Pituitary Chromophobe Adenoma Research Articles

Blindness from Intracranial Tumors

We analyzed the cause of blindness in 60 people with intracranial tumors. Twenty-three (38.3%) had binocular blindness, thirty-seven (61.2%) had monocular blindness. The most common tumors producing blindness were pituitary chromophobe adenomas and craniopharyngiomas. Blindness in this series resulted usually from intracranial tumors, which directly or indirectly involved the optic nerve or optic chiasma. These tumors were sometimes misdiagnosed when these patients were first examined by physicians. Specific ophthalmic examinations should permit the diagnosis to be made earlier.

Selective osmoreceptor dysfunction presenting as intermittent hypernatremia following surgery for a pituitary chromophobe adenoma

Intermittent hypematremia following hypothalamic surgery or trauma is usually attributed to the triphasic dysfunction of vasopressin release (diabetes insipidus, inappropriate vasopressin release, and diabetes insipidus). A 39-year-old patient had hypodipsia and intermittent hypematremia following hypothalamic surgery for a chromophobe adenoma. Mean arterial pressure fell by 25 percent during orthostasis testing and was associated with an increase in vasopressin levels from 1.3 μU/ml to 12 μU/ml. Plasma renin activity and aldosterone increased from 1.1 to 16 ng/ml per hour and from 6.7 to 39 ng/dl, respectively, and remained elevated for three and a half hours after tilt testing. Hypertonic saline infusion, on the other hand, increased serum osmolality from 290 to 304 mOsm/kg but did not result in a significant rise in vasopressin levels (all were less than 1 μU/ml). These results are consistent with a selective dysfunction of the osmoreceptor pathways of vasopressin release and intact volume receptor-mediated pathways. Patients with intermittent hypematremia following hypothalamic surgery or trauma should be questioned specifically regarding thirst. If it is impaired or absent, these patients should be watched carefully, not only for the development of triphasic dysfunction of vasopressin release, but also for a selective osmoreceptor dysfunction associated with thirst deficits as found in patients with “essential hypernatremia.”

The effect of thioridazine on prolactinoma growth in a schizophrenic man: Case report

Thioridazine was found to increase the serum prolactin level as well as the tumor size of a prolactin—secreting pituitary chromophobe adenoma in a schizophrenic man. He was then successfully treated with clonidine, an antinoradrenergic compound without antidopaminergic properties, which had no effect on serum prolactin or tumor growth. This case report highlights the importance of careful neuroleptic usage in patients in whom elevated prolactin levels are of concern and discusses alternative methods of treating psychosis when antidopaminergic medications are contraindicated.

Subacute and chronic toxicity studies of trinitroglycerin in dogs, rats, and mice

Subacute and chronic oral toxicities of trinitroglycerin (TNG) were studied in beagle dogs, CD rats, and CD-1 mice. No adverse effects were seen in dogs given up to 1 mg/kg/day of TNG for 4 weeks, then 5 mg/kg/day for 9 more weeks. Dogs given 25 to 200 mg/kg/day for 5 days had transient and dose-related severe methemoglobinemia, while 200 mg/kg/day produced depression; dogs given 1, 5, or 25 mg/kg/day for 12 months had transient and doserelated mild methemoglobinemia. Rats fed 0.1% TNG for 5 weeks, then 0.5% (230–234 mg/kg/day) for 8 more weeks had decreases in feed consumption and weight gain after the increase in dosage; rats fed 2.5% TNG (1406 or 1416 mg/kg/day for males and females, respectively) for 13 weeks suffered adverse effects, including weight loss, compensated anemia, and testicular degeneration, but they resumed gaining weight as feeding continued. Rats fed 1% TNG (363 or 434 mg/kg/day for males and females, respectively) for 2 years had decreased weight gain, decreased grooming, methemoglobinemia and its sequelae, cholangiofibrosis, hepatocellular carcinoma, and interstitial cell tumors of the testis. A decrease in the naturally occurring pituitary chromophobe adenoma and mammary tumors increased the life span of the females. Some rats fed 0.1% TNG (31.5 or 38.1 mg/kg/day for males and females, respectively) had mild hepatic lesions similar to those seen in rats fed the larger doses. No adverse effects were seen in mice fed up to 0.1% TNG for 3 weeks, then 0.5% for 10 more weeks. Mice fed 1% TNG (1022 or 1058 mg/kg/day for males, respectively) for 2 years had decreased weight gain, decreased grooming, and methemoglobinemia and its sequelae, but no obvious cellular changes as found in the rats.

