Long-term pathologic changes of alpha1-acid glycoprotein (orosomucoid) glycoforms in autoimmune thyroid disease.

OBJECTIVE: We measured alpha1-acid-glycoprotein (AGP) in patients with autoimmune thyroid disease to study a possible relationship between microheterogeneity of the naturally occurring glycoforms of AGP and autoimmune thyroid disease. DESIGN, PATIENTS, MEASUREMENTS: In a group of 12 fasting thyrotoxic patients (11 females, mean age: 43 years) with newly diagnosed Graves' disease (subgroup 1), we measured serum concentrations of total AGP and its 3 glycoforms (micromol/l, crossed affinity immunoelectrophoresis with con A in the first dimension gel) as well as total thyroxine, total triiodothyronine, thyrotropine, thyroid peroxidase antibodies (anti-TPO), antibodies against the TSH receptor (TRAb, TRAK), at baseline and after 12 months of antithyroid drug therapy (ATD). For comparison, 4 subgroups of thyroid patients (patients with Graves' disease and thyroid associated ophthalmopathy (TAO) (subgroup 2, n = 10), radioiodine treated Graves' patients (subgroup 3, n = 7), Graves' patients without TAO (subgroup 4, n = 13), patients with Hashimoto's thyroiditis (subgroup 5, n = 8)) and 25 normal controls (17 females, mean age: 38 years) were studied. RESULTS: In subgroups of TRAb positive Graves patients' serum levels of glycoform 1, 2 or 3 increased significantly (p < 0.005) after 12 months of ATD as compared to both baseline of that person or normal controls. No significant changes were found in the TRAb negative Hashimoto subgroup. CONCLUSION: Patients with autoimmune Graves' disease changed their relationship to AGP, and thus a role of AGP and its 3 glycoforms is suggested in the pathogenesis of Graves' disease.

[Exchange of paraclinical information between the primary and secondary health sectors]. / Paraklinisk informationsudveksling mellem den primaere og sekundaere sundhedssektor.

INTRODUCTION: The purpose of the study was to investigate the extent to which, biochemical test results obtained in the primary health sector could be regarded as valid information in the clinical assessment of patients admitted to hospital. METHODS: The study was based on a questionnaire, which was designed to assess the value of historical biochemical data in the initial diagnostic process. The data was transferred from the laboratory of Copenhagen general practitioners (KPLL) database to a computer terminal in the emergency medical ward at H:S Bispebjerg Hospital. RESULTS: It was possible to assess historical KPLL data on close to 80% of all hospitalised patients. In 50% of these patients, doctors indicated that the data always (96%) contributed to the diagnosis. In 70%, the data further contributed to the subsequent planning of diagnostic strategy. With regard to the initial diagnosis, comparison of KPLL data with data obtained on admission always resulted in a further classification of at least one condition. The comparison of KPLL data with admission data always led to a more precise plan for further diagnostic strategy. CONCLUSION: The comparison of KPLL data with admission data, significantly contributes to differentiate the initial diagnostic strategy. In turn, this seems to have a significant bearing on the planning of further diagnostic strategy. It is postulated that a computer-based information system, through which the primary and secondary health sectors can exchange patient-related clinical data, would lead to a more focused use of resources, and hold significant advantages for the patient.

Review of thyroid cancer cases among patients with previous benign thyroid disorders.

A previous register linkage study showed an increased risk of thyroid cancer among patients previously discharged from a hospital with a diagnosis of a benign thyroid disorder. In this study, we have reviewed all available medical records, first to validate the earlier result and second to describe the symptomatology of patients with a history of benign thyroid disorder prior to the cancer diagnosis. The previous study identified 189 patients with a benign and subsequent malignant thyroid disorder. Medical records were obtainable for 156 of these patients and were reviewed. For 104 patients, benign and malignant thyroid diseases were metachronous (a clearly separated disease history of the benign and malignant diseases), and for 48 patients synchronous. In 4 cases, thyroid cancer could not be confirmed. Among patients with metachronous thyroid disorders, all major benign thyroid disorders were represented including hot nodules, diffuse and multinodular toxic and nontoxic goiter. Symptoms preceding diagnosis of thyroid cancer included growth of goiter/nodules, globulus, stridor, hoarseness, and metastasis. No major differences were found among patients with metachronous and synchronous benign and malignant thyroid disorder, apart from the fact that all metastases were found among metachronous cases. This study confirmed the conclusion that patients with a previous history of goiter or nodules have an increased risk of thyroid cancer. However, thyroid cancer still occurs too infrequently to warrant screening in all patients with a previous history of goiter or nodules.

