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In order to offer data on the epidemiological profile of women with low bone density (LBD), we have considered information collected in the framework of a large cross-sectional study conducted on women around menopause attending a network of first level outpatients menopause clinics in Italy.During 1997 and 2000, a large cross sectional study was conducted on the characteristics of women around menopause attending a network of first level outpatients menopause clinics in Italy for general counseling about menopause or treatment of menopausal symptoms. Eligible for the study were women consecutively observed during the study period. Up to March 2000 a total of 42464 women (mean age 53 years) were observed at the 268 participating centers. Bone mass density was measured in 25113 cases, which are considered in this analysis. LBD (i.e. osteopenia or osteoporosis) was defined according to WHO classification.The frequency of LBD increased with age: in comparison with women agedor =51 years, the odds ratio (OR) of LBD was 1.5 and 2.2, respectively, in women aged 52-55 andor =56. No association emerged between LBD and parity: in comparison with nulliparae, the OR of LBD were 1.1 and 1.0, respectively, in women reported 1 or 2 or more full term pregnancies. Smokers were at increased risk of LBD, the corresponding OR being for smokers, in comparison with non smokers, 1.2 (95% confidence interval, CI, 1.1-1.3). In comparison with women in the lower tertile of body mass index, the OR of LBD decreased in subsequent tertiles, being, respectively, 0.9 and 0.7 in the middle and highest tertile. The OR of LBD was 2.2 in postmenopausal women, in comparison with premenopausal ones and the OR decreased increasing age at menopause. Ever OC users were at slightly decreased risk of LBD: in comparison with never OC users, the OR was 0.9 (95% CI 0.8-1.0) in ever OC users.The results of this large study confirm, in a Southern European population, the association of age at menopause and body mass on the risk of LBD, and suggest that ever OC women are at decreased risk of LBD.

Objective: To analyse determinants of hysterectomy for benign uterine conditions with or without oophorectomy in Italy, a country with among the lowest rates of hysterectomy worldwide. Methods: Between 1997 and 1999, a large cross sectional study was conducted on the characteristics of women around menopause attending a network of first level outpatients menopause clinics in Italy for general counselling about menopause or treatment of menopausal symptoms. A total of 25 644 women entered the study. Characteristics of women who underwent and women who did not undergo hysterectomy and oophorectomy were compared. Results: Out of the 25644 women considered, 4727 were hysterectomized (18.4%). Mean age at surgery was 46.8 years. The OR of hysterectomy decreased with increasing educational level: in comparison with women with primary and none education, the OR of hysterectomy was 0.8 (95% CI 0.7-0.9) and 0.6 (95% CI 0.5 0.7) respectively for women with intermediate or high university degree. Body mass index (BMI, kg m -2 ) was related to the frequency of hysterectomy; in comparison with women with BMI ≤ 23.8, the OR of hysterectomy was 1.2 (95% CI 1.1 1.3) and 1.4 (95% CI 1.2-1.5) respectively for women with a BMI 23.8-27.2 and > 27.2. The frequency, of bilateral oophorectomy increased with age at hysterectomy: in comparison with women who have had hysterectomy when aged ≤43 years, the OR of bilateral oophorectomy during hysterectomy was respectively 1.9, 3.4 and 4.3 in women who had hysterectomy at age 44 47, 48 51 and > 52 years. The frequency of bilateral oophorectomy was lower in more educated women: in comparison with women reporting none or primary degree the OR was 1.0 and 0.8 respectively for women with intermediate and high university degree. Conclusions: The results of this analysis indicate that hysterectomy for benign conditions is more frequently performed in less educated women, in nulliparae and in women with higher BMI. During hysterectomy for benign conditions, bilateral oophorectomy is more frequent in less educated women and its frequency increases with women's age.

