Salicylic acid stimulation of palmitic acid oxidation by rat skeletal muscle mitochondria.

The effects of salicylic acid on palmitic acid oxidation were studied using rat skeletal muscle mitochondria. Salicylic acid, in concentrations that exerted no effect on mitochondrial coupling (0.1 mM), significantly stimulated mitochondrial palmitic acid oxidation, with maximal stimulation occurring at subsaturating concentrations of substrate. In the same preparation, salicylate had no effect on the oxidation of palmitoylcarnitine or palmitoyl-CoA. Salicylate appears to augment the initial step of palmitic acid oxidation by lowering the apparent Michaelis constant (Km) of long chain fatty acid: CoASH ligase (AMP) (EC 6.2.1.3) for palmitic acid.

Resolution of recurrent thyroid cysts with tetracycline instillation.

Nine patients with recurrent purely cystic thyroid nodules after one or two previous cyst aspirations were treated with repeat cyst aspiration and instillation of intracystic tetracycline hydrochloride. All but two of the patients' cysts resolved completely and have not recurred after a follow-up period of 12 to 50 months (mean = 40). The remaining patients had a partial response that left them with clinically insignificant lesions. The procedure was well tolerated and obviated the need for further therapy in all patients. Cyst aspiration and tetracycline instillation is a safe and effective treatment of recurrent purely cystic thyroid nodules that eliminates the need for surgical excision.

Abnormal sella turcica. A tumor board review of the clinical significance.

Sixty of 146 patients with intracranial neoplasms or arterial aneurysms had roentgenographic abnormalities of the sella turcica. These abnormalities were most commonly due to chromophobe adenoma, craniopharygioma, and acromegaly, but ten of them were caused by lesions arising distant to the sella. There were also three cases of empty sella syndrome. Headache, visual disturbance, and sexual dysfunction were the most frequent presenting complaints, with visual field abnormality being most common. Pituitary dysfunction was manifested most frequently by alterations in growth hormone level and gonadotrophin secretion and less frequently by hypothyroidism and adrenocortical insufficiency. When the abnormal sella was associated with evidence of symptomatic intracranial disease, endocrine dysfunction, or visual field compromise as evidence of an anatomically aggressive intracranial neoplasm, specialized neuroroentgenographic localizing procedures were usually positive, and treatment for most of the causative lesions was highly effective.

The effects of oral fructose, sucrose, and glucose in subjects with reactive hypoglycemia.

We have evaluated the acute effects of orally administered 100-g loads of fructose, sucrose, or glucose given as drinks and of 100-g loads of fructose and sucrose given in cakes on the postprandial serum glucose, insulin, and cortisol responses in seven subjects with reactive hypoglycemia. We defined reactive hypoglycemia as a serum glucose nadir of 65 mg/dl or less, symptoms compatible with hypoglycemia occurring at or after the serum glucose nadir, a hypoglycemic index of greater than 1.0, and a rise in serum cortisol to greater than 20 micrograms/dl after the serum glucose nadir. The data demonstrated that (1) pure fructose given as a drink resulted in relatively flat serum glucose and insulin responses and did not cause a hypoglycemic reaction in any of the subjects, compared with the glucose drink, which caused a hypoglycemic reaction in any of the subjects; (2) ingestion of pure sucrose as a drink elicited significantly flatter serum glucose and insulin responses than did the glucose drink and was associated with some episodes of chemical hypoglycemia and symptoms, but did not result in a hypoglycemic reaction by our definition in any patient; and (3) ingestion of fructose cake led to serum glucose and insulin responses that were lower than those caused by ingestion of sucrose cake, but ingestion of neither fructose nor sucrose cake led to a hypoglycemic reaction by our definition in any patient. In conclusion, the use of fructose as a sweetening agent given either alone, in a drink, or with other nutrients in a cake resulted in markedly flatter serum glucose and insulin responses in subjects with reactive hypoglycemia. Fructose may thus prove useful as a sweetening agent in the dietary treatment of selected patients with reactive hypoglycemia.

