[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.

Pyridostigmine effects on TSH response to TRH in adult and children obese subjects.

Thyrotropin releasing hormone (TRH) administration is known to induce a greater TSH response in normal subjects than in obese subjects. In obesity even GH and PRL response to various stimuli are blunted, presumably because of an augmented somatostatinergic tone in obese subjects. Further studies have shown that pyridostigmine (Pyr), an acetylcholinesterase inhibitor, is capable of augmenting GH in obesity by means of somatostatin inhibition. In order to evaluate the possible interference of an increased somatostatinergic tone on TSH secretion, we studied the TSH response to a TRH bolus in 5 obese children with or without a pyr pretreatment. Similarly, we tested a group of 10 obese adult subjects, with TRH alone or TRH plus pyr administration, 30 min or 60 min before TRH. All subjects had a body weight of 30-50% greater than I.B.W. Our data show that a pretreatment with pyr, 60 min before TRH administration, significantly augments the TSH response in adult obese subjects but not in children; the modality of pyr administration seems to be crucial to evidenciate such an alteration since the pyr pretreatment is not effective when administered 30 min before TRH. The absence of this pyr effect in obese children induces to hypothesize that somatostatinergic tone is differentially modulated in children vs adult obese subjects.

Growth hormone response to growth hormone-releasing hormone in early abstinent alcoholic patients.

The alpha-2-adrenoceptor agonist clonidine is able to stimulate GHRH secretion directly or via beta-endorphin and, therefore, induces a GH release in normal subjects. This effect has been shown to be blunted in alcoholism during early abstinence, due to central alterations of adrenergic mechanisms. To evaluate pituitary responsiveness to direct stimulation with GHRH, we have studied the GH and PRL response to GHRH in 10 alcoholics during early abstinence. Our data indicate that the pituitary response to GHRH is intact in abstinent alcoholics, except in obese patients, who displayed a blunted GH response. GHRH did not increase PRL. The dissociation between clonidine and GHRH in GH stimulation could reveal a different neuroendocrine mechanism, in comparison with other psychiatric disorders (anorexia nervosa), in which such a dissociation is accompanied by a PRL response to GHRH.

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.

Endocrine evaluation of patients with benign lumps of the breast.

We studied 39 women with benign breast disease in order to evaluate their endocrine status. Two groups of women were distinguished: premenopausal (n = 22) and postmenopausal (n = 17). We determined basal concentrations of the following: follicle-stimulating (FSH) hormones, luteinizing hormone (LH), prolactin (PRL), estrone (E1), estradiol (E2), testosterone (T), androstenedione (A), dehydroepiandrosterone sulfate (DHEAS). We also assayed sex hormone-binding globulin (SHBG) and calculated the free androgen index (FAI). The samples in premenopausal subjects were collected in the follicular phase. There was no significant difference between the groups considered and normal control subjects for any of the hormones tested; there was no significant correlation between T concentration or E2/T ratios and SHBG levels; the FAI was not significantly different compared to normal subjects. In conclusion, even if basal steroid, gonadotropin, and SHBG levels do not indicate an unequivocal alteration, it is not possible to exclude subtle alterations in transport and local metabolism of steroids. The balance between steroids and SHBG seems to indicate small dysregulations, which could be of some importance.

Prolactin as a protective factor in stress-induced biological changes.

The adenohypophyseal hormone prolactin (PRL) is released during stress of physical and psychological nature. In animals, this hormone facilitates adaptive behavior, induces analgesia, and enhances grooming behavior. It also reduces corticosterone secretion and the incidence of gastric ulcers induced by physical stress. It is possible that PRL plays a protective role against stress-induced biological modifications in animals.

Response to human chorionic gonadotropin in patients with ovarian tumors.

The results of hCG stimulation on peripheral levels of androstenedione (A), testosterone (T) and estrone (E1) were examined in 14 patients with ovarian tumors and in 9 tumor-free subjects, after the menopause. Following hCG injection, 9 postmenopausal patients with ovarian tumors showed a significant rise in A peripheral levels. The responsive subjects generally had significant increases in A baseline levels, too. The remaining 5 subjects with advanced or poorly differentiated ovarian cancer with no stroma were not responsive to hCG. Moreover, in the tumor group, 7 subjects had increased baseline T and/or E1 and in 3 of them an increase of these steroids was observed following hCG. In the absence of ovarian tumor, no subject in the control group was responsive to hCG administration. The results of the present investigation seem to confirm the in vivo responsiveness to hCG of ovarian tumors.

Ultrasonic and endocrinologic relationships in spontaneous and induced follicular phase.

To correlate ovarian growth and follicular size with 17 beta-estradiol (E2) and androstenedione (A) peripheral levels, 20 induced cycles, 6 spontaneous ovulatory cycles and 6 spontaneous anovulatory cycles from 32 women during follicular phase were examined in order to obtain a better insight in the events involved in multiple folliculogenesis. In spontaneous ovulatory cycles, a significant correlation was obtained between E2 plasma levels and volume of the dominant follicle (p less than 0.05) as well as total follicular volume (p less than 0.01). Plasma A was significantly related with sonographic features likely related to ovarian stroma as well as preantral and antral subordinated follicles, which usually fail to ovulate. Significant correlation between E2/A peripheral ratio and volume of the dominant follicle(s) was also found (p less than 0.01). In anovulatory cycles, inverse significant correlation between E2 and sonographic aspects of degenerating antral follicles (p less than 0.001) was found, whereas a positive significant correlation between E2 and ovarian stroma was obtained (p less than 0.001). No correlation between peripheral A and any ovarian sonographic compartment was evident. However in the anovulatory cycles group a significant correlation between A v E2 peripheral levels was found, too. During HMG regimen, all the ovarian compartments seemed to be responsible for E2 peripheral levels. Ovarian stroma as well as preantral and multiple antral follicles were related to A levels. E2/A peripheral ratio did not result to be a good indicator of the large follicles. During "pure" FSH therapy, exclusive correlations between estrogen and large follicles as well as total follicular volume were found.(ABSTRACT TRUNCATED AT 250 WORDS)