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Biomedical subjects

P H Forsham

Publications and source records attributed to P H Forsham.

At least 19 recordsLinked to original sources
PubMed1986

An overnight high-dose dexamethasone suppression test for rapid differential diagnosis of Cushing's syndrome.

We have developed a high-dose dexamethasone suppression test that can be administered overnight with a single 8-mg dose and used the new procedure in the differential diagnosis of 83 patients with Cushing's syndrome. In 76 patients with surgically or pathologically proven cause--60 with Cushing's disease, 7 with the ectopic adrenocorticotrophic hormone syndrome, and 9 with adrenal tumors--suppression of plasma cortisol levels to less than 50% of baseline indicated a diagnosis of Cushing's disease. The test had a sensitivity of 92%, a specificity of 100%, and a diagnostic accuracy of 93%. These values equal or exceed those of the standard 2-day test whether based on suppression of urinary 17-hydroxycorticosteroids or plasma cortisol. We conclude that this overnight, high-dose dexamethasone suppression test is practical and reliable in the differential diagnosis of Cushing's syndrome.

17-Hydroxycorticosteroids↗
PubMed1983

Anovulatory effect of synthetic analogs of arginine vasotocin in the rat.

We synthesized a series of analogs of arginine vasotocin by systematically substituting each residue, and we then evaluated the anovulatory activity of these compounds in the rat, investigating the correlation between molecular structure and anovulatory, pressor, and antidiuretic activities. Substitution of the N-terminus cysteine with 3-mercaptopropanoic acid in arginine vasotocin and arginine vasopressin produced a 3- to 4-fold increase in both anovulatory and antidiuretic activity and only a 10% change in pressor activity. A similar substitution with lysine vasopressin produced no significant change in either anovulatory or antidiuretic potency; however, the pressor activity was reduced by half. Substitution of this cysteine in arginine vasotocin with 2-hydroxy-3-mercaptopropanoic acid produced an analog more potent in anovulatory activity than arginine vasotocin but less potent than [1-(3-mercaptopropanoic acid)]-arginine vasotocin. The most potent anovulatory analog synthesized was [1-(3-mercaptopropanoic acid)]-8-ornithine vasotocin, which gave a 10-fold increase in anovulatory activity, a 4-fold reduction in antidiuretic activity, and only a 10% increase in pressor potency when compared with arginine vasotocin. These data suggest that different receptors are involved in the anovulatory and antidiuretic responses, but that the anovulatory and pressor effects may be mediated through similar receptors. Further work is necessary to produce a peptide that possesses specific anovulatory activity.

Amino Acids↗
PubMed1983

Reduced solubility of short-acting soluble insulins when mixed with longer-acting insulins.

Using insulins from three manufacturers, we examined the recovery by radioimmunoassay of short-acting soluble insulin when mixed with long-acting insulin as a function of the ratio of the mixture and the time of pre-mixing. In ratios of 1:2, 1:3, and 1:5 (short- to long-acting insulin), all Novo, Nordisk, and Lilly short-acting insulins tested showed a significant loss of solubility when mixed with the respective company's long-acting insulin either for less than 75 s or for 20 min before centrifugation. In ratios of 1:1, Novo's Actrapid (regular) with Monotard (lente) and Lilly's regular with lente showed no significant loss of solubility when pre-mixed for less than 75 s, and the regular insulin also showed no significant loss when pre-mixed for 20 min. However, when Lilly's regular was mixed with either NPH or ultralente in a 1:1 ratio, a significant loss of solubility of the short-acting insulin occurred regardless of time [as was also found with Nordisk's Velosulin (regular) with insulatard (NPH)]. When Lilly regular was incubated with Lilly lente in ratios of 1:3 for less than 75 s, 20 min, 4 h, and 24 h before centrifugation, there was a progressive loss of solubility. In contrast, with the same ratios and times of pre-mixing, Lilly regular when mixed with Lilly NPH showed a rapid initial loss of solubility that plateaued by 20 min before centrifugation.(ABSTRACT TRUNCATED AT 250 WORDS)

Drug Combinations↗
PubMed1982

Hemoglobin A1 correlates with the ratio of low-to high-density-lipoprotein cholesterol in normal weight type II diabetics.

Because cardiovascular risk correlates with serum low density lipoprotein (LDL) cholesterol and is inverse with high density lipoprotein (HDL) cholesterol, the LDL-HDL cholesterol ratio has been advocated as a sensitive index of relative cardiovascular risk. In 50 normal weight insulin-treated Type II diabetic subjects, mean LDL-HDL ratios were significantly higher than for controls. In diabetic women, the LDL-HDL cholesterol ratio correlated with hemoglobin A1 better than any of the lipids or lipoprotein cholesterol fractions. When 8 poorly controlled diabetics were treated with insulin, the LDL-HDL ratio changed more significantly than did its component fractions, and the fall in LDL-HDL ratio paralleled the fall in hemoglobin A1.

Adult↗
PubMed1982

Cushing's syndrome: problems in management.

