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1.
Int J Obes (Lond) ; 40(1): 153-61, 2016 Jan.
Article in English | MEDLINE | ID: mdl-26271188

ABSTRACT

BACKGROUND: The term 'metabolically healthy obese (MHO)' is distinguished using body mass index (BMI), yet BMI is a poor index of adiposity. Some epidemiological data suggest that MHO carries a lower risk of cardiovascular disease (CVD) or mortality than being normal weight yet metabolically unhealthy. OBJECTIVES: We aimed to undertake a detailed phenotyping of individuals with MHO by using imaging techniques to examine ectopic fat (visceral and liver fat deposition) and myocardial function. We hypothesised that metabolically unhealthy individuals (irrespective of BMI) would have adverse levels of ectopic fat and myocardial dysfunction compared with MHO individuals. SUBJECTS: Individuals were categorised as non-obese or obese (BMI ⩾30 kg m(-2)) and as metabolically healthy or unhealthy according to the presence or absence of metabolic syndrome. METHODS: Sixty-seven individuals (mean±s.d.: age 49±11 years) underwent measurement of (i) visceral, subcutaneous and liver fat using magnetic resonance imaging and proton magnetic resonance spectroscopy, (ii) components of metabolic syndrome, (iii) cardiorespiratory fitness and (iv) indices of systolic and diastolic function using tissue Doppler echocardiography. RESULTS: Cardiorespiratory fitness was similar between all groups; abdominal and visceral fat was highest in the obese groups. Compared with age- and BMI-matched metabolically healthy counterparts, the unhealthy (lean or obese) individuals had higher liver fat and decreased early diastolic strain rate, early diastolic tissue velocity and systolic strain indicative of subclinical systolic and diastolic dysfunction. The magnitude of dysfunction correlated with the number of components of metabolic syndrome but not with BMI or with the degree of ectopic (visceral or liver) fat deposition. CONCLUSIONS: Myocardial dysfunction appears to be related to poor metabolic health rather than simply BMI or fat mass. These data may partly explain the epidemiological evidence on CVD risk relating to the different obesity phenotypes.


Subject(s)
Cardiovascular Diseases/prevention & control , Hyperlipidemias/physiopathology , Metabolic Syndrome/physiopathology , Non-alcoholic Fatty Liver Disease/physiopathology , Obesity/physiopathology , Cardiovascular Diseases/etiology , Cardiovascular Diseases/physiopathology , Cross-Sectional Studies , England/epidemiology , Female , Humans , Hyperlipidemias/epidemiology , Insulin Resistance , Magnetic Resonance Spectroscopy , Male , Metabolic Syndrome/complications , Metabolic Syndrome/epidemiology , Middle Aged , Non-alcoholic Fatty Liver Disease/epidemiology , Obesity/complications , Obesity/epidemiology , Phenotype , Prospective Studies , Risk Factors
2.
Int J Obes (Lond) ; 39(9): 1376-82, 2015 Sep.
Article in English | MEDLINE | ID: mdl-25971928

ABSTRACT

BACKGROUND/OBJECTIVES: Obesity is common following hypothalamic damage due to tumours. Homeostatic and non-homeostatic brain centres control appetite and energy balance but their interaction in the presence of hypothalamic damage remains unknown. We hypothesized that abnormal appetite in obese patients with hypothalamic damage results from aberrant brain processing of food stimuli. We sought to establish differences in activation of brain food motivation and reward neurocircuitry in patients with hypothalamic obesity (HO) compared with patients with hypothalamic damage whose weight had remained stable. SUBJECTS/METHODS: In a cross-sectional study at a University Clinical Research Centre, we studied 9 patients with HO, 10 age-matched obese controls, 7 patients who remained weight-stable following hypothalamic insult (HWS) and 10 non-obese controls. Functional magnetic resonance imaging was performed in the fasted state, 1 h and 3 h after a test meal, while subjects were presented with images of high-calorie foods, low-calorie foods and non-food objects. Insulin, glucagon-like peptide-1, Peptide YY and ghrelin were measured throughout the experiment, and appetite ratings were recorded. RESULTS: Mean neural activation in the posterior insula and lingual gyrus (brain areas linked to food motivation and reward value of food) in HWS were significantly lower than in the other three groups (P=0.001). A significant negative correlation was found between insulin levels and posterior insula activation (P=0.002). CONCLUSIONS: Neural pathways associated with food motivation and reward-related behaviour, and the influence of insulin on their activation may be involved in the pathophysiology of HO.


