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PubMed1975

Prolactin studies in "functionless" pituitary tumours.

Hyperprolactinaemia was found in all 17 women and in one out of six men who presented with hypogonadism and a radiologically enlarged sella turcica but no other clinical endocrine dysfunction. Some of the women also had galactorrhoea. The greater the level of hyperprolactinaemia in these 18 patients the larger their sellae turcica except in two patients with unusual features. The sella turcica was usually asymmetrically enlarged and there was rearly an upward extension of tumour, though the sella floor often showed some erosion on tomography. An oral dose of bromocriptine suppressed the hyperprolactinaemia in mose patients at the same rate as in normal post-partum women. Nine of the 18 patients with hyperprolactinaemia had low basal luteinizing hormone (LH) levels. The LH responsiveness to 100 mug of LH-releasing hormone (LHRH) was tested in 12, and eight showed subnormal values. Of eight biopsy specimens obtained four showed acidophil granules on light microscopy, and in five granules of various sizes were seen on electron microscopy.

Adult↗

PubMed1983

The use of stereotaxic chemical hypophysectomy in the treatment of thalamic pain syndrome.

Three patients with neurological injuries consistent with cerebral stroke subsequently developed pain over portions of the body contralateral to the injured hemisphere. Stereotaxic chemical hypophysectomy was used in the management of this pain after other surgical procedures and medical management had failed to provide relief. Postoperatively, all patients were treated for hypopituitarism. All developed transient diabetes insipidus, and one patient developed transient right third nerve palsy. No other complications were encountered. All three patients experienced significant pain relief within 48 hours of the procedure. By the date of discharge, two of the three patients reported complete, and the third greater than 80% pain relief. At the initial follow-up visit all patients were essentially pain-free. These patients have now been followed for 58, 39 and 19 months, and remain free of their original pain. During this time the intravenous administration of naloxone has failed to reproduce the preoperative pain. Pituitary function testing 1 year or more following operation demonstrated that none of the patients had an endocrinologically complete hypophysectomy. Recovery from transient diabetes insipidus was not associated with return of the original pain. The mechanism of action of stereotaxic chemical hypophysectomy in the relief of pain related to thalamic lesions remains unknown. The observation that naloxone failed to reproduce the preoperative pain casts doubt on the theory that augmentation of endogenous opiate release is the primary mechanism. Additional observations suggest that pain relief after hypophysectomy may be more directly the result of stimulation of a hypothalamic pain-suppressing mechanism than due to the elimination of pituitary hormones.

Aged↗

PubMed2003

Pituitary apoplexy induced by corticotrophin-releasing hormone in a patient with Cushing's disease.

Pituitary apoplexy can occur spontaneously or following anterior pituitary stimulation tests. Apoplexy is a rare complication of Cushing's disease. We report a 19-year-old woman who was admitted to the National Institutes of Health for evaluation of possible Cushing's syndrome. Her symptoms and initial laboratory work were suggestive of Cushing's disease. Magnetic resonance imaging (MRI) revealed a macroadenoma of the pituitary gland. As part of her evaluation she received corticotrophin-releasing hormone (CRH). Two days later she developed severe headache, accompanied by nausea and vomiting, followed by meningismus, ptosis and diplopia. A diagnosis of pituitary apoplexy was made and she was treated conservatively with dexamethasone. Her neurological symptoms resolved shortly afterwards. By the time of discharge her anterior pituitary function was suppressed. All symptoms and signs of Cushing's syndrome resolved thereafter. This is the first case to demonstrate that CRH administration can induce pituitary apoplexy in a patient with Cushing's disease. Therapy with glucocorticoids was effective in our case, suggesting that conservative treatment can be successfully and safely applied in certain cases with pituitary apoplexy.

Adenoma↗

PubMed2002

Progress in transsphenoidal hypophysectomy for treatment of pituitary-dependent hyperadrenocorticism in dogs and cats.

