James C. Melby

Intranasal aerosolized insulin. Mixed-meal studies and long-term use in type I diabetes.

We assessed the efficacy of intranasal aerosolized insulin containing laureth-9 as a surfactant in patients with Type I diabetes by fasting studies in 8 patients, mixed-meal studies in 15, and long-term home use in 8. The intranasal insulin (1 U per kilogram of body weight in 1 per cent laureth-9) was rapidly absorbed (in 15 minutes); it lowered the plasma glucose level by 50 per cent in 45 minutes in fasting normal controls and by 50 per cent in 120 minutes in fasting diabetics. The glucose-lowering potency depended on the insulin dose and surfactant concentration. Nasal irritation was proportional to surfactant concentration, with great variability among subjects. After intranasal insulin used before meals (1 U per kilogram in 1 per cent laureth-9), the two-hour postprandial glucose level increased above before-meal levels by 38 mg per deciliter, as compared with 191 mg per deciliter after intranasal placebo in patients with Type I diabetes (P less than 0.05). An outpatient feasibility study examining three months of use of intranasal aerosolized insulin before meals as a supplement to Ultralente insulin revealed that the aerosol was well tolerated, with glycemic control (as indicated by the percentage of glycohemoglobin, home glucose measurements, and hypoglycemic reactions) comparable to that during a subsequent three-month period of conventional subcutaneous insulin treatment. The results suggest that intranasal insulin has potential as an adjunct to subcutaneous insulin in the therapy of Type I diabetes.

Diagnosis and localization of aldosterone-producing adenomas by adrenal-vein cateterization.

EVEN when the diagnosis of primary aldosteronism is obvious before operation, there is no way to localize the adenoma. Preoperative demonstration of the tumor radiographically, as by retroperitonea...

Aldosteronism in Hypertension: The Spironolactone Response Test

Excerpt The demonstration of low plasma renin activity (PRA) and increased aldoestrone secretory rate (ASR) may not be sufficient to distinguish primary aldosteronism due to an aldosterone secretor...

Hypothalamic-Pituitary-Adrenal-Axis Hyperactivity in Bulimia

Hyperactivity of the hypothalamic-pituitary-adrenal axis, demonstrated by nonsuppression of plasma cortisol in the dexamethasone suppression test (DST), has been found in about 50% of patients with major depression. We administered the DST to 47 patients with bulimia and to 22 age- and sex-matched normal controls. Among the bulimics, 47% were nonsuppressors, significantly higher than the 9% prevalence of nonsuppressors in the controls, but similar to the prevalence reported for patients with major depression in other studies. This finding is consistent with evidence from studies of phenomenology, family history, and treatment response which suggest that bulimia may be related to affective disorder.

Endocrine abnormalities in patients with central serous chorioretinopathy

PURPOSE To investigate and to identify endocrine and metabolic abnormalities in patients with central serous chorioretinopathy (CSCR). DESIGN Observational case series. PARTICIPANTS Twenty-four patients with CSCR. METHODS Serum and urinary catecholamines, glucocorticoids, mineralocorticoids, serum testosterone, and thyroid-stimulating hormone (TSH) function were evaluated prospectively. RESULTS Fifty percent (12 of 24) of patients with active acute CSCR showed elevated 24-hour urine cortisol or tetrahydroaldosterone levels. Serum aldosterone levels were low in 7 of 24 (29.1%) patients. Single morning plasma catecholamine levels were elevated in 7 of 24 patients, although 24-hour urine metanephrines (catecholamine breakdown products) were normal. Serum testosterone and TSH levels were normal in nearly all (23 of 24) patients. CONCLUSION Many patients with acute CSCR have elevated 24-hour urine corticosteroids, which may contribute to the pathogenesis of the disorder. Endogenous mineralocorticoid dysfunction is a newly described feature of CSCR.

Simplified radioimmunoassay for aldosterone using antisera to aldosterone-γ-lactone

Abstract A simplified, non-chromatographic method for aldosterone-γ-lactone (2) radioimmunoassay is described, using a high titer aldosterone-γ-lactone antibody. This method takes six working hours for completion; the blanks are below the sensitivity of the assay (0–10 pg), and the intra and interassay coefficient of variation is 4.9% and 8.2% respectively. There is no significant variation with different plasma volumes assayed and the plot of added and assayed aldosterone gives a slope of 0.983. The negligible cross reactivity with other steroids and lactones eliminates the problem of interference by these substances.