CS comprises a group of disorders characterized by hypercortisolism. The variety of causes--pituitary-dependent CS (CD), adrenal tumor, and the ectopic ACTH syndrome--necessitates a variety of therapies--surgical, radiotherapeutic, and medical. Once a specific diagnosis is made, specific therapy can be instituted. Although some controversy persists regarding treatment, particularly that of CD, for most patients it is straightforward. However, in our experience with more than 60 patients, therapeutic dilemmas can arise in a number of circumstances, e.g. the patient with the radiologically normal sella or recurrent CD after adrenalectomy. In addition, the treatment of such conditions as the large ACTH-producing pituitary tumor, Nelson's syndrome, the malignant ectopic ACTH syndrome, and adrenal carcinoma is not entirely satisfactory. Our approach to these problems is illustrated by seven cases, and we emphasize that the proper management of CS requires both correct diagnosis and the logical application of all available therapies.

ACTH Syndrome, Ectopic↗
PubMed1981

Pituitary ACTH dependency of nodular adrenal hyperplasia in Cushing's syndrome. Report of two cases and review of the literature.

Cushing's syndrome due to nodular adrenal hyperplasia comprises a clinically and biochemically heterogeneous group of disorders whose pathogenesis is unclear. We describe two patients with atypical steroid dynamics and large unilateral adrenal nodules who had pituitary ACTH-dependent disease. In the differential diagnosis of Cushing's syndrome, we recommend repeated ACTH measurement and selective venous sampling-particularly in those patients with impaired dexamethasone suppressibility and abnormal findings on computerized tomography.

Adrenal Gland Neoplasms↗
PubMed1981

Cushing's syndrome: problems in diagnosis.

Cushing's syndrome, an unusual group of disorders characterized by hypercortisolism, must be considered in the differential diagnosis of such common clinical problems as hirsutism, menstrual irregularity, hypertension, diabetes mellitus, and obesity. Its distinct forms--pituitary-dependent Cushing's syndrome (Cushing's disease), adrenal tumor and ectopic ACTH syndrome--must be identified correctly so that specific therapy can be administered. In the majority of cases, use of a relatively simple diagnostic sequence will provide accurate and rapid diagnosis. However, in our experience with more than 60 patients, diagnostic difficulties may arise from a variety of conditions (e.g., drug interference, alcohol ingestion, and depression). In addition, unusual circumstances, such as unexpected responses to dexamethasone, may complicate the diagnosis. Our approach to these problems is illustrated through a report of seven cases, and we emphasize that the proper management of Cushing's syndrome mandates a thorough marshalling of all the available data.

ACTH Syndrome, Ectopic↗
PubMed1981

Silent pituitary apoplexy: subclinical infarction of an adrenocorticotropin-producing pituitary adenoma.

A young woman developed intermittent headaches and progressive hyperpigmentation after bilateral adrenalectomy for Cushing's disease. Results of sellar polytomography were abnormal. Her plasma ACTH levels increased to 4750-7340 pg/ml and did not rise with insulin-induced hypoglycemia. Although she experienced no clinical features associated with spontaneous infarction of a pituitary tumor, plasma ACTH levels fell to 474-575 pg/ml, and hemorrhagic necrosis was found in a 5-mm chromophobe adenoma at transsphenoidal surgery. Postoperatively, ACTH levels returned to normal (51-88 pg/ml), with the rest of her anterior pituitary function remaining intact 4 yr later. Spontaneous infarction of pituitary microadenomas may be subclinical, resulting in improvement of pituitary hormone hypersecretion without impairment of other anterior pituitary hormone secretion.

Adenoma, Chromophobe↗
PubMed1981

Selective venous sampling for ACTH in Cushing's syndrome: differentiation between Cushing disease and the ectopic ACTH syndrome.

We performed selective venous catheterization and sampling for ACTH in six patients with ACTH-secreting pituitary adenomas (Cushing's disease) and four patients with occult ectopic ACTH-secreting neoplasms. In five patients with Cushing's disease in whom the inferior petrosal sinus could be catheterized, ACTH levels were unequivocally higher than simultaneous peripheral values: The ratio was greater than 2.0, with a range of 2.2 to 16.7. In contrast, the inferior petrosal sinus-to-peripheral ACTH ratio in three patients with ectopic ACTH secretion was less than 1.5. In the fourth patient, an arteriovenous gradient of 6.8 was shown 2 years before a bronchial carcinoid tumor was clinically apparent. Central-to-peripheral ACTH ratios at the level of the jugular bulb and jugular vein were not diagnostic. We conclude that selective venous ACTH sampling from the inferior petrosal sinus is a reliable and useful aid in the differential diagnosis of Cushing's syndrome when standard clinical and biochemical studies are inconclusive.

ACTH Syndrome, Ectopic↗
PubMed1980

Increased growth hormone response to dopamine infusion in insulin-dependent diabetic subjects: indication of possible blood-brain barrier abnormality.

