Failure to reduce nicotine addiction in young adults with diabetes.
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Adolescent↗
Biomedical subjects
I A MacFarlane
Publications and source records attributed to I A MacFarlane.
Abnormal heart rate variability in adults with growth hormone deficiency.
GH-deficient (GHD) patients have increased risk of cardiovascular death and may have cardiac structural abnormalities. In non-GHD patients these are associated with cardiac autonomic dysfunction, and it is possible that autonomic dysfunction is also present in GHD patients. Power spectral analysis (PSA) of heart rate variability (HRV) indirectly measures cardiac autonomic tone and generates peaks at 3 frequency bands, very low frequency (VLF), low frequency (LF) and high frequency (HF). The area under the LF curve is considered to reflect predominantly cardiac sympathetic activity, whereas HF indicates parasympathetic activity. PSA of HRV was performed in 14 normotensive GHD patients (5 men and 9 women; mean age, 35.2 yr) and 19 healthy controls (9 men and 10 women; mean age, 38.3 yr). GHD patients had 26% lower normalized LF power (P < 0.004), 39% higher normalized HF power (P < 0.001), 28% lower normalized VLF power (P < 0.046), and 51% lower LF/HF ratio (an index of sympathovagal balance; P < 0.001) compared to controls. These data indicate that heart rate variability is abnormal in patients with GHD. The decreased sympathetic tone could be a consequence of reduced central sympathetic tone or altered cardiac responsiveness to autonomic control and may contribute to the increased cardiovascular risk in GHD patients.
Adult↗
The quality of life of adults with growth hormone deficiency: comparison with diabetic patients and control subjects.
OBJECTIVE: Adults with GH deficiency (GHD) frequently report a poor quality of life (QOL). Whether this poor QOL is specifically due to hormone deficiency or a non specific effect of a chronic condition is not known. We therefore assessed QOL in adults with hypopituitarism and GHD and compared scores with a group of patients with diabetes mellitus, another life-long condition with potentially serious complications and a group of healthy controls. PATIENTS: We studied 57 patients with hypopituitarism and GHD (peak stimulated GH response < 9 mU/l) (23 male, mean age 36.4 years, mean stimulated GH response 2.3 mU/l), secondary to a variety of hypothalamic-pituitary disorders. Fifty had been treated surgically (39 cranial surgery, 11 transsphenoidal) and 37 had received external cranial irradiation involving the hypothalamic region. Fifty-seven age and sex matched patients with diabetes mellitus (31 insulin treated, 18 on oral hypoglycaemic agents, 8 on diet alone) and 57 matched healthy controls were also studied. DESIGN AND MEASUREMENTS: We assessed and compared health related QOL in the 3 groups using 4 self rating questionnaires: Hospital Anxiety and Depression Scale, Self Esteem Scale, Mental Fatigue Questionnaire and Life Fulfilment Scale. In addition the GHD and diabetic groups also completed the Disease Impact Scale. RESULTS: The GHD group reported significantly more depression (P < 0.05) and mental fatigue (P < 0.05) and significantly less self esteem (P < 0.05) and life fulfilment (P < 0. 05) than either the group with diabetes or the controls. Patients with GHD reported significantly higher anxiety scores (P < 0.05) than the controls. Within the GHD group there were no differences in QOL scores between patients with pituitary tumours (n = 24), craniopharyngiomas/hypothalamic tumours (n = 18) or other brain tumours. In addition there were no significant differences according to surgical treatment modality or radiotherapy. However subgroup analysis revealed that the patients who had undergone transsphenoidal surgery (n = 11) differed significantly from the control group in life fulfillment and depression (P < 0.01) only and did not differ from the DM group in any of the questionnaires used. There were no significant differences between the group with diabetes and the control group in any of the measures except depression (P < 0.05). CONCLUSIONS: This study revealed a significant impairment of QOL in adults with GHD, particularly those who had undergone cranial surgery, when compared to matched patients with diabetes and healthy controls.