Cushing's disease or pituitary-dependent hyperadrenocorticism (PDH) is common in dogs and rare in cats. PDH is caused by a pituitary tumor producing adrenocorticotropin (ACTH). Pituitary imaging with computed tomography (CT) or magnetic resonance imaging (MRI) is required to assess the size and location of the pituitary adenoma in relation to the surgical landmarks. In a specialized veterinary institution, microsurgical transsphenoidal hypophysectomy has proven to be a safe and effective treatment for dogs (n=84) and cats (n=7) with Cushing's disease. Pituitary surgery requires a team approach and the neurosurgeon performing hypophysectomies must master a learning curve. The surgical results compared favorably with those for dogs with PDH treated medically with mitotane at the same institution. The recurrence rate after initially successful surgery increases with longer follow up-times. Pituitary function testing in 39 dogs with PDH treated with hypophysectomy revealed that, much more so than the other adenohypophyseal cell types, residual corticotropes present in the sella turcica after surgery are functional. Such normal ACTH secreting cells may maintain normocorticism whereas residual adenoma cells may lead to mild recurrence after relatively long periods of remission. Microsurgical transsphenoidal hypophysectomy is an effective treatment for canine and feline Cushing's disease.

Adrenocorticotropic Hormone↗

PubMed1983

Testing the anterior pituitary: hypoglycaemia produced by continuous intravenous insulin infusion.

The response of growth hormone, cortisol, and catecholamines to hypoglycaemia produced by a continuous intravenous infusion of insulin was investigated in 10 normal subjects and 15 patients with pituitary disease. The insulin infusion rate was started at 2 U/hour for adolescents, 4 U/hour for adults, and 6 U/hour for patients with acromegaly. If required the rate was increased during the test depending on changes in blood glucose, measured by a Reflomat with low reading glucose oxidase strips. Stopping the infusion when the blood glucose concentration had fallen to 2.0 mmol/l (36 mg/100 ml) resulted in a maximum further fall of 0.7 mmol/l (13 mg/100 ml) and a subsequent spontaneous rise in blood glucose concentration. The rise was identical in normal subjects and in patients with hypopituitarism, further evidence that pituitary hormones--in contrast to glucagon and catecholamines--are relatively unimportant in the recovery from hypoglycaemia. The only patient who required intravenous glucose to restore normoglycaemia was a patient with longstanding insulin dependent diabetes. A comparison with the conventional bolus injection test showed that continuous intravenous insulin infusion was more reliable in producing adequate but not excessive hypoglycaemia and the hormone responses were equivalent. The continuous intravenous insulin infusion may offer particular advantages in the investigation of growth hormone deficiency.

Adolescent↗

PubMed2006

Effect of nutrition during calfhood and peripubertal period on serum metabolic hormones, gonadotropins and testosterone concentrations, and on sexual development in bulls.

The objective of the present study was to characterize the effects of nutrition on circulating concentrations of metabolic hormones, gonadotropins, and testosterone during sexual development in bulls. Nutrition regulated the hypothalamus-pituitary-testes axis through effects on the GnRH pulse generator in the hypothalamus and through direct effects on the testes. Pituitary function (gonadotropin secretion after GnRH challenge) was not affected by nutrition. However, nutrition affected LH pulse frequency and basal LH concentration during the early gonadotropin rise (10-26 weeks of age). There were close temporal associations between changes in insulin-like growth factor-I (IGF-I) concentrations and changes in LH pulse frequency, suggesting a role for IGF-I in regulating the early gonadotropin rise in bulls. The peripubertal increase in testosterone concentration was delayed in bulls with lesser serum IGF-I concentrations (low nutrition), suggesting a role for IGF-I in regulating Leydig cell function. Serum IGF-I concentrations accounted for 72 and 67% of the variation in scrotal circumference and paired-testes volume, respectively (at any given age), indicating that IGF-I may regulate testicular growth. Bulls with a more sustained elevated LH pulse frequency during the early gonadotropin rise (high nutrition) had greater testicular mass at 70 weeks of age relative to the control group (medium nutrition), despite no differences in metabolic hormone concentrations after 26 weeks of age. Therefore, gonadotropin-independent mechanism regulating testicular growth might be dependent on previous gonadotropin milieu.

