M C Sheppard

University of Birmingham, Birmingham, England, United Kingdom

Are you M C Sheppard?

Claim your profile

Publications (309)1879.65 Total impact

  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Context: Biochemical control reduces morbidity and increases life expectancy in patients with acromegaly. With current medical therapies, including the gold standard octreotide LAR, many patients do not achieve biochemical control. Objective: To demonstrate the superiority of pasireotide LAR over octreotide LAR in medically naïve patients with acromegaly. Design: Prospective, randomized, double blind. Setting: 84 sites; 27 countries. Patients: 358 patients with medically naïve acromegaly (GH>5μg/liter or GH nadir≥1μg/liter post-OGTT, and IGF-1>ULN). Patients either had prior pituitary surgery but no medical treatment or were de novo with a visible pituitary adenoma on MRI. Interventions: Pasireotide LAR 40mg/28d (n=176) or octreotide LAR 20mg/28d (n=182) for 12 months. At months 3 and 7, titration to pasireotide LAR 60mg or octreotide LAR 30mg was permitted, but not mandatory, if GH≥2.5μg/liter and/or IGF-1>ULN. Main outcome measure: Proportion of patients in each treatment arm with biochemical control (GH<2.5μg/liter and normal IGF-1) at month 12. Results: Biochemical control was achieved by significantly more pasireotide LAR patients than octreotide LAR patients (31.3% versus 19.2%; P=0.007; 35.8% versus 20.9% when including patients with IGF-1 below the lower normal limit). In pasireotide LAR and octreotide LAR patients, respectively, 38.6% and 23.6% (P=0.002) achieved normal IGF-1, and 48.3% and 51.6% achieved GH<2.5μg/liter. 31.0% of pasireotide LAR and 22.2% of octreotide LAR patients who did not achieve biochemical control did not receive the recommended dose increase. Hyperglycemia-related adverse events were more common with pasireotide LAR (57.3% versus 21.7%). Conclusions: Pasireotide LAR demonstrated superior efficacy over octreotide LAR and is a viable new treatment option for acromegaly.
    Full-text · Article · Jan 2014 · The Journal of Clinical Endocrinology and Metabolism
  • [Show abstract] [Hide abstract]
    ABSTRACT: Context: Acromegaly is associated with reduced life expectancy, which has been reported to be normalized if treatment is successful in controlling GH/IGF-I levels. Objective: Most previous studies have invariably used the last available GH/IGF-I, which may be biased as it only assesses exposure at a single point in time. We compared the last available GH/IGF-I analysis to a "time-dependent" and cumulative method, during follow-up to assess risk of mortality in the West Midlands Acromegaly study (n = 501). Results: Using the last available GH, there was a statistically significant increase in mortality comparing groups as low as GH ≤ 1 μg/L vs >1 μg/L (relative risks [RR] 1.8, P = .03). This was not the case when using the "time-dependent method," where only comparisons of GH values of GH ≤5 μg/L vs >5 μg/L were suggestive of being associated with an increased risk of mortality (RR = 1.5, P = .08). When the time-dependent GH method of analysis was used, the RR of mortality at each level was lower and the associated P value was less significant. Irrespective of using the last available or time-dependent method, when IGF-I was divided into levels according to quartile or arbitrary cutoffs, there was no significant increase in mortality with higher levels. Conclusions: This study emphasizes the potential bias of using the latest available GH/IGF-I levels to predict mortality. Our study again highlights the limitations of IGF-I in predicting mortality.
