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Biomedical subjects

C G Beardwell

Publications and source records attributed to C G Beardwell.

At least 19 recordsLinked to original sources
PubMed1991

The effect of external pituitary irradiation on elevated serum prolactin levels in patients with pituitary macroadenomas.

The response of serum prolactin to external radiotherapy was studied in 58 patients (32 women) with pituitary tumours, aged between 16 and 75 years. Forty-four patients underwent pituitary surgery before radiotherapy. Six patients were irradiated with a regimen of 20 Gy in eight fractions over 10-11 days and the remainder received 35-42.5 Gy in 15 fractions over 20-22 days. Following radiotherapy, 44 patients received additional treatment with dopaminergic agonists. Prolactin levels ranged from 1078 to 491,000 mU/l (median 11,750 mU/l) before radiotherapy and all but three patients showed a fall in serum prolactin (measured 4 weeks after stopping bromocriptine in those on dopamine agonist therapy) during observation over periods of up to 154 months. All patients had evidence of pituitary fossa erosion or expansion at presentation and large tumours (Hardy-Vezina Grade 3-4) were more common in male patients (chi 2 = 10.08, p less than 0.01). The rate of fall of serum prolactin levels was greater in patients with true prolactin-secreting tumours when compared with those who had stalk or hypothalamic damage (p less than 0.005). The rate of decline of serum prolactin was also significantly related to the pre-radiotherapy value (rho = 0.519, p less than 0.01). A serum prolactin level less than 500 mU/l was achieved in 31 out of 44 patients treated with radiotherapy and dopaminergic agonist but only nine remained normoprolactinaemic when medication was discontinued for 4 weeks or more. The serum prolactin level fell permanently to less than 500 mU/l in two of 14 patients treated with radiotherapy only. Actuarial analysis of data from all patients indicated a 50 per cent probability that prolactin would be reduced to less than 500 mU/l by 10 years; this increased to 58 per cent for patients with smaller tumours (Hardy-Vezina grade 2).(ABSTRACT TRUNCATED AT 250 WORDS)

Adenoma↗
PubMed1990

Radiation and hypothalamic-pituitary function.

In adults, hypopituitarism is a common consequence of external radiotherapy. The clinical manifestations may be subtle and develop insidiously many years after radiotherapy. Anterior pituitary deficiencies can therefore only be detected by regular testing, including dynamic tests of GH and ACTH reserve. Although the deficiencies most commonly develop in the order GH, gonadotrophins, ACTH then TSH, this sequence may not be predictable in an individual patient and comprehensive testing is therefore required. The tests should ideally be performed annually for at least 10 years after treatment or until deficiency has been detected and treated. It is not only the patients with pituitary disease who are at risk of developing hypopituitarism after radiotherapy. Any patient who receives a total dose of irradiation of 20 Gy or more to the hypothalamic-pituitary axis is at risk of hypopituitarism, although the threshold dose may be lower than this. This is particularly important in the long-term survivors of malignant disease in whom endocrine morbidity may be relatively common and in whom this can be easily treated, with consequent improvement in quality of life. Whilst patients who receive a high total dose of irradiation are at increased risk of developing multiple deficiencies, a higher fraction size also increases the risk of anterior pituitary failure. There is good evidence that the earliest damage to the hypothalamic-pituitary axis after external radiotherapy is at the level of the hypothalamus. However, patients who undergo pituitary ablation with interstitial radiotherapy or heavy particle beams are likely to sustain direct damage to the pituitary. In these patients, the sequence in which individual pituitary hormone deficiencies develop is generally the same as that observed with the hypothalamic damage after conventional external radiotherapy. The increasing use of radiotherapy as a means of treatment for malignant disease means that new groups of patients with potential for endocrine dysfunction are emerging. Whole body irradiation in the preparation for bone marrow transplant is one such treatment and although hypothalamic-pituitary damage appears to be confined to GH deficiency in children, longitudinal experience is limited to date, particularly in adults. The treatment of malignant disease in childhood is of particular importance in terms of the delayed endocrine sequelae. The hypothalamic-pituitary axis may not be the only endocrine tissue damaged by treatment in these patients and management is therefore more complicated. In the growing child, the potential association of growth hormone deficiency, gonadal failure or premature puberty and thyroid dysfunction mean that expert endocrine supervision is essential for optimum long-term outcome.

