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PubMed2004

Successful treatment of childhood-onset Cushing's disease is associated with persistent reduction in growth hormone secretion.

OBJECTIVE: Although Cushing's disease (CD) rarely occurs in childhood, affected children commonly fail to achieve predicted adult height. Hypercortisolaemia results in reduced GH secretion and GH-deficiency may persist or demonstrate delayed recovery after successful treatment of CD in adults. Whether recovery of spontaneous GH secretion occurs following treatment of childhood CD has yet to be established. DESIGN AND PATIENTS: We performed a retrospective analysis of the GH status of 13 children (10 males; 12.8 +/- 1.0 years, mean +/- SE) who had undergone successful treatment of CD that occurred prior to the completion of linear growth. Each underwent transsphenoidal hypophysectomy, resulting in satisfactory control of glucocorticoid levels in 7/13 (54%). The remaining six patients (46%) received fractionated external beam irradiation (4500 Gy). At the time of GH assessment, circadian dynamics of cortisol were normal in eight patients and five were receiving titrated glucocorticoid replacement. MEASUREMENTS: GH status was assessed using the peak response to a provocative stimulus. Eleven out of 13 underwent testing with insulin-induced hypoglycaemia (nadir plasma glucose </= 2.2 mmol/l) and glucagon provocation was used in 2/13. Severe GH-deficiency was defined as a peak GH response < 9 mU/l, and a normal response as > 30 mU/l. Intermediate values were taken to represent subnormal GH status. Assessment of GH status was performed 39 +/- 10 months (median +/- SE) following successful treatment (range 9-108 months). RESULTS: Using these criteria 4/13 (31%) patients had severe GH-deficiency. Only 2/13 (15%) had a normal response. 7/13 (54%) achieved peak GH levels in the subnormal range. Those with multiple pituitary hormone deficiencies were most likely to have lower peak GH levels, but there was no clear effect of pituitary irradiation or relationship between duration post cure and peak GH response. CONCLUSION: GH-deficiency is common and may persist for many years following successful treatment of CD prior to completion of linear growth. External radiotherapy does not necessarily result in severe GH-deficiency in the short term. Assessment of GH status and consideration of GH treatment should be considered following treatment of CD in childhood and adolescence in order to maximize the opportunities to achieve a satisfactory final adult height. In those with subnormal GH responses, continued assessment is necessary to determine whether the GH axis subsequently recovers or if these patients develop features of the adult GH-deficiency syndrome.

Adolescent↗

PubMed1983

Convergent differentiation in cultured rat cells from nonkeratinized epithelia: keratinocyte character and intrinsic differences.

Epithelial cells derived from a variety of glandular and other nonkeratinized rat tissues (pituitary, thyroid, bladder, endometrium, trachea, seminal vesicle, prostate, and mammary epithelium) were serially cultivated using a feeder layer of lethally irradiated 3T3 cells. The epithelial cells grew as progressively expanding colonies, in some cases stratified, and were shown to form cornified envelopes upon ionophore-induced activation of cross-linking. Cultures derived from each tissue were distinguishable from the others by characteristic cellular appearance and colony morphology. Those examined in greater detail could be distinguished biochemically in three ways. (a) A majority of cells in sparse cultures of bladder, tracheal, endometrial, and vaginal epithelial cells were capable of envelope formation, whereas those from pituitary, thyroid, seminal vesicle, and mammary epithelia did not attain maximal envelope forming ability until after confluence. (b) Bladder, thyroid, and pituitary cells exhibited different electrophoretic profiles of keratins, which accounted for 20-50% of the cellular protein. (c) Bladder cells were distinguished from thyroid and pituitary cells by a greater suppression of envelope-forming ability by vitamin A. These observations showed that cells from many epithelia have the potential to express properties of keratinocytes in culture while maintaining morphological and physiological differences. Serial passage of these cells generated continuous lines.

Acyltransferases↗

PubMed2000

Sustained suppression of pituitary-gonadal axis with an injectable, in situ forming implant of leuprolide acetate.

