Population screening for autoimmune thyroid disease.

Whether or not healthy adults in the community would benefit from screening for autoimmune thyroid disease is controversial. Although the prevalence of unsuspected overt thyroid disease is low, a significant proportion of subjects tested will have evidence of mild thyroid failure or excess. This article assesses whether subclinical thyroid disease is of sufficient clinical importance to warrant screening and, once detected and confirmed, to justify therapy. Population screening for autoimmune thyroid disease is assessed against recently revised screening criteria, using data from epidemiologic studies. Recommendations are proposed that may be applied in any iodine-replete community.

The prevalence of hyperprolactinaemia and association with markers of autoimmune thyroid disease in survivors of the Whickham Survey cohort.

OBJECTIVE: Few data exist on the prevalence of hyperprolactinaemia in the community. This study was intended to determine the prevalence of hyperprolactinaemia in a sample closely matched to the current British population aged 38 years and over. DESIGN AND PATIENTS: The 1877 survivors at the 20-year follow-up of the Whickham Survey were a cross-sectional sample of the community aged 38 years and over. Serum was frozen and stored at -30 degrees C from 90% of the survivors (751 men, 924 women, median age 58 years (range 38 to 93 years)) who participated in the follow-up survey. MEASUREMENTS: Two years after the follow-up survey, serum prolactin concentrations were measured by ELISA/1 step sandwich assay (reference range < or = 600 mU/l in men and women). A repeat prolactin measurement was made in those subjects who had prolactin levels within the top 2.5% of men and women in this sample. RESULTS: At screening, 0.7% of the men and 2.5% of the women had serum prolactin levels greater than 600 mU/l. For men, 2.5% were above 400 mU/l. The prevalence of hyperprolactinaemia, if defined as greater than 400 mU/l in men and greater than 600 mU/l in women on repeat testing, was 1.4% in the men and 1.2% in the women. The aetiology in men was prolactin-raising drugs (n = 3), renal failure (n = 1), microprolactinoma (n = 1), and unknown (n = 2), and in women it was prolactin-raising drugs (n = 7), microprolactinoma (n = 1), and unknown (n = 1). Logarithmic transformation of serum prolactin concentrations produced Gaussian distributions with 95% reference ranges of 60-430 mU/l in men and 40-560 mU/l in women. No significant relationship was found in either sex between hyperprolactinaemia and age or evidence of autoimmune thyroid disease at either survey. In women, there was no association with age, distance beyond the menopause or duration of reproductive years but prolactin levels were slightly higher in those on oestrogen therapy (geometric mean prolactin 226 mU/l compared to 178 mU/l; t-test on log prolactin t = 3.79; P < 0.0001). CONCLUSIONS: This study has demonstrated that a gender-related reference range for serum prolactin is necessary. Pituitary pathology is not common and screening with measurement of serum prolactin is not warranted in middle-aged and elderly subjects. In asymptomatic subjects with modestly elevated serum prolactin levels (< 3 SD above the mean), extensive pituitary imaging and investigation is unwarranted. Autoimmune thyroid disease was not a significant cause of hyperprolactinaemia in this sample.

The incidence of diabetes mellitus in an English community: a 20-year follow-up of the Whickham Survey.

The original Whickham Survey documented the prevalence of diabetes and lipid disorders in a sample of 2779 adults aged 18 years and over, which matched the British population structure. The aim of the 20-year follow-up study was to determine the incidence and natural history of diabetes. Outcomes in terms of morbidity and mortality at follow-up were determined in over 97% of the original population. Ninety-four subjects had been identified and treated for diabetes since the first survey, including 17 subjects identified as having a fasting plasma glucose > or = 7.8 mmol l-1 at follow-up. The incidence of diabetes for the total population was 2.2 1000-1 year-1 (95% confidence interval 1.8, 2.6). The risk factors identified at first survey were corrected for age, cut-off at the 95 centile and entered into a log linear model. Those which strongly predicted development of diabetes in the total population were fasting blood glucose (odds ratio (OR) (with 95% confidence intervals) = 2.3 (1.5, 3.5)) and body mass index (OR = 2.2 (1.5, 3.3)) in men, and fasting blood glucose (OR = 2.6 (1.7, 4.1)) and fasting serum triglyceride (OR = 2.8 (1.8, 4.4)) in women. A logit model has enabled the calculation of the probability of developing diabetes 20 years later. It was the characteristics of becoming older such as obesity, hypertriglyceridaemia, and raised fasting blood glucose, rather than age itself, which were associated with the development of diabetes.

