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Biomedical subjects

R J Croughs

Publications and source records attributed to R J Croughs.

At least 55 records · Page 3Linked to original sources
PubMed1985

Bromocriptine therapy in acromegaly: effects on plasma GH levels, somatomedin-C levels and clinical activity.

Thirty-one patients with active acromegaly were treated with 10-20 mg bromocriptine daily for a period of 6-9 months. The clinical response was evaluated both by a subjective 'score of symptoms', and by a combined subjective and objective 'clinical and metabolic improvement score' (c-m score). The biochemical response was evaluated both by measurement of the mean of four plasma growth hormone (GH) determinations during the day and by measurement of plasma somatomedin-C (Sm-C) concentration. The clinical response as assessed by both methods showed a better correlation with changes in plasma GH levels (respectively r = 0.33; r = 0.50) than with changes in Sm-C levels (r = 0.20; r = 0.36). The study confirms that in some patients clinical improvement is not accompanied by a decrease of plasma GH concentration. However, it is not possible to identify a subgroup of patients who showed clinical improvement with a decrease of Sm-C levels, but whose plasma GH levels remained constant. It is concluded that measurement of plasma GH levels still appears to be the most useful biochemical assessment of disease activity in bromocriptine-treated acromegaly.

Acromegaly↗
PubMed1985

Changes of molecular forms of growth hormone in bromocriptine treated acromegaly in relation to changes of somatomedin-C and clinical response.

Eleven patients with active acromegaly were treated with 10-20 mg bromocriptine daily for a period of 6-9 months. The clinical response was evaluated by a 'clinical and metabolic improvement score'. The biochemical response was evaluated by measurement of both the mean plasma growth hormone (GH) level during the day and the somatomedin-C (Sm-C) concentration. Before and at the end of the treatment period plasma samples were fractionated by Sephadex G-100 chromatography in order to study the effects of chronic bromocriptine treatment on the concentrations of total GH and its different molecular forms. The main observations may be summarized as follows: Three immunoreactive components were observed on Sephadex chromatography corresponding to molecular weight above 100 000 (big-big GH), 40 000-60 000 (big GH) and 20 000-22 000 (little GH). Bromocriptine treatment induced preferentially a reduction of little GH. There was a very good correlation between the decrease of little GH and total GH, and both were significantly correlated with the clinical response. The correlation between the decrease of Sm-C values and that of little and total GH as well as between the decrease of Sm-C and the clinical response was poor. It is concluded that a) measurement of little GH is not superior to the determination of total GH in the assessment of disease activity of bromocriptine treated acromegalic patients; b) both methods are superior to the measurement of plasma Sm-C levels; c) clinical response out of proportion ot the fall of total GH which can be explained by a preferential reduction of little GH, has not been observed in our investigations.

Acromegaly↗
PubMed1984

Plasma growth hormone suppressive effect of bromocriptine in acromegaly. Evaluation by plasma GH day profiles and plasma GH concentrations during oral glucose tolerance tests.

In most studies reporting favourable results of chronic bromocriptine treatment in acromegaly, plasma GH levels are measured at fixed intervals during the day. Negative results are reported in one major study measuring plasma GH levels during oral glucose tolerance tests (Lindholm et al., 1981). This study does not mention the time interval between the last dose of bromocriptine and the performance of an OGTT, but due to the short duration of action of bromocriptine this may be critical. Therefore, in the present report the plasma GH suppressive effect of bromocriptine in acromegaly is studied using plasma GH day-profiles as well as OGTT's during continued bromocriptine administration and OGTT's at two different time intervals after the last dose of bromocriptine. Twelve patients with clinically active acromegaly were treated with 10-20 mg bromocriptine for 6-9 months. After 6-9 months during continued bromocriptine administration the plasma GH suppressive effect of bromocriptine was evaluated by the mean of four plasma GH determinations during the day and by the mean of seven plasma determinations during oral glucose tolerance tests (OGTT's) performed 1 h, 10 h and 34 h after the last dose. The percentage decrease of the mean plasma GH level during the day induced by chronic bromocriptine treatment showed a good correlation (r = 0.86, P less than 0.001) with the percentage decrease of the mean plasma GH level during OGTT, if the post-treatment test was carried out one hour after the last dose of bromocriptine.(ABSTRACT TRUNCATED AT 250 WORDS)

Acromegaly↗
PubMed1984

Changes in plasma GH levels and clinical activity during bromocriptine therapy in acromegaly. The value of predictive tests.

