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David M. G. Halpin, Jacky M. Burrin and Graham F. Joplin

Abstract

Serum testosterone was measured pre- and post-operatively in 31 women who obtained remission of Cushing's disease following treatment by interstitial irradiation of the pituitary gland. The mean serum testosterone was initially elevated at 3.35 nmol/l, with values ranging from 0.7 to 14.4 nmol/l. Following treatment the mean serum testosterone fell to 1.42 nmol/l (i.e. normal) and all but one of the 15 patients with initially elevated pre-treatment values obtained normal levels. The pre-treatment testoterone concentrations correlated significantly (r = 0.47; p = 0.019) with the midnight ACTH concentration. The likely determinant of the raised serum testoterone would appear to be the intensity of the ACTH drive, although an individual's inherent sensitivity to ACTH may also be a factor.

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Maria S. Venetikou, Mohammed A. Ghatei, Jacky M. Burrin, Sania Latif and Stephen R. Bloom

Abstract. A novel pituitary protein, 7B2, of approximately 180 amino acids has been suggested to colocalise with LH in the pituitary gonadotropes. Increased secretion of LH is known to occur in functionless pituitary tumours. We have therefore measured 7B2 immunoreactive equivalents in the 24-h medium of explant pituitary cultures prepared from 17 functionless, 20 somatotropic, 16 PRL secreting and 8 corticotropic adenomas. A synthetic fragment corresponding to amino acids 23–39 of 7B2 was used to raise antisera (rabbits), prepare radiolabel (chloramine T iodination) and also serve as the assay standard. 7B2-immunoreactive equivalents in the medium from the functionless tumours was 517 ± 149 pmol/l, significantly higher than that of the somatotropic tumours (248 ± 90 pmol/l, P < 0.05), prolactinomas (108 ± 37 pmol/l, P < 0.001) and corticotropin producing adenomas (107 ± 77 pmol/l, P < 0.001) (one-way analysis of variance). Gel permeation chromatography of medium obtained from functionless tumours revealed two immunoreactive 7B2 peaks one eluting at a coefficient of 0.28 corresponding to that of normal human pituitary extract and another eluting at a coefficient of 0.59. Gel chromatography profiles of medium obtained from somatotropic tumours contained similar immunoreactive 7B2 peaks (elution coefficient 0.28 and 0.57). These findings demonstrate that 7B2-like material is secreted by pituitary adenomas in explant culture with the highest level from functionless tumour cultures.

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Gareth Williams, Marius Kraenzlin, Laurence Sandier, Jacky Burrin, Adam Law, Stephen Bloom and G. F. Joplin

Abstract. Inappropriate hypersecretion of TSH was investigated in a 25 year old man whose hyperthyroidism had relapsed 4 years after subtotal thyroidectomy. Serum TSH levels were further increased by both TRH and metoclopramide and were partially suppressed by triiodothyronine (120 μ/day). The serum α-subunit: TSH molar ratio was < 1.0, and computerised axial tomography showed no evidence of a pituitary tumour. These features are characteristic of inappropriate TSH secretion due to thyrotroph resistance to thyroid hormones. A long-acting somatostatin analogue (SMS 201-995), 50 μg injected sc twice-daily for three days, suppressed TSH levels and nearly normalised thyroid hormone levels. Somatostatin analogues may be therapeutically useful in thyrotoxicosis due to non-tumoural inappropriate TSH hypersecretion.

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Maria S. Venetikou, Jacky M. Burrin, Christine A. Woods, Tom H. Yeo, Judith Brownell and Eric F. Adams

Abstract. Two novel dopaminergic drugs, designated CV 205-502 and CQP 201-403 have recently been developed by Sandoz Pharmaceuticals Ltd (Basle, Switzerland). The effects of these drugs on PRL and GH secretion by normal rat and tumorous human pituitary cells in vitro have been investigated. Low doses of both CV 205-502 and CQP 201-403 immediately and profoundly suppressed PRL secretion, which failed to recover up to 7 h after removal of the drugs. Similarly, CQP 201-403 significantly suppressed basal GH secretion by human pituitary somatotropic tumours in culture, and both drugs significantly reduced the stimulatory effect of GHRH. These effects are more potent and longer acting than the previously described in vitro effects of bromocriptine. It is concluded that CV 205502 and CQP 201-403 hold potential for the treatment of patients with hyperprolactinaemia and, possibly, also in patients with acromegaly.

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Michel Procopiou, Hazel Finney, Scott A Akker, Shern L Chew, William M Drake, Jacky Burrin and Ashley B Grossman

Objective

To define the test characteristics of an enzyme immunoassay (EIA) for plasma-free metanephrines (metanephrine and normetanephrine) in the diagnosis of pheochromocytoma and paraganglioma.

Design

Prospective observational design from a single University Hospital. Twenty-four hour urine for catecholamines and plasma for free metanephrines were collected from patients with a clinical suspicion of pheochromocytoma or paraganglioma. Patient records were reviewed for clinical data, follow-up, imaging and laboratory results to establish or exclude the diagnosis of pheochromocytoma.

Patients and methods

Out of 178 consecutive patients, 10 had a paraganglioma and 12 had a pheochromocytoma: 156 were finally judged not to harbour active tumors and were therefore considered as controls. The main outcome measure was the diagnosis or exclusion of paraganglioma or pheochromocytoma and test characteristics of plasma-free metanephrines measured by EIA.

Results

Urinary epinephrine had a sensitivity of 45.5% and norepinephrine a sensitivity of 75% (98.8% specificity) for the diagnosis of pheochromocytoma. Plasma-free metanephrine and normetanephrine both had a sensitivity of 66.7% and a specificity of 100%, but when combined (either positive) they demonstrated a 91.7% sensitivity with a preserved specificity of 100%. For the diagnosis of paraganglioma, urinary norepinephrine gave slightly better results than plasma-free metanephrines, but combined testing was of no additional value.

Conclusions

Plasma-free metanephrines measured by EIA have better diagnostic test characteristics than urinary catecholamines in the diagnosis of pheochromocytoma. The EIA offers a simple and effective measurement of plasma-free metanephrines.

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Michel Procopiou, Hazel Finney, Scott A Akker, Shern L Chew, William M Drake, Jacky Burrin and Ashley B Grossman

The authors and journal apologize for the error in the above paper which appeared in 161 (1) 131–140. The kits for the assay of free metanephrines were supplied by both Immunodiagnostic Systems Ltd (IDS), Tyne and Wear, UK and also Biotech-IgG (UK) Ltd, Wilmslow, UK.