Thyroid dysfunction in COVID-19 patients.

PURPOSE: "Non thyroidal illness syndrome" (NTIS) or "euthyroid sick syndrome" (ESS) is a possible biochemical finding in euthyroid patients with severe diseases. It is characterized by a reduction of serum T3 (fT3), sometimes followed by reduction of serum T4 (fT4). The relationship between thyroid hormones levels and mortality is well known and different studies showed a direct association between NTIS and mortality. The sudden spread of the 2019 novel coronavirus (SARS-CoV 2) infection (COVID-19) and its high mortality become a world healthcare problem. Our aim in this paper was to investigate if patients affected by COVID-19 presented NTIS and the relationship between thyroid function and severity of this infection. METHODS: We evaluated the thyroid function in two different groups of consecutive patients affected by COVID-19 with respect to a control group of euthyroid patients. Group A included patients hospitalized for COVID-19 pneumonia while patients requiring intensive care unit (ICU) for acute respiratory syndrome formed the group B. Group C identified the control group of euthyroid patients. RESULTS: Patients from group A and group B showed a statistically significant reduction in fT3 and TSH compared to group C. In group B, compared to group A, a further statistically significant reduction of fT3 and TSH was found. CONCLUSIONS: COVID-19 in-patients can present NTIS. FT3 and TSH serum levels are lower in patients with more severe symptoms.

Everolimus is a new anti-cancer molecule: Metabolic side effects as lipid disorders and hyperglycemia.

In the last few years, molecular targeted therapies have replaced traditional cytotoxic chemotherapy in the fight against many cancers to the extent that our understanding of tumor biology has become more sophisticated. This shift has markedly changed adverse event profiles, compared to cytotoxic chemotherapy, affecting a diverse range of organ systems. Everolimus was approved by the FDA in 2011 for the treatment of progressive pancreatic NE tumors. It is an inhibitor of mammalian target of rapamycin (mTOR) and exhibits antitumor activity via disruption of various signaling pathways and it's used in the treatment of advanced renal cell cancer, breast cancer and neuroendocrine tumors (NET); it's used also as anti-rejection agent for transplantation but with lower doses for anti-rejection (1.5-3.0 mg/day) than for anti-cancer (5-10 mg/day) treatment. Metabolic side effects are the most frequent reported and will be discussed in this review.

Influence of pyridostigmine on growth hormone (GH) response to GH-releasing hormone pre- and postprandially in normal and obese subjects.

The effect of pyridostigmine (PYR), an inhibitor of acetylcholinesterase, on the GH response to GH-releasing hormone (GHRH) before and after a meal was studied in 14 normal subjects (8 females and 6 males) and 21 obese subjects (13 females and 8 males). In normal subjects tested in a fasting state, PYR was capable of stimulating GH secretion and increasing the GH response to GHRH. These effects were not apparent after food, suggesting a reduction in cholinergic hypothalamic activity. In obese subjects tested in a fasting state, PYR was ineffective when administered alone. On the contrary, it was able to increase the GH response to GHRH. After food, the augmenting effect of PYR on the GH response to GHRH was not observed, whereas a delayed inhibition of the GH response was found after PYR plus GHRH treatment. Our findings support the hypothesis that cholinergic hypothalamic activity plays a pivotal role in impaired GH regulation and the altered sensitivity of GH secretion to metabolic fuels in obese subjects.

GH response to GHRH before and after meals at different hours of the day in obese patients.

In normal subjects several factors are involved in the regulation of the GH response to GHRH, such as nutritional status, metabolic fuels and neurotransmitters. We previously have shown a paradoxical increase in the GH response to GHRH after meals in obese patients, in contrast to the blunted GH response observed after feeding in normal subjects. We have further investigated this phenomenon, studying the GH response to GHRH before and after meal at three different hours during the day in 10 obese patients, aged 18-35 yr, in comparison to that in eight normal women, aged 20-35 yr. GHRH was injected in a fasting state or 1 hr after a standard meal (800 KCal). In obese subjects, after food ingestion the peak GH response to GHRH was increased at 0900h and 1300h and was significant when the patients were tested after lunch (1300h). On the contrary, in the evening the GH response to GHRH remained unchanged, both before and after feeding. These data point to an altered sensitivity of GH secretion to metabolic signals in patients with obesity.

Influence of naloxone infusion on prolactin and growth hormone response to growth hormone-releasing hormone in anorexia nervosa.

