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Surgical treatment of aldosteronism
Surgical COMBINED
Treatment
EXPERIENCES PETER
of Aldosteronism
AT THE MASSACHUSETTS MEMORIAL BENT BRIGHAM HOSPITALS
AND
THE
REGINALDH. SMITHWICK,M.D., J. HARTWELLHARRISON,M.D., LAURENCEUNGER, M.D. AND GEORGEP. WHITELAW, M.D., Boston, Massachusetts From tbe Departments of Surgery, Massachusetts Memorial Hospitals and Boston University School of Medicine, Boston University Medical Center, and tbe Department of Urology, Peter Bent Brigbam Hospital and Harvard Medical School, Boston, Massachusetts. Tbis work was supported in part by Research Grant H-4631. (Cr) from tbe National Institutes of Healtb. United States Public Healtb Service, Wasbinglbn, D. 6., and by a grant from tbe trustees under tbe wills of Cbarles A. King and Marjorie King.
HIS report deaIs with twenty patients who T were operated upon at the Massachusetts
MemoriaI or the Peter Bent Brigham Hospitals for aIdosteronism. Thirteen of these patients had cortica1 adenomas and appear to conform with the diagnostic criteria which Conn [x,2] has estabhshed for patients having primary aIdosteronism. Data concerning each of these patients are summarized in TabIes IA and IB. Five patients are Iisted under the heading, acquired aldosteronism. They did not have tumors, but otherwise had findings comparable to patients having primary aIdosteronism. The data for these patients are summarized in TabIes IIA and IIB. These tabIes aIso contain information regarding two patients with aIdosteronism secondary to renaI disease. In another articIe in this Symposium Conn, Knopf and Nesbit have analyzed their own experiences with eighteen cases of primary aIdosteronism and have reviewed and tabuIated the data which they were abIe to obtain from a review of 145 cases which had been reported in the Iiterature up to JuIy 1962. They have summarized the symptoms and physical findings in a Iarge number of cases; therefore, it seems unnecessary to persue these aspects of the matter further. Our report is concerned mainIy with the data upon which the diagnoses were based, results, iIIustrative case reports, American
Journal
o/ Surgery.
Volume
107, January
1964
surgica1 technic and certain aspects of preoperative preparation and operative and postoperative management. PRIMARYALDOSTERONISM There were thirteen patients in this group. (Tables IA and IB.) EIeven were women. TweIve had a single cortica1 adenoma, six of which were on the right and six on the left side. EIeven of the tweIve singIe tumors were benign, one was maIignant. The other patient had biIatera1 tumors which were maIignant. The tumors varied in size from 0.9 to 7.2 cm., the great majority being Iess than 3 cm. in diameter. Six of the fourteen tumors were less than 2 cm. in Iargest diameter and often much Iess than 2 cm. in cross section, so that they may be quite ffat and easy to overIook, especially if they are centraIIy Iocated in the substance of the gIand. The age of the patients varied from thirtyone to sixty years, and the known duration of hypertension from one and a haIf to eighteen years. Thus, primary aIdosteronism occurs preponderateIy in middIe aged or oIder women with elevated bIood pressure of several to many years ’ duration, and the cortica1 adenomas are smaI1, uniIatera1 and benign in the great majority of patients. The diagnosis shouId be suspected whenever hypertension is associated with a Iow IeveI of serum potassium. These two findings should be supported by further evidence. Table IA contains additiona preoperative information about these thirteen patients. In addition to the bIood pressure and serum potassium IeveIs, the vaIues for serum sodium, carbon dioxide and chIoride are aIso given. The sodium IeveI is typicaIIy norma or eIevated. The CO* vaIue 178
Treatment
of AIdosteronrsm
f .:.
z
2 m
%
2.0
Right
Right Left Right Left
E. H.
2.2
0.9 1.3
-
Grade 2
Grade 3
... I.1
Benign
Benign MaIignani MaIignant
Benign
Benign Benign Benign
Ietters
...
...
Negative
Negative
VacuoIar nephropathy Grade z Negative Grade 3 Negative Grade 2 Negative
Benign
Grade I
Grade z
Negative
Negative
..,
VacuoIar nephropathy
-__-
TubuIes
IB
I
Norma1
I
Normal
I
r4o/78
r 28/94 I 80/90 115/80
Normal Normal Norma1
Normal
Normal Normal Normal
Normal
Norma1 Normal Norma1
Norma1 = Peter Bent Brigham
Hospita
r35/8o
Normal Norma1 Normal
Excision of right corticai adenoma Right adrenaIect.omy Left adrenaIectomy BiIateraI tota adrenaIectomy
IO6/60
r 3o/7o 1466190 17O/IZO
Norma1 Normal Normal Norma1 Norma1 Normal Norma1 Norma1 NormaI
Left adrenalectomy Left adrenahzctomy Right adrenaIectomy
-
26/88 I
Norma1
Norma1
97/7x
Norma1
NormaI
r3o/9o
Normal
Norma1
Normat
Normal
Left adrenaIectomy
Post-
15
(yr.)
