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Endocrine-inactive pituitary adenomas.

I have described some of the currently known characteristics of a group of pituitary adenomas that produce no syndrome of hormone secretion. These tumors, termed endocrine-inactive, are engaged in low levels of endocrine activity and under certain circumstances can secrete hormones, primarily glycoprotein hormones and their subunits. I have advocated a more vigorous attempt to achieve total removal of these usually large tumors because of my conviction that many, although certainly not all, can be removed completely with preservation of anterior pituitary function and, possibly, recovery of lost anterior pituitary function. Transsphenoidal removal of endocrine-inactive tumors is safe as well as effective and, in the foreseeable future, will continue to be the treatment of first choice.

Adenoma↗

[Hypophyseal dysfunction and tumors].

Some pituitary hormones secrete hormones while others do not. Nonsecreting tumors can interfere with normal pituitary hormone secretion and produce tumor symptoms and signs like headaches and visual field defects. The most frequent hormone-secreting tumors are prolactinomas. Growth hormone or ACTH or gonadotropin or gonadotropin-alpha and beta chain-producing tumors are less frequent, TSH producing tumors are extremely rare. The most important elements of the diagnostic work-up are clinical signs and symptoms, assessment of pituitary function (measurement of TSH, free T4, LH, FSH, oestradiol/free testosteron, growth hormone, IGF-1, prolactin, ACTH, Cortisol, serum and urine osmolality), CT and/or MRI and, in patients with large tumors, a visual field exam. The treatment of choice of pituitary tumors is often surgery. Alternative therapies are radiation treatment (in nonoperable patients or when hormone levels are persistently elevated after pituitary surgery) and drug treatment (dopamine agonists in hyperprolactinemia, somatostatin analogues in acromegaly). Pituitary hormone deficiencies are treated depending on the specific deficiency with thyroxine, cortisone, oestrogen/gestagen/testosterone gonadotropines or ADH analogues.

Adenoma↗

Cushing syndrome in pregnancy.

The occurrence of pregnancy in the face of untreated Cushing syndrome is rare because of the high incidence of ovulatory disturbances experienced by patients with the disorder. A total of 58 patients with 65 pregnancies has been reported in the literature to date. Although pituitary-dependent adrenal hyperplasia is the most common etiology of Cushing syndrome in the general population, adrenal adenoma is more common in the pregnant population. Significant maternal morbidity is attributable to hypertension, congestive heart failure, and poor tissue healing. Prematurity and intrauterine growth retardation account for most of the perinatal morbidity; perinatal mortality is substantial. Treatment directed at relieving hypercortisolism has been instituted during pregnancy: Pituitary or adrenal surgery, chemotherapy, and pituitary irradiation have all been reported, with variable results. Information is lacking on any alteration of maternal morbidity after treatment. The impact of therapy on perinatal outcome appears limited to a reduction in the prematurity rate, but overall numbers are small and such a conclusion should be viewed with caution. No significant maternal or perinatal complications secondary to treatment itself were reported.

Cushing Syndrome↗

Long-term treatment of 189 acromegalic patients with the somatostatin analog octreotide. Results of the International Multicenter Acromegaly Study Group.

BACKGROUND: We wanted to determine the clinical and biochemical effects of long-term therapy with the somatostatin analog octreotide in 189 acromegalic patients. METHODS: Patients were treated at 23 medical centers for 6 days to 231 weeks (median, 24.2 weeks) with varying octreotide dosages (100 to 1500 micrograms/d; median, 300 micrograms/d). Serum growth hormone and insulin-like growth factor I (IGF-I) concentrations before and at the end of the study were compared, and correlations between the response to treatment with total daily dosage and duration of treatment were sought. RESULTS: The clinical response rate was 88%, irrespective of dosage or treatment duration. Serum growth hormone levels decreased in 172 (94%) of 182 patients and IGF-I levels decreased in 91 (92%) of 99. The mean pretreatment growth hormone level was 39.4 +/- 4.4 micrograms/L and decreased to 12.2 +/- 1.5 micrograms/L. Growth hormone levels decreased to less than 5 micrograms/L in 82 (45%) of 182 patients. The pretreatment IGF-I level was 5.62 +/- 0.41 U/mL and decreased to 2.64 +/- 0.19 U/mL; suppression to 2 U/mL or lower occurred in 46 (46%) of 99 patients. The degree of growth hormone suppression was associated with longer treatment duration but not with the total octreotide dosage per day. In 34 patients studied prospectively, pituitary tumor size decreased by greater than 20% in 15 (44%). Side effects occurred in 37% of patients and were most commonly transient loose alcoholic stools, pain at the injection site, and abdominal discomfort; severity was mild to moderate. Glucose tolerance was unchanged or improved in 52% and declined in 48% of 25 patients evaluated. CONCLUSIONS: Octreotide is an effective treatment for acromegaly that may be used as primary therapy or after surgery and/or pituitary irradiation.