Anorexia nervosa (AN) is frequently associated with anomalies of growth hormone (GH) and prolactin (PRL) secretion. We studied the GH and PRL responses to GHRH1-44 (50 micrograms IV) and the effect of a naloxone infusion (1.6 mg/hr), started 1 hr before GHRH administration, on this response in 12 female patients with AN, aged 15-30 yr, and in seven normal women, aged 19-27 yr, during the follicular phase as controls. In AN, GHRH induced an increase in GH levels similar to that observed in normal subjects. A significant inhibition of the GH response to GHRH was observed during naloxone infusion, similar to the inhibition in normal female subjects during the follicular phase. PRL levels showed a significant increment after GHRH alone and a slight, nonsignificant, PRL increment after GHRH during naloxone infusion in AN patients. In contrast a slight PRL decrease was observed after GHRH, both before and during naloxone infusion, in the normal subjects. Our study demonstrates that endogenous opioids play a role in influencing PRL secretion in patients with AN different from their role in normal subjects.

Acromegalic cardiomyopathy. Left ventricular filling and hypertrophy in active and surgically treated disease.

Myocardial hypertrophy and interstitial fibrosis are common in acromegalic hearts and may induce left ventricular (LV) dysfunction. The transmitral flow pattern was examined by pulsed-wave Doppler in 20 patients with active acromegaly and nine with acromegaly cured by pituitary microsurgery. Control groups consisted of 25 normal subjects and 13 patients with systemic hypertension. We related Doppler indices of LV filling (E and A peak velocities and E/A ratio) to the duration of acromegalic disease, the GH plasma levels and LV mass. The LV mass/BSA was significantly greater in active acromegaly (187 +/- 53 g/sq m) and systemic hypertension groups (161 +/- 48 g/sq m) than in cured acromegaly (125 +/- 35 g/sq m) and the normal control group (109 +/- 36 g/sq m) (p < 0.01 for both). No differences were found in the E peak velocity, A peak velocity, and E/A ratio in the groups with active acromegaly (E/A: 0.9 +/- 0.2), cured acromegaly (E/A: 0.9 +/- 0.3), and systemic hypertension (E/A: 0.8 +/- 0.5). An E/A ratio < 1 was found in 13 patients with active and four with cured acromegaly; (p = NS). In the active acromegaly group, the E/A ratio was related to either LV mass or the duration of disease (r:-0.45 and -0.47, respectively; p < 0.05). In the cured acromegaly group, the E/A ratio was related to the duration of disease before surgery (r:-0.70; p < 0.05) and not to LV mass (r:0.12). In conclusion, an impairment in LV filling may be present not only in the patients with active acromegaly but also in those successfully treated by surgery after a long duration of the disease, despite normal LV mass. These LV filling abnormalities may be in part determined by nonreversible myocardial changes, such as interstitial tissue fibrosis.

Opioid dysregulation in anorexia nervosa: naloxone effects on preprandial and postprandial growth hormone response to growth hormone-releasing hormone.

Previously, we have shown that in the opposite extremes of nutritional status, obesity and anorexia nervosa (AN), growth hormone (GH) response to growth hormone-releasing hormone (GH-RH) is not inhibited by the ingestion of a normal 800-cal meal consumed at lunch time (1 PM), which is at variance with results in normal subjects. However, in obese patients the postprandial increase in GH response to GH-RH is inhibited by an infusion of naloxone (NAL). In this study we have tested anorectic patients, performing the following tests at 1 PM: GH-RH test (50 micrograms IV) or, in a different day session, NAL (1.6 mg/h, starting 30 minutes before GH-RH) + GH-RH test (50 micrograms IV). The tests were performed in the following three different experimental conditions: (1) short-term fasting studies (lasting from breakfast), (2) long-term fasting studies (from midnight of the day before) and (3) postprandial studies (after a standard meal consumed 1 hour before the test). In AN, the GH response to GH-RH was not influenced by NAL infusion at 1 PM, in both short- and long-term fasting studies (short-term fasting: peak values after GH-RH alone, 26.5 +/- 6.5 ng/mL, during NAL, 28.0 +/- 3.3 ng/mL; long-term fasting: peak values after GH-RH alone, 32.2 +/- 6.8 ng/mL, during NAL, 30.6 +/- 4.0 ng/mL). A partial NAL-inhibitory effect was instead observed in postprandial studies, as evidenced by the calculation of areas under the curve ([AUCs] 1,662.1 +/- 90.0 after GH-RH alone v 1,090.5 +/- 245.4 ng/mL/h during NAL).(ABSTRACT TRUNCATED AT 250 WORDS)

Preoperative growth hormone response to thyrotropin-releasing hormone and oral glucose tolerance test in acromegaly: a retrospective evaluation of 50 patients.

