Objective: Vasculitis is a rare complication of anti-thyroid medications. There are 32 cases of antineutrophil cytoplasmic antibody (ANCA)-positive vasculitis in association with anti-thyroid medication reported in the English literature. The objectives of this study were to assess the frequency of positive ANCA in patients on long-term anti-thyroid medication, and to follow patients prospectively from commencement of medication to determine whether they became ANCA-positive after therapy. Design: Prospectively collected cross-sectional study of two groups of patients: (i) who had received long-term (>18 months) anti-thyroid medication, and (ii) newly diagnosed thyrotoxicosis before commencement of anti-thyroid medication attending clinic between 28 April 1998 and 30 September 1998. Data were collected for age, sex, ethnicity, underlying thyroid disease, medication and duration, and symptomatology. Results: Eight of 30 patients on long-term anti-thyroid medication (26.7%) were ANCA-positive. All ANCA-positive patients were female, seven were taking propylthiouracil (PTU) at the time of testing. ANCA-positive patients had taken PTU for a mean Ϯ S.D. of 7.9 Ϯ 10.2 years, compared with 0.8 Ϯ 2.2 years in ANCA-negative patients (Mann-Whitney, P < 0.0001). The ten patients with newly diagnosed thyrotoxicosis were ANCA-negative before commencement of carbimazole. One (10%) became ANCApositive within 8 months of therapy. Conclusions: In our population, ANCA-positivity in association with long-term anti-thyroid medication is common (26.7%). One patient who was ANCA-negative prior to anti-thyroid therapy has become ANCA-positive. ANCA should be tested in patients receiving long-term anti-thyroid medications, and in patients with adverse reactions. As PTU is more commonly associated with vasculitis and positive ANCA, carbimazole may be the preferred medication for long-term use. Patients with positive ANCA should be followed, and considered for definitive anti-thyroid therapy, to allow cessation of medication. ANCA-positivity may resolve after cessation of anti-thyroid medication.
The aim of this study was to determine the prevalence and extent of glycemic excursions (hypo- and hyperglycemic) in elderly patients with well-controlled type 2 diabetes using a Continuous Glucose Monitor System (CGMS) (Medtronic MiniMed). Elderly patients (>65 years old) with type 2 diabetes were recruited if their glycosylated hemoglobin (HbA1c) was <7.5% and if their oral hypoglycemic therapy included a sulfonylurea. Patients were asked to undergo two consecutive 72-h periods of continuous glucose monitoring at baseline and then again at 1 month (total 288 h). Patients were asked to record four self-monitored capillary blood glucose levels each day for calibration of the monitor and also to record meal times, exercise, and symptoms of hypoglycemia. The number of hyperglycemic (>144 mg/dL), hypoglycemic (<50 mg/dL), and borderline-hypoglycemic (50-65 mg/dL) events were determined (an event was defined as a glucose value that persisted for at least 15 min with or without symptoms). Twenty-five patients (21 men, four women) 73.9 +/- 4.4 years old with an HbA1c of 6.2 +/- 0.8% were each monitored for an average of 187.57 h. The mean glucose values were: fasting, 139 +/- 40 mg/dL; 2 h post-breakfast, 167 +/- 58 mg/dL; 2 h post-lunch, 157 +/- 53 mg/dL; and 2 h post-dinner, 149 +/- 49 mg/dL. Twenty patients (80%) experienced a total of 103 hypoglycemic events, and 14 of these patients experienced 54 events where the glucose levels were =40 mg/dL. Twenty-four patients (96%) experienced borderline-hypoglycemia (n = 229 events). Patients experienced a mean of 0.62 +/- 0.72 episodes of hypoglycemia (interstitial glucose <50 mg/dL) per day (four to five episodes overall), 0.35 +/- 0.6 episodes per day where the interstitial glucose was =40 mg/dL (two to three episodes overall), and 1.37 +/- 1.22 episodes of borderline-hypoglycemia (nine to 10 episodes overall). Each episode of hypoglycemia persisted for 78 +/- 73 min, and borderline-hypoglycemia for 45 +/- 11 min. Patients were hypoglycemic 3.3% of the time and borderline-hypoglycemic 3.7% of the time. No episode of hypoglycemia was recorded by any patient in his or her daily diary. High postprandial glucose values (>144 mg/dL 2 h postprandial) were recorded after 57% of all meals (breakfast 60%, lunch 57.5%, dinner 55.2%). The CGMS was generally well tolerated, but 52% of patients could not be studied for the full 12 days of monitoring. Thus hypoglycemia and excessive postprandial glycemic excursions are common in well-controlled patients with type 2 diabetes treated with a sulfonylurea with or without metformin. The CGMS is a useful research and clinical tool to assess glycemia in patients with type 2 diabetes but is not tolerated by all subjects.
