Fred D. Hofeldt

Ventilatory Control in Myxedema and Hypothyroidism

Alveolar hypoventilation is known to occur in myxedema. To clarify the role of hypoxic ventilatory drive and hypercapnic ventilatory drive in thyroid hormone insufficiency states, 10 patients with myxedema and seven with hypothyroidism (thyroid ablation) were studied before and after thyroid replacement. An index developed for hypoxic ventilatory drive was markedly reduced in myxedema: 17 plus or minus 4.7 (S.E.M.) (normal, 126 plus or minus 8.7) (P smaller than 0.01) and increased to 78 plus or minus 12.6 (p = 0.02) with thyroid hormone replacement. In the hypothyroid group this index was also depressed as compared to normal at 67 plus or minus 20 (p smaller than 0.01) and increased to 114 plus or minus 19 (p smaller than 0.02) with replacement. An index for hypercapnic ventilatory drive was depressed in myxedema, 0.69 plus or minus 0.01), but was not significantly depressed in hypothyroidism. With thyroid hormone replacement this index did not significantly increase in either group. We conclude that both myxedema and hypothyroid states produce depression of hypoxic ventilatory drive that is responsive to replacement therapy. This alteration in ventilatory control may contribute to the hypoventilation seen in myxedema.

Obstructive Sleep Apnea in Hypothyroidism

To determine the incidence and frequency of sleep apnea in persons with hypothyroidism, 11 consecutive patients with newly diagnosed disease were studied before and during thyroid hormone replacement therapy. Nine patients had episodes of apnea, with the number of episodes per hour of sleep ranging from 17 to 176 (mean, 71.8). Six of the nine patients were obese and had 99.5 episodes per hour compared with 16.3 episodes per hour in the 3 nonobese patients (p less than 0.02). After 3 to 12 months of thyroxine replacement therapy, mean apnea frequency decreased from 71.8 +/- 18.0 (SE) to 12.7 +/- 6.1 episodes per hour, without reduction in body weight. There were fewer changes in sleep stage per hour during treatment (22.1 +/- 4.9) than pretreatment (57.6 +/- 14.5). Carbon dioxide response tests done under non-loaded and flow-resistive loaded conditions before and during thyroxine replacement therapy showed increases in the loaded respiratory effort and ventilation during thyroxine treatment. Sleep apnea episodes are common in persons with untreated hypothyroidism, even with normal lung function. Thyroxine replacement therapy decreases apnea frequency, even without change in body weight.

Cushing's syndrome in pregnancy.

Fertility and childbearing rarely occur in Cushings syndrome because amenorrhea, oligomenorrhea, infertility, and abortions characterize the disease. Currently, a total of 53 cases of Cushings syndrome and pregnancy have been reported. When Cushings syndrome occurs during pregnancy, approximately 56 per cent of the cases are associated with adrenal cortical adenoma or carcinoma. Excluding Cushings disease, nearly 21 percent of the cases are caused by adrenal carcinoma. The maternal catabolic state of glucocorticoid excess contributes to poor fetal outcome with many of the cases complicated by either fetal wastage or prematurity. However, congenital malformations are not seen more frequently than in normal pregnancy. Pregnancy may or may not influence Cushings syndrome, but Cushings syndrome definitely complicates pregnancy.

Low dose radioiodide thyroid ablation in postsurgical patients with thyroid cancer

Sixty-four patients with well-differentiated carcinoma of the thyroid were treated with initial high (80 to 100 mCi) or low (less than 30 mCi) doses of I131 after bilateral subtotal thyroidectomy. A total of 36 patients in the various histologic categories were initially treated with the low dose of I131 (group 1), and a total of 28 patients were treated with the higher dose (group 2). Disease-free criteria were no visible tissue in the neck or body, a protein-bound radioactive iodine (PBI131) of less than 0.005 per cent per liter at seven days and/or whole body retention of less than 3 per cent at seven days. Of the patients receiving less than 30 mCi (group 1), 56 per cent with papillary carcinoma, 67 per cent with follicular carcinoma and 56 per cent with mixed carcinoma of the thyroid were rendered disease-free after this initial dose. Of the patients receiving the higher dose of I131 (group 2), 67 per cent with papillary carcinoma, 50 per cent with follicular carcinoma and 67 per cent with mixed carcinoma of the thyroid were rendered disease-free after this initial dose. Disease-free mean follow-up time was 5.17 years (group 1) and 5.82 years (group 2). There was no statistical difference in these mean follow-up times, nor was there a statistical difference in the net (total minus initial) dose of I131 needed to render the patient disease-free. These data demonstrate that low dose I131 therapy is as effective as the larger more routine doses of I131 given in this disease.

