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Veronica A Preda and Ashley B Grossman

We appreciate the letter from of Dr Soh et al. regarding our review on the use of etomidate in the treatment of Cushing's syndrome. We note that in their experience, our recommended dose regimen of 2.5 mg/h or thereabouts appears to be a safe and effective starting dose in most patients, and we note the utility and ease of use of the lipid formulation and its relative freedom from side effects compared with the more commonly used propylene glycol formulation; these are very helpful comments. Their experience in treating a further four patients is indeed further evidence of the usefulness of this agent.

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Veronica A Preda, Jonathan Sen, Niki Karavitaki and Ashley B Grossman

The authors apologise for the publication of an error in Table 2 of this article published in the European Journal of Endocrinology 167 137–143. They wish to make clear in Table 2 that they are stipulating the dose of etomidate and that the corresponding dose of hydrocortisone for complete blockade should be 0.5–1.0 mg/h. The correct table is published in full below.

Table 2

Treatment of hypercorticolism with etomidate: Recommendations.

Infusion rate optionsBlockadeCortisol levelBiochemical monitoringOther
Etomidate (IV) 0.04–0.05 m/kg per h=2.5–3.0 mg/hPartial to complete depending on clinical circumstance of the patientTitrate to serum cortisol 500–800 nmol/l in physiologically stressed patient, 150–300 nmol/l in non-physiologically stressed patientPotassium level Cortisol levelSedation scoring initially every two hours then every 12 hours after first 24 hours
Hydrocortisone IV 0.5–1.0 mg/hComplete (will need steroid replacement)<150 nmol/lPotassium level Cortisol level

This table could now be used as a practical guide for clinicians commencing infusions on the ward of etomidate and required hydrocortisone replacement.

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W M Drake, A B Grossman and R K Hutson

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Veronica A Preda, Jonathan Sen, Niki Karavitaki and Ashley B Grossman

This review addresses the practical usage of intravenous etomidate as a medical therapy in Cushing's syndrome. We reviewed the relevant literature, using search terms ‘etomidate’, ‘Cushing's syndrome’, ‘adrenocortical hyperfunction’, ‘drug therapy’ and ‘hypercortisolaemia’ in a series of public databases. There is a paucity of large randomised controlled trials, and data on its use rely only on small series, case study reports and international consensus guideline recommendations. Based on these, etomidate is an effective parenteral medication for the management of endogenous hypercortisolaemia, particularly in cases with significant biochemical disturbance, sepsis and other serious complications such as severe psychosis, as well as in preoperative instability. We suggest treatment protocols for the safe and effective use of etomidate in Cushing's syndrome.

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J. A. Verhelst, A. L. Froud, R. Touzel, J. A. H. Wass, G. M. Besser and A. B. Grossman

Abstract.

Quinagolide (CV 205-502, Sandoz), an octahydrobenzo (g) quinoline, is a new non-ergot dopamine agonist which has specific D2 receptor activity and a long half-life, making it suitable for once-daily treatment. Recent uncontrolled reports have suggested that quinagolide may be successfully used for the clinical management of hyperprolactinemia with fewer adverse reactions than bromocriptine. This study is the first to compare quinagolide in a double-blind manner with bromocriptine, given only once-daily instead of the usual multidose regimen. In the first phase we compared, in 7 hyperprolactinemic patients, the effects over 24 h of a single oral dose of 0.05 mg quinagolide with 2.5 mg bromocriptine. Compared with placebo, both bromocriptine and quinagolide showed potent PRL-inhibiting and GH-releasing effects, with comparable effects at 24 h; no significant changes were observed in TSH, LH, FSH or cortisol. Twelve hyperprolactinemic patients were then randomized to receive either once-daily bromocriptine or quinagolide in incremental doses for a period of six months. Both drugs were found to be equally effective, and no differences were seen either in adverse reactions or PRL levels during repeated diurnal sampling. We therefore conclude that quinagolide and bromocriptine are therapeutically equivalent in long-term use, and both are equally effective when given once a day. However, some patients intolerant of bromocriptine may respond better to quinagolide, and vice versa.