OBJECTIVE—Although it is accepted that elevated plasma homocysteine (tHcy) levels occur in end-stage renal disease and type 2 diabetes, the changes with milder renal dysfunction (e.g., microalbuminuria) are less clearly established. This study explores the relationship among tHcy, creatinine clearance (Ccr), and albumin excretion rate (AER) in a population with type 2 diabetes. RESEARCH DESIGN AND METHODS—A total of 260 patients with type 2 diabetes were screened in our outpatient clinic during 10 months. Fasting blood samples were collected, and AER was calculated from an overnight timed urine sample. Ccr was calculated using the Cockroft-Gault formula. RESULTS—A total of 198 subjects (76%) had normoalbuminuria (<20 μg/min), 50 subjects (19%) had microalbuminuria (20–200 μg/min), and 12 subjects (5%) had macroalbuminuria (≥200 μg/min). Those with microalbuminuria had higher levels of tHcy than those with normoalbuminuria (13.2 ± 7.8 vs. 11.3 ± 4.6 μmol/l, P < 0.05). Patients were then subdivided based on low Ccr (<80 ml · min−1 · 1.73 m−2) and normal Ccr (≥80 · min −1 · 1.73 m−2). None of the patients with macroalbuminuria had normal Ccr. In those with normoalbuminuria, tHcy levels were higher than in those with low Ccr than in those with normal Ccr (12.0 ± 4.6 vs. 10.0 ± 4.4 μmol/l, P < 0.01). The same was found for those with microalbuminuria (low Ccr versus normal Ccr: 14.6 ± 9.0 vs. 10.2 ± 2.8 μmol/l, P < 0.02). For normal Ccr, tHcy was similar irrespective of AER (normoalbuminuria versus microalbuminuria: 10.0 ± 4.4 vs. 10.2 ± 2.8 μmol/l, NS). For low Ccr, tHcy was higher in those with microalbuminuria versus normoalbuminuria (14.6 ± 9.0 vs. 12.0 ± 4.6 μmol/l, P = 0.01). Using multivariate regression, Ccr, but neither AER nor the presence of albuminuria, was an independent predictor of tHcy. CONCLUSIONS—These data strongly suggest that in patients with type 2 diabetes, the relationship between plasma tHcy and AER is largely due to associated changes in renal function, as defined by Ccr.
Pregestational diabetes mellitus (DM) is associated with adverse fetal and maternal outcomes. Studies suggest that optimal control of diabetes before and during pregnancy minimises these risks. There are few recent reviews of outcomes of pregnancies complicated by DM in Australia. Ninety-three pregnancies in women with DM at our hospital since 1989 were identified. We collected data for maternal age, type of diabetes, duration of therapy, complications of diabetes, maternal complications of pregnancy and fetal outcomes including malformations. The rate of pregnancy planning with optimal glycaemic control at conception was low in our population, particularly in patients with Type 1 diabetes. Women who smoked had worse glycaemic control, and a higher rate of miscarriage. There was a high rate of Caesarean section, particularly in those women with Type 1 diabetes (77.4%). The rate of Caesarean section was lower in planned pregnancies. There were no perinatal deaths. The number of neonates with major congenital anomalies was high (13%) in the Type 1 population. It is important to increase the rates of prepregnancy planning and to optimise glycaemic control before pregnancy. In many cases there has been a long interval between diagnosis and pregnancy, so all women with diabetes should receive counselling at frequent intervals about pregnancy and the importance of planning. Women who planned their pregnancies had improved outcomes, with decreased rate of Caesarean section, better glycaemic control and better neonatal Apgar scores. Women with diabetes should not smoke during pregnancy because of the increased risk of miscarriage and poorer glycaemic control.
Twenty-one patients who underwent surgical treatment for thyrotoxicosis and who were found at operation to have thyroid cancer are presented. Sixteen had Graves' disease and 5 had toxic nodular goiter. The group with Graves' is compared with 110 euthyroid patients with thyroid cancer who underwent their initial surgery in the same time period and who were of the same age (+/- 1 yr) and sex as the patients with Graves' disease. None of the thyrotoxic patients died during follow-up of 2-24 yr or developed subsequent metastases. The 1 patient with a local lymph node metastasis has not shown evidence of recurrence. Hypoparathyroidism appeared as a complication in only 1 patient. The size of tumors in the patients with Graves' disease was significantly smaller than in the euthyroid group. The course of the disease in both the patients with Graves' disease and the thyrotoxic group as a whole was relatively benign. This series does not support the recent suggestions that thyroid cancer in patients with Graves' disease is more aggressive than in either patients with toxic nodular goiter or euthyroid subjects. Patients with Graves' disease and thyroid cancer should be treated identically to other patients with thyroid cancer. Therapy should consist of total thyroidectomy followed by a postoperative 131I scan. Residual tissue or metastases found on the scan should be ablated with 6 GBq 131I. The patient should receive a suppressive dose of T4.
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