Rodent carcinogenesis bioassay with oxisuran, a selective immunosuppressive agent

The carcinogenic potential of oxisuran, a synthetic immunosuppressive agent, was studied for 80 weeks and 104 weeks in mice and rats, respectively. Groups of 50 mice and 70 rats of each sex received oxisuran at doses of 600, 240, and 40 mg/kg/day as dietary admixtures over the entire experimental period. Adequate survival rates allowed accurate statistical analysis of diagnosed neoplasia. Increased susceptibility to tumor development was not clearly demonstrated. In mice the only statistically significant increase in the incidence of malignancy was lung carcinomas in high dose females ( P < 0.05). However, lung carcinoma incidence was significantly decreased in mid- and low-dose male mice when compared to spontaneous control rates ( P < 0.01). Although not confirmed statistically, there was an increased incidence of lung carcinomas and liver cell adenomas in high dose male mice, and increased lymphoid tumors in all female treated groups. In rats, the incidence of liver cell adenomas in high dose animals of both sexes was increased, although confirmed statistically in males only ( P < 0.01). In high dose females, significantly decreased incidences of mammary fibroadenomas, pituitary chromophobe adenomas, and thyroid parafollicular cell tumors ( P < 0.01) contributed to an overall decrease in both benign tumors and in the combined benign and malignant tumor rates.

Sexual precocity in a boy due to hypersecretion of LH and prolactin by a pituitary adenoma

The paper reports on precocious puberty and galactorrhoea in a 4 8/12 year old boy. Roentgenograms of the skull showed slight lateral bulging of sella floor and pneumoencephalography indicated a pituitary adenoma with a suprasellar extension. Pre-operative study of anterior pituitary function was normal except for increased values of LH (900 mIU/ml), testosterone (2000 ng/ml) and prolactin (215 ng/ml). After removal of a chromophobe pituitary adenoma by transfrontal surgery the galactorrhoea disappeared within 10 days. Post-operative endocrine evaluation showed immediate normalization of LH, testosterone and prolactin values.

Recurrence of chromophobe pituitary adenomas after operation and postoperative radiotherapy.

The rate of recurrence is reported in a prospective study of 56 patients (28 men, 28 women) with large chromophobe pituitary adenoma (with or without hyperprolactinemia). The surgical approach was transfrontal in 44 and transseptosphenoidal in 12 patients. Cryoapplication was combined with the transsphenoidal operation. All but one patient received postoperative pituitary irradiation. Altogether, 11 (20%) clinical relapses (10 men) occurred between 0.5 and 6 years after the transfrontal operation. Patients that relapsed had had larger tumors than those remaining in remission. Occurrence of the tumors appeared with a deterioration of the visual field defect in 9 patients. There were no differences in the degrees of hypopituitarism in patients who relapsed as compared to patients remaining in remission.

Operative management of chromophobe pituitary tumour recurrences

Twenty-three operations were performed for recurrences of previously treated chromophobe pituitary adenomas. Eleven operations were transcranial, and 12 were transsphenoidal. Twenty-two patients were operated on because of deteriorating eyesight; this improved in ten patients, deteriorated further in three, and did not significantly change in the remaining nine patients. There was one postoperative death. The patients generally had hypopituitarism already at the time of diagnosis, and it tended to increase during treatment. The results are certainly worse than after primary operations, but there is no alternative for handling a sizeable recurrence that has already affected the optic pathways.

Hypothyroidism Secondary to Biologically Inactive Thyroid-Stimulating Hormone Secretion by a Pituitary Chromophobe Adenoma

A 50-year-old man, suffering from a large pituitary adenoma and panhypopituitarism, was found to have severely elevated thyrotrophin (thyroid-stimulating hormone [TSH]) levels (greater than 20.2 microunits/mL). The thyroxine (T4) level was low (less than 3.0 micrograms/dL). Thyroid sodium iodide I 131 uptake was low (5% at 24 hours). A TSH test result was normal, with a 24-hour 131I uptake of 52% and a normal-looking thyroid gland on scintiscan. After surgical removal of the pituitary chromphobe adenoma, T4 levels returned to normal (6.8 micrograms/dL) and TSH levels improved substantially (9.0 microunits/mL). Findings from repeated 131I uptake tests were normal (22% at 24 hours). Other pituitary functions improved also. These results suggest that the patient had biologically inactive TSH produced by the tumor. Removal of the tumor probably enabled recovery of the active TSH with the return of normal thyroid uptake and T4 production. Whenever hypothyroidism and high levels of TSH coexist with pituitary dysfunction, a TSH test is needed to distinguish between primary hypothyroidism and hypothyroidism secondary to biologic inactive TSH.

