L. Bianconi

THYROID FUNCTION EVALUATION BY DIFFERENT COMMERCIALLY AVAILABLE FREE THYROID HORMONE MEASUREMENT KITS IN TERM PREGNANT WOMEN AND THEIR NEWBORNS

Evaluation of thyroid status by measurement of free thyroid hormone concentrations seems particularly helpful in conditions with altered serum binding proteins. In pregnancy, a condition of increased thyroxine binding globulin, serum free thyroxine (FT4) and free triiodothyronine (FT3) concentrations have been reported to be normal, increased or decreased. In the present study we have measured serum total and free thyroid hormone concentrations in pregnant women, their newborns and nonpregnant women. Serum FT4 and FT3 concentrations have been measured with 10 different commercially available kits and the results obtained have been compared. Serum total thyroid hormone concentrations in pregnant women were significantly higher than in their newborns and in nonpregnant women. Maternal serum FT4 concentrations measured with the different kits were always significantly lower than values in nonpregnant women. Furthermore, with one kit, the mean maternal serum FT4 concentration was below the normal range and with many kits, a large number of maternal serum samples had serum FT4 concentrations below the normal range. With all kits, except two, neonatal serum FT4 concentrations were higher than values in their respective mothers and, in general, lower than values in nonpregnant women. Serum FT3 concentrations in nonpregnant women were in the normal range, except with one kit, in which the mean serum FT3 concentration was below the normal range. Serum FT3 concentrations in newborns resulted markedly lower than in parturient and in non pregnant women. With almost all kits, serum FT3 values were below the normal range in many maternal samples. With one kit, maternal serum FT3 concentrations resulted higher than in nonpregnant women, whereas with the other kits serum FT3 concentrations were lower. Despite the variability of serum FT4 and FT3 concentrasions, serum TSH concentrations in pregnant women and their newborns, resulted in the normal range. These findings suggest that many kits for the measurement of serum free thyroid hormone concentrations do not seem adequate to evaluate the real thyroid status of pregnant women and newborns. Therefore, in these physiological conditions the measurement by commercial kits of serum FT4 and FT3 concentrations do not offer a real advantage in respect to serum total thyroid hormone determination.

Postpartum thyroid dysfunction in an Italian population residing in an area of mild iodine deficiency

We have evaluated the occurrence of postpartum thyroid dysfunction (PPTD) in a group of 372 women residing in area of mild iodine deficiency. Thyroid function and autoimmune status were evaluated by means serum T4, T3, TSH measurement and detecting the presence of positive antithyroglobulin antibodies (AbTg), antimicrosomal antibodies (AbM) and thyroid-peroxidase antibodies (AbTPO) titers in women at parturition, at 1, 3, 6 and 12 months postpartum. New onset transient hypothyroidism occurred in 6.4% of women whereas transient thyrotoxicosis in only 1.8% of women. Transient hypothyroidism was not preceded by thyrotoxicosis as indicated by thyroid function tests and serum Tg concentrations. At parturition, the positivity of AbM and AbTPO titers and the presence of goiter appeared to be a risk factors for the development of PPTD.

Selenium administration does not cause thyroid insufficiency in subjects with mild iodine deficiency and sufficient selenium intake

Selenium is a trace element essential for the activity of type I 5′-deiodinase which converts thyroxine (T4) to 3,5,3′-triiodothyronine (T3). In iodine deficient hypothyroid children at low selenium dietary intake the supplementation of selenium induced a significant decrement of serum FT4 and T4 concentrations and an increase of serum TSH concentrations. Since in western countries selenium tablets begin to be largely consumed as a diet integrator, we have administered 100 μg/day of selenium as selenium methionine to 8 euthyroid female subjects with a positive iodine-perchlorate discharge test who had a previous episode of subacute or postpartum thyroiditis. We have studied subjects with positive iodine-perchlorate discharge test since the test indicates the existence of a subtle defect of thyroid hormone synthesis and therefore these subjects are prone to develop thyroid dysfunction. In contrast to previous findings in hypothyroid children at low iodine and selenium dietary intake, the supplementation of selenium did not decompensate thyroid hormone synthesis of euthyroid subjects with reduced thyroid iodine organification. The lack of ny effect of selenium on thyroid hormone synthesis even in subjects with subtle thyroid hormone synthesis defect may be due to the fact that these subjects had a sufficient selenium dietary intake before selenium supplementation and an only marginally reduced dietary iodine intake.

