Jerald S. Brodkey

Antihormone treatment of stage IV breast cancer

The antiestrogen Tamoxifen (T), given orally to 113 patients with stage IV breast cancer, induced objective remission in 50%. Duration of remission in the first 39 patients, with minimum 27 months follow up, is 18+ months; these results are equal to those of surgical hypophysectomy. T prolonged survival in responders. Older age, previous response to endocrine therapy and positive estrogen receptors predicted response to T. T was effective in hypophysectomized patients in whom serum growth hormone and prolactin were undetectable, but serum estrogens were present in low amount, suggesting a direct stimulatory effect of estrogens at the tumor level. Hypophysectomy induced further palliation after treatment with T, indicating that pituitary hormones may also play a role in the growth of some human breast cancers. Side effects from T were minimal. T is the initial treatment of choice for postmenopausal women with hormone responsive stage IV breast cancer. Cancer 43:444–450, 1979.

RECOVERY OF PITUITARY FUNCTION FOLLOWING SURGICAL REMOVAL OF LARGE NONFUNCTIONING PITUITARY ADENOMAS

Pituitary function was evaluated in eleven patients with large nonfunctioning pituitary adenomas before and 3 months after surgical adenomectomy. The longest anteroposterior dimension from the anterior wall to the dorsum of the sella on a lateral skull x‐ray ranged between 22 and 45 mm. All adenomas were confirmed histologically and had negative immunostaining for GH, PRL, ACTH and HCG.

Transsphenoidal hypophysectomy in breast cancer. Evidence for an individual role of pituitary and gonadal hormones in supporting tumor growth.

Transsphenoidal hypophysectomy was performed in 212 consecutive patients with metastatic breast cancer: 11 died within 30 days, two of surgical complications and nine of advanced metastatic disease. Two patients were unevaluable because of inadequate follow‐up in one and simultaneous radiation treatment in the other. Of 199 evaluable patients 42% had an objective remission. Duration of remission averaged 18+ months with 10 out of 84 patients still in remission. Presence of estrogen receptors in the tumor significantly predicted response to hypophysectomy. Of 156 patients in whom completeness of hypophysectomy was assessed, 128 were thought to have a complete removal as shown by the fact that their growth hormone and prolactin were undetectable after stimulation with arginine or chlorpromazine, respectively. Of 26 patients in whom TRH test was performed, TSH and prolactin were undetectable in 20. Of 23 patients where autopsy was performed only six had microscopic pituitary tissue remaining. Hypophysectomy induced remission in eight of 15 patients who had previously responded and then relapsed to the antiestrogen Tamoxifen and in four of 17 who had failed. Conversely, antiestrogen therapy induced remission in six of 26 patients who had previously responded to hypophysectomy and in whom serum estrogens were present in small amount. These data indicate that both gonadal and pituitary hormones play a role in the growth of some human breast cancers.

Gradual recovery of lactotroph responsiveness to dynamic stimulation following surgical removal of prolactinomas: Long-term follow-up studies☆☆☆

Prolactin-secreting pituitary adenomas were selectively removed through a transsphenoidal approach from 120 women. Basal serum PRL levels (measured one to six months after surgery) were normal in 96 patients and decreased appreciably but not to normal in the remaining 24 patients. Dynamics of PRL secretion were studied at three to four months in 81 patients who had normal basal PRL level. Two different patterns of response to provocative stimuli were noted in these patients. In one group (group I, n = 65), patients had greater than 100% rise in serum PRL following TRH or perphenazine (Pz) administration. However, when analyzed as a group, the mean +/- SEM incremental responses (delta PRL) to TRH and Pz in these patients (29.9 +/- 1.9, 20.4 +/- 1.5 ng/mL) were significantly less (P less than 0.005 and P less than 0.001) than those of normal women (38.8 +/- 5, 33 +/- 5 ng/mL, respectively). Nineteen of these patients were restudied 12 to 72 months after surgery. The responses to provocative stimulation at that time were improved and similar to normal women. In contrast, in the second group (n = 16) of patients (group II), the responses to stimulation with the same agents were blunted or absent and remained so during subsequent studies. Recurrence of the hyperprolactinemia was noted in 11 of the 16 patients in group II and in only two of 65 patients in group I. The daily serum PRL levels in the immediate postoperative period were higher in patients from group II than those from group I. We conclude that transsphenoidal surgery is an optimal form of therapy for patients with PRL-secreting adenomas.(ABSTRACT TRUNCATED AT 250 WORDS)

A Minimum Variance, Time Optimal, Control System Model of Human Lens Accommodation

Experimental data relating ciliary nerve stimulation and lens motion are used to identify the open-loop plant dynamics of the lens accommodation system via a parameter identication variation of the Kalman filter equations. Using the resultant minimum variance plant model, experimental closed-loop responses of the human accommodative system are predicted by synthesizing the system closed-loop controller. The resultant control signals are shown to minimize the time required to change the refractive state of the eye. The plant dynamic model and the closed-loop model are further verified by comparing their frequency responses to experimental data. The optimal performance of the lens system is compared to analogous performance of another ocular control system, and a possible general theory of optimal control is discussed.

Management of Acromegaly

Excerpt Acromegaly is a chronic disease not to be neglected. In addition to its metabolic abnormalities that are the consequence of excessive growth hormone secretion, neurologic sequelae can be ca...

Hypophysectomy for stage IV breast cancer.

Transnasal, transsphenoidal microsurgical hypophysectomy is a useful therapeutic procedure for patients with Stage IV breast cancer which can be peformed in selected patients with minimal morbidity and mortality. Functionally complete hypophysectomy can be accomplished with regularity, and anything less than this is considered to be a technical failure despite the fact that remissions may occur after incomplete hypophysectomy. In view of the recent outstanding results with antiestrogen therapy in patients with breast cancer, we recommend this as the initial treatment in those patients who are good candidates for endocrine therapy. Hypophysectomy has been shown to induce improvement after antiestrogen treatment, particularly in those patients who have had an initial response to antiestrogens as well as in a few patients who failed to benefit. Estrogen receptor measurements in the tumor tissue have been shown to be useful in selecting patients for hypophysectomy as well as for antiestrogen therapy. Prolactin receptors have been found in about 50 per cent of human breast cancers, and their potential usefulness in selecting patients for hypophysectomy is being explored. Hypophysectomy is a definitive therapeutic procedure that should not be used as a last resort in the terminally ill patient.

Prolactin secreting pituitary adenomas in women

The introduction of a radioimmunoassay for prolactin several years ago has increased our awareness and improved our understanding of the role of PRL in reproductive function in humans. It became evident with time, that the majority of pituitary tumors that were labelled as chromophobe or nonfunctioning were in fact secreting PRL. Of all pituitary tumors those secreting PRL account for approximately 50–55%. Thus PRL secreting pituitary tumors or prolactinomas are becoming a commonly encountered disease rather than a medical curiosity.

Anterior-pituitary function before and after transsphenoidal microsurgery for pituitary tumors

The introduction of transsphenoidal microsurgery represents a major improvement in the surgical management of functioning and non-functioning pituitary tumors. A distinct advantage of this technique is the ability to achieve selective tumor removal with preservation of normal pituitary tissue, especially in patients with small adenomas. Numerous reports in the literature have underscored the success of transsphenoidal surgery in correcting the hypersecretion of prolactin [1], growth hormone [2], and ACTH [3] due to a functioning pituitary adenoma. As it might be expected, the success of the surgery has been found to be inversely related to the size of the tumor, with the best results obtained in patients with microadenomas (i.e. <10 mm in diameter).