Subject(s)
Brain Injuries/physiopathology , Food , Functional Neuroimaging , Hypothalamus/physiopathology , Neural Pathways/physiopathology , Obesity/physiopathology , Photic Stimulation , Brain Injuries/psychology , Brain Mapping , Cerebral Cortex/physiopathology , Cues , Female , Humans , Hypothalamus/injuries , Male , Middle Aged , Obesity/psychology , Reward , United Kingdom
3.
Clin Endocrinol (Oxf) ; 80(3): 419-24, 2014 Mar.
Article in English | MEDLINE | ID: mdl-23909507

ABSTRACT

OBJECTIVE: To study the presentation, management and outcomes and to apply retrospectively the Pituitary Apoplexy Score (PAS) (United Kingdom (UK) guidelines for management of apoplexy) to a large, single-centre series of patients with acute pituitary apoplexy. DESIGN: Retrospective analysis of casenotes at a single neurosurgical centre in Liverpool, UK. RESULTS: Fifty-five patients [mean age, 52·4 years; median duration of follow-up, 7 years] were identified; 45 of 55 (81%) had nonfunctioning adenomas, four acromegaly and six prolactinomas. Commonest presenting features were acute headache (87%), diplopia (47·2%) and visual field (VF) defects (36%). The most frequent ocular palsy involved the 3rd nerve (81%), followed by 6th nerve (34·6%) and multiple palsies (19%). Twenty-three patients were treated conservatively, and the rest had surgery either within 7 days of presentation or delayed elective surgery. Indications for surgery were deteriorating visual acuity and persistent field defects. Patients presenting with VF defects (n = 20) were more likely to undergo surgery (75%) than to be managed expectantly (25%). There was no difference in the rates of complete/near-complete resolution of VF deficits and cranial nerve palsies between those treated conservatively and those who underwent surgery. Endocrine outcomes were also similar. We were able to calculate the PAS for 46 patients: for the group treated with early surgery mean, PAS was 3·8 and for those managed conservatively or with delayed surgery was 1·8. CONCLUSIONS: Patients without VF deficits or whose visual deficits are stable or improving can be managed expectantly without negative impact on outcomes. Clinical severity based on a PAS ≥ 4 appeared to influence management towards emergency surgical intervention.


Subject(s)
Pituitary Apoplexy/diagnosis , Pituitary Apoplexy/therapy , Acute Disease , Adenoma/complications , Adenoma/diagnosis , Adenoma/epidemiology , Adenoma/therapy , Adolescent , Adult , Aged , Female , Humans , Male , Middle Aged , Pituitary Apoplexy/epidemiology , Pituitary Apoplexy/etiology , Pituitary Neoplasms/complications , Pituitary Neoplasms/diagnosis , Pituitary Neoplasms/epidemiology , Pituitary Neoplasms/therapy , Retrospective Studies , Treatment Outcome , United Kingdom/epidemiology , Young Adult
4.
J Physiol ; 591(6): 1475-87, 2013 Mar 15.
Article in English | MEDLINE | ID: mdl-23318877

ABSTRACT

Polycystic ovary syndrome (PCOS) is associated with cardiovascular disease. The contribution of the nitric oxide (NO) dilator system to cutaneous endothelial dysfunction is currently unknown in PCOS. Our aim was to examine whether women with PCOS demonstrate impaired cutaneous microvascular NO function and whether exercise training can ameliorate any impairment. Eleven women with PCOS (age, 29 ± 7 years; body mass index, 34 ± 6 kg m(-2)) were compared with six healthy obese control women (age, 29 ± 7 years; body mass index, 34 ± 5 kg m(-2)). Six women with PCOS (30 ± 7 years; 31 ± 6 kg m(-2)) then completed 16 weeks of exercise training. Laser Doppler flowmetry, combined with intradermal microdialysis of l-N(G)-monomethyl-l-arginine, a nitric oxide antagonist, in response to incremental local heating of the forearm was assessed in women with PCOS and control women, and again in women with PCOS following exercise training. Cardiorespiratory fitness, homeostasis model assessment for insulin resistance, hormone and lipid profiles were also assessed. Differences between women with PCOS and control women and changes with exercise were analysed using Student's unpaired t tests. Differences in the contribution of NO to cutaneous blood flow [expressed as a percentage of maximal cutaneous vasodilatation (CVCmax)] were analysed using general linear models. At 42°C heating, cutaneous NO-mediated vasodilatation was attenuated by 17.5%CVCmax (95% confidence interval, 33.3, 1.7; P = 0.03) in women with PCOS vs. control women. Exercise training improved cardiorespiratory fitness by 5.0 ml kg(-1) min(-1) (95% confidence interval, 0.9, 9.2; P = 0.03) and NO-mediated cutaneous vasodilatation at 42°C heating by 19.6% CVCmax (95% confidence interval, 4.3, 34.9; P = 0.02). Cutaneous microvascular NO function is impaired in women with PCOS compared with obese matched control women but can be improved with exercise training.