The objective of these studies was to develop a leuprolide acetate depot based on an in situ forming drug delivery system (Atrigel(R)) to suppress the pituitary-gonadal axis and in turn the serum testosterone to chemical castration levels for a period of at least 3 months. Formulations with biodegradable lactide/glycolide copolymers that varied in molecular weight, lactide/glycolide ratio, and hydrophilicity were evaluated in rats for their efficacy by measuring serum testosterone levels. The effect of polymer irradiation was also investigated. Molecular weight of the polymers was characterized by gel-permeation chromatography, and retrieved implants at the termination of animal studies were assayed for residual drug content by high-performance liquid chromatography. These initial rat studies showed that a formulation containing a 75/25 lactide/glycolide copolymer dissolved in N-methyl-2-pyrrolidone with 3% w/w leuprolide acetate suppressed serum testosterone for a period of 3 months or longer. This formulation with its advantages of biodegradability, biocompatibility, ease of injection, and no need for removal after use should be beneficial in treating patients with hormonal-dependent prostate and mammary cancers, endometriosis, and precocious puberty. In addition, this formulation with its simple manufacturing process is expected to provide an economic benefit to the user compared with products currently available on the market.

Animals↗

PubMed1995

Effects of treatment with octreotide in acromegalic patients--a multicenter Italian study. Italian Multicenter Octreotide Study Group.

Treatment of acromegaly is effective in reversing the reduced life-span of patients only when serum growth hormone (GH) concentrations are lowered to less than 2.5 micrograms/l. Usual treatments achieve this goal in no more than 50-60% of patients. The effects of octreotide were studied in a prospective, open label study with 68 acromegalic patients enrolled in 10 Italian centers. Octreotide was administered sc at a dose of 100 micrograms t.i.d. for 1 year. After 3 months of therapy, octreotide was effective in decreasing serum GH levels below 2.5 micrograms/l in 16 out of 64 acromegalic patients (25%). Fifteen of them had pretreatment GH levels below 25 micrograms/l. Insulin-like growth factor I (IGF-I) levels normalized in about 40% of patients. No further GH reduction was observed after 1 year of treatment. The presence of abnormal GH responses to thyrotropin-releasing hormone (TRH) and gonadotropin-releasing hormone was reduced from 54 to 24% and from 16 to 12%, respectively. Tumor shrinkage was observed in 50% of 26 non-irradiated patients after 12 months of treatment. Both basal and TRH-stimulated serum prolactin levels significantly decreased in the 11 hyperprolactinemic patients. Although serum thyrotropin, free triiodothyronine and free thyroxine concentrations were not modified, a significant reduction of thyrotropin response to TRH was observed in the 9th month of therapy. In non-diabetic patients, an increase of mean blood glucose levels without modifications of fasting morning concentrations was found. About one-quarter of the patients with overt diabetes mellitus had an impairment of their metabolic control. Main clinical symptoms of acromegaly improved in 70-80% of patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Acromegaly↗

PubMed1987

Effect of low dose endometrial after-loading irradiation upon the hypophysis-ovarian axis.

Endometrial inactivation by irradiation, while simultaneously preserving the ovarian function is sometimes clinically indicated. We have found that after 1100 cGy (rad) the ovarian function remains intact, yet endometrial inactivation is unsatisfactory. Therefore, four premenopausal subjects, with clinical indications for eliminating disturbing uterine bleedings, received each an endometrial dose of 1600 cGy by using a Cathetron afterloading unit. When pre- and post-treatment cycles were compared, the circulating gonadotrophin and estrogen levels were unchanged in three subjects. Nine to 12 weeks after the treatments there were no signs of ovulation and the gonadotrophin levels were generally increased. None of the subjects had experienced any bleedings. We conclude that an endometrial dose of 1600 cGy is effective in inactivating endometrium, but may also lead to an impaired ovarian function and to a premature menopause.

Adult↗

PubMed1981

Interstitial pituitary irradiation with 90Y for the treatment of acromegaly. A reappraisal.

The management of 54 acromegalics referred to us between 1974 and 1978 has been analysed. Twenty-two patients were treated with pituitary implants of yttrium-90 (90Y). Eleven are in complete remission (mean growth hormone (GH) less than 11 mIU/l), 8 had improved (mean GH 11-20 mIU/l or 50% less than preoperatively) and 3 were poor responders. Two patients had temporary 6th nerve paresis. Seven patients are on replacement therapy. Thirty-one patients were not implanted for the following reasons with a number of patients having more than one: extension of the tumour into the sphenoid sinus 10, or above the sella 3, partially empty sella 9, internal carotids too close to midline 2, invisible landmarks 1, mild acromegaly 6, poor general health 3, declined investigations or operation 6. It is concluded that pituitary implant of yttrium is an effective and safe form of treatment in carefully selected patients.