Animals↗

PubMedDate not supplied

[Sequential infusion of GHRH 1-29NH2, LHRH and TRH for evaluating the hypophyseal reserve. Comparison with Politest].

Fourteen patients with pituitary lesions and 6 normal subjects underwent the following tests: a) LHRH (100 mcg) + TRH (200 mcg) + Human Insulin (0.1 UI/kg) i.v. (Politest "A"); b) LHRH (100 mcg) + TRH (200 mcg) + GHRH 1-29NH2 (100 mcg) i.v. (Politest "B"); c) GHRH 1-29NH2 (100 mcg) i.v. (GHRH-TEST). FSH, LH and PRL, as assayed in patients and controls in response to Politest "A" and "B", revealed no significant differences between the tests. Plasma TSH values were significantly higher after Politest "B" in both patients and normals. The GH response after Politest "A" and "B" was similar in magnitude and concordant in 88.8% of cases.

Adenoma↗

PubMed2003

Oral administration of the growth hormone secretagogue NN703 in adult patients with growth hormone deficiency.

OBJECTIVE: Little is known of the usefulness of GH secretagogues (GHSs) in GH-deficient (GHD) adults. The objective of this study was to determine the number of responders to treatment with NN703 in GHD adults. DESIGN: A multicentre, randomized, double-blind, and placebo-controlled study. PATIENTS: Ninety-seven GHD adults were included. MEASUREMENTS: The GH response before and after 1 week of oral treatment with NN703 (n = 83) or placebo (n = 14) was determined. The first and last dose of NN703 was 3 mg/kg, whereas the dose of NN703 was 1.5 mg/kg/day during the 6 days between the first and last doses. Furthermore, all 97 patients received 1 micro g/kg GH-releasing hormone (GHRH) 3 weeks after the last dose of NN703. RESULTS: Serum GH peak and area under curve (AUC) values after the first NN703 administration were greater than those after placebo administration (P < 0.05). However, after correction for the lower body mass index (BMI) in the NN703 group, this difference lost statistical significance. After 1 week of therapy, GH peak and AUC values were similar following the final doses of NN703 and placebo. Serum peak and AUC values of other anterior pituitary hormones were similar between the NN703 and placebo groups both after the first and last administration of study drug. Nine of the 83 patients (11%) responded with a serum peak GH concentration >or= 5 micro g/l after the first and/or last NN703 administration, whereas no patient responded after placebo administration. Serum IGF-I was unaffected by 1-week NN703 treatment, whereas serum IGFBP-3 was increased (P < 0.05 vs. placebo) also after correction for BMI. Mean serum peak GH concentration after GHRH administration was 2.1 micro g/l (+/-0.3, SEM), which was higher than that after the first NN703 administration (1.32 +/- 0.3, P < 0.05). CONCLUSION: NN703 administration was generally well tolerated. Eleven per cent of the GHD adult patients responded with a peak GH response >or= 5 micro g/l after the first and/or last administration of oral NN703. Although a majority of GHD adults will not respond to NN703, the present results suggest that oral NN703 treatment could be useful in some adult patients with moderately severe GHD. These patients may be identified by a test dose of GHS.

Administration, Oral↗

PubMed1995

[Endocrinological aspects of hypophyseal tumors].

