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Biomedical subjects

M Somma

Publications and source records attributed to M Somma.

At least 19 recordsLinked to original sources
PubMed1996

Transsphenoidal adenomectomy for microprolactinomas: 10 to 20 years of follow-up.

BACKGROUND: Transsphenoidal adenomectomy is an effective treatment fo r microprolactinomas. However, postoperative recurrence of hyperprolactinemia is not rare. This study was designed to evaluate the long-term outcome of women with microprolactinomas operated on by transsphenoidal approach. METHODS: We retrospectively studied 64 women with microprolactinomas who underwent transsphenoidal adenomectomy and were followed for 10 to 20 years. RESULTS: Postoperatively, 58 women (90%) had normal plasma prolactin concentrations (<20 microg/L). After a mean of 3.3 years, during which the women were asymptomatic with normoprolactinemia, 25 (43%) had a relapse of hyperprolactinemia (> or = 20 microg/L). However, their evolution varied. Fifteen women had symptomatic hyperprolactinemia. Computed tomography (CT) scans showed recurrent microadenomas in 2 women. The other 10 women had only hyperprolactinemia. Of these women, 5 had transient hyperprolactinemia (29 +/- 4 microg/L) for 5 years, after which prolactin declined to normal 13 +/- 3 microg/L). The remaining five patients had elevated prolactin (31 +/- 3 microg/L) throughout the follow-up period (10 to 20 years). CT scan did not show recurrent adenomas in these women. Thirty-three women remained normoprolactinemic and asymptomatic for a mean period of 12 years (range, 10 to 20 years). CONCLUSIONS: In conclusion, most of the patients with late relapse of hyperprolactinemia have slight functional hyperprolactinemia and remain asymptomatic with no evidence of tumor recurrence.

Adenoma↗
PubMed1996

Surgical outcome after repeated transsphenoidal surgery in acromegaly.

Transsphenoidal selective adenomectomy is the most efficient primary treatment for acromegaly. However, management of persistent or recurrent disease remains controversial. The objective of the present study was to evaluate the early and long-term efficacy and safety of a second transsphenoidal surgery performed in those cases. The results of a retrospective study of 16 patients undergoing reoperation by the senior author (J.H.) between 1970 and 1991 are reported. Reoperation was performed for persistent or progressive acromegaly in 11 patients, visual impairment in four, and disease recurrence in one. Normalization of growth hormone (GH) was defined as a basal GH level of less than 5 micrograms/L and suppression to less than 2 micrograms/L during the oral glucose tolerance test. Long-term follow-up data were available in 15 patients. The second transsphenoidal surgery induced a greater than 50% decrease of GH level in 11 patients. Three (19%) of 16 patients were cured according to the authors' criteria and remained so after 2, 7, and 20 years. Two more patients had a postoperative basal GH level of less than 5 micrograms/L but incomplete suppression during the oral glucose tolerance test. Thus, a total of five patients (31%) achieved a basal GH of less than 5 micrograms/L. One other patient who had no initial improvement after the second transphenoidal surgery had spontaneous normalization of his GH level after 13 years. The following complications of the second surgery occurred in three patients: one subarachnoid hemorrhage, two new visual field defects, one cranial nerve palsy, and one meningitis. Moreover, 10 patients (62.5%) developed one or more new pituitary hormone deficiencies. In conclusion, reoperation for persistent or recurrent acromegaly has low success and high complication rates. According to the authors' experience, this procedure should be reserved for patients unresponsive to other forms of therapy or with progressive visual impairment despite medical therapy.

Acromegaly↗
PubMed1994

Prolactinoma.

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Bromocriptine↗
PubMed1993

High prolactin levels in patients with Cushing's disease without pathological evidence of pituitary adenoma.

OBJECTIVE: This study was designed to compare the clinical and biochemical features of patients with Cushing's disease without pathological evidence of pituitary adenoma (n = 11) to those in whom a pituitary ACTH adenoma was documented (n = 11). DESIGN: The clinical and biochemical features of 11 patients with Cushing's disease without pathological evidence of pituitary adenomas were compared to 11 subjects with ACTH-secreting adenomas. The patients underwent transsphenoidal microsurgery between 1979 and 1989. During surgery, when an adenoma was not visualized, a partial hypophysectomy of the central mucoid wedge was performed. MEASUREMENTS: Cushing's disease was established by the clinical features of hypercortisolism and the high levels of 24-hour free urinary cortisol with no suppression in response to low, but with suppression in response to high, doses of dexamethasone. Basal and post TRH-GnRH plasma prolactin, FSH and LH levels were assessed in each patient before transsphenoidal microsurgery. RESULTS: Similar results were observed in patients with and without ACTH-secreting adenomas regarding cure rate, and free urinary cortisol levels both basal and after 2 days of dexamethasone, 8 mg daily. After surgery, plasma cortisol levels in cured patients were lower in subjects with ACTH-secreting adenomas than in those without pituitary tumours (P < 0.05). Areas under the curve of PRL (P < 0.002) and LH (P < 0.04) were significantly higher in patients without pituitary adenoma after TRH-GnRH administration. Compared to controls, the peak prolactin level after TRH-GnRH administration was higher in patients without pituitary adenoma (P < 0.005) and lower in those with ACTH adenoma (P < 0.005). Furthermore, a peak prolactin level equal to or greater than 1410 mU/l during the TRH-GnRH test was found in 11/11 patients without ACTH adenoma and 3/11 patients in the other group (P < 0.001), while the CT-scan findings were suggestive of pituitary adenoma in six patients of each group. CONCLUSION: This study suggests that patients with Cushing's disease without pituitary adenomas can be distinguished from those with ACTH-secreting adenomas by their high prolactin levels after TRH-GnRH administration.

Adenoma↗
PubMed1991

The clinical and endocrine outcome to trans-sphenoidal microsurgery of nonsecreting pituitary adenomas.

From 1962 to 1987, 126 patients underwent trans-sphenoidal surgery for primary treatment of pituitary adenomas unassociated with clinical or biochemical evidence of hormonal overproduction. There were 73 male and 53 female patients (mean age, 50 +/- 12 years). Before surgery, 56% of the patients (70 of 124) had headaches, 74% (94 of 126) had deterioration of vision, and 12% (15 of 126) had ophthalmoplegia. Endocrine evaluation revealed the presence of hypogonadism in 75% (87 of 115), adrenal insufficiency in 36% (46 of 126), and hypothyroidism in 18% (21 of 122). Plasma prolactin was increased in 65% (56 of 86) with a mean level of 39 +/- 14 micrograms/l (normal, 3 to 20 micrograms/l). Radiologic enlargement of the sella turcica was documented in all cases: 67% (84 of 126) had enclosed and 33% (42 of 126) had invasive adenomas. After surgery, vision was normalized or improved in 75% (71 of 94) of the patients. Thyroid, adrenal, and gonadal functions were improved in 14% (three of 22), 41% (19 of 46), 11% (ten of 87), were unchanged in 82% (100 of 122), 77% (97 of 126), 89% (102 of 115), and worsened in 15% (19 of 22), 8% (ten of 126), 3% (102 of 115), respectively. Permanent diabetes insipidus occurred in 5% (seven of 126). Two patients died during the immediate postoperative period. The recurrence rate in patients with a mean follow-up of 6.4 +/- 4.2 years was 21% (15 of 71). These data indicate that trans-sphenoidal microsurgery is an effective and safe initial treatment for patients with nonsecreting pituitary adenoma and may reverse hypopituitarism.

Adenoma↗
PubMed1990

Long term treatment with CV 205-502 in patients with prolactin-secreting pituitary macroadenomas.

