Biomedical subjects
Publications and source records attributed to V V Gossain.
With the recent availability of human insulin, we have entered a new era in therapy for diabetes mellitus. Human insulin is not a cure for diabetes; however, no disadvantages are known to be associated with its use at present. Human insulin costs less than the other purified insulins, and because of its potential advantages, human insulin deserves consideration for use in all newly diagnosed insulin- dependent diabetics.
It is generally recognized that smoking is associated with an increased risk for the development of coronary artery disease. Since it has been suggested that increased plasma renin activity (PRA) may be a risk factor for cardiovascular disease, PRA was measured in a group of smokers and nonsmokers. PRA was measured under basal conditions, following intravenous (IV) furosemide administration and after a short burst of smoking. In addition, the effect of nicotine on renin secretion was evaluated in vitro. Smoking was associated with a significant increase in pulse rate and systolic blood pressure, but no significant change in diastolic blood pressure in both groups. Basal PRA was similar among smokers and was not significantly influenced by smoking in either group. PRA increased significantly following IV administration of furosemide, but there was no significant difference between the two groups. Incubation of rat kidney slices with nicotine also did not result in increased renin secretion. These findings confirm that smoking affects the cardiovascular system, but no significant effect of smoking on PRA was observed both in vivo and in vitro experiments. These findings suggest that the increased risk for the development of coronary artery disease associated with smoking is not mediated by increased PRA.
Effect of smoking on the plasma levels of cortisol, growth hormone, and prolactin was evaluated in a group of smokers and nonsmokers. Plasma levels of these hormones were measured under basal conditions and following a short burst of smoking. In addition, to determine the mechanism of action of nicotine on the release of these hormones, rat renal cortical slices were incubated with nicotine and the generation of cyclic AMP was measured in vitro. Increasing concentrations of nicotine in the incubation medium resulted in increased generation of cyclic AMP. Basal levels of plasma cortisol were similar for both smokers and nonsmokers. After smoking, the cortisol levels increased significantly among smokers only and the levels achieved were significantly higher compared with nonsmokers. Mean prolactin curves were higher among nonsmokers compared with smokers, whereas growth hormone levels were similar in the two groups. These data suggest that the effects of smoking on pituitary/adrenal hormones differ among smokers and nonsmokers and that these effects may be mediated through increased generation of cyclic AMP induced by nicotine.
The mortality among patients with diabetic ketoacidosis (DKA) has been reported to be as high as 5% to 15%. To determine the outcome of DKA, we reviewed the charts of all patients admitted to one of our community affiliated hospitals for the period of January 1979 to December 1981. We identified 66 episodes of DKA in 42 patients. All patients received intravenous fluids. Insulin was given by continuous infusion in six (9%), by bolus only in 14 (20%), and by a combination of the two in 46 (71%). The mean time for recovery from DKA was similar in all three subgroups. All patients recovered from DKA and were discharged from the hospital; no deaths occurred. We conclude that it is possible to treat DKA effectively in a community hospital, with mortality approaching zero.
Allergy to insulin is extremely rare and is, in part, due to the differences in amino acid sequence of animal and human insulin. We report here a 37-year-old, white, pregnant woman who was allergic to beef/pork, purified pork, as well as human insulin. She reacted with a wheal and flare reaction in response to intradermal human and purified porcine insulins. She was desensitized to human insulin in order to continue insulin therapy during pregnancy. The course of this patient emphasizes that some patients are allergic even to human insulin and may require desensitization prior to insulin therapy.
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A 23-year-old woman presented with primary hypothyroidism and inability to lactate following uneventful childbirth. Endocrine evaluation revealed that she had autoimmune hypothyroidism and deficiencies of ACTH and prolactin. Despite partial hypopituitarism, she again conceived spontaneously, had an uneventful pregnancy and delivery but failed to lactate. Radiologic evaluation of the hypophysis, including CAT scan, was normal, and antibodies to anterior pituitary cells were not detected. The etiology of the pituitary insufficiency might have been autoimmune hypophysitis , a recently described entity in which anterior pituitary, along with the other endocrine glands, is destroyed by an autoimmune process. The clinical course suggested that women with pituitary insufficiency, although rare, are able to conceive and carry the pregnancy to term. Our patient illustrates that prolactin insufficiency does not preclude a successful outcome of pregnancy but can result in no lactation.