Local expansion of pituitary tumors causes nonspecific symptoms, including hormone insufficiency, that may exist for years before diagnosis. Although they are more specific, symptoms of pituitary hormone oversecretion may also remain unrecognized and give rise to difficult diagnostic problems. Gonadotropic tumors do not elicit specific endocrine symptoms, whether they secrete complete gonadotropins or their biologically inactive free subunits. Hyperprolactinemia is not due to tumor secretion in the majority of cases, including some with a tumor in the pituitary (compressive hyperprolactinemia). When acromegaly is suspected, the unequivocal proof of excess growth hormone secretion is not easy to obtain, due to intermittent growth hormone secretion, both in normals and in acromegalics. The large variety of tests available for the etiological diagnosis of hypercorticism indicates the diagnostic difficulties that can be encountered. Corticotrope pituitary adenomas may be minute, and ectopic corticotropin secretion may remain occult. But on the other hand, the quality of the diagnostic tools available improves constantly. This includes new hormone measurements, such as insulin-like growth factor 1 and its binding proteins, dynamic tests, selective pituitary blood drawing by inferior petrosal sinus catheterism, pituitary nuclear magnetic resonance imaging and somatostatin-analogue scintiscan. In addition to the improving techniques of transphenoidal neurosurgery and pituitary radiotherapy, medical management of pituitary tumors remains a distinct possibility. Tumor hormone secretion can be controlled in some cases by drugs such as dopaminergic agents, somatostatin analogues and gonadoliberin analogues, which may also exert an antitumoral mass effect. Within the next few years we will be confronted with an increasing number of incidentally discovered pituitary tumors, due to the frequent use of high-resolution intracranial imaging.

Acromegaly↗

PubMed2001

An audit of 500 subcutaneous glucagon stimulation tests to assess growth hormone and ACTH secretion in patients with hypothalamic-pituitary disease.

OBJECTIVE: The insulin tolerance test (ITT) is usually regarded as the 'gold standard' for the assessment of the hypothalamic-pituitary axis (growth hormone (GH) and ACTH) but must be used with caution and is contra-indicated in certain groups of patients. The glucagon stimulation test (GST) has previously been shown to be a good alternative when the ITT is contra-indicated and like the ITT stimulates both GH and ACTH secretion. There is however limited data on the use of the GST in patients with hypothalamic-pituitary disease. DESIGN AND PATIENTS: An audit of 500 GST was performed in 374 patients with hypothalamic-pituitary disease. Glucagon was administered via the subcutaneous route and bloods were taken at times 0 90 120 150 180 210 and 240 minutes. RESULTS: In the vast majority peak GH (84.4%) and cortisol (93%) responses occurred between 120 and 180 minutes Little information was obtained from the 240 minute sample. The medical supervision required was minimal and the side-effects encountered during this test were mild; 20% of the tests were associated with nausea occasionally with vomiting sweating or headaches. Four patients fainted but recovered quickly. CONCLUSIONS: This large audit has shown that the glucose stimulation test is well tolerated and can easily be performed in an out-patient setting with minimal medical supervision. The 240 minute sample added little additional information and could be omitted.

Acromegaly↗

PubMed1981

Hypophyseal gonadotropin insufficiency in a young woman with idiopathic hemochromatosis.

A 24-year-old women suffering from primary sterility was diagnosed in 1971 as having idiopathic hemochromatosis (IH). The diagnosis was made on the basis of high serum iron and high transferrin saturation, ferrokinetic studies, including iron absorption, liver biopsy showing heavy deposits of iron in the parenchymatous cells, and a family history. Except for slight elevations in the serum transaminases, there were no clinical or laboratory findings of liver pancreatic, myocardial, or dermal involvement by hemochromatosis. Endocrine evaluation revealed gonadotropin insufficiency as the cause of sterility. The patient was treated with periodic phlebotomies for seven years, and the mount of iron withdrawn during that time was calculated to be approximately 27 g. A repeat liver biopsy showed complete disappearance of the iron excess of the fibrotic changes that had been present in 1971. Repeated relevant clinical and laboratory studies did not reveal any pathological findings consistent with hemochromatosis. A complete endocrine evaluation, including stimulatory tests (luteinizing hormone releasing hormone, thyrotropin-releasing hormone, insulin, and metyrapone), disclosed only findings consistent with hypophyseal gonadotropin insufficiency, and these were attributed to iron deposition. It can be assumed that the prolonged treatment with phlebotomies prevented the development of liver, pancreatic, myocardial, or other clinical endocrine disease, but had no effect on the already damaged pituitary. The patient's clinical course followed the pattern recently described in other young patients with IH.

