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Biomedical subjects

R J Croughs

Publications and source records attributed to R J Croughs.

At least 37 records · Page 2Linked to original sources
PubMed1989

Familial Cushing's syndrome due to nodular adrenocortical dysplasia is an inherited disease of immunological origin.

Circulating immunoglobulins may be involved in the pathogenesis of familial Cushing's syndrome due to nodular adrenocortical dysplasia. The disease may also be part of a complex including cutaneous and cardiac myxomas, spotty pigmentation of the skin, and other signs of endocrine overactivity. In the present study of two sisters treated by complete adrenalectomy for Cushing's syndrome due to nodular adrenocortical dysplasia, and of their first-degree relatives, no evidence of associated disorders was present. However, the serum of both girls and of their mother contained immunoglobulins capable of stimulating adrenal DNA synthesis and cortisol production in vitro. The study supports the theory that familial Cushing's syndrome due to adrenocortical dysplasia is an inherited disease of immunological origin.

Adrenal Cortex↗
PubMed1989

Bromocriptine-responsive Cushing's disease associated with anterior pituitary corticotroph hyperplasia or normal pituitary gland.

Cushing's disease may originate from either the anterior pituitary lobe or the neurointermediate lobe, a major characteristic of the latter group being bromocriptine responsiveness. This study of two patients with Cushing's disease demonstrates that bromocriptine responsiveness also may be associated with anterior pituitary corticotroph hyperplasia or a normal pituitary gland. The two patients were a 14-yr-old boy (patient 1) and a 29-yr-old woman (patient 2); their cortisol production rates were 121 and 234 mumol/24 h (normal values, less than 80 mumol/24 h), respectively. A single oral dose of 2.5 mg bromocriptine resulted in a gradual decrease in plasma cortisol from 680 to 130 nmol/L after 6 h in patient 1 and from 640 to 170 nmol/L after 4 h in patient 2. Both patients then received medical treatment for a period of 2 yr. Whereas sodium valproate was ineffective, bromocriptine (5 mg/day) abruptly decreased the cortisol production rate to 60 mumol/24 h in patient 1 and to 138 mumol/24 h in patient 2, and both patients had a partial clinical remission. Despite an increase in bromocriptine dosage to 30 mg daily and 24 mg/day cyproheptadine, the clinical and biochemical remission was not sustained in patient 1, and no further improvement occurred in patient 2. Total hypophysectomy then was performed in both patients. Sections of the pituitary from patient 1 showed diffuse anterior pituitary corticotroph hyperplasia, with early nodule formation in some areas. The sections from patient 2 showed normal numbers and distribution of corticotrophs. We conclude that the heterogeneous nature of Cushing's disease cannot be explained on the basis simply of anterior vs. intermediate lobe origin of the disease.

Adolescent↗
PubMed1989

Primary hypothyroidism mimicking pituitary adenoma.

The case history is presented of a woman with secondary amenorrhoea, mild hyperprolactinaemia and pituitary enlargement with suprasellar extension, mimicking a pituitary adenoma. It appeared that she had primary hypothyroidism. After L-thyroxine treatment, all abnormalities disappeared. The literature on the combination of primary hypothyroidism, hyperprolactinaemia and pituitary enlargement is reviewed and the pathophysiology is discussed. It is concluded that determination of thyrotropin is essential in all patients with pituitary enlargement and hyperprolactinaemia.

Adenoma↗
PubMed1988

Transsphenoidal microsurgery as primary treatment in 25 acromegalic patients: results and follow-up.

Twenty-five patients with acromegaly were treated by transsphenoidal microsurgery. Fourteen patients (56%) were considered cured according to the following criteria: a. basal plasma GH less than 10 mU/l; b. glucose suppressed plasma GH less than or equal to 4 mU/l, and c. disappearance of TRH responsiveness if present preoperatively. Thirteen of the cured patients were re-evaluated after a mean follow-up period of 3.5 years (range 1.5 to 5.5 years). At that time, basal plasma GH was still less than 10 mU/l and glucose suppressed plasma GH was still less than or equal to 4 mU/l in all patients, indicating the practical value of our criteria. The remaining 11 patients (44%) received additional treatment by external pituitary irradiation and bromocriptine. Owing to surgery, 5 patients (20%) developed partial or panhypopituitarism.