    No preview · Article · Nov 2013 · The Journal of Clinical Endocrinology and Metabolism
  • Mark Sherlock · Conor Woods · Michael C Sheppard
    [Show abstract] [Hide abstract]
    ABSTRACT: Acromegaly is a rare disease characterized by excess secretion of growth hormone (GH) and increased circulating insulin-like growth factor 1 (IGF-1) concentrations. The disease is associated with increased morbidity and premature mortality, but these effects can be reduced if GH levels are decreased to <2.5 μg/l and IGF-1 levels are normalized. Therapy for acromegaly is targeted at decreasing GH and IGF-1 levels, ameliorating patients' symptoms and decreasing any local compressive effects of the pituitary adenoma. The therapeutic options for acromegaly include surgery, radiotherapy and medical therapies, such as dopamine agonists, somatostatin receptor ligands and the GH receptor antagonist pegvisomant. Medical therapy is currently most widely used as secondary treatment for persistent or recurrent acromegaly following noncurative surgery, although it is increasingly used as primary therapy. This Review provides an overview of current and future pharmacological therapies for patients with acromegaly.
    No preview · Article · Mar 2011 · Nature Reviews Endocrinology
  • Source
    F. Osman · A. Queiroga · M. Gammage · J. Daykin · M. Sheppard · J. Franklyn

    Preview · Article · Aug 2010 · Europace
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Subclinical hypothyroidism (SCH) and cognitive dysfunction are both common in the elderly and have been linked. It is important to determine whether T4 replacement therapy in SCH confers cognitive benefit. Our objective was to determine whether administration of T4 replacement to achieve biochemical euthyroidism in subjects with SCH improves cognitive function. We conducted a double-blind placebo-controlled randomized controlled trial in the context of United Kingdom primary care. Ninety-four subjects aged 65 yr and over (57 females, 37 males) with SCH were recruited from a population of 147 identified by screening. T4 or placebo was given at an initial dosage of one tablet of either placebo or 25 microg T4 per day for 12 months. Thyroid function tests were performed at 8-weekly intervals with dosage adjusted in one-tablet increments to achieve TSH within the reference range for subjects in treatment arm. Fifty-two subjects received T4 (31 females, 21 males; mean age 73.5 yr, range 65-94 yr); 42 subjects received placebo (26 females, 16 males; mean age 74.2 yr, 66-84 yr). Mini-Mental State Examination, Middlesex Elderly Assessment of Mental State (covering orientation, learning, memory, numeracy, perception, attention, and language skills), and Trail-Making A and B were administered. Eighty-two percent and 84% in the T4 group achieved euthyroidism at 6- and 12-month intervals, respectively. Cognitive function scores at baseline and 6 and 12 months were as follows: Mini-Mental State Examination T4 group, 28.26, 28.9, and 28.28, and placebo group, 28.17, 27.82, and 28.25 [not significant (NS)]; Middlesex Elderly Assessment of Mental State T4 group, 11.72, 11.67, and 11.78, and placebo group, 11.21, 11.47, and 11.44 (NS); Trail-Making A T4 group, 45.72, 47.65, and 44.52, and placebo group, 50.29, 49.00, and 46.97 (NS); and Trail-Making B T4 group, 110.57, 106.61, and 96.67, and placebo group, 131.46, 119.13, and 108.38 (NS). Linear mixed-model analysis demonstrated no significant changes in any of the measures of cognitive function over time and no between-group difference in cognitive scores at 6 and 12 months. This RCT provides no evidence for treating elderly subjects with SCH with T4 replacement therapy to improve cognitive function.
    Full-text · Article · Aug 2010 · The Journal of Clinical Endocrinology and Metabolism
  • [Show abstract] [Hide abstract]
    ABSTRACT: Pituitary disease is associated with increased mortality predominantly due to vascular disease. Control of cortisol secretion and GH hypersecretion (and cardiovascular risk factor reduction) is key in the reduction of mortality in patients with Cushing's disease and acromegaly, retrospectively. For patients with acromegaly, the role of IGF-I is less clear-cut. Confounding pituitary hormone deficiencies such as gonadotropins and particularly ACTH deficiency (with higher doses of hydrocortisone replacement) may have a detrimental effect on outcome in patients with pituitary disease. Pituitary radiotherapy is a further factor that has been associated with increased mortality (particularly cerebrovascular). Although standardized mortality ratios in pituitary disease are falling due to improved treatment, mortality for many conditions are still elevated above that of the general population, and therefore further measures are needed. Craniopharyngioma patients have a particularly increased risk of mortality as a result of the tumor itself and treatment to control tumor growth; this is a key area for future research in order to optimize the outcome for these patients.
