Acromegaly and diabetes mellitus associated with hyperthyroidism.

A 66-year-old woman with acromegaly and diabetes mellitus as well as primary hyperthyroidism is described. Serum GH Levels were inappprpriately high.MRI revealed an enlarged sella turcica with intrasellar mass. Her HbAlc was 12.2% and fasting blood glucose 8.89 mmol/l. Thyroid hormone levels in serum and thyroidal radioiodine uptake values were elevated, while TSH measurements in serum were low. Anti TPO antibodies were negative, TSH receptor antibodies were normal. Thyrotoxicosis as the first presenting illness in acromegaly was particulary uncommon. An ultrasound thyroid scan showed a multinodular goiter. Histology of the pituitary lesion showed a typical eosinophilic adenoma which only secreted GH when tested with specific immunostain. Post-operatively, the patient's clinical conditions improved, however, secondary hypoadrenalism appeared.

Outcomes of endoscopic papillectomy in elderly patients with ampullary adenoma or early carcinoma.

Outcomes for 14 elderly (age ≥ 70 years) patients (79.4 ± 1.0 years) who underwent endoscopic papillectomy for ampullary tumors were compared with those of 22 younger (age < 70 years) patients (52.5 ± 1.9 years). There were no differences in procedural success (100%), bleeding (5/14 vs. 6/22), adenoma recurrence (0/14 vs. 2/22) and median survival (24.0 vs. 25.5 months) between the elderly and younger patients. In younger patients, although adenoma recurrences (n=2) were managed endoscopically, invasive adenocarcinomas (n=3) were treated by pancreatoduodenectomy. All elderly patients with invasive (T2) tumors (n=5) were not surgically fit and underwent successful palliation with further endoscopic resection and stenting. Whilst all younger patients survived, five elderly patients died but three of these deaths were not cancer-related. Advanced age, therefore, did not adversely influence the outcomes of endoscopic papillectomy, suggesting it may be a treatment of choice for elderly patients with ampullary tumors or early cancer who are deemed unfit for surgery.

Apoplexy accompanying pituitary adenoma as a complication of preoperative anterior pituitary function tests.

Pituitary apoplexy occurs as a very rare complication of the pituitary function test. We have experienced two cases of pituitary apoplexy following anterior pituitary function tests for preoperative assessment: a triple bolus test and a TRH test. To elucidate such a rare complication, we outline our two cases and review 28 cases from the literature. The clinical characteristics, etiology, pathophysiology, and diagnostic and therapeutic implications are also discussed. The combined data suggest that pituitary function tests have the potential to precipitate pituitary apoplexy, and its manifestations range from a clinically benign event to a catastrophic presentation with permanent neurological deficits or even death, although most patients may fortunately have a good outcome. We suggest that the pituitary function test should not be done as a routine test, and when such a test is planned, the patient should be observed with caution for any symptomatic changes for at least 2 hours following the test for appropriate treatment. Further, MRI, especially enhanced studies, may provide an earlier diagnosis of the pituitary apoplexy since CT scan images often fail to demonstrate either density changes or obvious enlargement of the pituitary adenoma at the acute stage.

Transsphenoidal microsurgery in the treatment of acromegaly and gigantism.

Twenty-five patients with acromegaly and 3 patients with gigantism underwent transsphenoidal microsurgery in an attempt to remove the tumor and preserve normal pituitary function whenever possible. An adenoma was identified and removed in 27 of 28 patients. Evaluation 3--6 months postoperatively revealed a GH level less than 5 ng/ml in 29 patients, 5--10 ng/ml in 4 patients and 11--29 ng/ml in 4 other patients. Dynamics of GH secretion were normal in 11 patients who had normal pituitary function and are considered cured. Two patients with low or undetectable GH levels are also considered cured at the expense of being hypopituitary. Three of 7 patients with normal basal GH levels but abnormal dynamics of GH secretion relapsed within 1 yr. Eleven of the 13 patients considered cured did not have extrasellar extension, while 14 of the 15 patients not cured had extrasellar extension. Five patients who were not cured with surgery received radiation therapy. Three patients were treated with an ergot derivative, Lergotrile mesylate, after surgery and radiation therapy failed to normalize GH levels. Transsphenoidal microsurgery is an optimal form of therapy for patients with acromegaly or gigantism, especially those with no extrasellar extension. Dynamics of GH secretion are very useful in evaluating the completeness of adenoma removal.

Long-acting peptidomimergic control of gigantism caused by pituitary acidophilic stem cell adenoma.