Subject(s)
Exercise , Microvessels/physiopathology , Nitric Oxide/metabolism , Polycystic Ovary Syndrome/physiopathology , Vasodilation/physiology , Adult , Case-Control Studies , Enzyme Inhibitors/pharmacology , Exercise Therapy , Female , Heart Diseases/etiology , Heart Diseases/prevention & control , Heart Function Tests , Hot Temperature , Humans , Insulin Resistance , Laser-Doppler Flowmetry , Lipoproteins, LDL/blood , Microdialysis , Polycystic Ovary Syndrome/complications , Polycystic Ovary Syndrome/metabolism , Polycystic Ovary Syndrome/therapy , Regional Blood Flow/drug effects , Regional Blood Flow/physiology , Skin/blood supply , Vasodilation/drug effects , omega-N-Methylarginine/pharmacology
5.
Diabet Med ; 29(8): e205-10, 2012 Aug.
Article in English | MEDLINE | ID: mdl-22486277

ABSTRACT

AIMS: Studies investigating the acute effects of metformin have demonstrated actions on the incretin system and appetite regulatory hormones. There are limited data to support that these effects are sustained in the long term. We therefore studied the effects of chronic treatment with metformin on endogenous glucagon-like peptide 1, dipeptidyl peptidase-4 activity and active ghrelin (an orexigenic hormone) in obese patients with Type 2 diabetes mellitus. METHODS: Eight subjects [six male, age 58.7 ± 2.6 years, BMI 41.1 ± 2.9 kg/m(2) , HbA(1c) 69 ± 6 mmol/mol (8.5 ± 0.5%), mean ± sem] with drug-naïve Type 2 diabetes were studied for 6 h following a standard mixed meal, before and after at least 3 months of metformin monotherapy (mean dose 1.75 g daily). RESULTS: The area under the curve (AUC(0-6 h) ) for active glucagon-like peptide 1 was significantly higher on metformin (pre-metformin 1750.8 ± 640 pmol l(-1) min(-1) vs. post-metformin 2718.8 ± 1182.3 pmol l(-1) min(-1) ; P=0.01). The areas under the curves for dipeptidyl peptidase-4 activity and ghrelin were not significantly different pre- and post-treatment with metformin. CONCLUSION: Three months or more of metformin monotherapy in obese patients with Type 2 diabetes was associated with increased postprandial active glucagon-like peptide 1 levels. The effects of metformin on the enteroinsular axis may represent yet another important mechanism underlying its glucose-lowering effects.


Subject(s)
Diabetes Mellitus, Type 2/drug therapy , Dipeptidyl Peptidase 4/metabolism , Ghrelin/metabolism , Glucagon-Like Peptide 1/metabolism , Hypoglycemic Agents/therapeutic use , Metformin/therapeutic use , Obesity/complications , Area Under Curve , Diabetes Mellitus, Type 2/complications , Diabetes Mellitus, Type 2/metabolism , Female , Humans , Male , Middle Aged , Obesity/metabolism , Postprandial Period , Prospective Studies
6.
Ultrastruct Pathol ; 36(2): 85-8, 2012 Apr.
Article in English | MEDLINE | ID: mdl-22471430

ABSTRACT

A 69-year-old woman presented with visual disturbance. Perimetry testing revealed a bitemporal hemianopia. Brain MRI demonstrated a 2.2-cm gadolinium-enhancing pituitary mass. Previously she had been treated for hypothyroidism, hypertension, and dyslipidemia. She had hyperprolactinemia. Endoscopic transsphenoidal debulking improved her visual field defects. Histology showed a chromophobic adenoma. Electron microscopy showed elongated, polar cells with long, slender processes. The small uniform secretory granules were peripherally disposed, collecting heavily within cell processes. Based on electron microscopical characteristics the tumor is consistent with an ACTH-negative female gonadotroph adenoma. The parent cell of this rare variant of a pituitary adenoma is yet unknown.