OBJECTIVE It is widely accepted that arginine is a potent GH secretagogue in man, probably acting via inhibition of hypothalamic somatostatin release. Although many other amino acids are known to stimulate GH secretion, their effects and mechanisms of action have not been extensively studied in humans. The aim of the present study was to clarify the effect, if any, of methionine (MET) on GH secretion in children with normal short stature (normal height velocity and IGF-1 >100 μg/l). DESIGN We studied the effect of MET (0.2 g/kg intravenously (i.v.) over 30 min) on both basal and GHRH (1 μg/kg i.v. at 0 min)-induced GH secretion (group A) comparing its effect with that of arginine (ARG) at low and classical doses 0.2 and 0.5 g/kg i.v. over 30 min) (groups B and C). The effect of the combined administration of MET and ARG (0.5 g/kg i.v. over 30 min) (group D) on GH secretion was also studied. PATIENTS Thirty-four children (20 male and 14 female, age 12.8–14.0 years), divided into four groups. MEASUREMENTS Serum GH was measured in duplicate by immunoradiometric assay. RESULTS In group A, MET increased basal GH levels (peak, mean ± SEM 14.6 ± 2.6 vs 2.6 ± 0.6 mU/l; P

Ghigo E, Ceda GP, Valcavi R, Goffi S, Zini M, Mucci M, Valenti G, Muller EE, Camanni F. Effect of 15-day treatment with growth hormone-releasing hormone alone or combined with different doses of arginine on the reduced somatotrope responsiveness to the neurohormone in normal aging. Eur J Endocrinol 1995;132:32–6. ISSN 0804–4643 It is well known that both spontaneous and growth hormone-releasing hormone (GHRH)-stimulated GH secretion undergo an age-related decrease; in addition, there is supportive evidence that the GH hyposecretory state of aging is of hypothalamic origin. The aims of the study in 35 normal elderly subjects (20 males and 15 females aged 65–89 years) were to verify whether the low somatotrope responsiveness to GHRH (1 μg/kg) can be primed by a daily GHRH treatment and whether the potentiating effect of both high intravenous (0.5 g/kg) and low oral (8 g) doses of arginine (ARG) on GH response to GHRH is maintained with time. In group A (N = 14) the GH response to GHRH on day 1 (AUC: 373.5 ± 78.5 μg·1−1·h−1) was unchanged after 7 (3720 ± 38 μg·1−1·h−1) and 15 days (377.9 ± 63.8 μg·1−1·h−1) of daily GHRH administration. In group B (N = 6) the GH response to GHRH co-administered with iv ARG on day 1 (1614.2 ± 146.2 μg · 1−1 · h−1) was higher (p < 0.05) than that of GHRH alone (group A) and persisted unchanged after 7 (1514.7±366.5 μg·1−1·h−1) and 15 days (1631.7 ± 379.1 μg · 1−1 · h−1) of treatment. In group C (N = 15) the GH response to GHRH co-administered with oral ARG on day 1 (950.6 ± 219.4 μg·1−1 · h−1) was higher (p < 0.03) than that of GHRH alone (group A) but lower (p < 0.05) than that to GHRH plus iv ARG (group B). It was unchanged after 7 (816.2 ± 208.5 μg·1−1 · h−1) and 15 days (760.4 ± 165.0 μg · 1−1· h−1) of treatment; these responses were still higher (p < 0.05) than that to GHRH alone. Insulin-like growth factor I levels were not modified by any of the treatments. In conclusion, our results demonstrate that in normal aging the low somatotrope responsiveness to GHRH is not improved by prolonged treatment with the neurohormone but it is enhanced by the combined treatment with ARG and this effect does not vanish after a 15-day treatment period. The effect of ARG is present even after a low oral dose, although less markedly than after a high intravenous dose. F Camanni, Divisione di Endocrinologia, Ospedale Molinette, C. so Dogliotti 14, 10126 Torino, Italy

In man the GH-releasing hexapeptide His-DTrp-Ala-Trp-DPhe-Lys-NH2 (GHRP-6) has been shown to be active even after oral administration. On the other hand, it has been shown that arginine (ARG) totally restores the reduced somatotropic responsiveness to GHRH observed in aging. Based on the foregoing, in this study we verified the GH-releasing activity of oral GHRP-6 (300 µg/kg) in normal aging and the possible enhancing effect of 8 g oral ARG on the GH-releasing effect of GHRP-6. Eight young (age 24–32 yr) and 8 elderly (age 66–85 yr) subjects were studied. In all the GH response to GHRH (1 µg/kg iv) was also studied. Both IGF-I levels and the GH response to iv GHRH were lower in elderly than in young subjects (mean±SE, IGF-I: 65.1±9.1 vs 142.9±9.4 µg/L, p

