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To determine the effects of short-term fasting on carbohydrate tolerance, 10 obese women with noninsulin-dependent diabetes mellitus (NIDDM) were studied with meal tolerance tests before and after 3 days of fasting. After 3 days' fast, basal serum glucose declined from 15.2 +/- 0.9 to 7.5 +/- 0.7 mmol/L (273 +/- 17 to 135 +/- 13 mg/dL) (mean +/- SEM, p less than 0.001) and the glycemic response to the test meal (area under the glucose curve) improved by 31%. There were no changes in basal or postprandial insulin levels but a slight increase in serum c-peptide. Resting metabolic rate and the thermic effect of food were unchanged. There was a slight but insignificant change in basal and postprandial free fatty acid levels and a significant elevation of basal beta-hydroxybutyrate levels. Blood lactate rose significantly (from 0.9 to 2.0 mM) during the initial meal tolerance test, but no rise in lactate was seen in the meal tolerance test after fasting. Two subgroups of patients were identified based on the degree of glycemic improvement after short-term fasting. Those with lesser improvement in serum glucose showed overnight rises in serum glucose during the period of fasting (the dawn phenomenon), while those patients who normalized serum glucose showed a steady fall in serum glucose. This finding may help to predict the glycemic response to long-term calorie restriction. Carbohydrate tolerance improves in obese diabetic (NIDDM) women after 3 days of fasting, in contrast to the impairment of glucose tolerance seen in lean or obese nondiabetic subjects after fasting.(ABSTRACT TRUNCATED AT 250 WORDS)

From 1977 to 1988, 56 patients with a preoperative diagnosis of Cushing's disease were treated by transsphenoidal microsurgical exploration of the pituitary gland. In 42 patients, a discrete tumor was found and a selective adenomectomy was performed. Total hypophysectomy was performed in nine patients. In an attempt to preserve pituitary function, a technique of subtotal hypophysectomy was utilized in the remaining five patients. Regular and adequate follow-up results were obtained in 53 patients. A sustained remission was obtained in 45 of these 53 patients for a remission rate of 84.9%. Eight patients were classified as therapeutic failures. The causes for failure included: 1) invasive tumor; 2) hyperplasia mistaken for an adenoma; 3) a presumed ectopic source of adrenocorticotropic hormone; 4) misdiagnosis; 5) atypical tumor; and 6) recurrence of disease after remission. In cases of therapeutic failure, the original diagnosis of Cushing's disease must be reevaluated and treatment continued until sustained remission is achieved. Necessary measures to help avoid surgical failures and an approach for further diagnostic and therapeutic maneuvers in these cases are discussed.

We reviewed 4 patients with urothelial bladder cancer and hypercalcemia but without evidence of bony metastasis. Of the patients 2 presented with a leukemoid reaction (1 also had thrombocytosis). None of the patients had evidence of bone metastases or other causes of hypercalcemia, such as hyperparathyroidism, sarcoidosis or vitamin D intoxication. All 4 patients received aggressive therapy for the tumors. In each instance the serum calcium returned to normal following radiation therapy or tumor removal, lending support to the theory of humoral hypercalcemia of cancer. A diagnostic and therapeutic approach to such patients is outlined.

Although metastatic involvement of the thyroid is not commonly considered in the differential diagnosis of a patient with a thyroid mass, such involvement may be more frequent than has been previously appreciated. To evaluate the prevalence of this disorder, all patients with thyroid nodules referred in a 12-month period underwent fine-needle aspiration, regardless of history or scan results. Seventy patients were studied, six of whom had a previous history of malignant disease. Two of the latter had coincidental thyroid disease, but four (5.7% of the total series) had carcinoma metastatic to the thyroid gland. Two of these patients had had no evidence of malignancy for years prior to the appearance of the thyroid metastases. In one case, the metastasis was a functioning nodule. Fine-needle aspiration cytology provided prompt and accurate diagnosis in all patients. We conclude that metastatic carcinoma to the thyroid is not rare, its presentation may be confused with primary thyroid disease, and fine-needle aspiration cytology is the procedure of choice in such cases, and should be done early in the evaluation of all patients with thyroid nodules, regardless of the presumed etiology or function by scan.