    No preview · Article · Jun 2010 · Endocrine reviews
  • Beverly M.K. Biller · Michael Sheppard

    No preview · Article · Dec 2009 · Best Practice & Research: Clinical Endocrinology & Metabolism
  • [Show abstract] [Hide abstract]
    ABSTRACT: A number of retrospective studies report that patients with acromegaly have increased morbidity and premature mortality, with standardized mortality ratios (SMR) of 1.3-3. Many patients with acromegaly develop hypopituitarism as a result of the pituitary adenoma itself or therapies such as surgery and radiotherapy. Pituitary radiotherapy and hypopituitarism have also been associated with an increased SMR. Using the West MIDLANDS: Acromegaly database (n = 501; 275 female), we assessed the influence of prior radiotherapy and hypopituitarism (and replacement therapy) on mortality in patients with acromegaly. Median duration of follow-up was 14.0 yr (interquartile range, 7.9-21 yr). All-cause mortality was elevated [SMR, 1.7 (1.4, 2.0); P < 0.001]. On external analysis, prior radiotherapy, ACTH, and gonadotropin deficiency were associated with an elevated SMR [radiotherapy SMR, 2.1 (1.7-2.6); P = 0.006; ACTH deficiency SMR, 2.5 (1.9-3.2); P < 0.0005; and gonadotropin deficiency SMR, 2.1 (1.6-2.7); P = 0.037]. On internal analysis, the relative risk (RR) of mortality was increased in the radiotherapy [RR, 1.8 (1.2-2.8); P = 0.008] and ACTH-deficiency groups [RR, 1.7 (1.2-2.5); P = 0.004], but not in the gonadotropin- or TSH-deficiency groups. In the ACTH-deficient group, increased replacement doses of hydrocortisone greater than 25 mg/d were associated with increased mortality compared to lower doses. Radiotherapy and ACTH deficiency are significantly associated with increased mortality in patients with acromegaly. In ACTH-deficient patients, a daily dose of more than 25 mg hydrocortisone is associated with increased mortality compared to lower doses. These results have important implications for the treatment of patients with acromegaly and also raise issues as to the optimum hydrocortisone treatment regimens for ACTH-deficient patients.
    No preview · Article · Oct 2009 · The Journal of Clinical Endocrinology and Metabolism
  • [Show abstract] [Hide abstract]
    ABSTRACT: Acromegaly is associated with increased morbidity and mortality. Treatment options include surgery, radiotherapy, and medical therapy. The objective of the study was to examine the role of prolactin status, prior surgery, and radiotherapy on the response to medical therapy in patients with acromegaly and assess the relative efficacy of dopamine agonist therapy compared with somatostatin analog therapy. A total of 276 patients with acromegaly received either dopamine agonists (DA) and/or somatostatin analogs (SSA). One hundred seventy-two patients had received surgery and 73 radiotherapy prior to receiving medical therapy. One hundred ninety-eight of 276 received DA, and 143 of 276 received SSA. GH and IGF-I values at baseline and after 12 months on therapy were analyzed. In the DA group, basal prolactin concentration did not predict response to therapy, GH percent reduction: hyperprolactinemia, 26.7% (-10.4 to 48) vs. normoprolactinemia, 34.8% (0.2-53.2), P = 0.58; IGF-I percent reduction: hyperprolactinemia 30.0% (9.2-43.1) vs. normoprolactinemia 16.8% (4-37), P = 0.45. Prior surgery was not associated with any difference in response to DA: GH percent reduction (P = 0.1) and IGF-I percent reduction (P = 0.08). By contrast, prior radiotherapy was associated with an enhanced efficacy of GH response to DA, P = 0.02. In the SSA group, there was no effect of prior surgery or radiotherapy on response of GH, but radiotherapy was associated with less marked IGF-I percent reduction (P = 0.05). SSA were more potent than DA at decreasing both GH [62.8% (20.7-85%) vs. 42.4% (-6.5 to 68.6), P < 0.008] and IGF-I [SSA 40.4% (0-64.3) vs. 8% (0-40.8), P = 0.05]. The effects of DA are irrespective of baseline prolactin concentrations. Prior radiotherapy is associated with differences in GH and IGF-I response to DA and SSA therapy.
