM, bioelectrical impedance), waist to hip ratio (WHR), serum IGF-1, fasting blood glucose and lipid profile were measured. QOL was assessed in both groups using five interviewer administered self-rating questionnaires: The Nottingham Health Profile, Short-Form 36, Hospital Anxiety and Depression Scale, Mental Fatigue Questionnaire and Life Fulfilment Scale. The GHD group also completed the Disease Impact Scale. RESULTS: The data (mean (SD)) from males and females were analyzed separately. The male patients had a higher BMI than controls, 28.9(4.5) vs. 25.2(2.3) kg/m2 (P = 0.01) but the BMI in the female patients and controls was similar. In the female patients compared with the controls, FM was higher 39. 4(6) vs. 33.1(8.3) % (P = 0.02), WHR was also higher 0.9(0.08) vs. 0. 83(0.09) (P = 0.03) and serum IGF-1 levels were lower 10.8(6.4) vs. 18.2(6.5) nmol/l (P = 0.01). However, in the male patients, FM, WHR and IGF-1 levels were similar to the controls. Fasting blood glucose was similar in both male and female patients and the controls. Two female patients and one male control subject were taking lipid-lowering agents and were therefore excluded from the analysis of lipid profiles. Total cholesterol, triglyceride, LDL cholesterol, HDL cholesterol and total cholesterol/HDL cholesterol ratio were not significantly different for both male and female patients compared with the controls. The 27 patients with GHD reported significantly less energy (P < 0.05), mobility (P < 0.05) and personal life fulfillment (P < 0.01) than the 27 controls. There were significantly more problems with emotional reaction (P < 0.01), social isolation (P < 0.05) and mental fatigue (P < 0.05). Additionally the GHD group reported more impairment in areas of social functioning (P < 0.05), general health (P < 0.05) and mental health (P < 0.05). The GHD group reported a modest degree of disease impact (mean score of 14.1). There were no significant differences in the domains of material life fulfillment, pain, sleep, physical functioning, vitality, anxiety, depression, self-esteem or role physical functioning compared with the controls. CONCLUSION: Compared with control subjects, the elderly female patients with hypothalamic-pituitary disease and GHD had a significantly higher total fat mass, with the WHR indicating a more central fat distribution and lower female serum IGF-1 levels. In contrast, elderly male patients had similar total fat mass, WHR and IGF-1 levels compared to the controls. There were no significant differences in the lipid profiles between male or female patients compared to controls. However, many of the male patients were receiving androgen replacement which might have influenced these results. Low HDL cholesterol concentrations are probably a better predictor of future cardiovascular disease than raised LDL cholesterol levels in the elderly population and these were similar in patients and controls for both

Aged↗

Comparison of questionnaire, breath carbon monoxide and urine cotinine in assessing the smoking habits of Type 2 diabetic patients.

AIMS: Previous studies have suggested that the self-reporting of smoking amongst diabetic patients is unreliable, and that objective markers such as breath carbon monoxide (CO) or urinary cotinine are needed. As these studies have been mostly in young Type 1 diabetic patients, the reliability of smoking history has been assessed in a large group of older Type 2 diabetic patients. METHODS: Two hundred and ninety-nine Type 2 diabetic patients were investigated for smoking habits by unstructured questionnaire, breath CO, and urinary ratio. RESULTS: Mean age of the group was 63 (range 30-80) years and 41% were female. Direct questioning suggested 77 (26%) to be smokers, and of these 852 had raised (>1 microg/mg) urinary cotinine-creatinine , and 71% raised (>8 p.p.m.) breath CO. Assuming urinary cotinine-creatinine as the 'gold standard', the sensitivity, specificity and positive predictive values for questionnaire were 97%, 95% and 85%, respectively; and for breath CO they were 74%, 98%, and 93%. CONCLUSION: It is concluded that at least in this population of Type 2 diabetic patients, a structured smoking history appeared to identify current smokers with good accuracy.

Adult↗