Ketoconazole, an imidazole derivative known to inhibit cytochrome P450-dependent adrenal enzymes was given to a patient with a functioning adrenal rest tumor of the liver in preparation for surgery. The drug was administered in a stepwise manner for 42 days starting with 400 mg and reaching 1 g the last 4 weeks of the trial. Clear clinical improvement was evident early in the trial and was associated with evidence of amelioration of her hypercortisolism and striking changes in serum and urinary levels of steroid hormones and metabolites. Sex steroids in serum and urine fell dramatically from the first day to the end of the trial. Urinary 17-ketosteroid excretion fell from a basal average of 139 mg/24 h to near normal levels within a week of therapy; serum testosterone fell from a basal level of 2.4 to 0.18 ng/ml; serum 17 beta-estradiol fell likewise from 1096 to 150 pg/ml. In contrast, cortisol levels in serum and urine increased in the first 2 weeks of the trial and subsequently fell to values below the basal levels. Similarly, serum 17 alpha-OH-progesterone levels increased 63% above the basal levels by day 6 of the trial and declined afterwards. Nine months after successful tumor resection the patient is apparently cured as judged by steroid hormone levels and physical appearance. We conclude that ketoconazole was effective in blocking tumoral steroidogenesis which resulted in clinical benefit.

Research Methods and Procedures:According to a sampling scheme based on BMI, 33 adult obese women (BMI Ն 30) and 30 adult normal-weight women (BMI Ͼ 18.5 and Ͻ 25 kg/m 2 ) were recruited for this study. Women with chronic inflammatory diseases or acute pathology were excluded. Glucose, insulin, leptin, lipids, and tumor necrosis factor ␣ (TNF␣) were measured in fasting plasma samples. Insulin resistance was estimated through the homeostasis model assessment for insulin resistance method. The Ala54Thr allelic variant was determined by polymerase chain reaction, followed by restriction fragment-length polymorphism analysis. Results: The Thr54 allele was more frequent in obese than in nonobese women (47.0% vs. 31.7; p ϭ 0.08). Among obese women, higher TNF␣ concentrations were found when comparing the Thr54/Thr54 genotype (30.0 Ϯ 7.1 pg/mL) with either the Ala54/Thr54 genotype (21.2 Ϯ 8.4 pg/mL) or the Ala54/Ala44 genotype (20.1 Ϯ 7.0 pg/mL) (p Ͻ 0.05). In addition, higher fasting plasma insulin and leptin levels were found among Thr54/Thr54 homozygotes compared with the other genotypes (p Ͻ 0.05). Discussion: Our results suggest that the Ala54Thr polymorphism of the FABP2 gene is associated with obesity and insulin resistance. The effect of this polymorphism might be mediated by elevated production of TNF␣.

Early, indirect studies suggested that an important aspect of thyroid economy during pregnancy was a decline in plasma or serum inorganic iodide (PII) concentrations, but there is little information concerning circulating iodide concentrations as assessed by direct measurement. The present study was undertaken to determine the relationship between gestation and serum iodide concentrations as assessed by direct measurement of PII. PII concentrations, urinary iodide levels, and other parameters of thyroid economy were measured during the first, second, and third trimesters and after delivery in 16 women. Mean serum T4 concentrations were significantly higher in all 3 trimesters than those after delivery. Serum free T4 index concentrations were significantly higher in the first trimester than during later periods of gestation or after delivery, but serum TSH concentrations were not depressed in the first trimester. Serum thyroglobulin concentrations were similar during pregnancy and after delivery. There was wide variability in PII and urinary iodide concentrations during and after pregnancy, but there was no trend for PII concentrations to be depressed during pregnancy. Pregnancy, at least in iodine-sufficient regions, does not have an important influence on circulating concentrations of iodide.

Abstract. Vitamin D synthesis takes place in the skin due to solar ultraviolet-B (UVB) radiation. Several studies have shown the association between low sun exposure, non-melanoma skin cancer (NMSC) and a lack of vitamin D synthesis. Since such synthesis in the body depends on the exposure of the skin to solar UVB radiation (290-320 nm), experimental measurements of this type of solar radiation are important. Tarapaca University in Arica, Chile, established a solar UV radiation laboratory in 2006 and since then this laboratory has performed systematic experimental solar UVB measurements using a calibrated biometer instrument. The results, which are presented in the current study, showed the association between NMSC and MSC rates, and the time required to produce 1,000 IU vitamin D with latitudinal variation. Solar UV index (UVI) levels reported in 6 cities from the north to the south of Chile indicated that the UVI ratio of monthly mean values was 1.8 times higher in Arica than in Punta Arenas in January (summer in Chile), whereas it was 14 times higher in June (winter). This factor is an important consideration, since vitamin D synthesis is directly associated with the exposure of individuals to solar UVB radiation. A similar trend was observed in Antofagasta, Santiago, Concepcion, Valdivia and Punta Arenas. It can be concluded from these data that there is a direct association between NMSC rates and mortality, and UVB radiation, meaning that this type of cancer would not depend on vitamin D synthesis and therefore on calcium uptake. By contrast, MSC rates increased with decreased levels of vitamin D, and thus calcium uptake, in all cities, with the only exception being Punta Arenas.