Effects of oral contraceptive agents (mestranol and norethindrone) on carbohydrate metabolism were evaluated in a group of 18 healthy young women. Plasma glucose, insulin, and glucagon responses were evaluated after a glucose load (oral and intravenous) and an amino acid challenge (oral and intravenous). The oral glucose tolerance was normal and was unaltered by the use of oral contraceptive agents. However, following intravenous administration of glucose, plasma glucose levels were slightly but significantly elevated when subjects were using oral contraceptives. Plasma insulin concentrations were slightly but significantly higher than control values in response to oral and intravenous administration of glucose while subjects were using oral contraceptives. Plasma glucagon concentrations in response to oral and intravenous glucose were similar whether the subjects were using oral contraceptive agents or not. No significant differences from control values were observed after oral and intravenous amino acid challenges when subjects were using oral contraceptive agents. Mild elevations of glucose and insulin without any significant change in glucagon concentrations suggest that glucagon levels do not play a major role in the development of insulin resistance seen in some patients using oral contraceptive agents.
We describe a female patient with insulin-dependent diabetes mellitus and autoimmune thyroiditis. Transient hyperthyroidism developed in the postpartum period in two successive pregnancies, followed by temporary hypothyroidism with eventual full recovery. The clinical course was consistent with "silent thyroiditis" and the circumstantial evidence suggested that alterations in the antibody titers due to pregnancy may have been responsible for these episodes. This case study serves to emphasize that hyperthyroidism and hypothyroidism in the postpartum period may be transient, and this fact should be considered in therapeutic management of such a patient.
Pancreatic glucagon, the hyperglycemic hormone secreted by the alpha cells of the islets of Langerhans, promotes glycogenolysis, neoglucogenesis, lipolysis, and ketogenesis. Several abnormalities of glucagon secretion have been described in diabetes mellitus. These include absolute or relative hyperglucagonemia, exaggerated response to a protein load, and insufficient response to hypoglycemia. Although glucagon's role in diabetes has been challenged, the bulk of the evidence suggests that while insufficiency of insulin is the major abnormality involved, inappropriately elevated glucagon levels contribute to worsening of hyperglycemia. It is suggested that lowering of glucagon levels will result in better control of diabetes. To some extent, this can be achieved by continuous infusion of insulin in insulin-dependent diabetics. In addition, development of analogs of somatostatin holds promise of therapeutic benefit in both insulin-dependent and non-insulin-dependent types of the disease.
PRA and the inactive renin which is activated by cold (IR-C) were studied in a group of normal subjects and in patients with diabetes mellitus with and without the presence of nephropathy. The amount of renin activity, as measured after incubation of plasma at -5 C for 4 days, was called cold renin activity (CR. PRA was measured by a standard method. The difference between CR and PRA was used as a measure of IR-C. CR and PRA measurements were made on a normal salt diet, on a low salt diet, and after the administration of furosemide. In all three groups, CR and PRA were higher after salt depletion and following the administration of furosemide. A moderate but significant increase in IR-C was observed with these maneuvers in both groups of diabetes but not in normals. PRA and IR-C varied under different experimental conditions independent of each other. Although both PRA and IR-C were correlated with CR, no correlation was observed between PRA and IR-C. These findings suggest, although they do not prove, that the inactive renin is not a precursor of active renin. CR and IR-C were not significantly different between groups. PRA in patients with uncomplicated diabetes mellitus was normal or slightly high, whereas it was suppressed in patients with diabetes mellitus and nephropathy. The mechanism of suppressed PRA in patients with diabetes mellitus is not clear and may be related to the onset of renal disease itself.
Pregnancy in hypopituitarism is distinctly rare. The authors have recently seen a 26-year-old white woman who had amenorrhea. Endocrine evaluation demonstrated hypogonadotropic hypogonadism, decreased adrenocorticotropic hormone reserve, and low normal thyroid function. The patient, treated with estrogen replacement for a few cycles and with physiologic doses of hydrocortisone, spontaneously conceived and delivered a premature infant. The circumstantial evidence favored the occurrence of a spontaneous ovulation. The possibility that prior administration of cyclic estrogens and/or physiologic doses of cortisone facilitated gonadotropin release and subsequent ovulation remains unclear but cannot be completely excluded. The onset of premature labor may have been related to hypofunction of the anterior pituitary.
Twelve normal, healthy, clinically and biochemically proven euthyroid volunteer subjects (age 19-35) were administered a standard glucose tolerance test (100 g glucose orally) and thyroxine (T4), triiodothyronine (T3) and reverse triiodothyronine (rT3) levels were determined by specific radioimmunoassays to determine the acute effect of glucose and insulin on peripheral monodeiodination of thyroxine. The fasting levels of T4, T3, rT3 and free thyroxine were 82.4 nmol/l, 1.7 nmol/l, 0.52 nmol/l, and 0.22 nmol/l, respectively, and these levels were unchanged during the 3 hours post-glucose load. The rise and fall of glucose and insulin levels were typical of the standard responses normally observed in the glucose tolerance test. The variations in insulin and glucose levels were not correlated with thyroid hormone concentrations at any interval during the test. It is therefore concluded that dietary glucose does not acutely cause shifts in peripheral monodeiodination of thyroxine in healthy euthyroid subjects.
