Treatment with gonadotrophin releasing hormone analogue in advanced prostatic cancer

Repeated administration of long acting analogues of gonadotrophin releasing hormone diminishes gonadal function and in men decreases testosterone concentrations; for this reason the effect of the analogue buserelin was studied in prostatic carcinoma. Twelve consecutive patients with newly diagnosed locally advanced or metastatic carcinoma of the prostate were treated. Each patient received intranasal buserelin in divided dosages of either 600 or 1000 micrograms daily. Suppression of the gonadotrophins and testosterone occurred in all patients. Objective and subjective signs of regression of disease were seen in nine patients. Buserelin offers an effective treatment of metastatic prostatic cancer without the side effects and cardiovascular risks associated with oestrogen treatment.     

Growth hormone releasing factor: comparison of two analogues and demonstration of hypothalamic defect in growth hormone release after radiotherapy

Human pancreatic growth hormone releasing factor (hpGHRF(1-40] stimulates the release of growth hormone in normal subjects and some patients with growth hormone deficiency. A study comparing the shorter chain amidated analogue hpGHRF(1-29) with an equivalent dose of hpGHRF(1-40) in seven normal subjects showed no significant difference in growth hormone response between the two preparations. Six patients with prolactinomas were also tested; these patients had received megavoltage radiotherapy previously but had developed growth hormone deficiency as shown by insulin induced hypoglycaemia. In all six patients 200 micrograms hpGHRF(1-40) or hpGHRF(1-29)NH2 produced an increase in the serum growth hormone concentration. These data suggest that hpGHRF(1-29)NH2 may be useful for testing the readily releasable pool of growth hormone in the pituitary and that cases of hypothalamo-pituitary irradiation resulting in growth hormone deficiency may be due to failure of synthesis or delivery of endogenous GHRF from the hypothalamus to pituitary cells.     

Clinical screening of sterility cases for the possible presence of luteal phase defect (author's transl)]

Eighty consecutive cases of sterility was screened for suspected insufficiency of luteal function. The parameters used in the assessment were one value each for pregnandiol and oestrogen excretion, the basal temperature, the histological picture of secretory endometrium, as well as the activity of endometrial malate dehydrogenase and carbonanhydrase, or malate dehydrogenase and succinic dehydrogenase. Histological irregularities, a short luteal phase as indicated by the basal temperature, early abortion and a pregnandiol excretion of less than 1.9 mg were usually accompanied by low endometrial enzymatic acitvity. A comparison of pregnandiol excretion levels with the other four investigated parameters indicated that the number of negative findings increased with decreasing pregnandiol values. In this way, low oestrogen excretion values occurred more frequently with low pregnandiol values. However, when taken in conjunction with other findings, a low oestrogen value does not seem to be characteristic of luteal insufficiency. In certain cases the suspicion of luteal insufficiency increases with decreasing pregnandiol values and with the number of negative findings concerning basal temperature, endometrial histology and enzymatic activity, as well as oestrogen excretion. According to this point of view the incidence of a presumptive luteal phase defect was 33% in the present investigation.     

Outcome of transsphenoidal surgery for acromegaly using strict criteria for surgical cure

OBJECTIVE Previous studies of surgical treatment for acromegaly have used varied criteria for ‘cure’, but elevated GH levels are considered to be associated with continuing disease activity. We wished to analyse the results of transsphenoidal pituitary surgery for acromegaly and assess the longer-term outcome for patients not offered further treatment when post-operative levels of GH < 5 mU/l were achieved. DESIGN We studied a retrospective group of patients who underwent transsphenoidal surgery for acromegaly at St Bartholomew’s Hospital between 1985 and 1993. PATIENTS One hundred consecutive patients (53 male, mean age 46 years, range 18–68 years) undergoing transsphenoidal surgery for acromegaly were assessed. The patients were followed for a mean of 3.8 years (range 0.5–8 years) after operation. MEASUREMENTS GH levels are represented as a mean value from a four-point day curve taken at 0830, 1300, 1700 and 1900h. ACTH reserve was assessed basally and, if this was normal, with the insulin tolerance or glucagon tests. TSH, T4, PRL, LH, FSH, testosterone or oestradiol and plasma and urine osmolality were also measured. RESULTS Post-operatively, 42% of patients achieved a mean GH level of < 5 mU/l. The success of surgery was related to the preoperative GH level; 65% of the patients with preoperative GH levels < 20 mU/l but only 18% of the patients with GH levels > 100 mU/l achieved post-operative GH values < 5mU/l. In addition, tumour size influenced the outcome of surgery with 61% of patients with a microadenoma but only 23% of patients with a macroadenoma achieving post-operative GH levels of < 5 mU/l. Of the 42 patients considered in remission postoperatively (mean GH < 5 mU/l), 32 were available for long-term follow-up and were not offered any further treatment: only one of these has shown evidence of mild biochemical recurrence after a mean follow-up of 3.8 years (range 0.5–8). There were no peri-operative deaths. Two patients required surgical repair for CSF leaks and there were eight documented cases of meningitis. Permanent diabetes insipidus was noted in eight patients post-operatively. New anterior pituitary deficiency occurred in 21% of patients following surgery; 73% had unaltered pituitary function and in 6% recovery of partial hypopituitarism was noted. CONCLUSIONS The stated outcome of surgery depends on the criteria adopted. Safe GH levels (mean levels < 5 mU/l) can be achieved in 42% of an unselected series of patients with acromegaly and if the tumour is a microadenoma this figure rises to 61%. Based on the current evidence it is safe not to offer further treatment to those patients in whom post-operative GH < 5 mU/l are achieved.     

