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Funding Acknowledgements Type of funding sources: None. Background Sacubitril/valsartan (S/V) has demonstrated a significant benefit in decreasing mortality and morbidity in patients with heart failure with reduced ejection fraction (HFrEF) when compared to angiotensin inhibition. Recent studies demonstrated that the benefits of S/V encompass a positive cardiac remodeling, leading to a reduction of ventricular arrhythmias. The effect of S/V on the supraventricular arrhythmic burden is still unknown. Purpose To evaluate the effect of sacubitril/valsartan on the supraventricular arrhythmic burden in HFrEF patients with an implantable cardioverter defibrillator (ICD) or cardiac resynchronisation therapy-defibrillator (CRT-D) and remote monitoring. Methods The SAVE THE RHYTHM is a multicentre, observational, prospective registry is enrolling all patients with HFrEF, ICD or CRT-D actively followed through remote monitoring and starting treatment with sacubitril/valsartan. All patients are followed-up at least one year after sacubitril/valsartan start. The primary endpoint is the number of sustained atrial tachycardia or AF (AT/AF). Secondary endpoints include incidence of AT/AF in the total population, total burden of AT/AF (defined as the percentage of time in AT/AF per day), mean number of premature ventricular contractions (PVC) per hour and percentage of biventricular pacing per day (in patients with CRT-D). All primary and secondary endpoints are collected through remote monitoring. Results At the time of the second ad interim analysis, 188 patients (85.2% male, age 68 ± 10 years) were consecutively enrolled. In patients without permanent AF, treatment with S/V was associated with a reduced incidence of AT/AF episodes, which changed from 32.6% (before treatment start) to 24.3%, 20.5% and 6.9% according to the sacubitril/valsartan dose (24/26 mg, 49/51 mg and 97/103 mg respectively; p= 0.041). A significant decrease in the median annual number of AT/AF episodes was also seen in these patients (16/year before treatment; 12/year at 24/26 mg; 6/year at 49/51 mg and 1/year at 97/103 mg; p = 0.046). No significant differences were reported in terms of PVC or biventricular pacing (all p = NS). Patients with permanent AF experienced no benefits from sacubitril/valsartan therapy in terms of arrhythmic burden reduction. No new diagnosis of clinical AF was made after starting treatment with sacubitrl/valsartan in all patients. Conclusions Preliminary data suggest that therapy with S/V could reduce the episodes of AT/AF in patients with HFrEF and remote monitoring, and the benefit seems related to the maximum tolerated dose of S/V. No positive effect has been noted in patients with permanent AF.

The paper addresses the need for theoretical development in the field of store atmospherics. An investigation is carried out into the comprehensiveness of the traditional environmental psychology approach in accounting for all the hypothetical situations which result from the interaction between shoppers and the objective features of the environment. A framework which extends the traditional Stimulus-Organism-Response model is advanced. A 2x2 typological schema is developed to account for the possible outcomes of the interaction, namely Utilitarian Fit, Hedonic Fit, Rational Control and Emotional Submissiveness. The more important theoretical deductions are formalized through hypothesis. Research and managerial insights are suggested.

Polymer-metal granular thin films were grown by simultaneous ion beam sputtering from a composite target. Morphological analysis performed by transmission electron microscopy shows their granular fine structure. The samples' ageing process was monitored over an interval of many hours after the film deposition. A detailed study of the resistance vs. temperature behaviour was performed over the range 12–300 K; current-voltage measurements as a function of temperature are also reported. An unusual ln ( R ) ∞ T −1 dependence was found at low temperature. This behaviour is explained with theoretical arguments based on percolation theory.

The way in which the dopaminergic system controls GH secretion in infancy and adolescence was investigated by studying the effects on GH of a specific dopaminergic agonist apomorphine, and two antagonists, metoclopramide (MC), which can and domperidone (DOM), which cannot cross the blood-brain-barrier, (BBB), in 14 males and 6 females aged 8–17 years. Treatment with both antagonists was followed by a marked increase in Prl, whereas only MC stimulated GH secretion, suggesting that this action must occur inside the BBB if it is linked to antidopaminergic properties. GH secretion was also stimulated by apomorphine, which acts at the central level. The paradox posed by the presence of a central effect on GH secretion derived from both an agonist and an antagonist of the dopaminergic receptors is discussed.