Adult↗
Painful diabetic neuropathy.
Chronic painful diabetic neuropathy causes symptoms that can last for many years and severely impair the quality of life of affected patients. This review describes the epidemiology, pathophysiology and treatment of chronic neuropathic pain. Particular emphasis is placed on a comprehensive review of the management of painful symptoms through a detailed review of the published literature using a variety of databases particularly Medline and EMBASE.
Diabetic Neuropathies↗
Painful diabetic neuropathy.
Chronic painful diabetic neuropathy can cause a variety of challenges, particularly in successful treatment. The pain, which can last for years, can severely impair quality of life. Management is difficult, although the careful use of drugs can be significantly beneficial. Tricyclic and anticonvulsant drugs may be effective, with a variety of drugs available as second line agents. Newer non-drug systems such as electrical spinal cord stimulation represent exciting possibilities for the future management of this most difficult diabetic syndrome.
Analgesia↗
Apo E phenotype and changes in serum lipids in adult patients during growth hormone replacement.
OBJECTIVE: To determine whether apo E phenotype influences changes in lipid profiles induced by growth hormone replacement in growth hormone (GH)-deficient adults. DESIGNS: Patients were treated for 6 months with recombinant human GH (hGH), given in a dose of 0.125 U/kg per week for 4 weeks followed by 0.25 U/kg per week thereafter. The effects on serum lipids and the influence of apo E phenotype were examined. METHODS: Thirty patients (aged 35.1+/-11.8 years: mean +/- S.D.) with adult growth hormone deficiency with included in the study. Fasting serum samples were analysed for apo E phenotype total cholesterol, high-density lipoprotein (HDL)-cholesterol, triglycerides, lipoprotein (a) (Lp(a)) and IGF-I. Low-density lipoprotein (LDL)-cholesterol was calculated using the Friedwald formula. RESULTS: Six months of replacement treatment with hGH resulted in a reduction in HDL-cholesterol from 0.90+/-0.10 to 0.68+/-0.08 mmol/l (P<0.01), and a small, non-significant reduction in total cholesterol from 6.14+/-0.40 to 5.99+/-0.35 mmol/l (P = 0.06). There was no significant change in the other lipid parameters. The decrease in HDL-cholesterol concentration was greater in patients carrying the apo E2 allele (0.40+/-0.07 mmol/l, P<0.05) than in patients homozygous for the apo E3 allele (0.23+/-0.04 mmol/l) and patients carrying the apo E4 allele (0.15+/-0.36 mmol/l). Patients with the apo E4 allele had lower baseline cholesterol concentrations than patients lacking the apo E4 allele, and this persisted after treatment with hGH (P<0.05). CONCLUSIONS: Apo E phenotype may be a determining factor in the response of HDL-cholesterol to hGH in GH-deficient adults.
Adult↗
Cystic lymphocytic hypophysitis, visual field defects and hypopituitarism.
A 45-year-old man presented with anterior pituitary failure, requiring thyroxine, hydrocortisone and androgen replacement. An MRI scan revealed a large cystic pituitary mass and thickening of the pituitary stalk. Over three years, diabetes insipidus and bitemporal hemianopia developed and the cystic mass had enlarged on MR scanning. Transphenoidal resection was performed with normalisation of the visual fields. Histology revealed lymphocytic hypophysitis, which is rare in men. The presentation with cystic enlargement is unique.
Diabetes Insipidus↗
HDL-cholesterol reductions associated with adult growth hormone replacement.
