Hormone replacement therapy is associated with less coronary atherosclerosis in postmenopausal women.

Most observational studies indicate that hormone replacement therapy (HRT) protects women from cardiovascular disease. Two recent randomized trials, however, showed no reduction in coronary events with HRT in postmenopausal women. A randomized study evaluating subclinical atherosclerosis showed a beneficial effect of estrogen. In the current study we evaluated the association between HRT and coronary artery atherosclerosis, as quantified by coronary artery calcium score. Current users of HRT were significantly more likely to have a coronary artery calcium score less than 100 and were less likely to have a score greater than 400 than non-HRT users. After adjustment for cardiac risk factors, current use of HRT was associated with a significant reduction of coronary artery calcium score (-28; 95% confidence interval, -48 to -10). The average age of users was 59 yr, the mean duration of use was 9 yr, and the duration of HRT use was significantly associated with a reduction in coronary artery calcium. These results suggest that HRT suppresses atherosclerosis in the coronary arteries. The failure to modify the cardiovascular event rate in clinical trials could result from the adverse effect of HRT on complicated lesions. Additional mechanistic studies may help identify therapeutic strategies that could maximize a potential benefit of HRT on early atherogenesis while minimizing adverse proinflammatory and procoagulant effects on complicated plaque lesions.

Effect of thyroid hormone on plasma apolipoproteins and apoA- and apoB-containing lipoprotein particles.

METHODS: Apolipoprotein and apoB- and apoA-containing lipoprotein particle concentrations were determined in 10 athyreotic patients 4 weeks after withdrawal of Synthroid replacement therapy [T4, 0.96 +/- 0.66 microgram mL-1; thyroid-stimulating hormone (TSH), 62.7 +/- 22.8 muIU mL-1] and again 4 weeks after reinstitution of treatment. RESULTS: Thyroid hormone replacement was associated with significant decreases in plasma cholesterol (TC), triglyceride (TG), apolipoprotein B and apolipoprotein C-III (P < 0.01). Both the cholesterol ester-rich LP-B particles and triglyceride-rich LP-Bc particles declined significantly in response to thyroid hormone (LP-B withdrawal 81.6 +/- 24.0 vs. replacement 65.1 +/- 22.0; LP-Bc withdrawal 14.3 +/- 6.0 vs. replacement 10.9 +/- 4.8 mg%, P < 0.01). ApoC-III also decreased in high-density lipoprotein (HDL) (apoC-III-HS), and in very low-density lipoprotein (VLDL) + low-density lipoprotein (LDL) (apoC-III-HP), but this reduction was proportionate so that the apo-C-III-HS/apoC-III-HP ratio, an indirect estimate of the efficiency of lipoprotein lipase (LPL), was unchanged. Apolipoprotein A-I concentrations also decreased significantly (withdrawal 140.7 +/- 27.0 vs. replacement 127.1 +/- 30.0 mg%, P < 0.01) in parallel with the changes in LP-A-I and LP-A-I:A-II particles (LP-A-I withdrawal 35.8 +/- 7.7 vs. replacement 31.5 +/- 6.3; LP-A-I:AII withdrawal 104.9 +/- 20.0 vs. replacement 95.5 +/- 26.0; P < 0.05). CONCLUSION: These findings indicate that thyroid hormone influences the transport not only of both TG-rich and cholesterol-rich apoB-containing lipoprotein particles but also of those that contain apoAI.

Thyrotoxicosis.

Thyrotoxicosis is a clinical syndrome caused by circulation of excess thyroid hormones. Classic hyperkinetic thyrotoxicosis is readily recognizable. Atypical presentations, however, can lead to diagnostic dilemmas. The sensitive thyroid-stimulating hormone assay has become an invaluable tool in the diagnosis of thyrotoxicosis. Causes of thyrotoxicosis include Graves' disease, toxic multinodular goiter, toxic adenoma, thyroiditis, inappropriate secretion of thyroid-stimulating hormone, trophoblastic tumor, exposure to iodine, and use of drugs. Increased uptake of radioidine by the thyroid gland differentiates true hyperthyroidism from other causes of thyrotoxicosis. Graves' disease is the most common cause of hyperthyroidism. It is caused by antibodies to the thyroid-stimulating hormone receptor that are stimulatory in nature. Extrathyroidal manifestations of Graves' disease include orbitopathy, dermopathy, and acropachy. Therapy includes thionamides, radioactive iodine, surgical intervention, and other adjunctive modalities. Thyroid storm is a medical emergency that necessitates prompt and aggressive therapy.

The effects of hypothyroidism and replacement therapy on cholesteryl ester transfer.