Acromegaly↗

PubMed2003

Clinical laboratory findings and results of therapy in 55 patients with Cushing's syndrome.

In this study, 55 patients with Cushing's syndrome (CS) (50 female, 5 male; mean age 34 +/- 12.3 yr) who attended our clinics between the years 1983 and 2000 were retrospectively evaluated for clinical and laboratory features and modalities and results of therapy, due to a few similar studies over the last ten years. Cushing's disease was diagnosed in 39 patients (71%), adrenal adenoma in 13 patients (23.6%) and adrenal carcinoma in 3 patients (5.5%). Centripedal obesity, moon face, hypertension, hirsutism and purplish stria were the most frequent findings. Loss of normal serum F circadian rhythm was found in all patients with CS. The overnight 1 mg oral dexamethasone suppression test and low-dose dexamethasone suppression test (LDDST) yielded 100% and 100% diagnostic sensitivity for CS, respectively. Sensitivity and specivity of the high-dose dexamethasone suppression test (HDDST) in distinguishing Cushing's disease was found to be 82% and 100%, respectively. All of the patients with adrenal CS were not suppressed with HDDST. Sellar CT and/or MRI accurately identified the tumor in 58% of these patients. Recurrence was observed in 3 (11%) of the 28 patients with Cushing's disease, treated by transsphenoidal adenomectomy. Recurrence was diagnosed 1.5, 3 and 6 yr after the operation in these 3 patients. One patient had residue tumor. In our case series, bilateral adrenalectomy plus pituitary irradiation achieved the highest remission rate (100%) in Cushing's disease. In 2 out of 4 patients (50%) treated by left adrenalectomy associated with pituitary irradiation, recurrence was observed. Panhypopituitarism due to tumor apoplexy was observed in one of the patients with Cushing's disease. All of the patients with adrenal CS, the tumor was accurately localized with imaging methods before the operation. The appropriate operative procedure resulted in complete remission in patients with adrenal adenoma. Consequently, Cushing's disease was the most common form of CS. The overnight 1 mg oral DST and 24-h urine free F excretion (UFC) as screening tests, 2-day LDDST as diagnostic test and 2-day HDDST as differential diagnostic test were good studies. More successful outcomes have been achieved in treatment of Cushing's disease with the development of pituitary surgery in the recent years, as well as in our case series. Surgery is also curative for adrenal adenoma patients. Survival remains poor among carcinoma patients.

Adrenalectomy↗

PubMed1977

Endocrine morbidity in adults treated with cerebral irradiation for brain tumours during childhood.

Hypothalamic-pituitary function was assessed in 20 adult subjects who were treated with cerebral irradiation for brain tumours during childhood between 8 and 32 years earlier. Nine patients showed impaired growth hormone (GH) responses to hypoglycaemia, of whom, 7 are below the third centile for standing height. All GH deficient subjects received more than 2950 rads to the hypothalamic-pituitary axis with a maximum dose of approximately 5000 rads being used in one case. Three subjects have an elevated basal serum thyroid stimulating hormone (TSH) level and 2 of these show an exaggerated TSH response to thyrotrophin releasing hormone (TRH) but no patient was clinically or biochemically hypothyroid. The rest of hypothalamic-pituitary function was essentially normal. This study shows that multiple pituitary hormone deficiencies do no develop with time when the radiation dose is below a critical level. Thus it appears that there is a gradation of radiation damage to the hypothalamic-pituitary axis which is dependent primarily on the dose received rather than the time interval after radiotherapy.

Adolescent↗

PubMed1999

Radiotherapy in the management of giant pituitary adenomas.

BACKGROUND AND PURPOSE: The description of giant pituitary adenoma is not clear yet. In this study we tried to identify which adenomas can be defined as giant pituitary adenomas when tumor control and progression free survival (PFS) are taken as end points and we also tried to evaluate prognostic factors other than tumor size. MATERIALS AND METHODS: Between January 1981 and December 1997, 74 patients with pituitary macroadenomas more than 2 cm in size were treated. Of these 30 had tumors of more than 4 cm, while 44 patients were with tumors of 2-4 cm. Two patients received primary radiotherapy, while 72 were treated postoperatively. In the postoperative group, 52 patients underwent immediate radiotherapy after surgery and 20 were treated with irradiation after regrowth or progression of the tumor after initial surgery. The mean and median tumor doses were 5518 and 5425 cGy, respectively. RESULTS: Overall primary tumor control rate was 84%. The local control rates among patients with tumors more than 4 cm and among patients with tumors 2-4 cm after radiotherapy were 73 and 91%, respectively. PFS was 65% for patients who had a tumor size of more than 4 cm and 87% for the patients with tumor size of 2-4 cm (P = 0.09). Young age (<20) and tumors of unclassified histology were the bad prognostic factors. Six months after radiotherapy normalisation or improvement in hormonal hypersecretion and visual field and acuity deficits were 82 and 63%, respectively. CONCLUSION: Tumors more than 4 cm in size may be more convenient for the definition of 'giant pituitary adenoma' when tumor control and PFS are taken as the end points.

