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PubMed1994

Cushing's disease in children.

As with adults, the diagnosis of Cushing's disease in childhood can be difficult. The clinical presentation in children is distinctive in terms of the effects on growth and pubertal development. The biochemical diagnosis can usually be made with standard dexamethasone suppression testing, similar to such testing in adults. The clinical course of Cushing's disease in children tends to be more aggressive than in adults, as evidenced by higher rates of Nelson's syndrome after bilateral adrenalectomy and higher rates of recurrence after removal of corticotrope adenomas. TSS is well tolerated in children and has fewer side effects than other modalities. Currently, pituitary irradiation is best reserved as adjunctive therapy. Newer stereotactic computer assisted linear accelerator techniques (e.g., proton knife) may provide increased effectiveness with fewer side effects and be particularly useful in childhood Cushing's disease. Appropriate treatment of children with Cushing's disease can be compatible with satisfactory psychosocial adjustment and fertility in adulthood.

Adolescent↗
PubMed1994

Magnetic resonance imaging of radiation necrosis after radiotherapy for acromegaly: report of a case.

A total 5,600 cGy in 28 fractions in 44 days was delivered to a 53-year-old woman with acromegaly after transsphenoid removal of a pituitary adenoma. Sixteen months later, she suffered a progressive loss of vision. Radiation optic neuropathy was diagnosed. A T1-weighted imaging showed gadolinium-enhanced lesions in the optic chiasm, pituitary stalk and hypothalamus. Magnetic resonance imaging is uniquely suited to detect radiation injury to the sellar region. The complications of radiation therapy for benign tumor can be severe even by current standard procedures.

Acromegaly↗
PubMed1996

Bilateral simultaneous cavernous sinus sampling using corticotropin-releasing hormone in the evaluation of Cushing disease.

PURPOSE: To determine whether bilateral, simultaneous, cavernous sinus sampling after corticotropin-releasing hormone (CRH) stimulation offers as accurate detection and lateralization of Cushing disease as inferior petrosal sinus sampling does. METHODS: Seventeen consecutive patients with hypercortisolism and with high-dose dexamethasone suppression test results suggesting Cushing disease underwent bilateral cavenous sinus sampling with CRH stimulation. The diagnosis of Cushing disease was established in all patients by histologic examination or, if no tumor was found at surgery, by subtotal resection of the gland or radiation therapy resulting in eventual hypocortisolism or normal adrenal function and clinical remission. RESULTS: The sensitivity of cavenous sinus sampling with and without CRH in detecting Cushing disease was 94% and 71%, respectively. The abnormal side of the pituitary was correctly identified in all patients who had criteria for lateralization, yielding a positive predictive value of 100%. CONCLUSIONS: This small series suggests that cavernous sinus sampling with CRH is as accurate as inferior petrosal sinus sampling in detecting Cushing disease and perhaps more accurate in lateralizing the abnormality within the pituitary gland.

Adenoma↗
PubMed1998

Efficacy of cobalt 60 radiotherapy in dogs with pituitary-dependent hyperadrenocorticism.

OBJECTIVE: To determine efficacy of cobalt 60 radiotherapy in dogs with pituitary-dependent hyperadrenocorticism (PDH) that have detectable tumors but no neurologic abnormalities. DESIGN: Case series. ANIMALS: 6 dogs with PDH that had a detectable pituitary mass on magnetic resonance images. PROCEDURE: Radiation was delivered in 11 fractions during a 3.5-week period for a total dose of 44 Gy. Clinical signs were evaluated, a urinalysis and ACTH stimulation test were performed, and urine cortisol-to-creatinine ratio and plasma endogenous ACTH concentration were measured before, immediately after, and 1, 3, 6, 9, and 12 months after radiotherapy. Magnetic resonance imaging was repeated 1 year after radiotherapy. RESULTS: Clinical signs of hyperadrenocorticism resolved in 3 dogs but recurred in 2 of the 3. Clinical condition of 2 dogs improved but did not return to normal. One dog did not improve. Results of ACTH stimulation tests and urine cortisol-to-creatinine ratios correlated with clinical signs. Plasma endogenous ACTH concentration transiently decreased in all 6 dogs. One year after radiotherapy, size of tumors was decreased by 25% in 2 dogs; in the other 4 dogs, tumors could no longer be detected. None of the dogs developed neurologic abnormalities. Adverse effects of radiotherapy were mild. CLINICAL IMPLICATIONS: Radiotherapy did not result in adequate control of clinical signs of hyperadrenocorticism in 5 of 6 dogs, but size of pituitary tumors was dramatically reduced. Thus, it may be reasonable to recommend radiotherapy in dogs with PDH that have pituitary tumors for which greatest vertical height is 8 mm or more.

Adrenocortical Hyperfunction↗
PubMed2005

Hypothalamic-pituitary dysfunction after irradiation of nonpituitary brain tumors in adults.