Hypothyroidism secondary to biologically inactive thyroid-stimulating hormone secretion by a pituitary chromophobe adenoma: recovery after removal of the tumor

Hypothyroidism secondary to biologically inactive thyroid-stimulating hormone secretion by a pituitary chromophobe adenoma: recovery after removal of the tumor

Intraventricular hemorrhage from pituitary apoplexy

The case of a patient with a massive intraventricular hemorrhage arising from a pituitary chromophobe adenoma is described. This rare and disastrous complication was ascribed to the large suprasellar extension of the tumor and its close proximity to the floor of the third ventricle. Hemorrhage in the tumor extended along the path of least resistance and ruptured into the third ventricle. A partially treated hyperviscosity syndrome and chemotherapy for an unrelated malignancy (multiple myeloma) may have predisposed the patient to the necrosis and hemorrhage in the pituitary tumor.

Empty sella headache.

SYNOPSISHeadache was studied in a series of empty sella cases and the findings were compared with previous observations. Headache appeared to be very frequently associated with empty sella and its clinical features appeared distinguishable from migraine and tension headache, but very similar to pituitary chromophobe adenoma headache. Such an association seems to be in most cases pathogenetically significant and empty sella headache should therefore be included among the “secondary” headaches to be considered in the current diagnosis.

The use of monoclonal antibodies against human chorionic gonadotropin for immunoperoxidase staining of normal placenta, pituitary gland, and pituitary adenomas.

A monoclonal mouse antibody to human chorionic gonadotropin (hCG) was used in a modified unlabeled antibody enzyme-bridge staining method to demonstrate the localization of hCG in normal human placenta, pituitary gland, and six pituitary chromophobe adenomas. Mouse ascitic fluid containing monoclonal antibody could be diluted up to 1:500,000 for detection of hCG in the syncytiotrophoblast, whereas no staining was observed in the pituitary or adenomas even with high antibody concentrations (dilutions from 1:500 upward). Nonspecific background staining was negligible. These results demonstrate that monoclonal antibodies are suitable for immunohistochemical localization of antigens in tissues.

Host factors in “chromophobe” adenoma of the anterior pituitary: A retrospective study of 464 patients

To understand better the pathogenesis of pituitary chromophobe adenoma, we undertook a retrospective study of host factors, sexual function, associated diseases, and natural history. Data were obtained from the records of 464 patients in whom the disease was demonstrated by pathologic, radiographic, laboratory, and clinical means. The patients were drawn from the Presbyterian Hospital and the Neurological Institute of New York City; the study period comprised the years 1930–1964. The definitely positive findings are: peak age of onset 31–60 yr, a startlingly low (3%) prevalence of left-hand preference, a significantly earlier menopause (by 13 yr on average) than controls, a low frequency of marriage and a small number of offspring, the expected association with acromegaly (3.8%) and Cushing's syndrome (1.1%), an unexpectedly high frequency of diabetes mellitus (8.6%), perhaps in part responsible for the prevalence (7.5%) of coronary artery disease, a low rate of occurrence of fibromyomata uteri; the commonest chief complaint being visual symptoms in about two thirds of patients that sooner or later appear in nearly three quarters of the patients; and the much earlier onset (by years) of endocrinel than of neurologic dysfunction—particularly obvious in the form of early menopause. Suggestively positive findings are: a predilection of Jews and Old Americans for the disease, a somewhat low frequency of Rh negative individuals, a slightly early menarche, perhaps a high frequency of duodenal ulcer, and the “conventional” order of appearance of target gland failure—gonadal followed later by thyroidal and adrenocortical deficiency. This “classic” order of events should be viewed with caution because in this series as in earlier reports samples are small and data incomplete. The negative findings are: equal incidence in the two sexes (contrary to a few previous reports), absence of a distinctive physique, and normal frequency of ABO blood group distribution. Statistical analysis of the data demonstrates that large groups of patients are essential for accurate conclusions. Equally necessary are comparable control groups, with respect to era when studied, age, and racial mix. With regard to pathogenesis, the most promising leads to emerge from this study are (1) a careful genetic investigation is warranted to assess the frequent association with diabetes mellitus; and (2) the long period between earliest symptoms, which are usually endocrinel, and the neurologic symptoms that appear years later, suggests the need for a prospective laboratory study of patients suspected of harboring a chromophobe adenoma. Only in this way can one assess the importance of anterior pituitary target gland failure as a primary, not a secondary, event in the pathogenesis of chromophobe adenoma.

Morphometric analysis of secretory granules and prolactin levels in chromophobe pituitary adenoma.