Thirty acromegalic subjects underwent chronic CB154 therapy (10–20 mg daily) for periods ranging from 3 months up to 2 years. In 18 out of 21 patients, who exhibited consistent HGH reduction following acute administration of the drug, there was also during chronic treatment, a suppression of the plasma HGH levels exceeding 50 % of base line values, e.g. from mean daily values between 14–197 ng/ml (mean ± sem = 57.8 ± 12.4 ng/ml pre-treatment) to 2–19 ng/ml (mean 8.3 ± 1.2 ng/ml post-treatment). In 12 of the subjects who responsed to chronic CB154 treatment, the mean daily values of HGH were below 10 ng/ml. The suppression of plasma HGH was maintained unaltered throughout the whole course of therapy. In the 9 subjects, in whom no consistent HGH decrease was evidenced with acute CB154 administration, there was accordingly a minor or no suppression of HGH values during the chronic treatment. In 13 subjects, irrespective of the degree of their GH responses, the plasma prolactin levels were constantly inhibited by CB154; instead the drug failed to modify significantly the TRH or insulin-induced GH release. These changes in the hormonal parameters were paralleled by marked clinical amelioration and improvement of some of the metabolic alterations frequently encountered in acromegaly, e.g. reduced carbohydrate tolerance, increased insulin resistance, diminished fall of plasma phosphorus after insulin, decreased urinary excretion of phosphate, hyper hydroxyprolinuria and hyper-calciuria. Collectively, these data demonstrate that CB154 thrapy is effective in reducing HGH hyper-secretion in many acromegalic patients during long-term treatment.

SUMMARY 100 mg i.m. sulpiride (a dopamine-receptor-blocking drug) led to a significant rise in plasma TSH in normal women, in female patients with galactorrhoea, and, to a much more marked degree, in male and female patients with primary hypothyroidism. In the hypothyroid patients, there was a significant positive correlation between basal TSH and its maximum increment after sulpiride. The drug proved to be an even more potent stimulator of PRL, at least in subjects with normal blood PRL. Normal males, on the other hand, displayed no significant changes in TSH after sulpiride. Continuous administration (150 mg/day per os for 15 days) also resulted in enhancement of TSH in normal women. These results suggest that TSH release is controlled by a dopaminergic mechanism in man. The more accentuated TSH response in hypothyroid patients may perhaps be attributable to the absence of negative-feedback on the part of thyroid hormones.

2-Bromo-alpha-ergocryptine (CB-154), AN ERGOT ALKALOID THAT STIMulates dopaminergic receptors, caused a widely varying, but significant increase in plasma GH levels in normal subject whereas a marked and protractedfall in values was observed in some patients with acromegaly. It is suggested that these effects were mediated by activation of either hypothalamic or hypophyseal dopaminergic receptors. The fact that GH values fell to or near normal levels in 4/8 cases suggests that CB-154 may have therapeutic possibilities in acromegaly.

The effect of the somatostatin analog (GHRIH-A) D-Trp8, D-Cys14 on plasma levels of growth hormone, pancreatic glucagon, insulin and glucose was studied in four acromegalic patients and in four maturity-onset mild diabetics. Acromegalics received a bolus iv injection of 25 microgram of GHRIH-A, followed by a continuous infusion of 25 microgram in saline over an hour. Mild diabetics were submitted in two different days to two tests: arginine (30 g in 30 min) +/- GHRIH-A (bolus iv injection of 25 microgram followed by an infusion of 25 microgram/h over 120 min) and arginine + saline. GHRIH-A lead to a significant (2 p less than 0.01) fall in GH basal secretion in acromegalics, and significantly reduced the GH response to arginine in maturity-onset diabetics. The inhibitory effect of insulin secretion was less impressive, but significative in both groups. No significant changes in plasma pancreatic glucagon values were noted. In mild diabetics, GHRIH-A infusion induced a small but significant increase in the blood glucose increment due to arginine. Our data suggest that this somatostatin analog may be potentially useful only when GH suppression is the main therapeutic goal to be reached, as in acromegaly and in severe diabetic retinopathy, but not in metabolic control of mild diabetic patients with a good residual insulin secretion.

