Normal gastric inhibitory polypeptide response to oral glucose in hypothyroidism.

Although the action of gastric inhibitory polypeptide (GIP) on the beta cells of the pancreas is well documented, the effect of this hormone on insulin secretion in patients who are hypothyroid has not been studied. Hypothyroid patients demonstrate increased serum immunoreactive insulin levels in response to oral glucose when compared with euthyroid subjects. We postulated that a delayed and exaggerated response of GIP could account for the hyperinsulinaemic response. Nine thyroidectomized patients (aged 44.9 +/- 3.6 years) who were otherwise healthy but undergoing re-evaluation for recurrence of thyroid carcinoma, were given a 75 g oral glucose tolerance test (OGTT). These subjects were studied 6 weeks after thyroid hormone replacement had been stopped and while on hormone treatment. The serum glucose and plasma GIP responses to oral glucose were similar in the euthyroid and hypothyroid states. The serum insulin response as well as the areas under the curve for insulin following OGTT were significantly elevated (P < 0.01) during hypothyroidism. Solid-phase gastric emptying times studied in six patients who were euthyroid and hypothyroid were not different (35 +/- 12 versus 36 +/- 14 min respectively). None of the subjects had detectable levels of serum thyroglobulin, microsomal or parietal cell antibodies. In summary, we have confirmed a hyperinsulinaemic response to an OGTT and normal solid-phase gastric emptying rates in this form of hypothyroidism. We did not find significant differences in serum glucose or GIP responses and postulate this as evidence of resistance to the effects of endogenous insulin. The mechanism of alterations in carbohydrate tolerance in the hypothyroid state continue to remain unknown.

Sodium ipodate increases triiodothyronine action in vivo.

Sodium ipodate (IPO) has been shown to bind nuclear T3 receptors (NT3R) in vitro, but previous studies have conflicted in regard to demonstration of this interaction in vivo. We sought evidence for IPO-NT3R binding in vivo by giving large doses of IPO to thyroidectomized (TDX) rats replaced with low doses of T3. We predicted that IPO-NT3R binding would inhibit T3 induced increases in mitochondrial alpha glycerophosphate dehydrogenase activity (alpha-GPDH) in kidney, heart and liver. Three groups of ten euthyroid rats each received 13 daily injections of vehicle, or 6 or 12 mg/100 g body weight of IPO, respectively. Both doses of IPO resulted in decreases in serum T3 and increases in serum TSH. Liver and kidney alpha-GPDH, however, were decreased only in the group receiving 6 mg IPO. In addition, three groups of 30 TDX rats were implanted with osmotic minipumps that contained T3 in the following concentrations: 33, 69 and 96 ng/ul. Ten rats in each group received 13 daily injections of vehicle, or IPO (vide supra). The alpha-GPDH responses were complex in that there was significant interaction between T3 and IPO effects in the kidney (AxB F ratio 5.13, p less than 0.001) and liver (AxB F ratio 2.85, p less than 0.05). The major finding, however, was that alpha-GPDH was not significantly reduced by IPO in any T3 replaced group. Rather, in all three organs, alpha GPDH was significantly increased above that produced by T3 alone by at least one combination of IPO and T3. Changes in serum TSH also suggested that IPO could enhance T3 effects. We conclude that IPO-NT3R binding is not a prominent mechanism via which the drug attenuates T3 effects in vivo. The data suggest that IPO may enhance T3 effects at the cellular level and that this enhancement may not be reflected by routinely monitored serum TSH. The latter observation may have clinical importance.

Phosphoinositide turnover in human platelets is stimulated by albumin.

The effect of human serum albumin (HSA) on the hydrolysis of phosphatidylinositides in human platelets labeled with myo(3H)inositol was studied. Incubation of platelets with HSA (4 gm/dl) for 10 seconds increased IP2, and IP3, by 169% and 217% respectively. 93% of IP3 accumulated within the first 10 seconds. This effect was also shared by bovine serum albumin, although no changes in IP3 levels occurred with ovalbumin. All albumin species used induced 45Ca+2 release from platelets irrespective of its effect on IP3 accumulation. These findings indicate that albumin may function in biological systems by inducing intracellular signaling.

Pheochromocytoma associated ventricular tachycardia blocked with atenolol.

Ventricular tachycardia in patients with phenochromocytoma is rare. We report a patient with a norepinephrine-secreting extra-adrenal pheochromocytoma who had exercise induced ventricular tachycardia. Prior to diagnosis, the patient was treated with a selective beta 1 blocker, atenolol, which resulted in suppression of the dysrhythmia and amelioration of the hypertension. This is the first reported case of selective beta blockade suppressing ventricular tachycardia in a patient with a pheochromocytoma. Electrocardiographic abnormalities described in patients with pheochromocytoma are reviewed.