Twenty-seven patients with active acromegaly despite previous treatment by surgery and/or radiotherapy received bromocriptine in a dose of 10-20 mg daily for a period of 6-9 months. The results of chronic bromocriptine treatment were evaluated by measurement of plasma growth hormone (GH) levels during the day and by subjective and objective criteria of clinical activity. The results of chronic bromocriptine treatment were also compared with four biochemical criteria obtained before treatment e.g. basal plasma prolactin (Prl) levels and the plasma GH response to oral administration of 2.5 mg bromocriptine respectively iv administration of 200 micrograms TRH and 500 micrograms somatostatin. The main observations may be summarized as follows: 1) The mean pre-treatment GH levels during the day ranged from 6-207 mU/1. Hyperprolactinaemia was present in 6 patients. 2) During bromocriptine treatment mean plasma GH levels decreased to less than 50% in 11 patients (GH responders) whereas in 19 patients changes of mean plasma GH and of subjective criteria of clinical activity were concordant. 3) Glucose tolerance improved significantly (P less than 0.01) in 10 GH-responders and the urinary hydroxyproline/creatinine ratio decreased significantly (P less than 0.05) in 8 GH-responders. 4) Five out of 6 patients with hyperprolactinaemia belonged to the group of GH-responders. 5) A single dose of 2.5 mg bromocriptine induced a more than 50% decrease of plasma GH in 8 of 11 GH-responders and in 5 of 16 GH non-responders.(ABSTRACT TRUNCATED AT 250 WORDS)

Acromegaly↗
PubMed1984

Successful treatment with sodium valproate of a patient with Cushing's disease and gross enlargement of the pituitary.

Transfrontal hypophysectomy was performed in a patient with Cushing's disease and gross enlargement of the pituitary. Despite some reduction of cortisol production active Cushing's syndrome remained due to the presence of a tumour remnant. Medical treatment with the GABA-transaminase inhibitor sodium valproate induced hypocorticism necessitating corticosteroid substitution therapy. Nine months after sodium valproate withdrawal hypercorticism was documented. Re-institution of sodium valproate treatment induced hypocorticism again. As sodium valproate is known to induce a decrease of plasma ACTH in Nelson's syndrome, it is proposed that large tumours present at the time of diagnosis and those appearing after adrenalectomy may represent the spectrum of a single disorder. A prospective trial to study the effects of sodium valproate and other neurotransmitter modulating agents on the size and endocrine function of ACTH secreting macroadenomas is urgently needed.

17-Hydroxycorticosteroids↗
PubMed1984

Results of cyproheptadine treatment in dogs with pituitary-dependent hyperadrenocorticism.

Administration of cyproheptadine for 2 months to five dogs with pituitary-dependent hyperadrenocorticism (PDH) at a dose rate of 0.3 mg/kg per 24 h (group 1) and to four dogs with PDH at a dose rate of 1 mg/kg per 24 h (group 2) did not result in any clinical improvement. The hyperadrenocorticoid state, as indicated by the circulating cortisol levels, the urinary corticosteroid excretion and the response of the hypothalamo-pituitary-adrenal axis to lysine-vasopressin, thyrotrophin releasing hormone and dexamethasone did not change consistently, although there was a tendency to normalization of some parameters in the dogs of group 2. However, these changes were not found to be consistent for each individual dog but were limited to one parameter per dog. It is concluded that cyproheptadine is not suitable for the treatment of PDH in the dog.

Adrenal Cortex Hormones↗
PubMed1983

No acute effect of pimozide on the plasma GH levels in acromegaly.

In 34 acromegalic patients either untreated or inadequately treated by surgery and/or radiotherapy the plasma GH levels and plasma Prl levels were determined during 8 h after the acute administration of the dopamine agonist bromocriptine and during 150 min after the administration of the dopamine antagonist pimozide. A 50% or more suppression of the basal GH levels was arbitrarily defined as a positive response. Seventeen patients displayed a positive response to bromocriptine, 17 patients displayed a negative response to bromocriptine. Plasma Prl levels were elevated in 6 of 17 bromocriptine responders and in 2 of 17 bromocriptine nonresponders. There was no difference in the plasma GH response to pimozide administration in the patients with a positive or a negative GH response to bromocriptine. With one exception there was in no patient a positive GH response to pimozide. In further experiments the plasma GH response to pimozide was measured during 11 h in 6 bromocriptine sensitive and 6 bromocriptine insensitive patients. Again no difference was found between bromocriptine responders and non-responders. There was also no difference in the Prl response to bromocriptine or pimozide between GH responders and GH non-responders. The Prl response to pimozide was blunted in comparison to a control group. The present study does not not lend support to the idea that there is a fundamental difference in the degree of hypothalamic dopaminergic control of GH or Prl secretion between bromocriptine sensitive and bromocriptine insensitive patients with acromegaly.