In contrast with other dopaminergic drugs (L-dopa, apomorphine or bromocriptine) a 280 mug/min dose of dopamine infused for 120 min failed to induce an increase in plasma GH in 9 normal subjects. During dopamine infusion, no significant change in the GH response to arginine was also noted, whereas prolactin displayed a significant fall. In 15 acromegalic patients, on the other hand, the drug caused a marked fall in both GH (mean+/-SE; 71.1%+/-5.6) and prolactin (mean+/-SE; 67.6%+/-4.0) followed by a distinct rebound after the end of the test. There was a very close relation (P less than 0.001) between the maximum per cent decrease in GH during dopamine and after 2.5 mg bromocriptine by mouth. Dopamine also inhibited the GH response to TRH (4 patients). Since dopamine does not readily cross the blood-brain barrier, these results suggest that the stimulating effect of dopaminergic drugs on GH secretion in the normal subject is exerted via the CNS, whereas in acromegaly there is a direct action on structures lying outside the blood-brain barrier, probably in the hypophysis. Dopaminergic inhibition of prolactin is primarily the result of action on the hypophysis, as well as on the hypothalamus, in both normal and acromegalic subjects.

Clinical and/or biological improvement has been observed in 7 out of 17 patients with hyperprolactinemic amenorrhea followed for 6-15 months after the successful outcome of bromocriptine (Parlodel, Sandoz)- induced pregnancy. The ovulatory cycle was resumed in 2 out of these 7 patients (with subsequent spontaneous conception in 1); in 3 others the medroxyprogesterone acetate test became positive. In all cases, post-partum prolactin values were considerably reduced. The possible causes of this improvement are discussed, examining the present data and those in the literature. Regressive lesions, due for example to vascularization defects or hemorrhage occurring in the prolactin-secreting tissue, as a result of the hyperplastic stimulus of estrogens during pregnancy, are suggested as a possible explanation.

Renal excretion of phosphorus was studied in 52 acromegalic patients by means of the phosphate excretion index (PEI) described by Nordin and Fraser. Forty-eight patients were classified as having “active” acromegaly and 69% of these had PEI values below the lower limit of the range of a control series (39 subjects), whereas only 29% had plasma phosphorus values above the upper limit of the range of the controls. Postoperative PEI and plasma phosphorus values in patients classed as “inactive” after intrasellar implantation of 90Y, and who had normal adrenocortical function, were within normal limits. PEI also returned to normal in 7 patients classified as “improved.”

SUMMARY Plasma human growth hormone (HGH) concentrations were compared during four tests in which 0·9% NaCl solution only, propranolol, adrenaline or propranolol plus adrenaline were infused into six healthy volunteers. In five subjects, HGH levels during the infusion of saline, propranolol or adrenaline showed no significant increase and were virtually identical. During the test with propranolol plus adrenaline, however, there was an increase after adrenaline in spite of concomitant hyperglycaemia. The sixth volunteer showed a wide range of apparently spontaneous and irregular variations in HGH values throughout each of the four tests. These findings support the view that α-receptors stimulate and β-receptors depress HGH secretion, and show that adrenergically stimulated HGH secretion in man is not inhibited by hyperglycaemia.

Propranolol abolished the epinephrine-induced decrease in plasma potassium, in man. Propranolol also inhibited the rise in plasma lactic acid but only slightly affected the rise in blood glucose levels.

SUMMARY The effects of various adrenergic substances, either alone or in association with alpha and beta blocking agents, on human plasma growth hormone (GH) were studied in 36 normal volunteers. Plasma GH levels were unaffected by i.v. adrenaline (10 μg/min for 30 min) or by propranolol (1·5 mg/min for 10 min). Given together at the same doses, these drugs provoked sharp increases in plasma GH (from 8·5 to > 100 ng/ml; a mean increase of 30±8·02 (s.e.m.)). Reduction of the adrenaline dose to 7 μg/min produced a positive response in four out of six cases. The GH response to propranolol plus adrenaline was suppressed by simultaneous administration of phentolamine, but not significantly altered by glucose and aminophylline. Noradrenaline (7–14 μg/min for 30 min) produced no changes in plasma GH levels in six cases, while its association with propranolol was followed by an increase in only one out of four cases. Phenylephrine and tyramine were without effect, with or without propranolol. In five out of six cases, GH values gradually increased after oral administration of 1 g l-DOPA (from 4·2 to 85 ng/ml; mean, 30·2). This response was totally suppressed by phentolamine. It is considered that stimulation of GH by propranolol plus adrenaline and l-DOPA is mediated by alpha-adrenergic receptors. The possible role of a beta-inhibiting effect is discussed.