Thyroid ultrasonography in patients with a previous episode of amiodarone induced thyrotoxicosis

Amiodarone induced thyrotoxicosis (AIT) occurs most frequently in euthyroid patients with nodular goiter or Graves’ disease due to release of iodine from this iodine rich drug. However, some cases of AIT have been attributed to an inflammatory process of the thyroid gland due to amiodarone itself.We have studied the echographic pattern of the thyroid in 11 euthyroid patients who had an episode of AIT 32.4±3.6 months earlier due to amiodarone induced thyroiditis. There was a significant increase in dyshomogeneous echo patterns and hyperechogenecity which suggests fibrotic lesions. These findings were similar to those observed in 10 euthyroid patients who 77±12 months earlier had an episode of subacute thyroiditis (SAT). Thyroid volumes of control subjects and patients with a history of AIT and SAT were 10.9±1.4, 8.7±1.4 and 9.8±1.7, in the order. These values were not significantly different. These echographic findings, normal serum thyroid hormone and TSH concentrations and the absence of circulating antithyroid peroxidase antibodies suggest that underlying thyroid autonomy and Graves’ disease were not the cause of the previous episode of AIT. The presence of hyperechogenic and dyshomogeneous patterns appears the result of the healing of the inflammatory AIT process.

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.

Metergoline, naloxone, and sodium valproate did not modify arginine vasopressin response to insulin-induced hypoglycemia in man

The present study was carried out in order to determine whether insulin-induced hypoglycemia exerts its stimulatory effect on plasma concentrations of arginine vasopressin (AVP) by interacting with a serotonergic, a GABA-ergic or an opioid pathway. For this purpose, the effect of the serotonergic antagonist metergoline (10 mg/day for 4 days po), the GABA-ergic agonist sodium valproate (600 mg in three divided doses po) and the opioid-receptor blocker naloxone (10 mg in a iv bolus) on the AVP response during an insulin (0.15 lU/kg bw) tolerance test (ITT) was evaluated in three groups of 6 normal men each. In all men, control ITTs were performed without drug treatments. Basal and ITT-stimulated AVP secretion was not modified by drug administration, suggesting that serotonergic, GABAergic and naloxone-sensitive opioid receptors are not involved in the regulation of AVP secretion in response to insulin-induced hypoglycemia.

Subclinical hypothyroidism, overt thyrotoxicosis and subclinical hypothyroidism: the subsequent phases of thyroid function in a patient chronically treated with amiodarone.

In a patient chronically treated with amiodarone, subclinical iodine-induced hypothyroidism occurred as a result of excess iodine released from the amiodarone molecule. The patient was maintained on amiodarone and developed thyrotoxicosis as a result of a destructive process into the thyroid follicles. Amiodarone was withdrawn and methylprednisolone and methimazole treatment was started with resolution of the thyrotoxic phase. Months later, off therapy, the patient developed subclinical hypothyroidism. This is the first description of hypo-and hyperthyroidism in the same patient caused by amiodarone therapy. This unusual observation suggests that patients treated with amiodarone are at risk to develop hyperthyroidism even if they show laboratory findings consistent with hypothyroidism.

The infusion of somatostatin reduces the arginine-vasopressin response to insulin-induced hypoglycemia in man.

