220 SIR,-In 1981 a 29-year-old man was referred to our endocrine unit with the diagnosis of Nelson’s syndrome. At 24 years pituitarydependent Cushing...

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SIR,-In 1981 a 29-year-old man was referred to our endocrine unit with the diagnosis of Nelson’s syndrome. At 24 years pituitarydependent Cushing’s disease had been diagnosed at another hospital and he had undergone bilateral total adrenalectomy. The histological findings were "diffuse hyperplasia of the cortex with minimal nodularity". 2 years later skin pigmentation developed and plasma corticotropin (ACTH) concentrations ranged between 1000 and 1500 pg/ml. After a year the pigmentation worsened and plasma ACTH levels rose to 5000 pg/ml. The sella turcica was normal in size and morphology and bromocriptine 7-5-15 mg/day was given for about a year. No clinical and biochemical improvement was observed, and the plasma ACTH increased to 8000 pg/ml. Throughout the patient had been on replacement treatment with cortisone acetate 25 mg/day. 6 months ago, when the patient was seen here, he had diffuse skin pigmentation, cushingoid features, and hypertensive heart disease. Hypertension (180/120 mm Hg) was present but had not been treated for 2 years. The standard skull X-rays and linear tomography of the sella turcica did not reveal abnormalities compatible with pituitary microadenoma. However, a small hypodense intrasellar microadenoma was evident on the computerised tomographic scan with 5 mm cuts. Steroid treatment was withdrawn and hormone studies 14 or more days later frequently revealed very high plasma ACTH levels (6100-8500 pg/ml; normal<100) and above average cortisol levels (493-797 nmol/l; normal 140-700). 24 h urinary 17-hydroxycorticosteroid excretion was increased (51-66 Jimol; normal 8-22) and was not affected by low dose dexamethasone (46-3 mol in 24 h). 24 h urinary aldosterone excretion was normal (4 - 6-5 -5 /-lg; normal 3 -5-14) and plasma renin activity was suppressed both in supine and upright positions. An adrenal scan carried out after 6-methyl-C5Se)selenocholesterol (courtesy of Dr E. Reschini, 1st Medical Clinic, University of Milan) revealed a distinct area of increased concentration of radioactivity above the right kidney. Then the patient underwent pituitary adenomectomy by transsphernoidal route: his plasma ACTH levels fell to 1700-2000 pg/ml, while cortisol levels ranged between 570-690 nmot/1. The patient is now undergoing pituitary radiation by

telecobaltotherapy. Our experience and that of othersl,2 prompts us to advise close attention to the clinical status of patients with Cushing’s disease after bilateral "total" adrenalectomy. Clinical recurrence may suggest withdrawal of replacement therapy. In this event adrenal scintigraphy is of great value in establishing the presence of adrenal tissue either residual or ectopically located. Since the transsphenoidal approach offers a valuable tool in the treatment of Cushing’s disease, we do not suggest re-exploration of the abdomen. The treatment of choice in Cushing’s disease should be pituitary adenomectomy, but if bilateral total adrenalectomy cannot be avoided pituitary radiation therapy should be done subsequently, as pointed out by Chalmers and co-workers. Endocrine Unit, 2nd Medical Clinic, University of Milan, 20122 Milan, Italy



SiR,-Your editorial (Nov. 28, p. 1210) draws out "the view that aspirin is more dangerous than paracetamol [acetaminophen] when taken in overdosage". It also refers to comparative toxicity. Volans et al., U.K. study you cite do not draw your conclusion from their figures. They may have had good reasons. The data included only a few deaths in large numbers of poisonings, and it is not surprising that statistical analysis does not confirm that aspirin and paracetamol have different fatality rates. Half the patients took more than one drug, so the following analysis (by Fisher’s exact test) is inevitably crude: Herwig KR, Cerny JC, Beierwaltes WH. Pre-operative localisation of adrenal remnants. Surg Gynecol Obstet 1977; 145: 705-08. 2. Chalmers RA, Mashiter K, Joplin GF. Residual adrenocortical function after bilateral "total" adrenalectomy for Cushing’s disease. Lancet 1981; ii: 1196-99. 1. Freitas JE,

There is no indication of the seriousness of the attempt by the and paracetamol self-poisoners, though there is some indication that their motivation may have been different because, while usage of aspirin and paracetamol in the U.K. are approximately at the same level, Volans et al. found 453 cases who had taken aspirin only compared with 289 who had taken


paracetamol only. There is no direct evidence as to whether the aspirin and paracetamol dosage was similar, though Volans’ study of blood levels does give some indication. The lack of adequate pharmacokinetic data at poisoning levels of dosage limits the value of this approach but the following analysis does cast doubts on whether dosages were comparable. 62 - 6% of paracetamol takers had blood levels which, when allowances were made for the time after ingestion, were consistent with peak plasma paracetamol levels below 220 mg/1. Only 9 - 407o of recorded paracetamol figures exceeded 300 mg/1 whereas in the aspirin group, at the time the samples were taken, 48% had levels greater than 300 mg/1. All the deaths were in the 18% found to have levels greater than 500 mg/l. There was only one such finding in the paracetamol group. Since.neither the intentions of the subjects not the dosages taken by aspirin and paracetamol self-poisoners may have been comparable the inferences you have drawn about the relative toxicity of the drugs appears to be conjectural, nor can Volans’ data be used to confirm a significant difference in mortality rate. Aspirin Foundation, c/o Reckitt & Colman Ltd, London W4 2RW



SiR,—Dr Parkes’ review (Nov. 14, p. 1213) was most instructive, with regard to general sleep disorders. However, on


p. 1217 Parkes states that "electrophrenic stimulation in central I sleep apnoea seems of little value" and cites a paper by Riedy et al. which gives the opposite view ("electrophrenic stimulation for severe central apnoea has become a practical therapeutic modality when drug therapy is unrewarding"). We agree that the indications for such stimulation in sleep apnoea patients are not frequent and that stimulation is contraindicated in obstructive sleep apnoea. with However, there is a place for it in those sleep apnoea retention without It is also and obstruction. CO2 hypoxia occasionally useful in a few patients with upper airway obstruction whose nocturnal CO2 retention and hypoxia is demonstrated to 3 persist after tracheostomy.


Perhaps we might also draw attention to another recent review of respiratory aspects of sleep apnoea,4which adds a few other comments on the management of sleep apnoea. It also refers to the possibility, suggested by Remmers,that strychnine is useful in restoring upper airway muscle tone in obstructive sleep apnoea patients. the

Departments of Medicine and Cardiothoracic Surgery, Yale University School of Medicine,


New Haven, Connecticut 06510, U.S.A.



Riedy RM, Bachus BF,

Levine BE.



syndrome. Practical diagnostic

method Chest



1979; 75: 81-83. Glenn WWL, Phelps M, Gersten LM. Diaphragm pacing


the management of

central alveolar hypoventilation. In: Guilleminault C, Diment WC, eds. Sleep apnea syndromes. New York: Alan R. Liss, 1978: 333-46. Glenn WWL, Gee JBL, Cole DR, Farmer WC, Shaw RK, Beckman CB. Combined central alveolar hypoventilation and upper airway obstruction. Am J Med 1978; 64:

50-60. 4. Gee JBL, Remmers JE. Sleep apnea syndromes: Mechanisms and therapy. Comp Ther 1981; 7: 52-57. 5. Remmers JE, Anch AM, deGroot WJ, Baker JP Jr, Sauerland EK. Oropharyngeal

muscle tone in obstructive 447-54.

sleep apnea before and after strychnine. Sleep 1980, 3: