Eugenio Rasio

Recurrence of Hyperprolactinemia after Selective Transsphenoidal Adenomectomy in Women with Prolactinoma

To assess the long-term prognosis for women with prolactinoma after selective transsphenoidal adenomectomy, we followed 44 patients for 6.2 +/- 1.5 years. Group 1 (28 patients) had microprolactinomas, and Group 2 (16 patients) had macroprolactinomas. After surgery, normal plasma prolactin levels, resumption of menses, and cessation of galactorrhea were observed in 24 Group 1 patients (85 per cent) and 5 Group 2 patients (31 per cent). Hyperprolactinemia recurred in 12 of the 24 Group 1 patients and in 4 of the 5 Group 2 patients after 4 +/- 1.3 and 2.5 +/- 1.6 years of remission, respectively. There was no radiologic evidence of tumor recurrence in any patient, and no relation was found between the occurrence of pregnancy after surgery and the recurrence of hyperprolactinemia. Clinical and biologic features before surgery could not predict the long-term outcome. However, the immediate postoperative level of plasma prolactin was significantly lower in patients in whom normal prolactinemia (6.4 +/- 1.1 ng per milliliter) was maintained than in those who relapsed (11.7 +/- 1.5 ng per milliliter) (P less than 0.02). We conclude that recurrence of hyperprolactinemia after successful surgery is frequent but delayed. The immediate postoperative level of plasma prolactin may be a predictive risk factor.

Decreased sensitivity to insulin in women with microprolactinomas

To determine whether there exists an altered sensitivity to insulin in hyperprolactinemia, we studied, in 15 women with microprolactinomas, the insulin effects on glucose, PRL, GH, and cortisol before and after successful adenoma removal. Our results show that in women with microprolactinomas, the sensitivity to insulin is lower in hyperprolactinemia than in normoprolactinemia achieved by selective adenomectomy.

Hypothalamic-pituitary-adrenal axis in abdominal obesity: effects of dexfenfluramine.

OBJECTIVE Hyperactivity of the HPA axis is a possible mechanism underlying abdominal obesity. We aimed to evaluate in premenopausal women with abdominal obesity, (i) the hypothalamic‐pituitary‐adrenal (HPA) axis responses to direct pituitary stimulation with corticotrophin releasing hormone (CRH) and to opioid blockade with naloxone, and (ii) the interaction between short‐term serotoninergic activation with dexfenfluramine (dF), a serotonin‐release agonist, and these responses.

Evidence of a Tubular System for Transendothelial Transport in Arterial Capillaries of the Rete Mirabile

The arterial endothelial cells of the rete capillaries of the eel were examined by transmission electron microscopy on thin sections, on freeze-fracture replicas, by scanning electron microscopy, after cytochemical osmium impregnation and perfusion with peroxidase. The study revealed the existence of membrane-bound tubules and vesicles that open at both the luminal and abluminal poles of the cell and at the level of the intercellular space. The tubules are straight or present successive dilations and constrictions. They branch in various directions and intrude deeply into the cell cytoplasm, forming a complex tubular network within the cell. Immunocytochemical techniques were applied on immersion-fixed tissues and on perfusion of the capillaries with albumin and insulin. These demonstrated that the tubular–vesicular system is involved in the transport of circulating proteins. Furthermore, protein A–gold immunocytochemistry has revealed the association of actin with the membranes of this system. On the basis of these results, we suggest that the transendothelial transport of serum proteins takes place by a transcytotic process through a membrane-bound tubular–vesicular system and is equivalent to the large pore system presumed from functional studies.

Carbohydrate tolerance in gonadal dysgenesis

Among 42 patients with GD, one had clinical diabetes and 10 had chemical diabetes (26%) when tested by OGTT. The insulinogenic index was lower in patients with chemical diabetes than in patients with normal OGTT. Among 19 patients with isolated hypogonadotropic hypogonadism, similarly tested, three had chemical diabetes (15%). In a prospective study of 29 patients with GD tested repeatedly, the incidence of diabetic OGTT increased significantly with age. As glucose tolerance deteriorated, the plasma insulin response was delayed and the insulinogenic index decreased. The carbohydrate tolerance was unrelated to weight, estrogen replacement therapy, chromosomal pattern, and GH response. In six GD cases studied at a 6 year interval, the tolerance to oral glucose decreased with time whereas glucose utilization following its intravenous injection or tolbutamide administration was only slightly diminished; the plasma insulin was reduced by approximately 50% in response to each of these stimulations. These studies suggest that carbohydrate intolerance is frequently associated with GD and is due to a diminished beta-cell function.

GROWTH HORMONE‐RELEASING FACTOR INCREASES SERUM PROLACTIN CONCENTRATIONS IN NORMAL SUBJECTS AND IN PATIENTS WITH PITUITARY ADENOMAS

We have examined the serum growth hormone (GH) and prolactin (PRL) response to growth hormone releasing factor (hGRF‐(l‐44)NH2: (GRF) I μg/ kg i.v. bolus) in 16 acromegalic patients (eight of whom were hyperprolactinae‐mic), 13 patients with microprolactinoma, and 14 healthy subjects. The GH responses to‐TRH and to the somatostatin analogue SMS 201–995 were also studied in acromegalic patients. In these, and in patients with microprolactinoma, GH responses after GRF (P<0.001 vs saline) were variable. The absolute GH increase (calculated as area under the curve) in acromegalic patients (2489 ± 920 μg/l min), or in patients with microprolactinoma (1322 ± 279 μg/l min) was not different from that in controls (2238 ± 633 μg/l min). In addition, a significant increase in PRL release was observed after GRF in comparison to saline in acromegalic patients (P<0.01), in patients with microprolactinoma and in normal subjects (P<0001). The PRL increase was significantly correlated with basal PRL levels in acromegalic patients (r= 0.99, P <0.001) and in patients with microprolactinomas (r = 0.61, P<0.05). Furthermore, a significant correlation was found between GH rise after GRF and basal GH, and between GH rise after GRF and GH decrement after SMS in patients with acromegaly. These results suggest that GRF can stimulate PRL release by actions on the normal pituitary and on pituitary adenomas, including microprolactinomas. Moreover, the data suggest that in acromegaly there is a relative functional deficiency of hypothalamic somatostatin.