The objective of this study was to investigate the relationship between growth hormone (GH) dynamic tests (thyrotropin-releasing hormone [TRH] test and oral glucose tolerance test [OGTT]), insulin-like growth factor-I (IGF-I) plasma values, tumor size, and clinical outcome in patients with GH-secreting pituitary adenomas. Furthermore, we investigated the potential prognostic utility of the above biochemical parameters in the follow-up of patients with acromegaly. We studied 50 acromegalic patients (18 males and 32 females; mean age, 40 years; range, 16 to 69) who underwent trans-sphenoidal removal of a GH-secreting pituitary adenoma from 1990 to 1994. Preoperatively, we evaluated (1) GH plasmatic levels after an oral glucose load (OGTT) (blood samples were drawn at -15, 0, 30, 60, 90, 120, 150, and 180 minutes after oral administration of 0.75 g/kg body weight [BW] of glucose), (2) GH plasma levels after a TRH test (200 microg as an intravenous [IV] bolus), and (3) basal IGF-I plasma levels after an overnight fast. From 3 to 12 months after surgery we evaluated (1) GH plasma values after an OGTT, and (2) basal plasma IGF-I, free triiodothyronine (FT(3)), free thyroxine (FT(4)), thyroid-stimulating hormone (TSH), and urinary free cortisol. The same tests were performed every year for 5 years. All of the patients were classified into 4 subgroups according to the system of Hardy and Vezina. Preoperatively, "controlled" patients (n = 29) had a GH paradoxical response to TRH (n = 28) and an unresponsiveness to OGTT (n = 29); 23 of them belonged to the I and II classes. Only 5 poorly controlled patients (n = 21) showed a preoperative paradoxical response to TRH and 9 had a preoperative GH partial inhibition after OGTT; 19 of them belonged to the III and IV classes. Our data suggest that in the preoperative period in acromegalic patients the simultaneous presence of a GH paradoxical response to TRH and lack of GH inhibition after OGTT is inversely related to the tumor size and therefore more likely to be restored to normal by surgical treatment.

Sex-related naloxone influence on growth hormone-releasing hormone-induced growth hormone secretion in normal subjects.

The effect of opiate-receptor antagonist naloxone on growth hormone (GH) release after growth hormone-releasing hormone (GHRH) 1-44 administration was investigated in ten normal men and 18 normal women during different phases of their menstrual cycle. Naloxone was infused at a rate of 1.6 mg/h in women and 1.6- and 3.2 mg/h in men, starting one hour before GHRH administration (50 micrograms iv as a bolus). On different day sessions, naloxone, GHRH, or saline were administered as controls. Naloxone infusion reduced the GHRH-induced GH release in normal women. The mean % inhibition of peak GH response was 83% during follicular phase, 46.5% during periovulatory phase, and 77.6% during luteal phase. On the contrary, in normal men, both doses of naloxone infusion were ineffective in blunting the GH response to GHRH. Our studies indicate that naloxone infusion was capable of inhibiting GH release induced by direct stimulation with GHRH in normal women, suggesting an opiate-antagonist action at the anterior pituitary level. The absence of such an effect in normal men strongly indicates a sex dependence of naloxone effects and suggests a role of the sexual steroid environment in opioid modulation of pituitary hormone secretion.

Naloxone influence on the growth hormone, prolactin and thyrotropin response to thyrotropin releasing hormone in acromegalic patients.

In order to gain insight into the neuroendocrine mechanism underlying the paradoxical GH response to TRH in acromegalic patients, we have investigated the effect of an infusion of Naloxone (Nal, 1.6 mg/hr for two hours), on a TRH test performed both in responder (n = 9) and non-responder (n = 5) acromegalic patients. The response of GH, PRL and TSH to TRH injection were evaluated. NAL did not exert significant variations in the GH response, even if different patterns of GH response during NAL were observed in the group of TRH-responder patients. Similarly, TRH-induced PRL response was not significantly affected by the infusion of an opiate antagonist. On the contrary, a significant inhibition of the TSH response was observed in the group of TRH-responder patients (delta TSH after TRH 4.76 +/- 1.11 microU/ml, after NAL + TRH 2.81 +/- 0.99 microU/ml, p < 0.05). No significant effects were observed in the TRH non-responder patients (delta TSH after TRH 4.58 +/- 1.44 microU/ml, after NAL + TRH 6.26 +/- 3.27 microU/ml). The differences observed in the two groups of patients could be ascribed to a different endogenous somatostatinergic tone and could furnish a prognostic indication in acromegalic patients.