CV 205-502, a new long-acting nonergot dopamine agonist, was given to 15 patients (6 women and 9 men) with PRL-secreting pituitary macroadenomas. The compound was administered in a single daily dose for a period of 6-12 months. The treatment resulted in normalization of plasma PRL levels (less than or equal to 20 micrograms/L) in 5 of 6 women at a mean dose of 135 micrograms (range, 75-300 micrograms) and in 6 of 9 men at a mean dose of 192 micrograms (range, 75-300 micrograms). Among patients for whom computed tomographic scans were available before and after at least 6 months of therapy, definite tumor shrinkage occurred in 6 of 7 patients. Libido was improved in 5 of 6 women and in 6 of 8 men, galactorrhea disappeared in all cases (3 women and 1 man) and menses resumed in 3 of 5 women. Plasma testosterone rose to normal levels in 3 of 6 men who were not receiving testosterone injections. The PRL response to TRH was blunted in 4 of 6 patients with normalized basal PRL. Serum total cholesterol was reduced by CV 205-502 treatment in women from 5.35 +/- 0.49 to 4.63 +/- 0.51 mmol/L (P = 0.031) and in men from 5.93 +/- 0.89 to 5.28 +/- 0.82 mmol/L (P = 0.045). Side-effects included mainly headache, nausea, and dizziness. One side-effect or more occurred transiently and with mild intensity in 14 patients. No patient discontinued the therapy because of side-effects. In conclusion, CV 205-502 appears to be a safe and valuable compound in the treatment of patients with PRL-secreting macroadenomas.

Adult↗
PubMed1989

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-(1-44)NH2 (GRF) 1 microgram/kg i.v. bolus) in 16 acromegalic patients (eight of whom were hyperprolactinaemic), 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 less than 0.001 vs saline) were variable. The absolute GH increase (calculated as area under the curve) in acromegalic patients (2489 +/- 920 micrograms/l min), or in patients with microprolactinoma (1322 +/- 279 micrograms/l min) was not different from that in controls (2238 +/- 633 micrograms/l min). In addition, a significant increase in PRL release was observed after GRF in comparison to saline in acromegalic patients (P less than 0.01), in patients with microprolactinoma and in normal subjects (P less than 0.001). The PRL increase was significantly correlated with basal PRL levels in acromegalic patients (r = 0.99, P less than 0.001) and in patients with microprolactinomas (r = 0.61, P less than 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.

Acromegaly↗
PubMed1988

Defective dopaminergic regulation of prolactin secretion in patients with hyperprolactinemia.

In order to evaluate the dopaminergic control of the lactotroph, we examined the plasma prolactin response to metoclopramide (a dopamine receptor blocker, 10 mg iv bolus) and to dopamine (1 microgram/Kg/min iv infusion for 120 min) in 52 hyperprolactinemic female patients and 19 healthy volunteer women. Three diagnostic categories were included: "idiopathic" hyperprolactinemia (21), microadenoma (24), and macroadenoma (7). Patients from all groups showed a marked blunting of the prolactin response to metoclopramide as compared to the prolactin rise in normal women (p less than 0.001). However, normal responses were observed in 8 patients with idiopathic hyperprolactinemia and in one patient with adenoma. The magnitude of the prolactin response to metoclopramide (percent of baseline level) correlated negatively with the level of basal prolactin in each group except for macroadenoma patients. Dopamine infusion significantly (p = 0.015) reduced the mean plasma prolactin levels in hyperprolactinemic patients and normal women. However, patients with idiopathic hyperprolactinemia were hyposensitive to dopamine (p less than 0.05). Furthermore, microadenoma patients were less responsive to dopamine suppression than were the patients with macroadenoma (p less than 0.05). The results indicate the presence of a relative resistance to dopamine in patients with idiopathic hyperprolactinemia and in patients with microadenoma. They also suggest that in these patients, the decrease in prolactin response to metoclopramide may be explained by the relative refractoriness to endogenous dopamine.

Adenoma↗
PubMed1987

Distinctive features of prolactin secretion in acromegalic patients with hyperprolactinaemia.