Preventive care in diabetes mellitus. Current practice in urban health-care system.

Early identification and treatment of complications of diabetes mellitus may reduce the severity of the complications. As part of a program to reduce these complications in the Denver Department of Health and Hospitals patient population, our study determined how frequently preventive care, e.g., fundoscopic examinations, referral to an ophthalmologist, foot examinations, and assessment of cardiovascular risk factors, was provided to diabetic patients. With the use of billing records to identify a large sample of diabetic patients, a chart review of 544 patients was conducted. During the study year, the mean +/- SE number of visits to primary-care clinics was 5.7 +/- 0.22, with 86.4% having at least one visit. Most diabetic patients were seen by primary-care physicians; only 9% received care in a specialized diabetes clinic. Despite frequent primary-care visits, most diabetic patients in this county health-care system did not have documentation of care to detect complications of diabetes mellitus, and referral services for detection and treatment of these complications were infrequently used. Moreover, among patients seen on greater than or equal to 10 occasions in a primary-care setting, preventive care was not provided to 30% of the patients. Preventive care does not appear to be a regular part of a primary-care visit for most of the diabetic patients in this study.

Glucose tolerance in granuloma annulare.

Granuloma annulare (GA) may be associated with glucose intolerance. Twenty-one patients with GA were evaluated. Four patients were found to have frank diabetes mellitus and 2 were excluded from the data analysis because of obesity. The remaining patients and 14 age- and weight-matched controls had oral and intravenous glucose tolerance tests (GTT). During the oral GTT the fasting plasma glucose, the 2-h plasma glucose, the area of the glucose curve, the 1-h serum insulin, and the area of the insulin curve were all significantly greater in the GA patients than in the controls. During the intravenous GTT the immediately releasable insulin pool was intact, while the fasting plasma glucose and the area of the glucose curve were greater in the GA patients than in the controls. The data taken together suggest that glucose tolerance may be reduced in GA and that insulin resistance may exist.

Growth hormone responses following double pulse oral glucose administration in various clinical states.

The 8-h double pulse oral glucose test is proposed as an alternative screening procedure for determining the adequacy of growth hormone (GH) release. The second pulse of glucose is timely in suppressing GH release and delaying it for a more predictable controlled elevation. Peak GH (mean plus or minus SD) values following the double pulse glucose test were 17 plus or minus 10.2, 16.5 plus or minus 2.2, and 1.3 plus or minus 0.5 ng/ml in normal controls, short stature patients and GH deficient patients, respectively. Peak GH values following insulin hypoglycemia were 36.9 plus or minus 13.8, 21.9 plus or minus 23.0 and 1.8 plus or minus 1.1 ng/ml in normal controls, short stature patients and GH-deficient patients. Peak GH values during a 5-h oral glucose tolerance test were 16.4 plus or minus 6.0 and 10.2 plus or minus 3.3 ng/ml in normal controls and short patients, respectively. These differences in peak GH values between the various clinical and control groups were not significantly different except for the greater GH peak values reached in short patients in the double pulse glucose test compared to the 5-h oral glucose tolerance test. The rise in GH following double pulse oral glucose is more timely predictab-e than after the 5-h oral glucose test and involves less professional time than the insulin tolerance test as it does not require close medical supervision.

Reduced bone mineral content in totally thyroidectomized patients: possible effect of calcitonin deficiency.