Serum thyroglobulin levels predict total body iodine scan findings in patients with treated well-differentiated thyroid carcinoma

Forty-eight consecutive patients with treated thyroid carcinoma were studied with 131-I total body scans and serum thyroglobulin (hTg) levels. Serum hTg levels during thyroxine treatment accurately predicted scan results (chi square = 18.6, p < 0.001). All patients with negative scans (24 patients) had serum hTg levels (< 7 ng/ml whereas in patients with metastatic thyroid cancer (eight patients) they ranged from 11 to 690 ng/ml. In patients with iodine uptake confined to the thyroid bed (16 patients) serum hTg values ranged from 2 to 17 ng/ml. Serum hTg levels rose in patients with negative scans during hypothyroidism or after exogenous TSH suggesting that hTg levels are more sensitive than iodine scans in detecting residual thyroid tissue. Serum hTg levels could replace total body iodine scans in many patients with treated thyroid carcinoma.

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.

Are Abnormalities in Insulin Secretion Responsible for Reactive Hypoglycemia

Seventy patients with reactive hypoglycemia strictly defined by criteria which interpret the low blood glucose value in relationship to clinical and physiologic parameters, were studied to determine if abnormalities in insulin secretion could be demonstrated. These patients were separated into four groups: alimentary (N = 5), diabetic (N = 16), hormonal (N = 5), and idiopathic (N = 44). The findings in these patients were compared to normal control subjects and to weight- and disease-matched patient controls. All of the patients with hormonal and most patients with idiopathic reactive hypoglycemia (thirty-two of forty-four) demonstrated delayed insulin secretion regardless of the control group used for comparison. Diabetic reactive hypoglycemic patients exhibited delayed insulin secretion when compared to normal controls but not when compared to weight-matched diabetic controls. Excessive insulin secretion was consistently found only in the patients with the alimentary variety of reactive hypoglycemia. Using weight- and diseasematched control groups, no abnormalities in insulin secretion could be found to account for the hypoglycemia in the diabetic reactive hypoglycemic patients and some idiopathic reactive hypoglycemic (nine of forty-four) patients. These results help to explain the inconsistent findings of previous investigators and suggest that reactive hypoglycemia is a syndrome having multiple etiologies.

Preventive Care in Diabetes Mellitus: Current Practice in Urban Health-Care System

Early identification and treatment of complications of diabetes mellitus may reduce the severity of the complications. As part of a program to reduce these complications in the Denver Department of Health and Hospitals patient population, our study determined how frequently preventive care, e.g., fundoscopic examinations, referral to an ophthalmologist, foot examinations, and assessment of cardiovascular risk factors, was provided to diabetic patients. With the use of billing records to identify a large sample of diabetic patients, a chart review of 544 patients was conducted. During the study year, the mean ± SE number of visits to primary-care clinics was 5.7 ± 0.22, with 86.4% having at least one visit. Most diabetic patients were seen by primary-care physicians; only 9% received care in a specialized diabetes clinic. Despite frequent primarycare visits, most diabetic patients in this county healthcare system did not have documentation of care to detect complications of diabetes mellitus, and referral services for detection and treatment of these complications were infrequently used. Moreover, among patients seen on >10 occasions in a primary-care setting, preventive care was not provided to 30% of the patients. Preventive care does not appear to be a regular part of a primary-care visit for most of the diabetic patients in this study.

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.

“Masked” 21-hydroxylase deficiency of the adrenal presenting with gynecomastia and bilateral testicular masses

An infertile 27 year old man with precocious puberty is described. He presented in adulthood with unilateral and then bilateral gynecomastia, and subsequently testicular tumors developed. An early diagnosis of congenital adrenal hyperplasia would have avoided unnecessary surgery. Initial detailed metabolic evaluation led to the erroneous diagnosis of 11-hydroxylase deficiency because of the presence of an unusual steroid (21-desoxycortisol) in serum which was falsely reported as an increased 11-desoxycortisol (compound S). The observed low urinary pregnanetriol measurements would have supported this diagnosis. Subsequent specific measurements of 21-desoxycortisol established its presence in the serum and its major metabolite, tetrahydro-21-desoxycortisol, in the urine. The unique features in this case of 21-hydroxylase deficiency alert the physician to its unusual clinical presentation and the pitfalls that may be encountered when evaluating adrenal steroidogenesis.