    No preview · Article · Apr 2009 · The Journal of Clinical Endocrinology and Metabolism
  • K. Boelaert · J.A. Franklyn · M. Sheppard

    No preview · Article · Jan 2009
  • [Show abstract] [Hide abstract]
    ABSTRACT: The aims of treatment in patients with acromegaly are to achieve serum GH/IGF-I concentrations associated with cure or normalization of mortality and alleviation of symptoms. Using the West Midlands Acromegaly database (n = 501) we investigated the reliability of basal fasting GH in predicting nadir or mean GH during oral glucose tolerance test (OGTT) or GH day curve (GHDC), respectively, the degree of discordance between disease activity measured by GH and IGF-I values and the effect of radiotherapy on the above relationships. In total 773 OGTT and 507 GHDC were performed. Basal fasting GH was strongly correlated with nadir/mean GH on OGTT/GHDC (r = +0.87, P < 0.0001, r = +0.93, P < 0.0001, respectively). A basal GH < 2.5 microg/l was associated with a nadir/mean GH during OGTT/GHDC < 2.5 microg/l in 98.6% and 88.2% of cases, respectively. Elevated IGF-I was seen in 32.4% and 46.4% of patients with GH nadir values during OGTT < 1 and < 2.5 microg/l, respectively, and in 21.2% and 45.9% of GHDC with mean GH < 1 and < 2.5 microg/l, respectively. Radiotherapy increased the discordance in GH and IGF-I as markers of disease activity at GH < 2.5 microg/l (elevated IGF-I-values when OGTT nadir GH < 2.5 microg/l: radiotherapy 55.5%vs. no radiotherapy 36.9%, P = 0.002). There is a close relationship between a basal fasting GH < 2.5 microg/l and nadir/mean GH < 2.5 microg/l during OGTT/GHDC. There is a large discordance between disease activity when assessed by GH and IGF-I which is further increased by radiotherapy. These observations illustrate the challenge of defining appropriate biochemical end-points to achieve control of disease and normalization of mortality in acromegaly.
    No preview · Article · Oct 2008 · Clinical Endocrinology
  • [Show abstract] [Hide abstract]
    ABSTRACT: The V Consensus Group Meeting on 'Guidelines for Treatment of GH Excess and GH Deficiency in the Adult' was an international workshop held on February 20-22, 2006 in Santa Monica, California, USA. The principal aim of this meeting was to provide guidelines for the evaluation and treatment of adults with either form of abnormal GH secretion: GH excess or GH deficiency. The workshop included debates as to the choice of primary treatment, discussions of the targets for adequate treatment, and concluded with presentations on open issues germane to adult GH treatment including the role of GH in malignancies, the impact of longterm treatment on bone, and a cost-benefit analysis. The meeting was comprised of 66 delegates representing 13 different countries.
