Alton R. Sharpe

The influence of renal disease on the insulin I131 disappearance curve in man

Abstract Insulin I 131 disappearance curves were done in 3 normal patients donating a kidney to an uremic relative. There was no significant difference in the slopes of the curves done before and 2 weeks after nephrectomy. Clearance studies done before and 2 weeks after nephrectomy showed a significant reduction in inulin, PAH and creatinine clearance. Insulin I 131 disappearance curves were also done in 4 uremic patients receiving a renal homotransplant. They were done while the patient was uremic and again 2 weeks after renal transplantation when renal function was normal. A significant delay in the disappearance of insulin I 131 was noted in the uremic state. After transplantation, the slope of the insulin I 131 disappearance curve approximated that seen in the normal patients (donors). It is suggested that with the onset of renal disease, insulin-degradation is delayed so that it circulates undegraded for a prolonged period of time.

Abnormal carbohydrate metabolism in renal failure

From this review 2 facts become apparent:(1) that diabetics who develop renal failure have an amelioration of their diabetes, and (2) that an alteration of carbohydrate metabolism does exist in uremia which simulates diabetes mellitus and can be differentiated from true diabetes by the normal response to a tolbutamide tolerance test.71 The basic mechanisms behind this metabolic paradox lie in a failure of hepatic glycogenesis and in altered insulin metabolism. Several investigators have implicated a block of hepatic glycogenesis as the prime mechanism of production of the carbohydrate abnormality in uremia.52,63–66 Although the blood sugar may be elevated there seems to be an inability to convert into liver glycogen. The liver in uremia is similar to that seen in starvation, that is, a fatty liver with little or no glycogen stores. A uremic given a carbohydrate load can only dispose of it by utilizing it peripherally which he cannot do fully and the result of this lack of hepatic glycogenosis is an abnormal glucose tolerance curve. By the same token, if a uremic is given exogenous insulin he increases his peripheral utilization of glucose, drops his blood sugar level and has difficulty maintaining it at normal levels because there is no hepatic glycogen for glycosis. We feel this also is the mechanism of increasing “insulin sensitivity” in diabetics with renal failure. There seems to be an impairment of insulin degradation in uremia. The main sites of insulin degradation in the body is the liver and kidney. Several investigators have shown that the uremic kidney is no longer able to degrade insulin. It seems logical to presume the other major sites in insulin breakdown, the liver, is compromised in its function to degrade insulin. If uremia affects it so adversely that it no longer forms glycogen, it is not unreasonable to postulate that it adversely affects insulin breakdown. The postulate cited above, and whether insulin antibodies and/or binding play a significant role in uremia, await future work for clarification.

Gallium Scanning and Inflammatory Lesions

Excerpt To the editor: Although originally intended for use as a bone-scanning agent,67Ga was seen to localize in soft tissue tumors (1). Littenberg and colleagues (Ann Intern Med79:403-406, 1973) ...

Thyrotropin-induced hyperthyroidism: evidence for a common progenitor stem cell.

A 36-year-old woman with hyperthyroidism, elevated blood thyroid-stimulating hormone (TSH) and α-subunit levels, amenorrhea, hyperprolactinemia and no evidence of acromegaly, was found to have a pituitary adenoma containing TSH, α-subunit and growth hormone by immunohistochemistry. Preoperative testing revealed elevated TSH and α-subunit with no response to thyrotropinreleasing hormone (TRH) but a normal response in prolactin to TRH. Culture of the pituitary cells showed release of TSH, α-subunit and prolactin. In vitro, TRH failed to cause TSH discharge; however, it increased prolactin concentrations in the culture medium. Triiodothyronine, added to the pituitary cell culture, resulted in no inhibition of TSH and prolactin discharge. By electron microscopy, the adenoma cells showed features of thyrotrophs. However, some adenoma cells contained fibrous bodies characteristic of some growth hormone cell tumors and acidophil stem cell adenomas, suggesting that the adenoma originated in a common progenitor cell.

Glomerular filtration rate in children with advanced chronic renal failure: methods of determination and clinical applications.

The rationale, significance and pitfalls of currently available methods for the determination of glomerular filtration rates in children with advanced chronic renal diseases are reviewed. Normal renal clearances in infants and children from birth to adulthood are presented. Methods of serial measurements of renal function, especially by the reciprocals of serum creatinine concentrations, are evaluated. They are applied clinically to monitor the effectiveness of conservative and new modalities of treatment, such as dietary supplementation with essential amino acids plus their keto analogues, and to determine that 1,25-dihydroxyvitamin-D3 treatment of renal osteodystrophy does not accelerate the deterioration of renal function in children with chronic renal insufficiency.

Relative decreased splenic uptake of Tc-99m-sulfur colloid in patients with pancreatic carcinoma

Relative spleen/liver activity ratio was determined from posterior projection images using a photodensitometric method. Ratios from scans of 22 patients with proven pancreatic carcinoma (12 from rectilinear scans and 10 from scintillation camera images) were determined and compared to studies from patients documented as normal and to randomly selected liver/spleen imaging studies which had been previously interpreted as normal. The mean ratio from the pancreatic carcinoma group was significantly lower than the means of the respective normal groups (p[t] < .0001 for rectilinear scans and p[t] < .001 for scintigrams). There was no significant difference between the means of the proven normal and randomly selected normal groups or between the two pancreatic carcinoma groups. Splenic vascular alteration is discussed as a possible reason for decreased splenic distribution of Tc-99m-sulfur colloid in this patient group.