Administration of cholinergic agonists increases both basal and GH-releasing hormone (GHRH)-induced GH secretion, probably acting via inhibition of endogenous somatostatin release. The aim of our study was to verify in two groups of children with idiopathic short stature the effect of intranasal administration of neostigmine (inNS; 3 mg), a cholinesterase inhibitor, on basal GH levels as well as on the somatotroph response to GHRH when the peptide was administered either iv (ivGHRH; 1 microgram/kg) or intranasally (inGHRH; 10 micrograms/kg). In group A (n = 6; age, 10.6-16.0 yr) inNS induced a significant GH increase [inNS vs. saline, area under the curve (AUC; mean +/- SEM), 263.7 +/- 60.2 vs. 73.8 +/- 3.1 micrograms/L.h; P less than 0.03] and potentiated the somatotroph response to ivGHRH (inNS with ivGHRH vs. ivGHRH, 1316 +/- 183.0 vs. 644.9 +/- 154.5 micrograms/L.h; P less than 0.03). In group B (n = 6; age, 11.5-15.9 yr) ivGHRH induced a GH rise clearly higher than that induced by inGHRH (604.2 +/- 154.3 vs. 137.1 +/- 28.2 micrograms/L.h; P less than 0.03). Administration of inNS induced a GH rise similar to that occurring after inGHRH (AUC, 239.2 +/- 69.5 micrograms/L.h) and markedly increased the inGHRH-induced GH response (482.4 +/- 103.6 micrograms/L.h; P less than 0.05 and 0.03 vs. inNS and inGHRH, respectively), so that it overlapped with that induced by ivGHRH alone. In conclusion, cholinergic agonists such as neostigmine are able to increase both basal and GHRH-induced GH secretion in short children even when given intranasally. Combined intranasal administration of neostigmine and GHRH (10 micrograms/kg) is able to induce a GH rise similar to that induced by ivGHRH alone (1 microgram/kg), suggesting the potential usefulness of this combination cocktail and route of administration for the treatment of short stature.

Prevalence, phenomenology, comorbidity, functional impairment and familial correlates of juvenile panic disorder (PD) are described in this study. A clinical interview (Diagnostic Interview for Children and Adolescents-Revised) was administered to 220 children and adolescents consecutively referred to a Division of Child Neurology and Psychiatry. 23 subjects (10.4%), aged 7 to 18 years, fulfilled DSM-IV criteria for PD. Reported panic symptoms are described, according to gender and chronological age. High comorbidity with generalized anxiety disorder (74%) and depression (52%) was noted. Agoraphobia (56%) and other phobias (56%) were significantly more frequent than in two control groups of subjects with generalized anxiety disorder and with depression. Antecedent and/or associated separation anxiety disorder was reported in 73% of the patients. Functional impairment, assessed with a specific diagnostic instrument (Children's Global Assessment Scale) was significantly greater in PD patients than in depressed or anxious patients. 90% of patients had at least one parent with an anxiety disorder, 52% had one parent with depressive disorder, 33% had one parent with drug treated PD.

Aim of this study is to examine the effect of depressive comorbidity in 108 children and adolescents with Generalized Anxiety Disorder (GAD). Fifty-five patients with GAD and depression were compared with 53 patients with GAD without depression. Age, gender and socioeconomic status did not differentiate the groups. Patients with comorbid depression had significantly more anxiety symptoms than patients without depression. Clinical presentation of GAD and pattern of comorbidity was similar in the two groups. Subjects with comorbid depression showed a more severe functional impairment, assessed with C-GAS. Data are discussed in the light of conceptualizations about the relationship between anxiety and depression.

In the male sexual and aggressive drives are mostly centered on the penis, whose real or fantasied features strongly affect the way children and adolescents build up their own personal and gender identity. In some clinical conditions a shift of genital centrality from penis to testicles is evident. The most frequent is abnormality in the descent of testicles, especially cryptorchidism, characterized by an arrested descent of one or two testicles that remain in the abdomen. The aim of this paper is to define mechanisms by which cryptorchidism increases psychological vulnerability. Time of diagnosis and treatment, restoration of genital integrity, personality stability and familial interactions are considered as elements affecting psychopathological outcome. Behavioral and psychological features in children and adolescents with cryptorchidism are reviewed. A case report of an adolescent with unilateral cryptorchidism is reported and discussed, as an example of pubertal distortion in bodily and gender identity.

