Transsphenoidal Adenomectomy Research Articles

Chronobiological aspects of headache syndromes due to sellar or pituitary pathology.

A chronobiological study was carried out in headache syndromes due to empty sella or to pituitary G.H.- and PRL-secreting adenomas. In the empty sella syndrome only the chrono-organization of G.H. secretion was disturbed, whereas pl. PRL exhibited the usual circadian pattern. The circadian rhythms of pl. G.H. and pl. PRL were abolished in G.H.- and PRL-secreting pituitary tumors, respectively, and were again detectable when patients were cured by selective transsphenoidal adenomectomy. A normal circadian rhythmicity of pl. cortisol was demonstrable in the empty sella syndrome and in pituitary adenomas, both before and after surgery.

Pituitary function before and after transsphenoidal adenomectomy in patients with Cushing's disease.

Over the past 4 years 11 patients with Cushing's disease have been operated on by a transsphenoidal microsurgical technique. All patients had small intrahypophyseal adenomas found at operation. Eight of the 11 patients had a remission of the disease on the basis of clinical evaluation and hormonal studies. The endocrinological results revealed a transient state of hypocorticism in all successfully treated patients. Within 6-8 months after operation recovery of hypothalamic-pituitary-adrenal function and other tropin function took place. These findings, together with the absence of recurrence up to now, further confirm the efficacy of transsphenoidal surgery in the management of patients with Cushing's disease.

The recovery of the hypothalamo-pituitary-adrenal axis after transsphenoidal operation in three patients with Cushing's disease. The effect of prior external pituitary irradiation.

Abstract. The recovery of the hypothalamo-pituitary-adrenal axis after selective transsphenoidal adenomectomy was studied in 3 patients with Cushing's disease by measuring basal plasma ACTH and cortisol concentrations, cortisol secretion rate, the diurnal rhythm of cortisol, and the reaction of cortisol to lysine vasopressin (LVP), of compound S to metyrapone and of cortisol and growth hormone to an insulin-induced hypoglycaemia. The third patient had been treated previously by external pituitary irradiation. In 2 patients basal plasma ACTH levels returned within normal values before plasma cortisol, but no supra-physiological plasma concentrations of ACTH were seen as has been observed after withdrawal of exogenous glucocorticoids. With regard to the different stimulation tests: at first the normal reaction of plasma cortisol to LVP returned after 3 months, at the same time as the restoration of growth hormone secretion in response to hypoglycaemia. A normalization of the reaction to metyrapone was seen thereafter while finally the reaction of cortisol to an insulin-induced hypoglycaemia and the diurnal rhythm of plasma cortisol returned 15 to 18 months after operation in the first patient and after 12 months in the second patient. Selective adenomectomy had also been carried out in the third patient, as evidenced by normal TSH, LH and FSH secretion. Hypocortisolism, and a deficient ACTH and growth hormone secretion in response to the stimuli mentioned, however, did not normalize up till 22 months after operation. The restoration of the hypothalamo-pituitary-adrenal axis after selective pituitary adenomectomy in Cushing's disease was prevented in this patient by prior external pituitary irradiation.

Anterior Pituitary Function after Transsphenoidal Selective Adenomectomy in Patients with Cushing's Disease*

The anterior pituitary function in 25 patients with Cushing's disease was assessed before and after transsphenoidal adenomectomy. Pituitary adenoma was detected and removed in 24 cases, resulting in clinical remission in 22. Postoperative hypoadrenocorticism was observed in all of the cases with remission, necessitating substitution of glucocorticoid. One case had a recurrence after a year in remission. Plasma ACTH and cortisol rapidly decreased after surgery and remained at subnormal levels. However, diurnal rhythmicity of ACTH and cortisol appeared in 5 of 9 cases within 6 months after surgery and exhibited normal suppressibility in response to low dose dexamethasone. The impaired ACTH response to hypoglycemia was restored after surgery. The GH response to hypoglycemia and the TSH response to TRH were improved by correction of hypercorticism and became evident over time. These results suggest that preoperative impairment of anterior pituitary hormone secretion is secondary to hyperadrenocorticism and that ACTH hypersecretion by a primary pituitary adenoma is the primary etiology in Cushing's disease. We conclude that transphenoidal pituitary exploration should be considered as a first choice of treatment of Cushing's disease because of its high clinical remission rate in association with normalization of other endocrine functions.

Follow-up study on treatment in 27 patients with Cushing's disease: adrenalectomy, transsphenoidal adenomectomy and medical treatment.