OBJECTIVE: To study the effects of human growth hormone (hGH) replacement on serum lipids and lipoprotein (a) (Lp(a)) concentrations. DESIGN: A randomized double blind placebo controlled trial for 6 months followed by an open trial where all patients were treated with hGH for a further 6 months. Treatment was with recombinant hGH given in a dose of 0.125U/kg/wk increasing to 0.25U/Kg/wk. PATIENTS: Thirty two patients with growth hormone deficiency were recruited, but two withdrew because of side effects. Of the thirty patients (age 35.1 +/- 11.8 year; mean +/- SD) completing the study 13 of were assigned to the placebo group for six months and 17 to active treatment from the start. MEASUREMENTS: Fasting serum samples were analysed for total cholesterol, High density lipoprotein (HDL)-cholesterol, HDL-subfractions, triglycerides, lipoprotein (a) (Lp(a)) and IGF-1. LDL-cholesterol was calculated using the Friedewald formula. RESULTS: Compared to placebo, 6 months treatment with hGH therapy resulted in increased IGF-1 (37.6 +/- 4.1 vs. 14.0 +/- 2.2 nmol/l, P < 0.01), but there was no significant difference in any of the lipid parameters measured between placebo and active treatment groups at 6 months. hGH was associated with a decrease in HDL-cholesterol concentration from baseline to 6 months (0.97 +/- 0.08 to 0.76 +/- 0.10 mmol/l P < 0.01), especially within the HDL2 subfraction. This reduction was maintained at 12 months. There was no change in Lp(a) concentrations from 0 to 6 months (placebo -26 (-340 to 82), median and range, active -4 (-586 to 212) mg/l). There was no change in total cholesterol, LDL-cholesterol, triglycerides or proportion of HDL subfractions. CONCLUSIONS: Treatment with hGH can reduce serum HDL-cholesterol concentrations. Further investigation of this is required.
Adult↗
Diabetic peripheral neuropathy and quality of life.
The quality of life (QOL) of 79 people with type 1 and type 2 diabetes and 37 non-diabetic controls was assessed using the Nottingham Health Profile (NHP). The NHP consists of six domains assessing energy, sleep, pain, physical mobility, emotional reactions and social isolation. Symptomatic diabetic neuropathy was present in 41 of the patients. The neuropathy patients had significantly higher scores (impaired QOL) in 5/6 NHP domains than either the other diabetic patients (p < 0.01) or the non-diabetic (p < 0.001) controls. These were: emotional reaction, energy, pain, physical mobility and sleep. The diabetic patients without neuropathy also had significantly impaired QOL for 4/6 NHP domains compared with the non-diabetic control group (p < 0.05) (energy, pain, physical mobility and sleep). This quantification of the detrimental effect on QOL of diabetes, and in particular of chronic symptomatic peripheral diabetic neuropathy, emphasizes the need for further research into effective management of these patients.
Activities of Daily Living↗
Confusion after visiting the radiology department.
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Adrenal Insufficiency↗
Diurnal variation in blood pressure in insulin-dependent diabetic smokers and non-smokers with and without microalbuminuria.
In subjects with essential hypertension, loss of the normal nocturnal dip in blood pressure is associated with a greater risk of developing end-organ complications. In subjects with diabetes, smoking carries a similar association. To assess whether these factors may have an aetiological and synergistic role in the vascular complications of diabetes, 24-hour blood pressure monitoring was performed in insulin-dependent diabetic (IDDM) patients with normal albumin excretion (n = 19) and microalbuminuria (n = 21) of comparable age and duration of diabetes, and with no evidence of autonomic neuropathy or hypertension. The potential influence of smoking was examined by subdividing the groups, depending on smoking status. Ten of the microalbuminuric group and 9 of the normoalbuminuric group were current smokers, the remaining patients never having smoked. There was a significant difference between mean (+/-SD) daytime vs nocturnal blood pressure in patients with normal albumin excretion (114 +/- 3/70 +/- 4 vs 102 +/- 3/62 +/- 3 mmHg; p < 0.001) and microalbuminuria (109 +/- 5/75 +/- 5 vs 101 +/- 3/65 +/- 4 mmHg; p < 0.001) but mean blood pressure values did not differ significantly between the groups. A similar fall in nocturnal blood pressure was found in smokers and non-smokers with and without microalbuminuria (p < 0.001), but there was no difference between the mean blood pressure values in the different subgroups. In conclusion, normotensive IDDM patients, who do not have autonomic neuropathy, retain a significant diurnal variation in blood pressure, irrespective of smoking habit or presence of microalbuminuria.