CONTEXT: Hypothalamic-pituitary (HP) dysfunction is common in children treated with cranial radiotherapy (RT) for brain tumors, but there is little known about the risk of HP dysfunction in adults treated with RT for primary nonpituitary brain tumors. OBJECTIVE: The objective was to study the frequency of HP dysfunction in adults after RT for nonpituitary brain tumors. METHOD: We studied 56 adult patients who received external beam RT for primary nonpituitary brain tumors at time intervals of 12-150 months after RT. The control group consisted of 20 RT-naive patients with primary brain tumors. GH and adrenal axes were assessed using the insulin tolerance test or the glucagon stimulation test. Gonadotroph, thyrotroph, and lactotroph function were assessed using baseline blood measurements. The biological effective dose (BED) to the HP axis was calculated in the RT patients. RESULTS: Hypopituitarism was present in 41% of patients. The frequency of GH, ACTH, gonadotropin, and TSH deficiencies, and hyperprolactinemia was 32, 21, 27, 9, and 32%, respectively. Any degree of hypopituitarism and GH deficiency was significantly associated with longer time interval from RT and greater BED. However, gonadotropin deficiency and hyperprolactinemia were only related to BED, whereas ACTH deficiency was only significantly associated with the time interval from RT. One RT-naive patient was GH deficient. CONCLUSION: Adult patients treated with cranial irradiation for primary nonpituitary brain tumors are at high risk of hypopituitarism, which is time and dose dependent. Long-term surveillance and periodic evaluation are needed. We recommend that adult late effect clinics, similar to those for children, should be established.

Adrenocorticotropic Hormone↗
PubMedDate not supplied

[Effect of proton irradiation of the hypophysis on its gonadotropic and thyrotropic functions in patients with prolactinoma].

In order to study the effect of proton beam irradiation on prolactinoma cells and hypophyseal intact cells tests with i.v. administration of TRH (200 micrograms) and LH-RH (100 micrograms) were performed in 16 women with prolactin-secreting adenomas before and in 2 mos.-2 years after irradiation of the pituitary body with a high energy narrow proton beam (1000 MeV) at a dose of 40-120 Gy. A curative therapeutic effect of proton therapy which was low with respect to reproductive function recovery, was combined with lowered functional reserves of hypophyseal thyrotrophs and gonadotrophs. The informative value of the tests with the releasing hormones was shown for the determination of damage of hypophyseal intact cells. The results suggest refractivity of adenomatous lactotrophs to radiation exposure and the hypothalamic level of disorder of ovarian function regulation in this pathology.

Adult↗
PubMed1987

[Indications and results of pituitary radiotherapy after microsurgery in acromegaly. 15 cases].

The present treatment of acromegaly consists of selective adenomectomy followed, when unsuccessful, by pituitary gland irradiation. Fifteen acromegalic patients were evaluated after adenomectomy, then radiotherapy. Growth hormone assays were performed after carbohydrate load and administration of thyroid stimulating hormone. Somatomedins were measured by radiocompetition using the vector protein. Cure was obtained with adenomectomy alone in 3 of the 15 patients (mean follow-up 39 months). The remaining 12 patients were all cured by subsequent irradiation at the cost of pituitary insufficiency in one-third of them. Post-surgical cure of acromegaly can only be asserted from range of strict criteria. The best indicators of persisting activity are high levels of growth hormone and/or somatomedins. A solitary somatotropic dysregulation does not necessarily herald a relapse.

Acromegaly↗
PubMed1981

Subhypothalamic grafts of human pituitary adenomas in total-body irradiated rats.

Human pituitary adenomas proliferate neither in cell culture nor in athymic "nude" mice. We propose that one or several of the humoral factors necessary for the growth of pituitary adenomas is missing in these experimental environments. The purpose of our experiments was to examine the possible influence of the hypothalamus in supporting cellular proliferation, and thus adenoma growth. Fragments from four human pituitary adenomas (three pituitary prolactinomas; one ACTH-secreting adenoma) were transplanted into the pituitary fossa of total-body irradiated, hypophysectomized rats. The rats were killed after two weeks and perfused with a mixture of formalin and India ink. Histologic examination of serial sagittal sections through the pituitary fossa and the adjacent brain showed: vascularization of the grafts from the pituitary stalk and from the scar tissue in the sphenoid bone; survival of some adenomas; and numerous mitoses in an ACTH-secreting specimen obtained from a patient who had Cushing's disease. We conclude from these experiments that as yet unidentified hypothalamus factors are essential for the growth of certain types of pituitary adenomas.

Adenoma↗
PubMed1975

Mammary carcinogenesis-enhancing effect of adrenalectomy in irradiated rats with pituitary tumor MtT-F4.

