Partially autonomous cortisol secretion by incidentally discovered adrenal adenomas

ELSEVIER

ENDOCRINE ROUNDS Partially Autonomous Cortisol Secretion by Incidentally Discovered Adrenal Adenomas H&he

Recent

Lavoie and And& Lacroix

studies of the function

of adrenal

‘incidentalomas”

have re-

vealed that a proportion of those tumors secrete cortisol insufficiently to produce overt clinical Gushing’s syndrome, but that their autonomous cortisol production can suppress the hypothalamo-pituitaryadrenal (HPA) axis to various degrees; this neea!s to be recognized to avoid acute adrenal insufficiency after adrenalectomy. Several diagnostic approaches have been utilized to identify the partially autonomous cortisol-secreting suppression

adenomas.

It has been suggested that a lack of normal

of cortisol (>l4O nmoUL) on the morning

after I-mg oral

dexamethasone at bedtime would identify most functional autonomous cortisol-secreting tumors. Based on this criterion, approximately 18% of published cases of incidentalomas would secrete cortisol autonomously.

However,

other tests indicating

axis, such as abnormal

adrenal

alterations

iodocholesterol

of the HPA

uptake or decreased

plasma levels of dehydroepiandrosterone sulfate (DHAS), were found to be present in up to 79%86% of incidentalomas. This is illustrated by the description of three patients with incidentalomas with plasma cortisol levels < 140 nmollL in 2 of 3 patients after I-mg dexamethasone overnight; however, various degrees of HPA axis suppression demonstrated creased

by an i.v. dexamethasone

plasma

DHAS

(4-mg)

levels and unilateral

uptake. After laparoscopic

adrenalectomy,

suppression

adrenal

were

test, de-

iodocholesterol

the response of plasma cor-

tisol to 250&g i.v. of ACTH (l-24) was subnormal

in 2 of 3 patients and

was restored to normal within 2 months. We conclude that the criterion of a plasma cortisol level > 140 nmoUL, after an overnight I-mg dexamethasone suppression test, underestimates the incidence of partially autonomous cortisol-secreting adrenal adenomas. The literature on this subject is reviewed, and recommendations for evaluation treatment are presented. (Trends Endocrinol Metab 1995;6:191-197).

and

HCkne Lavoie and Andre Lacroix are at the Division of Endocrinology, Metabolism, and Nutrition, Department of Medicine, and Research Center, Hhtel-Dieu de Montreal, UniversitC de Montr&I, Mont&J, QuCbec, H2W lT8, Canada.

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Case Reports Case 1

A 57-year-old woman was referred in October 1994 for evaluation of a left adrenal mass measuring 3.4 cm in diameter; this was identified by an abdominal scan performed for the investigation of a 14-kg weight loss. During the last year, the patient had noticed insomnia, increased nervousness, palpitations, headaches, and a loss of appetite. She weighed 53 kg and stood 158 cm, and presented no physical signs of hypercorticism or hyperandrogenism. Her blood pressure varied between 145180 and 1601 100 mm Hg sitting, with a heart rate of 65-88 beats per min; a fall of blood pressure up to 35/10 mm Hg, without changes in heart rate, occurred irregularly without symptoms during upright posture. Physical examination was otherwise unremarkable. Laboratory studies showed normal electrolytes, creatinine, and glucose levels. The 24-h urinary catecholamine and metanephrine were within normal limits, and I3 ‘I-metaiodobenzylguanidine (13’1-MIBG) scintigraphy did not reveal any significant adrenal uptake. Plasma cortisol diurnal rhythm and free urinary cortisol levels were within normal range (Table 1); following oral administration of 1-mg dexamethasone at bedtime, the plasma cortisol level was at 97 nmol/L, fasting at 0800 h on the following morning. However, plasma cortisol did not suppress normally during an i.v. 4-mg dexamethasone test (Figure l), reaching a nadir of only 125 nmol/L (normals: < 51 nmol/L). Plasma ACTH levels were found to be at the lower range of normal, at 2.0-2.4 pmol/L basally (normal: 2-l 1 pmol/L), and were suppressed by dexamethasone infusion to 0.1 pmol/L at 2200 h, whereas the cortisolemia remained incompletely suppressed, at 152 nmol/L. The ACTH and cortisol responses to 1 pg/kg ovine corticotropinreleasing hormone (CRH) i.v. were subnormal, with a maximal ACTH response from 1.2 to 3.2 pmol/L, and of corti-