Therapy of Cushing Disease: A Consensus for Pituitary Microsurgery

Excerpt Transsphenoidal pituitary adenomectomy has emerged as the primary treatment of choice for Cushing disease. The overall cure rate of histologically proved pituitary tumors approaches 90% in ...

Inborn error in the terminal step of aldosterone biosynthesis. Corticosterone methyl oxidase type II deficiency in a North American pedigree

Profound salt wasting developed in a male infant who had marked reductions in serum and urinary aldosterone concentrations despite striking hyperreninemia. Coincident elevations in plasma and urinary levels of specific 18-hydroxysteroids localized the defect to corticosterone methyl oxidase Type II, the adrenal enzyme responsible for the final step of aldosterone synthesis. Salt replacement but not hydrocortisone ameliorated the clinical and metabolic abnormalities. Evaluation of 33 other family members disclosed the biochemical disorder in six other subjects who were affected in an autosomal-recessive pattern with variably severe clinical manifestations and abnormal ratios of 18-hydroxycorticosterone (or its metabolites) to aldosterone. This inborn error in aldosterone biosynthesis must be distinguished from other heritable, salt-losing defects in adrenal steroidogenesis.

Hypothalamic-pituitary-adrenal function in non-AIDS patients with advanced HIV infection.

Patients with acquired immune deficiency syndrome (AIDS) are reported to have increased basal cortisol and reduced stimulated cortisol release, but the dysfunction in the hypothalamic-pituitary-adrenal (HPA) axis is not yet understood in patients with human immunodeficiency virus (HIV) infection during the advanced stage of disease that precedes the development of AIDS. To understand the status of the HPA axis during this phase of HIV infection, 25 non-AIDS ambulatory patients with advanced HIV infection and without evidence of adrenal or pituitary insufficiency were studied. Ovine corticotropin-releasing hormone was administered (1 microgram/kg BW) intravenously and plasma cortisol and adrenocorticotropin (ACTH) were measured over the following 120 minutes. Based on a standard response curve, obtained from CRH testing of 10 HIV negative volunteers with no HPA abnormalities, 13 patients were found to have normal response (group 1), 6 patients had reduced ACTH and cortisol response (group 2) and 6 patients had normal ACTH with reduced cortisol response (group 3). Basal cortisol and basal ACTH were comparable for control subjects and groups 1, 2, and 3. This suggests that, in advanced non-AIDS HIV patients with no clinical evidence of pituitary or adrenal disease, about 25% (group 2) have reduced pituitary reserve with high basal ACTH and cortisol, and about 25% (group 3) have reduced adrenal reserve with high basal cortisol and inappropriately normal basal ACTH, whereas about 50% (group 1) maintain normal HPA axis activity with increased basal cortisol secretion. The exact physiopathologic mechanism is not yet known, but an enhanced CRH production by the hypothalamus may explain the alterations in the HPA axis in advanced HIV disease.

18-Hydroxy-Deoxycorticosterone in Human Hypertension

18-Hydroxy-ll-deoxycorticosterone (18-OH-DOC) was isolated from human adrenal vein blood in concentrations of the same magnitude as is aldosterone, and its structure was proved by a variety of methods including mass spectral analysis. Angiotensin infusions failed to evoke a rise in 18-OH-DOC secretion, whereas ACTH increased 18-OH-DOC secretion up to 20-fold. The secretion rate of 18-OH-DOC determined by isotope dilution in healthy subjects was similar to the range of aldosterone secretion. Excretion of the ring A reduced glucuronide metabolite, 18-hydroxy-tetrahydro-deoxycorticosterone (18-OH-TH DOC), in urine proved to be a valid index of secretion of 18-OH-DOC. 18-OH-DOC secretion was estimated in a variety of hypertensive disorders and found to be significantly elevated in a few (3 of 12) patients with essential hypertension, suppressed plasma renin activity, low or normal aldosterone secretion, and who had significant reduction in blood pressure with spironolactone. A single patient became normotensive on prolonged dexamethasone suppression of ACTH and 18-OH-DOC secretion. The possibility that 18-OH-DOC is a precursor of some more oxygenated and, perhaps, more active mineralocorticoid is suggested.