Gigantism is caused by GH hypersecretion occurring before epiphyseal long bone closure and usually is associated with pituitary adenoma. A 15-yr-old female patient presented with accelerated growth due to a large pituitary tumor that was surgically resected to relieve pressure effects. Second surgery to remove residual tumor tissue was followed by administration of octreotide LAR, a long-acting depot somatostatin analog, together with long-acting cabergoline. Height was over the 95th percentile, with evidence of a recent growth spurt. Serum GH levels were more than 60 ng/mL (normal, <10 ng/mL) with no suppression to 75 g oral glucose, and serum PRL (>8,000 ng/mL; normal, <23 ng/mL) and insulin-like growth factor I levels (845 ng/mL; age-matched normal, 242-660 ng/mL) were elevated. Histology, immunostaining, and electron microscopy demonstrated a pituitary acidophil stem cell adenoma. Tumor tissue expressed both somatostatin receptor type 2 and dopamine receptor type 2. The Gs alpha subunit, GHRH receptor, and MEN1 genes were intact, and tumor tissue abundantly expressed pituitary tumor transforming gene (PTTG). Serum GH and PRL levels were controlled after two surgeries, and with continued cabergoline and octreotide LAR GH, PRL, and insulin-like growth factor I levels were normalized. In conclusion, administration of long-acting somatostatin analog every 4 weeks in combination with a long-acting dopamine agonist biweekly controlled biochemical parameters and accelerated growth in a patient with gigantism caused by a rare pituitary acidophil stem cell adenoma.

Anterior pituitary function before and after trans-sphenoidal microsurgical resection of pituitary tumors.

Anterior pituitary lobe function was measured pre- and postoperatively in 40 patients with pituitary tumors who were managed surgically by the trans-sphenoidal approach. Of 23 patients with normal anterior lobe function preoperatively, 21 (91%) were normal postoperatively. Of 17 preoperatively impaired patients, 7 (40%) regained normal function, 3 (18%) improved, 4 (24%) remained the same, and 3 (18%) were further impaired by the surgery. In this small series, the likelihood of recovery of pituitary function varied inversely with the degree of preoperative impairment and the size of the tumor, suggesting that more aggressive surgical management of small, minimally symptomatic pituitary tumors is justified.

Double adenomas of the pituitary: a clinicopathological study of 11 tumors.

Of more than 3000 cases of surgically removed pituitary adenomas, 11 were defined as "double adenomas," i.e., 2 morphologically or immunocytologically distinct tumors. In 8 cases, the lesions exhibited differing histological features and immunophenotypes; in 2 specimens, distinct ultrastructural features were noted as well. In another instance, despite histological and immunocytological uniformity, the two neoplastic components demonstrated distinct ultrastructure. In yet another case, the two adenomas were consecutively removed; despite similar histological features, they differed in immunocytological and ultrastructural characteristics. Last, in one case, the adenoma was histologically uniform, but a portion of the mass exhibited immunoreactivity by ultrastructural features distinct from those of the remainder of the lesion. Hormonal excess attributed to both tumors could be correlated with endocrine manifestations in two cases. Double adenomas of the pituitary occur infrequently. In routine histological sections of surgical material, they are often difficult if not impossible to identify. Presented herein are clinical and endocrinological data on 10 cases of double pituitary adenomas correlated with morphological and immunocytochemical results. The literature regarding multiple adenomas is reviewed as are the diagnostic and therapeutic difficulties associated with these rare lesions.

Transsphenoidal microsurgery for pituitary tumors associated with hyperprolactinemia.

The results of transsphenoidal microsurgery in treating 37 patients (30 women and seven men) with pituitary tumors associated with hyperprolactinemia are presented. Immediate (10-day) postoperative fasting prolactin levels were normal (less than 25 ng/ml) in 19 of 26 patients whose preoperative prolactin level was less than 200 ng/ml, and in only three of 11 patients in whom preoperative prolactin was greater than 200 ng/ml. Twelve of 13 patients with normal preoperative pituitary-target organ function maintained normal axes postoperatively. Thirteen other patients had preoperative deficiencies in one or more pituitary-target organ axes. Postoperatively, in these latter 13 patients, a pituitary-target organ axis that was deficient preoperatively returned to normal in six cases; there was no change in five, and there was impairment in another axis in four instances. Although gross total tumor removal was believed to be complete in 35 of 37 patients, serial postoperative prolactin determinations in four of these 35 patients indicate tumor regrowth. The authors conclude that transsphenoidal microsurgery is currently the operative procedure of choice for the majority of pituitary tumors associated with hyperprolactinemia.

Acidophil stem-cell pituitary adenoma in a prepubescent female. Case report.

