Maurice Somma

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.

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 μg/l (normal, 3 to 20 μg/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.

Cognitive decline in patients with Cushing's syndrome

Chronic exposure to elevated glucocorticoid levels in Cushings syndrome (CS), is associated with deficits in cognitive function and in emotion. The hippocampus plays a crucial role in the behavioral manifestations of the syndrome as it is richest in glucocorticoid receptors and is thus particularly vulnerable to glucocorticoid excess. The wide distribution of glucocorticoid receptors throughout the cerebral cortex, however, suggests that several cognitive functions can also be affected by the dysregulation of glucocorticoids. In this study, we investigated how an excess of glucocorticoid hormones affects cognitive processes. Nineteen patients with chronic hypercortisolemia due to CS were compared to healthy controls matched for age, sex, education, and occupation in tests of processing of visual and spatial information, memory, reasoning and concept formation, language and verbal functions, and attention. Multivariate and univariate analyses revealed overall differences in tests of treatment of visual and spatial information, reasoning and concept formation as well as in verbal and language performance, with poorer performance from CS patients. Differences were also observed in nonverbal aspects of memory and in attention tasks. The results suggest that chronic exposure to elevated levels of cortisol is associated with deficits in several areas of cognition, particularly those involving processing of selective attention and visual components. This study also shows that hormones play an important role in the modulation of cognitive function and that their influence on cerebral structure and function merits closer scrutiny. ( JINS , 2000, 6 , 20–29.)

Prolactin secretion in sixty-five patients with galactorrhea

Pituitary prolactin (PRL) secretion was evaluated in 65 galactorrheic individuals with nonfunctioning hypothalamic-pituitary tumors, acromegaly, prolactin-secreting tumors, Chiari-Frommel syndrome, Argonz-del Castillo syndrome, history of phenothiazine or α-methyldopa intake, primary hypothyroidism, use of contraceptive medications, and in patients with idiopathic galactorrhea. Mean serum prolactin concentrations in patients with prolactin-secreting pituitary tumors were significantly higher than those in other groups but over all there was no correlation between the serum prolactin levels and the grade of galactorrhea. Neither a single elevated serum prolactin level nor the degree of suppressibility after L-dopa administration was diagnostic of a pituitary tumor. However, a history of consistently high serum prolactin concentrations was highly indicative of a prolactin-secreting tumor.

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.

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.

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 Cushings disease without pathological evidence of pituitary adenoma (n= 11) to those in whom a pituitary ACTH adenoma was documented (n= 11).

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 > 80 ng/ml or > 1600 mU/l), basal plasma PRL and the TRH‐induced response correlated with basal plasma GH (correlation coefficients of 0‐9, P < 0 001 and 0‐74, P <0 02, respectively). The PRL response to TRH also correlated with GH response to TRH (r= 0 38, P <0 01). In contrast, in patients with moderately elevated PRL (20 to 80 ng/ ml), and in those with normal plasma PRL (< 20 ng/ml or < 400 mU/1), 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.

Pituitary responses to synthetic luteinizing hormone-releasing hormone in thirty-four cases of amenorrhea or oligomenorrhea associated with galactorrhea

Pituitary responses to 100 mcg. of luteinizing hormone-releasing hormone (LH-RH) administered subcutaneously were studied in 34 cases of amenorrhea or anovulatory oligomenorrhea associated with galactorrhea. Twenty-six patients had pituitary prolactin-secreting tumors (group I); eight patients had a normal sella turcica and remission of the syndrome either spontaneously or after thyroid replacement therapy (group 2). Follicle-stimulating hormone (FSH) and luteinizing hormone (LH) responses to LH-RH were variable in each group of patients, ranging from poor to exaggerated, and no statistically significant difference could be observed between the groups. A positive correlation was found between FSH pituitary responses and basal FSH levels (r=0.50; P less than 0.01). No positive correlation was observed between either LH responses and basal LH levels or the gonadotropin responses and plasma estradiol levels, serum prolactin concentrations, duration of amenorrhea, or size of the tumor.

ACTH-secreting medullary carcinoma of the thyroid: Monitoring of clinical course with calcitonin and cortisol assays and immunohistochemical studies

The clinical course of a patient with Cushings syndrome secondary to metastatic medullary carcinoma of the thyroid was documented with serial calcitonin and cortisol assays and tumor immunohistochemistry studies. Cortisol levels were originally markedly elevated but returned to normal after total thyroidectomy. These levels rose again when the patient developed liver metastases but normalized during chemotherapy, never to rise again despite the appearance of cervical lymph node metastasis. Calcitonin levels remained elevated throughout the course. The original tumor was composed of two cell lines: one containing both calcitonin and ACTH and another containing only calcitonin‐reacting cells. However, the cervical metastasis showed a marked decrease in both cell lines with fever than 1% of cells reacting to ACTH, and only 25% to calcitonin. The almost total disappearance of ACTH‐reacting cells may have been therapeutically induced or may represent a consequence of tumor progression.