Plasma cortisol following injection of 1-39 or 1-18 ACTH.

Forty units of 1-39 ACTH of animal origin or 0.4 mg of synthetic 1-18 ACTH administered at 8 A.M. via either the intramuscular route to 10 subjects with intact adrenocortical function produced comparable increases in plasma cortisol at 1, 2, and 6 hours. The increase in plasma cortisol lasted at least 6 hours but less than 12 hours after intravenous crystalline 1-39 ACTH and at least 16 hours but less than 24 hours after the same dose of 1-39 ACTH administered as a depot gel via the intramuscular route. However, neither intravenous nor the intramuscular injection of 1-39 ACTH produced increases that were still evident at 24 hours. Following either the intramuscular or intravenous injection of 0.4 mg of the synthetic 1-18 ACTH, the plasma cortisol increase was still evident at the 24th hour. Our findings indicate that the plasma cortisol responses to either 40 units of exogenous 1-39 ACTH of animal origin or to 0.4 mg of a synthetic 1-18 ACTH are most consistent in the first 6 hours following either intravenous or intramuscular injection.

The so-called diabetes mellitus of ataxia telangiectasia.

Achados de 26 casos da literatura, somados aos 3 casos aqui descritos, sugerem que cerca de um terco dos pacientes com ataxia telangiectasia tem glicemia de jejum normal com hiperglicemias apos a ingestao oral de glicose. Estes achados enquadram-se nos criterios para tolerancia a glicose diminuida do assim chamado diabetes quimico. O diabetes do tipo II estava presente em apenas um dos 29 pacientes e nenhum deles tinha a deficiencia total de insulina que se encontra no diabetes tipo I. Entao, as hiperglicemias da ataxia telangiectasia representam apenas tolerancia diminuida a glicose e sao claramente distintas do diabetes, seja tipo I ou II. A frequente hiperinsulinemia basal ou apos sobrecarga de glicose de ataxia telangiectasia, com ou sem hiperglicemias, e compativel com a hipotese de bloqueio ou diminuicao de numero de receptores para insulina

Discrepancies between glycosuria and home estimates of blood glucose in insulin-treated diabetes mellitus.

Glycosuria can be a misleading indicator of blood or plasma glucose levels. Thus glycosuria may be present when blood glucose levels are within the normal fasting or postprandial range, and it may be absent when the blood glucose is distinctly above normal. In such patients the blood glucose must be measured, preferably by the patient, as a guide to insulin and other therapy. However, urine glucose tests are valid indicators in a minority of patients and are essential in all patients for the detection of acetone.

Parameters of good control in diabetes mellitus.

Optimal control of diabetes should achieve not only euglycemia and normal levels of glycosylated hemoglobin but also absence of the reversible concomitants of diabetes such as red cell rigidity, hyperlipidemia, increased capillary permeability, enlargement of the kidneys, proteinuria, etc. Unfortunately, in most patients consistent euglycemia cannot be assured even with two daily injections of insulin. However, self-measurement of blood glucose as a guide to insulin taken before each meal and at bedtime can, in selected patients, increase the frequency of normal glucose levels without undue hypoglycemia.

Remissions of diabetes mellitus after weight reduction by jejunoileal bypass.

Limited weight loss following jejunoileal bypass in 24 diabetic persons who were still distinctly overweight five to ten months after a mean weight decrease of 78 lbs. was accompanied by a return of normal fasting glucose and insulin levels, normal insulin responses, and a decrease in glucose intolerance. The glucose disappearance rate had improved in the majority of the subjects, but only three had attained values in the normal range. Concomitants of the undue hyperglycemia and/or obesity included labile and, rarely, sustained hypertension and/or cardiomegaly. The blood pressure returned to normal but heart size did not change. Electrocardiographic abnormalities noted in about one-half of the patients persisted after the operation. Triglyceride and cholesterol levels decreased. No patients had diabetic retinopathy visible on funduscopy. Proteinuria did not change in three patients. Neuropathy consisting of absent ankle reflexes and/or decreased vibration perception noted in one-half of the subjects persisted despite the improvement in carbohydrate metabolism.

Jet injection of insulin during self-monitoring of blood glucose.

Insulin-dependent diabetes mellitus has been treated with four jet injections of insulin (regular insulin before each meal and intermediate insulin at bedtime) during self-monitoring of blood glucose levels. The blood glucose levels generally remain within 60 and 150 mg/dl.

Unresponsiveness to exogenous TSH in obesity.