Acromegaly↗
PubMed1988

Response of luteinizing hormone secreting pituitary adenoma to a long-acting somatostatin analogue.

A large pituitary tumour was discovered in a 20 year old man who came to medical attention because of grand-mal seizures. The tumour produced biologically active LH as demonstrated by supranormal plasma LH and plasma testosterone values. Free alpha-subunit values were also elevated. In contrast, plasma FSH was in the lower normal range. Transsphenoidal operation failed to remove all tumour tissue. Detailed studies were carried out in the postoperative period. TRH and GnRH administration were associated with a rise of plasma LH and alpha-subunit, whereas plasma FSH was low and unresponsive. Bromocriptine treatment was ineffective. In contrast, both during and after treatment with SMS 201-995 for 6 weeks, a decrease of basal plasma LH values was observed. Furthermore, the administration of a single dose of SMS 201-995 reproducibly induced a decrease of plasma LH lasting for a period of about 6 h. The study suggests that SMS 201-995 may be useful in the treatment of patients with gonadotrope cell adenomas.

Adenoma↗
PubMed1988

Primary treatment of macroprolactinomas with Parlodel LAR.

Five patients, 3 women and 2 men, with macroprolactinomas characterized by extrasellar extension and basal plasma prolactin levels ranging from 4.6 to 102 U/l received six monthly injections of 50-100 mg Parlodel LAR, an injectable long-acting repeatable form of bromocriptine. The following observations were made: 1. Plasma prolactin levels fell dramatically in all patients and values in the normal range were obtained in 3 patients. 2. In all patients, the onset of tumour reduction was visible on CT scans made one week after the first Parlodel LAR injection. After six Parlodel LAR injections, tumour size was reduced by more than 75% in 3 patients and by 50-75% in two patients. 3. Diminished visual acuity (one patient), bitemporal hemianopia (2 patients), and oculomotor and trochlear nerve dysfunction (one patient) were restored to normal after the first Parlodel LAR injection. 4. Hypogonadism normalized in 2 patients and improved in one patient, whereas plasma gonadotropins remained low in the 2 postmenopausal women. In one patient with hypothyroidism and hypocorticism, thyroid and adrenal functions normalized. It is concluded that bromocriptine retard (50-100 mg monthly) is a useful alternative for oral treatment of patients with prolactinomas, especially in those patients with compliance problems on oral bromocriptine therapy.

Adenoma↗
PubMed1988

Effects of bromocriptine on corticotrophin, melanotrophin and corticosteroid secretion in dogs with pituitary-dependent hyperadrenocorticism.

Dogs with spontaneous pituitary-dependent hyperadrenocorticism were divided into two groups, one with normal plasma concentrations of alpha-MSH (normal alpha-MSH dogs, n = 26) and the other with high plasma concentrations of alpha-MSH (high alpha-MSH dogs, n = 14), on the presumption that high alpha-MSH concentrations indicated a parent cell of pars intermedia origin. The urinary corticoid/creatinine ratios of the high alpha-MSH dogs were significantly higher than those of the normal alpha-MSH dogs. The percentage decrease of the corticoid/creatinine ratios following dexamethasone administration was significantly higher in the normal alpha-MSH dogs than in the high alpha-MSH dogs. Dexamethasone resistance occurred in both the normal alpha-MSH dogs (4 out of 26) and the high alpha-MSH dogs (7 out of 14), indicating a relative rather than an absolute difference. The short-term effect of orally administered bromocriptine, at a dose (10 micrograms/kg body weight) known to be effective in lowering prolactin concentrations in dogs, was investigated by measuring concentrations of cortisol, ACTH and alpha-MSH in plasma at 4, 6 and 8 h after administration. Significant decreases were observed for cortisol in both groups and for alpha-MSH only in the high alpha-MSH dogs. The effect of 5 days of bromocriptine administration (10 micrograms at 12-h intervals) was assessed by measurements of urinary corticoid/creatinine ratios. Considering both groups as a whole, only the corticoid/creatinine ratios of the high alpha-MSH dogs decreased significantly on the first day of treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal Cortex Hormones↗
PubMed1987

Organization of ovine corticotropin-releasing factor immunoreactive neurons in the canine hypothalamo-pituitary system.

