Long-term follow-up of patients with hyperthyroidism due to Graves' disease treated with methimazole. Comparison of usual treatment schedule with drug discontinuation vs continuous treatment with low methimazole doses: a retrospective study.

Antithyroid drugs may be proposed as the firstline therapy for hyperthyroidism due to Graves' disease since some patients undergo prolonged remission after drug withdrawal. On the other hand, some studies, though controversial, indicated that methimazole (MMI) has some immunomodulating activity. We retrospectively analyzed 384 consecutive patients newly diagnosed with Graves' disease in the years 1990-2002 to ascertain whether long-term therapy with low doses of MMI may prevent relapse of thyrotoxicosis. Two hundred and forty-nine patients were included in our study. The date of reduction of MMI dose to 5 mg/day was considered time 0 for survival analysis. In 121 MMI was discontinued in less than 15 months after time 0 (group D), while in the remaining 128 a daily MMI 2.5-5 mg dose was maintained (group M). One hundred and thirty-five patients were excluded for inadequate response to MMI, relapse of thyrotoxicosis that could be related to an improper withdrawal or reduction of MMI, inadequate or too short followup, iodide contamination, steroid or interferon therapy, pregnancy or post-partum. D and M groups did not differ for clinical and hormonal parameters except age, which was lower in D (p=0.019). Age > vs < 35 yr was relevant in survival analysis; therefore patients were divided in 2 groups according to this age cut-off. In younger patients relapse of thyrotoxicosis occurred in 15 patients of group D 2.4-39.6 months (median 19.0) after time 0, and 8 M after 5.9-40.0 (21.3) months, while 14 D and 5 M maintained euthyroidism until the end of the observation after 31.8-95.3 (56.6) months and 30.4-62.1 (46.5) months, respectively. Survival analysis indicated that the risk of relapse was similar in group D and M. In older patients relapse of thyrotoxicosis occurred in 40 patients of group D after 8.2-65.8 (25.4) months and 29 M after 5.8-62.5 (22.4) months, while 52 D and 86 M maintained euthyroidism until the end of the observation, 20.1-168.0 (46.7) months and 24.1-117.4 (53.4) months respectively. Survival analysis indicated that the risk of relapse was increased in group D. Therefore long-term treatment with low doses of MMI seems to prevent relapse in Graves' disease in patients above 35 yr of age. This should be confirmed in a prospective study.

Reduced serum levels of dehydroepiandrosterone sulphate in adrenal incidentalomas: a marker of adrenocortical tumour.

BACKGROUND AND OBJECTIVE: Reduced serum levels of dehydroepiandrosterone sulphate (DHEAS) have been shown in patients with Cushing's syndrome resulting from adrenocortical adenoma, in contrast with normal DHEAS levels in patients with Cushing's disease. The aim of this study was to verify whether patients with incidentally discovered adrenocortical adenomas also have reduced levels of DHEAS. DESIGN: Evaluation of serum DHEAS, serum and urinary cortisol, plasma ACTH and low dose dexamethasone suppression test in patients with adrenal incidentaloma and Cushing's syndrome. PATIENTS: Thirty-two patients with adrenal incidentaloma and, as controls, 17 patients with overt Cushing's syndrome, were studied. RESULTS: Serum DHEAS levels lower than normal were found in 21/24 (87.5%) patients with adrenocortical incidentaloma, but in only 1/8 patients with a mass of non-adrenocortical origin. This patient had massive bilateral metastatic infiltration of both adrenal glands and primary adrenal failure. The prevalence of low DHEAS levels in the two groups was significantly different (P = 0.0001). In patients with adrenocortical incidentaloma, the prevalence of low DHEAS levels was significantly higher (P = 0.0001) than that found for some hormonal alterations indicating pre-clinical hypercortisolism (high urinary cortisol, unsuppressed serum cortisol after low dose dexamethasone administration and low plasma ACTH). Low DHEAS levels were found in all patients with Cushing's syndrome due to adrenocortical adenoma but in none of those with Cushing's disease. CONCLUSIONS: Our results indicate that the finding of low DHEAS levels can be considered a marker of the adrenocortical origin of an adrenal incidentaloma, provided adrenal failure has been excluded.

Autonomic nervous activity in obese subjects before and after caloric restriction.

The heart rate response to deep breathing (DB test) and standing (30:15 r test) and the blood pressure response to standing (LS test) and sustained handgrip (HG test) were assessed in 19 obese subjects and 15 age matched lean controls. The results of DB, 30:15 r and LS tests were not significantly different in both groups. The diastolic blood pressure increase during handgrip was significantly higher in obese than in control subjects. After a period of caloric restriction the tests were repeated in 9 patients who had obtained a weight loss of at least 5 kg: a significant decrease in heart rate, diastolic blood pressure and 30:15 r results was observed, whereas the caloric restriction did not cause significant variations in the results of DB, LS and HG tests. Our results suggest that in obese patients some autonomic nervous changes can occur before and after weight loss.

Autonomic neuropathy and sexual impotence in diabetic patients: analysis of cardiovascular reflexes.

Four cardiovascular tests exploring autonomic nervous function (Deep Breathing, 30:15 ratio, Lying to Standing, Hand Grip) have been performed in 38 diabetic patients with erectile failure (mean age 53.2 years, range 34.5-60.5) and in 35 diabetic subjects without sexual dysfunctions (mean age 52.8 years, range 45-60.5). In our study Deep Breathing test was abnormal in 21 patients with erectile failure (55.3%) and in 9 patients without sexual dysfunction (25.7%) (P less than 0.05). Seven patients with sexual impotence (18.4%) and 2 subjects without sexual dysfunction (5.7%) showed abnormal results of 30:15 ratio test. The Lying to Standing test was not abnormal both in impotent and in non impotent subjects, while the Hand Grip test was abnormal in 7 patients with impotence (18.4%) and in 8 patients without sexual dysfunction (22.9%). Results obtained from Deep Breathing test were significantly lower (P less than 0.01) in impotent (10.25 +/- 6.10 beats/min) than in non impotent patients (14.63 +/- 6.85 beats/min). Lower 30:15 ratios were also found in patients with erectile failure (1.09 +/- 0.10 vs 1.12 +/- 0.09). The tests exploring the sympathetic function did not show any difference between the two groups of patients. The present study confirms the major role of parasympathetic impairment in the pathogenesis of sexual dysfunctions in diabetic men. Cardiovascular tests can be a first-step diagnostic tool in the assessment of diabetic impotence.