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At least 595 records · Page 33Linked to original sources

Hypothalamo-pituitary disconnection in the fetal sheep.

In this study we have applied the technique of hypothalamo-pituitary disconnection (HPD) to the fetal sheep at 108-112 days of gestation. The pituitary is surgically disconnected from the hypothalamus by the removal of the neural component of the median eminence above the level of the portal circulation. This procedure results in the complete disconnection of the pituitary from the hypothalamus. After HPD, the lactotroph response to the dopamine antagonist chlorpromazine was significantly reduced (p less than 0.005) indicating the functional isolation of the pituitary gland from the hypothalamus. The increase in plasma prolactin in response to exogenous thyrotrophin-releasing factor was maintained following HPD. HPD resulted in the complete atrophy of the pars nervosa. At 132-135 days of gestation after HPD there was no change in the volume or appearance of the pars distalis; small infarcts were observed in the pars distalis of some HPD fetuses, but these occupied less than 1% of the volume of the anterior lobe of the pituitary. There was a significant increase (p less than 0.05) in the volume of the pars intermedia after HPD. Gestation was prolonged for at least 8 days beyond normal term following HPD, indicating that the processes integral to the initiation of parturition at term had been disrupted. We conclude that HPD provides a good in vivo model for the investigation of the activity of the isolated pituitary gland, and for the examination of the role of neuroendocrine mechanisms in fetal sheep development in the latter third of gestation.

Animals↗

Extrasellar prolactinomas: successful management of 24 patients using bromocriptine.

24 patients with an extrasellar prolactinoma (mean prolactin 4,722 ng/ml), 8 of whom had previously had surgery, received 5-40 mg bromocriptine daily for 13-252 weeks. The mean prolactin level had fallen 89% at 2 days, 95% at 6 weeks, and 15 patients achieved normal values. Tumor shrinkage occurred in all 9 patients rescanned within 2 weeks and later was documented in 23; in 18 the extrasellar tumour disappeared. 12 patients had visual abnormalities; 7, including 2 who had been completely blind, improved within 1 week. 2 patients had normal prolactin levels after withdrawal of bromocriptine, 1 following radiotherapy and the other during two uncomplicated pregnancies. Bromocriptine is safe and effective. We conclude that medical treatment should always precede surgery unless pituitary apoplexy causes sudden deterioration of vision. Most patients will subsequently require radiotherapy or surgery for permanent cure.

Adult↗

Failure of steroid replacement to consistently normalize pituitary function in congenital adrenal hyperplasia: hormonal and MRI data.

Exogenous glucocorticoid replacement in patients with congenital adrenal hyperplasia (CAH), who due to an adrenal 21-hydroxylase enzyme deficiency are unable to produce endogenous glucocorticoids, is aimed at normalizing hypothalamic-pituitary-adrenal function. Excess androgen production by the adrenals is thus decreased. Despite standard glucocorticoid replacement doses (12.5-40 mg, 10.5-27 mg/m2/day hydrocortisone equivalents) 4 of 7 patients ranging in age from 14 to 33 years had abnormalities of the pituitary on MRI. Three appeared to have microadenomas and 1 had an empty sella. Five (3 salt wasters, 2 simple virilizers) of these 7 patients had 60-min p.m. ovine corticotropin-releasing hormone (oCRH) stimulation studies. The mean (logarithm) area under the ACTH curve for 0-60 min after oCRH stimulation was significantly greater in patients than controls (p < 0.0001). Mean ACTH at each time point before and after oCRH stimulation was similarly greater in patients than controls (p < 0.05). Two of these patients had pituitary microadenomas, 1 had an empty sella; all 3 were salt wasters. Despite standard glucocorticoid replacement, adolescent and young adult patients with CAH tend to have high basal ACTH and ACTH hyperresponsiveness to oCRH, as well as structural abnormalities of the pituitary. The inevitable periods of under- and overexposure to glucocorticoids in CAH patients may over time cause abnormalities of the hypothalamic-pituitary-adrenal axis.

17-alpha-Hydroxyprogesterone↗

Effects of synthetic LH-RH and TRH on pituitary function in anencephalic infants.