Primary hyperparathyroidism. Our experience.

We report our experience in the clinical presentation and management of 12 patients with primary hyperparathyroidism, who underwent successful surgery. Comparing our results with those previously reported in the literature, we have attempted to correlate the kind of parathyroid lesion, the magnitude of hypercalcemia and PTH increase, and clinical symptoms. Often these relationships are intriguing; we have tried to classify our patients describing four groups, according to clinical and humoral findings: 1) patients with very mild hypercalcemia and aspecific symptoms; 2) patients with a finding of recurrent hypercalcemia and prevalent renal involvement; 3) patients with severe hypercalcemia, plurisystemic involvement and general decay; 4) patients with medical emergencies. Finally, some considerations on rare histological pictures (hyperfunctioning carcinoma, oxyphil cell adenoma) are reported.

[Reevaluation of the I-dopa test in acromegaly: anatomo-clinical and prognostic correlations]. / Rivalutazione del test alla I-dopa nell'acromegalia: correlazioni anatomo-cliniche e prognostiche.

It is known that in acromegalic patients the GH secretion exhibits a pattern of response to various stimuli that differs from that observed in normal subjects. We have evaluated the paradoxical GH response to 1-Dopa in acromegaly, in order to clarify the relationships between this datum and the tumour size, the basal GH secretion, the GH response to TRH and the long-term prognosis. MATERIALS AND METHODS. 34 acromegalic patients, 12 men and 22 women, aged 35-70 yr, participated in this study. They were divided in 4 classes, according to Hardy's classification of pituitary neoplasias: (1) intrasellar microadenomas, < 10 mm (n = 8); (2) intrasellar macroadenomas, > 10 mm (n = 14); 3) adenomas with local expansion (n = 9); (4) adenomas with extrasellar expansion (n = 3). All patients underwent a 1-Dopa-test; 18 of them underwent a TRH-test. Basal postoperative GH and basal pre- and postoperative PRL levels were also determined. RESULTS. The basal preoperative GH values in all patients ranged between 16 and 278 ng/ml. 22 patients showed a paradoxical response to 1-Dopa, 12 were non-responders. The following results were observed in the different classes: [table: see text] Moreover, 10 subjects (56%) were TRH-responders (9 of them were also 1-Dopa-responders, 1 was non-responder) and 8 were TRH non responders (6 were 1-Dopa non-responders, 2 were 1-Dopa responders). Basal postoperative GH values were > 5 in 17 1-Dopa responders and in 9 non responders. Basal preoperative PRL levels were > 25 ng/ml in 7 1-Dopa responders and in 2 non responders. After surgery, basal PRL became normal in 5 responder patients. DISCUSSION. In a previous work we have correlated the paradoxical GH response to TRH with tumour size and GH levels, observing a higher percentage of paradoxical response in patients in class I and II and, postoperatively, lower GH levels in preoperative TRH responders. So, we have underlined the good prognostic feature of a preoperative paradoxical response. In this paper we have evaluated the paradoxical GH response to 1-Dopa in the different Hardy's classes and compared it with the GH levels and the GH response to TRH. The results show that a paradoxical response can be observed more frequently in small (class I) adenomas than in greater size ones, and in presence of lower GH basal levels. Moreover, a concordance between 1-Dopa and TRH tests can be observed. CONCLUSIONS. The results clearly indicate that the responses to dynamic GH tests should be evaluated considering the anatomic characteristics of the neoplasias. It could be suggested that the paradoxical response can be expressed only when hypothalamus-pituitary interactions are intact.

[Thyroid metastasis of a renal carcinoma. 3 clinical cases]. / Metastasi tiroidea di carcinoma renale. Tre casi clinici.

