Acute beta-interferon or thymopentin administration increases plasma growth hormone and cortisol levels in children.

The interaction between the immune and endocrine systems has recently been investigated. Hodgkin's disease represents a model of immune disturbance frequently associated with endocrine impairment. The present study evaluated the effect of the acute administration of beta-interferon or thymopentin on plasma growth hormone, prolactin and cortisol levels in children with Hodgkin's disease (N = 8) and age- and sex-matched healthy controls (N = 8). beta-interferon (1,000,000 IU), thymopentin (50 mg) or placebo (saline) were injected after two basal blood samples (-15 and 0) and further samples were drawn at 15, 30, 45, 60, 90 and 120 min. Plasma growth hormone, prolactin and cortisol levels were measured by specific RIAs. Plasma prolactin levels did not show significant change following beta-interferon or thymopentin injection in either the controls or the patients. In the patients with Hodgkin's disease, beta-interferon injection induced a significant increase in both plasma growth hormone and cortisol levels, while thymopentin was not effective. In controls both thymopentin and beta-interferon administration increased plasma growth hormone and cortisol levels. These results indicate that beta-interferon and thymopentin are immune substances active on the release of growth hormone and cortisol in healthy children. The lack of effect of thymopentin in children with Hodgkin's disease suggests an impairment of the immune-endocrine interaction in these patients.

Reduced spinal bone density in young women with amenorrhoea.

To assess the influence of diminished oestrogen production on bone density, we studied 23 amenorrhoeic women and 20 controls (age range 16-29 years) divided into four groups: group 1: 6 patients with idopathic hypogonadotrophic hypogonadism with primary amenorrhoea (IHH); group 2: 5 patients with delayed puberty owing to thalassaemia major (TM); group 3: 12 patients with secondary hypothalamic amenorrhoea (HA); group 4: 20 women with normal menses (controls). Secondary sexual characteristics had developed in all except the women with TM. Groups 1 and 2 had never menstruated and group 3 had been amenorrhoeic for 6 months to 3 years. The control group was studied during the follicular phase of the cycle. None of the patients were taking oestrogens at the time of observation. Plasma concentrations were determined for 17 beta-oestradiol (E2), deidroepiandrosterone sulphate (DHEA-S), cortisol (F), prolactin (PRL), thyroid hormones (T3 and T4), and gonadotrophins (LH and FSH). Spinal bone mineral density (BMD g/cm2) was assessed by dual photon absorbiometry. BMD (mean +/- 1SD) was reduced in the patients (group 2: 0.920 +/- 0.95; group 1: 0.980 +/- 0.94; and group 3: 1.037 +/- 0.75) as compared with the controls (1.290 +/- 0.95) (P less than 0.01). In the three groups of patients, plasma E2 levels were lower than 50 pg/ml and were positively correlated with the BMD. As expected, plasma gonadotrophin levels were highly and significantly reduced (P less than 0.01) in the patients, compared with that of the controls. These results suggest that reduced spinal BMD in hypogonadic women may be related to the lack of oestrogenic influence on bone metabolism.(ABSTRACT TRUNCATED AT 250 WORDS)

[Melorheostosis linear scleroderma with osteopoikilosis. Description of a clinical case]. / Sclerodermia lineare meloreostotica con osteopecilia. Descrizione di un caso clinico.

A case of melorheostosis with osteopoikilosis and linear scleroderma is reported. The authors emphasize the rarity of the disease, the complexity of the therapeutic approach to the patient.

Prolactin changes after administration of agonist and antagonist dopaminergic drugs in puerperal women.