27 patients with Cushing's disease were treated over a period of 18 years at the Departments of Medicine and Surgery, Nagoya University School of Medicine and the following results were obtained. 1) Adrenalectomy. 21 of 27 patients with Cushing's disease underwent adrenalectomy. 19 patients had total bilateral adrenalectomy and 2 patients unilateral adrenalectomy. 4 patients died, the cause of death not being related directly to adrenalectomy. 9 of 15 bilaterally adrenalectomized patients had hyperpigmentation even though they had been given substitution therapy with cortisol 20-30 mg daily. They had elevated plasma ACTH levels, which were not completely suppressed by 2 mg of dexamethasone or 2.5 mg of bromocriptine per day. 2) Adenomectomy, 5 patients had adenomectomy via the transsphenoidal approach. 3 patients were cured but one of them has required postoperative substitution therapy with cortisol for hypopituitarism for one year until today. 2 of 5 adenomectomized patients had a recurrence of Cushing's syndrome after remission for 6-8 months. One of these recurrent cases has been subsequently treated successfully with bromocriptine, a dopaminergic drug. 3) Medical treatment. 2.5 mg per day of bromocriptine has been effective in 2 patients without a pituitary adenoma and ineffective in the other 4 patients with a pituitary adenoma. 24 mg per day of cyproheptadine, an antiserotoninergic drug was not effective in any of the 4 patients with a pituitary adenoma.

Changes in Pituitary Hormones during and following Transsphenoidal Removal of Prolactinomas

Abstract Prolactin (PRL) and other pituitary hormones (luteinizing hormone, follicle-stimulating hormone, growth hormone [GH], thyrotropin stimulating hormone) were measured before, during, and after transphenoidal pituitary adenomectomy in 16 patients with hyperprolactinemia. The diagnosis of prolactinoma was made in three of the 16 patients by the absence of PRL response to thyrotropin-releasing factor (TRF) and a dopamine receptor antagonist, metoclopramide, without radiologic evidence of an adenoma. Contrary to findings in subjects with normal PRL values, the PRL rise in response to anesthesia and operation was absent. Other pituitary hormones, with the exception of GH, which increased during anesthesia and operation, exhibited no acute changes. In 11 of 16 cases, complete tumor removal was achieved as determined by the rapid decline of PRL levels to normal values within 24 to 48 hours after operation and by subsequent clinical follow-up. This finding documents that the adenoma is the main source of excessive PRL secretion. The circulating half time of immunoreactive PRL determined by frequent sampling in these patients was variable, ranging from 74 to 190 minutes, significantly longer than the previously reported value of 15 minutes determined by bioassay. Although a transient decline was evident, serum PRL levels remained elevated in those patients with incomplete tumor removal. These findings suggest that a single measurement of serum PRL within 24 to 48 hours following transphenoidal adenomectomy is a reliable indicator of the success or failure of the procedure.

Changes in pituitary hormones during and following transsphenoidal removal of prolactinomas

Prolactin (PRL) and other pituitary hormones (luteinizing hormone, follicle-stimulating hormone, growth hormone [GH], thyrotropin stimulating hormone) were measured before, during, and after transphenoidal pituitary adenomectomy in 16 patients with hyperprolactinemia. The diagnosis of prolactinoma was made in three of the 16 patients by the absence of PRL response to thyrotropin-releasing factor (TRF) and a dopamine receptor antagonist, metoclopramide, without radiologic evidence of an adenoma. Contrary to findings in subjects with normal PRL values, the PRL rise in response to anesthesia and operation was absent. Other pituitary hormones, with the exception of GH, which increased during anesthesia and operation, exhibited no acute changes. In 11 of 16 cases, complete tumor removal was achieved as determined by the rapid decline of PRL levels to normal values within 24 to 48 hours after operation and by subsequent clinical follow-up. This finding documents that the adenoma is the main source of excessive PRL secretion. The circulating half time of immunoreactive PRL determined by frequent sampling in these patients was variable, ranging from 74 to 190 minutes, significantly longer than the previously reported value of 15 minutes determined by bioassay. Although a transient decline was evident, serum PRL levels remained elevated in those patients with incomplete tumor removal. These findings suggest that a single measurement of serum PRL within 24 to 48 hours following transphenoidal adenomectomy is a reliable indicator of the success or failure of the procedure.

Circadian regulation of growth hormone secretion after treatment in acromegaly.

In eight patients who underwent transsphenoidal adenomectomy for acromegaly,baselineplasma GH levels were consistently less than 8 ng/ml during 1–4 yr postoperatively. Plasma GH was measured every 20 min for 24 h, and the responses to oral glucose, iv TRH, and oral bromocriptine were examined during the follow—up. The 2-h mean (±SD) GH value varied from 1.1 ± 0.9 to 10.8 ± 4.9 ng/ml. Statistical analysis of these mean values allowed identification of two groups of patients. In each group I patient (five cases), the mean 24-h GH level was less than or equal to 2.0 ng/ml. One to four daytime GH secretion peakswith intervening periods oflow secretory activity were observed. In all five cases, a significant nocturnal GH rise was found; this rise coincided with the onset of deep sleep in only two patients. Responses to dynamic tests returned t o normal after surgery in this group. In group II patients (three cases), the mean (±SD) 24-h GH levels varied from 46 ± 1.0 to 10.8 ± 4.9 ng/ml. Two patients presented ...