The development of ischemic heart disease in relation to autoimmune thyroid disease in a 20-year follow-up study of an English community.

The original Whickham Survey documented risk factors for cardiovascular disease and the prevalence of thyroid disorders in a sample of 2779 adults that closely matched the British population. A 20-year follow-up study has determined outcomes in terms of morbidity and mortality from ischemic heart disease in over 97% of the original survey population. Analysis of deaths from all causes and from ischemic heart disease showed no association with antithyroid antibody status identified at first survey. A multiple logistic regression using the development of ischemic heart disease in the total population at follow-up as the dependent variable found that the significant predictor variables for men were age, cholesterol, mean arterial blood pressure, smoking history, and skinfold thickness index. For women only age, cholesterol, and mean arterial blood pressure were significant. The presence of autoimmune thyroid disease, as defined by either hypothyroidism, positive antithyroid antibodies, or raised serum thyrotropin at first survey, was not significant. A retrospective cohort study of a subsample of women identified at first survey with positive antithyroid antibodies or raised serum thyrotropin and closely matched controls found no significant association with mortality or development of ischemic heart disease. There is no evidence from this study to suggest that evidence of autoimmune thyroid disease identified 20 years ago is associated with an increased risk of ischemic heart disease.

The incidence of thyroid disorders in the community: a twenty-year follow-up of the Whickham Survey.

BACKGROUND AND OBJECTIVE: The original Whickham Survey documented the prevalence of thyroid disorders in a randomly selected sample of 2779 adults which matched the population of Great Britain in age, sex and social class. The aim of the twenty-year follow-up survey was to determine the incidence and natural history of thyroid disease in this cohort. DESIGN, PATIENTS AND MEASUREMENTS: Subjects were traced at follow-up via the Electoral Register, General Practice registers, Gateshead Family Health Services Authority register and Office of Population Censuses and Surveys. Eight hundred and twenty-five subjects (30% of the sample) had died and, in addition to death certificates, two-thirds had information from either hospital/General Practitioner notes or post-mortem reports to document morbidity prior to death. Of the 1877 known survivors, 96% participated in the follow-up study and 91% were tested for clinical, biochemical and immunological evidence of thyroid dysfunction. RESULTS: Outcomes in terms of morbidity and mortality were determined for over 97% of the original sample. The mean incidence (with 95% confidence intervals) of spontaneous hypothyroidism in women was 3.5/1000 survivors/year (2.8-4.5) rising to 4.1/1000 survivors/year (3.3-5.0) for all causes of hypothyroidism and in men was 0.6/1000 survivors/year (0.3-1.2). The mean incidence of hyperthyroidism in women was 0.8/1000 survivors/year (0.5-1.4) and was negligible in men. Similar incidence rates were calculated for the deceased subjects. An estimate of the probability of the development of hypothyroidism and hyperthyroidism at a particular time, i.e. the hazard rate, showed an increase with age in hypothyroidism but no age relation in hyperthyroidism. The frequency of goitre decreased with age with 10% of women and 2% of men having a goitre at follow-up, as compared to 23% and 5% in the same subjects respectively at the first survey. The presence of a goitre at either survey was not associated with any clinical or biochemical evidence of thyroid dysfunction. In women, an association was found between the development of a goitre and thyroid-antibody status at follow-up, but not initially. The risk of having developed hypothyroidism at follow-up was examined with respect to risk factors identified at first survey. The odds ratios (with 95% confidence intervals) of developing hypothyroidism with (a) raised serum TSH alone were 8 (3-20) for women and 44 (19-104) for men; (b) positive anti-thyroid antibodies alone were 8 (5-15) for women and 25 (10-63) for men; (c) both raised serum TSH and positive anti-thyroid antibodies were 38 (22-65) for women and 173 (81-370) for men. A logit model indicated that increasing values of serum TSH above 2mU/l at first survey increased the probability of developing hypothyroidism which was further increased in the presence of anti-thyroid antibodies. Neither a positive family history of any form of thyroid disease nor parity of women at first survey was associated with increased risk of developing hypothyroidism. Fasting cholesterol and triglyceride levels at first survey when corrected for age showed no association with the development of hypothyroidism in women. CONCLUSIONS: This historical cohort study has provided incidence data for thyroid disease over a twenty-year period for a representative cross-sectional sample of the population, and has allowed the determination of the importance of prognostic risk factors for thyroid disease identified twenty years earlier.