Dose-Response Relationship, Radiation↗
PubMed1990

Low-dose pituitary irradiation for acromegaly.

External radiotherapy has been used as primary treatment for acromegaly in 29 patients and in combination with surgery in 41 patients in whom growth hormone levels remained elevated postoperatively. Fourteen further patients who did not receive radiotherapy have also been studied, four of whom had undergone surgical treatment. Radiotherapy schedules consisted of 20 Gy in eight fractions over 11 days (n = 23) or 35-40 Gy in 15 fractions over 21 days (n = 47). Growth hormone hypersecretion was either unchanged or increased with time in non-irradiated patients. In those patients who underwent radiotherapy, the likelihood of the mean GH level during GTT falling to less than 5 mU/l was unaffected by the total dose of radiation administered. However, patients with a pre-radiotherapy GH level of less than 30 mU/l showed a significantly increased probability of achieving a post- radiotherapy GH level less than 5 mU/l (P = 0.002). Previous surgery, initial serum prolactin and the age or sex of the patient did not predict the successful outcome of radiotherapy. In view of the known dose dependency of radiation-induced hypopituitarism, lower radiation dose schedules (20 Gy; eight fractions in 11 days) can be used in acromegaly with some benefit, especially in younger patients. However, all patients should undergo operative removal of as much GH-secreting tissue as possible, in order to lower GH levels and increase the probability of achieving a cure following radiotherapy.

Acromegaly↗
PubMed1990

Long-term follow-up of low-dose external pituitary irradiation for Cushing's disease.

Twenty-four patients (three male) with Cushing's disease, aged between 11 and 67 years, were treated with low-dose external pituitary irradiation (20 Gy in eight fractions over 10-12 days) and followed for between 13 and 171 months (median 93 months). Eleven patients (46%) went into remission 4-36 months after irradiation, but five subsequently relapsed. Two of these received no further active treatment, one underwent successful pituitary surgery, one underwent a second course of low-dose external irradiation (as yet unsuccessful) and one has been treated with metyrapone for a total of 75 months. One of the 13 patients who did not respond received a further course of low-dose pituitary irradiation with prompt remission and two have received metyrapone for 41 months and 15 years without ill effect. One patient died from cerebrovascular disease. The remaining nine patients underwent bilateral adrenalectomy (one after unsuccessful pituitary surgery) with rapid resolution of hypercortisolism. Five of these patients have developed hyperpigmentation and elevated ACTH levels (range 505-1150 ng/l). A pituitary microadenoma has been demonstrated on CT scan in three and successfully removed by microadenomectomy. In the present series, the low incidence of radiation-induced hypopituitarism and absence of other complications attributable to radiotherapy suggest that low-dose pituitary irradiation may be a useful treatment option in selected patients. However, long-term follow-up has demonstrated a high relapse rate and failure to prevent Nelson's syndrome in adrenalectomized patients, indicating that it should not be used as primary treatment in preference to selective adenomectomy.

Adolescent↗
PubMed1979

Normal growth despite abnormalities of growth hormone secretion in children treated for acute leukemia.