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M Giusti, G Delitala, G Marini, B Uggias, P Sessarego, GM Besser, A Grossman and G Giordano

The aim of the study was to evaluate the effect of the guanyl derivative of the opioid analogue D-ala2,MePhe4-Met-enkephalin-(o)-ol (G-DAMME) on pituitary secretion in healthy elderly men. Nine healthy elderly men (65–88 years) and 10 young adults (20–30 years) were studied. GH, PRL, gonadotropins, cortisol (to evaluate the effect on ACTH) and TSH were measured after G-DAMME (0.25 mg iv) or placebo administration. In elderly men, the GH response to G-DAMME was reduced or absent, while prompt GH release was found in all young men. G-DAMME lowered LH levels in young men but not in elderly men. No significant variations in FSH levels after G-DAMME and placebo were noted in either group of subjects. A similar and significant rise in PRL and TSH, and a fall in cortisol, after G-DAMME was observed in both elderly and young adults. We have demonstrated that the sensitivity to opioid modulation by G-DAMME on PRL, TSH and cortisol secretion is unchanged with aging. On the other hand, the data indicate that LH and GH responsiveness to G-DAMME change with age.

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C J Peters, H L Storr, A B Grossman and M O Savage

Background: Corticotrophin-releasing hormone (CRH) was identified by Vale and co-workers in 1981 and has since been used extensively in the diagnosis of ACTH-dependent Cushing’s syndrome (CS). It was hoped that the CRH test would discriminate between pituitary and ectopic ACTH secretion. In adults, a rise from basal to peak plasma cortisol of ≥20% and ACTH of ≥50% is consistent with Cushing’s disease (CD).

Methods: Twenty-seven paediatric patients, with CD (mean age ± s.d. 13.1 ± 3.2; range 6.4–17.8 years) were investigated in our centre between 1982 and 2005.

Results: During the CRH test, all patients showed an increase in cortisol of >20% (range 106–554%). In one patient with ectopic ACTH syndrome, there was no increase in cortisol after CRH. In six paediatric patients with CS due to primary adrenal hyperplasia, no patient showed an increase in cortisol after CRH of >1%.

Conclusions: A further suggested use of CRH is to increase the sensitivity of the central to peripheral and interpetrosal ratios of ACTH during inferior petrosal sinus catheterisation (IPSS). Bilateral IPSS with human CRH (hCRH) has been performed in our unit in 21 children with CD, as part of the preoperative preparation prior to transsphenoidal surgery (TSS). Its principal role was to identify the site of the microadenoma. Sixteen of 21 patients (76%) who underwent IPSS with hCRH were cured following TSS. In our view, the CRH test is of value during IPSS by clarifying the position of the microadenoma and in this way contributed to the overall outcome of TSS in paediatric patients with CD.

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R. C. Castro, J. G. H. Vieira, A. R. Chacra, G. M. Besser, A. B. Grossman and A. M.J. Lengyel

Abstract

Obese patients are characterised by several neuroendocrine abnormalities, including characteristically a decrease in growth hormone responsiveness to GH-releasing hormone. In normal subjects, the GH response to GHRH is enhanced by the acetylcholinesterase inhibitor, pyridostigmine. We have studied the effect of this drug on GH secretion in gross obesity. Twelve obese patients were studied (mean weight 156% of ideal) and compared with a group of 8 normal volunteers. Each subject was initially studied on two occasions, in random order, with GHRH (1–29) NH2 100 μg iv alone and following pretreatment with pyridostigmine 120 mg orally one hour prior to GHRH. In obese patients, the GH response to GHRH was significantly blunted when compared to controls (GH peak: 20 ± 4 vs 44 ± 16 μg/l; mean ± sem). After pyridostigmine, the response to GHRH was enhanced in the obese subjects, but remained significantly reduced compared to non-obese subjects treated with GHRH and pyridostigmine (GH peak: 30 ± 5 vs 77 ± 20 μg/l, respectively). In 6 subjects, higher doses of GHRH or pyridostigmine did not further increase GH responsiveness in obese patients. Our results suggest that obese patients have a disturbed cholinergic control of GH release, probably resulting from increased somatostatinergic tone. This disturbed regulation may be responsible, at least in part, for the blunted GH responses to provocative stimuli.

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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.