Gerald S. Kidd

Pancreatic Diabetes Mellitus

Diabetes mellitus caused by pancreatic exocrine disease is a unique clinical and metabolic form of diabetes. The diagnosis of pancreatic diabetes caused by chronic pancreatitis may be elusive because it is occasionally painless and often not accompanied by clinical malabsorption until after hyperglycemia occurs. Diabetic patients with pancreatic calcification or clinically demonstrable pancreatic exocrine dysfunction will manifest the unique aspects of pancreatic diabetes described herein. Like other forms of diabetes, the primary hormonal abnormality in pancreatic diabetes is decreased insulin secretion. Patients with this disorder are unique in that they have low glucagon levels that respond abnormally to several physiological stimuli, blunted epinephrine responses to insulin-induced hypoglycemia, and malabsorption. In addition, they often have concomitant alcohol abuse with hepatic disease and poor nutrition. These characteristics result in increased levels of circulating gluconeogenic amino acids, decreased insulin requirements, a resistance to ketosis, low cholesterol levels, an increased risk of hypoglycemia while on insulin therapy, and the clinical impression of brittle diabetes. Retinopathy occurs at a rate equal to that of insulin-dependent diabetes but may be less severe in degree. Other complications of pancreatic diabetes have been less well studied but may be expected to be seen more frequently as these patients survive longer. The characteristics of pancreatic diabetes suggest that a conservative approach be taken in regard to intensive insulin therapy and tight blood glucose control.

Skeletal responsiveness in pseudohypoparathyroidism: A spectrum of clinical disease

Three cases of pseudohypoparathyroidism with roentgenographic evidence of hyperparathyroid bone disease are described. Renal resistance to exogenous parathyroid hormone (PTH), the hallmark of pseudohypoparathyroidism, was documented by markedly blunted or absent urinary phosphate and cyclic AMP responses to parathyroid extract. At the time of diagnosis all patients were hypocalcemic and hyperphosphatemic with elevated serum alkaline phosphatase levels and subperiosteal resorption noted on skeletal films. Bone biopsy in one patient revealed a histologic appearance consistent with hyperparathyroidism. Serum PTH levels, measured in two patients while they were hypocalcemic, were elevated. None of the patients had short stature, brachydactyly, subcutaneous calcification or mental deficiency. These cases are compared to the 15 well-documented cases previously reported. The presently available information on pseudohypoparathyroidism indicates a variable skeletal response to PTH mediated by several factors extrinsic to bone and suggests that pseudohypoparathyroidism with hyperparathyroid bone disease is one extreme of a clinical spectrum of skeletal responsiveness to PTH. This disorder is part of an expanding clinical picture which makes pseudohypoparathyroidism a diagnostic consideration in any patient with unexplained hypocalcemia, hyperphosphatemia, elevated alkaline phosphatase levels or metabolic bone disease.

Lactic Acidosis in Pheochromocytoma

Lactic acidosis is not generally recognized as a complication of pheochromocytoma. We review three prior case reports of lactic acidosis in patients with pheochromocytoma and one report of lactic acidosis following epinephrine poisoning and describe an additional case report of a patient with lactic acidosis in whom an unsuspected pheochromocytoma was discovered at autopsy. The pathophysiology of lactic acidosis in pheochromocytoma is related to the effect of catecholamines on intermediary metabolism and the peripheral circulation. Although the possible development of lactic acidosis in persons with pheochromocytoma is underappreciated, the differential diagnosis of lactic acidosis should include this tumor.

Fine needle aspiration of the thyroid: Use in an Average health care Facility

Fine needle aspiration of the thyroid is suggested as an initial diagnostic procedure in the evaluation of thyroid nodules. Some proponents of the procedure, however, believe that fine needle aspiration should be restricted to centers in which each operator obtains at least 500 biopsy specimens annually. Reviewed were 155 biopsy specimens obtained over three and one-half years, and the sensitivity of fine needle aspiration was determined to be 100 percent, the specificity to be 47.4 percent, and the accuracy to be 73 percent. A review of the literature revealed the sensitivity in larger series to range between 92 and 98 percent, specificity to range between 52 and 99.5 percent, and accuracy to range between 56.1 and 91.3 percent. The surgical yield of carcinoma was 64 percent in patients evaluated with fine needle aspiration, whereas the yield was 26 percent in those who underwent surgery without fine needle aspiration. These results appear to justify the use of fine needle aspiration in the evaluation of nodular thyroid disease at average-sized health care centers.

A longitudinal assessment of bone loss in women with levothyroxine-suppressed benign thyroid disease and thyroid cancer.