Comparison of non-mydriatic retinal photography with ophthalmoscopy in 2159 patients: mobile retinal camera study.

OBJECTIVE: To determine whether non-mydriatic Polaroid retinal photography was comparable to ophthalmoscopy with mydriasis in routine clinic screening for early, treatable diabetic retinopathy. DESIGN: Prospective study of ophthalmoscopic findings according to retinal camera screening and ophthalmoscopy and outcome of referral to ophthalmologist. SETTING: Outpatient diabetic clinics of three teaching hospitals and three district general hospitals. PATIENTS: 2159 Adults selected randomly from the diabetic clinics, excluding only those registered as blind or those in wheelchairs and unable to enter the screening vehicle. MAIN OUTCOME MEASURES: Numbers of patients and eyes correctly identified by each technique as requiring referral with potentially treatable retinopathy (new vessel formation and maculopathy) and congruence in numbers of microaneurysms, haemorrhages, and exudates reported. RESULTS: Camera screening missed two cases of new vessel formation and did not identify a further 12 but indicated a need for referral. Ophthalmoscopy missed five cases of new vessel formation and indicated a need for referral in another four for other reasons. Maculopathy was reported in 147 eyes with camera screening alone and 95 eyes by ophthalmoscopy only (chi 2 = 11.2; p less than 0.001), in 66 and 29 of which respectively maculopathy was subsequently confirmed. Overall, 38 eyes received laser treatment for maculopathy after detection by camera screening compared with 17 after ophthalmoscopic detection (chi 2 = 8.0; p less than 0.01). Camera screening underestimated numbers of microaneurysms (chi 2 = 12.9; p less than 0.001) and haemorrhages (chi 2 = 7.4; p less than 0.01) and ophthalmoscopy underestimated hard exudates (chi 2 = 48.2; p less than 0.001). CONCLUSIONS: Non-mydriatic Polaroid retinal photography is at least as good as ophthalmoscopy with mydriasis in routine diabetic clinics in identifying new vessel formation and absence of retinopathy and is significantly better in detecting exudative maculopathy.

Renal replacement treatment for diabetic patients in Newcastle upon Tyne and the Northern region, 1964-88.

OBJECTIVES: To review the experience of renal replacement treatment in diabetic patients treated in Newcastle upon Tyne and the Northern region from 1964 to 1988, and to compare the morbidity and mortality of diabetic patients treated with dialysis or transplantation with those of matched controls of non-diabetic patients. DESIGN: Retrospective study of clinical case notes. SETTING: Renal units of the Northern region, particularly that in Newcastle upon Tyne. PATIENTS: All 65 diabetic patients treated by renal replacement treatment in Newcastle upon Tyne from 1964 to 1987; 42 diabetic patients were matched with 42 non-diabetic patients according to age, sex, year of starting treatment, and type of treatment (dialysis or transplantation). MAIN OUTCOME MEASURES: Sex, age, renal biopsy findings, blood pressure, history of diabetic treatment, and plasma creatinine concentration at the start of renal replacement treatment. History of renal replacement treatments, suitability for transplantation, history of transplantation, cumulative survival, and cause of death during follow up. Survival of technique, cumulative survival of the first peritoneal catheter and history of peritonitis in patients treated with continuous ambulatory peritoneal dialysis; source of graft, histocompatibility antigens, duration of associated stay in hospital, and graft survival in patients receiving renal or pancreatic transplant. RESULTS: 1259 Patients with chronic renal failure were accepted for renal replacement treatment in Newcastle upon Tyne, of whom 65 (5%) had diabetes. The first was accepted in 1974, and between 1974 and 1980 another 15 were treated (mean age 42 years; 4% of new patients). From 1981 to 1987, 49 diabetic patients (mean age 44; 9% of new patients) were treated. Fifty patients (77%) had insulin dependent diabetes and the remaining 15 (23%) non-insulin dependent diabetes. On average, the patients were aged 25 (range 5-57) when diabetes was first diagnosed and 44 (range 24-70) at the start of renal replacement treatment. The mean age at the start of treatment was 40 for patients with non-insulin dependent diabetes and 58 for patients with non-insulin dependent diabetes. Transplantation was performed in 33 of the diabetic patients, whose mean age was lower than that of those who did not receive a transplant (41 v 48 respectively, p less than 0.05). Comparison between the 42 diabetic patients and matched controls showed that the overall survival at five years was 46% and 77% respectively. The three year survival of the diabetic patients who did not receive a transplant was poor (41% v 79% respectively). Of patients transplanted, survival at five years was 73% in the diabetic patients and 90% in the controls. However, there was no significant difference in the five year graft survival (64% v 46% respectively). CONCLUSIONS: Diabetes adversely affects morbidity and mortality in patients having renal replacement treatment, but renal transplantation seems to be the best option for treating diabetic patients with end stage renal failure.