Prolactin (PRL) is an anterior pituitary hormone which plays a large part in the reproductive function of mammals. Its only well-documented effect in humans is that of initiating and maintaining lactation. Among hypothalamic neurotransmitters regulating the anterior pituitary function, dopamine (DA) is currently considered to correspond to the PRL-inhibiting factor. The central control mechanisms which induce high PRL levels in puerperal women are not well understood. To study DA tonus in puerperium we tested plasma PRL levels in different groups of puerperal subjects (6 per group) after acute administration of direct or indirect DA agonists or placebo: DA, L-dopa (a DA precursor), L-dopa plus carbidopa (a peripheral dopa-decarboxylase inhibitor), nomifensine (a DA-releasing and blocking or reuptake agent) and amphetamine (a DA releaser). The same tests with the same drug doses were performed on groups of healthy volunteers. A consistent reduction in plasma PRL levels after both direct and indirect DA agonist drugs compared to placebo was evident in puerperal and in control women. A different trend was only observed with the use of DA and amphetamine in puerperal subjects, who, unlike controls, failed to show a rebound in plasma PRL levels after the termination of drug infusion. These findings support the view that the inhibitory control of tuberoinfundibular neurons over PRL secretion is maintained in puerperium and changes in the affinity of DA receptors are related to the endocrine milieu which occurs during gestation.

Prolactin secretion after surgery or bromocriptine treatment of prolactinoma.

In prolactinoma patients, the unresponsiveness of prolactin (PRL) to dynamic tests with thyrotropin-releasing hormone (TRH) or dopamine agonist or antagonist drugs suggests that the disease is caused by the failure of central dopaminergic inhibition. The absence of PRL secretory response to dopamine or TRH in prolactinoma patients also may be an effect of the disease. Twenty-six women diagnosed by dynamic tests and radiologic examination as having PRL-secreting adenoma were treated surgically (15) or with bromocriptine (11) and their condition was evaluated one to three years later by TRH, nomifensine, and domperidone tests. Basal PRL levels decreased after surgery and bromocriptine treatment. At the time of the follow-up study, PRL levels were elevated in six of the 15 surgically treated patients and in six of the 11 treated with bromocriptine. Thyrotropin-releasing hormone, nomifensine, and domperidone produced standard PRL responses in normoprolactinemic patients but not in hyperprolactinemic patients. These results indicate that the alteration of TRH or dopaminergic receptors in the regulation of PRL secretion in prolactinoma is related to the disease and disappears when the tumor is removed or treated successfully with bromocriptine.

Changes in immunoreactive beta-endorphin, methionine-enkephalin and ACTH in bone marrow cells and fluid from leukemic children.

The present study demonstrates the presence of the endogenous opioid peptides, beta-endorphin (beta-EP) and methionine-enkephalin (MET-ENK), and of ACTH in cell homogenates and interstitial fluid from sternal biopsy of leukemic children. The peptides were identified by chromatography and radioimmunoassay. In leukemic children with lymphoblastic cells present in the sternal sample, concentrations of immunoreactive (ir) beta-EP in the cell homogenate, but not in the fluid, were significantly higher than in leukemic children with normal bone marrow. In contrast, ir MET-ENK and ir ACTH did not differ between the two study groups either in the cell homogenate or in the fluid. These data suggest the presence of a complex system of opioid peptides in the cells and interstitial fluid of bone marrow of leukemic children with the highest concentrations of ir beta-EP appearing in samples collected during the active phase of the disease, and may suggest a possible role of opioid peptides as immunomodulatory substances.

Plasma opioids in the newborn in relation to the mode of delivery.

Elevated plasma concentrations of beta-lipotropin (beta-LPH) and beta-endorphin (beta-EP) are present in vaginally delivered babies in the first 24 h of life. To establish if fetal distress or different types of delivery influence the secretion of these peptides in the neonatal period, we studied 16 vaginally delivered newborns (VD), 11 neonates extracted through elective cesarean section (CS) and 8 babies suffering from acute intralabor fetal distress (FD). In all groups of newborns the plasma levels of beta-LPH and beta-EP were measured in arterial and venous cord blood, at 1 and 24 h from delivery. beta-LPH and beta-EP were determined by specific radioimmunoassays after silicic acid extraction and Sephadex G-75 column chromatography. In cord plasma, there were no differences between arterial and venous concentrations of either beta-LPH or beta-EP in any of the groups. In the 1st h after delivery the plasma levels of VD newborns were similar to umbilical cord values (beta-LPH: 19.9 +/- 5.2; beta-EP: 18.1 +/- 2.4), while those of CS (beta-LPH: 30.6 +/- 4.5; beta-EP: 30.1 +/- 5.8) and FD (beta-LPH: 64.9 +/- 11.8; beta-EP: 65.7 +/- 24.4) showed a significant increase. At the 24th h of life the plasma concentrations of both peptides decreased significantly in the three groups, but CS and FD babies showed significantly higher plasma values than VD newborns (p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Domperidone in defective and insufficient lactation.