    No preview · Article · Oct 2008 · Journal of endocrinological investigation
  • Source
    K Boelaert · AA Syed · N Manji · M C Sheppard · R L Holder · S C Gough · JA Franklyn
    [Show abstract] [Hide abstract]
    ABSTRACT: There is little consensus regarding the most appropriate dose of radioiodine ((131)I) to be administered to patients with hyperthyroidism. To compare the efficacy of fixed dose regimens of (131)I in curing hyperthyroidism and to define simple clinical and biochemical factors that predict outcome in individual patients. Consecutive series of hyperthyroid subjects treated with (131)I. Single Secondary/Tertiary Care Hospital Clinic. A total of 1278 patients (1013 females and 262 males, mean age 49.7 years) presenting with hyperthyroidism between 1984 and 2006. Treatment with (131)I using a fixed dose regimen. Probability of cure and risk of development of hypothyroidism following a single dose of (131)I. Patients given a single dose of (131)I of 600 MBq (n = 485) had a higher cure rate (84.1%) compared with those receiving either 370 MBq (74.9%, P < 0.001) or those given 185 Bq (63%, P < 0.001). An increased incidence of hypothyroidism by 1 year was evident with higher doses (600 MBq: 60.4%; 370 MBq: 49.2%, P = 0.001; 185 Bq: 38.1%, P < 0.001). Binary logistic regression analysis identified a 600 Bq dose of (131)I [adjusted odds ratio, AOR 3.33 (2.28-4.85), P < 0.001], female gender [AOR 1.75 (1.23-2.47), P = 0.002], lower presenting serum free T4 concentration [AOR 1.01 (1.01-1.02), P < 0.001] and absence of a palpable goitre [AOR 3.33 (2.00-5.56), P < 0.001] to be independent predictors of cure. Similarly, a 600 MBq dose [AOR 3.79 (2.66-5.38), P < 0.001], female gender [AOR 1.46 (1.05-2.02), P = 0.02], younger age [AOR 1.03 (1.02-1.04), P < 0.001], absence of a palpable goitre [AOR 3.85 (2.38-5.88), P < 0.001] and presence of ophthalmopathy [AOR 1.57 (1.06-2.31), P = 0.02] were identified as independent factors predicting the probability of development of hypothyroidism at one year. Based on these findings, formulae to indicate probability of cure and risk of hypothyroidism for application to individual patients were derived. Simple clinical/biochemical criteria can be used to predict outcome after (131)I treatment. These factors determine that males, those with severe biochemical hyperthyroidism, and those with a palpable goitre require larger doses (600 MBq) in order to achieve cure.
    Preview · Article · May 2008 · Clinical Endocrinology
  • John Ayuk · Michael C Sheppard
    [Show abstract] [Hide abstract]
    ABSTRACT: The increased mortality associated with acromegaly was first demonstrated in early epidemiological studies. Since the seminal paper by Wright et al. in 1970, nearly 20 studies have analyzed mortality rates in over 5,000 patients with acromegaly. Overall standardized mortality rates are approximately two times higher than in the general population, relating to an average reduction in life expectancy of around 10 years. The excess deaths are due predominantly to cardiovascular, cerebrovascular and respiratory disease. Malignancy deaths have been high in some studies but not others; in the largest series looking at cancer mortality in acromegaly, overall cancer deaths were not increased, but colon cancer mortality was higher than expected. In 1993, Bates et al. first demonstrated that outcome was related to the latest measurable growth hormone (GH), and treatment to reduce GH levels led to improved outcomes. Other factors predicting poor outcome include the presence of hypertension and diabetes. On the basis of current evidence, a latest GH of less than 2-2.5 mug/L is a better predictor of good outcome than a normal insulin-like growth factor-1 (IGF-1), possibly due to discrepancy between GH and IGF-1 at low GH levels. There is some evidence to suggest a more stringent GH cut-off (less than 1 mug/L) may yield additional benefit but further studies are required to investigate any added risk of increased mortality from hypopituitarism. Radiotherapy has been linked specifically to cerebrovascular mortality and its use in patients with acromegaly must involve a careful risk-benefit analysis in each case.
