Angelo Gnudi

COMPARISON OF METHIMAZOLE, METHIMAZOLE AND SODIUM IPODATE, AND METHIMAZOLE AND SATURATED SOLUTION OF POTASSIUM IODIDE IN THE EARLY TREATMENT OF HYPERTHYROID GRAVES’DISEASE

We have evaluated three regimens for the rapid control (10 days’therapy) of thyrotoxicosis in hyperthyroid Graves’disease: methimazole (MMI, 40 mg/ day), MMI and sodium ipodate (MMI + Na Ipodate, 1 g/day and MMI and saturated solution of potassium iodide (MMI + SSKI, 6 drops twice daily). When serum T4 and T3 concentrations were analysed as the percent change from pre‐treatment values, the following results were observed. Serum T4 concentration decreased in the three treatment groups and the decrease was similar in the MMI and MMI + SSKI groups but significantly lower than in the MMI + Na ipodate group. The serum T3 concentration decreased to the normal range in all seven MMI + Na Ipodate treated patients by the fourth day of treatment and the per cent decrease in serum T3 from pre‐treatment values was significantly greater than in the MMI and MMI + SSKI treated patients. The decrease in serum T3 was similar in the latter two groups. Heart rate decreased in all three groups, but the decrease was significantly more in the MMI+Na ipodate treated patients. The present findings suggest that the rapid control of hyperthyroid Graves’disease is similar in patients treated with MMI and MMI + SSKI and that the combination of MMI + Na Ipodate is more efficacious since the decrease in serum T3 concentrations and heart rate was significantly greater in the MMI + Na ipodate‐treated patients.

Plasma and Skeletal Muscle Free Amino Acids in Type I, Insulin-treated Diabetic Subjects

Insulin-dependent diabetes mellitus (IDDM) induces plasma amino acid (AA) abnormalities, including low alanine and high branched-chain (BCAA). While insulin treatment restores plasma AA pattern, proline, methionine, valine, isoleucine, and total BCAA remain elevated in skeletal muscle intracellular water. This suggests that the restoration of plasma AA concentrations is not a satisfactory index of recovered AA metabolism in IDDM.

Cord blood iodothyronine and thyrotropin concentrations in newborns of mothers exposed to povidone iodine in the last trimester

In the present study, we have evaluated thyroid function in neonates at delivery and in their mothers who used vaginal povidone-iodine (PVP-I) during the last trimester of pregnancy. Newborns and their mothers without a history of iodine exposure, admitted to the same department and residing in the same geographical area served as controls. Maternal serum thyroxine (T4), triiodothyronine (T3), reverse triiodothyronine (rT3) and thyrotropin (TSH) concentrations at delivery were not significantly different between the two groups of pregnant women. Cord blood thyroid hormone concentrations in the newborns of iodine exposed mothers were not significantly different from those in control newborns. In contrast, cord blood TSH concentrations in the neonates of mothers exposed to PVP-I during the last trimester of pregnancy were significantly higher than values in control neonates (p < 0.05). These data confirm that the fetal thyroid gland, even in the last trimester of pregnancy, does not adapt completely to the inhibitory action of iodine on thyroid hormone synthesis and/or release.

EFFECTS OF THE GABAERGIC AGENT SODIUM VALPROATE ON THE ARGININE VASOPRESSIN RESPONSES TO HYPERTONIC STIMULATION AND UPRIGHT POSTURE IN MAN

In order to evaluate the possible influence of GABAergic neurotransmission on the arginine vasopressin (AVP) response to osmotic and pressure volumetric stimuli, the GABAergic drug sodium valproate was administered by mouth (200 or 400 mg 16 h, 8 h and just before tests) to eight normal men before osmotic (i.v. infusion of 0.51 m NaCl for 2 h) and orthostatic (standing upright and maintaining an orthostatic position for 20 min) tests. In both experimental conditions, the AVP rise was significantly lower in the presence than in absence of sodium valproate. The maximum AVP responses in the control orthostatic and osmotic tests were respectively 2.3 and 2.5 times higher than basal levels. When 600 mg sodium valproate was given, the maximum AVP rise in response to hypovolaemic and osmotic stimuli were respectively 1.75 and 2.1 times higher than basal value. Similar results were obtained giving 1.2 g sodium valproate. These results suggest that in man a GABAergic pathway is involved in the AVP responses to hypovolaemic and hyperosmotic stimuli.

Naloxone decreases the inhibiting effect of ethanol on the release of arginine-vasopressin induced by cigarette smoking in man

In order to establish whether ethanol exerts its inhibiting effect on the nicotine-induced release of arginine-vasopressin (AVP) by interacting with an opioid pathway, six normal volunteers were treated with naloxone (2 or 4 mg as IV bolus, plus 5 or 10 mg infused over 105 minutes) during (2 nonfilter) cigarette smoking and ethanol (50 mL to 110 mL of whiskey) drinking. In addition, control experiments with naloxone, ethanol, or cigarette smoking alone were performed. When given alone, naloxone and ethanol did not modify AVP secretion, whereas nicotine increased plasma AVP levels by about 2.5-fold. This effect was completely blocked by ethanol. In the presence of naloxone, AVP rose only by about 1.7-fold in response to nicotine. Since naloxone only partially reversed the inhibiting effects of ethanol, only a partial involvement of opioid peptides in ethanol action might be supposed. Alternatively, ethanol and naloxone-sensitive opioids might produce their inhibiting effects on AVP rise in response to nicotine through independent pathways.