Adult↗
Pituitary tumours presenting in the elderly: management and outcome.
OBJECTIVE: In elderly patients there are few data on the efficacy and safety of pituitary surgery and radiotherapy (DXT). The aim of the present study was to assess the mode of presentation, treatment and outcome of patients > 64 years with a pituitary tumour presenting to a regional neuroendocrine service. DESIGN: A retrospective case note review of all patients with a pituitary tumour, from 1986 to 1993, was performed with DXT information from computerized records. PATIENTS: Forty-four patients were identified: median age 70 (65-83) years; 25 males; followed for a mean of 34 (range 0-84) months. RESULTS: The commonest presenting symptom was with visual disturbance (24 patients) with a further 9 with asymptomatic visual field defects. Five patients had acromegaly and two prolactinoma. Thirty-two patients underwent transsphenoidal surgery (TSS) (with post-operative DXT in 14 cases) and 6 craniotomy. Two patients had DXT as the primary procedure and four were observed. Visual fields improved in 21 of 29 patients. Perioperative complications occurred significantly more often after craniotomy (5/6) than after TSS (6/32) (P < 0.01). Eight patients died during the follow-up period (three deaths tumour related; one death followed DXT). CONCLUSIONS: Pituitary adenoma is a remediable cause of visual disturbance in the elderly. Most tumours were non-functioning. Age alone is not a contraindication to active treatment particularly with transsphenoidal surgery and radiotherapy.
Adenoma↗
Quality of life, body composition and muscle strength in adult growth hormone deficiency: the influence of growth hormone replacement therapy for up to 3 years.
OBJECTIVE: Adults with GH deficiency complain frequently of low energy levels, emotional lability and mental fatigue resulting in a low perceived quality of life (QOL). Body composition is altered with increased fat mass and decreased lean body mass and muscle strength is reduced. The aims of this study were to determine the effects of replacement GH treatment on: (a) body composition and muscle strength and (b) QOL, using specifically selected and adapted measures. DESIGN: A 12-month study (double-blind placebo-controlled for the first 6 months and open for the second 6 months) of GH replacement injections (0.125 iu/kg/week for the first month and 0.25 iu/kg/week for the following 5 months of each study period) in GH deficient adults on QOL, body composition and muscle strength. This was followed by an open study of a further 12 months' GH treatment assessing QOL and muscle strength. Finally, QOL was assessed after up to 3 years of GH replacement treatment. PATIENTS: Thirty of the 32 adult patients with GH deficiency enrolled completed the initial 12-month study (10 male, mean age 33.5 years, mean (SD) stimulated serum GH response 3.0 mU/l (2.86)). Nineteen patients then opted to continue GH treatment. Of these, 13 patients were available for assessment after a further 12 months' and 24 months' treatment. MEASUREMENTS: Health-related QOL was assessed using 2 specifically adapted scales for adults with GH deficiency: the Life Fulfillment Scale and the Impact Scale. In addition 4 other self-rating questionnaires were used: Nottingham Health Profile, Hospital Anxiety and Depression Scale, Self Esteem Scale and Mental Fatigue Scale. Body composition was assessed by DEXA and quadriceps muscle strength by measuring maximum voluntary contractions. RESULTS: In the initial 12 months' placebo-controlled study perceived energy levels increased after 6 and 12 months of GH treatment (P < 0.01 compared with baseline) in the patients receiving GH for the full 12-month period. There were no changes in energy levels throughout the study in the group receiving placebo for the first 6 months. Also small improvements in impact scores were found after 6 months of GH treatment (P < 0.05) but this was not sustained at 12 months. In both GH and placebo groups life fulfillment worsened after 6 months, but then improved to baseline values after 12 months. In the patients who persisted with GH replacement, energy levels continued to improve (at 2 years, P < 0.01 compared with baseline) but then fell (at 3 years, P = NS compared with baseline). A similar pattern was observed in emotional reaction scores. However, improvements in self-esteem were maintained (at 3 years, P < 0.05 compared with baseline). Body composition altered favourably over the initial 12-month study period with a significant increase in lean mass and decrease in fat mass in both groups after 6-12 months of GH. There were no changes in muscle strength in either group during the initial 12-month study. However, in the patients who were available for assessment after a further 12 months of GH treatment, muscle strength increased significantly (P < 0.02 compared with baseline). CONCLUSION: GH replacement treatment for 6-12 months leads to significant improvements in body composition (DEXA) but longer-term treatment may be needed to increase muscle strength. Self-esteem scores improve and are maintained after 3 years of treatment. Energy levels and emotional reaction improve during treatment for up to 2 years but decline thereafter.