    No preview · Article · Apr 2008 · Reviews in Endocrine and Metabolic Disorders
  • [Show abstract] [Hide abstract]
    ABSTRACT: In clinically euthyroid subjects on long-term amiodarone therapy free thyroxine (T4) concentrations were increased and free triiodothyronine (T3) levels reduced. There was also a marked increase in reverse T3 in the treated group. These changes are consistent with inhibition of peripheral deiodination of T4 and reverse T3. Despite the rise in T4 serum thyrotrophin (TSH) levels were increased, suggesting an effect of amiodarone on the anterior pituitary. To investigate the interaction of amiodarone with the cellular actions of thyroid hormones we examined the influence of the drug in vitro on the binding of T3 to isolated nuclei prepared from rat anterior pituitary tissue. Amiodarone inhibited the nuclear binding of T3 in a dose dependent fashion. Addition of amiodarone in vitro also stimulated TSH release from cultured rat anterior pituitary cells, consistent with a T3 antagonistic effect. These studies provide evidence for a direct influence of amiodarone on the thyrotroph, mediated via nuclear T3 receptor binding.
    No preview · Article · Mar 2008 · Clinical Endocrinology
  • [Show abstract] [Hide abstract]
    ABSTRACT: Previous studies have suggested that minor changes in thyroid function are associated with risk of atrial fibrillation (AF). Our objective was to determine the relationship between thyroid function and presence of atrial fibrillation (AF) in older subjects. A population-based study of 5860 subjects 65 years and older, which excluded those being treated for thyroid dysfunction and those with previous hyperthyroidism. Main outcome measures included tests of thyroid function (serum free thyroxine [T(4)] and thyrotropin [TSH]) and the presence of AF on resting electrocardiogram. Fourteen subjects (0.2%) had previously undiagnosed overt hyperthyroidism and 126 (2.2%), subclinical hyperthyroidism; 5519 (94.4%) were euthyroid; and 167 (2.9%) had subclinical hypothyroidism and 23 (0.4%), overt hypothyroidism. The prevalence of AF in the whole cohort was 6.6% in men and 3.1% in women (odds ratio, 2.23; P<.001). After adjusting for sex, logistic regression showed a higher prevalence of AF in those with subclinical hyperthyroidism compared with euthyroid subjects (9.5% vs 4.7%; adjusted odds ratio, 2.27; P=.01). Median serum free T(4) concentration was higher in those with AF than in those without (1.14 ng/dL; interquartile range [IQR], 1.05-1.27 ng/dL [14.7 pmol/L; IQR, 13.5-16.4 pmol/L] vs 1.10 ng/dL; IQR, 1.00-1.22 ng/dL [14.2 pmol/L; IQR, 12.9-15.7 pmol/L]; P<.001), and higher in those with AF when analysis was limited to euthyroid subjects (1.13 ng/dL; IQR, 1.05-1.26 ng/dL [14.6 pmol/L; IQR, 13.5-16.2 pmol/L] vs 1.10 ng/dL; IQR, 1.01-1.21 ng/dL [14.2 pmol/L; IQR, 13.0-15.6 pmol/L]; P=.001). Logistic regression showed serum free T(4) concentration, increasing category of age, and male sex all to be independently associated with AF. Similar independent associations were observed when analysis was confined to euthyroid subjects with normal TSH values. The biochemical finding of subclinical hyperthyroidism is associated with AF on resting electrocardiogram. Even in euthyroid subjects with normal serum TSH levels, serum free T(4) concentration is independently associated with AF.