The clinical use of anti-dopaminergic drugs to stimulate plasma PRL levels, to induce lactogenesis and maintain an adequate lactation has been widely suggested, taking into consideration the main inhibitory role of hypothalamic dopamine on PRL secretion. We therefore studied the effects of domperidone (DOM), a direct anti-dopaminergic drug with a low tendency to be secreted in the milk and which does not cross the blood-brain barrier, on inducing lactogenesis in 8 puerperal women with a history of defective lactogenesis (group A) and inducing galactopoiesis in 9 puerperal women who showed 2 weeks after delivery an insufficient lactation (group B). A placebo treatment was performed in 7 and 8 puerperal women with the same characteristics of group A and B, respectively. PRL plasma levels were assayed in basal conditions and after suckling from the 2nd to the 5th day of puerperium in group A and through a 10-day treatment in group B. In both groups domperidone-treated subjects always showed baseline PRL levels and daily milk yield significantly higher than those of the placebo group (P less than 0.01). The lack of any side-effects and the positive results suggest a high usefulness of such a drug in inducing and/or maintaining successful breast feeding, which is at present considered so important for a healthy development of infants.

Calcium homeostasis in the first days of life in relation to feeding.

Determinations of serum calcium (Ca), phosphorus (P), magnesium (Mg), calcitonin (CT) and parathyroid hormone (PTH) were carried out in full term newborn infants during the first 168 h of life. The infants were randomly assigned to two different diets: glucose and breast feeding (BF) only or early formula feeding (F). The Ca serum levels decreased from birth to the 24th h; after that time they increased until the 72nd h. The values of serum Ca at the 48th and 72nd h were significantly lower in the F than in the BF group. In contrast, the P serum levels increased from birth to the 48th h and then they decreased; the values of serum P at the 48th h were significantly higher in F than in the BF group. The CT serum levels increased from birth to the 24th h and then they decreased. No difference between the F and BF groups was found during the first 48 h, while at the 72nd h the F group demonstrated significantly higher values of serum CT. PTH serum levels also increased from birth to the 24th h with significantly higher values at the 72nd h in the F group. The results of this investigation demonstrate that the difference in feeding in the first hours of life affects the calcium homeostasis and the secretion of hormones involved in the regulation of serum Ca levels.

Central opioid receptor activity in patients affected by puerperal, idiopathic and tumoral hyperprolactinemia.

The aim of our study was to evaluate the activity of opioid receptors involved in the regulation of prolactin secretion in different kinds of hyperprolactinemic states (puerperal, idiopathic and tumoral subjects). Prolactin plasma level changes were measured after the acute administration of a met-enkephalin synthetic analogue. FK 33-824, and placebo. The prolactin-releasing effect of this drug, evident in control subjects, was blunted in patients affected by idiopathic hyperprolactinemia, and absent in puerperal and tumoral patients. These results indicate that hyperprolactinemia affects the activity of central opioid receptors, with the most evident effects in patients with highest prolactin plasma levels.

Calcitonin and parathyroid hormone in newborn infants with fracture of the clavicle.

Determinations of serum calcium (Ca), phosphorus (P), calcitonin (CT), and parathyroid hormone (PTH) were carried out in 36 full-term newborn infants with fracture of the clavicle (CF) and in 46 normal neonates (N). At the 6th hour of life the CF neonates demonstrated lower serum Ca and higher serum CT in comparison with normal infants. In the hours following, no significant differences between the two groups for the Ca levels were found, whereas serum CT remained significantly higher in the CF newborns at the 24th, 48th, and 72nd hour of life. Significant differences between normal and CF infants in the PTH serum levels were detected only at the 48th hour, when PTH was lower in the CF newborns. The results of this investigation indicate that the fracture of the clavicle is a significant and peculiar factor in stimulating CT secretion. Serum Ca level appeared to be controlled by CT rather than auto-regulating the secretion of the hormone.

