Goldmann perimetry in acromegaly: a survey of 307 cases from 1951 through 1996.

OBJECTIVE: Because visual pathway lesions are a common complication of pituitary tumors, visual field examinations in patients with acromegaly were studied. Proportion and outcome of visual field defects in patients with acromegaly were evaluated. DESIGN: Large, retrospective case series. PARTICIPANTS: We reviewed 307 cases of acromegaly seen from 1951 through 1996 at a single referral center. METHODS: Kinetic visual field testing had been performed with the Goldmann perimeter, and the frequency of visual field defects and their correlation with other clinical manifestations and characteristics of the adenoma were examined. MAIN OUTCOME MEASURES: Repeat visual field examinations. RESULTS: Of the 307 patients included in the analysis, a visual field defect that could be attributed to the pituitary adenoma was observed in 62 (20.2%) during follow-up. Visual field defects were bilateral in 38 (61.3%) of these cases. Patients with visual field abnormalities were significantly younger (P = 0.04), had larger tumors (P < 0.001), had more suprasellar extensions (P < 0.001), and had higher levels of growth hormone in their serum (P = 0.04) than patients free of visual field defects. At the end of the follow-up period, visual field examination remained abnormal in 32 (10.4%). Return to a normal visual field examination after treatment was more frequently observed in patients who were less than 40 years of age at the time of diagnosis (P = 0.004). Secondary empty sella syndrome was the main cause of visual field defects after treatment. Abnormal visual field, either at the time of diagnosis or during follow-up, decreased from 27% of patients between 1951 and 1975 to 15.4% of patients between 1976 and 1996, when modern neuroimaging techniques became available. CONCLUSIONS: Endocrinologic and neuroimaging follow-up of patients with acromegaly should be accompanied by ophthalmic assessment. Factors predictive of visual field defects have been identified.

Plasma chromogranin A in pheochromocytoma, primary hyperparathyroidism and pituitary adenoma in comparison with catecholamine, parathyroid hormone and pituitary hormones.

Plasma levels of chromogranin A (CgA) were measured by ELISA in 22 patients with pheochromocytoma (18 non-metastatic, 3 metastatic, and 1 mixed neuroendocrine-neural tumor), 9 patients with primary hyperparathyroidism, and 9 patients with pituitary adenoma. The plasma levels of CgA were compared with norepinephrine, epinephrine, parathyroid hormone and pituitary hormones, i.e., growth hormone and prolactin. In pheochromocytoma, CgA in preoperative plasma of the patients without metastasis was 228 +/- 38 U/L (mean +/- SEM) and significantly higher than healthy controls (30 +/- 11 U/L, n = 40). Plasma CgA was decreased after removal of the tumors (28 +/- 6.0 U/L), except in three patients with metastatic pheochromocytoma and a mixed neuroendocrine neural tumor. The concentration of CgA in the patients with non-metastatic pheochromocytoma was significantly correlated with that of plasma norepinephrine (P < 0.005, r = 0.68) and urinary norepinephrine (P < 0.05, r = 0.65), but not with that of epinephrine. There was an exceptional case in which CgA was extremely high, but the CA level was normal. This tumor was a highly malignant pheochromocytoma with extensive metastases composed of small tumor cells which were occasionally positive for tyrosine hydroxylase immunohistochemically. These cells were considered to be poorly differentiated tumor cells and synthesized a very small amount of norepinephrine. Plasma levels of the patients with primary hyperparathyroidism and the patients with pituitary adenoma were 44 +/- 4 U/L and 48 +/- 8 U/L, respectively. Only one patient with a growth hormone-producing pituitary adenoma had a high level of CgA. Plasma CgA is a useful tumor marker for pheochromocytoma, even for malignant pheochromocytoma without elevated CA level, but not for hyperparathyroidism, or pituitary adenoma.

[Transsphenoidal microsurgical removal of GH-secreting pituitary adenoma in: a report of 200 cases].