The epidemiology of hypothyroidism--an update.

Comparison of studies of the prevalence and incidence of hypothyroidism is hampered by differing definitions and population samples. Using a uniform set of diagnostic criteria, the prevalence of previously undiagnosed, spontaneous, overt hypothyroidism in community-based studies has been estimated between 2-4/1000 total population world-wide. If all cases of previously diagnosed hypothyroidism, previous thyroid surgery and radioiodine treatment are included, this prevalence rises to approximately 10/1000, and if subclinical cases are included, then the prevalence is probably over 50/1000 total population. The annual incidence of overt hypothyroidism is between 1-2/1000 for female and around 2/10,000 for males, with individuals having previously elevated TSH and positive circulating thyroid autoantibodies, being particularly at risk. The question of widespread population screening for hypothyroidism is unsettled, but it is probably not cost-effective unless incorporated as part of a screening programme for other conditions such as cervical cancer, or targeted at high risk groups such as post-menopausal women. The combination of serum TSH estimation and a high clinical index of suspicion should detect most patients with thyroid dysfunction, although detailed studies on the use of the more sensitive assays in the detection of both hyper- and hypothyroidism have yet to be published.

A trial of the calcium antagonist nisoldipine in hypertensive non-insulin-dependent diabetic patients.

The antihypertensive and metabolic effects of a new calcium antagonist nisoldipine (10 to 20 mg at night) were investigated in 14 mild to moderately hypertensive non-insulin-dependent diabetic patients (median age 62, range 50-70 years). In a 12-week placebo controlled single blind study, sitting and standing blood pressure were significantly lowered (p less than 0.001). Heart rate was unchanged as were blood urea, creatinine, bilirubin, mmol/l (mean +/- SEM) and uric acid concentrations. Plasma sodium levels fell during active therapy (142 +/- 0.5 mmol/l (mean +/- SEM) versus 139 +/- 0.5 (p less than 0.001) and remained lower during the washout period. Plasma calcium concentrations increased during nisoldipine therapy (2.41 +/- 0.02 versus 2.51 +/- 0.03 mmol/l, p less than 0.001) and returned towards baseline during the washout period. Plasma ionized calcium concentrations showed similar changes but plasma sodium and calcium remained within the normal laboratory ranges in all patients at all times. Serum triglyceride concentrations fell (placebo 1.9 +/- 0.02 mmol/l vs nisoldipine 1.6 +/- 0.2, p less than 0.05), but fasting cholesterol was unchanged. Fasting blood glucose, and the blood glucose response to oral glucose challenge (75 g) showed no differences though HbA1 concentrations fell (10.6 +/- 0.7 versus 9.2 +/- 0.05%, p less than 0.05) and tended to rise when the drug was withdrawn. Haemoglobin concentrations also fell during active therapy (14.7 +/- 0.4 vs 14 +/- 0.32 g/dl p less than 0.001) and also remained lower after the washout period (13.9 +/- 0.03 g/dl).(ABSTRACT TRUNCATED AT 250 WORDS)

Recurrent pregnancy-induced polyuria and thirst due to hypothalamic diabetes insipidus: an investigation into possible mechanisms responsible for polyuria.

A young patient developed hypothalamic diabetes insipidus due to histiocytosis in infancy and was satisfactorily treated with Pitressin. As a teenager she no longer had thirst or polyuria after treatment was stopped. These symptoms only returned during her two pregnancies. When non-pregnant her urine output was 1.7-2.0 1/24 h, basal plasma osmolality 288-290 mOsm/kg, and during pregnancy 24 h urine volume was 4.5-5.21, plasma osmolality 278-280 mOsm/kg. Studies on osmoregulation of thirst and AVP release, and on renal sensitivity to the V2 agonist desmopressin and endogenous vasopressin were performed in pregnant and non-pregnant states. She had no circulating antibodies to AVP, and the effect of pregnancy-associated vasopressinase was eliminated. Results showed lowered basal plasma osmolality and osmolar thirst threshold in pregnancy but no failure of the renal concentrating mechanism. Plasma AVP concentrations after osmotic stimulation were lower in pregnancy. We propose that she developed thirst and polyuria during pregnancy because of lowering of her osmolar thirst threshold to plasma osmolalities which caused her to drink sufficient quantities of fluid to further reduce AVP secretion. We cannot exclude, however, the possibility that there was increased clearance of circulating AVP.