Adult↗
A six-year follow-up study of smoking habits and microvascular complications in young adults with type 1 diabetes.
One hundred insulin-dependent diabetic patients (age < 45 years, 53 smokers) were followed for six years. The age, duration of diabetes and mean glycated haemoglobin levels, were comparable between the smokers and non-smokers. Microvascular complications (retinopathy and increased urine albumin excretion) were commoner and more severe in the smoking group at six years, particularly in heavy smokers. Of the 45 original smokers reviewed at six years, 12 (27%) had stopped, six of whom had developed microvascular complications. Only two of the 'heavy' initial smokers, likely to be at most risk, had stopped smoking, and three original non-smokers had started smoking.
Adolescent↗
Diazoxide treatment for insulinoma: a national UK survey.
A survey of UK patients receiving the drug diazoxide, revealed 40 patients with insulinoma on this treatment. Mean age (+/- SD) was 67 +/- 18 years, and 74% were female. Duration of treatment was 7 +/- 6 years (range 1-22). Most (55%) patients were treated with diazoxide because of tumour non-localisation (including failed previous surgery). Metastatic disease (20%) and poor surgical risk (10%) were other indications. Side-effects (notably fluid retention and hirsutism) were common (47%) but not troublesome. Treatment was highly effective--59% were symptom free and 38% had only occasional symptoms. Only one patient had frequent hypoglycaemia despite treatment. We conclude that diazoxide is effective in the management of insulinoma. Side-effects are common but not problematic. Treatment should be considered for all patients not cured by surgery, or unsuitable for surgical treatment.
Adult↗
Smoking habits of black South African patients with diabetes mellitus.
Cigarette smoking is a major arteriosclerotic risk factor, and this is enhanced by the presence of diabetes mellitus. Although smoking rates are increasing in many African countries, they have been little studied. We have critically assessed smoking among black diabetic and general medical patients at Baragwanath Hospital in Soweto, South Africa. As well as direct questioning of patients, we also used urinary cotinine:creatinine ratio as an objective marker. The admitted smoking rate was 16% in 118 diabetic patients, compared with 22% in 105 medical patients. Using a validated biochemical index of smoking (urinary cotinine:creatinine > 1.0 microgram mg-1) the rates were 37% and 33%, respectively. Most of the excess however was due to women who took snuff, and when excluded, the estimated real rates were 20% (diabetic) and 24% (medical). Amongst diabetic smokers mean cotinine:creatinine ratio was higher than in medical smokers (4.7 +/- 6.0 v 1.8 +/- 2.0 micrograms mg-1) despite admitted similar smoking consumption. A separate control group of British smokers had a mean level of 3.6 +/- 1.3 though their consumption was twice that of the South African groups. We conclude that smoking is common among South African black diabetic patients (20%), though it is less than reported figures for the black general population (28%), and British diabetic patients (35%). Questionnaire studies may seriously underestimate smoking rates, though this effect is considerably less in African compared with British smokers. Urinary cotinine also allows quantification of the 'smoking load', which is rarely reflected by admitted cigarette consumption.
