Clinical and Physiologic Studies Using Diazoxide in the Treatment of Hypoglycemia*

Abstract

The initial observation by Drash and Wolffl that diazoxide was beneficial in the treatment of patients with certain types of hypoglycemia has now been adequatelyIn general, hypoglycemia associated with increased plasma insulin has been most amenable to diazoxide treatment, but other conditions, such as glycogen storage disease, have also responded.8 Although diazoxide interferes with pancreatic insulin p r o d u~t i o n , 5 ,~.~,~~ evidence has accumulated that this is not the only mechanism by which it elevates the blood glucose.eJ2 The present studies were undertaken to assess the clinical usefulness of diazoxide in a patient with hypoglycemia secondary to a metastatic malignant mesothelioma. For comparative purposes, another patient with metastatic islet cell carcinoma was also treated, and some studies were done to learn more about the mechanism by which the drug inhibits pancreatic insulin release. Methods and MaterialsPatient C.C. : This 33-year-old male with proven metastatic islet cell carcinoma has been reported previ0us1y.l~ Despite the presence of proven hepatic metastases since 1960, he remained relatively asymptomatic as long as he ate frequently and did not engage in much physical activity; increased activity was associated with symptomatic hypoglycemia. Fasting blood glucose values were low normal. Although intermittent courses of glucagon injections increased his tolerance for physical activity, they still did not permit him to return to work. His weight gradually increased from 195 pounds to 230 pounds. ResuIts of a physical examination were normal except for a palpable liver edge at the right costal margin. Diazoxide, 100 mg b i d . (twice a day) was started in February, 1965. The dosage was gradually increased to 400 mg b.i.d., at which time hyperglycemia and glycosuria occurred, and the dosage was reduced to 200 mg b i d . He has been satisfactorily maintained on this dose, and has been able to return to work. Symptoms of hypoglycemia returned only when he omitted his medication. Excessive hair growth has been noted but has not been troublesome. He has not had any fluid retention. Results of urinalysis and hematologic studies were in the normal range. BUN was 15 mg%, and the uric acid 3.8 mg%. Hepatic function studies and liver scan showed normal results.Patient A.H.:** This 54-year-old female was well until 1959, when she developed anorexia and had a 40-pound weight loss. An abdominal tumor was removed at that time, and later review of the histologic sections confirmed a diagnosis of malignant mesothelioma. Following surgery she was asymptomatic. In 1964, a hysterectomy was done for a prolapsed uterus. Metastatic disease was found at that time, and a biopsy again indicated malignant mesothelioma. She was asymptomatic until April, 1965, when she was admitted to another hospital These studies were supported by grants AM-08333, AM-09159 and FR-56 from the