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Table 1. Initial cortisol profiles in the three cases of incidentalomas Msma cortisol (nmoV4 a.m.: p.m.: Dexamethasone 1 mg overnight Cortisoluria: (nmol/day)

Notmal range

cuse 1

cuse2

399 225 97

327;42 1 122;127 92

749; 1086 544; 404 246

125;184

118; 64

81; 183;159; 238; 136;191; 146; 191; 192

solemia from 542 to 649 nmol/L after 30 min. Plasma levels of dehydroepiandrosterone sulfate (DHAS) were decreased to 1.7 pmol/L (normal: 2.2-15.1), whereas androstenedione and free testosterone levels were normal. A 1311-6-iodomethyl-19norcholesterol (NP-59) scan performed without dexamethasone suppression revealed an uptake limited to the left adrenal gland mass location (Figure 2). A left adrenalectomy performed by the laparoscopic approach revealed a 5.0 X 3.0 X 3.4-cm tumor typical of an adrenocortical adenoma on pathological examination; the adjacent adrenal cortex was of normal appearance. One week postoperatively, plasma cortisol levels were normal basally, at 349 mnol/L, and increased to 663 nmol/L (normal: > 552 at 30 min, and

cuse 3

138-733 50% <140 50-280

>662 at 60 min) following stimulation with 250 pg ACTH l-24 i.v. (Cortrosyna, Grganon, West Hill, ONT). Two months postoperatively, morning plasma cortisol levels suppressed normally to < 28 nmol/L following I-mg oral dexamethasone overnight. The patient was feeling well; her appetite and weight were returning to normal. 2

Case

The past medical history of this 67-yearold woman included a transient cerebral ischemic attack in 1973, coronary insufficiency necessitating bypass surgeries in 1976 and 1987, hepatitis C, and a 7-year history of high blood pressure. She complained of dizzy spells with upright posture, hot flashes, and abdomi-

Figure 1. Intravenous dexamethasone test performed in the three patients with incidentalomas. Dexamethasone was infused at a rate of 1 mg/h from 1100 h to 1500 h, and blood samples were collected at the indicated time points for measurement of cortisol levels. Individual results are shown for case 1 (squares), case 2 (triung/es), case 3 (octagons), and the range of values in seven control individuals are shown by the shaded area. Oexa lmg/hr

800

.

+

nal pain. She underwent an abdominal computed tomography (CT) scan, which revealed the presence of a left 3.0-cm heterogeneous adrenal mass for which she was referred to our service in August 1993. On physical examination, she measured 149 cm and weighed 60 kg; her blood pressures varied between 156 and 220 mm Hg systolic and between 74 and 80 mm Hg diastolic. She presented no physical evidences of hypercorticism. The laboratory investigation included plasma Na+: 139 mmolL, K+: 4.5 mmolL; the 24-h urinary catecholamine and r3rI-MIBG scintigraphy were normal. Plasma cortisol cycles and 24-h urinary excretion of free cortisol were also within the normal range (Table 1); plasma morning cortisol level was 92 nmol/L after an overnight suppression test with I-mg of dexamethasone. However, the cortisol suppression following the i.v. 4-mg dexamethasone test was less than normal, with a nadir of 123 nmol/L at 0900 h on day 2; ACTH levels were within the normal range. The plasma DHAS level was decreased to 0.8 pmol/L, whereas free testosterone, estradiol (postmenopausal), aldosterone, and renin levels were normal. The NP-59 scan performed without dexamethasone showed a large uptake over the left adrenal, but no uptake on the contralateral side (Figure 2). A 3.0 X 2.6 X 3.0-cm adrenocortical adenoma (normal adjacent adrenal) was removed by a left laparoscopic adrenalectomy performed under hydrocortisone coverage during 48 h. One week later, the 24-h cortisoluria was decreased to 25 nmol/day (normal: 90-330); basal plasma cortisol was normal at 342 nmoliL, but increased suboptimally to 508 nmol/L 60 min after 250 pg CortrosynQoi.v. Oral hydrocortisone, 20 mg in the morning, was prescribed, and 2 months later, the response to ACTH (l-24) stimulation was normal (284+679 nmol/L). Case 3