Oxytocin enhances thyrotropin-releasing hormone-induced prolactin release in normal menstruating women *

The effects of oxytocin (OT) on basal thyrotropin-releasing hormone (TRH)-stimulated thyrotropin (TSH) and prolactin (PRL) secretion were evaluated in normal menstruating women during follicular, periovulatory, and luteal phases. Two different studies were performed. In one study, 15 subjects were treated with OT or saline; in the other study, 20 women were tested with TRH alone or in combination with OT. Results during follicular, periovulatory, and luteal phases were similar. OT did not produce any effect on basal serum TSH and PRL levels and on the TRH-stimulated TSH secretion, whereas it significantly enhanced the PRL response to TRH. At all examined phases during the menstrual cycle, the mean peak PRL response was reached within 20 minutes after TRH injection, and the peak was about three times higher than basal value when TRH was given alone and about four times when OT was present. These data suggest that in normal women OT is not involved in the control of basal and TRH-stimulated TSH secretion and of basal PRL release. In contrast, the enhancement of the TRH-induced PRL release suggests that OT plays a role in the control of the acutely stimulated PRL secretion. Because results were similar regardless of the phase of the menstrual cycle, estrogen and/or progesterone do not appear to be involved in the effect of OT on the TRH-induced PRL release.

Abnormal thyroid stimulating hormone, prolactin, and growth hormone responses to thyrotropin releasing hormone in abstinent alcoholic men with cerebral atrophy.

The thyroid stimulating hormone (TSH), prolactin (PRL), and growth hormone (GH) responses to thyrotropin releasing hormone (TRH), the Wechsler Adult Intelligence Scale (WAIS) for cognitive impairment, and computed tomographic scans were evaluated in 15 nondepressed alcoholic men after 4 weeks of abstinence and in 10 normal controls. Both cognitive impairment and cerebral atrophy were found in 13 of the alcoholics. Eight alcoholics (seven with cerebral atrophy) had blunted TSH and PRL responses to TRH and a TRH-induced paradoxical increase of GH. This study demonstrates that besides affecting the TSH response to TRH, alcoholism often induces alterations of the PRL and GH secretory patterns in response to TRH. The severe brain damage caused by long-term alcoholism might be involved in the pathogenesis of these neuroendocrine alterations.

Nicotinic-cholinergic involvement in arginine-vasopressin response to insulin-induced hypoglycemia in normal men

In order to establish whether arginine-vasopressin (AVP) release in response to insulin-induced hypoglycemia is mediated by a muscarinic and/or nicotinic cholinergic pathway, 12 normal men had an insulin tolerance test (ITT) in basal conditions and after treatment with the muscarinic receptor blocker pirenzepine (40 mg IV (intravenously) ten minutes before ITT in six subjects) or the nicotinic receptor antagonist trimethaphan (0.3 mg/min X 30 min IV before ITT in six subjects). The drugs did not modify arterial blood pressure nor produce side effects capable of altering AVP secretion. Pirenzepine administration did not change AVP response to hypoglycemia, whereas trimethaphan significantly reduced AVP increase by about 50% during the ITT. These data suggest the involvement of a cholinergic-nicotinic mechanism in regulation of AVP response to hypoglycemia.

Naloxone abolishes the inhibiting effect of somatostatin on the release of oxytocin evoked by insulin-induced hypoglycemia in humans☆

The effect of somatostatin (SRIH) on the release of oxytocin (OT) in response to hypoglycemia during insulin tolerance test (ITT) was studied in seven normal men. Subjects were injected intravenously with 0.15 U/kg insulin alone (control test) or together with SRIH (4.1 micrograms/min x 90 min), naloxone (10 mg in an IV bolus), or the combination of the two substances. Plasma OT concentrations rose significantly during ITT; the OT response was significantly reduced by the treatment with SRIH and increased in the presence of naloxone. When both SRIH and naloxone were given, the OT response to hypoglycemia did not differ from that observed in the control test. These findings provide evidence that the effect of hypoglycemia on plasma OT levels is sensitive to the inhibition by SRIH and by naloxone-sensitive endogenous opioids. Because naloxone reversed the inhibiting effects of SRIH, an involvement of opioid peptides in SRIH action might be supposed. Alternatively, SRIH and naloxone-sensitive opioids might produce their inhibiting effects on OT rise in response to hypoglycemia through independent pathways.

Dopaminergic control of TSH secretion in endogenous depression

To evaluate whether the inhibitory control exerted by endogenous dopamine on thyroid-stimulating hormone (TSH) secretion is altered in patients with major depressive disorder, 11 depressed patients and 9 normal controls were tested with the dopaminergic receptor antagonist domperidone (10 or 20 mg i.v.). The administration of domperidone induced a significant increase in circulating TSH levels in the normal controls, but not in the depressed patients. These data excluded the possibility that the dopaminergic inhibition of TSH secretion is enhanced in depression. To establish whether domperidone failure was due to a reduced dopaminergic tone, domperidone was administered before stimulation of TSH secretion with thyrotropin-releasing hormone (TRH) (200 micrograms i.v.). The TSH response to TRH was significantly lower in the depressed than in the control subjects, regardless of domperidone priming. However, in both groups domperidone enhanced the TRH-induced TSH release by 50%. These data suggest that the dopaminergic control of TSH secretion is not altered in patients with endogenous depression and that a reduced capacity of the pituitary to secrete TSH might be responsible for the reduced TSH responsiveness to TRH and domperidone.