IntervaI
,operativt
I
_
-
2%
6 wk. 12 mo. 3
r
~
Carcinoma Left side explored first; carcinoma of Ieft adrenaf gland
...
..
Cerebrovascular accident preoperatively. Slight improvement without drugs
.
. .
2
I
...
3 3
eIetumor
CerebrovascuIar accident preoperativeiy
Blood pressure vated unti1 removed
Diagnosis based on urine pH, eIectrocardiogram and renal biopsy Tumor found at autopsy
Comment
2%
4%
5
BP. . ref ‘ractory to drugs; died five years postoper cident atively of cerebr O\
Norma1
Blood Pressure (mm. Hg)
Norma1
BiIateraI splanchnicectomy pIus excision of right cortical adenoma BiIateraI spIanchnicectomy in 1952; adrenaIs not expIored Bilateral splanchnicectomy in 1952; right adrenaIectomy in 1956 Excision of left corticai adenoma Excision of Ieft cortical adenoma
EIectrocardiogram?
ADENOMAS)
Urine
_--~
-
CORTICAL
EIectroIytes
(ADRENAL.
TABLE
Operation
ALDOSTERONISM
Benign
Grade I
Benign
Grade 3
...
,
Benign
Benign
L-
Arterioles
Renal Biopsy
Memorial HospitaIs; 11 lsetts * Numbers = I f Normal as regards e vi dence of hypokalemia.
C. E. C.
‘fl;.. :*I?.
Left
Right
9. 1M. P.
.
0.9 4.0 I.3 7.2
Left Left Right
6. A. H. 7. B. G. 8. C. B.
IO.
2.2
Left
5. D. G.
2.Y
Left
4. L. B.
2.5
5.0
Right
M.DeS.
2.
3. M-C.
1.0
Right
ccm.)
C.W.
_
Side
PathoIogic Condition
Adenomas
Size
I.
Case* and Patient
Cortical
PRIMARY
Treatment
of Atdosteronrsnl
-I
normal
plasia
plas,a
was normai
8s t0 evidence
of IwpokaIemia.
subtotal
adrenalectomy
adrenalectomy
adre-
Brigham
total
Hospital.
adrenaIectomy
Normal
-
Norma I
Norma I
Norma I
1
Norma I
~
Urine
-
-
I
rr4/94
f 30/70
140/w
I 20/80
I44/94
I 40/85
i
I
es=
-
I
YT.
comatose
14 mo.
4 yr.
yr.
4 Yr.
3%
8 mo.
2%
y
Interval
ative
I ‘ostoper-
in shock,
11 Negative
1Negative
’Negative
1Negative
-
i mm.
gram?
Hg)
Blood Pressure
cardio-
r_=
-
GLANDS)
Electro-
ADRENAL
Died three weeks postoperatively,
-7
NORMAL
Normal
Secondary Aldosteronism
total
total
adrenalectomy
splanchnicectomy;
OR
in
adrenal-
(60 per cent)
right
nephrectomy
Bilateral
Right
B&tend
Bilaterd
left total
BiIateraI
nalectomy,
in 1959
total
spIanchnicectomy
Operation
IXB
ALDOSTERONISM
TABLE HYPERTR~PHY
biIatera1
Left tot&
Peter Bent
Normal
Grade 3
=
atrophy
tubular
letters
pyelone(marked),
phritis
athy
nephrop
VZXCU&I
Negative
Negative
Chronic
Grade z
Hospital;
hyper-
Memorial
Nodular
hyper-
hyper-
hyper-
Nodular
Nodular
Nodular
Massachusetts
f Electrocardiogram
* Numbers
F. N. L.
=
Grossly
normal
M. M.
Grossly
rq.
plasia N0iXlal
plasia
NClrmZll
4.0
E. T. D.
5.8
9.4
J. C.
trophy
hyper-
? slight
Grade 2
athy
plasia Normal
nephrop
hyper-
D.
trophy
VXUOhr
ectomy Grade 2
plasia Nodular
plasia
Hyper-
1946;
Negative Bilateral
hyper-
2
-
Nodular
Grade
-_
Tub&s
Biopsy
hyper-
Left
Renal
Arteride5
I
HYPERPLASIA,
Nodular
Right
. ~
II .2
Left
PathoIogy
~3. S. G.
S.
(pm.)
- ~
7.5
J.
-
Right
Weight
Giands
12. M. A.
,I.
p
and
Patient
Case*
Adrenai
-
(NODULAR
ACQUIRED
j
mo.
both
and uremic
pyeionephritis
artery
of renal
struction chronic
arteriosclerotic
and
ob-
nonfunctioning
giands
kidney;
(64 sm.)
adrenal
Patient cured without
reremoving
requiring
was physiologi-
accident
w.