From July 1979 to April 1992, 212 cases of GH-secreting pituitary adenoma were treated transsphenoidally by microsurgical technique, of whom two hundred cases monitored with their GH levels at preoperative and postoperative periods. The majority of cases totally 132 cases were of macroadenoma, and 68 cases were of microadenoma. 138 cases were operated on after April 1986. The cure and remission rate averaged to 72.5%, rising from 44.4% (before 1986) to 80.5% for microadenoma and from 31.4% to 69.1% for macroadenoma due to improvement of technique and accumulation of experience. One patient died of angiocardiopathy suddenly during operation. Mortality rate was 0.5%. The follow-up observation of postoperative GH levels in 52 cases revealed that the GH levels within 2 weeks after operation were the same as in 3-6 months. It is thought that the early GH levels may represent the surgical results. The surgical technique is described and factors influencing the surgical results, prevention and treatment of operative complications are discussed in this paper.

The choice of treatment after incomplete adenomectomy in acromegaly: proton--versus high voltage radiation.

The authors report the results of a study designed to compare the effectiveness of two different types of radiation in patients with acromegaly where surgical therapy had failed to normalize growth hormone (GH). Longterm follow-up after conventional high voltage radiation in 17 patients and proton therapy in 13 patients confirmed a similar reduction of GH levels in both groups. After 4.5 years a decrease of about 80% was achieved. After "conventional radiation" GH was normal in 8 (47%) and near normal in 6 (35%) while proton therapy resulted in normalization in 5 and improvement in 5 (38%). The slightly better results of "conventional radiation" must be attributed to lower pretreatment levels of GH. Side effects as additional pituitary deficits and oculomotor palsies were more often seen after proton treatment. Since the results of both radiation methods are similar and proton therapy has a tendency to more serious side effects we recommend "conventional radiation" as secondary treatment of acromegaly.

Plasma growth hormone half-life after selective removal of adenoma in acromegalics determines the outcome of surgery.

We measured plasma GH levels during transsphenoidal surgery in eight patients with acromegaly. After removal of the adenoma GH levels fell monoexponentially in six subjects while they were still under general anaesthesia, but no decrease was noted for two other subjects. Normal postoperative GH and Somatomedin-C levels were found for those patients who exhibited a reduction in GH during surgery. During follow-up studies one patient with a normal GH level exhibited a paradoxical reaction to TRH, attributed to tumour remnants. The plasma half-life found for five patients was 18-33 min; for another cured subject it was longer, i.e. 58 min. The major fraction of the circulating GH, as determined by gel-chromatography, was mol. wt 22,000; this applied for six subjects, while the patient with the long plasma half-life appeared to have a mol. wt 33,000 variant. From this study we conclude that a clear drop in the plasma GH level after removal of the adenoma predicts a favourable outcome of surgery; however, if some tumour remnants are left behind, paradoxical reactions may occur despite normal basal GH levels.

Long-term treatment of acromegaly with the somatostatin analogue SMS 201-995 over 6 months.

This study examined the effects of the long-acting selective mini somatostatin analogue (SMS) 201-995 in two acromegalic patients who were treated for 3 and 6 months, respectively. During treatment the mean growth hormone levels (25.3 and 20.8 ng/ml vs 5.9 and 10.6 ng/ml) and somatomedin C levels (6.2 and 6.2 IU/ml vs 3.3 and 3.8 IU/ml) decreased and the patients reported an improvement in their symptoms. The main side effect was an increase in stool fat excretion which did exceed the normal range (less than 7 g/day) in one patient. Five acromegalics who received 2 X 50 micrograms SMS 201-995/day for 5 days showed a significant increase of stool fat excretion (1.7 vs 3.5 g/day; p less than 0.05). Fasting blood glucose levels, glucose tolerance, and glycosylated hemoglobin were not essentially effected. It is concluded that SMS 201-995 offers new possibilities in the treatment of acromegaly. The gastrointestinal and diabetogenic side effects of this substance, however, should be carefully monitored.

Human pancreatic growth hormone-releasing factor (hpGRF-44) in acromegaly before and after adenomectomy. Modifications induced by somatostatin (GHRIH) infusion.