Thyroid function in hyperemesis gravidarum.

Twenty-five patients with severe persistent vomiting were studied. On admission they were given the diagnosis of hyperemesis gravidarum. Hyperemesis was defined as vomiting of sufficient severity to warrant admission to hospital and iv therapy, which was not associated with any other condition known to cause vomiting other than the pregnancy itself. Ten (40%) of the patients had free thyroxine levels which were elevated on admission with hyperemesis. The free thyroxine normalised when the patients were well but still pregnant and remained normal post partum. Longitudinal data for nine other thyroid parameters are given and all illustrate the transient nature of the disturbed function in hyperemesis gravidarum.

Adipocyte insulin binding and insulin sensitivity in 'brittle' diabetes.

Adipocyte insulin binding and insulin sensitivity to stimulation of lipogenesis were assessed in a group of extremely 'brittle' diabetic patients who were resistant to subcutaneous insulin therapy and had required frequent and prolonged hospital admission. These patients had significantly lower maximum adipocyte insulin binding (1.78 +/- 0.18%) than age-, sex- and weight-matched stable diabetic control subjects (2.57 +/- 0.36%; p less than 0.05). Scatchard analysis suggested that the decreased binding was secondary to reduced receptor affinity with no change in receptor number. Adipocytes from the brittle subjects displayed resistance to insulin stimulation of lipogenesis compared with those from diabetic or normal control groups (half-maximal stimulation at 34 +/- 4, 15 +/- 3 and 13 +/- 2 pmol/l respectively; p less than 0.01 between brittle and stable diabetic groups). In the one subject who was treated with intraperitoneal insulin, the changes in insulin binding and sensitivity were found to have reverted towards normal. The peripheral tissue abnormalities of brittle diabetes may exacerbate the clinical syndrome although the relationship of these changes to the primary cause of the syndrome is uncertain.

Mortality from diabetic nephropathy in the United Kingdom.

Deaths in diabetic subjects dying under 50 years of age in the United Kingdom during 1979 have been analysed with special reference to diabetic nephropathy. Fifteen percent of 447 deaths were from nephropathy. Uraemic deaths from nephropathy were particularly common in those whose diabetes was diagnosed under 31 years old, and responsible for over one-quarter of deaths in this age group. Most deaths from nephropathy occur before 30 years' duration of diabetes and are rare in those of longer duration, suggesting that some diabetic patients are more and others less prone to this complication. There were more men than women in a ratio of approximately 1.3:1. Severe retinopathy is usually present in end-stage renal failure causing blindness in one out of three cases, and impaired vision in a further one out of three. Blind patients were not otherwise more severely affected by diabetic complications than others. It is estimated that approximately three-quarters of the diabetic subjects who develop end-stage renal failure from nephropathy may be suitable for dialysis or transplantation.

Intermediate acting insulin given at bedtime: effect on blood glucose concentrations before and after breakfast.

Six C-peptide deficient diabetics receiving twice daily mixtures of short and intermediate acting insulins were selected for study because of persistently raised blood glucose concentrations before and after breakfast. They were investigated to assess the effect of moving their evening injection of intermediate acting insulin to bedtime. The patients' usual twice daily insulin treatment was optimised and compared with the bedtime regimen during inpatient metabolic studies and an outpatient crossover study. With the conventional injection regimen blood glucose concentration rose sharply from 0500 to reach a fasting mean value of 10 +/- SE 1 . 6 mmol/l (180 +/- 29 mg/100 ml) and 16 . 8 +/- 2 . 2 mmol/l (303 +/- 40 mg/100 ml) after breakfast. By contrast, when the evening dose of intermediate acting insulin was delayed until bedtime the nocturnal rise in blood glucose concentration started later and was significantly lower both fasting (7 . 5 +/- 1 . 1 mmol/l (135 +/- 20 mg/100 ml); p less than 0 . 02) and after breakfast (13 . 2 +/- 1 . 4 mmol/l(238 +/- 25 mg/100 ml); p less than 0 . 02). Fasting blood concentrations of ketone bodies (3-hydroxybutyrate) were also significantly decreased. Plasma free insulin concentrations showed the predicted changes in five of the six patients. Blood glucose profiles collected over four months during the outpatient study confirmed the beneficial effect of giving intermediate acting insulin at bedtime.