Selective Transsphenoidal Adenomectomy in Women with Galactorrhea-Amenorrhea

POST, KALMON D.; BILLER, BRUCE J.; ADELMAN, LESTER S.; MOLITCH, MARK E.; WOLPERT, SAMUEL M.; REICHLIN, SEYMOUR Author Information

Transsphenoidal adenomectomy in Cushing's disease, with special emphasis on residual adenohypophysial function (author's transl)

The success of transsphenoidal adenomectomy in 10 patients with Cushing's disease was judged by the residual adenohypophysial function. Surgery was indicated mainly by endocrinological results. Radiologically, the sella turcica was slightly enlarged in three cases, which had all macroadenomas with the diameter of more than 10 mm. The other seven had microadenomas 3-7 mm in diameter with normal-sized sella. In two cases, localized bulging of the floor was confirmed by polytomography. In one case the adenoma was far away from the midline and was completely buried in the It-lateral wing. All the others were located in the center of the adenohypophysis. Complete adenomectomy involving adjacent normal tissue resulted in amazing clinical improvement with hypoadrenocortisolism in all cases except one in which the surgical maneuvers appeared incomplete. The preoperative basal levels of plasma ACTH were 135.6±27.5 pg/ml (M±S.E.) and responsiveness to insulin hypoglycemia was absent in all cases with a loss of diurnal rhythmicity, whereas conspicuous ACTH responsiveness to 8-lysine vasopressin (LVP) was observed in most cases, as shown by the increase from 107.8±23.8 to 362.5±98.7 pg/ml. The postoperative basal plasma ACTH levels dropped to 24.6±11.3 pg/ml and their responses to LVP became blunted in most cases with a peak value of 57.0±21.4 pg/ml, whereas hypoglycemic responses became positive in most cases, as shown by the peak value of 62.7±12.6 pg/ml. The diurnal rhythmicity of plasma ACTH and cortisol became apparent in all five cases examined 6 months after surgery. Preoperative plasma GH responses to insulin hypoglycemia were impaired in all cases and the peak value did not exceed 10 ng/ml in any case. Postoperatively, the peak value significantly increased at an average of 7.9±3.9 ng/ml (M±S.D.) and in four cases it exceeded 10 ng/ml. TSH responses to TRH and LH to LH-RH were also significantly improved postoperatively. FSH responses to LH-RH and PRL to TRH did not change significantly. These results support the concept that ACTH hypersecretion of pituitary adenoma is the primary abnormality in Cushing's disease and hypothalamic CRF activity is suppressed by long-standing hypercortisolism. Furthermore, the hypothalamic-pituitary functions of other anterior pituitary hormones such as GH, TSH and LH are impaired by hypercortisolism and could be returned to normal by selective transsphenoidal adenomectomy. We conclude that this operation is the first choice of treatment of Cushing's disease for clinical and endocrinological improvements.

Selective total removal of a growth-hormone-secreting adenoma: Evidence that acromegaly is a primary pituitary disease

Acromegaly is caused by hypersecretion of growth hormone by the pituitary. There is some debate as to whether the primary etiology of the disease is abnormal hypothalamic stimulation of the pituitary or a primary pituitary tumor. This paper presents a case of acromegaly in which growth hormone dynamics in response to stimulation and suppression tests were abnormal. After transsphenoidal adenomectomy of a small tumor, growth hormone levels returned to normal and suppression and stimulation test results reverted to normal within 1 wk postoperatively and remained normal for 2 yr. The findings suggest that the acromegaly in this case was due to a primary pituitary dysfunction. Microsurgical removal of growth-hormone-secreting tumors provides a unique opportunity to study the etiology of acromegaly.

BROMOCRIPTINE TREATMENT OF SEVEN WOMEN WITH PRIMARY AMENORRHOEA AND PROLACTIN‐SECRETING PITUITARY TUMOURS

Seven women with primary amenorrhoea and hyperprolactinaemia were treated with bromocriptine. All the women had started to develop secondary sex characteristics at normal age but pubertal development stopped and menarche did not occur. Radiological signs of a pituitary tumour were found in all the women. Before the pituitary tumour was diagnosed, four women had been given longterm cyclical oestrogen replacement therapy. Three women had received primary tumour therapy with surgery and/or irradiation but had persistent hyperprolactinaemia. The basal luteinizing hormone (LH) levels were low in four of the women while all the women had normal basal levels of follicle-stimulating hormone (FSH) and normal or exaggerated gonadotrophin responses to luteinizing hormone-releasing hormone (LHRH). None of the women had evidence of endogenous oestrogen production before treatment. Bromocriptine treatment normalized the raised serum prolactin levels (46-2900 microgram/l) in all but one woman, in whom the prolactin level decreased from 160 to 38 microgram/l. Regular ovulatory menstrual cycles appeared in four women, one of whom had previously been treated by transsphenoidal adenomectomy followed by external irradiation. Two other women with persistent hyperprolactinaemia after previous surgical and/or irradiation treatment of large pituitary tumours did not menstruate after more than one year of treatment with bromocriptine. One infertile patient with a microadenoma conceived at the first ovulation on therapy and developed symptoms and signs of tumour growth during pregnancy.