The clinical finding of metastasis to the thyroid is a very rare event. When a metastasis from a renal carcinoma is diagnosed, it is usually the distant evidence of a tumour discovered and removed surgically months or years before, or it may be the first clinical sign of an as yet undiagnosed asymptomatic renal tumour. A case of massive retrosternal goiter in a 65-year-old patient, operated on for a right renal carcinoma (nephrectomy 6 years before), is reported. The goiter, causing compression symptoms and dyspnoea, was treated by total thyroidectomy. The pathological diagnosis was metastasis from renal carcinoma. The authors present a second case of nodular goiter, in a 79-year-old woman, 9 years after a right nephrectomy for a renal carcinoma. The expanding nodule, diagnosed intraoperatively as carcinoma, was treated by total thyroidectomy. The postoperative pathological diagnosis was metastasis from renal carcinoma. The authors report a third case of an expanding nodule of the thyroid, in a 65-year-old patient, diagnosed intraoperatively as a metastasis from renal carcinoma, treated by right lobectomy and isthmusectomy. An abdominal CT scan revealed a renal asymptomatic tumor, treated by right nephrectomy. The diagnosis can be established by means of fine needle aspiration biopsy preoperatively or intra- or postoperative histology. Surgical therapy may resolve the compression symptoms and improve the prognosis.

[Long-term anticonvulsant therapy and calcium and phosphorus metabolism]. / Terapia cronica anticomiziale e metabolismo calcio-fosforico.

The authors examined 114 epileptic patients who were taking anticonvulsant drugs from different periods of time. Serum and urinary calcium and phosphorus and serum alkaline phosphatase levels have been studied. Roentgenographic researches have been made in order to asses the bone mineral content. Urinary D-glucaric acid excretion as a quantitative index of hepatic enzyme induction has been determined in some subjects. The results show the presence of minor alterations both in calcium and phosphorus metabolism and in bone structure at a subclinical level. These findings suggest the importance of climatic and nutritional factors in the development of bone alterations pointed out by several authors in epileptic patients on long-term anticonvulsant therapy.

Cardiovascular reactivity and plasma prolactin response to mental stress in normals and hypertensives.

Central dopaminergic activity (CDA) may be involved in blood pressure control as a negative modulator of sympathetic outflow. In this study the plasma PRL changes produced by mental stress (a colour-word conflict test, CWT) were investigated in normals (NT, n.15) and stable hypertensives (HT, n.16) and the PRL response, as a possible index of CDA was correlated to the cardiovascular and the plasma renin activity (PRA) responses as indexes of peripheral sympathetic outflow. A significant (p less than 0.05) slight decrease in mean values of PRL was observed in normals after the CWT but no change was found in hypertensives. No correlation was found between the PRL responses to CWT and the maximal mean arterial pressure changes or the PRA changes whether the groups were considered separately or together. These findings indicates that PRL does not appear to be a reliable index of the CDA involved in blood pressure control.

Paradoxical growth hormone response to thyrotropin-releasing hormone in acromegaly. Clinical correlations and prognostic value.

We have investigated the effect of TRH on the release of GH in 20 acromegalic patients (14 females and 6 males) before and after selective removal of a pituitary tumour via transsphenoidal route. The follow-up period was 8 years. Pre-operatively the paradoxical response was present in 15 patients (75%). Mean GH values in TRH responders were significantly lower than in non-responders. According to the size and expansion diffusion of the adenoma, the patients were divided into 3 classes. The percentage of paradoxical response in patients in class III was significantly lower than in the other two classes. Postoperatively, mean GH values in pre-operative TRH responders were significantly lower than in non-responders; among 15 responders, 13 (86%) had postoperative GH levels under 5 micrograms/l; among 5 non-responders only 2 (40%) had GH values under 5 micrograms/l. Postoperatively 8 patients still had GH responsiveness to TRH: 6 with GH levels persistently (follow-up 8 years) under 5 micrograms/l and 2 with elevated GH values. The other 7 patients, who were responders pre-operatively and non-responders postoperatively, persistently exhibited low GH levels, except one subject who showed an increase in GH levels with reappearance of the paradoxical response, two years after surgery. These results suggest: 1. the paradoxical response may be expressed only when the hypothalamus-pituitary interactions are intact; 2. the disappearance of the paradoxical response cannot surely suggest a remission, and 3. the presence of a pre-operative paradoxical response is a good prognostic feature.

Calcium antagonists and hormone release. VIII. Effects of verapamil infusion on C-peptide to insulin molar ratio in normal subjects and obese subjects with normal glucose tolerance.

