Although iodine-induced thyrotoxicosis was reported to occur in patients with obvious underlying thyroid disorders, it is not known to occur in patients with apparently normal thyroid glands. From ten such cases evidence is presented that thyrotoxicosis: a) appeared during treatments by iodide or organic-iodine-containing drugs, in the absence of any past history of thyroid disorder; b) was accompanied by almost undetectable radioidine uptake which nevertheless could be activated by TSH; c) subsided spontaneously within a few weeks or months after stopping the high intake of iodine; d) and left, after a period of hypothyroidism, an apparently normal thyroid gland which had resumed normal size, function, uptake, and suppressibility.
Objectives: To examine the cost-effectiveness of strategies for management of primary asymptomatic hyperparathyroidism: surgical strategies and medical follow-up versus surgery. Design: We used a Markov state-transition decision-analytic model for an hypothetical cohort of 55-year-old women to compare with a lifetime horizon costs and effectiveness of bilateral neck exploration (BNE), unilateral neck exploration (UNE), video-assisted parathyroidectomy (VAP) and lifelong medical follow-up shifting for either BNE or UNE in case of disease progression. Methods: Data on localization tests, complications and treatment efficacies were derived from a systematic review of the literature. Outcomes were expressed as quality-adjusted life years (QALY). Costs (€2002) discounted at 3% yearly were estimated from the health care system perspective. Results: In the base-case analysis, VAP strategy (VAPS) was the most effective and BNE strategy (BNES) was the least costly. UNE strategy (UNES) had an incremental cost-effectiveness ratio of €2688/QALY versus BNES and VAPS of €17 250/QALY in comparison with UNES. Surgical management was more effective than medical follow-up with acceptable incremental cost-effectiveness ratios. VAPS became less effective than UNES over 71 years. Differences between UNES and VAPS were sensitive to success and complication rates, quality-of-life weights and procedural costs. Medical follow-up strategies became the most effective if quality-of-life weight for this condition was higher than 0.99. Conclusions: Surgery is more effective than medical follow-up at a reasonable cost and can be preferred except in patients choosing medical follow-up. Minimally invasive surgery is cost-effective compared to the traditional surgical approach.
The overnight 1-mg dexamethasone suppression test is a very good screening test for subjects suspected of having Cushing's syndrome. To simplify the procedure, we evaluated the 1-mg dexamethasone suppression test with measurement of salivary cortisol. We performed this test with plasma and salivary cortisol measurements in 27 patients with Cushing's syndrome and 64 normal controls. The sensitivity and specificity of plasma cortisol measurements were 100% and 87%, respectively, for a cut-off point of 100 nmol/l, in accordance with previous studies. The results of salivary cortisol showed the absence of overlap between the two groups, with a sensitivity and specificity of 100% for a cut-off point of 2.8 nmol/l. On a larger series, however, one might occasionally miss the diagnosis of a patient with Cushing's syndrome. Therefore, we favor a cut-off point of 1.9 nmol/l, the sensitivity remaining at 100% and the specificity being 94%. In conclusion we recommend the overnight dexamethasone suppression test with measurement of salivary cortisol as a screening test for Cushing's syndrome.
Phorbol esters inhibit the binding of insulin to its receptors on U-937 monocyte-like and HL-60 promyelocytic leukemia human cell lines. Within 20-30 min, exposure of these cells to 12-0-tetradecanoylphorbol 13-acetate (TPA) at 37 "C results in a 50 % reduction of the specific binding of '251-insulin. Half-maximal inhibition occurs at 1 nM TPA. Other tumor-promoting phorbol esters also inhibit '251-insulin binding in a dose-dependent manner which parallels their known promoting activity in vivo. TPA does not alter the degradation of the hormone nor does it induce any shedding of its receptors in the medium. The effect of phorbol esters is dependent on temperature and cell type. It is less prominent at 22 "C than at 37 "C. It is reversible within 2 h at 37 "C. TPA reduces the binding of insulin predominantly by increasing its dissociation rate. This effect results in an accelerated turnover of the hormone on its receptors.Phorbol esters are tetracyclic diterpenes that are potent tumor-promoting agents in some tissues (e.g. mouse skin) [1,2] while they induce differentiation in others [3-51. They bind to specific receptors on the cell surface [6] and evoke multiple biological and biochemical changes when added to cultured cells ([7] for review). The nature of the responses initiated by these compounds in vivo as well as in vitro has many similarities with those of growth-stimulating polypeptide hormones such as epidermal growth factor (EGF). Recently is has been demonstrated that phorbol esters reduce the number [8] or the affinity [9,10] of EGF receptors, while they clearly potentiate the biological effects of EGF [lo-131.In addition, these tumor promoters possess insulin-like activity (stimulation of glucose transport and oxidation) in a number of cell types [I41 and they facilitate the growthpromoting action of insulin on 3T3 fibroblastic cells [ l l -131. The binding of insulin to its receptors has been reported to be unaltered by phorbol esters in 3T3 [9] and Hela cells [15]. Since this has also been the case for the binding of nerve growth factor, concanavalin A, multiplication-stimulating activity and low-density lipoproteins to their receptors [9], it was thought that tumor promoters specifically alter the EGF binding. This observation might be related, however, to the cell types under investigation. Thus, in his study of EGF and phorbol receptors in mouse OTT-6050 embryonal carcinoma cells [16], Salomon incidentally reported that TPA (12-0-tetradecanoylphorbol 13-acetate) inhibits the binding of '" I-insulin.In the present investigation we have examined the effect of phorbol esters on the insulin-receptor interaction in the U-937 monocyte-like [5] and the HL-60 promyelocytic leukemia [3,4] human cell lines. The HL-60 cells possess specific receptors for insulin [17-191 and phorbol esters [20] and they are sensitive to the action of these agents [14,21].Ahhreviutions. Hepes, 4-(2-hydroxyethyl)-l-piperazineethanesulfonic acid; TPA, 12-0-tetradecanoylphorbol 13-acetate; EGF, epidermal growth factor.Ou...
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