The absolute bioavailability of reboxetine enantiomers was assessed in six male and six female volunteers. In a two-way crossover study, subjects received 1.0 mg reboxetine orally and 0.3 mg reboxetine as an intravenous bolus. The R,R(-) and S,S(+) enantiomers in serial plasma and urine samples were determined by a validated LC-MS-MS method. There were no significant differences between treatments for clearance or dose-corrected AUC(0-infinity) values. The absolute bioavailability was 0.919 and 1.02 for R,R(-) reboxetine and S,S(+) reboxetine, respectively. A secondary objective of the study was to assess gender effects on pharmacokinetics of the enantiomers. Significant differences in volume of distribution between genders were observed, but differences in weight-corrected volumes were not significant. Weight-corrected systemic clearance and oral clearance tended to be lower in males, but this difference reached statistical significance only for weight-corrected oral clearance of R,R(-) reboxetine. C(max) after oral administration was 40 and 48% higher in women than men for R,R(-) reboxetine and S,S(+) reboxetine, respectively. These results indicate that reboxetine enantiomers are well absorbed after oral administration and that little first-pass metabolism occurs. There are no clinically significant effects of gender on the pharmacokinetics of reboxetine enantiomers.

Objective Cabergoline is now established as an effective and well-tolerated treatment for prolactinoma. However, there are relatively few published data on the treatment of macro-, as opposed to micro-, prolactinoma. We have therefore reviewed the efficiency and safety of cabergoline in the treatment of patients with prolactin-secreting macroadenomas treated on a compassionate basis. Study design and patients Eighty-five patients with prolactin-secreting macroadenomas were treated with cabergoline 0.25 to 10.5 mg per week (median 1 mg) given to one to seven doses. Treatment durations ranged between 3 months and 8 years. Sixty-five patients (32 intolerant, 16 resistant) had been treated previously with other dopamine agonists. Pretreatment prolactin levels ranged between 80 and 8300 micrograms/I and tumour maximum diameters were between 11 and 42 mm. Measurements Serum prolactin, visual fields if initially abnormal, occurrence of menses or return of libido and potency, blood chemistry and adverse events were assessed at 1 month and then at 3-month intervals during treatment. Pituitary computed tomography or magnetic resonance imaging was usually repeated at 3 months and 1 year, then yearly, in most patients (n = 62). Results Normalization of prolactin levels was achieved in 52 patients (61.2%) and a prolactin decrease of at least 75% of pretreatment values occurred in 24 others (28.2%). Of the 20 de novo patients, 17 had prolactin normalized and the remainder had at least 75% reduction. Disappearance of tumour image was found in eight of 62 evaluable patients (12.9%) and reduction of the largest diameter by at least 25% in another 33 (53.2%), with an overall success rate of 66.1%; among the 17 evaluable de novo patients the success rate was 82.3%. Fifteen of 21 patients who failed to show tumour shrinkage had previously demonstrated resistance/intolerance to other prolactin-lowering treatments. Of the 12 patients with visual field defects at baseline, six normalized and two showed an improvement. Menses resumed during cabergoline treatment in 79.5% of premenopausal women. Restoration of potency was reported by seven of eight evaluable men. Adverse events were recorded in 24.7% of cases, four of whom (4.7%) discontinued treatment. Conclusions Although the present data were not obtained in a formal study we conclude that cabergoline is an effective and well-tolerated treatment for macroprolactinoma patients.