Fetomaternal opioid levels and parturition.

The present study evaluates the plasma level changes in beta-lipotropin and beta-endorphin in nine women at term throughout spontaneous labor, in ten pregnant women undergoing elective cesarean section in the absence of uterine contractions, and in ten women submitted to emergency cesarean section because of fetal distress occurring during labor. A basal plasma sample was taken before labor in the 39th week of pregnancy. Two subsequent samples were then obtained before and after parturition, together with umbilical cord samples at birth. beta-lipotropin and beta-endorphin were measured by radioimmunoassay after silicic acid plasma extraction and gel filtration. In cases of spontaneous labor, there was a progressive increase in opioid concentrations as labor progressed, the maximal values being observed after delivery. Cord values were similar to those observed in the mother, without showing any relationship to them. Pregnant women undergoing cesarean section in the absence of labor show constant beta-lipotropin and beta-endorphin concentrations both before and after fetal extraction, both values being significantly lower than those found at delivery after spontaneous labor. beta-Endorphin neonatal levels were significantly higher than in the respective mothers and were in the same range as those of infants born through vaginal delivery. In the third group (cesarean section performed at the first stage of labor), presurgical opioid levels were higher than in women at the same stage of spontaneous labor, whereas postextraction values showed a wide range, with mean values similar to those observed after spontaneous delivery.(ABSTRACT TRUNCATED AT 250 WORDS)

Steroid secretion by the prepubertal human testis.

It has been demonstrated that the human testis secretes testosterone and, to a smaller extent and less constantly, also androstenedione. Testosterone, progesterone, 17 alpha-hydroxyprogesterone and 20 alpha-dihydroprogesterone have been measured in the spermatic and peripheral venous blood of prepubertal boys undergoing surgery for undescended testis or inguinal hernia repair. The spermatic plasma levels of testosterone and progesterone were significantly higher than peripheral levels. A significant spermatic-peripheral gradient was not found for 17 alpha-hydroxyprogesterone and 20 alpha-dihydroprogesterone. These studies demonstrate that the secretory pattern of the human prepubertal testis is different from that of the adults.

[Serum levels of parathormone, calcium, magnesium and phosphorus in the perinatal period]. / Livelli serici di paratormone, calcio, magnesio e fosforo nel periodo perinatale.

Two groups of newborns on different diets were studied: group A was given artificial milk, while group B was breast fed. Blood samples from the cord artery and vein were taken at birth and further blood samples after 1, 6, 12, 24, 48, 72, 96 and 168 hours. No baby underwent more than three blood samples. Calcium (Ca), magnesium (Mg), phosphorus (P) and parathormone (PTH) were measured in all samples. There was a rapid increase in PTH levels in all subjects in the first hours after birth. At 48th the babies in group A had significantly higher serum levels of P than the group B subjects, and their serum Ca and Mg levels were significantly lower. At 72th PTH serum levels were significantly higher in group A, while Ca and Mg levels were significantly higher in group B. In conclusion, the subjects demonstrated a normal secretion of PTH at birth, and the type of diet notably influenced the homeostasis of calcium in the perinatal period.

Possible testicular 3 beta-hydroxysteroid dehydrogenase deficiency in cryptorchid neonates.

In order to explain the impaired neonatal secretion of testosterone (T) in cryptorchid neonates, plasma levels of luteinizing hormone (LH), follicle stimulating hormone (FSH), precursors of T, and T were measured in bilateral cryptorchid and control babies from the first to the 90th day of life. RIA of steroids was performed after plasma ether extraction and celite ethylen glycole column chromatography. In comparison to the neonatal period, plasma LH, dehydroepiandrosterone (DHA), and T were increased in both groups at the 60th day, although cryptorchids showed significantly lower T level (1018 +/- 168 pg/ml) than controls (1985 +/- 410 pg/ml, p less than 0.001). At the same time, androstenedione (A) and 17 alpha-hydroxy-progesterone (17P) remained unchanged. Dihydrotestosterone (DHT) concentrations were higher in cryptorchids in the neonatal period, and increased in both groups at the second to third month of life. The T/DHT ratio was significantly higher in cryptorchids in all age groups. These data indicate that (1) neonatal T formation probably occurs through the delta 5 pathway; (2) impaired T secretion in cryptorchid neonates could be due to a deficiency of 3 beta-hydroxysteroid dehydrogenase; and (3) cryptorchid neonates exhibit an elevated 5 alpha-reductase activity of unknown origin.

