Evaluation of Intraoperative and early postoperative Growth Hormone Levels for Transsphenoidal Resection in Acromegaly

Acromegaly is characterized by elevated serum levels of growth hormone (GH) and
Insuline growth factor 1 (IGF-1). In most cases this is due to a growth
hormone producing pituitary adenoma. Transsphenoidal resection is the primary
treatment option for this condition (7).

In current guidelines the postoperative criteria for remission are considered a
nadir GH level on an oral glucose tolerance test (OGTT) of *1 ug/l (1 ug/l =
2.7 mE/l) and a normalized IGF-1 (7). These biochemical criteria have shown to
indicate safe levels of GH secretion and absolute remission in substantially
all surgical cases (1).

Guidelines currently recommend to perform an OGTT and IGF-1 measurement 12
weeks postoperatively in order to determine remission (7). During this period
definite remission is awaited and no additional treatment is started (surgical
re-exploration, medical therapy, radiotherapy).

Determination of remission in direct postoperative phase enables more adequate
treatment. Re-exploration, which is the first choice after primary surgery
failed to achieve remission, is facilitated in the early postoperative period
(first week). Within the same week surgical remission could be attained
omitting other additional treatments and unnecessary additional radiological
and endocrinological studies.

GH has a short half-life and it has been demonstrated to show rapid
intraoperative and postoperative decline (4). This makes it an possible
adequate marker for quick postoperative and even intraoperative predictor of
remission (4). Although current guidelines recognize correlation of early
postoperative GH levels (<2 ug/ml) and long term remission, exact correlation
is unknown (7). Intraoperative measurements of GH levels are considered not
clinically useful given current literature (7). The few studies evaluating GH
levels are all retrospective in design which limits their value for guidelines
(2,3,4,5,6).

Our study will be the first to prospectively evaluate early postoperative GH
levels in relation to surgical remission. In order to enlarge our subject
numbers for current study other Dutch university medical centers are approached
for possible future participation. Current assay used for GH in our
institution does not support immediate display of results. Our study is needed
to determine if such assay is useful to facilitate GH evaluation during surgery.

1. Ronchi CL, Varca V, Giavoli C, Epaminonda P, Beck-Peccoz P, Spada A, Arosio
M.
Long-term evaluation of postoperative acromegalic patients in remission with
previous and newly proposed criteria. J Clin Endocrinol Metab. 2005
Mar;90(3):1377-82.

2. Kim EH, Oh MC, Lee EJ, Kim SH. Predicting long-term remission by measuring
immediate postoperative growth hormone levels and oral glucose tolerance test
in
acromegaly. Neurosurgery. 2012 May;70(5):1106-13.

3. Abe T, Lüdecke DK. Recent primary transnasal surgical outcomes associated
with
intraoperative growth hormone measurement in acromegaly. Clin Endocrinol (Oxf).
1999 Jan;50(1):27-35.


4: van den Berg G, van Dulken H, Frölich M, Meinders AE, Roelfsema F. Can
intra-operative GH measurement in acromegalic subjects predict completeness of
surgery? Clin Endocrinol (Oxf). 1998 Jul;49(1):45-51.


5: Valdemarsson S, Ljunggren S, Cervin A, Svensson C, Isaksson A, Nordström CH,
Siesjö P. Evaluation of surgery for acromegaly: role of intraoperative growth
hormone measurement? Scand J Clin Lab Invest. 2001;61(6):459-70.

6: Sarkar S, Jacob KS, Pratheesh R, Chacko AG. Transsphenoidal surgery for
acromegaly: predicting remission with early postoperative growth hormone
assays.
Acta Neurochir (Wien). 2014 Jul;156(7):1379-87;

7: American association of clinical endocrinologists medical guidelines for
clinical practice for the diagnosis and treatment of acromegaly * 2011 update

8: Feelders RA, Bidlingmaier M, Strasburger CJ, Janssen JA, Uitterlinden P,
Hofland LJ, Lamberts SW, van der Lely AJ, de Herder WW. Postoperative
evaluation
of patients with acromegaly: clinical significance and timing of oral glucose
tolerance testing and measurement of (free) insulin-like growth factor I,
acid-labile subunit, and growth hormone-binding protein levels. J Clin
Endocrinol
Metab. 2005 Dec;90(12):6480-9

Determination of prognostic value of intraoperative growth hormone levels on
postoperative curation for acromegaly in patients undergoing transsphenoidal
resection of pituitary adenoma.

prospective

Low, additional collecting of blood will be done when patients are under
general anesthesia from protocolar placed arterial catheter. Postoperatieve
growth hormone levels will be determined from protocolar collected blood
samples.