SUMMARY A study has been made of the inorganic serum phosphorus pattern in twenty-one acromegalic subjects during the 'augmented insulin tolerance test'. The serum phosphorus curve differed from normal in an elevated fasting level and, more especially, a reduction in the maximum fall. The latter anomaly is far more marked and constant than those found in the blood-sugar curve, and would thus seem to be a reliable criterion for the 'activity' of acromegaly.

An attempt was made to determine whether 6α-methyl-17α-acetoxyprogesterone (MAP) was as active as a glucocorticoid in man, as in experimental animals. This steroid was administered as a substitute for cortisone to 5 patients with definite signs of adrenal insufficiency. The subcutaneous administration of MAP in doses of 100 mg per day caused the prompt and complete disappearance of the symptoms attributable to glucocorticoid insufficiency which had developed when cortisone had been replaced by 9α-fluoro-hydrocortisone. When substitution treatment was carried out with MAP only, compensation was practically the same as with the daily administration of 50 mg cortisone. The glucose-tolerance and the insulin tests demonstrated that MAP administered subcutaneously displayed a marked glycogenetic activity.

Plasma prolactin (PRL) and human placental lactogen (HPL), and urinary estriol and pregnanediol were studied during pregnancies induced with bromocriptine (Parlodel, Sandoz) in 10 cases of hyperprolactinemia. Previous selective adenomectomy or intrasellar implantation of radioactive gold (198Au) failed to induce a complete remission in 3 of these subjects. PRL rapidly increases after bromocriptine withdrawal, reaching values higher than those in normal women in the same stage of pregnancy within a few weeks. At term, pathological PRL levels occurred in 3 subjects only (with distinct alterations of the sella turcica). Estriol, pregnanediol and HPL were normal in all cases. These findings suggest that PRL levels higher than those normally observed during pregnancy do not alter fetoplacental endocrine function.

The effect of propranolol on 1 g i.v. tolbutamide-induced insulin response was studied in 11 subjects. The drug depressed this response, the effect being more noticeable in the patients receiving 200 mg/ dayper os for three days. The corresponding blood glucose curves, however, were unaffected by propranolol. The finding suggest that the beta-receptors play a part in sulphonylurea-induced insulin secretion in man.

In all mammalian species studied so far, growth hormone (GH) is released in a pulsatile manner which would be crucial for proper somatomedin secretion and normal growth rhythm (Martin 1978; Muller 1987). This is true also in humans beings, in whom a deficiency in spontaneous GH pulsatility isassociated with short stature (Howse et al. 1977; Albertsson-Wikland et al. 1983; Thorner et al. 1986). However, an shown by Spiliotis et al. (1984), a reduced spontaneous GH secretion during the day is not always due to a pituitary secretory inability. In fact, there are many children in whom, in spite of low 24-h GH secretion, a marked somatotroph responsiveness to provocative tests is present. These children have been defined as having GH neurosecretory dysfunction, i.e., an altered GH neuroregulation that leads to a GH deficiency. Therefore, from a clinical viewpoint, the importance of studying the neural control of GH secretion is evident.

The effect of propranolol on certain insulin-induced metabolic changes in man. The effects of 0.2 mg/kg/body weight propranolol perfused in 10' on insulin-induced (0.15 I.U./Kg i.v.)changes in blood glucose, pyruvate, lactic acid, phosphorus, and potassium levels were examined in 12 normal volunteers. The blood glucose curve was substantially unaffected. Insulin-induced increases in lactate and pyruvate were inhibited to a varying degree, namely 78% (61-93%) and 44% (0.94%) respectively. The fall in phosphorus was reduced in a more constant manner (mean 48; range 37-57%) in all subjects, while that of potassium was not altered. The data indicate that these insulin-induced changes are significantly, though variably, attributable to beta-adrenergic activity on the part of endogenous catecholamines released during insulin-induced hypoglycaemia.