We have studied the relationship between abnormalities of the growth hormone-somatomedin axis and growth in 26 children previously treated for acute lymphatic leukemia. Each child had previously received cranial irradiation, was in complete clinical and hematologic remission, and off all drugs. The mean standing height SDS of the 26 children was significantly less than normal. There was no significant difference between the mean standing height SDS, height velocity SDS, somatomedin activities, and degree of bone age retardation between the 17 children who received the higher dose of cranial irradiation (Group 1) and the nine who had the lower dose of cranial irradiation (Group II). Furthermore, there was no significant reduction in mean height velocity SDS, somatomedin activity, or bone age in either group when compared to normal age-matched controls. The peak GH responses to both insulin hypoglycemia and an arginine test were significantly lowered in Groups I and II when compared to a control group of children. We conclude that only a minority of children, who previously received cranial irradiation for ALL were clinically GH deficient and, therefore, likely to benefit from GH therapy despite the finding that the majority of these children had reduced GH responses to pharmacologic stimuli.

Age Determination by Skeleton↗
PubMed1979

Acromegaly due to production of a growth hormone releasing factor by a bronchial carcinoid tumor.

We have studied growth hormone production in a patient with a bronchial carcinoid and acromegaly. The absence of growth hormone from the carcinoid tumour was demonstrated by extraction, cell culture and immunoperosidase techniques. Using a linked perfusion culture system, effluent from the bronchial carcinoid tumour culture stimulated a rapid release of growth hormone from a rat pituitary monolayer. This is the first time evidence of growth hormone releasing activity by a bronchial carcinoid has been demonstrated in a production.

Acromegaly↗
PubMed1979

Radiation-induced hyperprolactinaemia in a treated acromegalic.

A 31-year-old acromegalic was normoprolactinaemic after partial removal of her pituitary tumour. The post-operative external pituitary irradiation lowered the mean growth hormone (GH) level from 75 mU/1 to less than 1 mU/1 within 2 years. However, at the same time hyperprolactinaemia developed. These changes in the GH and prolactin levels were confirmed 3 and 4 years after irradiation. The cause of the hyperprolactinaemia was radiation-induced hypothalamic damage. Therefore it is suggested that similar damage may occur in patients receiving external pituitary irradiation for 'prolactinomas' and that this mechanism may contribute to the persistent hyperprolactinaemia observed in such patients.

Acromegaly↗
PubMed1978

Testicular function following irradiation of the human prepubertal testis.

Testicular function was studied in ten men, aged between 17 and 36 years, who had received irradiation for a nephroblastoma during childhood. The dose of scattered irradiation to the testes ranged from 268 to 983 rad. Eight subjects had either oligo- or azoospermia (0 to 5.6 million/ml), seven of whom had an elevated serum follicle-stimulating hormone (FSH) level. One subject showed evidence of Leydig cell dysfunction with a raised serum luteinizing hormone level (LH) and a low plasma testosterone concentration. A second group of eight prepubertal males, aged between 8 and 14 years, were studied. These had also been irradiated for abdominal malignancies during childhood and received a similar dose of irradiation to the testis as the first group studied. The plasma testosterone levels were within the normal range for prepubertal boys in all eight. The mean gonadotrophin levels were not significantly different from the mean levels of normal prepubertal males. Thus irradiation-induced damage to the germinal epithelium in prepubertal boys produces raised FSH levels after puberty but not before it. We conclude, therefore, that inhibition has a minor role in the control of the prepubertal hypothalamic-pituitary testicular axis and its contribution to gonadal control of gonadotrophin secretion changes with sexual maturation.

Adolescent↗
PubMed1978

Growth impairment in children treated for brain tumours.

Growth and growth hormone (GH) secretion were studied in 14 children with brain tumours before radiation and chemotherapy and at various time intervals afterwards. The peak GH response to hypoglycaemia was normal in all patients before radiation. In 6 patients the peak GH response was impaired 1 year after radiation, and in a seventh it was normal at 1 year but impaired 2 years after radiation. In 12 of 13 patients the growth velocity during the first year of chemotherapy was below the 3rd centile, although none of these had an initial standing height below the 3rd centile. Thus it appears that poor growth in such children occurs irrespective of whether radiation-induced GH deficiency develops. The cause of this impaired growth is unknown.

Adolescent↗
PubMed1977

Acromegaly.

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Acromegaly↗