Acromegaly↗

[Criteria for surgical therapy of hypothalamo-hypophyseal Cushing's syndrome].

This article tries to give criteria for the two possible modes of treatment of the pituitary-dependent Cushing's syndrome. Patients (n = 6) who show no secondary complications on Cushing's disease should undergo implantation of 90Y and/or 192Ir into the pituitary gland. After implantation, the excessive secretion of ACTH is suppressed to normal values. The symptoms of Cushing's syndrome disappear. Following the operation, certain patients must also receive hormonal replacement therapy. Fertility is not always preserved. Total adrenalectomy as the alternative procedure is performed in adults with advanced symptoms of the disease (n = 3) and in children (n = 3). Following removal of the adrenal glands, the symptoms of Cushing's syndrome disappear. The appearance of Nelson's tumor after adrenalectomy (10% in the literature) is discussed.

Adenoma↗

The role of adrenalectomy in Cushing's syndrome.

Forty-four patients with Cushing's syndrome were treated by adrenalectomy between 1975 and 1989. Twenty patients had adrenal adenomas: 13 with obvious Cushing's syndrome and 7 whose disease was subclinical, detected after evaluation of an incidentally discovered adrenal mass (es). Twelve patients underwent bilateral adrenalectomies for Cushing's disease after failed transsphenoidal explorations and pituitary irradiation. Six patients had primary adrenal hyperplasia, five as manifestations of Carney's complex. Two others underwent bilateral adrenalectomies for ectopic adrenocorticotropic hormone from carcinoid tumors. Four patients had adrenocortical carcinoma treated with transabdominal adrenalectomy. Three are alive from 8 years to 5 months. There was one postoperative death (2.3%) caused by coagulopathy and multiple organ failure and three (7%) minor postoperative complications. Follow-up showed good to excellent results in 95% of patients. It is concluded that adrenalectomy provides prompt relief from the severe morbidity of Cushing's syndrome regardless of the cause. It is the treatment of choice for adrenal adenomas, carcinomas, primary hyperplasia, and selected patients with Cushing's disease.

Adenoma↗

Acromegaly in Ibadan--a report of six cases.

Six patients with acromegaly were seen over a six year period at the University College Hospital, Ibadan, Nigeria. There were 5 males and 1 female giving a sex ratio which differed from the equal sex prevalence observed in larger caucasian series. The diagnosis was made strictly on clinical grounds with corroborative evidence from x-ray of the skull and limbs. An unusual and unexpected finding was the observation of a hernia or a history of herniorrhaphy in 4 out of the 5 male acromegalics. It was not certain whether the association was real or what the explanation might be. Transfrontal surgery was the only definitive form of treatment that could be offered to the patients because of lack of facilities for transphenoidal adenomectomy or pituitary irradiation. The operation was refused by 4 of the 5 patients to whom surgery was recommended because of cultural fears regarding operations on the brain. Bromocryptine was prescribed as an alternative therapy but its scarcity and prohibitive cost precluded any serious compliance. There is a need to highlight the problems of the silent sufferer of endocrine disorders in developing countries.

Acromegaly↗

MR imaging of the ectopic bright signal of posterior pituitary regeneration.

High-field-strength MR studies of 13 patients with sellar and/or parasellar tumors revealed an aberrant location of the posterior pituitary bright signal in the hypothalamus in seven cases and in relation to the pituitary infundibulum in six cases. Five of the MR studies were obtained in patients who had not had surgery and had pituitary adenomas producing compression and/or destruction of the posterior lobe. In the other eight cases, the aberrant bright signal occurred after hypophysectomy in seven patients and after removal of a craniopharyngioma in the eighth. Accumulation of neurosecretory material and regeneration of pituitary tissue in these ectopic locations have been documented previously in animal experiments and in a few reports in humans after hypophysectomy. MR imaging now provides further corroborative evidence in vivo of this process in which a "miniature posterior lobe" is formed.

Adenoma↗

[The role of radiation therapy in treating hypophyseal adenomas].