To verify the diagnostic capacity of some dynamic tests of the prolactin (Prl) secretion, the findings obtained by high-resolution computed tomography (CT) were compared with results obtained from tests using nomifensine (NOM) domperidone (DOM) and thyrotrophin-releasing hormone (TRH) in 72 patients with pathological hyperprolactinaemia. None of the patients with tumours had a positive Prl response to NOM or to DOM administration; however, a positive response to these tests was present in only 24 and 41%, respectively, of the patients with normal CT picture. The results of TRH testing were similar to those obtained with DOM. Different neuroendocrine patterns were disclosed by comparing pituitary Prl and thyrotrophin (TSH) responses to DOM: 1) some subjects had a reduced Prl response together with an exaggerated or normal TSH response to DOM; they comprised patients with tumour, empty sella, and normal CT picture; 2) other patients with normal CT picture had a positive Prl and a normal TSH response to DOM. These results demonstrate that a negative Fri response to NOM and DOM characterizes all patients with adenoma; however, the tumour-like responses in patients with no visible tumours seem to reduce the diagnostic value of these tests, unless the latter may predate the radiological appearance of an adenoma. On the other hand, a positive Prl and a normal TSH response to DOM exclude the presence of a pituitary tumour. This diagnostic finding is strengthened by the positive response also to NOM. Whatever may be the diagnostic validity of dynamic tests, they provide sound information on the functional state of dopamine neurotransmission.

The prolactin (PRL)-releasing effect of domperidone (DOM), a novel antidopaminergic drug which does not cross the blood-brain barrier, was investigated in normoprolactinemic subjects, in subjects with physiologic puerperal hyperprolactinemia or pathological hyperprolactinemia. DOM (4 mg i.v.), administered to 8 normoprolactinemic women, induced a clear-cut and sustained rise in plasma PRL, with peak levels occurring 15-30 min postinjection; the effect of the drug was also evident in 3 normoprolactinemic women at the dose of 0.25 mg i.v. Also in 8 puerperal women (postpartum day 2) intravenous administration of 4 mg DOM was followed by an increase in plasma PRL (51-517% of baseline levels, 15-45 min postinjection). Administration of DOM (4 mg i.v.) to 16 subjects with pathological hyperprolactinemia, evidenced the presence of 14 DOM-nonresponder (maximum percent increase of baseline PRL 48%) and 2 DOM-responder subjects. In 8 of the DOM-nonresponder subjects the existence of a pituitary tumor was established at surgery by selective removal of an adenoma (7 subjects) or a teratoma (1 subject): of the 6 subjects who did not undergo surgery, 3 had biochemical and/or radiologic evidence suggestive of a PRL-secreting tumor and 1 was acromegalic. These results indicate that DOM is capable of releasing PRL both in normoprolactinemic subjects and subjects with puerperal hyperprolactinemia. In contrast, DOM is unable to modify PRL levels in most subjects with pathological hyperprolactinemia, with proven or suspected pituitary tumors.

Recently, a new long-acting form of bromocriptine (Parlodel LA, Sandoz) has been developed and it has already been found to be effective in lowering plasma PRL levels in normal volunteers and postpartum women. This work reports the clinical, hormonal and radiological effects of a single 50 mg dose of long-acting bromocriptine in 10 patients with tumorous hyperprolactinemia (2 microprolactinomas, 6 macroprolactinomas, 1 acromegaly and 1 nonsecreting macroadenoma). A rapid and long-lasting (28 days) normalization of PRL levels was observed in patients with microprolactinoma, acromegaly and nonsecreting adenoma. None of the 6 patients with macroprolactinoma underwent normalization of plasma PRL, but the latter was markedly reduced (61–80% of basal levels). A second injection of the drug in 5 macroprolactinoma patients induced a further reduction of plasma PRL levels in 2 of them. No changes in the tumor size were observed either after the first or the second injection of long-acting bromocriptine in any of the patients. This injectable form of bromocriptine induced nausea and/or mild hypotension Jasting a few h in 4 of the 10 patients and was better tolerated than the oral form as regards both the duration and intensity of the side effects. Thus, as this drug has proved to be efficacious and well tolerated by the patients, this long-acting form of bromocriptine may be a valid therapeutical approach for initiating medical treatment of patients with prolactinoma.