Acromegaly↗
PubMed1983

Changes in bone metabolism during treatment of acromegaly.

Bone metabolism was studied in 17 acromegalic patients, who responded to either medical treatment with bromocriptine (12 patients), or to transsphenoidal surgery (5 patients). Parameters of bone turnover decreased, e.g. serum acid phosphatase (9.2 +/- 0.7 vs 8.1 +/- 0.6 U/l, P less than 0.05) and the ratio of hydroxyproline/creatinine (33.6 +/- 4.4 vs 18.3 +/- 2.0, P less than 0.01) in the urine. No changes were observed in parathyroid function or concentrations of calcitonin. Serum 1,25-dihydroxycholecalciferol decreased (32.6 +/- 3.6 vs 20.6 +/- 1.8 ng/l, P less than 0.01) and 24,25-dihydroxycholecalciferol increased (4.3 +/- 0.6 vs 6.7 +/- 1.0 micrograms/l, P less than 0.05). No correlation between the percentual changes in serum growth hormone levels and 1,25-dihydroxycholecalciferol was found, suggesting an indirect effect of growth hormone on the renal 25-hydroxycholecalciferol-1-alpha-hydroxylase. The possible mechanisms involved are discussed, including the effects of growth hormone and somatomedin on bone.

25-Hydroxyvitamin D3 1-alpha-Hydroxylase↗
PubMed1983

Sodium valproate and cyproheptadine may independently induce a remission in the same patient with Cushing's disease.

A patient with Cushing's disease was unsuccessfully treated by pituitary surgery and external pituitary irradiation. One year later sodium valproate treatment induced a remission and finally hypocorticism developed. After drug withdrawal hypercoticism recurred. Treatment with cyproheptadine again induced hypocorticism necessitating corticosteroid substitution therapy. Biochemical characteristics of this patient included responsiveness to bromocriptine and cyproheptadine in acute tests. The study demonstrates that sodium valproate and cyproheptadine may both be effective independently in the treatment of the same patient with Cushing's disease. It is proposed that the disease is due to an ACTH producing tumour of pituitary intermediate lobe origin.

Adrenocorticotropic Hormone↗
PubMed1983

Urinary corticoids in the diagnosis of canine hyperadrenocorticism.

In 20 healthy experimental dogs the 24 hour urinary corticoid excretion as measured by cortisol radioimmunoassay on two consecutive days varied from 0.5 to 3.3 nmol/kg/24 hours and from 0.3 to 3.6 nmol/kg/24 hours. In 20 dogs with otherwise proven spontaneous hyperadrenocorticism these values varied from 4.4 to 35.7 nmol/kg/24 hours and from 3.6 to 26.8 nmol/kg/24 hours respectively. Corticoid/creatinine ratios in morning urine samples of 28 healthy pet dogs were 1.2 to 6.9 X 10(-6). In 27 dogs with spontaneous hyperadrenocorticism all ratios exceeded the range observed in the healthy pet dogs.

Animals↗
PubMed1982

Plasma cortisol response to thyrotrophin releasing hormone and luteinizing hormone releasing hormone in healthy kennel dogs and in dogs with pituitary-dependent hyperadrenocorticism.

The change in the plasma concentration of cortisol after the administration of thyrotrophin releasing hormone (TRH) and LH releasing hormone (LH-RH) was studied in normal dogs and in dogs with pituitary-dependent hyperadrenocorticism (PDH). The normal dogs showed a small but significant increase in the plasma concentration of cortisol 15 min after intravenous injection of TRH and LH-RH. In ten of the dogs with PDH the response to TRH was not significantly different from that in the normal dogs, but in 13 the response was significantly greater. In 15 of the dogs with PDH the response to LH-RH administration was within or below the range of responses in the normal dogs and in only one dogs was the response to LH-RH greater than that in the normal dogs. These findings are discussed in relation to the pathogenesis of PDH.