Adult↗

PubMed1976

Galactorrhea-amenorrhea syndromes: etiology and treatment.

Fifteen patients with galactorrhea-amenorrhea syndromes were studied before, during, and after treatment with bromergocryptine. Galactorrhea and amenorrhea were noted after pregnancy (6 patients), after oral contraceptive therapy (5 patients), and in association with pituitary adenoma (4 patients). Before treatment prolactin values were elevated ranging from 27 to 125 ng/ml, while luteinizing hormone and progesterone levels failed to show ovulatory peaks or luteal phase progression. Eleven patients had luteinizing hormone-releasing hormone tests before therapy. Response was normal in 8, subnormal in 2 pituitary adenoma, and supranormal in 1 patient with premature ovarian failure. Treatment with bromergocryptine was associated with a lowering of serum prolactin, cessation of lactation in all, and return of ovulatory menses in 14 of 15 patients. All relapsed when therapy was discontinued. Four patients became pregnant while on therapy. Long-term bromergocryptine therapy is effective for all forms of galactorrhea-amenorrhea syndromes studied.

Adenoma↗

PubMed1983

LRF and TRF test during long-term danazol treatment: increase of the LH and FSH responses but decrease of the prolactin and TSH responses.

Seven patients suffering from severe endometriosis were treated with danazol 200 mg X 3 daily for 6 months. Clinical symptoms were alleviated and menses disappeared in response to the treatment. After cessation of the treatment the menstrual bleedings returned in 1-3 months. Blood samples for determination of gonadotrophins, prolactin (Prl), oestradiol (E2), progesterone, thyroid hormones and thyrotrophin in radioimmunoassays were taken and a combined TRF and LRF test carried out in the follicular phase before treatment, at the 6th month of treatment and after reappearance of the first menses. There were no statistically significant changes in the basal levels of serum FSH, LH or TSH during the danazol treatment. Neither was there any change in episodic secretions of FSH, LH or Prl, as determined by the mean coefficients of variation of the hormone levels in seven consecutive samples taken at 20 min intervals. On the other hand, serum E2, Prl and thyroid hormone levels were significantly decreased in the 6th month of treatment. In the TRF-LRF test the responses of serum FSH and LH were significantly higher and those of serum Prl and TSH significantly lower during danazol treatment than before. Prl responses remained lowered after the treatment. It appears that low serum oestrogen levels, induced by the danazol treatment, sensitize the pituitary gonadotrophs to exogenous LRF, but make the sensitivity of thyrotrophs and lactotrophs lower to exogenous TRF. These results thus indicate that danazol does not make the pituitary gonadotrophs insensitive to LRF, but danazol may rather inhibit the secretion of hypothalamic LRF.

Adult↗

PubMed1989

Pituitary testing with and without bromocryptine in an aspermic man with elevated serum prolactin/FSH levels.

Pituitary testing is reported in an aspermic man with elevated serum FSH levels and hyperprolactinemia. Responses to clomiphene administration were normal. Serum LH responses to a double bolus of GnRH were substantially increased during bromocryptine therapy but FSH responses were similar with and without bromocryptine. These findings suggest that the elevated prolactin levels inhibited the GnRH-LH axis in this patient even in the presence of elevated serum FSH levels.

Adult↗

PubMed1977

Galactorrhea: a study of 235 cases, including 48 with pituitary tumors.

An analysis of 235 patients with galactorrhea (5.5 per cent males) showed that 20 per cent of all patients, and 34 per cent of women with associated amenorrhea, had radiologically evident pituitary tumors; these patients had the highest serum prolactin concentrations. The largest single group (32 per cent) consisted of women with idiopathic galactorrhea without amenorrhea; prolactin was normal in 86 per cent of these cases. Five patients had the empty-sella syndrome. Prolactin response was tested in selected patients by thyrotropin-releasing hormone, chlorpromazine, L-dopa, 24-hour sampling and other means. Tests with thyrotropin-releasing hormone were most useful in identifying patients with pituitary tumors. Surgery and radiotherapy lowered prolactin to a similar degree in patients with tumor, but galactorrhea, and amenorrhea often persisted after treatment. The ergot derivatives, bromergocryptine and lergotrile mesylate, lowered prolactin in all 18 patients with idiopathic hyperprolactinemia or pituitary tumor, stopped galactorrhea in over 50 per cent, restored menses in over 70 per cent, and allowed pregnancy in three.