Adenoma↗

PubMed1999

Growth, puberty, and endocrine functions in patients with sporadic or familial neurofibromatosis type 1: a longitudinal study.

OBJECTIVE: This study prospectively evaluates parameters of growth, puberty, and attained adult height in children with sporadic or familial occurrence of neurofibromatosis type 1 (NF-1), followed up longitudinally, to define the most important factors affecting these parameters. PATIENTS AND METHODS: The study was made up of 89 patients (55 boys, 34 girls) with sporadic (n = 45) or familial NF-1 (13 affected fathers and 31 affected mothers). The average age at referral was 8.9 years (range 8.5-15 years), and the average follow-up period was 8.5 years (6-15 years). A total of 28 patients attained adult height at the time of the report. Anthropometric measurements and bone age determinations were performed at 6- to 12-month intervals. As indicated, central nervous system (CNS) imaging was performed on 60 patients. Serum levels of thyroid stimulating hormone, free T4, lutheinizing hormone, follicle stimulating hormone, testosterone or estradiol, cortisol, and prolactin were measured in all patients periodically, and the pituitary growth hormone reserve was assessed in 32 short patients. RESULTS: CNS pathology was found in 23 of the 89 patients. A total of 6 patients required neurosurgery, and 2 patients had cranial irradiation. Of these patients, 3 were receiving recombinant growth hormone and thyroxin replacement therapy and 5 patients with precocious puberty were treated with a gonadotropin-releasing hormone analog. All other patients had normal endocrine tests. Precocious puberty was recorded in 5 patients and was more common among the familial cases. The 5 patients with precocious puberty also had CNS pathology. Short stature (<10th percentile) was observed in 25.5% of the patients during the prepubertal period with a significant gradual reduction of their relative height for age (standard scores) during puberty. Short adult height was noted in 12 (43%) of 28 patients, and only 50% of the 28 patients attained an adult height that was appropriate for their respective target height. Short stature was more common among patients with familial NF-1, particularly if the father was affected, and among those patients with CNS pathology. Parental short stature was observed in 39% of the mothers and in 33% of the fathers (59% and 54% among the affected parents, respectively). Tall stature (>90th percentile) was observed in 4 of 89 patients (4.5%), who all had CNS tumors. A highly significant correlation was found among all adult height-predicting parameters (r =.79), and attained adult height was best correlated with the target height (r =.7; n = 28). CONCLUSIONS: Short adult height is an important characteristic of NF-1 and deserves to be emphasized in the evaluation and follow-up of these patients during childhood. Short adult height is strongly linked with familial background of NF-1, in particular if the affected parent is the father, and is affected adversely by the relatively poor pubertal growth. Despite normal pituitary gland and thyroid function tests in most children and adolescents with NF-1, increased incidence of precocious puberty was observed. As the clinical expression in the second generation is more pronounced, the underlying mechanism seems to be mediated by genetic factors that are yet undefined.

Adolescent↗

PubMed1990

The clinical use of somatostatin analogues in the treatment of cancer.