Subject(s)
Adenoma/ultrastructure , Pituitary Neoplasms/ultrastructure , Polar Bodies/ultrastructure , Adenoma/complications , Aged , Cells, Cultured , Female , Gonadotrophs/pathology , Hemianopsia/etiology , Humans , Microscopy, Electron , Pituitary Neoplasms/complications
9.
Br J Neurosurg ; 25(3): 337-8, 2011 Jun.
Article in English | MEDLINE | ID: mdl-21355768

ABSTRACT

Over the last decade subarachnoid haemorrhage (SAH) has increasingly been recognised as a cause of hypopituitarism. We report on the case of a patient with evidence of growth hormone deficiency manifesting after a period of time, with a favourable response to growth hormone replacement. This is followed by a review of the current literature.


Subject(s)
Human Growth Hormone/deficiency , Hypopituitarism/etiology , Subarachnoid Hemorrhage/complications , Adult , Humans , Male , Treatment Outcome
10.
Clin Endocrinol (Oxf) ; 73(5): 678-85, 2010 Nov.
Article in English | MEDLINE | ID: mdl-20738316

ABSTRACT

OBJECTIVE: Ghrelin inhibits sympathetic nervous system (SNS) activity in rodents. We studied the effect of ghrelin on healthy humans, in obesity and in vagotomized subjects. DESIGN: Randomized, double-blinded, placebo-controlled crossover. SUBJECTS: Seven lean [mean body mass index (BMI) 23·6 ± 0·9 kg/m(2) ], seven morbidly obese (mean BMI 50·9 ± 4·4 kg/m(2) ) and seven post-gastrectomy subjects (mean BMI 22·0 ± 1·1 kg/m(2) ). MEASUREMENTS: Subjects were randomized to intravenous ghrelin (5 pmol/kg/min) or saline over 270 min. Subjects had a fixed calorie meal and a free choice buffet during the infusion. Heart rate variability (HRV) was measured. Total power (TP) represents overall autonomic function, low-frequency (LF) power represents sympathetic and parasympathetic activity, and high-frequency (HF) power represents parasympathetic activity. Very low (VLO) frequency represents the frequency band associated with thermogenesis. RESULTS: Preliminary anova analysis, looking at all three subject groups together, showed that ghrelin had an overall highly significant inhibitory effect on TP (P = 0·001), HF power (P = 0·04), VLO power (P = 0·03) and no effect on LF (P = 0·07). Further subset analysis revealed that ghrelin had a significant effect on TP (P = 0·03), borderline effect on LF power (P = 0·06) and no effect on HF power (P = 0·1) in healthy controls. By contrast in obese subjects, ghrelin had no effect on TP (P = 0·3), LF (P = 0·5) and HF (P = 0·06) and also no effect in the vagotomized subjects on TP (P = 0·7), LF (P = 0·7) and HF (P = 0·9). Ghrelin had no effect on the LF/HF ratio. CONCLUSIONS: Ghrelin inhibits SNS activity in healthy controls with a moderate effect on parasympathetic nervous system activity but had no effect on obese subjects. Vagotomized subjects also did not respond to ghrelin, suggesting the vagus nerve is important for the effects of peripheral ghrelin on the SNS.


Subject(s)
Autonomic Nervous System/physiology , Ghrelin/pharmacology , Obesity, Morbid/physiopathology , Vagus Nerve/physiology , Adult , Aged , Autonomic Nervous System/drug effects , Blood Glucose/metabolism , Blood Pressure/drug effects , Cross-Over Studies , Female , Gastrectomy , Heart Rate/drug effects , Humans , Insulin/blood , Male , Middle Aged , Parasympathetic Nervous System/drug effects , Parasympathetic Nervous System/physiopathology , Stomach Neoplasms/surgery , Sympathetic Nervous System/drug effects , Sympathetic Nervous System/physiopathology , Thermogenesis/drug effects , Vagotomy
11.
Growth Horm IGF Res ; 20(3): 220-5, 2010 Jun.
Article in English | MEDLINE | ID: mdl-20185347