Amines: possible causative agents in the development of bronchial hyperreactivity in workers manufacturing polyurethanes from isocyanates

Investigations of respiratory symptoms among workers in a factory producing polyurethane foam included measurement of air pollution with amines and isocyanates and a simultaneous health investigation of the exposed workers. An increased bronchial reactivity to inhaled methacholine was found in the study group compared with two unexposed control groups. This finding, together with visual disturbances in the exposed group, were assumed to be caused mainly by the volatile amines. The concentrations of isocyanates in air were well below 0.005 ppm. The amine concentration was 1000 to 10 000 times higher than the isocyanate concentration. The most volatile amine, N-methylmorpholine, occurred in the air in concentrations higher than 10 ppm. The results indicate that not only the isocyanates but also the amines might well be responsible for respiratory symptoms among exposed workers in polyurethane foam production.     

Pituitary imaging using a labelled somatostatin analogue in acromegaly

OBJECTIVE: A number of neoplasms are known to express somatostatin receptors, and the use of somatostatin receptor imaging in their localization has recently been described. We have looked at the use of an 123I-labelled Tyr3-octreotide analogue of somatostatin in the visualization and functional characterization of growth hormone-secreting pituitary adenomas. PATIENTS: Fifteen patients with biochemically-proven acromegaly were scanned using this agent. In eight of these we also assessed acute GH responses to octreotide in order to correlate these responses with tumour uptake characteristics. MEASURES: Planar and single-photon-emission computerized tomographic (SPECT) images of the head were obtained using a gamma-camera at 10 minutes, and 4 and 24 hours, after injection of the radiopharmaceutical. Blood for serum GH was sampled for 12 hours after administration of a single dose of 100 micrograms octreotide. RESULTS: Twelve of the acromegalic subjects showed significant uptake of the radiopharmaceutical in the pituitary fossa. Of the eight patients in whom we assessed acute GH responses, five demonstrated a significant fall in GH in response to octreotide. These subjects also showed positive uptake in the pituitary on scanning. The three patients who had no fall in GH had no uptake on scanning. CONCLUSIONS: Uptake of 123I-labelled Tyr3-octreotide in the pituitary fossa appears to correlate closely with the presence of a therapeutic response to octreotide.     

Gene deletion causing adrenal hypoplasia congenita and hypogonadotrophic hypogonadism

We report a patient with X-linked adrenal hypoplasia congenita and hypogonadotrophic hypogonadism in whom there were no clinical or biochemical features of either glycerol kinase deficiency or Duchenne muscular dystrophy. (The adrenal hypoplasia congenita and glycerol kinase loci map in Xp21 distal to Duchenne muscular dystrophy, and proximal to DXS727.) DNA isolated from our patient was analysed by PCR amplification with primers for appropriate loci in the Xp21 region. This analysis revealed the absence of DXS319, which lies near the adrenal hypoplasia congenita deletion critical region, and the presence of DXS727, which is distal to the gene. The absence of glycerol kinase deficiency biochemically and clinically was consistent with the presence of one glycerol kinase exon product from PCR primers P17/P18 which lies within the glycerol kinase gene. The hypogonadotrophic hypogonadism is universally found in X-linked adrenal hypoplasia congenita and is thought to be pituitary in origin. These findings suggest that a gene locus resulting in hypogonadotrophic hypogonadism is present in the Xp21 region and is an integral part of the adrenal hypoplasia congenita gene or in close relationship to it.