0’

10

I

1

/

I

I

12

14

16

18

20

lime (hours)

192

1

t

22

24

I1

II

&?

903

This 69-year-old woman with non-insulin-dependent diabetes of 15 years’duration was admitted for acute pyelonephritis in April 1993. A left adrenal mass was found on abdominal ultrasound, and an adrenal CT scan confirmed the presence of a 2.5 X 3.0-cm nodule. The patient was taking Premarina, 0.625 mg p.o. daily, for menopausal replacement therapy. On physical examination, she mea-

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dexamethasone showed an uptake on the left adrenal side only (Figure 2). A left laparoscopic adrenalectomy, performed with steroid coverage during 48

adenomas

h, confirmed the presence of a 3.0 X 2.5 X 2.0-cm adrenocortical adenoma with

grees (Beierwaltes

a small rim of normal adjacent adrenal cortex. One week later, the basal plasma cortisol level was normal at 502 nmol/L, but did not increase beyond 553 nmol/L 60 min after stimulation with 250 pg Cortrosyna i.v. Hydrocortisone (20 mg) was administered orally every morning during 2 months, and the response to ACTH (l-24) was restored to normal (377-773 nmol/L).

were found to secrete cortisol

at a rate not sufficient

to produce overt

clinical signs of hypercorticism,

but suffi-

cient to alter the HPA axis to various deet al. 1973, Charbonnel

et al. 1981, Bogner et al. 1986, Viikkala et al. 1989, Hensen et al. 1990, Jockenhijvel et al. 1992, Reincke et al. 1992, Kobayashi et al. 1993, Osella et al. 1994); this needs to be recognized

because such patients can

be considered at risk to develop acute adrenal insufficiency

(Huiras et al. 1989). In

view of the increasing

frequency

of this

problem, and of the controversy concerning the extent

of the investigation

re-

quired, it appeared useful to review the literature on this topic.

??

Discussion

The wider availability of radiological stud-

Evidence for Autonomous Secretion

47.8 kg. There were no clinical signs of Cushing’s syndrome. Her blood pressures varied between 158 and 180 mm Hg systolic and between 62 and 85 mm Hg diastolic. Laboratory investigation conducted a few weeks after resolution of the pyelonephritis revealed normal plasma elecurinary catecholamine, and trolytes, 1311-MIBG adrenal scan. Plasma levels of

ies to evaluate abdominal symptoms using ultrasound, computed tomography (CT), and magnetic resonance imaging (MRI), has greatly increased the detection of incidentally discovered adrenal masses (incidentalomas); their prevalence was estimated to be 0.6%1.9% in CT series (Glazer et al. 1982, Abecassis et al. 1985) 1.4%-8.7% in autopsy series of general populations (Hedeland et al. 1968, Kokko et al. 1967) and up to 12.4% in essential hypertension and 16.5% in diabetes mellitus (Russi et al. 1945, Hedeland et al. 1968). Incidentalomas are found by CT in 82% of homozygous and 42% of heterozygous patients with congenital adrenal hyperplasia (Jaresch et al. 1992). Clinical and radiological evaluations can usually exclude metastatic lesions, adrenal cysts, myelolipomas, and hemorrhages. The majority of incidentalomas were initially considered as nonfunctional, based on measurement of basal adrenal steroid levels (Prinz et al. 1982, Copeland 1983). In the absence of overt signs and symptoms of hypertension, or clinical hypercorticism