To characterize further the impact of thyroid dysfunction on the transport of cholesterol in plasma, we studied plasma lipids and cholesteryl ester transfer (CET) in 10 hypothyroid women before and 3 months after thyroid replacement therapy. CET, estimated as the net mass transfer of CE from HDL to the apolipoprotein B-containing lipoproteins (very low density and low density lipoproteins) was significantly decreased at 4 h (P < 0.05) and 6 h (P < 0.001) when the patients were hypothyroid (T4, 2.01 +/- 1.4; TSH, 55.5 +/- 39.9 microIU/mL) and increased to normal levels after hormone replacement and restoration of eumetabolism. Plasma lipid levels in the hypothyroid state closely resembled those in a female reference group, although total plasma cholesterol fell significantly [pretreatment, 218 +/- 36 vs. posttreatment, 192 +/- 49 (P < 0.025); control, 218 +/- 28 mg/dL (mean +/- SD)] after treatment. Concentrations of cholesteryl ester transfer protein (CETP) were unchanged (pretreatment, 2.35 +/- 0.83 vs. posttreatment, 2.30 +/- 1.19 mg/dL). The results of recombination studies using different lipoprotein fractions suggest that decreases in CET during hypothyroidism may be secondary to acceptor lipoprotein (low density and very low density lipoprotein) changes in the hypothyroid state and not to changes in the concentration of CETP itself.

Diseases of the adrenal cortex.

The adrenal cortex is functionally a three-dimensional gland that secretes glucocorticoids, mineralocorticoids, and sex steroids. Of these three classes of steroids only the gluco- and mineralocorticoid hormones are necessary to sustain life. The availability of sensitive and specific radioimmunoassays has permitted accurate measurement of practically every steroid hormone secreted by the adrenal cortex. As in other endocrinopathies, suppression studies are employed when hyperfunction is suspected, while provocative tests are used to detect hypofunction. These dynamic studies enable the clinician to evaluate the functional status of the adrenal cortex. The anatomic configuration of the adrenal cortices is delineated by high-resolution computed tomography (and magnetic resonance imaging), obviating the need for invasive procedures such as venography or arteriography. The disorders of the adrenal cortex can be viewed from the dual perspectives of hyperfunction and hypofunction. Clinical expressions of hyperfunctional adrenocortical syndromes include Cushing's syndrome, primary hyperaldosteronism, and the adrenogenital syndrome. The expressions of hypofunctional syndromes include Addison's disease and selective hypoaldosteronism. The diagnosis and treatment of these disorders are outlined in this issue.

Glucose homeostasis during anesthesia and surgery in infants.

Baseline, preinduction, postinduction, and postsurgical plasma samples were collected for glucose, insulin, and cortisol in 16 neonates and infants. Glucose infusion rate was maintained constant (mean +/- SD 4.1 +/- 1.2 mg/kg/min) prior to and during surgery; additional fluid losses during surgery were replaced by fluids without dextrose. The weight at the time of surgery was 3,038 +/- 1,397 g. Postnatal age at the time of study ranged from one day to 40 weeks and the duration of surgery was 83 +/- 35 minutes. Plasma glucose values were higher than baseline values soon after induction of anesthesia (88 +/- 11 v 130 +/- 36 mg/dL; P less than .05); postsurgical glucose values were significantly higher than postinduction values (210 +/- 109 mg/dL v 130 +/- 36 mg/dL, P less than .01). Postsurgical plasma glucose had a negative correlation with weight of infants at the time of study (P less than .01; r = .61). Insulin changes were minimal and variable. Cortisol values did not change significantly from baseline values until the end of surgery (11.9 +/- 8.3 v 22.2 +/- 10.6 micrograms/dL; P less than .05). Hyperglycemia (greater than 150 mg/dL) was noted in 10/16 infants. This study indicates that glucose levels should be monitored and that additional fluid losses should be replaced by fluids without dextrose in neonates undergoing surgical procedures since hyperglycemia is a common occurrence.

The clinical utility of a heterologous radioimmunoassay for human prolactin.

A specific and sensitive double antibody radioimmunoassay for human prolactin has been developed utilizing anti-human prolactin and purified ovine prolactin for radioiodination. Employing this radioimmunoassay, as little as 1.5 ng of prolactin can be quantified in a ml of human serum. The prolactin in serum detected by the radioimmunoassay behaved in a similar manner to purified human 125-I-labled prolactin on polyacrylamide gel electrophoresis. Exogenous prolactin could be completely recovered when varying amounts were added to a constant volume of serum. In normal control and primary hypothyroid subjects, intravenous administration of thyrotropin-releasing hormone elicited a peak prolactin response 30 min post-injection. Hyperthyroid and hypopituitary subjects did not manifest a significant increase in serum prolactin concentration after the injection. Subjects with functional galactorrhea had high resting prolactin levels and exhibited peak increase in serum prolactin concentration at 60 min following the administration of thyrotropin-releasing hormone.