The effect of an iv infusion of somatostatin (SRIH) (4.1 μg/min × 90 min) on the basal secretion of arginine-vasopressin (AVP) and on the AVP response to insulin (0.15 IU/Kg) — induced hypoglycemia was studied in 6 normal men. Basal AVP secretion was not modified by SRIH administration. The blood glucose decrements induced by insulin were similar in the control insulin-tolerance test (ITT) and in the ITT + SRIH test, whereas the AVP response to hypoglycemia was significantly lower in the presence of SRIH. The mean peak AVP increase was three times higher than the basal value in the control ITT, but only two times during SRIH administration. Infusion of higher doses of SRIH (7 μg/min × 90 min) produced similar results. These data suggest the involvement of a somatostatinergic mechanism in regulation of AVP response to hypoglycemia.

Increase by naloxone of arginine vasopressin and oxytocin responses to insulin-induced hypoglycemia in obese men

The present study was carried out to establish whether the low arginine vasopressin (AVP) and oxytocin (OT) responses to insulin-induced hypoglycemia observed in obese men was due to alteration of the opioid control of posterior pituitary function. For this purpose, the AVP and OT releasing effect of insulin (0.15 lU/kg bw) — induced hypoglycemia was tested in eight normal weight men and in 10 age-matched obese subjects, without and with the previous treatment with the specific opioid receptor antagonist naloxone (3 mg in an iv bolus). In a control study, naloxone was given alone to the same subjects. Obese men showed similar basal glucose, AVP and OT levels, which remained unmodified after treatment with naloxone alone. Insulin induced a similar decrement of blood glucose levels in all subjects, with a nadir at 30 min. Plasma levels of AVP and OT rose strikingly in normal and obese subjects with mean peak responses at 30 min for AVP and at 45 min for OT. However, both AVP and OT responses were significantly lower in obese than in control subjects. Pretreatment with naloxone did not modify the AVP and OT responses to hypoglycemia in normal weight subjects, whereas it significantly enhanced both hormonal responses in obese subjects. In the presence of naloxone normal controls and obese subjects showed similar responses of both AVP and OT to hypoglycemia. These data indicate that an abnormal activity of endogenous opioids might account for the hypothalamic posterior pituitary dysfunction, which is responsible for the low AVP and OT responses to insulin-induced hypoglycemia in obesity.

5-HT1-, but Not 5-HT2-Serotonergic, M1-, M2-Muscarinic Cholinergic or Dopaminergic Receptors Mediate the ACTH/Cortisol Response to Metoclopramide in Man

The possible mediation of dopaminergic, muscarinic cholinergic and/or serotonergic receptors in the response of ACTH/cortisol to metoclopramide (MCP) was evaluated in 27 normal men. All subjects were tested with MCP (10 mg in an intravenous bolus plus placebo or saline, NaCl 0.9%, control test). For the other tests (experimental tests), the men were divided into three groups of 9 subjects each. One group was tested with MCP in the presence of the dopaminergic agonist bromocriptine (5 mg p.o. 3 h before MCP), another group was tested with MCP plus the M1- and M2-muscarinic-cholinergic antagonist atropine (1.2 mg in an intravenous bolus, just before MCP) or the M1-muscarinic receptor blocker pirenzepine (40 mg in an intravenous bolus 10 min before MCP). The third group was tested with MCP after treatment with the selective 5-HT1-serotonergic receptor blocker metergoline (10 mg/day p.o. in 5 divided doses for 4 days before MCP) or the 5-HT2-serotonergic receptor antagonist ketanserin (10 mg as a slow 3-min intravenous injection, 5 min before MCP). ACTH and cortisol rose by 45 and 55%, respectively, in response to MCP. The basal levels of ACTH and cortisol were not modified by bromocriptine, atropine, pirenzepine, metergoline or ketanserin treatment. Both ACTH and cortisol responses to MCP did not change significantly after bromocriptine, atropine, pirenzepine or ketanserin administration, whereas they were completely abolished by pretreatment with metergoline. Additional experiments were performed in order to evaluate whether the effect of metergoline on the ACTH/cortisol response to MCP depends on the amount of the serotonergic antagonist (dose-response study).(ABSTRACT TRUNCATED AT 250 WORDS)