Somatostatin is a regulatory hormone or tissue factor which plays an inhibitory role in the normal regulation of several organ systems, including the central nervous system, hypothalamus and pituitary gland, the gastrointestinal tract and the exocrine and endocrine pancreas. Sandostatin is an analogue of somatostatin which has characteristics which makes it a better compound for clinical use than native somatostatin: it inhibits GH preferentially over insulin. It has a long half-life in the circulation, causing a prolonged inhibitory effect in somatostatin-responsive target organs. It is active after subcutaneous administration and rebound hypersecretion does not occur. Sandostatin is very well tolerated by most patients. Somatostatin receptors remain present on a variety of tumours which arise in tissues that contain these receptors normally. High numbers of somatostatin receptors have been found on GH-secreting pituitary tumours and on most metastatic endocrine pancreatic tumours and carcinoids. Sandostatin treatment ameliorates clinical symptoms in most acromegalic patients while GH hypersecretion and elevated concentrations of circulating IGF-I are well controlled. In most patients hormonal hypersecretion from endocrine pancreatic tumours and carcinoids is also suppressed during Sandostatin therapy. This results in an instant improvement in the quality of life. There is preliminary evidence of control of tumour growth. The presence of high numbers of somatostatin receptors on tumours enables in vivo receptor-imaging, with 123iodine coupled to a somatostatin analogue. This newly developed technique provides for the first time the possibility of localization of the primary tumours and their metastases and a prediction of which patients may respond to treatment with Sandostatin. Theoretically this somatostatin-receptor imaging technique represents a new approach which may be extended to other receptor-containing tumours. Therefore it may provide a new, powerful alternative to tumour localization performed with monoclonal antibody technology. Another potential development is the use of beta-emitting isotopes coupled to somatostatin analogues for therapeutic irradiation. Somatostatin analogues exert potent inhibitory effects on the growth of a variety of experimental tumour models in animals. Several mechanisms of action have been proposed including the direct antiproliferative effects of somatostatin and its analogues in a variety of tumour cell cultures. Most well-differentiated human brain tumours like meningiomas and low-grade astrocytomas contain somatostatin receptors, while undifferentiated brain tumours mainly contain EGF receptors. Fifteen percent of human breast carcinomas contain somatostatin receptors; those which do have a better prognosis. It can be concluded that somatostatin is an endogenous, naturally occurring inhibitory growth factor.(ABSTRACT TRUNCATED AT 400 WORDS)

Acromegaly↗

PubMed1972

Unexpected resistance to x-irradiation in a strain of hybrid mammalian cells.

The radiosensitivities of a strain of mouse fibroblasts (Cl-1D), of rat pituitary cells (GH(1)2C(1)), and of a hybrid between the two (alpha-RST) have been studied. Their mean chromosome numbers were 50, 70, and 111, respectively. The hybrid cells were much more resistent to radiation than either of the parent strains. The range of the D(0) (reciprocal of the slope, and therefore a measure of radiosensitivity) for the linear portion of the survival curves for each cell line was: Cl-1D, 134-142 R; GH(1)2C(1), 154-170 R; and alpha-RST, 248-274 R. There were no significant differences in the magnitude of the shoulder or extrapolation number of the survival curves, nor in the ability of the three cell strains to accumulate and repair sublethal radiation damage. It appears unlikely that the unusual resistance of the hybrid strain is simply related to the increase in chromosome number; more likely, it involves some interaction between the two genomes. The study of somatic cell hybrids may offer further insight into the factors controlling the radiosensitivity of mammalian cells.

Animals↗

PubMed2000

Telomerase activity and the expression of telomerase components in pituitary adenoma with malignant transformation.

BACKGROUND: Telomerase activity responsible for cellular immortality may participate the development of human cancers. Telomerase is a multisubunit ribonucleoprotein composed of at least three components: hTERT, hTERC, and TEP1. This is the first report showing telomerase activity and telomerase component expression in pituitary adenoma with histological malignant transformation. DESCRIPTION: A 16-year-old male with a prolactin-producing pituitary adenoma with metastasis is presented. The patient underwent three partial resections of an intra- and suprasellar lesion over a 2-year period and received focal irradiation. Eight years after the first admission, a metastatic lesion to the subarachnoid space around the medulla oblongata was detected and the lesion was resected as the fourth operation. Furthermore, the suprasellar lesion showed regrowth and partial resection was performed as the fifth operation. The last two specimens were diagnosed as pituitary carcinoma. Radiotherapy with gamma knife was performed for the residual suprasellar lesion and a new lesion in the left temporal lobe after the fifth operation. Telomerase activity was examined by TRAP/TRAP-HPA methods, qualitatively and quantitatively. Telomere length was examined by Southern blot analysis, and the expression of telomerase components (hTERT, hTERC, and TEP1) was examined by reverse transcriptase-polymerase chain reaction (RT-PCR). The MIB1 index, telomerase activity, and hTERT expression increased according to histologic malignancy chronologically in this patient. None of the specimens showed immunoreactivity for p53, EGFR, or bc12. No telomerase activity was detected in pituitary adenomas without malignant transformation, other benign brain tumors, or normal brain tissues. CONCLUSION: We report a patient with pituitary adenoma transforming to carcinoma. The tumor cells acquired immortality and revealed malignant transformation during the course of the disease, that was proved by an increase of telomerase activity and hTERT expression.