To determine if differeing degrees of levothyroxine (LT4) suppression therapy for benign and malignant thyroid disease are associated with proportionately increased rates of bone loss, this longitudinal assessment of bone densitometry changes (single-photon and dual-photon absorptiometry) was conducted in three groups of subjects: 24 thyroid cancer patients who were treated with near-total thyroidectomy, radiodine ablation, and aggressive LT4-suppression; 44 patients who were treated with more conservative LT4-suppression for benign thyroid disorders; and 24 normal controls. Bone densitometry values were adjusted for age, weight, heigh, and menopausal status. The rates of bone loss in benign LT4-suppressed patients were greater than those in controls at the midradius, distal radius, lumbar spine, and femoral neck. The rates of loss in the thyroid cancer patients were also greater than those in the controls at all four sites and greater than in the benign LT4-suppressed patients at the midradius, distal radius, and femoral neck but not in the lumber spine. Rates of bone loss were not significantly correlated with LT4 dose or with the serum level of T4 or TSH. LT4-suppression therapy for benign throid disease is associated with accelerated bone loss. More aggressive LT4-suppression for thyroid cancer is associated with even greater bone loss, particularly in cortical bone regions. These risks must be weighed against the benefits of LT4 therapy in individual patients.

Lithium-associated thyrotoxicosis.

Primary hypothyroidism developed in a 57-year-old woman treated for eight years with lithium carbonate for manic-depressive illness, and nine months later she became thyrotoxic. Although autoimmune disease appeared to be responsible, lithium was suspected to play a contributory role in both phases of her illness. This is the first reported case of hyperthyroidism following hypothyroidism in a lithium-treated patient. The 24 reported cases of lithium-associated thyrotoxicosis and the possible mechanisms that may explain this poorly understood phenomenon are also reviewed.

Pure primary hyperaldosteronism due to adrenal cortical carcinoma

A 47-year-old woman is described who had pure primary hyperaldosteronism due to an adrenal cortical carcinoma. This may represent the first such case in which modern laboratory tests allowed specific diagnosis and exclusion of hypersecretion of other adrenal steroids, and also the first reported case in which modern localizing procedures have been utilized. Other interesting facets of the case include calcification of the tumor, visualization with 131l iodomethylnorcholesterol , metaplastic histologic changes, and coexistent bilateral renal artery fibromuscular disease.

Mild chronic watery diarrhea-hypokalemia syndrome associated with pancreatic islet cell hyperplasia: Elevated plasma and tissue levels of gastric inhibitory polypeptide and successful management with nicotinic acid

A 46 year old woman is described who had a 13 half year history of watery diarrhea associated with hypokalemia and hypochlorhydria. The diarrhea was secretory as measured by triple lumen tube perfusion and was associated with an increased concentration of fasting plasma immunoreactive gastric inhibitory polypeptide (GIP) of 750 pg/ml which was stimulated to 4,000 pg/ml after a standard meal. The diarrhea decreased after partial pancreatectomy. Diffuse pancreatic islet cell hyperplasia was present and, although GIP was unmeasureable in the pancreas of normal subjects, it was at least 83 ng/g wet weight in this patient. Postoperatively, the patients diarrhea responded dramatically to the oral administration of nicotinic acid.

Case Report: Hyperthyroidism Following Hypothyroidism

ABSTRACT Two patients are presented who developed autonomous thyrotoxicosis following a diagnosis of primary hypothyroidism. In one of these patients, antibodies to the TSH receptor were typical of Graves’ disease when measured as thyrotropin binding inhibitor immunoglobulins (TBII) and as human thyroid adenylate cyclase stimulating (HTACS) activity, while a needle biopsy of the thyroid gland was consistent with lymphocytic thyroiditis. Twenty-one other reported cases of this unusual sequence found in the literature are reviewed. This occurrence is more common than is generally appreciated.

Glucose Tolerance in Granuloma Annulare

Granuloma annulare (GA) may be associated with glucose intolerance. Twenty-one patients with GA were evaluated. Four patients were found to have frank diabetes mellitus and 2 were excluded from the data analysis because of obesity. The remaining patients and 14 age- and weight-matched controls had oral and intravenous glucose tolerance tests (GTT). During the oral GTT the fasting plasma glucose, the 2-h plasma glucose, the area of the glucose curve, the 1-h serum insulin, and the area of the insulin curve were all significantly greater in the GA patients than in the controls. During the intravenous GTT the immediately releasable insulin pool was intact, while the fasting plasma glucose and the area of the glucose curve were greater in the GA patients than in the controls. The data taken together suggest that glucose tolerance may be reduced in GA and that insulin resistance may exist.