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Cent Eur Neurosurg 2003; 64(1): 6-11
DOI: 10.1055/s-2003-37145
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© Georg Thieme Verlag Stuttgart · New York

The Use of Postoperative ACTH Levels as a Marker for Successful Transsphenoidal Microsurgery in Cushing’s Disease

Postoperative ACTH-Werte als Marker der erfolgreichen transsphenoidalen Adenomektomie bei Morbus CushingJ. Flitsch1 , U. J. Knappe1 , D. K. Lüdecke1
  • 1Arbeitsbereich Hypophysenchirurgie, Klinik für Neurochirurgie, Universitätsklinikum Hamburg-Eppendorf, Hamburg
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Publication History

Publication Date:
12 February 2003 (online)

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Zusammenfassung

Fragestellung: Der unmittelbar nach Tumorentfernung stattfindende Hormonabfall von ACTH oder anderer POMC-Metabolite lässt keine Aussage hinsichtlich der Radikalität der Tumorexstirpation eines ACTH-sezernierenden Hypophysenadenoms bei Morbus Cushing zu. Dennoch sollte der Hypophysenchirurg in der Lage sein, so früh wie möglich das operative Ergebnis zu beurteilen, um gegebenenfalls eine frühe Reoperation planen zu können. Zur Zeit wird der postoperative Abfall des Kortisols in den subnormalen Bereich als Kriterium für die Heilung weitgehend anerkannt. In dieser Studie untersuchten wir, ob frühe postoperative ACTH-Bestimmungen als Marker für das unmittelbare postoperative Ergebnis als auch für die Langzeitremission aussagekräftig sind.
Methode: In diesem prospektiven Studiendesign wurden 147 Patienten, die sich von 1990 bis 1996 einer primären Operation bei Morbus Cushing unterzogen, untersucht. Der frühe postoperative ACTH-Abfall wurde bestimmt und mit dem Langzeitverlauf verglichen. ACTH-Bestimmungen wurden unmittelbar nach Tumorausräumung, nach 1, 2, 4, 8 und 12 Stunden sowie am darauffolgenden Morgen durchgeführt. Weitere ACTH-Bestimmungen folgten an verschiedenen Tagen während des stationären Aufenthaltes. Glukokortikoide wurden erst bei Nachweis des Hypokortisolismus substituiert.
Ergebnisse: Bei 95 Operationen (65 %) wurden postoperativ subnormale ACTH-Werte (< 10 ng/l) während des stationären Aufenthaltes gemessen. Zwei dieser Patienten erlitten ein Rezidiv des Morbus Cushing nach 66 bzw. 100 Monaten (2 %). Von 29 Patienten, die postoperativ ACTH-Werte zwischen 10 und 20 ng/l aufwiesen (20 %), benötigte ein Patient eine weitere Behandlung für den persistierenden (3,5 %) bzw. ein Patient für den rezidivierenden Morbus Cushing (3,5 %). Zwölf Patienten (8 %) wiesen postoperativ ACTH-Werte zwischen 20 und 30 ng/l auf, davon wurde ein Patient am persistierenden (8 %) bzw. 4 Patienten am rezidivierenden Morbus Cushing behandelt (33 %). Im Falle von 11 Patienten mit ACTH-Werten über 30 ng/l (7 %) bestand bei 8 Patienten die Erkrankung weiter fort (73 %) bzw. rezidivierte bei zwei Patienten (18 %).
Schlussfolgerung: Subnormale (< 10 ng/l) bzw. niedrig normale (< 20 ng/l) postoperative ACTH-Werte innerhalb der ersten sieben postoperativen Tage können als frühe Marker sowohl für die komplette Tumorextirpation als auch für die Langzeitremission bei Morbus Cushing angesehen werden. Das Risiko einer persistierenden oder rezidivierenden Erkrankung steigt mit der Höhe der postoperativen ACTH-Werte. Bei normalen ACTH-Spiegeln sind weitere Untersuchungen der ACTH- Kortisol-Sekretion wie zum Beispiel Funktionstests indiziert.

Abstract

Objectives: The declines of ACTH and other POMC metabolites immediately after tumor extirpation do not predict the complete tumor removal of an ACTH-secreting pituitary adenoma in Cushing’s disease. However, the pituitary surgeon should be in a position to evaluate the surgical result as soon as possible for the eventual planning of early repeat surgery. So far, subnormal serum cortisol levels after surgery are widely accepted as the criterion for cure. We investigated whether the early postoperative ACTH concentration is a reliable marker for the initial surgical outcome as well as the long-term remission.
Methods: In a prospective study, 147 patients undergoing primary transsphenoidal microsurgery for Cushing’s disease between 1990 and 1996 were investigated. The early postoperative ACTH courses were reviewed and compared with the long-term outcome. ACTH measurements were performed immediately after tumor excision, 1, 2, 4, 8, and 12 hours later, and the following morning. Further ACTH levels were determined on various days of the hospital stay. Glucocorticoids were not given until hypocortisolism was proven.
Results: Ninety-five patients (65 %) presented with subnormal ACTH levels (< 10 ng/l) during their postoperative stay, of whom two patients (2 %) experienced recurrence of disease after 66 and 100 months. Of 29 procedures with early postoperative ACTH levels ranging from 10-20 ng/l (20 %), one patient received further treatment for persistent (3.5 %) and one patient for recurrent Cushing’s disease (3.5 %). Of 12 patients (8 %) with early postoperative ACTH levels in between 20 to 30 ng/l, one patient received further treatment for persistent (8 %) and four patients for recurrent disease (33 %). ACTH levels of more than 30 ng/l, found in 11 patients (7 %), were accompanied by persistent (8 patients, 73 %) or recurrent (2 patients, 18 %) Cushing’s disease.
Conclusion: Subnormal (< 10 ng/l) or low normal (< 20 ng/l) postoperative ACTH levels within the first 7 days after surgery can be regarded as early markers for complete removal of an ACTH adenoma as well as indicators for long-term outcome in Cushing’s disease. The risks of persistence or recurrence of Cushing’s disease rise with the level of early postoperative ACTH values. Normal ACTH levels should result into further evaluation of the ACTH-cortisol secretion, for example by stimulation- or suppression tests.

Schlüsselwörter

ACTH - Kortisol - Morbus Cushing - Rezidiv - Remission - Transsphenoidale Mikrochirurgie

Key words

ACTH - cortisol - cushing’s disease - recurrence - remission - transsphenoidal microsurgery

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Dr. J. Flitsch

Neurochirurgische Klinik · Universitätsklinikum Hamburg-Eppendorf (UKE)

Martinistr. 52

20246 Hamburg

Phone: +49/40/4 28 03-27 65

Fax: +49/40/4 28 03-59 82

Email: flitsch@uke.uni-hamburg.de

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