Bone mineral density in postmenopausal women treated with L-thyroxine.

PURPOSE: To determine if bone mineral density is decreased in postmenopausal women treated with 1-thyroxine, and, if any decrease is observed, whether it is related to overtreatment with thyroid hormone, to deficiency of calcitonin, or to other factors. PATIENTS AND METHODS: The study consisted of 19 postmenopausal women between 50 and 75 years of age treated with 1-thyroxine for 5 years or longer, and 19 matching control subjects with no thyroid disease. Bone mineral density of the spine and hip was measured by dual-photon absorptiometry. Plasma calcitonin concentrations and serum thyroid hormone levels were determined by radioimmunoassays. RESULTS: The 1-thyroxine-treated women had lower bone density in the lumbar spine (1.013 g/cm2 [95% confidence interval, 0.945 to 1.081] versus 1.134 g/cm2 [1.026 to 1.242], p = 0.043); in the femoral neck (0.736 g/cm2 [0.694 to 0.778] versus 0.809 g/cm2 [0.747 to 0.872], p = 0.040); in Ward's triangle (0.576 g/cm2 [0.530 to 0.623] versus 0.694 g/cm2 [0.617 to 0.770], p = 0.011); and in the trochanteric area (0.626 g/cm2 [0.581 to 0.672] versus 0.722 g/cm2 [0.651 to 0.794], p = 0.027). The maximal increase in calcitonin following calcium infusion was 1.37 ng/L (95% confidence interval, -0.44 to 3.17) in the 1-thyroxine-treated patients versus 18.8 ng/L (95% confidence interval, 10.0 to 27.5) in normal women, p less than 0.001. The average dose of 1-thyroxine was 120 micrograms/day; 16 of the 19 patients had normal serum thyroxine levels. However, TSH levels were low in 13 of the 19, suggesting that 1-thyroxine treatment was supraphysiologic. Seven of the 19 patients had a history of hyperthyroidism in the distant past; these patients, considered separately, had significantly reduced bone density in the hip. The other 12 patients, considered separately, did not have a statistically significant loss of bone density. CONCLUSIONS: Long-term 1-thyroxine therapy is associated with decreased density of the spine and hip. Since subclinical hyperthyroidism, decreased calcitonin responsiveness, and a history of hyperthyroidism were demonstrated in some or all of these patients, these factors must be considered as possible causes of the decreased bone density.

Oral clonidine for rapid control of accelerated hypertension.

Thirty emergency-room patients, 15 men and 15 women, from 27 to 64 years old with diastolic blood pressures (DBP) greater than 115 mm Hg, were admitted to an open-label, oral loading trial of clonidine. At this time, their supine mean arterial pressures (MAP) averaged 150 +/- 2 mm Hg. An initial clonidine dose of 0.1 to 0.2 mg was to be followed every hour by another 0.1 mg until the DBP had been lowered to a level allowing treatment to be continued on an ambulatory basis or until a total of 0.5 mg had been given. A satisfactory response--defined as a reduction of the supine DBP to 105 mm Hg or lower if the baseline was between 115 and 135 mm Hg, or reduction of a baseline DBP greater than 135 mm Hg by at least 30 mm Hg--was achieved in all but one of the patients in an average of 118 minutes; the mean dose required was 0.26 mg. The mean reduction from the baseline MAP was 23.1 +/- 0.9%. Drug-related adverse experiences comprised drowsiness and dry mouth in 13 patients. Thereafter, 28 of the patients were chronically treated with clonidine for an average of 73 days. In 24 patients treated for at least 80 days, the daily clonidine dose averaged 0.375 mg. All the patients required concurrent diuretic therapy. A satisfactory response (as defined above) to this maintenance treatment was shown by 85% of the patients, and full blood-pressure control (supine DBP less than 95 mm Hg) was attained in 78%.(ABSTRACT TRUNCATED AT 250 WORDS)

Chronic thyroiditis and mitral valve prolapse.

Mitral valve prolapse is more prevalent in patients with autoimmune diffuse toxic goiter, suggesting a possible etiologic association. The prevalence of mitral valve prolapse was determined in 75 patients with chronic lymphocytic thyroiditis, another autoimmune thyroid disorder, and in 50 healthy control subjects. Mitral valve prolapse was found in 31 of 75 (41%) patients with chronic lymphocytic thyroiditis and in 4 of 50 (8%) controls (odds ratio, 8.10; 95% confidence interval, 2.64 to 24.83; p less than 0.0005). The age-race adjusted odds ratio was 9.26 (95% confidence interval, 2.83 to 30.26; p less than 0.0005). No correlation between the prevalence of mitral valve prolapse and the presence of hypothyroidism, serum antithyroid antibodies, or the duration of chronic lymphocytic thyroiditis was found. The prevalence of mitral valve prolapse is substantially increased in patients with the autoimmune thyroid disorders.

Obesity and caloric intake: the National Health and Nutrition Examination Survey of 1971-1975 (HANES I).

Most published studies have failed to show a greater food intake in obese subjects than in nonobese. However, the sample sizes in most of these studies are small and the methodologies open to question. HANES I is based on a probability sample of 20,749 people, representative of the civilian noninstitutional population of the U.S. We analyzed a subsample of 6219 nonpregnant adults whose diet was not influenced by illness or drugs and who stated that their intake, estimated by dietary interview, represented their usual pattern. Neither the caloric intake nor the caloric intake adjusted for physical activity level and age was higher in the obese subjects. This suggests that, unless estimates of food intake differ in accuracy between obese and nonobese subjects, factors other than overeating should be given increased consideration in the etiology of obesity.