Of the amino acids arginine is the most potent GH secretagogue in man. It potentiates the GH response to GHRH, exerts a weaker PRL-releasing effect, stimulates insulin and glucagon and induces a biphasic glucose variation. The potency and effects of other amino acids on pituitary and pancreatic hormones need to be clarified. In 43 children with normal short stature (5.3-14.0 yr; 30 M and 13 F) the effects of the infusion of phenylalanine (Phe, 0.08 g/kg), histidine (His, 0.1 g/kg), and leucine (Leu, 0.08 g/kg) on basal and GHRH-stimulated GH secretion and on PRL, insulin and glucose levels were studied and compared with those of arginine at high (hArg, 0.5 g/kg) or low dose (lArg, 0.2 g/kg). Phe increased basal (p < 0.05) but not GHRH-stimulated GH levels, induced PRL and insulin rises (p < 0.03 and p < 0.03), and did not change glycemia. Though a trend toward an increase in basal GH levels was found after His, His and Leu did not significantly modify either basal or GHRH-induced GH secretion nor basal PRL, insulin and glucose levels. Both hArg and lArg increased basal (p < 0.0001 and p < 0.05, respectively) and GHRH-stimulated GH levels (p < 0.006 and p < 0.006). hArg increased both PRL (p < 0.002) and insulin levels (p < 0.005) more (p < 0.0005 and p < 0.004) than lArg (p < 0.005 and p < 0.005), while glucose levels showed a similar increase followed by a similar decrease. We conclude that in childhood: a) Phe significantly increases GH secretion but, differently from Arg, does not potentiate the response to GHRH, suggesting different mechanisms of action of these amino acids; b) differently from His and Leu, Phe is a PRL and insulin secretagogue but is less potent than Arg; c) Arg has the highest stimulatory effect on pituitary and pancreatic hormones.

Reportedly, the responsiveness of somatotrope cells to GHRH is reduced in elderly humans but it is totally restored by arginine (ARG) which likely acts by inhibiting hypothalamic release of somatostatin. As this effect was observed after infusion of high doses of the amino acid, in this study, we compared the effect of iv administration of 30, 10 and 5 g ARG(group A, B and C, respectively) as well as oral administration of 8 g ARG(group D) on the GH response to 1 microgram/kg i.v.GHRH in 27 healthy elderly subjects (11 M and 16 F, age 70-86 yr, BMI 21-25 kg/m2). In group A (n = 7) 30 g i.v. ARG strikingly enhanced the GHRH-induced GH rise (peak, mean +/- SE: 41.5 +/- 4.4 vs 11.7 +/- 5.3 micrograms/L, p < 0.05). Similarly, in group B (n = 6) and D (n = 7) 10 g i.v. and 8 g oral ARG enhanced the GH response to GHRH (20.9 +/- 4.7 vs 8.3 +/- 2.8 micrograms/L, p < 0.03 and 31.0 +/- 5.3 vs 11.4 +/- 3.4 micrograms/L, p < 0.03, respectively). In contrast, in group C (n = 7) 5 g i.v. ARG failed to modify the GHRH-induced GH rise (6.0 +/- 1.6 vs 3.5 +/- 0.9 micrograms/L). The GH responses to GHRH alone did not significantly differ amongst groups; the GH responses to GHRH and ARG were not significantly different among groups A, B and D and were greater than the GH response in group C. These results show that the GH response to GHRH in elderly subjects is enhanced even by low iv doses of arginine and by the orally administered amino acid, the lowest effective dose being 8 g. Moreover, they imply that the combined administration of GHRH and arginine may be a useful approach to restore the impaired function of the GH-IGF axis in aging.

GH secretion was evaluated in 214 children and adolescents (age, 5-16 yr; 160 males and 54 females) with short stature (height,or = 5th percentile) by assessing mean spontaneous overnight GH concentration (normal values,or = 3 and 3.9 micrograms/L for prepubertal and pubertal subjects, respectively) and responsiveness to stimulation with GH-releasing hormone combined with pyridostigmine (normal peak values,or = 20 micrograms/L). Plasma insulin-like growth factor-I (IGF-I) was also measured. According to their GH secretory status, children were grouped as follows: group I, 154 subjects with normal spontaneous and stimulated GH (43 slow-growing and 111 normally growing); group II, 39 subjects with low spontaneous, but normal stimulated, GH (27 slow-growing and 12 normally growing); group III, 18 slow-growing subjects with low spontaneous and stimulated GH; and group IV, 3 subjects with normal spontaneous, but low stimulated, GH. The following conclusions were drawn. 1) Forty-five slow-growing subjects (21% of the total sample) had GH deficiency; 27 (12.6%) belonged to group II (with a preserved GH pituitary reserve, denoting a hypothalamic dysfunction) and 18 (8.4%) to group III (with a reduced GH pituitary reserve). 2) Forty-three slow-growing children in group I had normal GH secretion but low mean IGF-I, which may indicate nutritional problems or a biologically hypoactive GH molecule. 3) The remaining 111 subjects in group I (52%), with normal growth rate, but low mean parental height, were considered as having familial and/or constitutional short stature. GH responses after pyridostigmine plus GH-releasing hormone were normal in all children with a normal growth rate. These findings show that besides clinical evaluation, the assessment of spontaneous GH secretion, GH pituitary reserve, and IGF-I concentration allows proper pathophysiological characterization of short stature. By this approach, the frequency of GH deficiency in our sample was higher than commonly thought.