We have investigated the relationship between the plasma PRL concentrations of 98 untreated acromegalic patients and the GH levels during basal and dynamic conditions. Hyperprolactinaemia was present in 27 patients. In patients with marked hyperprolactinaemia (PRL greater than 80 ng/ml or greater than 1600 mU/l), basal plasma PRL and the TRH-induced response correlated with basal plasma GH (correlation coefficients of 0.9, P less than 0.001 and 0.74, P less than 0.02, respectively). The PRL response to TRH also correlated with GH response to TRH (r = 0.38, P less than 0.01). In contrast, in patients with moderately elevated PRL (20 to 80 ng/ml), and in those with normal plasma PRL (less than 20 ng/ml or less than 400 mU/l), no such correlations were found. Immunostaining for PRL was positive in 24 out of 25 adenomas of patients with hyperprolactinaemia, while no PRL was found in the tumour tissue of 10 normoprolactinaemic patients. In conclusion, our data suggest the existence of two populations of acromegalic patients with hyperprolactinaemia, one group with correlations between GH and PRL secretion, and the other without.

Acromegaly↗
PubMed1985

Effects of alloxan-induced diabetes on dopaminergic receptors in rat striatum and anterior pituitary.

The binding of [3H]-spiroperidol after 4 weeks of hyperglycemia was determined in the rat striatum and anterior pituitary. Alloxan-induced diabetes increased the number of dopaminergic binding sites in the striatum but not in the anterior pituitary. The interaction of metoclopramide with striatal dopaminergic receptors was slightly modified, while that of dopamine, bromocriptine and haloperidol was unaffected. These results suggest that chronic hyperglycemia exerts selective effects on nigrostriatal dopaminergic system in the rat.

Alloxan↗
PubMed1985

Acromegaly: biochemical assessment of cure after long term follow-up of transsphenoidal selective adenomectomy.

This study reports the clinical and biological follow-up 5-11 yr after transsphenoidal selective adenomectomy in 25 patients with acromegaly. Eight patients had microadenomas, and 17 had macroadenomas. Initial normalization of plasma GH levels (basal values, less than 5 ng/ml; glucose-suppressed concentrations, less than 2.5 ng/ml) was achieved in all 8 patients with microadenomas and in 13 patients with macroadenomas. Of these, 3 patients with normal GH levels and dynamics had relapse of GH hypersecretion after intervals between 1-6 yr after microadenoma removal. Recurrence of pituitary adenoma was documented by surgery in 1 patient and by computed tomographic scanning in 2 others. Normal basal and glucose-suppressed plasma GH concentrations were maintained 7.4 +/- 0.5 (+/- SEM) yr after adenomectomy in 7 patients with microadenomas and in all 10 patients with macroadenomas. Thus, 88% of the patients with microadenomas and 59% of the patients with macroadenomas were cured, and the overall cure rate was 68%. We conclude that recurrence of acromegaly after successful surgery may occur late after adenoma removal and that it cannot be predicted by normal postoperative GH levels and dynamics. However, in view of the overall cure rate, transsphenoidal adenomectomy remains a most valuable treatment for acromegaly.

Acromegaly↗
PubMed1984

Dopaminergic binding sites in human pituitary adenomas other than prolactinomas.

Binding studies of [3H]-spiroperidol, a potent dopamine antagonist, were performed on dispersed cells obtained from 2 mixed PRL- and GH-secreting adenomas, 3 GH-secreting adenomas and 4 'nonsecreting' pituitary tumors. Saturable, high affinity binding sites for [3H]-spiroperidol were identified in the two adenomas of mixed PRL and GH secretion, in 2 of 3 GH-secreting adenomas and in 2 of 4 'nonsecreting' adenomas. These data indicate that dopaminergic binding sites are present in some GH-secreting adenomas in the absence of PRL hypersecretion and in some 'nonsecreting' pituitary adenomas.

Adenoma↗
PubMed1984

Interaction of sulpiride with human pituitary dopaminergic receptors is sodium dependent.

The effects of various drugs on [3H]-spiroperidol binding to human anterior pituitary and prolactinoma membranes are studied in the presence and in the absence of sodium chloride in the incubation medium. It is shown that in the absence of NaCl, 1-sulpiride is significantly less potent in displacing the radioactive ligand from its dopaminergic binding sites than in the presence of NaCl. On the contrary, the interaction of neuroleptics (d-butaclamol and haloperidol) and dopamine agonists (apomorphine and bromocriptine) was unaffected by the NaCl conditions.