To further investigate the relationship between calcitonin deficiency and osteoporosis, we have measured bone mineral content (BMC) by single photon absorptiometry in patients made iatrogenically calcitonin deficient by prior total thyroidectomy for thyroid cancer. Compared to sex-, age-, height-, and weight-matched normal controls, male patients had a significantly lower mean BMC at the midradius (1.162 +/- 0.02 vs. 1.301 +/- 0.05 g/cm; P less than 0.02) and the distal radius (1.180 +/- 0.04 vs. 1.338 +/- 0.04 g/cm; P less than 0.01). Female patients also had a significantly lower BMC at the midradius compared to those of a similarly matched group of normal controls and a group of patients on L-T4 suppression for nodular goiters (0.791 +/- 0.04 vs. 0.896 +/- 0.05 vs. 0.891 +/- 0.03 g/cm; P less than 0.025). We conclude that calcitonin deficiency from surgical thyroidectomy is associated with significant decreases in bone mineral content in both sexes. This lends further support to the concept that calcitonin deficiency may be an important causative factor in the development of osteoporosis.

Altered hypothalamic-pituitary-adrenal responsiveness to dexamethasone-insulin tolerance test in active acromegaly.

Eight acromegalic patients showed a plasma cortisol (11-OHCS) rise after insulin hypoglycemia which was similar to that seen in control patients, with mean peak values (+/-SEM) of 23.2 +/- 3.5 mug/100 ml and 27.2 +/- 3.3 mug/100 ml, respectively. One mg of dexamethasone was given the evening prior to repeat insulin hypoglycemia (DEX-ITT). After dexamethasone, the control subjects showed a mean post hypoglycemic plasma 11-OHCS rise to 18.3 +/- 2.3 mug/100 ml. In contrast, acromegalic patients had a negligible rise is plasma 11-OHCS, despite a comparable degree of hypoglycemia. These data indicate that, in active acromegaly, abnormal hypothalamic-pituitary-adrenal suppressibility can be induced to insulin hypoglycemia after dexamethasone.

The effects of theophylline and nifedipine on corticotropin-stimulated cortisol secretion.

The adrenal cortisol response to corticotropin appears to involve both calcium and cyclic adenosine 3',5'-monophosphate (cAMP) as intracellular mediators. In 10 healthy male volunteers, the short-term administration of theophylline, which affects both intracellular calcium and cAMP, lowered basal cortisol levels but augmented the in vivo cortisol response to short-term corticotropin stimulation. Short-term administration of nifedipine, a calcium channel antagonist, had no effect on basal or peak cortisol levels but reduced the incremental cortisol response to corticotropin. The effects of both theophylline and nifedipine, although statistically significant, were modest and of questionable clinical significance but should be considered in the interpretation of the clinical corticotropin stimulation test. They may also provide some insight into the post-receptor actions of corticotropin.

Covert hypothyroidism presenting as a cardiovascular event.

Hypothyroidism presenting with classic signs and symptoms is generally easily recognized. Less often, patients with hypothyroidism may present with symptoms and laboratory abnormalities suggestive of cardiovascular disease. In this article, we describe six such patients. Hypothyroidism was suspected when creatine phosphokinase (CPK) levels were persistently elevated. The diagnosis was confirmed by thyroid function tests, and thyroid hormone therapy resulted in resolution of symptoms and CPK elevations. Persistently elevated CPK levels associated with cardiovascular symptoms but without demonstrable myocardial damage should prompt consideration of covert hypothyroidism.

Lithium-associated thyrotoxicosis.

Primary hypothyroidism developed in a 57-year-old woman treated for eight years with lithium carbonate for manic-depressive illness, and nine months later she became thyrotoxic. Although autoimmune disease appeared to be responsible, lithium was suspected to play a contributory role in both phases of her illness. This is the first reported case of hyperthyroidism following hypothyroidism in a lithium-treated patient. The 24 reported cases of lithium-associated thyrotoxicosis and the possible mechanisms that may explain this poorly understood phenomenon are also reviewed.

Radioiodine-induced thyroid storm. Case report and literature review.

