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To study the effect of raloxifene on the response to conjugated estrogen cream or nonhormonal moisturizer in postmenopausal women with preexisting signs of vaginal atrophy.Postmenopausal women with preexisting and untreated vaginal atrophy were enrolled in this parallel, placebo-controlled, randomized study. A total of 187 women were randomized to four treatment groups: daily oral raloxifene (60 mg per day) or a placebo in a double-blind manner plus one application of conjugated estrogen cream (0.5 g) or one applicator full of nonhormonal moisturizer, open label. The conjugated estrogen cream or nonhormonal moisturizer was applied daily for the first 2 weeks, and then twice weekly thereafter for 3 months. Efficacy of treatment regimens on signs and symptoms of vaginal atrophy was evaluated by monitoring objective and subjective parameters.Signs and symptoms of vaginal atrophy improved in all four treatment groups. Raloxifene did not diminish the magnitude of improvement when administered with either vaginal preparation. Conjugated estrogen cream produced a statistically greater improvement in signs (P.05) but not in individual symptoms or overall satisfaction relative to nonhormonal moisturizer.Postmenopausal women with evidence of preexisting vaginal atrophy may use either low-dose conjugated estrogen cream or nonhormonal moisturizer to treat the atrophy concurrently with raloxifene (60 mg per day).

Bone mass is purportedly reduced by an endogenous or exogenous excess of thyroid hormone or, perhaps, by calcitonin deficiency. Patients who have undergone thyroidectomy could be subject to all of these effects, yet their practical implications in terms of fracture risk are poorly defined. Interpretation is further hampered by the focus on women, where results may be influenced by involutional osteoporosis. Consequently, we assessed the potential for fractures among the 136 Rochester, Minnesota men who underwent thyroidectomy between 1935 and 1979, relative to a group of age-matched control men from the community. With 2194 person-years of follow-up in each group, survival free of any fracture of vertebra, proximal humerus, distal forearm, pelvis, or proximal femur was similar in the two groups (p = 0.23), and the relative risk of any of these fractures for thyroidectomized patients versus their controls was increased only 1.5-fold (95% CI, 0.7-3.2). The difference was entirely accounted for by a statistically significant excess of proximal femur fractures in the men with thyroidectomy. Risk factors for fractures among men with thyroidectomy included greater age at surgery, greater extent of surgery, and the presence of risk factors for secondary osteoporosis. Thus, thyroidectomy, performed mainly for adenoma or goiter, seems to have little overall influence on the risk of age-related fractures in men. However, the association with hip fractures requires further evaluation.

The roles of parathyroid hormone (PTH) and calcitonin (CT) in the pathogenesis of familial benign hypercalcemia (FBH, or hypocalciuric hypercalcemia) are uncertain. Thus we performed studies in 26 patients with FBH, 12 patients with primary hyperparathyroidism (HPT), and 20 normal volunteers, to answer these questions: are plasma levels of intact or biologically active PTH frequently elevated in FBH? Is plasma intact PTH nonsuppressible during calcium infusion? Is there blunting of the C cell CT response to calcium infusion as occurs in primary HPT? We used three methods for measurement of PTH: a mid region-specific radioimmunoassay (iPTH, antiserum GP-1M), an extraction-concentration bioassay (bioPTH, stimulation of cAMP generation in osteoblastlike cells), and a two-site immunoradiometric assay (IRMA) for intact PTH. PTH levels were significantly elevated in primary HPT by all three methods, but mean PTH was normal in FBH and 85–92% of values overlapped the normal range. During 5 minute calcium infusions (2 mg Ca2+ per kg) iPTH values fell little, but bioPTH and intact PTH fell sharply in all three groups. Mean calcium-induced decreases of intact and bioPTH were indistinguishable from normal in FBH, but PTH levels generally remained elevated at 5 minutes in primary HPT. In FBH basal and postinfusion CT levels were normal. The data show that, in the majority of patients with FBH, PTH concentrations and bioactivity in blood are within the normal range and are suppressed rapidly to very low levels with further increases of calcium. The data suggest that the abnormality of parathyroid function in FBH differs from that in primary HPT. There was no deficiency of CT or C cell responsiveness in FBH, another difference from primary HPT. Nonetheless, in 8–15% of cases, measurement of PTH could not discriminate FBH from primary HPT.

Lymphosarcoma of domestic dogs is often accompanied by hypercalcemia. We have carried out studies to determine the usefulness of this common canine neoplasm as a model for paraneoplastic hypercalcemia. The study population consisted of 27 healthy control dogs, 13 with hypercalcemic lymphosarcoma, and 28 normocalcemic dogs with lymphosarcoma. Studies included measurement of circulating calcium, phosphorus, creatinine, immunoreactive parathyroid hormone (iPTH) and prostaglandin E2 (iPGE2) concentrations, and determination of in vitro bone-resorbing activity in supernatant culture media from normal and neoplastic lymphoid tissue. Hypercalcemia was severe in the affected group (mean ± SE, 14.9±0.5 mg/dl, normals 10.1±0.1 mg/dl) and associated with decreased renal function (serum creatinine 2.0±0.4 mg/dl, normal 0.8±0.1 mg/dl,P

THERE is considerable evidence that many people with diabetes mellitus of either juvenile or adult onset have moderately reduced bone mass (osteopenia).1 2 3 4 5 6 7 8 9 10 11 12 13 14 For example,...

