Anita Cavallo

Insulin resistance with acanthosis nigricans: The roles of obesity and androgen excess☆

The roles of hyperandrogenemia and obesity in the syndrome of severe insulin resistance with acanthosis nigricans were evaluated in studies of 11 females with this condition. Our results in these subjects were compared to evaluations of control subjects matched for degree of androgen excess or obesity. Fasting insulin levels were 3-, 5-, and 15-fold higher in the obese (OB), hyperandrogenemic (HO), and acanthosis nigricans (AN) groups, respectively, when compared to normal females. Responsiveness to a standard bolus of exogenous insulin was 78% of normal in the OB group, 40% of normal in the HO group, and 30% of normal in the AN group. Insulin binding to monocytes from both the OB group, and the HO group was modestly diminished primarily due to decreased receptor number. As a group, AN subjects when compared to either normal or weight-matched controls, demonstrated a significant decrease in monocyte insulin binding predominantly due to a decrease in receptor number. However, two patients in the AN group had normal insulin binding suggesting a postreceptor mechanism for the insulin resistance in at least some of these subjects. In vivo glucose utilization insulin dose response curves were determined in 3 acanthotic subjects using the euglycemic clamp technique. All 3 of these subjects had a right shift of the curve and diminished maximal utilization, consistent with combined receptor and postreceptor defects in insulin action. In evaluating the relationship between hyperandrogenemia, insulin resistance, and acanthosis nigricans, significant correlations among basal levels of plasma insulin, and both testosterone and androstenedione were demonstrated.(ABSTRACT TRUNCATED AT 250 WORDS)

DiGeorge syndrome: Long-term survival complicated by Graves disease

I. Brown HW: Congenital structural muscle anomalies. In Allen JH, editor: Strabismus Ophthalmic Symposium. 1. St. Louis, 1950, CV Mosby, pp 205. 2. Mein J: Superior oblique tendon sheath syndrome. Br Orthop J 28:70, 1971. 3. Rayner J, Hiatt RL: Bilateral Browns superior oblique tendon sheath syndrome. Ann Ophthalmol 5:506, 1970. 4. Goldhammer Y, Smith JL: Acquired intermittent Browns syndrome. Neurology 24:666, 1976. 5. Stein R: Posttraumatische intermittierence Pseudoparese des Musculus obliquus inferior. Mbl Augenheilkl 147:712, 1965. 6. Sims J: Acquired apparent superior oblique tendon sheath syndrome. Br Orthop J 28:112, 1971. 7. Clark E: A case of apparent intermittent overaction of the left superior oblique. Br Orthop J 23:116, 1966. 8: Sanford-Smith JH: Intermittent superior oblique tendon sheath syndrome. Br J Ophthalmol 53:412, 1969. 9. Killian P J, McClain B, Lawless O J: An unusual manifestation of rheumatoid arthritis. Arthritis Rheum 20:1080, 1977.

Melatonin circadian rhythm in childhood depression

Abstract The authors examined melatonin circadian rhythms in childhood depression by measuring integrated plasma melatonin concentrations in hourly blood samples, obtained by constant withdrawal during 24 hours, in nine depressed boys and 10 control boys similar in age and pubertal development. Mean 24-hour and mean overnight melatonin concentrations were significantly lower in the depressed boys. These preliminary results indicate that melatonin secretion is decreased in childhood depression, as in adult depression. Further studies are needed to examine the usefulness of melatonin as a marker for the trait of depression.

The use of plasma androstenedione in monitoringtherapy of patients with congenital adrenal hyperplasia

Therapy of congenital adrenal hyperplasia tranditionally is monitored by the amount of urinary 17-KS. However, 24-hour urine collections are difficult to obtain and are often unreliable. Measurement of the plasma concentrations of androgens, such as delta or T, would therefore be a more convenient way to determine the efficacy of treatment. Over a period of 2 to 24 months, 23 patients were periodically assessed by clinical examination, bone age, and determinations of plasma delta, plasma T, and 24-hour urinary 17-KS. Plasma T concentration correlated well with clinical control in females and in preadolescent males, but not in infant and pubertal males. By contrast, plasma delta concentration correlated well with clinical control in either sex, regardless of stage of puberty. The present study suggests that monitoring plasma delta concentration is useful in the long-term management of patients with CAH.

Is there a thyrotoxic cardiomyopathy in children

We measured left ventricular ejection fraction by radionuclide angiocardiography at rest and during graded exercise in eight thyrotoxic children. Five patients were reassessed after return to a clinically euthyroid state. In the thyrotoxic state the left ventricular ejection fraction was 69% +/- 8% at rest, and increased normally by 7% to 10% during exercise in four patients but did not change significantly or decreased by as much as 8% in the other four patients. The change in left ventricular ejection fraction during exercise correlated inversely with serum concentrations of thyroxine (r = -0.82, P less than 0.02) and triiodothyronine (r = -0.88, P less than 0.01). A comparison between patients who had normal left ventricular response to exercise with those who had abnormal response while thyrotoxic failed to uncover any significant differences between their resting ejection fractions or resting and exercise heart rates and systolic blood pressures. Three abnormal and two normal responders were reassessed after return to a clinically euthyroid state. The left ventricular ejection was 64% +/- 6% at rest, and increased during exercise in all patients. Our study suggests that thyrotoxicosis causes diminished left ventricular reserve (compensated functional cardiomyopathy) in some patients, but appears to be reversible. Severity of thyrotoxicosis, as measured by thyroid hormone blood levels, may be a determining factor in the development of functional cardiomyopathy.

Evaluation of 5-hydroxytryptophan administration as a test of pineal function in humans

We tested the hypothesis that acute 5-hydroxytryptophan (5-HTP) administration would cause an increase in concentrations of plasma melatonin to levels observed during the spontaneous nocturnal melatonin surge. We administered 5-HTP orally (5-12 mg/kg) to 10 healthy children and 5 healthy adults, and measured melatonin concentrations in plasma samples obtained every 30 min for 3-6 h. There was no appreciable increase in melatonin after 5-HTP stimulation, even though a melatonin increase has been reported in sheep treated with 5-HTP.

RESPONSES OF HYPERTHYROID CHILDREN TO EXERCISE

We studied responses to exercise in 8 children with untreated hyperthyroidism (H), ages 8-17 yr. Graded exercise was performed on a supine cycle ergometer with workload increments every 3 min until exhaustion. Left ventricular (LV) ejection fraction (EF) was measured by radioangiocardiography. Resting heart rate (HR), 115±14, and systolic blood pressure (SBP), 134±12, increased at peak exercise to 187±26 and 177±24, respectively. Physical working capacity index (PWC) was 8.5±3.2 kg-m/min.kg, mean work to exhaustion (MWE) 259±38 kg-m/min, maximal endurance index (MEI), 195±52. Resting EF was .68±.08. Based on exercise EF response patients were divided into 2 groups: Group I (n=4) had a rise in EF of .05 to .10 above resting EF, a normal response. Group II (n=4) had less than .05 increase or an actual decrease in EF by .03 to .10, suggesting decreased LV reserve; one patient had poor LV wall motion. A comparison between groups I and II showed no significant differences in exercise time, maximum HR or SBP, ECG responses, or in PWC, MWE and MEI. The correlation coefficient between ΔEF (exercise EF minus resting EF) and T4 was r=-.87 (p<0.05) and between ΔEF and T3, r=-.93 (p<0.001). The data indicate that H may cause LV dysfunction as determined by abnormal response in EF to exercise, which cannot be predicted by standard exercise parameters;severity of H, by T3 and T4 levels, may be a determining factor in the occurrence of cardiac dysfunction.