cortisol were slightly elevated on estrogen replacement therapy, but diurnal rhythm was preserved and urinary free cortisoluria was repeatedly normal. However, plasma cortisol suppressed only to 246 nmol/L after overnight 1-mg dexamethasone administration; suppression with i.v. dexamethasone test was clearly subnormal. Plasma DHAS and free testosterone levels were decreased to 0.2 pmol/L and 0.5 pmol/L (normal: 0.7-7.6) respectively; plasma ACTH levels were normal at 5-7 pmol/L. An NP-59 adrenal scintigraphy without

or hyperandrogenism, some authors have suggested to avoid any further hormonal evaluations (Ross and Aron 1990, Gross and Shapiro 1993) and to monitor only tumor growth to select candidates for surgery. Other authors, conducting more detailed investigations, have brought attention to the existence of “silent” pheochromocytomas (Sutton et al. 1981, Krane 1985) and of subclinical autonomous adeglucocorticoid-producing nomas (Beierwaltes et al. 1973, Hensen et al. 1990, Reincke et al. 1992, Osella et al. 1994). Some patients with adrenocortical

Figure 2. NP-59 adrenal scans in the three cases of incidentalomas. The scans were performed without preparation with dexamethasone. The figure illustrates posterior views obtained 10 days after injection of 0.5 mCi of the tracer: the kidney locations, obtained by glucoheptonate scans, are indicated by the tracings.

sured 152 cm and weighed

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Beierwaltes report

Cortisol

et al. (1973) were the first to

two patients

with unilateral

take of NP-59 in adrenal adenomas out clinical excess

or biochemical

steroid

evidence

production.

gested that the adenomas ficient

cortisol

upwith-

They

of

sug-

produced

suf-

to suppress partially

the

HPA axis and showed that ACTH administration

could elicit normal iodocholes-

terol uptake in the contralateral the similarity but

nontoxic,

pointed

adrenal;

with 13iI uptake thyroid

out.

Rizza

by hot,

nodules

was

et al. (1978)

sug-

gested that the asymmetric

iodocholest-

erol uptake may be explained by the distribution

of the tracer

lipid content,

in the adenoma

rather than by an autono-

mous steroid production. was clarified

This question

by the demonstration

of a

larger adrenal vein cortisol output from the tumor side, with frequent et-al adrenal 1987).

suppression

The functionality

contralat-

(Gross

et al.

of incidentalo-

mas was also provided by the presence of steroidogenic

enzymes

by immunohistochemical 1992)

and

analysis;

mRNA

cortical

(Racz

of the enzymes

adjacent

nonneoplastic tumor

(Suzuki

et al.

et al.

1993)

atrophy and decreased

activity creased

in the tumors

steroid

were found adrenals. content

in In-

(Kobay-

ashi et al. 1993, Racz et al. 1993), and cortisol secretion from cells dispersed from the adenomas stimulation

(Bogner

in response to ACTH et al. 1986, Racz et

al. 1993), also confirmed the steroidogenic activity of these tumors.

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Table 2. Clinical and hormonalcharacteristics of partially autonomouscortisol-producingincidentalomas Number of cases

Author

Excess urinary coriisol

flex 1 mg F:>UO nmol/L

Adrenal Adrenal ACTH scintigraphy insu~ciency suppressed unilateral postop Comments

Beietwahes et al. (1973)

2

o/2

ND

ND

2/2a

ND

Rizza et al. (1978) Charbonnel et al. (1981) Bertagna and Orth (1981) Beyer and Doe (1986) Bogner et al. (1986)

4 1

O/4 O/l

ND ND

ND l/l

414 l/l

ND O/l

3

213’

ND

l/3

ND

ND

1 1

O/l l/l

ND ND

l/l ND

ND ND

O/l O/l

Gross et al. (1987)

7

l/7

o/7

ND

717

ND

Laudat et al. (1988)

10

o/10

o/10

o/10

ND

ND

McLeod et al. (1990)

7

215

S/6

616

l/7

Huiras et al. (1989) Virkkala et al. (1989)