We examined the incidence and clinical and economic consequences of primary hyperparathyroidism in residents of Rochester, Minn, from 1965 through 1976; 90 cases were found. From January 1, 1965, to June 31, 1974, the average annual incidence was 7.8 +/- 1.2 (mean +/- S.D.) cases per 100,000 population. However, after the introduction of routine measurement of serum calcium, the average annual incidence rose to 51.1 +/- 9.6 cases per 100,000. Even after availability of routine measurement of serum calcium, the annual incidence of primary hyperparathyroidism among persons 39 years of age or younger remained below 10 cases per 100,000. However, the annual incidence increased sharply in persons 40 or more years of age, reaching 188 cases per 100,000 among women 60 years of age and over and 92 cases per 100,000 among men 60 and over. For the last 1.5 years of the study, the average annual age-adjusted incidence of primary hyperparathyroidism was 27.7 +/- 5.8 per 100,000. The frequency of urolithiasis fell from 51 to 4 per cent (P less than 0.001), and the proportion of cases without symptoms or complications of primary hyperparathyroidism rose from 18 to 51 per cent (P less than 0.005). The median charge in 1977 for diagnosis and treatment of primary hyperparathyroidism was $1700. (N Engl J Med 302:189-193, 1980).

To determine the relative importance of parathyroid gland enlargement and alterations in calcium sensing (set-point changes) in the pathogenesis of uremic secondary hyperparathyroidism (2 degrees HPT), we investigated the relationship between estimates of parathyroid gland size and calcium-mediated parathyroid hormone (PTH) suppression in 19 normocalcemic 2 degrees HPT patients on chronic maintenance hemodialysis. We compared our results to calcium-mediated PTH suppression in 12 normal volunteers, 12 patients with familial benign hypocalciuric hypercalcemia (FBHH), a disorder of abnormal calcium sensing, and 9 subjects with primary hyperparathyroidism (1 degree HPT), which is characterized by both calcium set-point abnormalities and parathyroid gland enlargement. We found that the 2 degrees HPT group displayed a distinctive pattern of calcium-mediated PTH suppression characterized by a failure to normally suppress PTH at supraphysiologic ionized calcium concentrations, similar to 1 degree HPT, but without the rightward shift of the calcium-PTH suppression curve that characterizes calcium sensing abnormalities in FBHH and 1 degree HPT. In the patients with 2 degrees HPT, hypercalcemic suppression resulted in an ending PTH (as a percent of baseline) that was significantly higher (39.8 +/- 4.47%), and a slope of the calcium-PTH suppression curve that was significantly less negative (-4.8 +/- 0.53), compared to respective values of 19.4 +/- 1.81% (P = 0.0009) and -9.0 +/- 1.02 (P = 0.001) in normals and 19.1 +/- 2.49% (P = 0.001) and -9.6 +/- 1.11 (P = 0.0006) in FBHH. Values of ending PTH and slope in 2 degrees HPT patients, however, were similar to those found in 1 degree HPT (49.8 +/- 6.35%, P = 0.21 and -4.5 +/- 0.74, P = 0.72). The ionized calcium concentration required to attain half maximal PTH suppression (EC50) in 2 degrees HPT (1.20 +/- 0.02 mmol/liter) was not significantly different from normals (1.25 +/- 0.01 mmol/liter, P = 0.12) but was significantly less than in 1 degree HPT (1.52 +/- 0.02 mmol/liter, P0.0001) and in FBHH (1.44 +/- 0.02 mmol/liter, P0.0001). More importantly, we found a significant linear correlation between the natural logarithm of gland size and ending PTH suppression (r = 0.71, P0.001) and slope of the calcium-PTH curve (r = 0.67, P = 0.002) in 2 degrees HPT. Thus, calcium non-suppressible PTH secretion in 2 degrees HPT does not represent a simple set-point error, but rather correlates with the degree of parathyroid gland enlargement.

A 17-year-old woman manifested fever, abdominal pain, headache, and hypertension caused by a solitary, benign pheochromocytoma. She also had hypercalcemia and elevated plasma immunoreactive calcitonin levels. After removal of the pheochromocytoma, calcium and calcitonin levels returned to normal. Studies of peripheral and tumor venous blood showed no excess or ectopic parathyroid hormone secretion, but the tumor contained and secreted calcitonin. Sporadic pheochromocytoma may secrete calcitonin and cause hypercalcemia by non-parathyroid hormone-mediated mechanisms. The potential is clearly present for confusion with multiple endocrine neoplasia, type 2 (medullary thyroid carcinoma, pheochromocytoma, and primary hyperparathyroidism).

Excerpt To the editor: I enjoyed Bilezikian's timely and well-thought-out article on the medical management of primary hyperparathyroidism (1). However, in regard to his remarks on cimetidine and p...

Excerpt To the editor: Fogelman and colleagues (1) show increased total-body retention of technetium-99m diphosphonate in a small group of patients with primary hyperparathyroidism and equate this ...

Excerpt Several well-established indications for treatment with ingested calcium salts include hypoparathyroidism, osteomalacia, osteoporosis, renal failure with phosphate retention and secondary h...

Familial benign hypercalcemia (hypocalciuric hypercalcemia) was diagnosed in 125 members of 21 families. The syndrome was generally characterized by autosomal dominant inheritance of symptomless, nonprogressive hypercalcemia with normal serum immunoreactive parathyroid hormone concentrations, parathyroid glands that had normal gross and histologic features, relatively low urinary excretion of calcium, and failure to achieve normocalcemia after subtotal parathyroidectomy. Affected persons had normal longevity and no discernible increase in other medical problems except gallstones. The parathyroid glands were not seen using high-resolution ultrasonography. Plasma calcitonin and calcitriol levels were normal or low. Skeletal mass was normal as assessed by photon absorptiometry of the radius and lumbar spine, and fractures were not more frequent. Familial benign hypercalcemia or hypocalciuric hypercalcemia is a distinctive heritable syndrome that should always be considered in the differential diagnosis of asymptomatic hypercalcemia.