(1). Assessment of thyroidal and other indices in 275 instances of obesity with body weight excesses up to 200 percent or more of the ideal revealed absent thyroidal I131 uptake responses to TSH in about one out of five patients. Moreover, basal thyroidal I131 uptake of 10 percent or less, prolongation of ankle reflex time, or high levels of serum cholesterol were present in a minority. Also, occasional instances of unduly elevated serum TSH titers were found. Some of the indices deviated from normal more often with the greater excesses of body weight or with increased age. (2). These findings are consonant with a hypothesis that routine thyroidal or related indices are sporadically abnormal in massive obesity almost always without overt hypothyroidism or myxedema, that total unresponsiveness to exogenous TSH is surprisingly frequent, and that such unresponsiveness represents an unexplained endocrine anomaly in association with gross overweight. (3). Our data suggest that some obese persons are not able to respond to exogenous TSH, nor, presumably, to increases of endogenous TSH. This could result in an economy of caloric expenditure and play a contributory role in the genesis or the perpetuation of the obesity.

Thyroid hormone-like effects without thyrotoxicosis during one year's therapy with NA-DT3 for hypercholesterolemia.

A thyroid hormone analogue, sodium dextro-triiodothyronine (NaDT3), at a dosage of 1 mg/day for 1 or 2 yr, decreased serum cholesterol levels about 30% in 26 hyperlipidemic adults. There were less sustained decreases in the serum phospholipids, and occasional lowering of the serum triglycerides, but no effects on body weight, blood pressure, or pulse rate. Changes recognized as variable concomitants of spontaneous or induced thyrotoxicosis, such as transient increases in fasting blood glucose, calcium, and globulin, persistent rises in alkaline phosphatase, and nonsustained decreases in hematocrit are consonant with the fact that Na-DT3 exerts about one tenth of the thyroid hormone activity of LT3. These changes, however, appear to represent actions of iodinated amino acids apart from those effects that result in clinical thyrotoxicosis.

Endocrine and metabolic indices during progestin (quingestanol) therapy.

Quingestanol at 300 y/day was well tolerated during 1 to 12 months of therapy of pre-menopausal and menopausal women with minimal changes, if any, in a battery of routine endocrine and metabolic indices. Serum inorganic phosphorus levels were slightly above the pre-therapy range but still within normal limits during the 12 months of treatment and the mean relative blood volume or hematocrit during the latter 6 months was slightly above the starting value.

Clinical and ultrastructural observations in a kindred with normo-hyperkalaemic periodic paralysis.

Electron microscopic studies of muscle biopsies from clinically unaffected sibs in a family with normo-hyperkalaemic periodic paralysis with variable myotonia have revealed dilatation of the sarcoplasmic reticulum similar to that observed in affected members. This supports the view that such dilatation is not only a significant and likely primary ultrastructural change but that it may precede clinical manifestations and represent an anatomical marker of the genetic trait. Identical dilatation of the sarcoplasmic reticulum was found in the clinically unaffected father of the affected and unaffected grandchildren of the propositus. This raises the possibility that this non-consanguineous member contributed to the genetic trait or its manifestations in the grandchildren of the index patient since similar dilatation of the sarcoplasmic reticulum was not observed in the muscles of healthy control subjects.

Prolonged progestin (quingestanol) therapy of menopausal diabetic women.

The reduction of high serum LH levels toward or to normal in diabetic women in the menopausal range recorded during the first year of treatment with a synthetic progestin, 17-alpha-ethynyl-19-nortestosterone acetate, 3-cyclopentylenol ether (quingestanol acetate), was maintained during the second and third years of daily ingestion of this steroid. Normal LH and normal or high FSH levels prior to therapy were not affected. Other endocrine indices, including serum PBI and T4, plasma 11(OH) corticosteroids, serum growth hormone titers, insulin responses to oral glucose, and urinary excretion of 17-ketosteroids, Porter-Silber chromogens, and 11-desoxycortisol metabolites, estrogens, and creatinine remained relatively unchanged during quingestanol therapy. At the 36th month of treatment, a small increase in fasting blood glucose levels with greater hypoglycemia after oral carbohydrate was noted, but this probably reflected the natural history of treated diabetes mellitus. The decrease in urinary steroid responses to partial blockade of adrenal 11-beta hydroxylase by metyrapone observed in the 12th month of quingestanol therapy was not evident at the end of 24 and 36 months of treatment. Quingestanol therapy was associated with maintenance of the increase in serum sodium from low-normal to mid-normal concentrations noted during the first year of treatment. Serum chloride increases were less frequent. Other serum electrolytes, solutes, proteins and other nitrogenous constituents, lipids, and enzymes and formed blood elements generally fluctuated within the pre-therapy ranges. Body weight, blood pressure, pulse rate, electrocardiograms, and perception of vibrations were about the same prior to and at the completion of the three-year course of therapy. The steroid was well tolerated.