Gonadotropin levels were measured in 65 postmenopausal women admitted to the intensive care unit. Sixteen patients (25%) were hypogonadotropic as measured by luteinizing hormone (LH) and follicle-stimulating hormone (FSH) levels of 5 IU/L or less, and only 20 patients (31%) were found to have gonadotropin levels within the expected postmenopausal range (greater than or equal to 30 IU/L). No significant differences in prolactin or free thyroxine levels were found, but the cortisol level was higher and the total thyroxine level lower in the hypogonadotropic group. The patients in the hypogonadotropic group also seemed more seriously ill, with a longer duration of hospitalization, an increased total number of days in the intensive care unit, an increased number of days in the intensive care unit before gonadotropin sampling, a higher incidence of parenteral hyperalimentation, lower serum albumin levels, and higher mortality. Stimulation of the gonadotropin-releasing hormone performed on 10 patients showed a blunted response in patients with baseline LH and FSH levels of 10 IU/L or less. Of 10 patients followed up sequentially, 6 showed a rise in gonadotropin levels that paralleled recovery, 1 died with low gonadotropin levels, and 3 continued to have low gonadotropin levels 17, 34, and 82 days, respectively, after initial screening. Critically ill postmenopausal women may exhibit a marked fall in gonadotropin, LH, and FSH levels. This disease in gonadotropin levels in response to illness is reversible and results from pituitary unresponsiveness to gonadorelin hydrochloride.

To address the role of proficiency testing in the medical usefulness of laboratory tests, nine steps involved in the generation and application of a laboratory test result are identified and discussed: test ordering, patient preparation, specimen, sample, analysis, result, reporting, recognition, and action. Clinical uses of test results are enumerated. Good clinical skills are necessary for optimal test efficiency. Clinicians should improve their selection of tests, pay attention to proper patient preparation, and refine the process of interpretation of test results using disease-based reference ranges and more formal analysis of predictive value. By better definition of the clinical uses of laboratory tests, appropriate attention can be directed to steps in the laboratory domain such as medically relevant goals for accuracy and precision. With clearer understanding of the testing process, proficiency testing for monitoring laboratory performance can be more fully utilized. Audit models should be developed that include assessment of the outcome of the laboratory testing process.

In the post-thyroidectomy patient who has received I-131 ablation for thyroid carcinoma, focal uptake on repeat total body images is usually interpreted as being indicative of functioning thyroid metastases. The differential of focal I-131 activity in such a patient has been described. This report adds to the differential by presenting a case of benign sialadenitis that caused focal neck uptake a year after ablation therapy with I-131.

Carcinomatous involvement of the thyroid is a most unusual cause of hyperthyroidism and thyroiditis, with only a few cases reported in the literature. The authors present a 35-year-old woman with signs, symptoms, and laboratory findings of hyperthyroidism, and subacute thyroiditis that was due to extensive replacement of the thyroid gland by adenocarcinoma (shown by fine needle aspiration). After chemotherapy with vincristine and cisplatin, the swelling of the thyroid resolved, thyroidal uptake of radioactive iodine increased, and mild hypothyroidism developed. Despite the improvement in her thyroid status, she died from progressive malignancy. This case illustrates the value of fine needle aspiration cytology where doubt exists in the diagnosis of thyroid disorders.

Although powerful tools are available for the measurement of bone density, the diagnosis of osteoporosis is still made largely on clinical grounds. Bone density measurement is not recommended for routine screening, but it may be useful in deciding whether to treat high-risk patients and in following the effects of treatment. Estrogen therapy is used for the prevention of osteoporosis in women with early menopause and as treatment within five to seven years of menopause. Several agents currently being tested offer promise in restoring normal strength to osteoporotic bone.

Isovolumic left ventricular (LV) preparations were isolated from guinea pigs 16-18 hr after IP injection of either saline (control groups) or 4 mg/kg of Escherichia coli endotoxin (shock groups). The tissues were then subjected to mechanical performance comparisons in a carefully regulated coronary perfusion system. Endotoxicosis consistently resulted in myocardial contractile dysfunction as evidenced by significantly low values for LV systolic pressure and maximal rates of LV pressure rise (+dP/dtmax) and fall (-dP/dtmax). There was a distinct tendency for spontaneous tachybradydysrhythmias in the shock groups, but the LV contractile deficit was not dependent upon beating frequency. Also, LV function curves (systolic pressure vs end-diastolic pressure) generated by shock hearts were shifted downward and to the right of control curves, in the direction of inotropic failure. Thus, cardiodynamic adjustments during endotoxin shock may reflect and be limited by underlying dysfunction intrinsic to the heart itself; by 16-18 hr, the resulting functional changes in LV myocardium are manifested in an isolated environment and do not depend on depressive constraints operative in the intact host.