Aim of this study was to verify whether arginine (ARG), which likely inhibits hypothalamic somatostatin release, has an enhancing effect on the GHRH-induced GH rise, even when administered orally at low dose. To this goal we studied the effects of 4 g orally administered ARG, either hydrochloride (ARG-H) or aspartate (ARG-A), on both basal and GHRH (1 μg/Kg iv) -stimulated GH secretion in 31 children with familial short stature (11 males and 20 females, aged 5.5–13.8 yr, pubertal stage l–lll, and compared the results with those of iv infusion of 0.5 g/kg ARG-H. Oral ARG-H (Group A,n=11) induced a significant increase of basal GH levels (4.2±1.3 vs 1.0±0.4 μg/L, p

There is evidence that GH secretion is reduced in normal elderly subjects as well as in patients with Alzheimer''s disease (AD). To clarify the mechanisms underlying this GH hyposecretory state in 14 elderly subjects (age 65–75 years) and 15 AD patients (age 61–78 years), we studied the effects of both pyridostigmine (PD, 120 mg orally), a cholinesterase inhibitor, and arginine (ARG, 0.5 g/kg i.v.), two substances likely acting via inhibition of hypothalamic somatostatin, on GH response to GHRH (1 (µg/kg i.v.). The GH response to PD alone was also studied. Twenty-two young healthy volunteers were studied as control group. Basal GH levels were similar in young, elderly and AD subjects (0.7 ± 0.2, 0.8 ± 0.2 and 0.9 ± 0.2 µg/1). IGF-I levels were lower (p < 0.005) in elderly (73.9 ± 8.2 µg/1) and in AD subjects (108.0 ± 5.9 µg/l) than in young subjects (288.7 ± 22.1 µg/l); however, they were higher (p < 0.01) in AD patients than in the elderly subjects. The PD-induced GH release did not significantly differ in young, elderly and AD subjects while the GH responses to GHRH in the elderly (AUC: 297.9 ± 49.2 µg/l/h) and in AD subjects (437.6 ± 93.5 µg/l/h) were lower (p < 0.01) than in young subjects (658.6 ± 100.1 µg/l/h). PD potentiated the GH response to GHRH both in elderly and in AD subjects (901.7 ± 222.4 and 1,070.3 ± 207.2 µg/l/h, p < 0.005) but these responses were lower (p < 0.0001) than those recorded in young subjects (2,041.1 ± 245.6 µg/l/h). ARG potentiated the GHRH-induced GH rise both in elderly and in AD subjects (1,545.2 ± 246.0 and 1,659.3 ± 196.8 µg/l/h,p < 0.001) but in this case, the GH response to GHRH + ARG overlapped with that in young subjects (2,140.2 ± 229.5 µg/l/h). In contrast to young subjects, in elderly and in AD subjects, the potentiating effect of ARG on GHRH-induced GH rise was higher (p < 0.01) than that of PD. These results show that testing neural controls of GH secretion with different neuroactive substances does not allow to differentiate normal aging from AD. In both groups, somatotroph responsiveness to GHRH is potentiated by the enhancement of the cholinergic activity but much more by ARG, which is compatible with the presence of a cholinergic impairments.

The authors report their experience with the diagnosis and surgical correction of varicoceles in 20 patients. They stress the usefulness of the Doppler Ultrasound for the diagnosis of subclinical varicocele.