A study of the effect of alpha-methyl-1-tryosine (metyrosine) blockade (2 g/d for 2 d) of dopamine (DA) synthesis on the PRL and TSH response to domperidone (DOM) and TRH in normal women and subjects with pathological hyperprolactinaemia is reported. In the normal subjects, there was a marked increase in basal PRL (51.7 +/- 11.1 vs 5.7 +/- 1.0 ng/ml) and the PRL and TSH responses to DOM were abolished. The PRL response to TRH was also reduced. In the hyperprolactinaemic subjects, metyrosine had no effect on basal PRL nor on the virtually non-existent PRL response to DOM, whereas it abolished the exaggerated TSH response. The conclusion is drawn that the response of both PRL and TSH to DA receptor blockers is really dependent upon DA inhibitory tone. A fall in this tone can also be postulated as responsible for the hyporesponsiveness of PRL to DOM frequently observed in pathological hyperprolactinaemia. In addition, the fact that metyrosine also abolished the exaggerated TSH response to DOM shows that the latter is totally dependent on enhanced DA inhibition of the thyrotrophs. Lastly, the reduced PRL response to TRH after metyrosine indicates that DA partly determines the ability of the lactotrophs to respond to TRH.

To find if endorphins can influence hormonal responses mediated by noradrenergic pathways, we examined the effects of naloxone, an opiate receptor blocker, on the GH and insulin responses to clonidine, a drug which acts by stimulation of α-adrenergic receptors. Intravenous clonidine (0.15 mg in 10 min) induced a significant fall of plasma insulin and a marked increase of plasma GH. Intravenous naloxone (bolus of 1.6 mg followed by 50 μg/min) did not change the insulin response to clonidine, and seemed to induce only a slight delay in the GH response.

Following previous work showing that i.v. arginine induces a fall in blood phosphorus and an increase in blood potassium in normal subjects, investigation of the mechanism underlying these metabolic changes was extended to a group of 14 insulin-dependent diabetics and a further 6 normal volunteers. In the diabetics, arginine (0.5 g/kg body weight) in 30 min caused a slight, but significant fall in blood phosphorus (delta = -0.40 +/- 0.04 mg/ml p less than 0.01). This was well below the fall noted in the normal subjects, which, as demonstrated in the earlier study, is to a great extent mediated by insulin. The increase in blood potassium was much more marked than in the normal subjects (delta = + 1.42 +/- 0.15 mEq /l; p less than 0.001) and rose to pathological levels (5.6 to 6.5. mEg/l) in 9 out of 14 patients. There were no significant changes in blood pH, plasma osmolality, or plasma aldosterone. Inhibition of the glucagon response to arginine by means of a priming dose of 250 micrograms somatostatin, followed by infusion of 1,500 micrograms/hr, did not abolish the rise in blood potassium. These findings indicate that insulin protect against arginine-induced hyperkalaemia and that this metabolic alteration does not depend on glucagon, acidosis, enhance plasma osmolality, nor the suppression of aldosterone secretion. Persons with low insulin secretion due, for example, to stress or diabetes, run the risk of pathological hyperkalaemia if subjected to i.v. infusion of arginine.

Prolactin (PRL) and growth hormone (GH) secretion have been evaluated in 17 acromegalic patients following acute administration of two dopamine (DA) receptor antagonists, i.e. sulpiride (SULP) and domperidone (DOM). Six patients had persistent hyperprolactinemia. In 8 normoprolactinemic patients, i.m. injection of 100 mg SULP elicited only a slight rise in plasma PRL, which was strikingly lower than that SULP induced in control subjects. Likewise, an i.v. bolus injection of DOM (4 mg) was barely effective to raise plasma PRL in the 11 normoprolactinemic and the 6 hyperprolactinemic patients. DOM was instead capable of inducing a clear-cut rise in plasma PRL in normoprolactinemic controls and in a group of subjects with puerperal hyperprolactinemia. Neither drug affected GH secretion in acromegalic patients. It is proposed that a defective tuberoinfundibular DA function or, alternatively, a diminished PRL reserve due to a decrease pituitary lactotroph mass may be responsible for the blunted PRL responsiveness of acromegalics. However, standing the paucity of present knowledge on the pituitary PRL secretory pool in acromegalics, neither hypothesis seems capable to account satisfactorily for the reported results.