It is known that calcium-antagonist drugs can modify the insulin response to various secretagogues. In order to clarify whether calcium-antagonist effect was directed at the level of pancreatic insulin secretion or hepatic insulin extraction and further investigate the pathogenesis of hyperinsulinemia in obesity, an oral glucose tolerance test (OGTT) was performed in basal conditions and during a Verapamil infusion (VE, 5 mg/h x 3.5 h) in 12 normal subjects and 14 obese patients with normal glucose tolerance.(ABSTRACT TRUNCATED AT 250 WORDS)

Opioid-dopaminergic interactions in primary empty sella.

Previous studies have indicated different abnormalities of PRL secretion in patients with primary empty sella (PES). Since it is known that endogenous opiates and dopamine interact in modulating PRL secretion, we have studied the effect of an opiate receptor blockade (with Naloxone, NAL, 1.6 mg/h as a continuous infusion) on anterior pituitary hormones and on PRL responsiveness to metoclopramide (MCP), in 10 premenopausal normoprolactinemic patients with PES, studied in follicular phase, in order to investigate neurotransmitter abnormalities present in such a syndrome. NAL failed to significantly affect LH and FSH basal levels; on the contrary, slight but significant increases in PRL and GH secretion were observed. NAL partially blunted the PRL responsiveness to the dopaminergic blockade, which was very marked when tested after MCP alone. These data confirm that the modulation of anterior pituitary hormone secretion is different in PES patients, when compared with normal subjects. The infusion of NAL induced a "paradoxical" increase in hormones (PRL and GH) which are normally stimulated by endogenous opiates; but, on the other side, it blocked the marked PRL responsiveness to the dopaminergic blockade, which is characteristic of PES syndrome. This phenomenon seems to indicate that the relationships between dopaminergic and opiatergic neurons could be modified by the neuroanatomic alteration which is present in this complex syndrome.

Naloxone effects on post-prandial glucose, insulin and C-peptide levels in obese subjects.

In order to investigate the relationships between glucose metabolism, insulin secretion and endogenous opioids in obese patients, we have studied the effects of a naloxone infusion on insulin and C-peptide release after a normal meal (800 kcal) eaten at 12.00 hr in 16 obese women, aged 20-61 yr, with a BMI ranging from 25 to 37.2 kg/m2, with normal glucose tolerance (Group 1) and with NIDDM (Group 2). Naloxone was administered in a bolus of 1.6 mg i.v., followed by a continuous infusion of 4 mg in 2 hr starting immediately after feeding. In Group 1 naloxone infusion significantly increased the glucose levels, but insulin secretion was unaffected. In Group 2, naloxone infusion failed to modify significantly the postprandial levels of glucose, insulin and C-peptide. Therefore, in our study naloxone infusion seems to have beta-endorphin-like effects in non-diabetic obese subjects by increasing their glycemic levels, with no evidence of expected insulin decrease. In diabetic obese patients we observed a trend towards decrease in glycemic values during naloxone infusion, as expected, due to insulin plasma levels increase. By these data we can hypothesise a complex regulatory role of opioids in metabolic balance in obesity. In diabetic patients, naloxone can improve the surviving insulin secretion with better glucose tolerance. In non-diabetic subjects naloxone exerts its effects, probably, on peripheral organs.

Calcium antagonists and hormone release. VII. Effects of gallopamil infusion on insulin and C peptide release in normal subjects.

It is known that insulin release is calcium-dependent and that calcium-antagonists, blocking calcium transport across cell membranes, inhibit it, especially interfering with the second phase of insulin secretion. Gallopamil (GAL) is a new calcium-antagonist that, although structurally similar to verapamil, has more potency. It blocks slow calcium channels and fast sodium channels. Even if it has been demonstrated in vitro, there is no evidence that GAL is able to impair the glucose-induced insulin release in humans. We have submitted five normal subjects (24-36 yr old) to oral glucose tolerance test (OGTT, 75 g of glucose p.o.) and OGTT plus GAL infusion test (1 mg i.v. as a bolus, followed by a 2 mg/hr infusion for 2.5 hr, starting 30 min before glucose load), in two different days, to determine the effects of GAL on insulin and C peptide release after oral glucose load. In opposite with verapamil effects, we found that GAL did not reduce the peak levels of insulin and C peptide, but the peak response was delayed and the incremental areas tended to increase during GAL infusion, so that an impairment of glucose tolerance was equally obtained. This study indicates that different calcium-antagonist drugs exert differential effects on insulin release and their action on glucose homeostasis should be kept in mind because of the large use of these drugs in cardiac patients.