Laura Abad

Effect of the TNFα-308 G/A Polymorphism on the Changes Produced by Atorvastatin in Bone Mineral Density in Patients with Acute Coronary Syndrome

Aims: To evaluate the effect of atorvastatin on bone mass and markers of bone remodeling in patients with acute coronary syndrome depending on the tumor necrosis factor-α (TNFα)-308 G/A polymorphism. Methods: Sixty-two patients with acute coronary syndrome (35 males and 27 females), average age 60 ± 10 years, were included. Patients were given low (10–20 mg) and high doses (40–80 mg) atorvastatin according to their baseline levels of cholesterol and triglycerides and their index of vascular risk. Patients were studied during hospital admission (baseline) and at 12 months of follow-up. Cholesterol, triglycerides, total calcium, phosphorus, magnesium, osteocalcin and urinary deoxypyridinoline were determined in all patients at baseline and at 12 months of follow-up. Densitometric studies were conducted in the lumbar spine (L2–L4), femoral neck and trochanter using an X-ray densitometer. The TNFα-308 G/A polymorphism was determined by the polymerase chain reaction.Results:Forty-five patients were homozygous for G/G (72.5%) and 17 were heterozygous for G/A (27.5%). The prevalence of osteoporosis (T score ≤2.5 in the lumbar spine and/or hip) was 33% for the G/G genotype and 35% for the G/A genotype, with no statistically significant differences between groups. There was a statistically significant increase in bone mineral density (BMD) in the lumbar spine (1.107 ± 0.32 vs. 1.129 ± 0.23; p = 0.0001) in patients with the G/G genotype. No changes were observed in patients with the G/A genotype. Conclusion: In patients with acute coronary syndrome, atorvastatin increases lumbar spine BMD solely in patients with the G/G genotype of the TNFα-308 G/A polymorphism.

Levels of DKK1 in patients with acute myocardial infarction and response to atorvastatin

The Wnt-LPR5 signalling pathway plays an important role in skeletal homeostasis, especially in regulating osteoblastic activity. Activation of this pathway is regulated by various inhibitors, including DKK1. The objective of this study was to evaluate DKK1 levels in patients with ischemic heart disease, the response to atorvastatin and the relationship with bone mass. Twenty-one patients with acute myocardial infarction and twenty-three controls with a mean age of 61 ± 9 years with acute coronary syndrome were included. Patients were allocated to low (10-20mg) and high doses (40-80 mg) of atorvastatin according to baseline levels of cholesterol and triglycerides and the index of vascular risk. Patients were studied at hospital admission (baseline) and at 12 months of follow up. DKK1 was determined in all patients at baseline and at 12 months of follow up. Densitometric studies were conducted in the lumbar spine (L2-L4) and the femoral neck and trochanter using an X-ray densitometer. Patients had higher levels of DKK1 than controls, (111 ± 41 nmol/l versus 84 ± 27 nmol/l, p=0.014). Osteoporotic patients had higher levels of DKK1 (137.5 ± 33 nmol/l versus 95.4 ± 36 nmol/l, p=0.021). Analysis of the response to atorvastatin showed reduced DKK1 levels. In conclusion, in patients with acute coronary syndrome, atorvastatin decreases DKK1 levels. This may be a previously unreported mechanism of action of atorvastatin on bone, stimulating the Wnt signalling pathway and increasing bone mass.

Light Symptoms following a High-Dose Intentional L-Thyroxine Ingestion Treated with Cholestyramine

Adult exposure to L-thyroxine has a wide range of presentations: most adults either do not develop symptoms or only become minimally symptomatic. Appropriate treatments after exposure to L-thyroxine have yet to be established. A 26-year-old woman with a suicidal intention was witnessed to ingest approximately 50 L-thyroxine tablets, each containing 0.1 mg L-thyroxine (total dose 5 mg). Cholestyramine was administered (4 g every 8 h p.o.). Vital signs were monitored every 6 h and the hormone levels (L-thyroxine and thyroid-stimulating hormone) every 24 h. The thyroxine levels increased, and the thyroid-stimulating hormone levels decreased, with a normalization of the L-thyroxine level on postingestion day 6. Hypertension, dysrhythmias, and delusions did not appear in our patient. Only distal tremor and diaphoresis appeared on day 1 after ingestion. Cholestyramine has been used in cases of iatrogenic hyperthyroidism, in patients with Graves’ disease, and in patients with digoxin intoxications, with good responses in all cases and a low incidence of side effects. This case illustrates the potential utility of cholestyramine to treat L-thyroxine intoxications.

Ghrelin and Bone Mass in Postmenopausal Hypertensive Women

Background: Ghrelin, a recently discovered peptide mainly secreted by the stomach, has an orexigenic effect which stimulates secretion of the growth hormone. It also has vasodilator effects which reduce blood pressure and stimulate in vitro, bone formation. Objectives: To evaluate the effect of ghrelin on bone mass and bone remodeling markers in postmenopausal hypertensive women. Material and Methods: 25 postmenopausal hypertensive women, light to moderate based on the JNC-VII criteria, were studied. They had a mean age of 58 ± 8 years, a body mass index of 28 ± 6 and a hypertension development time of 65 ± 84 months. Osteocalcin, PTHi, 25-vitamin D, ghrelin in serum and deoxypiridinoline in urine were determined in all patients. A lumbar spine densitometer was made (DXP Lunar, Madison, Wisc., USA). Results: Diminished levels of ghrelin were observed in the osteoporotic group (40 ± 19 vs. 78 ± 40, p = 0.027). When the patients were separated according to ghrelin tertiles, a greater bone mass was observed in the upper tertiles, which was associated with a decrease in the urinary deoxypiridinoline. When the total population was analyzed, no relation between the ghrelin and bone mass was found, nor with any of the parameters of calcium metabolism. Only a statistically significant relation between ghrelin and deoxypiridinoline was observed (r = –0.428, p = 0.026). Conclusions: In postmenopausal hypertensive women, ghrelin may produce a protecting effect over bone mass through an anticatabolic mechanism manifested by a decrease of bone resorption.

Intoxicación con levotiroxina: manifestaciones clínicas y manejo terapéutico

RESUMEN La intoxicacion por levotiroxina no es frecuente, siendo el grupo de edad con mayor prevalencia, la edad pediatrica. La dosis toxica no esta clara, dosis por debajo de 5 mg de levotiroxina, no suele asociarse a la aparicion de sintomas. Los sistemas mas afectados en una intoxicacion por T4 son el cardiovascular, sistema nervioso simpatico y gastrointestinal. Los sintomas aparecen desde unas horas potingesta, hasta varios dias despues. En las horas posteriores a la ingestion de levotiroxina, los niveles de T4 y T3 no reflejan la severidad del cuadro clinico, no obstante la monitorizacion hormonal es importante para dirigir la agresividad terapeutica y marcar el pronostico del cuadro. Por ello, se deben realizar controles diarios de T3, T4 y TSH. Tambien son necesarias realizar determinaciones cada 4 horas de temperatura, tension arterial y frecuencia cardiaca para controlar posibles complicaciones. La utilizacion de betabloqueantes y las tecnicas de descontaminacion gastrointestinal son mencionadas por multiples autores. Otras opciones tambien descritas son el acido iopanoico, el propiltiouracilo, En resumen, la intoxicacion por levotiroxina puede ser un cuadro potencialmente frecuente y grave, por ello es necesario describir unas normas de manejo terapeutico de esta entidad.