    No preview · Article · May 2007 · Archives of Internal Medicine
  • Michael C Sheppard

    No preview · Article · Mar 2007 · Clinical Endocrinology
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: This study sought to prospectively evaluate the prevalence of cardiovascular abnormalities in patients with overt hyperthyroidism before and after antithyroid therapy. Overt hyperthyroidism is associated with recognized cardiovascular effects believed to be reversed by antithyroid therapy; however, increasing data suggest significant long-term cardiovascular mortality. A total of 393 (312 women, 81 men) consecutive unselected patients with overt hyperthyroidism were recruited and compared with 393 age- and gender-matched euthyroid control subjects. Hyperthyroid patients were re-evaluated after antithyroid therapy. Findings in patients and matched control subjects were compared at presentation, after treatment when patients had subclinical hyperthyroidism biochemically, and when patients were rendered biochemically euthyroid. All had a structured cardiovascular history and examination, including measurements of blood pressure (BP) and pulse rate. All had resting 12-lead electrocardiogram and 24-h digital Holter monitoring of cardiac rhythm. A higher prevalence of cardiovascular symptoms and signs, as well as abnormal hemodynamic parameters, was noted among hyperthyroid patients at recruitment compared with control subjects. Cardiac dysrhythmias, especially supraventricular, were more prevalent among patients than among control subjects. Palpitation and dyspnea, postural decrease in systolic pressure, and atrial fibrillation (AF) remained more prevalent in treated hyperthyroid subjects with subclinical hyperthyroidism compared with control subjects, and remained more prevalent after restoration of euthyroidism. Predictors for successful reversion to sinus rhythm in those with AF associated with hyperthyroidism were lower BP measurements at recruitment and an initial hypothyroid state induced by antithyroid therapy. Mortality was higher in hyperthyroid subjects than in control subjects after a mean period of follow-up of 66.6 months. Cardiovascular abnormalities are common in patients with overt hyperthyroidism at presentation, but some persist despite effective antithyroid therapy.
    Full-text · Article · Feb 2007 · Journal of the American College of Cardiology
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Population-based screening has been advocated for subclinical thyroid dysfunction in the elderly because the disorder is perceived to be common, and health benefits may be accrued by detection and treatment. The objective of the study was to determine the prevalence of subclinical thyroid dysfunction and unidentified overt thyroid dysfunction in an elderly population. A cross-sectional survey of a community sample of participants aged 65 yr and older registered with 20 family practices in the United Kingdom. Exclusions included current therapy for thyroid disease, thyroid surgery, or treatment within 12 months. Tests of thyroid function (TSH concentration and free T4 concentration in all, with measurement of free T3 in those with low TSH) were conducted. EXPLANATORY VARIABLES: These included all current medical diagnoses and drug therapies, age, gender, and socioeconomic deprivation (Index of Multiple Deprivation, 2004). Standardized prevalence rates were analyzed. Logistic regression modeling was used to determine factors associated with the presence of subclinical thyroid dysfunction. A total of 5960 attended for screening. Using biochemical definitions, 94.2% [95% confidence interval (CI) 93.8-94.6%] were euthyroid. Unidentified overt hyper- and hypothyroidism were uncommon (0.3, 0.4%, respectively). Subclinical hyperthyroidism and hypothyroidism were identified with similar frequency (2.1%, 95% CI 1.8-2.3%; 2.9%, 95% CI 2.6-3.1%, respectively). Subclinical thyroid dysfunction was more common in females (P < 0.001) and with increasing age (P < 0.001). After allowing for comorbidities, concurrent drug therapies, age, and gender, an association between subclinical hyperthyroidism and a composite measure of socioeconomic deprivation remained. Undiagnosed overt thyroid dysfunction is uncommon. The prevalence of subclinical thyroid dysfunction is 5%. We have, for the first time, identified an independent association between the prevalence of subclinical thyroid dysfunction and deprivation that cannot be explained solely by the greater burden of chronic disease and/or consequent drug therapies in the deprived population.