Binding, Competitive↗
PubMed1984

Elevated secretion of androstenedione in a patient with a Leydig cell tumour.

In this study, we report the case of a 48-year old man with a well-encapsulated Leydig cell tumour, azoospermia, decreased libido and impotence. The basal peripheral blood levels of testosterone, dihydrotestosterone, 5 alpha-androstane-3 alpha,17 beta-diol and oestradiol were normal and oestrone was moderately increased. In contrast, androstenedione was extremely elevated at 521 ng/dl (normal: 88 +/- 60 ng/dl). Upon hCG stimulation, plasma testosterone increased 2.1-fold while androstenedione increased 1.4-fold. Plasma LH and FSH were also elevated and their response to LRH was exaggerated. At the time of surgery the levels of androstenedione in the spermatic vein plasma, as well as in the testicular tumour were elevated. In contrast, testosterone levels in the spermatic vein blood were decreased indicating a partial deficiency of 17 beta-hydroxysteroid dehydrogenase in the tumoural tissue. A follow-up study revealed that the contralateral testis did not respond to hCG although the sex steroid concentrations in the peripheral plasma were within normal limits. Plasma gonadotrophins remained elevated. These results demonstrate that this Leydig cell tumour secreted high amounts of androstenedione into the blood and that the contralateral testis exhibited an impaired androgenic function.

Androstenediol↗
PubMed1983

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.

Adenoma↗
PubMed1983

Differential effects of a low dose dopamine infusion on prolactin secretion in normal and hyperprolactinemic subjects.

The PRL inhibitory effect of dopamine (DA) in human in vivo studies has been previously demonstrated with DA infusions at rates generally exceeding 2 micrograms/kg . min. We report here the effects of a DA infusion administered at a rate of 0.02 microgram/kg . min for 180 min to 10 normal subjects and 25 hyperprolactinemic patients with pituitary tumors (13 microprolactinomas, 8 macroprolactinomas, and 4 expanding nonsecreting pituitary adenomas). Serum free DA concentrations during the 3-h DA infusion reached an average of 0.8 +/- 0.1 ng/ml (about an 8- to 10-fold rise from basal levels). DA produced a significant (P less than ) 0.001) decline in plasma PRL levels in both normal subjects and hyperprolactinemic patients. There was a negative linear correlation between the serum DA concentrations and the percent PRL variation from basal levels (r = -0.58; P less than 0.001). The comparison of RPL responses between the different groups revealed that the mean percent overall PRL inhibition was significantly lower in patients with microprolactinomas than in normal subjects (P less than 0.02). On the other hand, PRL inhibition was greater in patients with nonsecreting adenomas than in either patients with microprolactinomas or those with macroprolactinomas (P less than 0.001). From 90-180 min, PRL suppression was also greater in patients with nonsecreting adenomas than in normal controls (P less than 0.05). The present study shows that 1) slight elevations of plasma DA are sufficient to inhibit PRL secretion, suggesting that DA acts as major physiological PRL-inhibiting factor, 2) there is a relative PRL resistance to DA inhibition in microprolactinoma patients; and 3) PRL is hyperresponsive to DA in expanding nonsecreting pituitary tumors.

Adenoma↗
PubMed1981

Effects of naloxone on insulin-induced release of pituitary hormones.

To evaluate the role of endogenous opiates on the regulation of the pituitary hormonal stress response, we have studied in six normal subjects the insulin-induced secretion of PRL, GH, and ACTH with and without naloxone, a specific opiate antagonist. During hypoglycemia, naloxone infusion reduced plasma PRL levels at 90 min, lowered the overall GH response, and enhanced that of ACTH. These observations suggest that endogenous opiates have a modulatory role in the stress-induced secretion of pituitary hormones.

Adrenocorticotropic Hormone↗