Acidophil stem-cell pituitary adenomas account for less than 5% of pituitary tumors. Only 15 cases have previously been reported, with a mean age of occurrence of 38.7 years. A case of this unusual tumor is reported in a prepubertal girl. Clinical symptoms included prominent behavioral disturbance with associated headache and visual disturbance. There was marked elevation of serum growth hormone concentration without clinical features of growth hormone excess, suggesting that this tumor has the capacity to excrete biologically inactive hormones. The clinical and pathological features of this unusual invasive pituitary tumor are reviewed; the age spectrum for this neoplasm must be expanded to include prepubertal children.

CSF prolactin determination in patients following operation for pituitary tumor.

Serial cerebrospinal fluid (CSF) and plasma prolactin concentrations were determined from patients during prolactin stimulatory testing with thyrotropin-releasing hormone or during pneumoencephalographic stress. Six patients had been operated on for suprasellar extension of pituitary tumor and one had been irradiated for suprasellar extension of a pituitary tumor. Prior to testing, four patients had had no clinical evidence of tumor recurrence and 3 patients had had tumor recurrence. One of the recurrent tumors had again extended into a suprasellar location. Basal CSF prolactin was undetectable in all patients who had had no recurrence. In 3 of the 4 patients without recurrence, however, prolactin became detectable in CSF during stimulatory testing. CSF prolactin values also increased during stimulatory testing in the patient with suprasellar recurrence of the tumor. A basal CSF-to-plasma prolactin ratio was 0.1 or less in all patients without recurrence. In the 2 patients with recurrence but without suprasellar extension, the CSF-to-plasma prolactin ratio was 0.18 or less. The patient with suprasellar recurrence had a strikingly elevated CSF-to-plasma prolactin ratio of 1.1. Thus, an increase of CSF prolactin during stimulatory testing does not necessarily indicate suprasellar recurrence of a pituitary tumor. However, an elevated CSF-to-plasma prolactin ratio appears to remain a valid indicator of suprasellar extension despite prior pituitary surgery.

Monitoring of visual function during parasellar surgery.

Damage to the visual system is an unfortunate complication of surgery in the area of the optic chiasm. It is now possible tomonitor the functional status of the visual system intreoperatively at regulat intervals. This is accomplished by recording the Visual Evoked Response to flashes of light from light-emitting-eiodes. These diodes are embedded in a special plastic shell which inserts under the eye lids of each eye. Since the light comes from the diodes in the plastic shell, there is no need to disturb the surgical procedure when a test run is desired. A record is obtained by averaging 100 three-per-second flashes.

Ectopic growth hormone-releasing adenoma in the cavernous sinus--case report.

A 55-year-old woman presented a rare ectopic pituitary adenoma in the right cavernous sinus manifesting as acromegaly. The tumor was removed via transsphenoidal approach. Intraoperative observation showed the adenoma was located entirely within the right cavernous sinus, and separated from the normal pituitary gland by the medial wall of the cavernous sinus. There was no communication between the tumor and the pituitary. Histological examination showed a growth hormone-releasing adenoma. Including our case, only eight of 86 reported ectopic adenomas have occurred in the cavernous sinus. Such ectopic presentation may be responsible for failed transsphenoidal surgery for endocrinologically active tumors.

Effect of long-term treatment with somatostatin analogue (SMS 201-995) on pituitary tumor shrinkage in acromegaly--report of two cases.

The effect of long-term somatostatin analogue (SMS 201-995) treatment in two acromegalic patients is reported. Continuous tumor shrinkage was observed even after 129 and 139 weeks of treatment with 600 micrograms of SMS 201-995 daily. A huge and firm adenoma underwent shrinkage during treatment with SMS 201-995. No serious side effect appeared during 160 weeks of treatment. SMS 201-995 has a longterm tumor shrinkage effect and improves endocrinopathies.

[Long-term results of radiation therapy for pituitary adenoma--analysis of 386 cases].

A total of 386 cases of pituitary adenoma treated in our hospital from Jan. 1963 to Jan. 1986 is reported. Of them, 117 were treated by operation alone, 97 by radiotherapy alone and 172 by operation plus radiotherapy. 119 cases (group A) treated before April 1980 were mostly diagnosed by pneumoencephalography or cerebral angiography, treated, by conventional operation, followed by radiation therapy with 60Co or linear accelerator. 267 cases (group B) treated after April 1980 arrived at the correct diagnoses by CT scan and endocrine assay, treated by microsurgery, followed by radiotherapy with linear accelerator. All patients were followed for 2-23 years. The response rates of groups A and B were 90.7% and 94%. The results were better in patients treated by surgery combined with irradiation. The recurrence rate of radiation or surgery alone was higher than that of combined therapy. It is indicated that the optimal treatment for pituitary adenoma is surgery combined with radiotherapy. Besides, the introduction of CT scan and microsurgery has improved the diagnosis and treatment results of pituitary adenoma.

[Hypofunction of peripheral target-gland after radiotherapy of pituitary adenoma--an analysis of 140 cases].