Morphometric analysis of secretory granules was performed in 16 chromophobe adenomas: seven undifferentiated cell adenomas (group A), two of which were accompanied by mild hyperprolactinemia and nine prolactin cell sparsely granulated adenomas (group B), all associated with hyperprolactinemia. The results of morphometry were correlated with levels of prolactin in tumor and serum. The range of granule diameters was similar in both groups but granule size frequency was different resulting in a characteristic histogram for each group. Poor relationship existed between granule mean diameter and prolactin in tissue of the group B. In the same group there was virtually no linear relationship between serum prolactin on one side and granule mean diameter, granule density or tissue prolactin on the other. Also in the group B a paradoxical inverse relationship was found between granule density and tumor prolactin. Apparently, in prolactin cell adenoma a sizable part of hormone is located outside of mature secretory granules. An abundance of immature granules, misplaced exocytosis, crinophagia or defect in packaging of the hormone could all explain this paradox but the last possibility seems most plausible.

Studies of the components of an oral contraceptive agent in albino rats. I. Estrogenic component.

Albino rats were fed ethynylestradio to the diet for 2 yr at dosage levels (0.006--0.008 and 0.06--0.08 mg/kg) of about 10 and 100 times the recommended human dose as used in a combination oral contraceptive. The treated rats had typically estrogenic effects on a dose-related basis, including growth retardation, alopecia, liver enlargement and increase in cell alterations, and increased survival rate. Females had uterine changes and males had gonadal atrophy. At the higher dose level, females had gonadal atrophy and adrenal enlargement and animals of both sexes had cystic mastopathy. Rats of either sex given the higher dose had an increased incidence of liver neoplastic nodules and pituitary chromophobe adenomas, and males had an increased incidence of mammary fibroepithelial tumors. Treated rats of either sex had neither increased tumor incidence rates overall, nor increased numbers of tumors compared to control rats. In fact, females had a significant delay in onset of tumor development and less potential for their ultimate development than control females.

Nasal Visual Field Loss by Intracranial Lesions of the Optic Nerve Pathways

Five patients developed nasal visual field defects as a result of involvement of the intracranial portion of the optic nerves. The cause in each patient, respectively, was as follows: (1) dolichoectatic carotid arteries, (2) optochiasmatic arachnoiditis, (3) meningioma of the olfactory groove, (4) pituitary apoplexy, and (5) pituitary chromophobe adenoma. The common factor in these cases was probably impaired circulation in the prechiasmal arterial anastomotic network. The nasal visual field loss present in these cases was characterized by a pattern similar to that seen in glaucoma but with impairment of visual acuity. The superior nasal visual field was usually normal and the lower temporal visual field often defective.

Sudden, unexpected deaths due to primary intracranial neoplasms.

In 10,995 consecutive medicolegal autopsies, there were 19 deaths due to an unsuspected primary intracranial neoplasm. Nine (47.4%) of the tumors were in the astrocytoma-glioblastoma category. The remainder included four cases of oligodendroglioma and one case each of medulloblastoma, microglioma, meningioma, teratoma, colloid cyst and pituitary chromophobe adenoma. In six cases, death occurred following abrupt loss of consciousness, or else the patient was found dead. In five of these six cases, there were no known preceding symptoms. The remaining 13 patients exhibited the characteristic symptoms produced by intracranial neoplasms, including symptoms of increased intracranial pressure, epilepsy, and psychiatric manifestations. Only one patient presented with a focal neurologic deficit which resolved in 24 hours. A comparison of the duration and type of symptomatology exhibited by these patients with a hospital patient population in which death was caused by a previously diagnosed primary intracranial neoplasm and an autopsy was performed underscored 1) the shorter duration of acute symptomatology, 2) the nonlocalizing nature of the symptoms manifested, 3) the lack of progression or change in symptoms in those patients in whom epilepsy was the primary manifestation of their underlying disease, and 4) the lower incidence of focal neurologic deficits as the presenting symptoms in our series.

Sphenoidal pituitary adenoma

A 62 year old female died of a chromophobe pituitary adenoma of the sphenoid bone. A normal pituitary gland was present within the sella turcica. She also had a chief cell parathyroid adenoma, a papillary thyroid carcinoma, and an ovarian thecoma (multiple endocrine neoplasia syndrome).

Aseptic Necrosis of Bone

To the Editor.— In a recent article in theArchives(138:750-754, 1978), Dr Abeles and coauthors associated high corticosteroid doses with the development of aseptic necrosis of bone; however, small doses seem to have a similar effect. A 44-year-old man is under my care who had received a total left hip replacement for aseptic necrosis a few months ago. In 1974 the patient had a chromophobe pituitary adenoma removed and has taken 7.5 mg of prednisone daily since this time. He has never had any large dosage of cortisone. He is hypertensive and suffered a mild stroke about one year ago. It is possible that the reduced activity owing to the right-sided paresis, the stress of placing the body weight to the left side, and a gonadal deficiency that is due to hypopituitarism have also contributed to the development of the aseptic necrosis of his left hip joint.