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PubMed1985

Effect of growth hormone-releasing factor on growth hormone release in children with radiation-induced growth hormone deficiency.

Five male children who received cranial irradiation for extrahypothalamic intracranial neoplasms or leukemia and subsequently developed severe growth hormone (GH) deficiency were challenged with synthetic growth hormone-releasing factor (GRF-44), in an attempt to distinguish hypothalamic from pituitary dysfunction as a cause of their GH deficiency, and to assess the readily releasable GH reserve in the pituitary. In response to a pulse of GRF-44 (5 micrograms/kg intravenously), mean peak GH levels rose to values higher than those evoked by the pharmacologic agents L-dopa or arginine (6.4 +/- 1.3 ng/mL v 1.5 +/- 0.4 ng/mL, P less than .05). The peak GH value occurred at a mean of 26.0 minutes after administration of GRF-44. These responses were similar to those obtained in children with severe GH deficiency due to other etiologies (peak GH 6.3 +/- 1.7 ng/mL, mean 28.0 minutes). In addition, there was a trend toward an inverse relationship between peak GH response to GRF-44 and the postirradiation interval. Prolactin and somatomedin-C levels did not change significantly after the administration of a single dose of GRF-44. The results of this study support the hypothesis that cranial irradiation in children can lead to hypothalamic GRF deficiency secondary to radiation injury of hypothalamic GRF-secreting neurons. This study also lends support to the potential therapeutic usefulness of GRF-44 or an analog for GH deficiency secondary to cranial irradiation.

Adolescent↗
PubMed1976

Pituitary hormone responses to hypothalamic releasing hormones in acromegaly.

The pituitary reserve of GH, prolactin, TSH, LH, and FSH has been studied in a group of 13 acromegalic patients with the aim of evaluating the pituitary function and the activity of the disease. Plasma GH, TSH and polactin were determined after thyrotrophin releasing hormone (TRH) administration, plasma gonadotrophins and GH after luteinizing hormone releasing hormone (LH-RH) administration. The plasma TSH response to TRH was generally blunted in the patients treated with pituitary irradiation; however, none of the patients with diminished TSH reserve had signs of hypothyroidism. Six acromegalics showed prolactin basal levels higher than controls; none had galactorrhoea; 4 of them complained of impairment of the gonadal function. The prolactin response to TRH was variable and not related to prolactin basal levels. A subnormal LH reserve after LH-RH stimulation was observed in 5 out of 10 patients; 4 of them had also clinical signs of hypogonadism. A normal FSH response to LH-RH was present in all patients. A non-specific GH response to TRH and/or LH--RH was obtained in about half of the acromegalics studied. The GH responsiveness to TRH and/or LH-RH was not related to the activity of the disease or to a specific derangement of the hypothalamo-pituitary function. A concordant response was observed only between GH and prolactin response to TRH; the highest prolactin responses to TRH were obtained in the GH responsive patients. Each patient showed a constant GH pattern of response on repeated testing. Even after pituitary irradiation the pattern of GH response was unchanged in spite of lowered GH plasma levels.

Acromegaly↗
PubMed2003

[Diagnosis and treatment of sellar germinoma].

That eleven patients with sellar germinomas were confirmed by pathological examinations were retrospectively reviewed. In the 11 patients, 2 were males and 9 were females. Mean age was 16.8 years old and mean history was 2.6 years. Among them, 11 patients had diabetes insipidus, 6 patients had visual disturbances, 5 patients had retarded growth, and 5 patients had hypopituitary function. The diameter of tumor was 1-3 cm in 8 cases and greater than 3 cm in 3 cases. MRI showed hypointensity or homogeneous on T1-weighted images in 8 cases. The tumors were fibrous, purple grey or reddish in color with rich blood supply. Germinomas were confirmed by postoperative pathological examinations. All patients received postoperative irradiation. Postoperative follow-up was from 3 months to 6 years. Diabetes insipidus was improved in 9 cases. Visual function were improved in 4 cases, but hypopituitarism and retarded growth were unchanged. In conclusion, when MRI shows sellar parenchyma tumor with unclear boundary in young patients with diabetes insipidus and hypopituitarism, sellar germinoma should be highly suspected. Otherwise, radiation therapy may profitably aid to confirm the diagnosis since irradiation is the main treatment of sellar germinomas.

Adolescent↗
PubMedDate not supplied

[Several indicators of lipids, blood hormones and T-cell unit of the immune system in mice with increased body mass at distant periods after local irradiation of the thymus, hypothalamus-hypophysis and gonads].