2 20

o/2 2119

l/l o/15

l/l ND

Hensen et al. (1990) Rosen and Swartz (1992) Jockenhlivel et al. (1992)

13 1

o/13 O/l

3113 l/l

2113 ND

18

l/18

9118’

l/18

Reincke et al. (1992)

66d

l/4

8166

Suzuki et al. (1992)

15

6115’

Kobayashi et al. (1993) Osella et al. (1994) Flecchia et al. (1995) This report

14

S/lob

Total (%)

36d 22 3

l/36 4122 o/3

246

261177 (15)

313

212 O/8

ND 4119: unilateral; s/19: bilateral” ND ND

O/l O/l

ND

ND

618

ND

417

ND

2115

ND

ND

ND

ND

13/13”

3/14

7136 3122 113

8136 S/22 l/3

14124” 21122 313

l/14 ND o/3

36/l 95 (18)

341137 (25)

80/101 (79)

Contraiateral adrenal scan uptake ? by ACTH Lipid-related-uptake ? Adjacent adrenal atrophy Dex 2 + 8 mg: no L Dex 2 + 8 mg: no 1 Adjacent adrenal atrophy ? Adrenal venous cortisol t Evening cortisoluria: lO/lO Postop glucocorticoid Rx: 4/s l/2: recent prednisone O/l 1: progression in unoperated cases

1 ACTH to CRH: 13/13 Adjacent adrenal: no atrophy 3 cases: partial 2 lhydroxylase deficiency 4/S: adjacent adrenal atrophy 8/12: adjacent adrenal atrophy dex 2 + 8 mg no 1: 71 14 1 plasma DHAS: 42% 1 plasma DHAS: 86% 313 F not 1 by 4-mg i.v. dex

1l/60 (18)

CRH, corticotropin-releasing hormone; dax, dexamethasone; F, cortisol; ND, not determined. * Adrenal scintigraphy performed under dexamethasone suppression. * Measured as urinary 17-hydroxycorticoids. E Morning plasma cortisol: ~84 nmolL after dexamethasone 2 mg at bedtime. d Excluding proven cases of adrenal cysts, carcinomas, metastasis, aldosteronomas, or pheochromocytomas.

Endocrine Producing

Evaluation of CortisolIncidentalomas

Different investigation protocols were used to determine which patients with clinically silent incidentalomas may have partially autonomous cortisol-producing adenomas. Twenty-four-hour urinary free cortisol levels are not sufficient to detect subclinical cortisol-pro-

194

ducing adenomas, as they were elevated in only 15% of cases (Table 2); however, evening (2000-2400 h) urinary cortisol levels were elevated in 10 of 10 adenomas without clinical or other biochemical Cushing’s syndrome (Laudat et al. 1988). It has been suggested that an insufficient suppression of cortisol (>140 nmol/L) on the morning after

I-mg oral dexamethasone at bedtime would identify functional autonomous cortisol-secreting tumors (Reincke et al. 1992, Osella et al. 1994). Using this criterion, 18% of incidentalomas, overall, failed to suppress normally (Table 2); in the three largest screening studies of incidentalomas, 8 of 66 (12%) (Reincke et al. 1992), 7 of 36 (19%) (Osella et al.