The article reviews various methods for the exposure of pituitary adenomas to the effect of radiation applied either as the only measure or in combination with surgery and drug therapy. The indications for radiotherapy are discussed according to the size and hormonal activity of the tumor.

Adenoma↗

[Serum anti-protease activity in the evaluation of results of proton hypophysectomy].

The activity of the alpha 1-antitrypsin and alpha 2-macroglobulin were studied in 16 breast cancer patients and 25 hypophyseal adenoma patients prior to and at varying time after proton "hypophysectomy". A high alpha 1-antitrypsin level and a normal alpha 2-macroglobulin level were found in all the breast cancer patients. An increase in both blood serum inhibitors was detected in hypophyseal adenoma. The dependence of the alpha 1-antitrypsin content on a subclinical stage of generalized metastatic spread was revealed in the course of 2 years following "hypophysectomy" in the patients with disseminated breast cancer. In the hypophyseal adenoma patients the activity of both inhibitors returned to normal 1 year after treatment and remained within normal during 3 years of follow-up. It was regarded as a positive therapeutic effect. The above findings make it possible to propose the determination of the activity af alpha 1-antitrypsin in breast cancer and alpha 1-antitrypsin and alpha 2-macroglobulin in hypophyseal adenoma as an additional test for the evaluation of the results of proton "hypophysectomy".

Adenoma↗

Medical therapy of hyperprolactinemia.

Although many causes of hyperprolactinemia exist, medications and prolactin-secreting pituitary tumors (prolactinomas) are the most common etiologies. The mainstay of medical management for pituitary tumors as well as for most causes of hyperprolactinemia is bromocriptine. The drug can be used alone or in conjunction with other therapeutic modalities, including surgical resection and pituitary irradiation, depending on the clinical scenario. Bromocriptine can lower serum prolactin, reduce tumor size, and restore fertility in those patients during pregnancy. As bromocriptine is not always well tolerated and requires frequent dosing, newer agents that may diminish side effects and improve compliance are under investigation.

Humans↗

Proton radiotherapy with the Uppsala cyclotron. Experience and plans.

From 1957 to 1968, the 230-cm synchrocyclotron at the Gustaf Werner Institute was used for clinical tests with a 185 MeV proton beam. The radiotherapeutic research was part of an extensive research programme in physics, chemistry, biology and medicine. Only a small series of patients were treated. A brief review of the early development and clinical experience of the cyclotron activities at Uppsala from 1957 to 1968 is given. The former accelerator is now being converted. Beams are expected to be available in the new radiotherapy treatment rooms in 1986. Plans for the new facilities with special reference to alternative methods of proton acceleration and beam transport, i.e. fixed beams or an gantry system are presented. The corresponding activities at the Institute of Theoretical and Experimental Physics (ITEP) in Moscow are also referred to thanks to a bilateral research programme which has existed in the past and from which the Uppsala group has benefited greatly.

Brain Neoplasms↗

[Rehabilitation of young craniopharyngioma patients].

The course of rehabilitation in 11 young patients with craniopharyngeoma was investigated. With intelligence well-preserved, neuropsychological diagnosis revealed impairments in rate and persistence in virtually all patients; behaviour disorders were present in 8 of the 11 patients, with efforts to distinguish psychoorganic from psychoreactive causality however not always successful. The neuropsychological deficits and behavioural deviations mentioned, rather than complications of a medical nature (1 of 11), resulted in only 2 patients having been able to maintain their premorbid educational/vocational status. The rehabilitative outcomes obtained in patients with clear-cut indications of diencephalic lesion (among them variations in vigilance, polyphagia, adipsia) had been unsatisfactory, whereas, in the other behaviourally disordered patients, successful outcomes were achieved by a therapeutic approach tailored to the specific needs of the individual condition.

Adolescent↗

A new method for treatment of unresectable, recurrent brain tumors with single permanent high-activity 125iodine brachytherapy.

We describe a new method for treating unresectable recurrent brain tumors in previously-irradiated patients with localized high-dose intracranial brachytherapy of 10,000-30,000 rads using permanent implantation of a single high-activity 125Iodine seed. For unresectable recurrent previously-irradiated pituitary tumors, a single high-activity 125Iodine seed is permanently implanted into the center of the tumor with an interstitial needle inserted under fluoroscopic guidance via a transsphenoidal approach. For unresectable recurrent meningiomas, a single high-activity seed is permanently implanted into the tumor at craniotomy. The clinical course of five patients treated by this method is described. Excellent long-term local control was obtained in all implanted cases. There were no intraoperative, postoperative, or chronic complications.

Adenoma↗