In hybrid mice it was shown that the local irradiation of zones of thymus, hypothalamus-hypophysis (0.5, 1 and 10 Gy in both cases) and gonads (10 Gy) resulted in significant increase in weight at long terms after irradiation. In animals with increased weight the amount of lipids raised, balance of hormones and state of thymus-dependent unit of immune system changed, and exterior symptoms of early aging were observed. After irradiation of spleen and thigh muscles (10 Gy in both cases) all indices at the same period corresponded to age control.

Aging↗
PubMedDate not supplied

Evidence that irradiation of far-infrared rays inhibits mammary tumour growth in SHN mice.

To evaluate the effect of irradiation of far infrared rays (FIR), the growth of spontaneous mammary tumours of SHN mice was compared among 3 groups: the control was kept until the end of experiment on the normal rack in the absence of FIR and Experimental group I was constantly exposed to FIR. Experimental group Il was raised as the control followed by movement to the FIR rack after mammary tumour appearance. While there was little difference between the control and Experimental group I in mammary tumour growth for 16 days, Experimental group II was significantly lower than the control in this parameter. Furthermore, the percentage of rapidly growing tumours showing greater than 200% of growth rate was apparently lower in Experimental group II. Associated with this, epidermal growth factor receptor expression in mammary tumours, anterior pituitary weight and serum leptin level were significantly decreased in Experimental group II. The findings suggest that whole-body FIR irradiation at ambient temperature could be a possible way of a hyperthermic therapy for tumours.

Animals↗
PubMed1980

[Radiation therapy of endocrine orbitopathy. 1st communication: clinical results (author's transl)].

Ten patients with serious endocrine orbitopathy underwent radiation therapy of the retrobulbar orbital tissue. Between the 2nd and the 13th week preceding radiotherapy, exacerbation of the clinical symptoms had appeared in all the patients, and distinct symptoms of infiltrative tissular processes were seen beside bulbar protrusion. Of the cases, 5 suffered from marked extra-ocular myopathy, 6 from corneal lesions, and one patient had lost his visual faculty. Index numbers for the degree of the orbitopathy (4-11, average 6.7) were established in all cases, and a total focal dose amounting to maximally 1000 cGy for each retrobulbar target volume was administered in one series. The pituitary gland was not included in the radiation field. Indices for the degree of ophthalmopathy were reduced by at least 3 points (average 3.7). Swelling of soft tissue and bulbar protrusion were decreased primarily. No improvement of myopathy was obtained but aggravation also did not occur. Recurrences appeared in 4 patients, at the earliest 4 months, at the latest 24 months after the end of the therapy. The present findings have shown orbital irradiation as an effective method for the treatment of endocrine orbitopathy.

Adult↗
PubMed1975

Experimental endocrinopathies.

Methods are described for maintaining hypophysectomized rats (model for panhypopituitarism). Prolactin-secreting pituitary tumors can be induced in rats or mice by administration of estrogens; thyroid stimulating hormone-secreting tumors will occur in some mice after thyroid ablation by radioactive iodine. Estrogens in hamsters usually produce intermediate lobe tumors of the pituitary associated with hypothalamic degeneration. Sex hormone-secreting adrenal tumors can follow surgical gonadectomy in mice. Spontaneous corticoid-secreting adrenal tumors may occur spontaneously in Osborne-Mendel rats. Secretory gonadal tumors have been induced by transplantation of a gonad into the spleen of a gonadectomized host. Both secretory and non-secretory ovarian tumors can be produced by irradiation or chemical carcinogens in mice. In some mice, secretory testicular tumors can be produced by estrogen administration. Thyroid tumors can be induced in rodents by various kinds of goitrogens and irradiation. Parathyroid hyperplasia may occur with spontaneous renal disease in rats. A syndrome simulating diabetes mellitus can occur in rare strains of mice or can be induced by chemical destruction of the islets of Langerhans with alloxan.

Adenoma, Islet Cell↗
PubMed1988

Endocrine function following high dose proton therapy for tumors of the upper clivus.