Adult↗
The development, reliability and validity of a disease specific quality of life model for adults with growth hormone deficiency.
OBJECTIVE: Adults with GH deficiency frequently complain of lack of energy, fatigue, social isolation and problems with sexual relationships resulting in a low perceived quality of life. Previous studies of quality of life (QOL) in GH deficient adults have involved small numbers of patients and used measures not specifically designed for this patient population. We have devised a health related QOL model specifically designed for use in adults with GH deficiency and to assess the impact of future GH replacement therapy. DESIGN: Six measurements were chosen for inclusion in the model. Two were adapted for use after clinical interviews with 12 adult GH deficient patients: the Impact and the Life Fulfilment scales. The others were the Nottingham Health Profile, the Hospital Anxiety and Depression Scale, the Self-Esteem Scale and the Mental Fatigue Questionnaire. The reliability of the 6 measures was assessed by 2 methods: test re-test correlation and internal consistency (Cronbach's alpha). The validity of the Impact and Life Fulfilment scales was assessed by correlation with the other 4 scales. PATIENTS: Questionnaires were completed by 32 adults with hypothalamic pituitary disorders and GH deficiency (11 male, mean age 35.1 years), with a stimulated maximum serum GH response less than 10 mU/l (mean 2.96). Two had previously received GH injections in childhood. The questionnaires were also completed by 32 age and sex matched control subjects. RESULTS: The 6 scales had test re-test correlations of 0.70-0.92 indicating reliability over time. The Impact and Life Fulfilment Scales and the Mental Fatigue Questionnaire had Cronbach's alpha scores of greater than 0.6 indicating their potential for use in clinical trials. The Impact and Life Fulfilment scales correlated significantly with many physical and psychological domains from the other 4 scales indicating these were valid in the assessment of health related QOL in GH deficient adults. Compared to the controls the patients with GH deficiency were significantly psychosocially disadvantaged in terms of depression, self-esteem, mental fatigue and life fulfilment. CONCLUSION: The results of the reliability and validity studies indicate that this health related quality of life model for use with adults with GH deficiency is a potentially valid and reliable tool that could be used to assess the effect of GH treatment.
Activities of Daily Living↗
Hypogonadotrophic hypogonadism and primary amenorrhoea associated with increased melatonin secretion from a cystic pineal lesion.
A 17-year-old girl presented with primary amenorrhoea and failure to develop secondary sexual characteristics, although her height was above the 90th centile. Endocrine investigations revealed hypogonadotrophic hypogonadism (basal LH and FSH levels < 0.5 U/l; FSH rose to 2.0 U/l and LH to 1.0 U/l after GnRH). ACTH, GH, TSH and PRL secretion were normal. A magnetic resonance scan revealed no abnormality in the pituitary, pituitary stalk or hypothalamus but demonstrated a partly cystic enhancing lesion in the pineal region. Melatonin production (assessed as urinary 6-sulphatoxymelatonin: aMT6s) at baseline was markedly increased: 459-530 ng/kg/24 h compared with aged-matched controls: 136 +/- 69 (P = 0.01). However, melatonin production retained a largely normal rhythm with increased production during the night. Treatment with ethinyloestradiol 100 micrograms daily had no apparent effect on the production of melatonin. Treatment with atenolol, 100 mg daily at 1600 h, was associated with suppression of nocturnal melatonin secretion but a brisk rebound in the morning and a considerably delayed peak excretion time (10.2 h) compared with controls (3.9 h). It is likely the pineal lesion, which may be hyperplasia or possibly even tumour, was responsible for the increased melatonin secretion. These data support the hypothesis that melatonin may have a causal role in hypogonadotrophic hypogonadism.
Adolescent↗