To test the hypothesis that cerebral capillaries, which share the embroyologic and morphologic characteristics of retinal capillaries, might have the same abnormal permeability in diabetic patients, we investigated the growth hormone response to a small amount of peripherally administered dopamine (1.5 microgram/kg.min). Consistent with the known exclusion of systemic dopamine from brain parenchyma, no rise was observed in 12 normal subjects. In 10 of 12 juvenile-onset, insulin-dependent diabetic patients, however, a substantial growth hormone rise occurred (peak value, 19.2 +/- 3.0 ng/ml [mean +/- SE]). Comparision of metabolic and cardiovascular responses to the infusion in both groups did not suggest that higher circulating levels of dopamine had been achieved in the diabetics. Other growth hormone stimuli (apomorphine in decreasing amounts, glucagon, and graded physical exercise) failed to indicate that hypothalamic hypersensitivity could account for the consistent rise. We postulate that an abnormal permeability of the blood-brain barrier in the diabetic patients permitted exposure of the hypothalamic structures regulating growth hormone secretion to a greater fraction of the infused dopamine.

Adult↗
PubMed1980

Endocrine responses to sugar ingestion in man. Advantages of fructose over sucrose and glucose.

Nine normal subjects ingested 100 gm. glucose, fructose, and sucrose on separate days after an overnight fast. Plasma glucose, fructose, insulin, glucagon, growth hormone, and triglyceride levels were then measured over the following 5 hr. Plasma glucose and insulin peaks were both significantly lower after fructose ingestion as compared with glucose and sucrose. Plasma glucagon suppression was significantly less after fructose. Growth hormone showed a late stimulation after glucose and sucrose but did not rise after fructose intake. Triglyceride levels were significantly increased at 3 to 5 hr. after fructose ingestion.

Adult↗
PubMed1979

Feedback-controlled dextrose infusion during surgical management of insulinomas.

Through the use of a feedback-controlled dextrose infusion system, we obtained continuous monitoring of the blood glucose level in a patient undergoing surgery for multiple pancreatic beta-cell tumors. In addition, this device infused dextrose at variable rates to maintain a predetermined euglycemic level of 90 mg/dl. Before locating the source of excessive insulin production, the maximum dextrose infusion rate of 400 mg/min was required; but after extirpation of multiple insulinomas, the dextrose-infusion rate declined whereas the blood glucose level rose above the preselected level. These results emphasize the usefulness of a monitoring and infusion system not only in protecting the patient from the hazard of hypoglycemia under anesthesia but also as an aid in determining whether all insulin-secreting tumors have been removed.

Adenoma, Islet Cell↗
PubMed1979

Diabetic management by insulin infusion during major surgery.

In five insulin-requiring, uremic diabetic patients undergoing renal transplantation, we infused insulin intravenously at a low rate to maintain plasma glucose levels between 100 and 200 mg/100 ml. In those patients receiving 100 mg or more of prednisone per day and 5 per cent dextrose solution, the hourly infusion rate was determined from tthe following equation: insulin (U) = plasma glucose value divided by 100. When prednisone was not given or when the patient was thin, the ratio became: plasma glucose value divided by 150. Results were compared with those of nineteen similar transplant patients treated with conventional subcutaneous insulin therapy during surgery, and significantly better glucose control was achieved with the low dosage, intravenous infusion.

Adult↗
PubMed1979

Dopamine during alpha- or beta-adrenergic blockade in man. Hormonal, metabolic, and cardiovascular effects.

We studied the contribution of alpha- and beta-adrenergic receptor activation to the cardiovascular, metabolic, and hormonal effects of dopamine. At a concentration of 1.5 mug/kg.min, the infusion of dopamine in 12 normal volunteers was associated with a transient but significant rise in pulse rate, which was prevented by propranolol. Venous plasma glucose did not change throughout the experiments, and a mild increase in plasma free fatty acid levels observed during the administration of dopamine alone was antagonized by propranolol. In contrast, neither the beta-adrenergic blocker, propranolol, nor the alpha-adrenergic blocker, phentolamine, was effective in inhibiting the dopamine-induced rise in plasma glucagon (from 82+/-9 to 128+/-14 pg/ml; P < 0.005) and serum insulin (from 7.5+/-1 to 13+/-1.5 muU/ml; P < 0.005) or its suppression of plasma prolactin (from 8.5+/-1 to 5.2+/-0.8 ng/ml; P < 0.001). Although serum growth hormone levels did not change during the infusion of dopamine alone, an obvious rise occurred in three subjects during the combined infusion of propranolol and dopamine. Whereas some metabolic and cardiovascular effects of dopamine are mediated through adrenergic mechanisms, these observations indicate that this is not the case for the effects of this catecholamine on glucagon, insulin, and prolactin secretion, and thus provide further support for the theory of a specific dopaminergic sensitivity of these hormonal systems in man.

Adrenergic alpha-Antagonists↗
PubMed1979

Phentolamine and the action of somatostatin in man.

The inhibition by somatostatin (SRIF) of basal and arginine-stimulated glucagon, insulin, and glucose levels was compared with that obtained when SRIF was preceded by alpha-adrenergic blockade with phentolamine. No noteworthy differences were observed, except that the characteristic rebound of insulin upon discontinuation of SRIF was significantly lower with phentolamine (P less than 0.01). These results indicate that inhibition of basal and arginine-stimulated glucagon and insulin secretion by SRIF in man is not mediated through activation by alpha-adrenergic receptors.

Adult↗