The distribution of corticotropin-releasing factor immunoreactive (CRF-i) cell bodies and varicose fibers in the hypothalamus and the pituitary of the canine brain was studied by indirect immunofluorescence. CRF-i cell bodies were demonstrated mainly in the periventricular zone of the third ventricle, while some CRF-i cell bodies were scattered throughout the ventral part of the caudomedial hypothalamus. CRF-positive fibers were mostly situated in the median eminence. In addition some CRF-positive fibers were detected in the ventromedial aspect of the lateral hypothalamus forming a pathway arising from the CRF-i cell bodies, running via the median eminence through the infundibular stalk and terminating in the pars nervosa of the pituitary. The localization of the cell bodies and their projection points towards a possible (patho)physiological role of this peptide-transmitter system in the release of ACTH and beta-endorphin.

Animals↗
PubMed1987

Some functional aspects of canine corticotrophs.

To examine the regulation and functional significance of canine pituitary pars intermedia corticotrophs, ACTH and cortisol responses to CRF were studied in healthy dogs before and after treatment with dexamethasone. In addition the effects of the dopamine agonist bromocriptine and the dopamine antagonist pimozide were investigated. In the latter two instances prolactin concentrations were also measured. Finally the pituitaries were studied immunocytochemically for ACTH and alpha-MSH. No response of ACTH or cortisol to bromocriptine was observed. Pimozide caused a slight rise in ACTH levels in some dogs. However, prolactin levels significantly decreased with bromocriptine and increased with pimozide. Injection of synthetic ovine CRF to dogs was followed by sharp increases in ACTH and cortisol values. These responses were obliterated by prior treatment with dexamethasone. In 1 of 4 dogs given dexamethasone before euthanasia, there were few pars distalis cells with ACTH(1-24) immunopositivity, although persistence of ACTH(1-24) reaction was noted within cells of the pars intermedia. The results indicate that none of the CRF-induced ACTH secretion in dogs is derived from pars intermedia corticotrophs. Dosages of bromocriptine and pimozide that clearly alter prolactin secretion do not consistently affect ACTH levels.

Adrenocorticotropic Hormone↗
PubMed1986

Regulation of prolactin secretion in canine pituitary-dependent hyperadrenocorticism.

In 15 dogs with pituitary-dependent hyperadrenocorticism (PDH) the basal prolactin concentrations (means of 6 determinations; range 2.8-24.7 micrograms/l) were significantly higher than those of 23 healthy control dogs (0.9-10.5 micrograms/l). In five dogs with hyperadrenocorticism due to adrenocortical tumour (ATH) the prolactin concentrations were also significantly elevated, but still significantly lower than the values of the dogs with PDH. The prolactin concentrations of the dogs with PDH responded supranormally to TRH-stimulation, whereas in the dogs with ATH the response was not significantly different from the results in the control dogs. Following bromocriptine administration the plasma prolactin concentrations of the dogs with PDH decreased considerably but remained higher than the values obtained in the control dogs and the dogs with ATH. It is concluded that PDH in the dog is associated with a disturbance in the regulation of prolactin secretion, that is not secondary to hypercortisolism per se.

Adrenal Cortex Diseases↗
PubMed1986

Familial Cushing's syndrome due to nodular adrenocortical dysplasia. A putative receptor-antibody disease?

Two sisters aged 13 and 19 years suffering from familial Cushing's syndrome due to nodular adrenocortical dysplasia are described. Pituitary adrenocortical function tests indicated the presence of adrenal autonomy. Adrenal scintigraphy showed bilateral symmetrical uptake indicating the bilateral character of the autonomous process. Complete adrenalectomy was performed in both girls. The adrenals were of about normal weight showing numerous dark brown pigmented nodules and small perivascular lymphocytic infiltrates. Serum immunoglobulin preparations obtained from both girls stimulated adrenocortical cell growth in a cytochemical bioassay system. It is proposed that circulating growth factors may be involved in the pathogenesis of the disease.