Thyroid storm developed following radioiodine therapy in a 43-year-old man with Graves' disease, weight loss, myopathy, severe thyrotoxic hypercalcemia, and a pituitary adenoma. The hypercalcemia may have been a significant, and previously unreported, predisposing factor for the radioiodine-associated thyroid storm. This case and 15 other well-documented cases of radioiodine-associated storm found in the literature are reviewed, as are several other cases of less severe exacerbations of thyrotoxicosis associated with radioiodine therapy. Although not often seen, these complications are often fatal. High-risk patients, such as the elderly, those with severe thyrotoxicosis, and those with significant underlying diseases, may benefit from preventive measures such as the judicious use of thyrostatic medications during the periods before and after isotope administration.

Pure primary hyperaldosteronism due to adrenal cortical carcinoma.

A 47-year-old woman is described who had pure primary hyperaldosteronism due to an adrenal cortical carcinoma. This may represent the first such case in which modern laboratory tests allowed specific diagnosis and exclusion of hypersecretion of other adrenal steroids, and also the first reported case in which modern localizing procedures have been utilized. Other interesting facets of the case include calcification of the tumor, visualization with 131l iodomethylnorcholesterol , metaplastic histologic changes, and coexistent bilateral renal artery fibromuscular disease.

Low dose radioiodide thyroid ablation in postsurgical patients with thyroid cancer.

Sixty-four patients with well-differentiated carcinoma of the thyroid were treated with initial high (80 to 100 mCi) or low (less than 30 mCi) doses of I131 after bilateral subtotal thyroidectomy. A total of 36 patients in the various histologic categories were initially treated with the low dose of I131 (group 1), and a total of 28 patients were treated with the higher dose (group 2). Disease-free criteria were no visible tissue in the neck or body, a protein-bound radioactive iodine (PBI131) of less than 0.005 per cent per liter at seven days and/or whole body retention of less than 3 per cent at seven days. Of the patients receiving less than 30 mCi (group 1), 56 per cent with papillary carcinoma, 67 per cent with follicular carcinoma and 56 per cent with mixed carcinoma of the thyroid were rendered disease-free after this initial dose. Of the patients receiving the higher dose of I131 (group 2), 67 per cent with papillary carcinoma, 50 per cent with follicular carcinoma and 67 per cent with mixed carcinoma of the thyroid were rendered disease-free after this initial dose. Disease-free mean follow-up time was 5.17 years (group 1) and 5.82 years (group 2). There was no statistical difference in these mean follow-up times, nor was there a statistical difference in the net (total minus initial) dose of I131 needed to render the patient disease-free. These data demonstrate that low dose I131 therapy is as effective as the larger more routine doses of I131 given in this disease.

"Masked" 21-hydroxylase deficiency of the adrenal presenting with gynecomastia and bilateral testicular masses.

An infertile 27 year old man with precocious puberty is described. He presented in adulthood with unilateral and then bilateral gynecomastia, and subsequently testicular tumors developed. An early diagnosis of congenital adrenal hyperplasia would have avoided unnecessary surgery. Initial detailed metabolic evaluation led to the erroneous diagnosis of 11-hydroxylase deficiency because of the presence of an unusual steroid (21-desoxycortisol) in serum which was falsely reported as an increased 11-desoxycortisol (compound S). The observed low urinary pregnanetriol measurements would have supported this diagnosis. Subsequent specific measurements of 21-desoxycortisol established its presence in the serum and its major metabolite, tetrahydro-21-desoxycortisol, in the urine. The unique features in this case of 21-hydroxylase deficiency alert the physician to its unusual clinical presentation and the pitfalls that may be encountered when evaluating adrenal steroidogenesis.

Reactive hypoglycemia.