The pituitary endocrine function in 4 anencephalic infants was studied by measuring the concentrations of growth hormone, prolactin, thyroid-stimulating hormone (TSH), follicle-stimulating hormone (FSH) and luteinizing hormone (LH) in umbilical venous serum. There was no significant difference in hormone levels between the anencephalic and normal infants. The response of FSH and LH was negative after administration of 10 micrograms of luteinizing hormone-releasing hormone. The TSH levels after administration of 50 micrograms of TRH elevated about 4- to 6-fold over pre-administration levels. These results indicate that the hypothalamo-pituitary axis of the human fetus initiates its function from mid-pregnancy; TSH may have an autoregulating system of the pituitary itself.

Anencephaly↗

Cell proliferation activities on skin fibroblasts from a short child with absence of one copy of the type 1 insulin-like growth factor receptor (IGF1R) gene and a tall child with three copies of the IGF1R gene.

The type 1 IGF receptor (IGF1R) is required for normal embryonic and postnatal growth. The aim of this study was to determine whether we could detect abnormal IGF1R function in skin fibroblasts from children with an abnormal copy number of the IGF1R gene. We report two children with altered copy number of the IGF1R gene who presented with abnormal growth. Case 1 is a girl with intrauterine growth retardation, postnatal growth failure, and recurrent hypoglycemia. Pituitary function tests were normal. Routine karyotype analysis identified a deletion on 15q26.2, and a fluorescence in situ hybridization study using IGF1R probes showed only a single IGF1R gene. Case 2 was large for gestational age, with birth weight and length at or above 97th percentile, and showed rapid early postnatal growth. He was found to have a recombinant chromosome 15 containing a partial duplication at 15q (q25-qter). A fluorescence in situ hybridization study using the same probes showed three copies of the IGF1R gene. In a mitochondrial activity assay, skin fibroblasts from the subject with only one copy of IGF1R showed slower growth, whereas cells from the subject with three copies of IGF1R showed accelerated growth compared with controls. IGF1R phosphorylation, as assessed by Western blot, and IGF1R binding studies were decreased compared with controls in the child with one copy of the IGF1R and increased in the child with three copies of the gene. Our data are consistent with the concept that IGF1R gene copy number is of functional and clinical importance in humans.

Body Height↗

Clinical review: Early morning cortisol levels as a predictor of remission after transsphenoidal surgery for Cushing's disease.

INTRODUCTION: We describe the use of serum cortisol and ACTH levels on postoperative d 1 and 2 as remission predictors after transsphenoidal surgery for Cushing's disease (CD). METHODS: Morning cortisol and ACTH levels were drawn daily after surgery; glucocorticoids were withheld until evidence of hypocortisolemia. Early remission was defined retrospectively as a subnormal morning cortisol level [< or =140 nmol/liter (< or =5 microg/dl)] on postoperative d 1 or 2 and sustained remission as subsequent eucortisolemia. RESULTS: Of 40 consecutive adults with CD (mean age 39 yr), 80% achieved early remission. Of 39 patients with a minimum follow-up of 14 months (mean 33 months), 31 (79.5%) achieved sustained remission at a mean follow-up of 32 months, including 30 of 31 (97%) with early remission and one of eight (12%) without early remission (P < 0.0001). Sustained remission was achieved in 26 of 28 (93%) patients having their first operation, compared with five of 11 (45%) with a prior unsuccessful operation (P < 0.001). For the 32 patients in early remission vs. the eight in nonremission, mean nadir cortisol levels were 57.6 +/- 33.0 (2.05 +/- 1.2 microg/dl) vs. 631.1 +/- 352.2 nmol/liter (22.9 +/- 12.8 microg/dl) (P < 0.0001), and nadir ACTH levels were 11.9 +/- 6.5 vs. 64.1 +/- 54.6 ng/liter (P < 0.001). Of 31 patients with sustained remission, 100% had subnormal morning cortisol levels, whereas 31% had subnormal ACTH levels (P < 0.0001). CONCLUSIONS: Serum morning cortisol levels on postoperative d 1 and 2 without glucocorticoid replacement provide a safe, simple, and reliable measure of early remission for CD and are predictive of sustained remission. This method allows for consideration of a repeat operation during the same hospitalization in patients with persistent hypercortisolemia.

Adrenocorticotropic Hormone↗