The influence of human pancreatic growth hormone-releasing factor (hpGRF-44) on GH secretion was investigated in 15 patients with active acromegaly. Following the administration of hpGRF-44 (1 microgram/kg, iv) mean (+/- SE) serum GH level increased from 22.4 +/- 6.3 ng/ml to 42.9 +/- 8.2. ng/ml (peak, p less than 0.01). The pattern and the magnitude of the GH rises were widely variable and it was possible to identify three types of responses: in fact in 2 cases a very large serum GH rise, eight folds over baseline, was observed, in 7 patients a clear GH stimulation, two-three fold over baseline was noticed and in 6 patients no significant GH modifications were seen. No correlation was found between the response to hpGRF-44 and the existence of abnormal GH responses to dopamine infusion, TRH and dopamine-sulpiride test. In 5 acromegalic patients hpGRF-44 was injected again after transsphenoidal adenomectomy. The magnitude of serum GH response decreased in one hyperresponsive patient, increased in 2 previously unresponsive cases and did not change in the remaining cases. In 6 GH responsive patients hpGRF-44 was injected at 120 min during a 4 hour infusion of somatostatin (GHRIH, 3.33 micrograms/min). GHRIH infusion significantly suppressed GH levels in all the patients and blunted the hpGRF-44 stimulated GH increase. The different patterns of GH response to hpGRF-44 in acromegalic patients suggest a different sensitivity of the adenomatous somatotrophs and a possible contribution by normal GH-secreting cells to hpGRF-44 induced GH response.

The role of prolactin in the inhibitory action of bromocriptine on growth hormone secretion in acromegaly.

UNLABELLED: Bromocriptine treatment results in clinical improvement and inhibition of plasma GH levels in only part of the acromegalic patients. The possible role of the simultaneous presence of Prl and GH in GH-secreting pituitary adenomas was investigated with regard to the inhibitory action of bromocriptine on GH secretion and the paradoxical increase of GH release in reaction to TRH. Surgically obtained pituitary tumour tissue from 35 consecutive acromegalic patients was studied immunohistochemically. In 21 patients no Prl was present in the tumour tissue. These patients had normal plasma Prl levels. In the other 14 patients Prl was present in the tumour tissue. Hyperprolactinaemia was found in 10 of these 14 patient. Plasma GH levels from 2 till 10 h after the administration of 2.5 mg bromocriptine measured before operation were significantly more suppressed in the patients with mixed GH/Prl-containing than in those with pure GH-containing pituitary adenomas, being 38 +/- 4% and 65 +/- 4% of basal values, respectively (P less than 0.01). The response of GH to TRH, however, did not differ significantly between the two groups. CONCLUSIONS: 1. In about 70% of patients with 'mixed' GH/Prl containing adenomas, hyperprolactinaemia is present. 2. The simultaneous presence of Prl and GH in a GH-secreting pituitary tumour increases the sensitivity of GH secretion to bromocriptine. 3. The plasma Prl level is of value to predict which patients with acromegaly are likely to respond to bromocriptine with an inhibition of GH secretion.

Childhood acromegaly successfully treated with interstitial irradiation using yttrium-90.

A child with a growth hormone producing tumour presented at the age of 4 1/2 years. The onset of the disease was at 18 months of age. Treatment was given with three doses of interstitial irradiation using yttrium-90 implants. There were no local complications from the procedures. Now, 11 years after diagnosis, she is asymptomatic, of normal appearance, and her height and the size of the pituitary fossa are normal. Growth hormone levels are almost normal, thyroid function is intact, and she is maintained on prednisone and sex hormones.

[Effects of somatostatin upon prolactin secretion both in normal subjects and in patients presenting pituitary adenoma (author's transl)]. / Effets de la somatostatine sur la sécrétion de prolactine. Etude chez des sujets normaux et chez des patients ayant un adénome hypophysaire.

In normal subjects somatostatin cannot modify the plasma levels of prolactin when they are in a normal range or when they are pharmacologically increased. In the case of pituitary adenoma (prolactinic or eosinophilic), the response of prolactin to somatostatin varies widely. In some patients there is a marked decrease of the prolactin levels while in others no modification is observed.

Prolactin-secreting tumors and hypogonadism in 22 men.

We studied 22 men with prolactin-secreting pituitary tumors and hypogonadism. Twenty complained of impotence, nine had visual impairment, and three experienced galactorrhea. None of the 17 patients undergoing operation or radiotherapy, or both, were subsequently normoprolactinemic. In all 13 patients treated with bromocryptine major clinical improvement was associated with a decrease in serum prolactin levels and in nine with an increase in serum testosterone. Two patients receiving testosterone replacement therapy showed improved potency only after bromocryptine was administered. The results indicate that hyperprolactinemia frequently induces hypogonadism in men, that bromocryptine ameliorates symptoms of disease previously unchanged by operation or radiotherapy, and that the impotence observed may not be solely the result of hypogonadism.