Page 3 - Long-term surveillance following resection of pheochromocytoma

Kumar et al

tively to document complete resection of the tumor. When metastatic recurrences 45%). The incidence of new events
the postoperative metanephrines fail to normalize, persistent did not decline after five years of followup, but estimates
disease should be strongly suspected. Further imaging test- after 10 years of followup were imprecise due to the small
ing to confirm and locate residual catecholamine-secreting numbers of patients for whom data were available. Again,
tissue should be undertaken. extra-adrenal disease, age <20 years, familial pheochromo-
cytoma, and tumor size >150 mm appeared to correlate with
Recommendation 2: We suggest repeating plasma and/or an increased risk of recurrence. 17
24-hour urinary metanephrines at first postoperative fol- In both these studies, the incidence of new events is lower
lowup to ensure complete resection (Strong recommenda- than previous estimates. Even after long and uneventful follow-
tion, Low-quality evidence). up, there can be recurrent disease. This appears more common
in cases of familial and extra-adrenal disease. There is no tumor
Recommendation 3: We suggest monitoring for PPGL size below which there is no risk of a new event nor is there
recurrence by annually measuring plasma-free metaneph- any subgroup in which followup may be safely abandoned.
rines and/or 24-hour urinary fractionated metanephrines
(Strong recommendation, Low-quality evidence). Recommendation 4: We suggest annual followup for at
least 10 years following complete resection to monitor for
Duration of followup local or metastatic recurrences or new tumors (Weak rec-
ommendation, Very low-quality evidence).
In a recent systematic review, Amar et al studied the inci-
dence and factors associated with recurrence or new tumors Recommendation 5: We suggest high-risk patients (young,
16
after complete resection of pheochromocytomas. They genetic disease, larger tumor and/or a paraganglioma) be
included 38 studies from 1980–2012 on patients with pheo- offered lifelong annual followup (Weak recommendation,
chromocytomas who had complete resection and at least Very low-quality evidence).
one month of followup. The incidence rates from individual
studies were pooled in a meta-analysis. Specific conditions
Of the 38 studies included, there was one random -
ized control trial and one prospective cohort study, with Mild or borderline elevations in metanephrines
the rest being retrospective cohorts. There was a total of Some patients only have a mild or moderate elevation in free
2509 patients. The median age of patients was 42 years and plasma metanephrines levels (less than fourfold increase)
median tumor size was 48 mm. The duration of followup preoperatively. In this subset, secondary confirmatory test-
ranged from 14–180 months, with a median of 84 months. 16 ing can be pursued, often facilitated by an endocrinology
The overall rate of recurrent disease was calculated as referral. These include clonidine suppression testing and
0.95 events/100 person-years (95% confidence interval [CI] chromogranin A testing.
0.68, 1.21), which equates to a five-year cumulative inci- Clonidine suppresses norepinephrine production by the
dence of 4.7%. Of these new events, 22% were new tumors, sympathetic nervous system but not by pheochromocyto-
23% were local recurrences, and 55% were metastases. mas. Determining normetanephrine levels before and after
The median time from surgery to recurrent disease was 60 clonidine administration can help confirm the diagnosis in
months, and ranged from 3–204 months. 16 equivocal cases. 18
Factors associated with recurrence were also studied. Chromogranin A determination exists in secretory vesicles
Familial disease was identified as as a main independent risk of the neuroendocrine and nervous systems and has been
factors of recurrent disease. The presence of extra-adrenal dis- The presence of extra-adrenal dis- shown to be elevated in patients with pheochromocytoma.
ease (paraganglioma) was a strong predictor, and younger age Determining preoperative chromogranin A levels can help
and large tumor size were weak predictors of recurrence. 16 confirm the diagnosis, and in such cases, can also be used
The European Society of Endocrinology guideline reported for annual postoperative surveillance. 19
results from the European Network for the Study of Adrenal
Tumours (ENS@T) database comprised of 1153 patients from Recommendation 6: We suggest using annual clonidine sup-
six centers. A total of 701 patients had complete resec- pression or chromogranin A testing for followup of patients
17
tion of the primary tumor and documented followup of at with positive preoperative results (Weak recommendation,
least six months. In this database, 34% had a genetic or Very low-quality evidence).
syndromic disease, median age was 46 years, and median
tumor size was 44 mm. Median followup was 54 months. Biochemically negative disease
The risk of recurrence was 10 % over the first five years Pheochromocytomas can rarely be biochemically negative.
of followup (new tumors 42%, local recurrences 13%, and This appears to occur most frequently in cases of extra-

374 CUAJ • December 2019 • Volume 13, Issue 12