SUMMARY There is evidence indicating that the cholinergic system positively modulates GH release probably by inhibiting somatostatinergic tone. In the present study, the effects of cholinergic enhancement by pyridostigmine, (PD), a cholin-esterases inhibitor, on GH release in normal adults (n= 14) (NA) and in both normal (n = 5) (NC) and short children (n = 19) (SC) with familial short stature (n =7) or constitutional growth delay (n= 12) were studied. In SC the insulin hypoglycaemia (IH)-induced GH increase was also studied. In both NC and SC 60 mg orally PD induced a significant GH increase with mean peak at 90 min (mean ± SEM 11.0 ± 2.2 ng/ml in NC and 11.2 ± 2.3 ng/ml in SC). The GH areas under response curve (AUC) were 379.3 ± 76.6 and 327.8 ±43.2 ng/ml/h in NC and SC respectively. In NA 120 mg orally PD induced a significant GH increase with mean peak at 120 min (5.1 ± 11 ng/ml) which was significantly lower (P < 0.05) than that observed in both NC and SC. This statistical difference was strengthened by evaluating AUC (NA: 205.6 ± 33.7 ng/ml/h, P < 0.05 vs NC and SC). The correlation of drug dosage with body area ruled out that this difference could be related to the different PD dose in adults and children. In SC, IH induced a GH increase significantly lower than that observed after PD (GH peak 7.8 ± 0.6 vs 16.4 ± 1.9 ng/ml P

A case of true hermaphroditism with 46, XX/46, XY karyotype is reported. The propositus, reared as a male, showed ambiguous external genitalia with perineoscrotal hypospadias, and internal genitalia represented by bilateral ovotestes, normal uterus and tubes. Periodic menstrual bleedings appeared at puberty. The endocrinologic data demonstrated the secretory activity of both the ovarian and the testicular tissue. The analysis of red cell, lymphocyte and serum markers, done on the propositus and on his parents, failed to show any evidence of double fertilization. On this basis, the origin of the XX/XY condition (mosaicism versus chimerism) and its developmental consequences are discussed.

In the treatment of hyperprolactinemia bromocriptine is generally administered in 3 daily doses during the day. Due to the limited compliance of patients under this long term regimen, in 16 hyperprolactinemic patients we investigated the efficacy and tolerability of the treatment with this dopaminergic drug administered as a single evening dose. This dose was the same which the patients had been assuming previously on a tid basis. Chronic treatment (4-12 months) with an oral single evening dose of bromocriptine is able to control plasma PRL at least as well as the traditional tid regimen (2.8-21.6 ng/ml vs 1.2-31.8 ng/ml). Furthermore, during this single dose regimen the side effects were of lesser intensity and extent. Since the compliance of the patients with the single dose regimen was very good and the efficacy the same in reducing plasma PRL and controlling the clinical manifestations with a lower rate of side effects, we suggest to extend this regimen to all patients with hyperprolactinemia treated with bromocriptine after successful reduction of plasma PRL levels is obtained.

The effect of 100 mg im sulpiride on plasma Prl levels was studied in 10 normal females, 21 patients with galactorrhoea and normal plasma Prl, 10 women with puerperal hyperprolactinaemia and 27 patients with amenorrhoea-galactorrhoea and high plasma Prl levels. The response to sulpiride in patients with galactorrhoea but normal Prl was slightly higher (P < 0.05) than that observed in normal women, but only if expressed in per cent. Women with puerperal hyperprolactinaemia respond to the drug with a marked increase in Prl (mean ± sem: 563.0 ± 142.8%), even though their baseline values are already very high (mean ± sem: 133.6 ± 23.8 ng/ml). By contrast, there is a lower or no response to sulpiride in 13 women with pituitary tumour. The same was true in 11 patients with hyperprolactinaemia of uncertain aetiology but also 10 of these subjects presented signs suggestive of a tumour. In the last 3 patients with pathological hyperprolactinaemia in whom a consistent Prl increase after sulpiride was observed, hyperprolactinaemia was probably not of tumourous origin. On the basis of these results, the sulpiride test appears promising for discriminating between organic and 'functional' cases of enhanced Prl secretion.

To verify if the low estrogen regimen could condition the TSH hyperresponsivity and PRL hyporesponsivity to antidopaminergic drugs seen by us and others in patients bearing prolactinoma, the effect of ethynilestradiol treatment (50 micrograms/day/14 days) on TSH and PRL responses to domperidone in 6 women with tumoral hyperprolactinemia and hypoestrogenemia were studied. Estrogenic treatment was unable to modify the TSH and PRL responsiveness either to domperidone and TRH. These data do not support the hypothesis that hypoestrogenemia could cause the peculiar TSH and PRL pattern in response to antidopaminergic drugs, in patients bearing prolactinoma. Also the TRH releasable pool of TSH and PRL in these patients seems to be unaffected by estrogenic treatment.