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(1995), 18 of 22 cases (82%) with unilateral iodocholesterol uptake had cortisol levels > SO nmol/L, but only 3 of 22 (14%) had > I40 nmol/L after overnight suppression with 1-mg dexamethasone. Cortisol suppressibility after an overnight low-dose of dexamethasone was less in patients with adrenal unilateral scintigraphic uptake than in patients without adrenal uptake (Virkkala et al. 1989). We have found that the i.v. 4-mg dexamethasone test (Abou Samra et al. 1985) is very sensitive and useful in the differential diagnosis of hypercorticism (Lacroix et al. 1992 and unpublished observations): it was more useful than the 1-mg overnight test here to distinguish subtle alterations in the HPA axis in the three cases reported. Caution should be used in interpreting the results in patients using estrogens, as high doses of potent estrogens can alter suppression by dexamethasone (Nugent et al. 1965, Asfeldt 1969), although conjugated estrogens up to 1.25 mg daily were found not to modify the normal range (Treece et al. 1977). Spurious lack of suppression after low-dose dexamethasone can also be found with stress, depression, affective disorders, alcoholism, or with drugs such as barbiturates, phenytoin, meprobamate, methaqualone, amicarbamazepine, and noglutethimide, Interpretation of Dexamethasone rifampin. It would thus appear that by Suppression Tests using as normal a plasma cortisol level of < 140 nmok’L after 1 mg dexamethasone The upper limit of normal of morning overnight, the incidence of partially aucortisol, following a single overnight tonomous tumors will be substantially dose of 1 mg dexamethasone, has varied underestimated; this may explain the difgreatly between 96.6 and 276 nmol/L ference in test positivity with the adrenal (3.5 and 10 p/dL) (Nugent et al. 1965, iodocholesterol scintigmphy and plasma Pavlatos et al. 1965, Crapo 1979, Hensen DHAS levels (Table 2). et al. 1990); the value of 140 nmol/L (that is, close to 5 pg/dL) was used in some Risk of Adrenal Insufficiency studies (Reincke et al. 1992, Osella et al. Acute adrenal insufficiency following 1994, Flecchia et al. 1995), whereas surgical removal of incidentalomas was Hensen et al. ( 1990) used a level of 100 also initially described in two patients nmol/L. It must be remembered that the (Huiras et al. 1989); another patient died mean level of cortisol following overnight dexamethasone suppression in 24 h after removal of an incidentaloma normal nonstressed individuals was of and the contralateral adrenal was found 30 + 10 (mean 2 SD) nmol/L, with un- to be completely atrophic (McLeod et al. 1990). Evidence of clinically significant detectable levels in more than 50% of adrenal insufficiency was reported overindividuals (Pavlatos et al. 1965). It apall in 19% of cases, although more subtle pears quite likely that many patients evidence of suppression of the HPA axis with partially autonomous cortisol-procan be present during several months ducing adenomas would have cortisol levels between SO-140 nmol/L after 1-mg postoperatively (McLeod et al. 1990, Reincke et al. 1992, Kobayashi et al. 1993, dexamethasone suppression and be Osella et al. 1994). Atrophy of the adja falsely interpreted as normally suppresscent adrenal cortex was reported in sevible; in fact in the study of Flecchia et al.

1994), 9 of 18 (50%) (Jockenhovel et al. I992), and 3 of 22 (14%) (Flecchia et al. 1995) of adrenocortical tumors met this criterion; however, in 2 out of 3 cases presented here, as well as in 7 of 7 (Gross et al. 1987), in 10 of 13 (Hensen et al. 1990), and in 8 of 8 (Virkkala et al. 1989) other cases of clearly partially autonomous cortisol-producing tumors, the diagnosis would be missed because plasma cortisol levels were < 140 nmoVL following an overnight 1-mg dexamethasone test. Suppressed ACTH levels were found in 25% of incidentalomas (Table 2); however, more sophisticated tests using CRH stimulation demonstrated partial suppression of ACTH response in several patients (Hensen et al. 1990, Reincke et al. 1992, Osella et al. 1994). Recent studies reported that 42% (Osella et al. 1994) or up to 86% (Flecchia et al. 1995) of patients with incidentalomas had decreased plasma levels of DHAS, possibly reflecting early suppression of the HPA axis; DHAS were also decreased in our 3 cases, as well as in others (Beyer and Doe 1989, Hensen et al. 1990). The most consistent abnormality noted (79%), however, was unilateral or dexamethasone nonsuppressible adrenal scintigraphic uptake of iodocholesterol.

