Catamenial insulin reactions treated with a long-acting gonadotropin releasing hormone agonist.

Exacerbation of a variety of symptoms during the menstrual cycle is a well-described phenomenon. The exact causes of these changes are poorly understood, and no specific and efficacious therapy has been described. We successfully treated a patient with severe catamenial insulin reactions with a long-acting gonadotropin releasing hormone agonist to suppress menstrual function and added a combination of estrogen and progestin to offset any adverse effect of the resultant hypoestrogenemia for 1 year.

Insulin autoimmunity as a cause of hypoglycemia.

"Autoimmune" hypoglycemia is a syndrome consisting of fasting hypoglycemia, hyperinsulinemia, and insulin-binding antibodies in a patient who has never been exposed to exogenous insulin. The stimulus for insulin-antibody formation and the mechanism of the hypoglycemia in this condition remain unknown. Three patients with this rare syndrome had severe hypoglycemia of limited duration. Two had received a drug containing a sulfhydryl group (methimazole and penicillamine) as treatment for an autoimmune disorder (Graves' disease and rheumatoid arthritis, respectively). A third patient who underwent surgery for a suspected insulinoma was found to have pancreatic beta cell hyperplasia. Drugs containing a sulfhydryl group may have a role in the etiology of the syndrome. Additionally, our findings suggest a relationship between circulating insulin antibodies and beta cell hyperplasia.

Flocculation and loss of potency of human NPH insulin.

In late 1986, several vials of Humulin N (NPH human insulin, recombinant DNA origin) came to our attention because of a clumped, white coating on the inside of the vials. To determine the frequency of this phenomenon, we surveyed 100 consecutive patients who used Humulin N. Ten patients had encountered 21 vials of flocculated insulin in the previous 12 mo, reflecting an incidence of 1 per 72 vials. Insulin drawn from affected vials was markedly reduced in potency: 20.9 +/- 3.4 U/ml vs. the labeled potency of 100 U/ml. Several patients reporting flocculated insulin, including one hospitalized with ketoacidosis, experienced unusual and unexplained elevation in blood glucose concentration for several days before flocculation was observed. Patients who use NPH human insulin should be aware of this phenomenon and carefully inspect their vials for evidence of insulin precipitation before each injection.

Localization of abnormal parathyroid glands using thallium-201.

Ectopically located parathyroid adenomas may be difficult to find during initial neck exploration. They account for over 70 percent of missed adenomas found at reexploration. Preoperative localization of parathyroid adenomas would reduce unnecessary dissection and possibly reduce the number of negative results of initial neck exploration. Before reoperative parathyroid surgery is performed, some means of localization is mandatory to detect ectopic adenomas in the neck and mediastinum. Computed tomography and ultrasonography cannot effectively evaluate the mediastinum. Angiography and venous parathyroid hormone sampling are invasive, costly, and tedious to perform. We have shown that thallium-201 will accurately localize ectopic parathyroid adenomas. All 10 adenomas found in positions not immediately adjacent to the thyroid gland were detected by thallium-201 scintigraphy. One was a mediastinal adenoma resected with a median sternotomy. Our results suggest that thallium-201 scintigraphy should be the initial localization procedure of choice before all reexplorations. Its use before initial explorations, as well, will enable the surgeon to immediately direct attention to the area of the localized adenoma. If mediastinal uptake is found to be present, then median sternotomy may be performed during initial surgery provided a thorough neck exploration is performed first.

Radioimmunoassay for partially degraded thyrotropin.

A radioimmunoassay for partially pepsin degraded bovine thyrotropin (bTSH) was developed and used to examine human thyrotropin (hTSH) preparations and sera obtained from patients with Graves' ophthalmopathy for the presence of cross-reactivity. As little as 4 microunits of the hTSH (68/38) reference preparation produced inhibition of binding in the radioimmunoassay, but none of the sera obtained from patients with Graves' disease (n = 26) contained detectable cross-reactivity. These data indicate that there is a substantial amount of partially degraded thyrotropin in human pituitary extracts, but none detectable in the sera of patients with Graves' ophthalmopathy.

Acute complications associated with insulin infusion pump therapy. Report of experience with 161 patients.

We determined the frequency of acute complications associated with insulin pump therapy in 161 insulin-dependent patients followed up for a total of 2,978 patient-months. Diabetes control improved substantively with pump therapy, but 42% of the patients experienced one or more acute complications while using insulin pumps. Infected infusion sites, ketoacidosis, and hypoglycemic coma occurred once in every 27, 78, and 175 patient-months, respectively. More patients experienced ketoacidosis after the onset of pump therapy than in an equivalent interval immediately before the onset of pump therapy. Ketoacidosis also occurred in more patients using pump therapy than in a comparison group of 165 patients receiving conventional insulin injections surveyed during an equivalent period. The frequency of hypoglycemic coma was not significantly changed by pump therapy.

Long-term metabolic control with insulin pump therapy. Report of experience with 127 patients.

To determine the long-term efficacy of insulin-pump therapy, we analyzed trends in glycosylated hemoglobin concentrations in 127 patients with Type I diabetes using insulin pumps for periods ranging from 13 to 47 months. In the first year of pump therapy the average glycosylated hemoglobin concentration improved in 83 per cent of the patients, as compared with the value before pump therapy. Although only 11 of the 127 subjects had normal glycosylated hemoglobin values before pump therapy, 33 had a normal average value during the first full year of pump use (P = 0.0001). This favorable trend persisted for the three-year duration of the study. Seventeen of the 19 patients who subsequently discontinued insulin-pump therapy had improved glycosylated hemoglobin values during the period of pump use. Eleven of the 19 patients remained available for follow-up study; the glycosylated hemoglobin concentration became worse in 7 when they returned to conventional treatment. We conclude that the improvement in metabolic control repeatedly demonstrated in short-term studies with the insulin pump can be maintained for a period of years.

Clinical use of the insulin infusion pump in 100 patients with type I diabetes.

We investigated the efficacy of insulin-pump therapy in insulin-dependent diabetics, aged 18 to 69 years, by comparing the metabolic control achieved in 100 patients using this technique with that previously obtained by conventional insulin therapy. Patients were followed during pump therapy for as long as 15 months. Fasting and nonfasting blood glucose levels (mean +/- S.E.M.) decreased from 201 +/- 6 and 213 +/- 6 mg per deciliter (11.2 +/- 0.3 and 11.8 +/- 0.3 mmol per liter), respectively, to 158 +/- 5 and 145 +/- 3 mg per deciliter (8.77 +/- 0.3 and 8.05 +/- 0.2 mmol per liter) after one month of pump therapy (P less than 0.001). Ninety-three patients had improved blood sugar control; 71 per cent had a mean blood sugar concentration of 150 mg per deciliter (8.3 mmol per liter) or less after six months. Glycosylated hemoglobin values became normal in 44 per cent of 88 patients who had follow-up determinations. In over 500 patient-months there were four episodes of ketoacidosis and five episodes of serious hypoglycemia. Three patients abandoned pump therapy. We conclude that insulin-pump therapy is acceptable to patients and that it can be successfully applied to clinical practice and large-scale research studies.