Cancer risk in individuals with benign thyroid disorders.

The risk of cancer was examined in a cohort of 57,326 individuals who were discharged from a Danish hospital with a diagnosis of myxedema, thyrotoxicosis, or goiter. Although the general risk of cancer was only slightly increased, the risk of several sites was significantly above expected. The risk of thyroid cancer especially, was increased with standardized incidence ratios among women of 2.1 (myxedema), 2.5 (thyrotoxicosis), and 6.6 (nontoxic goiter). The increase in risk was present even many years after discharge, indicating that surveillance was not the only explanation. Furthermore, an increased risk was noted for cancer of the kidney in women discharged with myxedema (standardized incidence ratios [SIR] = 1.8) and thyrotoxicosis (SIR = 1.3), for cancer of the bladder in women discharged with myxedema (SIR = 1.5) and nontoxic goiter (SIR = 1.3), and for cancer of the hematopoetic system in women discharged with myxedema (SIR = 1.4) and nontoxic goiter (SIR = 1.4). The findings indicate that thyroid disorders may be related to cancer risk of several specific sites other than the thyroid.

Sarcoidosis with extensive cutaneous ulceration. Unusual clinical presentation.

A 70-year-old white woman with sarcoidosis and insulin-resistant diabetes mellitus presented with extensive cutaneous ulcerations. Both the cutaneous lesions and the systemic features of sarcoidosis showed a dramatic improvement during oral corticosteroid therapy. When extensive cutaneous ulcerations are present, it is important to consider sarcoidosis, as these may be the only presenting sign of the disease. Unlike ulcerated necrobiosis lipoidica diabeticorum, sarcoidal ulcerations may respond well to treatment with oral corticosteroids.

Nadolol, propranolol, and thyroid hormones: evidence for a membrane-stabilizing action of propranolol.

Ten normal subjects participated in a placebo-controlled, randomized, parallel study to determine the effects on thyroid hormones of chronic (4 wk) propranolol or nadolol, including observation for 2 wk after their discontinuation. Subjects took placebo for 1 wk, then propranolol or nadolol doses increased weekly to 240 mg/day by 3 wk. After 1 wk of placebo, after 2 wk of the highest dose of propranolol or nadolol, and 2, 4, 6, 9, and 13 days after their discontinuation, thyroid hormone levels were measured by radioimmunoassay and heart rate responses to exercise were assessed. Both drugs induced equal and high degrees of exercise tachycardia inhibition. Propranolol decreased 3,3'5-triiodothyronine (T3) levels, increased 3-3'-5'-triiodothyronine (rT3) levels, tended to increase thyroxine levels, but did not increase thyroid-stimulating hormone levels. After discontinuation of propranolol, rT3 levels slowly (day 6) returned to values after placebo, suggesting delayed recovery of 5'-deiodination. There was no evidence of any rebound in T3 levels after withdrawal of propranolol. Nadolol induced no significant changes in the thyroid hormones measured. The data agree with the known effects of propranolol on thyroid hormones in normal man and show that nadolol does not have these effects when given chronically at an equivalent beta-blocking dose. The likely explanation is that the membrane-stabilizing activity of propranolol alters thyroid physiology by interfering with 5'-deiodinase.

Oncogenic osteomalacia associated with a mesenchymal chondrosarcoma.

A patient with phosphaturic osteomalacia without chemical or pathological evidence of hyperparathyroidism and subnormal urinary cyclic AMP excretion was treated with vitamin D and phosphates for 9 months with partial improvement of osteomalacia, but not phosphaturia. Subsequent removal of a mesenchymal chondrosarcoma of the foot led to prompt resolution of phosphaturia and healing of the osteomalacia. Although 1,25-dihydroxyvitamin D levels were not obtained before vitamin D therapy, the levels noted during continued severe phosphaturia preoperatively were not lower than those obtained several months postoperatively during the healing phase. Studies done 1 year after tumor removal showed normalization of phosphaturia, urinary cyclic AMP, and bone histology. We suggest that the tumor elaborated products which promoted nonparathyroid mediated phosphate excretion independently from any effects on vitamin D metabolism.

Minoxidil in refractory hypertension: benefits, risks.

The blood pressure of 18 patients with refractory hypertension was controlled by treatment with Minoxidil in combination with Propranolol and diuretics. Ten of these patients were studied prospectively and were found not to have deterioration of carbohydrate tolerance while on Minoxidil therapy. Pericardial effusions occurred in 40% of the patients, including 2 with normal renal function. This untoward effect of prolonged use Minoxidil warrants further study.