    Full-text · Article · Jan 2007 · Journal of Clinical Endocrinology & Metabolism
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Thyroid nodules and goiter are common, and fine-needle aspiration biopsy (FNAB) is the first investigation of choice in distinguishing benign from malignant disease. The objective of the study was to assess whether simple clinical and biochemical parameters can predict the likelihood of thyroid malignancy in subjects undergoing FNAB. The design was a prospective cohort. The study was conducted at a single secondary/tertiary care clinic. One thousand five hundred consecutive patients without overt thyroid dysfunction (1304 females and 196 males, mean age 47.8 yr) presenting with palpable thyroid enlargement between 1984 and 2002 were evaluated by FNAB of the thyroid. There were no interventions. Goiter type was assessed clinically and classified as diffuse in 183, multinodular in 456, or solitary nodule in 861 cases. Serum TSH concentration at presentation was measured in a sensitive assay in patients presenting after 1988 (n = 1183). The final cytological or histological diagnosis was determined after surgery (n = 553) or a minimum 2-yr clinical follow-up period (mean 9.5 yr, range 2-18 yr). The overall sensitivity and specificity of FNAB in predicting malignancy were 88 and 84%, respectively. The risk of diagnosis of malignancy rose in parallel with the serum TSH at presentation, with significant increases evident in patients with serum TSH greater than 0.9 mU/liter, compared with those with lower TSH. Binary logistic regression analysis revealed significantly increased adjusted odds ratios (AORs) for the diagnosis of malignancy in subjects with serum TSH 1.0-1.7 mU/liter, compared with TSH less than 0.4 mU/liter [AOR 2.72, 95% confidence interval (CI) 1.02-7.27, P = 0.046], with further increases evident in those with TSH 1.8-5.5 mU/liter (AOR 3.88, 95% CI 1.48-10.19, P = 0.006, compared with TSH < 0.4 mU/liter) and greater than 5.5 mU/liter (AOR 11.18, 95% CI 3.23-8.63, P < 0.001, compared with TSH < 0.4 mU/liter). Males (AOR 1.8, 95% CI 1.04-3.1, P = 0.04), younger patients (AOR 1.1, 95% CI 1.01-1.15, P = 0.025), and those with clinically solitary nodules (AOR 2.53, 95% CI 1.5-4.28, P = 0.001) were also at increased risk. Based on these findings, a formula to predict the risk of the diagnosis of thyroid malignancy in individual patients, taking into account their gender, age, goiter type determined clinically, and serum TSH, was calculated. The risk of malignancy in a thyroid nodule increases with serum TSH concentrations within the normal range. In addition to patient's gender, age, and goiter type, the serum TSH concentration at presentation is an independent predictor of the presence of thyroid malignancy. We propose that these simple clinical and biochemical factors can serve as an adjunct to FNAB in predicting risk of malignancy.
    Preview · Article · Nov 2006 · Journal of Clinical Endocrinology & Metabolism

Publication Stats

11k Citations
1,879.65 Total Impact Points


  • 1983-2013
    • University of Birmingham
      • • School of Clinical and Experimental Medicine
      • • Centre for Endocrinology, Diabetes and Metabolism (CEDAM)
      • • Department of Primary Care Clinical Sciences
      • • Group of Medical Science and Education
      Birmingham, England, United Kingdom
  • 1982-2008
    • Queen Elizabeth Hospital Birmingham
      Birmingham, England, United Kingdom
  • 2007
    • Aston University
      Birmingham, England, United Kingdom
  • 1988-2006
    • The Queen Elizabeth Hospital
      Tarndarnya, South Australia, Australia
    • Newcastle University
      Newcastle-on-Tyne, England, United Kingdom
  • 1998
    • University Hospitals Birmingham NHS Foundation Trust
      • Department of Medicine
      Birmingham, England, United Kingdom
    • Temple University
      • Department of Biochemistry
      Filadelfia, Pennsylvania, United States
  • 1996
    • LKC Switzerland Ltd.
      Basel-Landschaft, Switzerland
    • The University of Western Ontario
      • Department of Paediatrics
      London, Ontario, Canada
  • 1995
    • University of Oslo
      Kristiania (historical), Oslo, Norway
    • Ealing, Hammersmith & West London College
      Londinium, England, United Kingdom
  • 1991
    • The University of Manchester
      • School of Biomedicine
      Manchester, England, United Kingdom