Hypothalamic-pituitary function was studied in 31 patients before and after cranial irradiation for nasopharyngeal carcinoma. The estimated radiotherapy (RT) doses to the hypothalamus and pituitary were 3979 +/- 78 (+/- SD) and 6167 +/- 122 centiGrays, respectively. All patients had normal pituitary function before RT. One year after RT, there was a significant decrease in the integrated serum GH response to insulin-induced hypoglycemia. In the male patients, basal serum FSH significantly increased, while basal serum LH and testosterone did not change. Moreover, in response to LHRH, the integrated FSH response was increased while that of LH was decreased. Such discordant changes in FSH and LH may be explained by a defect in LHRH pulsatile release involving predominantly a decrease in pulse frequency. The peak serum TSH response to TRH became delayed in 28 patients, suggesting a defect in TRH release. Twenty-one patients were reassessed 2 yr after RT. Their mean basal serum T4 and plasma cortisol levels had significantly decreased. Hyperprolactinemia associated with oligomenorrhoea was found in 3 women. Further impairment in the secretion of GH, FSH, LH, TSH, and ACTH had occurred, and 4 patients had hypopituitarism. Thus, progressive impairment in hypothalamic-pituitary function occurs after cranial irradiation and can be demonstrated as early as 1 yr after RT.
To explore further the relation between admission glucose concentration and outcome in stroke, we measured glucose, fructosamine, and glycosylated hemoglobin concentrations on admission in 216 patients seen within 24 hours after the onset of their first stroke. Fructosamine concentration reflects the degree of glycemia in the preceding 4-6 weeks and glycosylated hemoglobin concentration reflects that in the preceding 3 months. Based on clinical, computed tomographic, and necropsy findings, strokes were classified as cortical infarction, lacunar infarction, or intracerebral hemorrhage. Analyses were done including and excluding 47 diabetic patients. No correlation between neurologic outcome as mortality and fructosamine or glycosylated hemoglobin concentration was found. Survival showed a significant correlation with admission glucose concentration only for patients with intracerebral hemorrhage. Our results suggest that hyperglycemia is unlikely to worsen the outcome of acute stroke and that hyperglycemia probably represents either a latent diabetic state or a stress response. (Stroke
Eight patients, one male and seven females, with no pre-existing hypothalamic-pituitary disease, who developed symptoms of hypopituitarism following cranial irradiation for nasopharyngeal carcinoma were studied 5 years or more after radiotherapy. All were GH deficient. Four of the patients with no GH response during insulin tolerance tests (ITT) showed increased GH in response to synthetic human growth hormone releasing factor (GRF-44). Four patients had impaired cortisol responses to ITT, and gradual but diminished cortisol responses to ovine corticotrophin releasing factor (CRF-41). There was no significant difference between mean peak increments in response to ITT and those in response to CRF-41. TSH responses to TRH were delayed in five and absent in two patients; four of these had low free T4 index. Prolactin was raised in all seven women and increased further in response to TRH. Two patients had impaired gonadotrophin responses to LHRH. None of the patients had clinical or biochemical evidence of diabetes insipidus. These data suggest that post-irradiation hypopituitarism in these patients results from radiation damage to the hypothalamus leading to varying degrees of deficiency of the hypothalamic releasing or inhibitory factors.
Fifty-one patients with hyperprolactinaemia (23 with macroadenoma, 23 with microadenoma, and five with idiopathic hyperprolactinaemia) were treated with bromocriptine for 2-12 years (4.9 +/- 2.9 years, mean +/- SD). During therapy, the serum PRL levels were suppressed into the normal range in all but five patients. In these five patients, despite the high circulating PRL, gonadal function returned to normal in three, while in the other two gonadotrophin reserve was impaired even before therapy. Gel chromatography showed that one of these patients had a high proportion of a large molecular weight form of PRL. Twenty-four patients received bromocriptine as the sole method of treatment for over 2 years (3.4 +/- 2.3 years). In five out of the 24 subjects (21%), serum PRL remained normal with no clinical symptoms after prolonged drug withdrawal (1-4 years). Twenty-one patients received radiotherapy in conjunction with bromocriptine therapy. Of these 11 had prior surgery. After a follow-up of 6.0 +/- 3.0 years after radiotherapy, serum PRL remained within the normal range in 6 out of 21 subjects (29%), 1-4 years after bromocriptine withdrawal. One of the patients had impaired GH response to insulin hypoglycaemia developing after radiotherapy. We conclude that prolonged bromocriptine treatment is an effective treatment for prolactinomas.
Two adult patients with unilateral hypoplastic optic nerves, absent septa pellucida and hypopituitarism are described. Patient 1, aged 20, presented with diabetes insipidus due to partial vasopressin deficiency. Patients 2, aged 29, presented with focal epilepsy. Both had short stature. They showed absent growth hormone (GH) response to insulin-hypoglycaemia or glucagon, but responded to 100 \g=m\ggrowth hormone releasing factor (GRF-44) with a rise in circulating GH, suggesting a hypothalamic defect in GH release though a co-existing pituitary defect cannot be excluded. Other hypothalamic-pituitary functions were normal. These two patients probably represent the milder form of the clinical spectrum of septo-optic dysplasia which, with the extensive use of CT brain scans, will be increasingly encountered by physicians attending adult patients.
A 27 year old woman with histiocytosis X had an unusual initial presentation with features of primary hypothyroidism and a goitre. Diagnosis was made by lung and thyroid biopsies. Endocrine tests showed the presence of hypopituitarism and a discrete suprasellar mass, consistent with hypothalamic histiocytosis X, was demonstrated by computerised tomography. Radiotherapy and chemotherapy arrested the clinical progression of the disease.
Eighteen patients with non-insulin dependent diabetes mellitus (NIDDM), hypertension and nephropathy were randomized to receive captopril or enalapril for 6 months. Two patients with serum creatinine of greater than 400 mumol/l had to be excluded from the study because of rapidly deteriorating renal function after starting treatment. Of the remaining patients, 7 received captopril and 9 received enalapril. Blood pressure control was achieved in about 50% of patients with either drug alone. Serum creatinine and creatinine clearance were unchanged in both groups but there was a greater tendency for the former to increase in patients with higher pretreatment values. Proteinuria was reduced at 1 month only in the enalapril group which also showed a significant elevation of serum potassium after treatment. Captopril and enalapril have only a modest antihypertensive action in patients with NIDDM and nephropathy. Their use in patients with renal insufficiency must be balanced against the risk of further aggravating the deterioration of renal function.
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