Adenoma↗

PubMedDate not supplied

The risk of radiation-induced carcinogenesis after external beam radiotherapy of Graves' orbitopathy.

PURPOSE: In order to estimate the risk of radiation-induced carcinogenesis after external beam radiotherapy of Graves' orbitopathy, we made dosimetric measurements with thermoluminescent dosimeters in a male Rando phantom using our treatment technique. METHODS: We produced dose-volume histograms from 5-mm CT slices using our treatment planning system. In this way we estimated the irradiation dose received by the main surrounding organs such as the brain, the bone and the eyeball. We use 6-MV X-ray for the treatment of Graves' orbitopathy and our total dose is 2,000 cGy, 200 cGy per fraction. Clinical target volume was limited to the retrobulbar orbital content and medial rectus muscle, sparing the lenses, lacrimal glands and the sella turcica. All dosimetric measurements with thermoluminescent dosimeters were made 3 times. RESULTS: We found that the dose to the right lens was 101.6 mGy and to left lens 103.4 mGy. Average absorbed doses to red bone marrow, thyroid, lung, esophagus, bone surface, skin and brain, respectively, were estimated to be 523, 21, 4, 5, 81, 29, 47 mGy. Then, using tissue weighting factors specified by the International Commission of Radiation Protection, the resulting total effective dose was calculated to be 66.8 mSv. CONCLUSION: The risk factor for fatal cancer development derived from human epidemiological data is presently assumed to be 10% per Gy. In patients treated by our method of retro-orbital external beam radiotherapy for Graves' orbitopathy, there is a 0.0067 (or 7 per 1,000 persons or 0.7%) risk of developing fatal radiation-induced cancer.

Disease-Free Survival↗

PubMed1981

The effects of growth hormone therapy in children with radiation-induced growth hormone deficiency.

The effects of growth hormone (GH) therapy were studied in 6 children, previously treated for brain tumours which did not directly involve the hypothalamic-pituitary axis, and who had received cranial irradiation between 2.1 and 10 years earlier. All 6 were short with a standing height standard deviation score (SDS) from -1.7 to -3.3. Impaired growth hormone responses to an insulin tolerance test (ITT) were observed in all 6 and to a Bovril stimulation test in 5 children. The remainder of pituitary function was essentially normal. All 6 were prepubertal and 5 had a retarded bone age. During the pre-treatment year the 6 children's growth rates varied fom 2.0 to 5.1 cm. Subsequently all received human GH in a dose of 5 units 3 times weekly for 1 year. The growth rate in each was at least 2 cm greater during the treatment year than the pre-treatment year. Growth during the treatment year ranged from 6.0 to 10.1 cm. In 5 of the 6 the improvement in growth rate could be totally ascribed to the GH therapy. In the sixth there was significant pubertal maturation during the treatment year and only in this subject did the bone age advance at a significantly greater rate than the chronological age.

Adolescent↗

PubMedDate not supplied

Food restriction and spontaneous motor activity in male mice: effects of feeding pattern, far-infrared ray and bamboo grass leaf extract.

The effects on spontaneous motor activity of the pattern of restricted feeding, far-infrared ray (FIR) irradiation or free access in drinking water containing Sasa Health, a bamboo grass leafextract, were examined in SHN male mice at 2-3 months of age. In mice whose diet was restricted to 60% of the control, fed at 9:00 or 17:00 hours, the level of spontaneous behaviour was elevated 1 hour before the respective feeding time (8:00 or 16:00 hours). The activity was stimulated by FIR in both the control and food-restricted mice, but to a much higher degree in the latter. Treatment with Sasa Health in drinking water lowered the elevated activity level in food-restricted mice. Plasma component levels and organ weights were modulated by FIR or Sasa Health. The findings revealed that, not only the restricted feeding itsel, but also its pattern, significantly affected behaviour and that FIR and Sasa Health modified the deleterious effects of restricted feeding.

Administration, Oral↗

PubMed2005

Bone mineral density at diagnosis and following successful treatment of pediatric Cushing's disease.