ABSTRACT

BACKGROUND: Adult GHD syndrome is associated with clustering of adverse cardiovascular (CV) risk factors such as abnormal body composition, dyslipidemia, insulin resistance and abnormal haemostatic factors. There is a wealth of evidence linking CV events with elevated levels of inflammatory markers (hs-CRP and IL-6) in the general population; however data on their abnormalities in GHD and specially the effects of GH replacement (GHR) on these inflammatory markers are limited. OBJECTIVE: To study the effects of GHR on inflammatory markers, glucose homeostasis and body composition in a cohort of adults with recently diagnosed severe GHD due to hypothalamic pituitary disease. DESIGN: Fifteen hypopituitary adults (11 males, mean age 48.5 years) with recently diagnosed, severe GHD were recruited. Patients received GHR (in addition to other pituitary hormone replacements) titrated to clinical response and to normalize age and gender adjusted IGF-1 levels. Weight, waist hip ratio (WHR), body composition, fasting plasma glucose and insulin, insulin resistance index (HOMA-IR), fasting serum lipid levels, hs-CRP, IL-6 and TNF-alpha were measured at baseline and following a minimum 6 months of stable maintenance GHR. RESULTS: GHR resulted in a physiological increase in IGF-1 SDS [median -0.6 to +0.39, P<0.0001], improved quality of life (mean pre-treatment AGHDA score 16 vs. post-treatment score 7, P<0.0001) and reduction in WHR (0.94 vs. 0.92, P=0.01). There were no significant changes in body weight and composition. Levels of hs-CRP (log transformed, mean (SD)) were significantly reduced following GHR (pre 1.21 (0.9) vs. post 0.27 (0.9), P<0.0001) but TNF-alpha and IL-6 levels remained unchanged. Fasting glucose (mmol/L) [4.6 (0.1) vs. 5.1 (0.1), P=0.003], fasting insulin (muU/mL) [9.4 (8.1) vs. 12.1 (9.2), P=0.03] and HOMA-IR [1.2 (1.0) vs. 1.5 (1.1) P=0.02] (all pre-GHR vs. post-GHR and mean (SD)) significantly increased following GHR indicating increased insulin resistance. Significant improvements were noted in fasting LDL-cholesterol (LDL-C) and HDL-cholesterol (HDL-C) levels following GHR [3.4 (0.9) vs. 2.9 (0.7), P=0.03 and 1.2 (0.2) vs. 1.3 (0.2), P=0.02, respectively] (all pre-GHR vs. post-GHR and mean (SD)). Levels of total cholesterol and triglycerides did not change following GHR. CONCLUSIONS: Physiological GHR for at least 6 months in hypopituitary adults with recently diagnosed severe GHD resulted in favourable changes in hs-CRP, WHR, fasting LDL-C and HDL-C levels all of which are recognised CV risk markers. However, there remains a high prevalence of obesity in this population and given the worsening of insulin sensitivity in the short term with GHR, monitoring and aggressive treatment of established CV risk factors is essential to reduce premature atherosclerotic CVD in this patient population.


Subject(s)
Biomarkers/blood , Growth Disorders/drug therapy , Hormone Replacement Therapy , Human Growth Hormone/pharmacology , Human Growth Hormone/therapeutic use , Adult , Body Composition/drug effects , Cardiovascular Diseases/blood , Cardiovascular Diseases/etiology , Female , Growth Disorders/blood , Growth Disorders/complications , Growth Disorders/metabolism , Human Growth Hormone/blood , Human Growth Hormone/deficiency , Humans , Inflammation/blood , Inflammation/etiology , Inflammation Mediators/blood , Insulin-Like Growth Factor I/analysis , Insulin-Like Growth Factor I/metabolism , Male , Middle Aged , Quality of Life , Risk Factors , Severity of Illness Index
12.
Curr Med Res Opin ; 25(2): 395-400, 2009 Feb.
Article in English | MEDLINE | ID: mdl-19192984

