RSS-Feed abonnieren
DOI: 10.1055/s-2006-921430
© Georg Thieme Verlag Stuttgart · New York
Nelson's Syndrome - 46 Years Later: Clinical Experience with 37 Patients
Nelson-Syndrom: Klinische Erfahrung anhand von 37 Patienten mit Verlauf bis 46 JahrePublikationsverlauf
Publikationsdatum:
03. März 2006 (online)
![](https://www.thieme-connect.de/media/zblneurochir/200601/lookinside/thumbnails/10.1055-s-2006-921430-1.jpg)
Abstract
Objective: Pituitary tumours occurring after bilateral adrenalectomy for Cushing's disease (Nelson's syndrome) are frequently aggressive, so an early diagnosis and careful management are of prime importance. For a new insight into this entity it is necessary to analyse the factors predisposing to its development and the course of the disease, as well as the methods of diagnosis and modalities of treatment. Patients and Methods: Thirty-seven patients with Nelson's syndrome were observed, 32 women and 5 men, aged 16 to 61 years at the time of pituitary tumour detection (at present, 27 to 82 years old). The diagnostic methods included clinical observation, imaging examinations (X-ray studies, CT, MRI), hormonal evaluation (especially ACTH and cortisol levels during replacement therapy) and ophthalmologic investigations. Neurosurgery was the main method of treatment. Results: The clinical analysis indicated that young age at the time of adrenalectomy, pregnancy, insufficient replacement therapy and fulminant course of Cushing's disease were the main factors predisposing to Nelson's syndrome. MRI appeared to be the most valuable imaging method, as this detected Nelson's tumours in the microadenoma stage in 7 patients. Plasma ACTH levels varied between 32.6 pmol/l in an early phase to 2 000 pmol/l in the full-blown syndrome. Absolute temporal scotomas found in ophthalmologic examinations were an early abnormality. The best results after therapy were obtained in patients treated by neurosurgery using a transsphenoidal approach in an early stage. Conclusions: MRI, ophthalmologic examination and plasma ACTH determination were the most valuable investigations for early diagnosis of Nelson's syndrome. Early neurosurgery offered the best outcome in our group of patients.
Zusammenfassung
Einleitung: Hypophysentumoren, die nach beidseitiger Adrenalektomie wegen eines Morbus Cushing auftreten (Nelson-Syndrom) verhalten sich häufig aggressiv, sodass eine frühe Diagnose und ein sorgfältiges Management von großer Wichtigkeit sind. Um neue Einsichten in diese Entität zu gewinnen, erscheint es notwendig, die Faktoren, die zu ihrer Entwicklung und dem Krankheitsverlauf prädisponieren, erneut zu analysieren, ebenso wie die Methoden der Diagnose und die Behandlungsmodalitäten zu beurteilen. Patienten und Methoden: 37 Patienten mit Nelson-Syndrom wurden beobachtet, 32 Frauen und 5 Männer zwischen 16 und 61 Jahren zum Zeitpunkt der Tumorentdeckung (gegenwärtig 27 bis 82 Jahre alt). Die diagnostischen Methoden schließen klinische Beobachtung, bildgebende Untersuchungen (Röntgen, CT, MRT), Hormonbestimmungen (insbesondere ACTH und Kortisonspiegel während der Hormonersatztherapie) und ophthalmologische Untersuchungen ein. Neurochirurgische Therapie war die hauptsächlich angewendete Behandlungsmethode. Ergebnisse: Die klinische Analyse zeigte an, dass ein junges Alter zum Zeitpunkt der Adrenalektomie, Schwangerschaft, ungenügende Hormonersatztherapie und ein fulminanter Verlauf des Cushing-Syndroms die Hauptfaktoren waren, die zur Entwicklung eines Nelson-Syndroms prädisponierten. MRT erschien die wertvollste Methode der Bildgebung zu sein, die einen Nelson-Tumor im Stadium des Mikroadenoms bei 7 Patienten diagnostizieren konnte. Plasma-ACTH-Spiegel variierten zwischen 32,6 pmol/l in der Frühphase bis zu 2 000 pmol/l während des voll entwickelten Syndroms. Absolute temporale Skotome waren bei der ophthalmologischen Untersuchung eine frühe Anormalität. Die besten Therapieresultate konnten durch neurochirurgisches Vorgehen über einen transsphenoidalen Zugang in einem frühen Stadium erreicht werden. Schlussfolgerung: MRT, ophthalmologische Untersuchungen und Plasma-ACTH-Bestimmungen waren die wichtigsten Untersuchungen für die Frühdiagnose eines Nelson-Syndroms. Frühe neurochirurgische Intervention führte zum besten Ergebnis in dieser Patientengruppe.