Spermatic and peripheral venous plasma concentrations of progesterone, 17 alpha-hydroxyprogesterone, and 20 alpha-dihydroprogesterone in prepubertal boys.

Testosterone, progesterone, 17 alpha-hydroxyprogesterone, and 20 alpha-dihydroprogesterone have been measured in the spermatic and peripheral venous blood of 17 prepubertal boys undergoing surgery for undescended testis or inguinal hernia repair. Mean (+/-SE) spermatic testosterone and progesterone (538 +/- 212 and 704 +/- 110 pg/ml, respectively) were significantly higher (P less than 0.005) than peripheral levels (91 +/- 11 and 419 +/- 71 pg/ml, respectively). No significant spermatic-peripheral gradient was found for 17 alpha-hydroxyprogesterone and 20 alpha-dihydroprogesterone. These in vivo studies demonstrate that the secretory pattern of the prepubertal testis is different from the adult testis.

Spermatic and peripheral venous plasma concentrations of dehydroepiandrosterone sulfate in prepubertal and pubertal boys.

Dehydroepiandrosterone sulfate (DEAS), a major adrenal product, is quantitatively one of the most important steroids found in human testicular tissue. However, conflicting data have been reported about the testicular production of DEAS 'in vivo'. We have measured the spermatic and peripheral concentrations of testosterone (T) and DEAS in two groups of prepubertal (Group I, N = 18) and pubertal (Group II; N = 11) boys undergoing surgery for undescended testis, inguinal hernia or varicocele. Mean (+/- SE) spermatic concentrations of DEAS (77 +/- 16 and 113 +/- 19 micrograms/dl in Group I and II respectively) were not significantly different from peripheral concentrations (70 +/- 13 and 130 +/- 16 micrograms/dl in Group I and II respectively). Mean spermatic concentrations of T (153 +/- 101 and 7515 +/- 4314 ng/dl in Group I and II respectively) were significantly different from peripheral concentrations (9 +/- 1 and 149 +/- 53 ng/dl; P less than 0.001 in both groups). Spermatic and peripheral levels of T and DEAS found in prepubertal boys were significantly lower than those found in pubertal boys. Spermatic levels of DEAS were not significantly related with spermatic levels of T in both groups. Our data show that, as in adult subjects, no significant spermatic-peripheral DEAS gradient is present in prepubertal and pubertal boys.

[The effects of diet on the secretion of calcitonin in the newborn infant]. / Effetti della dieta sulla secrezione di calcitonina nel neonato.

Determinations of serum calcium (Ca), phosphorus (P) and calcitonin (CT) were carried out in two groups of full term newborn infants: 80 on bottle feeding (group A) and 80 breast feeding (group B). Samples of blood were drawn at 1, 6, 12, 24, 48, 72, 96 and 168 hours of life. Each newborn was tested no more than twice. No differences between the two groups could be detected before the 72th hour. At that time, the Ca of group A was significantly lower than Ca of group B while the CT and P were significantly higher in the same group A. So that, the P serum level appears to be one of the most important factor regulating the homeostasis of Ca after the first 72 hours of life.

[The secretion of calcitonin in the newborn infant in relation to the method of delivery]. / La secrezione di calcitonina nel neonato in relazione alle modalita' del parto.

Determinations of serum (Ca) and calcitonin (CT) were carried out in 80 full term newborn infants. 40 of them were born by elective Caesarean section (ECS) while 40 were born by normal vaginal delivery (VD). Samples of blood were drawn at 1, 24, 48, 168 hours of life. Each newborn was tested no more than twice. Serum Ca of ECS at 24th hour was significantly less than Ca of VD. At the same time CT of ECS was significantly higher than CT of VD. A negative significant correlation between Ca and CT was observed. The data demonstrate the key role of CT in the homeostasis of Ca in the first hours of life. In addition, the results were suggestive for a dependence of CT secretion on the stress of birth.