The endocrine status of patients receiving proton radiation for tumors of the upper clivus was reviewed to evaluate the effect of high dose treatment on the pituitary gland. The fourteen patients had chordomas or low grade chondrosarcomas and were all treated by the same techniques. The median tumor dose was 69.7 Cobalt Gray Equivalent (CGE) with a range from 66.6 to 74.4 CGE. (CGE is used because modulated protons have an RBE of 1.1 compared to 60Co). The daily fraction size was 1.8-2.1 CGE. The median follow-up time is 48 months, ranging from 30 to 68 months. All treatments were planned using a computerized multi-dimensional system with the position of the pituitary outlined on the planning CT scan. Review of the dose distribution indicated that the dose to the pituitary ranged from 60.5 to 72.3 CGE, with a median of 67.6 CGE. One female patient had decreased thyroid and gonadotropin function at the time of diagnosis and has been on hormone replacement since that time. The other three females were all pre-menopausal at the time of radiotherapy. At this time four patients (3 males and 1 female) have developed endocrine abnormalities 14 to 45 months after irradiation. All four had evidence of hypothyroidism and two have also developed corticotropin deficiency. The three males had decreased testosterone levels; the female patient developed amenorrhea and hyperprolactinemia. All four are asymptomatic with ongoing hormone replacement.

Adolescent↗
PubMed1993

Bilateral adrenalectomy: low mortality and morbidity in Cushing's disease.

OBJECTIVE: We assessed the current role of bilateral adrenalectomy in the overall management strategy of hypercortisolism. DESIGN: Retrospective review of case notes. PATIENTS: Twenty-six patients (20F/6M); mean age 46 years (range 15-70 years), median duration of follow-up 5.25 years (0.6-19.1 years) who had undergone bilateral adrenalectomy at the Royal Victoria Hospital since 1972. Eighteen had had prior transsphenoidal surgery which did not control the hypercortisolism. MEASUREMENTS: Morbidity, mortality, incidence of Nelson's syndrome. RESULTS: Surgery was performed through bilateral postero-lateral incisions (20 patients) or a long epigastric incision (six patients). The mean combined weight of the adrenals at surgery was 11.2 g. Twenty patients received subcutaneous heparin and 18 antibiotic prophylaxis peri and post-operatively. There was no operative mortality. Minor complications included one post-operative wound infection and a small pneumothorax requiring drainage. Major complications occurred in two other patients, both with pre-existing invasive pituitary tumours and considered at high risk because of age and general debility. One patient had a massive pulmonary embolus and the other a subphrenic abscess post-operatively. This latter patient, the only mortality, died from an unrelated cause three years post-operatively. Six patients have subsequently undergone pituitary surgery and three have received external pituitary irradiation therapy for expanding tumours. CONCLUSIONS: Bilateral adrenalectomy, in experienced hands, is a relatively safe and useful management option in patients with hypercortisolism. Growth of a pituitary adenoma post-operatively is now the most worrying complication.

Adolescent↗
PubMedDate not supplied

[Pituitary-gonadal function following therapy of testicular relapse in boys with acute lymphoblastic leukemia].

Testicular function was evaluated in 8 boys with acute lymphoblastic leukemia (ALL) and testicular relapse following another course of intensive chemotherapy with unilateral or bilateral orchidectomy and/or testicular irradiation. LH- and FSH-secretion was studied in all using a standardized LHRH-test. In addition, a HCG-test was performed in 6 boys. In prepuberty, all boys examined showed normal LH- and FSH-values. Beginning at 9 to 10 years, elevated basal and/or stimulated LH- and FSH-values were occasionally noted in contrast to the consistently elevated values after the age of 12. Using the HCG-test, we found a testosterone response only in patients receiving gonadal irradiation of 1 100 and 1 500 rads (2 patients). No response was elicited in those with radiation doses of 2 400 and 3 000 rads. We conclude that high dose gonadal irradiation and chemotherapy cause temporary and possibly permanent impairment of spermatogenesis and Leydig cell function in boys with ALL and testicular relapse.

Castration↗
PubMed1978

Hypopituitarism following pituitary irradiation for acromegaly.

Endocrine evaluation is reported in 8 acromegalic patients who received 5,500 rad to the pituitary from a linear accelerator. There was a mean decrease in hGH levels of 72%. Plasma testosterone levels were low in 1 of the 6 male patients prior to pituitary irradiation and were below normal in all male patients on the final evaluation (3.1 +/- 0.2 SD years postirradiation). Deficiency of TSH secretion developed in 2 patients following irradiation. This rather high incidence of postirradiation partial hypopituitarism was not anticipated, and is thought to be related to radiation necrosis of the normal pituitary tissue which surrounds the adenoma.