ABSTRACT

OBJECTIVE: There is evidence that microalbuminuria and overt nephropathy may progress more slowly in long duration (> 20 years) type 1 diabetes (T1DM). To explore this further, we examined the characteristics of chronic kidney disease (CKD) in a large cohort of long duration T1DM in the United Kingdom (UK). RESEARCH DESIGN AND METHODS: We studied the UK 'Golden Years' cohort--a group of 400 patients from various parts of the UK with T1DM > 50 years duration. Demographic and clinical information were obtained. HbA(1c), lipids, creatinine and urinary albumin-creatinine ratio (ACR) were measured. Microalbuminuria was defined as 2.5-25.0 mg/mmol for males and 3.5-25.0 mg/mmol for females; macroalbuminuria was defined as an ACR > 25.0 mg/mmol for both sexes. RESULTS: Mean age was 69 years and duration of diabetes 55 years. Nine percent had macroalbuminuria and 27% microalbuminuria. No patient had stage 5 CKD. Microalbuminuria was associated significantly with increased diabetes duration (p = 0.02), male sex (p = 0.02), smoking (p = 0.002), higher HbA(1c) (p < 0.0001), raised triglycerides (p = 0.04), and peripheral vascular disease (PVD) (p < 0.0001). Macroalbuminuria had significant associations with smoking (p = 0.02), raised triglycerides (p = 0.01), raised creatinine (p = 0.02), PVD (p = 0.01) and hypertension (p = 0.01). CONCLUSIONS: We conclude that microalbuminuria and CKD are common, even at long duration (> 50 years) of T1DM, and have similar characteristics and associations as they do with shorter disease duration. There is a striking absence, however, of stage 5 CKD, but selection bias may be an important confounder since patients with advanced disease may have not survived.


Subject(s)
Diabetes Mellitus, Type 1/complications , Kidney Failure, Chronic/complications , Adolescent , Adult , Child , Chromatography, High Pressure Liquid , Cohort Studies , Female , Humans , Male , United Kingdom
13.
Clin Endocrinol (Oxf) ; 71(2): 195-201, 2009 Aug.
Article in English | MEDLINE | ID: mdl-19178509

ABSTRACT

BACKGROUND: Apart from their role in insulin secretion and glucose homeostasis, the incretin hormones glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP) exert a number of extra-pancreatic effects which in the case of GIP remain largely unknown. DESIGN/PATIENTS: Six obese male patients with diet-controlled type 2 diabetes (T2DM) and six healthy lean male subjects were studied. The protocol included four experiments for each participant that were carried out in randomized order and included: GLP-1 infusion at a rate of 1 pmol/kg/min for 4 h, GIP at a rate of 2 pmol/kg/min, GLP-1 (at 1 pmol/kg/min) with GIP (at 2 pmol/kg/min), and placebo infusion for 4 h. Energy expenditure (EE) was measured throughout with indirect calorimetry and subjects were given a series of visual analogue scales to rate hourly their hunger, fullness, urge to eat and prospective consumption of food. Immediately following termination of the infusions all subjects were offered a free choice buffet lunch and total calorie and macronutrient intake was calculated. RESULTS: During GIP infusion there was a trend for healthy subjects to report higher hunger scores and a reduction in EE only when compared with placebo. These parameters remained unchanged in patients with T2DM. Ad libitum energy intake after all four infusions was the same in both groups. CONCLUSION: We report here for the first time that GIP infusion may impact on resting EE and subjective appetite sensations in normal weight healthy subjects and further studies with larger numbers of subjects are required to help define more conclusively the precise role of GIP in energy balance in humans.


Subject(s)
Diabetes Mellitus, Type 2/drug therapy , Diabetes Mellitus, Type 2/psychology , Energy Metabolism/drug effects , Gastric Inhibitory Polypeptide/administration & dosage , Administration, Topical , Adult , Appetite/drug effects , Case-Control Studies , Diabetes Mellitus, Type 2/metabolism , Gastric Inhibitory Polypeptide/chemical synthesis , Humans , Male , Middle Aged , Taste/drug effects
14.
BMJ Case Rep ; 20092009.
Article in English | MEDLINE | ID: mdl-21686754

ABSTRACT

Thyrotropin (TSH)-secreting pituitary adenomas (TSHomas) are rare tumours. 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 tumour expansion. We studied the effects of thyroid ablative treatment on tumour size and thyroid status in two patients with TSHomas. Patients studied were: (1) a female 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. 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. Ablative thyroid treatment can be a safe and successful option to treat TSHomas.