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eral series (Charbonnel et al. 1981, Bogner et al. 1986, Reincke et al. 1992, Suzuki et al. 1992, ~acz et al. 1993), but did not always correlate with clinical evidence of adrenal insufficiency. Evolution of Cortisol-Producing Incidentalomas

Although patients were believed not to have clinical evidence of hypercorticism, weight loss and improvement of hypertension or glycemic control were reported postoperatively by several authors (Reincke et al. 1992, Kobayashi et al. 1993, Osella et al. 1994 ). The evolution of nonfunctioning incidentalomas was also studied. No progression was found in 1 patient during a S-year period (Charbonnel et al. 1981). Vi&ala et al. (1989) found no evolution in 11 cases followed during 1849 months. Hensen et al. (1990) reported that 1 of 3 patients with preCushing status evolved to overt Cushing’s syndrome within 1 year. In 18 cases monitored during 1 l-101 months, progression of 1 case each to overt and to preclinical hypercorticism was found (Jockenhovel et al. 1992). Osella et al. (1994) followed 9 patients (8 with normal dexamethasone suppression) and found 2 tumor size progressions, and 2 other cases of subtle alterations of HPA axis over a I2-month period. No large follow-up study has been conducted yet in cases with clearly autonomous subclinical cortisol-secreting tumors to determine the real incidence of progression toward overt Cushing’s syndrome. However, given the relatively high prevalence of incidentalomas, and the relatively low prevalence of overt adrenal Cushing’s syndrome, the progression is probably not very common. Suggested Protocol of Investigation and Therapy

Our current protocol for incidentalomas includes, in the absence of clinical manifestations of recent hypertension, diabetes, or overt hypercorticism or hyperandrogenism, the exclusion of silent pheochromocytomas by urinary metanephrine or catecholamine determinations, and by MRI or r3’I-MIBG scanning. In addition, basal plasma levels of electrolytes, cortisol, DHAS, and 24-h urinary excretion of free cortisol are obtained; in the presence of hirsutism, testosterone and 17_hydroxyprogesterone are determined basally, and an

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19.5

ACTH stimulation test is performed to exclude late-onset congenital adrenal hyperplasia. This is followed by an overnight I-mg dexamethasone test: if the morning plasma cortisol level is above 50 nmolk, an i.v. 4-mg dexamethasone and a NP-59 adrenal scan without dexamethasone preparation are performed. If suppression is normal, but the mass is irregular, between 2 and 4 cm, with either increased enhancement after contrast on CT, or somewhat intense T2 signal on MRI (negative 13’I-MIBG), a NP-59 scan is performed without dexamethasone preparation; a relatively decreased uptake on the tumor side would prompt laparoscopic surgery to eliminate an adrenocortical cancer. Adrenal biopsy would be reserved only for suspected metastatic lesions. Our indications for surgery include obviously overtly oversecreting tumors of the adrenal medulla or cortex. The significant decrease in surgical morbidity, which we have found using a laparoscopic approach to adrenalectomy (Gagner et al. 1993 and 1994), has led us to recommend surgery for incidentalomas above 3-3.5 cm (Prinz et al. 1982, Glazer et al. 1982, Katz and Shirkhoda 1985). A careful evaluation of the HPA axis is always performed prior to adrenalectomy, and if a significant suppression is noted, hydrocortisone hemisuccinate (SO-100 mg i.v. every 8 h) is provided during surgery, and recovery is monitored postoperatively prior to discontinuation of glucocorticoid coverage. In addition to tumor size considerations, for partially cortisol-secreting adeautonomous nomas, we currently recommend surgery in the presence of clear ACTH suppression, hypertension, diabetes, or other potential signs of hypercorticism such as osteoporosis: in the absence of such manifestations, the relatively low frequency of progression of incidentalomas suggests that observation with 6-12 monthly reevaluations would be indicated.

??

Acknowledgments

The collaboration of the Endocrinology Division staff for patient care and referral; of Marie-Th&se Cat-on, RN., for endocrine testing; of Edouard Bolte, M.D., for endocrine laboratory studies; of Odile for radiological Prosmanne, M.D., interpretation; of Raymond Taillefer,

196

01995,

M.D., for nuclear medicine studies; of Michel Gagner, M.D., for surgery; and of Louis Gaboury, M.D., for pathology studies is gmatly appreciated.

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