Adolescent↗
PubMed1986

Response to neurotransmitter modulating drugs in patients with Cushing's disease.

We designed a systematic study of patients with Cushing's disease to compare the results of acute experiments with cyproheptadine, sodium valproate and bromocriptine with the results of chronic treatment with sodium valproate. In 13 patients the plasma cortisol response to single doses of 2.5 mg bromocriptine, 6 mg cyproheptadine and 300 mg sodium valproate was assessed over 4-8 h. All patients were then treated with sodium valproate 200 mg three times a day for a period of 3 months. Subjects were classified as responders when there was a reduction in plasma cortisol by at least 50% below the basal level in two consecutive plasma samples during one of these tests, and/or clinical remission and normalization of cortisol production rate during sodium valproate treatment. Four patients responded significantly to at least one of the agents (group I) and 9 did not (group II). In group I three patients were bromocriptine responsive and one of these responded also to cyproheptadine; in this patient both sodium valproate and cyproheptadine were able to induce a remission during chronic treatment. In the one patient of the responder group who was bromocriptine insensitive, sodium valproate treatment also induced a remission. In two patients of the responder group sodium valproate treatment was ineffective. However, in both patients chronic treatment with bromocriptine induced a marked clinical improvement associated with a decrease of cortisol production rate. There was no difference between the groups in sex, age, clinical presentation, duration or severity of hypercortisolism. In one patient in group I a macroadenoma with suprasellar extension was present, while a microadenoma was detected in four patients in group II.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1986

No effect of treatment with sodium valproate on plasma growth hormone in bromocriptine unresponsive acromegaly.

Administration of sodium valproate for 6 months at a dose of 300 mg three times daily to 7 bromocriptine unresponsive acromegalic patients who all but one had been treated with pituitary surgery and/or radiotherapy in the past did not result in a significant reduction of the plasma growth hormone (GH) level or in any clinical improvement. It is concluded that sodium valproate is not suitable for the treatment of acromegalic patients who do not show a favourable response to bromocriptine.

Acromegaly↗
PubMed1986

Bromocriptine treatment of prolactin secreting macroadenomas: a radiological, ophthalmological and endocrinological study.

Twelve patients, six women and six men, with macroprolactinomas characterized by extrasellar extension and basal plasma prolactin levels greater than 6 U/l were treated with 10-20 mg bromocriptine daily in four divided doses for a mean period of 2.4 years (range 0.5-3.5 years). The following observations were made: Plasma prolactin levels fell dramatically in all patients and values in the low normal range were obtained in 10 patients. Tumour size was reduced by more than 75% in 11 patients and by 50-75% in one patient. Tumour-reduction was associated with the development of a partial empty sella in eight cases. In four cases the pituitary became visible. Diminished visual acuity (three patients), bitemporal hemianopia (three patients), unilateral or bilateral central scotomas (three patients) and oculomotor palsy (two patients) restored to normal. Hypogonadism (all patients), hypothyroidism (six patients) and hypocorticism (three patients) improved or normalized in most cases. It is concluded that in the medical treatment of macroprolactinomas 10-20 mg bromocriptine in four divided doses effectively reduces both plasma prolactin level and tumour size.

Adenoma↗
PubMed1986

Characterization of alpha-MSH-like immunoreactivity in human plasma.

We report new information on the presence of alpha-melanotropin(alpha-MSH)-like immunoreactivity in the peripheral circulation of the adult human. Pooled blood from 20 patients with non-endocrine diseases was subjected to a Sep-pak pre-purification followed by a high pressure liquid chromatographic (HPLC) fractionation. The eluate from the HPLC column was analyzed by a radioimmunoassay (RIA) specific for the C-terminal part of the alpha-MSH molecule. From this it appeared that alpha-MSH was the major alpha-MSH-like immunoreactive peptide present in human blood with a level of 2-5 pg/ml. This level is similar to the one determined by direct measurements in Sep-pak pre-purified human plasma (median 2.0 pg/ml, n = 11). Des-acetyl alpha-MSH was present in human blood in only a minor quantity. We discuss this finding in view of earlier reports on alpha-MSH-like immunoreactivity in human pituitary tissue.

Adrenocorticotropic Hormone↗