Acromegaly↗
PubMed1977

Irradiation of the head. Immediate effect on growth hormone secretion in children.

Plasma growth hormone (GH) was determined in samples obtained hourly from 1000 h to 0700 h before, and after a 3 week course of "prophylactic" cranial irradiation, in ten leukemic children who had no clinical or laboratory evidence of central nervous system involvement. The mean per hour value of GH prior to irradiation (4.1 +/- 2.4 ng/ml) was similar to that of 7 endocrinologically normal children (4.09 +/- 2.4 ng/ml), a finding strongly suggesting normal pituitary function prior to irradiation. Following irradiation GH levels at each hour were, in general, lower than before. The difference is statistically significant at 0100 h. The peak GH responses were lower following than preceeding irradiation (p less than 0.02). The findings suggest an immediate suppressive effect of irradiadiation on the apparently normal hypothalamic pituitary axis in children.

Adolescent↗
PubMed1986

Gd-DTPA in clinical MR of the brain: 2. Extraaxial lesions and normal structures.

Fifteen patients with suspected extraaxial tumors were evaluated with MR before and after intravenous injection of Gadolinium-DTPA (Gd-DTPA). Meningiomas (7), neurinomas (4), chordomas (2), a previously irradiated dural metastasis, and a giant aneurysm were studied. All the lesions except the dural metastasis enhanced. In two patients with asymptomatic meningiomas, the use of Gd-DTPA with MR allowed definitive diagnosis of the lesions when the routine MR did not. Gd-DTPA also provided improved definition of intracranial tumor margins, produced differential enhancement of dura and nasopharyngeal mucosa from tumor, and caused enhancement of the choroid plexus, some venous structures, the pituitary gland, and its stalk. The enhancement of the pituitary suggests a role for Gd-DTPA in the diagnosis of microadenomas. Routine T2-weighted images without Gd-DTPA were useful in differentiating neurinomas from meningiomas. Judicious use of Gd-DTPA should improve the ability of MR to detect extraaxial lesions, delineate their extent, and characterize their perfusion.

Aged↗
PubMed2003

Androgens and male fertility.

Androgens play a crucial role in the development of male reproductive organs such as the epididymis, vas deferens, seminal vesicle, prostate and the penis. Furthermore, androgens are needed for puberty, male fertility and male sexual function. High levels of intratesticular testosterone, secreted by the leydig cells, are necessary for spermatogenesis. Intratesticular testosterone is mainly bound to androgen binding protein and secreted into the seminiferous tubules. Inside the sertoli cells, testosterone is selectively bound to the androgen receptor and activation of the receptor will result in initiation and maintenance of the spermatogenic process and inhibition of germ cell apoptosis. The androgen receptor is found in all male reproductive organs and can be stimulated by either testosterone or its more potential metabolite dihydrotestosterone. Severe defects of the androgen receptor may result in abnormal male sexual development. More subtle modulations can be a potential cause of male infertility. Treatment of an infertile man with testosterone does improve spermatogenesis, since exogenous administrated testosterone and its metabolite estrogen will suppress both GnRH production by the hypothalamus and Luteinising hormone production by the pituitary gland and subsequently suppress testicular testosterone production. Also, high levels of testosterone are needed inside the testis and this can never be accomplished by oral or parenteral administration of androgens. Suppression of testosterone production by the leydig cells will result in a deficient spermatogenesis, as can be seen in men taking anabolic-androgenic steroids. Suppression of spermatogenesis by testosterone administration is also the basis for the development of a male contraceptive. During cytotoxic treatment or irradiation suppression of intratesticular testosterone production cells may prevent irreversible damage to the spermotogonial stem cells.

Androgens↗
PubMed1984

Incidence of anterior pituitary deficiency after radiotherapy at an early age: study in retinoblastoma.

Thirty-one patients treated for retinoblastoma in the first few years (3 months to 3 years and 6 months) of life were studied 2 to 15 years later. Radiotherapy delivered 1 300 to 6 500 rads to the hypothalamo-pituitary area. Growth deficiency was documented in 30% of all cases. Other pituitary deficiencies were the exception. The critical dose for GH insufficiency is between 2 000 and 3 000 rads, as in older children or adults. Our study does not support the hypothesis that the hypothalamo-pituitary area is more sensitive to radiation at an early age. Furthermore, conservative therapy of retinoblastoma leads to double lateral irradiation and will increase the number of GH deficient children after retinoblastoma.

Adolescent↗