Key words
Nelson's syndrome - pituitary tumour - ACTH - Cushing's disease
Schlüsselwörter
Nelson-Syndrom - Hypophysegeschwulst - ACTH - Cushing-Krankheit
References
- 1 Aron D C, Schnall A M, Sheeler L R. Cushing's syndrome and pregnancy. Am J Obstet Gynecol. 1990; 162 244-252
- 2 Bonicki W, Kasperlik-Załuska A, Koszewski W, Zgliczyński W, Wisławski J. Pituitary apoplexy: endocrine, surgical and oncological emergency. Incidence, clinical course and treatment with reference to 799 cases of pituitary adenomas. Acta Neurochir. 1993; 120 118-122
- 3 Cohen K L, Noth R H, Pechinski T. Incidence of pituitary tumours following adrenalectomy. Arch Intern Med. 1978; 138 575-579
- 4 Fukushima T. Transsphenoidal microsurgical treatment of Nelson's syndrome. Neurosurg Rev. 1985; 8 185-194
- 5 Grua J R, Nelson D H. ACTH-producing pituitary tumours. Endocrinol Metab Clin North Amer. 1991; 20 319-362
- 6 Hodgkinson S C, Allolio B, London J, Lowry P. Development of a non-extracted two-site immunoradiometric assay for corticotropin utilizing extreme amino- and carboxy-terminally directed antibodies. Biochem J. 1984; 218 703-706
- 7 Howlett T A, Plowman P N, Wass J AH, Rees L H, Jones A E, Besser G M. Megavoltage pituitary irradiation in the management of Cushing's disease and Nelson's syndrome: long-term follow-up. Clin Endocrinol. 1989; 31 309-323
- 8 Jenkins P J, Trainer P J, Plowman P N, Shand W S, Grossman A B, Wass J AH, Besser G M. The long term outcome after adrenalectomy and prophylactic pituitary radiotherapy in adrenocorticotropin-dependent Cushing's syndrome. J Clinical Endocrinol Metab. 1994; 79 165-171
- 9 Karl M, Wichert G, Kempter E, Katz D A, Reincke M, Monig H, Ali I U, Stratakis C A, Oldfield E H, Chrosous G P, Shulte H M. Nelson's syndrome associated with a somatic frame shift mutation in the glucocorticoid receptor gene. J Clin Endocrinol Metab. 1996; 81 124-129
- 10 Kasperlik-Załuska A, Hartwig W, Nielubowicz J, Rudowski W, Migdalska B, Kobuszewska-Faryna M, Załuska J. Clinical analysis of 111 cases of adrenocortical hyperfunction. Results of surgical treatment. Endokrynol Pol. 1978; 29 273-288
- 11 Kasperlik-Załuska A, Migdalska B, Hartwig W, Wilczyńska J, Marianowski L, Stopińska-Głuszak U, Łozińska D. Two pregnancies in a woman with Cushing's syndrome treated with cyproheptadine. Brit J Obstet Gynaecol. 1980; 87 1171-1173
- 12 Kasperlik-Załuska A, Nielubowicz J. Cushing's disease. Lancet. 1981; 1 1428
- 13 Kasperlik-Załuska A A, Nielubowicz J, Wisławski J, Hartwig W, Załuska J, Jeske W, Migdalska B. Nelson's syndrome: incidence and prognosis. Clin Endocrinol. 1983; 19 693-698
- 14 Kasperlik-Załuska A A, Abdel-Fattah M H, Jeske W, Puciłowska J. Plasma ACTH levels and β-endorphin-like immunoreactivity following administration of luteinizing hormone-releasing hormone in Nelson's syndrome. Eur J Obstet Gynecol Reprod Biol. 1986; 21 199-205