One hundred and forty cases of pituitary adenoma, treated by surgery plus radiotherapy or radiotherapy alone from 1978 to 1985, were analysed as to the incidence of hypothalamo-pituitary and peripheral target-gland hypofunction after radiotherapy. The incidence of hypothyroidism, hypogonadism and hypoadrenalism was 51.7%, 61.4% and 17.8%, respectively. Thyroid and gonad were vulnerable following hypothalamo-pituitary hypofunction, and the incidence was 19.2% and 23.5% individually, and 27.1% simultaneously. The incidence of hypoadrenalism was 7.1%. The total incidence of target-gland hypofunction was 10.7%. Hypofunction of the posterior lobe of the pituitary often occurred after operation. For patients treated with radiotherapy alone, the incidence of hypothalamo-pituitary and target-gland hypofunction was high because of higher irradiation dose. Hormonotherapy was successful in the treatment of hypopituitarism and target-gland hypofunction. For radiotherapy of pituitary adenoma, DT 40-45 Gy and treatment field 4 x 4 cm are recommended.

Sudden blindness from pituitary apoplexy: a report of two cases.

Two cases of acidophil adenoma of the pituitary causing sudden blindness from pituitary apoplexy are presented. The tumours had been clinically silent, without producing any symptoms of endocrine dysfunction. Radiological evidence was very conclusive. Transfrontal craniotomy with decompression resulted in quick and dramatic visual improvement. The interesting syndrome of clinical manifestations is discussed.

[Acromegaly and sleep apnea syndrome (author's transl)]. / Acromégalie et apnée du sommeil.

Acromegaly associated with a Sleep Apnea Syndrome has but exceptionally been reported. Polygraphic recordings of sleep have been carried out in parallel with the determination of pituitary hormonal secretions, during the nycthemeral period before and after surgical treatment of the adenoma. There appears a Sleep Apnea Syndrome of the predominant obstructive type; the Apnea index is: 57 (N less than or equal to 4); the hypnogram is considerably jagged, with more than a thousand wakings and changes in the sleep stages, due to a great number of apneas. The deep slow sleep never occurs: no stages 3 and 4. The physiological peak of G.H. secreted in the beginning of the deep slow sleep thus does not appear in the Sleep Apnea Syndrome. The existence of a "false negative" criteria of a cured Acromegaly must be taken into consideration. The Sleep Apnea Syndrome must be differentiated from Narcolepsy and the usual Pickwickian syndrome. The Sleep Apnea Syndrome and Acromegaly seem to be two separate diseases, each one evolving independently. The cure of Acromegaly has not led to the cure of the Sleep Apnea Syndrome and the latter has not prevented the clinical and biological cure of Acromegaly. This may be an argument in favor of the independence of Acromegaly towards some hypothalamic structures.

[Endonasal removal of pituitary growth hormone-adenoma: report of 56 cases].

Fifty-six cases of pituitary GH-adenoma removed by endonasal method are reported. In 50 cases, plasma hGH decreased postoperatively. According to biological evaluation, 18 patients were cured, 21 were improved and 17 presented no change. Postoperative high hGH (greater than or equal to 5 ng/ml) indicated that there were some residual functioning tumor cells in the Sella. Such cases must be followed up regularly in order to assess when and what treatment should be given. Postoperative radiation usually raises the curability of acromegaly. Endonasal method is simple, effective and less injurious to the neighboring structure of the nose.

[Downward migration of the optic system after transsphenoidal approach of a giant eosinophilic adenoma (author's transl)].

Headache and visual impairment resulting from downward migration of the optic system in an acromegalic patient, occurred after one year postoperatively. A 25-year-old woman with eosinophilic adenoma was operated on via transsphenoidal approach and irradiated (5,000 rads) following the operation. After the operation, bitemporal hemianopia was thoroughly improved and serum HGH level was also markedly decreased after radiation therapy. One year later, headache and visual impairment recurred. Pneumoencephalogram revealed that the infundibular and optic recessus of the third ventricle were elongated and descended into the sella turcica. The second operation was performed by subfrontal approach and the optic system was found to be migrated into the sella, which we assumed to be the cause for the recurrence of the headache and visual field defect. In order to prevent this type of complication, it would be recommended to fill up the dead space in the sella with bone or cartilage fragments in addition to muscle pieces, as was suggested by Guiot et al.

[Sleep apnea syndrome in acromegalic patients]. / Zespól bezdechów podczas snu u chorych z akromegalia.

The aim of this report was to analyse the sleep apnea rate and its clinical picture in acromegaly patients before and after the surgical treatment. The authors investigated both hormones levels and spirometric coefficients. They found, that surgical removal of microadenoma from transphenoidal approach led to the fast regression of the syndrome.