Mammary carcinomas were found at autopsy 98--100 days after irradiation in 12 of 14 (86%) multiparous Fischer female rats which had been adrenalectomized and given grafts of secretory pituitary tumor strain MtT-F4 soon after exposure to gamma-rays or fission neutrons. A single carcinoma was found in 1 of 10 unirradiated, MtT-bearing, adrenalectomized animals. When adrenalectomy was not done, no tumors were found in 8 unirradiated or in 13 irradiated MtT-bearing rats rats. In view of the well-established finding that Cortisol is essential for milk production, we suggested as a working hypothesis that, in the presence of high titers of mammotropic hormone and adrenal corticoids, differentiation of a given cell for milk secretion reduced that cell's proliferative potential. When such differentiation was precluded by adrenocorticoid deficiency, more irradiation-altered mammary epithelial cells retained their high proliferative potential and contributed to carcinoma formation.

Adrenal Cortex Hormones↗
PubMed1990

Early effects of cranial irradiation on hypothalamic pituitary function.

Hypothalamic pituitary functions were studied in 25 patients before and 6 months after cranial irradiation with or without radiosensitizing chemotherapy for nasopharyngeal carcinoma. The estimated average total dose was 5,000 cGy to the hypothalamus and pituitary gland. The radiosensitizing chemotherapy used was endoxan, 4900 +/- 873 mg and/or methotrexate 113 +/- 30 mg. All patients had normal pituitary function before radiotherapy. Six months after radiotherapy, there was a significant increase in baseline serum thyrotropin (TSH) and follicle-stimulating hormone (FSH) levels. The TSH response to thyrotropin-releasing hormone (TRH) was significantly increased, suggesting primary hypothyroidism due to neck irradiation. The peak serum TSH response to TRH became delayed in 21 patients, suggesting a defect in TRH release. In male patients who did not receive radiosensitizing chemotherapy, the FSH response to luteotropic hormone-releasing hormone (LHRH) increased while the luteinizing hormone (LH) response decreased. But in male patients who also received radiosensitizing chemotherapy, both the FSH and LH responses to LHRH increased. The adrenocorticotropic hormone (ACTH) response to ovine corticotropin-releasing hormone (CRH) did not change, while the integrated cortisol response increased. The growth hormone (GH) response to growth hormone-releasing hormone (GRH) did not change. The GH response to insulin tolerance test (ITT) increased and may be explained by the more severe hypoglycemia induced by the same dosage of insulin after radiotherapy or the recovery from the previous wasting caused by radiotherapy. There was no significant increase in serum prolactin. In conclusion, we demonstrated impairment of the hypothalamus-pituitary-endocrine gland axes as early as 6 months after cranial irradiation with or without chemotherapy.

Adolescent↗
PubMed1989

Late regrowth of pituitary adenomas after irradiation and/or surgery. Hazard function analysis.

A retrospective analysis was performed on all patients with pituitary adenomas treated at the Radiation Oncology Center, Mallinckrodt Institute of Radiology, St. Louis, Missouri. Of 210 patients treated from April 1954 through December 1982, 70 were treated with radiotherapy alone (RT), 121 received immediate postoperative RT (2 to 6 weeks), and 19 received RT following surgical failure. The mean follow-up time from the date of diagnosis for those patients alive at the time of last follow-up was 13.0 years (range, 3.0 to 30.0 years). Actuarial progression-free survival was analyzed up to 30 years. The 10-, 20-, and 30-year progression-free survival was 80.5%, 73.5%, and 73.5% for those patients treated with irradiation alone and 92.8%, 71.2%, and 44.0% for those treated with immediate postoperative irradiation. The median time to first failure from initial diagnosis by original treatment was 3.8 years for surgery alone, 4.2 years for RT only, and 10.2 years for surgery plus postoperative RT. Analysis for risk of recurrence per 5-year interval was performed using a hazard function analysis. The risk of recurrence after radiotherapy alone was greatest during the first 5-year interval after treatment and decreased to zero by 20 years. However, the risk of recurrence after primary surgery and postoperative radiotherapy revealed an increasing risk for recurrence up to 30 years after treatment. The concept of "cure" for pituitary adenomas requires extended follow-up.

Actuarial Analysis↗
PubMed2001

Multiple intracranial recurrent tumors with hyperprolactinemia combined with a parasellar malignant fibrous histiocytoma long after transfrontal surgery and irradiation to a pituitary adenoma.

We herein describe a 40-year-old woman with hyperprolactinemia, an empty sella and two extrasellar intracranial recurrent tumors which were revealed 23 years after the first transfrontal craniotomy and 18 years after the second transfrontal surgery and irradiation to a provable prolactin-producing pituitary macroadenoma. One recurrent tumor was in the right orbital apex causing right oculomotor nerve palsy, and the other tumor was in the right apex partispetrosae and foramen jugulare. Although her serum prolactin level decreased after the administration of bromocriptine mesilate, and the size of the two tumors remained unchanged, a malignant fibrous histiocytoma, which might have been induced by the irradiation 18 years before, grew rapidly in the right suprasellar-prepontine cistern to the right pedunculus cerebralis, leading to a poor prognosis. This case confirmed the importance of the life-lasting follow-up of pituitary adenomas treated with surgery and/or irradiation therapy. Not only ectopic recurrence of the primary tumor but also post-irradiation tumors may become apparent long after the removal of the primary tumor.

Adult↗