The effect of tolbutamide on renin secretion in rats was studied in vivo, and in vitro. Administration of tolbutamide in doses of 12.5 and 25 mg/kg body wt ip to two groups of rats produced no significant change in plasma renin activity compared to the control group. In the in vitro experiments renal cortical slices were incubated with increasing concentrations of tolbutamide (0--4 mg/ml). No significant increase in the net renin production was observed, whereas the concentration of cyclic AMP increased significantly in the incubation medium. These findings suggest that in the intact rats tolbutamide does not increase plasma renin activity. In the renal cortical experiments although tolbutamide increased cyclic AMP production, the increase may not have been sufficient to stimulate the net renin production. These results are of biological significance because of the possible effects of tolbutamide and increased plasma renin activity on the cardiovascular system.
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Plasma glucose, insulin, and alpha-cell glucagon profiles were examined in ten adults with uncomplicated primary hyperparathyroidism before and 8-12 week after surgical removal of a single parathyroid adenoma. Treatment restored abnormal serum calcium and phosphorus concentrations to a normal range and reduced serum parathyroid hormone levels from 47 +/- 4 to 16 +/- 4 mu 1 Eq/ml (normal = 0-40). Plasma glucose curves during 100-g oral glucose tolerance, 30 min intravenous glucose (1.5 g/min), or arginine infusions (1.0 g/min) did not differ before and after surgery. However, basal and peak insulin concentrations were higher before treatment during these tests (p less than 0.05). Basal glucagon levels were unaffected by hyperparathyroidism (72 +/- 7 versus 77 +/- 7 pg/ml). Peak 30 min values after arginine provocation were also similar before and after treatment as was maximal suppression of basal glucagon during glucose infusions. Four patients also received 400 g lean beef meals. Glucose and glucagon responses over 240-min periods were nearly identical before and after surgery despite higher insulin levels before treatment. It is concluded that elevated serum parathyroid hormone and plasma insulin concentrations in primary hyperparathyroidism do not relate to abnormalities of plasma alpha-cell glucagon in the basal state or after glucose, arginine, or protein administration.
Two patients with psychogenic polydipsia developed hyponatraemia, one in association with administration of hydrochlorothiazide and the other with that of tolbutamide. It is suggested that the increased fluid intake in such patients may make them more susceptible to the development of hyponatraemia from thiazide or sulphonylurea compounds.
An unusual finding of elevated free thyroxine (FT4) concentration coexistent with familial low thyroxine-binding globulin (TBG) is described in a euthyroid patient. Clinical and other laboratory tests were normal and consistent with a clinical diagnosis of euthyroidism. Low TBG (TBG capacity 3-10 mug/100 ml) was confirmed by various electrophoretic procedures and by TBG immunoassay (0.9 mg/100 ml). Serum T4 concentration was low (2.0-5.5 mug/100 ml). Triiodothyronine (T3) resin uptake was increased (88-93%) and the free thyroxine index was normal. Twenty-four-hour thyroidal 131I uptake was normal and varied between 13-20%. Serum thyroid-stimulating hormone (less than 2 muunits) and T3 concentration (80 ng/100 ml) were also normal. Long-acting thyroid stimulator (LATS) was not present. Free T4 concentration measured by dialysis procedure was markedly elevated (9.2-12.1 ng/100 ml). Pulse T3 and T4 tracer kinetic studies by the single compartmental method revealed accelerated blood disappearance of T4 (t 1/2 = 3.7 days) but normal disappearance of T3 (t 1/2 = 2.1 days). Extrathyroidal hormonal iodine pool (569 mug) was in the range of normals. T4 degradation rate (144 mug/70 kg/day) was moderately elevated over the euthyroid mean values, but was still close to or within the upper normal range. T3 degradation was normal (34 mug/day). Failure to develop hyperthyroidism in the presence of elevated free T4 levels, but with normal T3 concentration and dynamics, may suggest that T3, not T4, plays a major role in regulating metabolic activity; alternatively, euthyroidism in this low-TBG patient despite elevated free T4 concentration may simply be explained on the basis of a daily T4 disposal rate which was not clearly abnormal.