Racial difference in salivary sodium-potassium ratio in low renin essential hypertension.

We have studied the relationship between plasma renin activity (PRA) and the salivary sodium-potassium (Na-K) ratio, an index of mineralocorticoid effect, in 223 patients with essential hypertension. In 24 white patients with low PRA, the median Na-K ratio was 0.74, which was significantly lower than the ratio of 1.40 in 54 normal white subjects and the ratio of 1.10 in 34 white hypertensive patients with normal PRA. The Na-K ratio in 71 black patients with low PRA was 1.06, which was not significantly lower than the ratio of 1.50 in 38 black normal subjects or the ratio of 1.56 in 94 black hypertensive patients with normal PRA. These findings indicate a difference in salivary Na-K ratios between white and black patients with low renin essential hypertension and suggest a racial difference in the pathophysiology of this form of hypertension.

The salivary sodium/potassium ratio in hypertension: relation to race and plasma renin activity.

We have studied the relationship between plasma renin activity (PRA) and the salivary Na:K ratio, an index of mineralocorticoid effect, in 223 patients with essential hypertension. In 24 white patients with low PRA the median Na:K ratio was 0.74, which was significantly lower than the ratio of 1.40 in 54 normal white subjects (P less than .005) and the ratio of 1.10 in 34 white hypertensive patients with normal PRA (P less than .005). The Na:K ratio in 71 black patients with low PRA was 1.06, which was not significantly lower than the ratio of 1.50 in 38 black normal subjects or the ratio of 1.56 in 94 black hypertensive patients with normal PRA. These findings indicate a difference in salivary Na:K ratios between white and black patients with low renin essential hypertension, and suggest that mineralocorticoid excess may be a more frequent cause of low renin essential hypertension in white than in black patients.

A comparison of chlorthalidone-reserpine and hydrochlorothiazide-methyldopa as step 2 therapy for hypertension.

Two fixed-combination drugs commonly used in the step 2 treatment of hypertension, chlorthalidone plus reserpine and hydrochlorothiazide plus methyldopa, were compared in an evaluation of efficacy and adverse reactions. Ninety-one percent of the chlorthalidone-reserpine group achieved diastolic blood pressures of 90 mmHg or lower compared with 55% of the hydrochlorothiazide-methyldopa group. The incidence of adverse reactions in the chlorthalidone-reserpine group was 31% compared with an incidence of 64% in the hydrochlorothiazide-methyldopa group.

Serum immunoglobulins in hypertension.

We measured serum immunoglobulins in 52 persons whose blood pressure was higher than 140/90 mm Hg, and 52 normotensive controls matched for age, sex and race. All were selected from a population of actively employed persons undergoing a routine health evaluation. Contrary to previous reports, the hypertensive subjects did not have higher levels of IgG or IgA than the controls. Sixteen hypertensive subjects with mean blood pressure higher than 115 mm Hg did not have elevated IgG or IgA levels when analyzed separately. Serum IgM was significantly lower in the 52 hypertensive subjects (125 +/- 67 mg/dl vs 171 +/- 85 mg/dl, p less than 0.01). Our subjects failed to show the increase in immunoglobulins reported by others. The most likely reasons for this is the mildness of their blood pressure elevation, although the absence of immunoglobulin elevation in the small number with more marked hypertension does not support this explanation.

Postmenopausal estrogen therapy.

PIP: The benefits and potential risks of estrogen use in post menopausal women were discussed at the 61st Annual Meeting of the Endocrine Society. The proven benefits of estrogen treatment include: 1) relief of symptoms such as hot flashes and atrophic changes in the vagina and breast due to a postmenopausal decrease in estrogen; and 2) a diminution of the degree of menapausal osteoporosis, a major health problem in aged 65 and older. Studies have shown a consistant improvement in the maintenance of skeletal mass when estrogen therapy is given. Adverse reactions to estrogen include an increase hepatic secretion of renin substrate resulting in increased blood pressure. Also, studies show both an increased coagulability of blood and cholesterol supersaturation of bile. Prime concern to women treated with the hormone therapy is the two to eight fold increase in risk of developing uterine cancer which increases with duration of estrogen use. Estrogen, although itself not a carcinogen appears to maintain the uterus in a condition that allows it to more readily respond to a carcinogenic stimuli. The relationship of estrogen use to lipoprotein metabolism and coronary heart disease is yet another area to be further studied.^ieng

The pressor response to angiotensin II in patients with low renin essential hypertension.

The etiology of low renin essential hypertension (LREH) has not been established with certainty, but mineralocorticoid excess has been implicated frequently in its pathogenesis. The finding of several investigators of a normal exchangeable sodium space and extracellular fluid volume, however, does not support this hypothesis. To evaluate the possible role of sodium and water retention in LREH, the pressor response to infused angiotensin II (A II) was determined and compared to that of normal subjects and that of subjects with normal renin essential hypertension (NREH). This approach was based on the known suprasensitivity of vascular receptors to A II in situations in which sodium and water compartments are expanded as they are, for example, in proven hypermineralocorticoid states such as primary aldosteronism. In this study, we found that subjects with LREH demonstrated no increased pressor response to graded doses of A II; this suggests that LREH is not primarily mediated by sodium and water retention.