The Authors report their experience with stapler model T.A. 30 in lung resections; 100 stapled sutures were carried out in the IV Surgical Department of the University "La Sapienza" of Rome, during the period 1980-88. The use of stapler with two rows of staples allows a secure closure of the bronchial stump. Moreover, it prevents granulomas caused by suture material. The bronchopleural fistulas, serious complications of manual suturing, did not occur. Finally, this method is simpler and rapidly feasible in comparison with classic ones.

Serum total and free T4 and T3, thyroxinebinding globulin (TBG) and TSH, basal and 20, 30 and 60 min after TRH (200 μg, iv), were evaluated in 125 hypothyroid patients (38 with severe, 23 with mild, and 64 with subclinical hypothyroidism), in 35 euthyroid subjects with autoimmune thyroiditis, and in 51 healthy controls. T4/TBG and T3/TBG ratios were also calculated. A significant decrease in all indices of thyroid function except for T3 occurred simultaneously with a significant increase in basal and TRH-stimulated TSH levels from healthy subjects to subclinical hypothyroids, from subclinical to mild and from mild to severe hypothyroids; euthyroid patients with autoimmune thyroiditis did not differ from healthy subjects. All severe hypothyroid patients had low T4 as well as free T4 (FT4), free T3 (FT3), T4/TBG and T3/TBG ratios, but among mild and subclinical hypothyroids direct determination of FT4 and FT3 proved to be a better index of thyroid function than determination of T4 and T3 even after correction for TBG levels. FT4 was the most commonly abnormal index (19 of 23 subjects with mild and 14 of 64 with subclinical disease). Regression analysis showed that FT4, T4/TBG ratio, T4, and FT3 had a significant inverse correlation with TSH in hypothyroid patients. Discriminant analysis showed that among the thyroid parameters, FT4 is the variable which discriminates best between control subjects and the 3 groups of hypothyroid patients. These data extend previous reports and in a large series of patients confirm the biological meaning and the clinical value of direct measurement of serum free thyroid hormones in hypothyroidism. Nevertheless, the finding that both FT4 and FT3 are in the normal range in some patients with mild and in most with subclinical hypothyroidism indicates that increased TSH secretion remains the most sensitive index of thyroid failure.

The new long-acting ergoline derivative cabergoline was given orally in a single dose of 300 micrograms to 15 hyperprolactinemic patients (including 4 acromegalic patients, 2 of whom were dopamine responsive). Serum PRL and GH levels were determined before and 3, 4, and 6 h and 1, 2, 3, 4, 5, 6, and 7 days after treatment. A control test with a single oral dose of 2.5 mg bromocriptine was also performed; serum PRL and GH levels were measured at the same time intervals for 2 days. Cabergoline induced a marked fall in serum PRL which began within 3 h and continued for 7 days. The maximal decrease ranged between -49.2% and -55.2% and occurred after 2-5 days. This maximal effect was only slightly less than that 6 h after bromocriptine treatment (-63.8%). After cabergoline treatment, serum GH levels did not change significantly in either nonacromegalic or acromegalic patients, whereas the two dopamine-responsive acromegalic patients had a marked GH fall after bromocriptine. A moderate blood pressure decrease, more evident in the standing position, occurred after both cabergoline and bromocriptine treatments. The only symptomatic side-effect was orthostatic hypotension after cabergoline in an elderly woman. These data indicate that cabergoline has potent and prolonged dopaminergic activity and may prove suitable for once weekly treatment of hyperprolactinemic patients.