Acromegaly↗

PubMed1992

Long term follow-up of Cushing's disease treated with reserpine and pituitary irradiation.

Twenty adult patients with Cushing's disease treated with long term reserpine administration in combination with a single course of external pituitary irradiation were followed. Eleven patients experienced long term remissions of 15.5 +/- 8.9 (mean +/- SD) yr (55%) after a mean irradiation dose of 53.9 +/- 11.4 Gy and a mean duration of reserpine administration of 24.3 +/- 9.3 months. The long term remission rates of the patients irradiated with 50 Gy or less (n = 9; 45.0 +/- 7.1 Gy) and those with more than 50 Gy (n = 10; 61.3 +/- 3.3 Gy; excluding 1 irradiated with 66 Gy who developed brain necrosis) were 56% (5 of 9) and 60% (6 of 10), respectively, and did not differ significantly. There were no significant differences between the 2 groups with regard to the duration of reserpine administration or pretreatment clinical features. At the latest examination, regardless of the irradiation dose, all 9 patients with long term remission showed a higher level of plasma cortisol or 11-hydroxycorticosteroids in the morning than in the evening, normal suppressibility of plasma cortisol with overnight 1 mg dexamethasone (9 of 10), and well preserved responses of other pituitary hormones to various loading tests: normal responses of plasma ACTH to CRH (6 of 9), TSH (7 of 8), and PRL (5 of 8) to TRH and age-related normal responses of GH to GRH (4 of 8), LH (6 of 8), and FSH (6 of 8) to GnRH. These findings suggest that long term reserpine administration in combination with a conventional dose of pituitary irradiation is useful in the treatment of Cushing's disease.

Adolescent↗

PubMedDate not supplied

[Prolactin-secreting pituitary gland adenoma. Present-day possibilities of diagnosis and treatment].

Among the 230 pituitary adenomas that we treated, 23 patients aging from 20 to 39 had a prolactin-secretary pituitary adenoma and were all demonstrating an amenorrhea-galactorrhea syndrom. It is not always very fast to establish the more and more frequently observed etiology of this clinical state, especially when the existence, or not, of a pituitary adenoma is concerned. A total endocrinological study (determination of serum prolactin and inhibition and stimulation tests) of all hypothalamic-hypophyseal-peripheric axis must be done, as well as precise radiological studies, able of showing small distortions of the sella turcica. On our patients, the diagnosis of a pituitary tumor and the surgical intervention have never been decided on the base of only one element of the diagnosis. We now think that only the presence, at the same time, of clinical, radiological and biological signs, however small they are, allows the decision for a surgical intervention when prolactin-secreting pituitary adenoma is suspected.

Adenoma↗

PubMed1976

Diagnosis of prolactin-secreting pituitary microadenoma.

Four women with secondary amenorrhea associated with hyperprolactinemia were studied. Baseline hormonal evaluation, including serum FSH, serum LH, TSH, T3, T4, and plasma cortisols were normal. Plain sella turcia x-rays were also normal. Prolactin-secreting pituitary microadenomas were found in all of the patients only after further diagnostic studies were done. These studies included polytomography of the sella turcia, dynamic pituitary testing of growth hormone reserve, ACTH reserve, gonadotropin reserve, and prolactin suppression with L-dopa. The early diagnosis of a small prolactin-secreting adenoma may be possible if several diagnostic criteria are ulilized. The most sensitive techniques available are: (1) polytomography, (2) the magnitude of plasma prolactin evaluation, and (3) the failure of suppression of prolactin secretion with L-dopa. Our findings emphasize the importance of an extensive evaluation of all women with amenorrhea associated with hyperprolactinemia.

Adenoma↗