- 15 Kasperlik-Załuska A A, Wisławski J, Nielubowicz J, Bonicki W. An unusual case of Nelson's syndrome. Endokrynol Pol. 1989; 40 143-148
- 16 Kasperlik-Załuska A, Niegowska E, Migdalska B, Jeske W, Zieliński M. A correlative study between cortisol and ACTH in Cushing's disease following bilateral adrenalectomy and in Nelson's syndrome. Endokrynol Pol. 1992; 43 314-321
- 17 Kasperlik-Załuska A A, Walecki J, Jeske W, Migdalska B, Janik J, Bonicki W, Brzezinski J, Makowska A. Early diagnosis of Nelson's syndrome. J Mol Neurosci. 1996; 7 87-90
- 18 Kasperlik-Załuska A A, Walecki J, Brzezinski J, Jeske W, Migdalska B, Bonicki W, Brzezinska A, Makowska A. MRI versus CT in the diagnosis of Nelson's syndrome. Eur Radiol. 1997; 7 106-109
- 19 Kelly P A, Samandouras G, Grossman A B, Afshar F, Besser G M, Jenkins P J. Neurosurgical treatment of Nelson's syndrome. J Clin Endocrinol Metab. 2002; 87 5465-5469
- 20 Kemink L, Pieters G, Hermus A, Smals A, Kloppenborg P. Patient's age is a simple predictive factor for the development of Nelson's syndrome after total adrenalectomy for Cushing's disease. J Clin Endocrinol Metab. 1994; 79 887-889
- 21 Kemink S AG, Smals A GH, Hermus A RMM, Pieters G FMM, Kloppenborg P WC. Nelson's syndrome: A review. Endocrinologist. 1997; 7 5-9
- 22 Kemink S AG, Grotenhuis J A, De Vries J, Pieters G FMM, Hermus A RMM, Smals A GH. Management of Nelson's syndrome: observations in fifteen patients. Clin Endocrinol. 2001; 54 45-52
- 23 Liddle G W, Island D, Meador C K. Normal and abnormal regulation of corticotropin secretion in man. Recent Prog Horm Res. 1962; 18 125-166
- 24 Moore T J, Dluhy R G, Williams G H, Cain J P. Nelson's syndrome: frequency, prognosis, and effect of prior pituitary irradiation. Ann Int Med. 1976; 85 731-734
- 25 Nelson D H, Meakin J W, Dealy J B, Matson D D, Emerson K JR, Thorn G W. ACTH-producing tumor of the pituitary gland. N Engl J Med. 1958; 259 61-64
- 26 Nelson D H, Meakin J W. A new clinical entity in patients adrenalectomized for Cushing's syndrome. J Clin Invest. 1959; 38 1028-1030
- 27 Nelson D H, Meakin J W, Thorn G W. ACTH-producing pituitary tumors following adrenalectomy for Cushing's syndrome. Ann Int Med. 1960; 52 560-569
- 28 Pereira M AA, Halpern A, Salgado L R, Mendonça B B, Nery M, Liberman B, Streeten D HP, Wajchenberg B L. A study of patients with Nelson's syndrome. Clin Endocrinol. 1998; 49 533-539
- 29 Wisławski J, Kasperlik-Załuska A A, Jeske W, Migdalska B, Janik J, Załuska J, Bonicki W. Results of neurosurgical treatment by a transsphenoidal approach in 10 patients with Nelson's syndrome. J Neurosurg. 1985; 62 68-71
Anna A. Kasperlik-ZałuskaMD, PhD, Professor of Medicine
Department of Endocrinology · Centre for Postgraduate Medical Education
Cegłowska 80
01-809 Warsaw
Poland
Telefon: +48/22/8 34 31 31
Fax: +48/22/8 34 31 31
eMail: anna@ultima.neostrada.pl