Circulating thyroglobulin antibodies (TgAb) and microsomal antibodies (MsAb) and thyroid function (total and free T4 and T3, TSH basal and after TRH) have been evaluated in 92 hyperprolactinaemic patients (82 females and 10 males; 9 with macroprolactinoma, 22 with microprolactinoma, 4 with acromegaly, 5 with organic lesions of the hypothalamus, 2 with empty sella, 2 with idiopathic hypopituitarism, 2 with primary hypothyroidism, and 46 with idiopathic hyperprolactinaemia). Thyroid function was normal in all cases except 3 with hypothalamic disease and central hypothyroidism, the 2 patients with primary hypothyroidism and 2 with thyrotoxicosis (one due to Graves' disease and one to autonomous thyroid adenoma). High titres of TgAb (≥1/1250) and/or MsAb (≥ 1/1600) were found in the subject with Graves' disease, in one acromegalic, in the 2 primary hypothyroids, and in 12 women with either adenomatous or idiopathic hyperprolactinaemia; low titres of one or both antibodies were found in 9 other euthyroid women and in the one with toxic adenoma. In a control population of 185 subjects studied with the same methods, the prevalence of TgAb and/or MsAb positive (low titres) was 3.3% in females and 2.5% in males. Diffuse thyroid hyperplasia was clinically detectable in 12 euthyroid women and in the one with Graves' disease; 3 others had been previously operated for nodular goitre with histological evidence of Hashimoto's thyroiditis (2 cases) or for a cold nodule; a single thyroid nodule was present in the woman with toxic adenoma and in one euthyroid woman. Most of these subjects also had circulating TgAb and/or MsAb, and a few had increased TSH secretion. No significant differences were found in mean thyroid hormone and TSH levels between euthyroid hyperprolactinaemic subjects and healthy controls, but TRH-stimulated TSH levels were significantly higher in thyroid antibodies positive than negative subjects. These data, in agreement with a few previous reports, suggest that autoimmune thyroid disorders (especially asymptomatic autoimmune thyroiditis) occur in hyperprolactinaemic women with a prevalence far exceeding that observed in many surveys in the general population.

A healthy young man developed unilateral claudication due to an isolated lesion of his external iliac artery, At operation, this was found to be obliterated by atherosclerotic change of long standing. No evidence of systemic disease was noted. A vascular reconstruction has allowed the patient to return to an active life style.

Ghigo E, Arvat E, Rizzi G, Goffi S, Grottoli S, Mucci M, Boghen MF, Camanni F. Growth hormonereleasing activity of growth hormone-releasing peptide-6 is maintained after short-term oral pretreatment with the hexapeptide in normal aging. Eur J Endocrinol 1994;131:499–503. ISSN 0804–4643 The reduced activity of the growth hormone (GH)–insulin-like growth factor I (IGF-I) axis in aging may contribute to changes in body composition. As this GH insufficiency is due to hypothalamic pathogenesis, the availability of GH-releasing peptides (GHRPs), such as GHRP-6 (His-d-Trp-Ala-Trp-d-Phe-Lys-NH2) which is active even after oral administration, might be useful to restore it. The aim of our study was to verify the effectiveness of oral administration of GHRP-6 in normal elderly subjects and to investigate whether its GH-releasing activity is maintained or vanishes after short-term oral treatment. Seven normal elderly women (aged 65–82 years) were studied. The effect of oral administration of 300 μg/kg GHRP-6 on GH secretion was investigated before and after 4 days of treatment with the hexapeptide given twice daily. The GH response to the maximal effective dose of GHRH (1 μg/kg iv) also was studied. Before treatment, oral administration of 300 μg/kg GHRP-6 elicited a clear GH rise (peak 10.7 ± 3.3 μg/l; AUC 353.1 ± 90.6 μg·l−1·h−1). which was significantly higher (p < 0.01) than that induced by intravenous GHRH (peak 5.1 ± 1.5 μg/l; AUC 106.5 ±43.9 μg · l−1·h−1). After 4 days of treatment with GHRP-6, the GH response to the hexapeptide was maintained, with a trend towards an increase (peak 16.8 ± 2.9 μg/l; AUC 499.8 ± 107.2 μg·l−1·h−1). The IGF-I levels were not increased significantly after treatment (77.1 ± 8.4 vs 84.1 ± 12.2 μg/l). In conclusion, our results demonstrate that, in aging, oral GHRP-6 administration elicits a GH response that is higher than the maximal effective dose of intravenous GHRH and that the effect of the hexapeptide does not vanish after short-term treatment. More prolonged treatment and/or more frequent administrations of GHRP-6 are likely needed to increase IGF-I levels. F Camanni, Division of Endocrinology, Department of Pathophysiology, Ospedale Molinette, C.so Dogliotti 14, 10126 Torino, Italy