Bone mineral density (BMD) is frequently reduced in children and adolescents with Cushing's disease (CD), but there is little follow-up data after cure. BMD was determined by dual energy X-ray absorptiometry (DEXA) in two groups of patients with CD. Group 1 comprised 8 patients, 5 males and 3 females, aged 12.4 yr (8.2-16.8), assessed at diagnosis. Group 2 comprised 11 subjects, 6 males and 5 females, diagnosed at age 13.3 yr (6.4-17.4), cured by transsphenoidal surgery (TSS) (no.=7) or TSS + pituitary irradiation (no.=4). They had measurement of BMD, at mean age of 18.3 yr (11.1-28.5), i.e. 4.5 yr (0.8-11.4) after cure. Four patients, mean age 20.2 yr (17.6-22.4), had repeated DEXA'scans, 1-4 times, for up to 5.8 yr. After cure, GH deficiency was present in 9 patients and treated with hGH in 8. In Group 1, patients' L2-L4 volumetric (v)BMD Z-score was variable with a mean of -1.04 (-3.21-0.11). L2-L4 vBMD Z-score values correlated negatively with midnight cortisol (p < 0.05). In Group 2, mean L2-L4 vBMD was -0.38 (-1.0-0.13); and in 7/11, mean femoral neck (FN) areal (a)BMD Z-score was 0.14 (-1.62-2.46). FN aBMD Z-score was higher than L2-L4 aBMD Z-score (p < 0.05). In patients with repeated scans, mean change in L2-L4 vBMD Z-score was 0.20 (-0.15-0.45), and mean change in FN aBMD Z-score 0.03 (-0.53-0.38). These findings show variability of BMD at diagnosis and near normal BMD after cure of pediatric CD, suggesting that with appropriate replacement of pituitary hormone deficiency normal peak bone mass is achievable.

Absorptiometry, Photon↗

PubMed2000

Postoperative radiotherapy in acromegaly is effective in reducing GH concentration to safe levels.

OBJECTIVE: Several studies have established that in treated acromegaly mortality is only normalized in patients achieving a serum GH concentration below 5 mU/l. Few studies however, have addressed results of radiotherapy using this strict criterion. The aim of our study was to assess the efficacy of postoperative radiotherapy in reducing serum GH concentration below 5 mU/l. PATIENTS AND METHODS: Forty acromegalic patients who underwent radiotherapy for postoperative persistent disease after transsphenoidal surgery were studied. Mean time of follow-up after radiotherapy was 123+/-11.1 months. A serum GH concentration of <5 mU/l was used to define remission. RESULTS: Following surgery mean GH concentration decreased from 120.8+/-21 mU/l to 24.4+/-5.2 mU/l and mean GH concentration prior to radiotherapy, administered after a mean of 8.2+/-2.7 (0.5-96) months postoperatively was 26.0+/-5.1 mU/l. Using individual regression plots, GH was reduced to 50% by radiotherapy after a mean of 27+/-5 months (range 3-105 months). The observed mean GH concentration as measured at follow-up visits was reduced by 55% (-36-95%) after the first year, by 65% (-29-97.3%) after 2 years and by 78% (-29-99%) after 5 years. We could not demonstrate a significant correlation between a normalized GH concentration on the one hand and tumour size, preradiotherapy GH concentration or duration of follow-up on the other hand. During follow-up, GH-suppressive medical therapy was used in 11 patients, five of whom were still using medication at the end of follow-up. Eight patients had a follow-up of less than 5 years and three of them had a serum GH concentration of <5 mU/l at their latest follow-up visit (38%). At 5 years of follow-up after radiotherapy, 24 out of 32 patients had a GH level of <5 mU/l without medication (75%). At 10 years following irradiation, 16 of 21 patients (76%) had a GH level of <5 mU/l without medical treatment. At 15 years follow-up, a serum GH concentration of <5 mU/l was observed in 13 out of 15 patients (87%) without GH suppressive medication. At the latest follow-up visit, serum GH concentration below 5 mU/l was present in 75% of patients (30 out of 40) without medical therapy after a mean of 10.4+/-0.9 years, but five patients required octreotide up to the end of follow-up. Twenty-seven out of 37 patients with available IGF-I data had normal IGF-I at the end of follow-up (73%). Fifty percent of patients needed substitution therapy for (partial) hypopituitarism after 10 years and 75% after 15 years of radiotherapy. CONCLUSION: In our group of patients who were incompletely cured by surgery, but had a significant postoperative decrease of serum GH concentrations, radiotherapy was able to achieve 'safe' serum GH concentrations in the majority in the long term.

Acromegaly↗