Adrenal Cortex↗
PubMed1981

Hypothalamic catecholamine levels in dogs with spontaneous hyperadrenocorticism.

Hypothalamic norepinephrine (NE) and dopamine content was studied in dogs with spontaneous and iatrogenic hypercortisolism and in untreated normal dogs. The concentration of NE in the hypothalamus was subnormal in 4 of 8 dogs with pituitary-dependent hyperadrenocorticism (PDH), whereas long-term administration of corticotropin or cortisone acetate did not result in low hypothalamic NE content. In dogs with hyperadrenocorticism due to adrenocortical tumor subnormal as well as normal and high hypothalamic NE levels were found. Hypothalamic as well as striatal dopamine content did not differ among groups of dogs with PDH, adrenocortical tumor, corticotropin treatment, cortisone treatment and in untreated normal dogs. The subnormal hypothalamic NE levels in dogs with PDH may be involved in the hypersecretion of ACTH found in this disease. The normal hypothalamic dopamine levels in dogs with PDH are not consistent with a dopaminergic-depletion as the cause of PDH.

Adrenal Gland Neoplasms↗
PubMed1979

Adrenocortical function tests in dogs with hyperfunctioning adrenocortical tumours.

The response has been studied in nine dogs with hyperadrenocorticism due to adrenocortical tumours to the administration of dexamethasone, insulin, lysine-vasopressin and tetracosactide by measuring the changes in plasma cortisol concentration. Administration of dexamethasone did not produce a decrease in the plasma concentration of cortisol in any of these dogs. Administration of insulin caused slight increases in the plasma concentration of cortisol in four out of eight dogs. Lysine-vasopressin increased the plasma concentration of cortisol in eight out of nine dogs, three responded supranomally. Eight out of the nine dogs responded to tetracosactide administration, three responded supranormally, It is concluded that in the dog, in contrast to man, the lysine-vasopressin test cannot be used to differentiate between pituitary-dependent hyperadrenocorticism and hyperadrenocorticism due to an adenocortical tumour. Apparently pituitary ACTH is not completely depleted in dogs with hyperfunctioning adrenocortical tumours.

Adrenal Cortex Function Tests↗
PubMed1978

Biochemical characterization of pituitary-dependent hyperadrenocorticism in the dog.

The biochemical characterization of 22 cases of pituitary-dependent hyperadrenocorticism in the dog, is reported. The principal characteristics of the disease include excessive and non-rhythmic production of cortisol, decreased sensitivity of the hypothalamic-pituitary system to the suppressive effects of dexamethasone, decreased responsiveness of the pituitary-adrenocortical system to the stimulus of insulin-induced hypoglycaemia and increased responsiveness of the system to stimulation with lysine-vasopressin. From these observations it is concluded that pituitary-dependent hyperadrenocorticism in the dog is a valid model for study of the pathogenesis of the disease in man. For the diagnosis of hyperadrenocorticism itself, the measurement of the concentration of corticosteroids in a single sample of plasma obtained 8 h after intravenous injection of 0.01 mg dexamethasone/kg was sufficient. The level of 11-hydroxycorticosteroids was less than 140 nmol/1 plasma in normal dogs, whereas higher values were found in dogs with hyperadrenocorticism. For purposes of differential diagnosis, measurement of the level of corticosteroids in the plasma both before and 4 h after intravenous injection of 0.05 mg dexamethasone/kg is adequage: suppression is obtained only in cases of pituitary-dependent hyperadrenocorticism.

11-Hydroxycorticosteroids↗
PubMed1978

Hypothalamic corticotrophin releasing factor activity in dogs with pituitary-dependent hyperadrenocorticism.

Hypothalamic corticotrophin releasing factor (CRF) activity was determined in five dogs with spontaneous hyperadrenocorticism and in three control animals (one untreated, one treated with high doses of ACTH for 2 months and one treated with high doses of cortisone for 2 months). Hypothalamic CRF activity was low or undetectable in four dogs with Cushing's syndrome due to an adrenocortical tumour. The results are compatible with a pituitary origin for pituitary-dependent hyperadrenocorticism in the dog but are not conclusive; direct information about the rates of hypothalamic CRF secretion is required.

Adrenocortical Hyperfunction↗