15.
Diabet Med ; 25(10): 1234-6, 2008 Oct.
Article in English | MEDLINE | ID: mdl-19046204

ABSTRACT

AIMS: To explore the association between dyslipidaemia and albuminuria at the extreme of diabetes duration. METHODS: Data and samples were collected from 400 patients with extreme duration (> 50 years) of Type 1 diabetes in the UK (Golden Years Cohort). Urinary albumin-creatinine ratio (ACR), glycated haemoglobin (HbA(1c)), creatinine, non-fasting triglycerides, total cholesterol, high-density lipoprotein- and low-density lipoprotein-cholesterol were analysed in all patients. RESULTS: Thirty-six percent of patients had albuminuria (micro- or macroalbuminuria). After adjusting for age, gender, HbA(1c), disease duration and presence of macrovascular disease, hypertriglyceridaemia was more likely to be associated with the presence of albuminuria. CONCLUSIONS: High triglycerides may be a potential risk factor for progression of diabetic nephropathy at the extreme of diabetes duration, but the benefit of targeting this aggressively remains to be evaluated further.


Subject(s)
Albuminuria/blood , Diabetes Mellitus, Type 1/blood , Hypertriglyceridemia/blood , Aged , Chi-Square Distribution , Cohort Studies , Disease Progression , Female , Humans , Logistic Models , Male , Middle Aged , Statistics, Nonparametric , Time Factors
16.
Eur J Clin Invest ; 38(9): 622-7, 2008 Sep.
Article in English | MEDLINE | ID: mdl-18837737

ABSTRACT

BACKGROUND: Adults with growth hormone deficiency (AGHD) have an adverse body composition with an increased prevalence of obesity. It is not known whether growth hormone replacement (GHR) results in alterations in energy intake (EI) and/or energy expenditure (EE). The aim of the study was to investigate the effects of GHR on EI and EE. MATERIALS AND METHODS: Nineteen hypopituitary adults (14 males, 5 females, mean age 46.2 years) with severe GHD (peak GH response to glucagon

Subject(s)
Energy Intake/drug effects , Energy Metabolism/drug effects , Growth Disorders/drug therapy , Growth Hormone/deficiency , Growth Hormone/therapeutic use , Adult , Body Composition , Female , Growth Disorders/metabolism , Growth Hormone/pharmacology , Humans , Male , Middle Aged , Obesity/complications , Risk Factors , Treatment Outcome
17.
J Neurol Neurosurg Psychiatry ; 78(1): 93-5, 2007 Jan.
Article in English | MEDLINE | ID: mdl-17172570

ABSTRACT

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.


Subject(s)
Pituitary Neoplasms/complications , Thyroid Gland/surgery , Thyrotoxicosis/etiology , Thyrotoxicosis/surgery , Thyrotropin/metabolism , Adult , Female , Humans , Male
18.
Diabet Med ; 23(9): 1021-4, 2006 Sep.
Article in English | MEDLINE | ID: mdl-16922710

ABSTRACT

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.


Subject(s)
Diabetic Neuropathies/complications , Pain/etiology , Aged , Aged, 80 and over , Chronic Disease , Community Health Services , Epidemiologic Methods , Female , Humans , Male , Middle Aged , Pain/drug therapy , Pain Measurement , Prognosis , Treatment Outcome
19.
Postgrad Med J ; 82(966): 280-4, 2006 Apr.
Article in English | MEDLINE | ID: mdl-16597817

ABSTRACT

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.


Subject(s)
Cardiovascular Diseases/etiology , Diabetes Mellitus, Type 2/complications , Diabetic Angiopathies/complications , Obesity/complications , Adult , Aged , Blood Pressure , Body Mass Index , Diabetes Mellitus, Type 1/complications , Diabetes Mellitus, Type 2/blood , Diabetes Mellitus, Type 2/physiopathology , Female , Humans , Lipids/blood , Male , Middle Aged , Obesity, Morbid/complications , Outpatient Clinics, Hospital , Risk Factors
20.
Diabet Med ; 22(4): 393-8, 2005 Apr.
Article in English | MEDLINE | ID: mdl-15787662

ABSTRACT

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.


Subject(s)
Diabetic Neuropathies/therapy , Electric Stimulation Therapy/methods , Pain, Intractable/therapy , Spinal Cord/physiopathology , Activities of Daily Living , Adult , Aged , Analgesics/administration & dosage , Diabetic Neuropathies/complications , Diabetic Neuropathies/rehabilitation , Drug Administration Schedule , Electric Stimulation Therapy/adverse effects , Electrodes, Implanted , Follow-Up Studies , Humans , Long-Term Care/methods , Male , Middle Aged , Pain Measurement , Pain, Intractable/etiology , Pain, Intractable/rehabilitation , Treatment Outcome
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