Reactive hypoglycemia is a relatively uncommon meal-induced hypoglycemic disorder. Most patients with adrenergic-mediated symptoms have a diagnosis other than reactive hypoglycemia. In many patients with this self-diagnosis, other disorders can be attributed as a cause for symptoms, especially neuropsychiatric disease. The continued use of the terminology "functional hypoglycemia" only contributes vagueness to our correct understanding of this metabolic condition. There are a number of conditions associated with postprandial hypoglycemia. One category is the reactive hypoglycemias, which occur in patients with diabetes mellitus (diabetes reactive hypoglycemia), gastrointestinal dysfunction (alimentary reactive hypoglycemia), hormonal deficiency states (hormonal reactive hypoglycemia), and a large patient group characterized as having idiopathic reactive hypoglycemia. Of these causes the alimentary, hormonal, and diabetic patients are less disputed, whereas the idiopathic reactive hypoglycemic group has been referred to as a "nondisease" group. Characteristic alterations in insulin secretion accompany each of these conditions. In bona fide patients, dysinsulinism or hyperinsulinism usually accounts for the hypoglycemia. Some patients may have increased insulin sensitivity, but this association is doubtful or very rare. Patients with this meal-related eating disorder are characterized as ingesting excessive quantities of refined carbohydrate. In the research setting, the disorder can easily be elicited with the oral glucose tolerance test. However, to establish clinical relevance, the hypoglycemia needs documentation in the home setting with measurements of blood glucose during a postpradial symptomatic episode. The reactive hypoglycemic patients are frequently confused with patients with underlying psychiatric illness. Both syndromes are similar, with adrenergic-mediated symptoms and a common characteristic personality as noted on Minnesota Multiphasic Personality Inventory (MMPI) testing. Patients with bona fide meal-related reactive hypoglycemia should be treated primarily with dietary restriction of refined carbohydrates; other patients may require medications.

Use of the Anger scintillation camera for determining thyroid uptake.

Nineteen patients, representing a spectrum of thyroid function, were studied. The mean 24-hr thyroid 131I uptakes determined by a standard counting procedure and by our scintillation camera counting method were 15.0% and 16.4%, respectively, for the entire patient population. The 24-hr 131I uptakes from these two methods correlated with a coefficient of 0.99. A high degree of correlation between the two methods was found in evaluating euthyroid and hypothyroid patients and a similar finding was noted in the one hyperthyroid patient studied.

Comparison of 4- and 24-hr thyroid scans with 123I: concise communication.

Thyroid scans were performed at 4 and 24 hr after administration of Na123I solution in 124 examinations. The 4-hr and 24-hr scans were found to be of equal diagnostic value. Thus, in individuals with structural thyroid abnormalities, one can effectively reduce the time required for scan evaluation from the standard 24 hr to 4 hr.

Reactive hypoglycemia.

The hypoglycemoses include a large category of distinctly unique entities. Guidelines for a clinical, physiological approach to these disorders is presented. Within this diagnostic spectrum of hypoglycemia lies the reactive hypoglycemic disorders that are characterized by their postprandial onset, adrenergic mediated symptoms, and relatively benign causes. The spectrum of reactive hypoglycemia includes early alimentary-reactive hypoglycemia, late diabetic-reactive hypoglycemia, hormonal deficiency states, and idiopathic hypoglycemia. A new postprandial hypoglycemic disorder, fructose 1-6 diphosphatase, can be added to this list. The frequent sampling of blood-glucose values in the postprandial state will frequently lead to the finding of a biochemically low blood-glucose value of below 50 ml/100 ml, and these individuals show no hypothalamic-pituitary-adrenal stress to the low blood sugar and do not manifest adrenergic symptoms. Their low blood-glucose value simply reflects the transition in intermediary metabolism between the fed and fasting state and provides a biochemical marker of this event. We refer to this asymptomatic biochemical event as transitional low blood-glucose state. It has no clinical implication and may frequently be confused with the bona fide reactive hypoglycemic disorders. Using a symptomatic, counter-regulatory model to define hypoglycemia as a bona fide disorder, findings are presented in patients with the varying types of reactive hypoglycemia, and their results are compared to normal controls and to a weight-matched and disease patient controls. Abnormalities in insulin secretion are discussed as relating to the pathophysiology causal in the hypoglycemia. An approach to therapy is presented based upon the classification of the patient as to the type of hypoglycemia and their abnormalities in insulin secretion.