o
8
2
?” i;’ 0
3
“*
_i g 4 postoperatively
therapy
complete placement
tally
Adrenalectomy
SmalI
I
13
-. from cerebrovascular
Died
__
comments
Treatment
ot’ Aldosteronism hypertension is characteristicall> not rapid13 progressive, excessively severe or of the malignant variety (papilledema). In summary, we would believe that in the absence of renal disease or diuretic treatment the following findings justify the diagnosis of primary aldosteronism and expIoration of the adrenal gIands: (I ) hypertension: mild to severe; (2) plasma K, persistently low; (3) plasma C02, norma or elevated; (4) plasma Na, normal or elevated; (5) urine K, high when serum K low; (6) urine, often high pH, Iow specific gravity; (7) eIectrocardiogram, usuaIIy shows evidence of hypokalemia. IdeaIIy, the folIowing information should be obtained if possibIe: (I) norma1 urinary I 7-hydroxycorticosteroids always, and (2) a t- urinary aldosterone IeveI. If no tumor is found, the diagnosis w&d be congenital or acquired aIdosteronism. The resuIts of operation were good as regards the effect on blood pressure levels, the carcIiovascuIar system in general and the eIectroIyte pattern. As shown in TabIe IB, the bIood pressure return.ed to norma or near norma in twelve patients. In one, the diagnosis was made at autopsy. In four patients, the cortical adenoma was removed and the rest of the adrena gland was preserved. In seven, uniIateraI total adrenaIectomy incIuding removal of the adenoma was performed. In one patient, bilatera1 total adrenalectomy with remova of the adenomas was performed. This was the onIy patient who required repIacement therapy. This possibility must be anticipated, although it wiI1 rarely be necessary in patients with primary aIdosteronism. The electrocardiograms reverted to normal so far as evidence of hypokalemia was concerned as did urinary pH, specific gravity and potassium content. Several patients will be commentecl upon briefly. One patient (Case I) was a forty-six year old woman with hypertension of eighteen years’ known duration at the time of operation fifteen years ago. BiIateraI splanchnicectomy was performed. On exploration of the adrenal glands, a I cm. cortical adenoma of the right adrenal gland was found and removed. Renal biopsy specimens were also obtained. The patient has been weI1. BIood pressure was 140/78 mm. Hg fifteen years later and her genera1 CardiovascuIar status was exceIIent. This patient was operated upon long before Conn described the entity of aldosteronism and is one of many who have undergone
1s high or norma I. Only about half the CO, determinations lvere elevated so that it is not necessary to have persistent evidence of nlkalosis to make the diagnosis. By contrast, it is very unusual to find the potassium level anything but reduced. When normal, which it may I e occasionally, it is usuaIIy at the Iolyer range of normal. In this connection, it is important to know whether the patient has been taking any of the thiazide derivatives, since they cause a depression of the serum potassium and elevation of CO, IeveIs. In this case the drug shouId be eIiminated and the K and CO, values repeated at frequent intervaIs for atl!east one month. If the potassium vaIues are persistently Iow and the CO, vaIues norma or eIevated, the presumptive diagnosis is primary aIdosteronism in the absence of evidence of a renaI factor. The serum chloride is generaIIy normal or occasionally a little below normal. The urinary specific gravity and pH vary, but the specific gravity wil1 often be Iow and the pH high. The evidence so far referred to makes the diagnosis almost certain. However, an additional finding which virtuaIIy clinches the diagnosis is a persistentlv high urinary potassium excretion. As sholvn in TabIe IA, this was found to be the case in a11 ten patients in whom this observation was made. The excretion of more than 30 mEq. of sodium and at Ieast 35 mEq. of potassium is typical of primary aIdosteronism. Since this determination is available to most its importance as a diagnostic physicians, criterion is emphasized. Also important, but not widely available, are determinations of serum or urinary aIdosterone Ievels. They may be normal or elevated and probabIy are eIevated in a11 patients at some time. OnIy a few laboratories are capabIe of performing this analysis accurately at the present time. In only two of our thirteen patients was the IeveI of aldosterone excretion known. Patients with primary aIdosteronism excrete normal amounts of I 7-hydroxycorticosteroids in the urine, so that if possibIe, this determination should be made. This information was rareIy avaiIabIe in our cases. FinaIIy, the electrocardiogram usuaIIy shows evidence of hypokaIemia and did so in eIeven of our thirteen patients. The various diagnostic criteria are discussed in much greater detai1 in the papers by Conn, Knopf and Nesbit, and ReIman in this Symposium. Both emphasize that the ‘83
Smithwick,
Harrison,
Unger and Whitelaw
FIG. z.. Right adrenal gland (Case 3, Tables IA and IB), a flat inconspicuous adenoma measuring z. cm. can be seen in the Iower left portion of the gland. The rest of the gland shows nodular hyperplasia.
FIG. I. Low and high power views of renal showing vacuolar nephropathy of the tubules, of hypokaIemia. (Case I, Tables IA and IB.)
tubules typical
removal of a cortical adenoma at spIanchnicectomy. Among these patients there are undoubtedly others who had primary aldosteronism. Potassium and sodium determinations were not obtained routinely in these patients as the flame photometer was not in use. The diagnosis of primary aIdosteronism seems warranted in retrospect in this patient, since the pH of the urinary specimen was uniformly high and the specific gravity low. The electrocardiogram had changes typical of hypokaIemia. The renal biopsy showed tubuIar vacuolar nephropathy, typica of that which may be noted when hypokaIemia is present. (Fig. I .) Another patient (Case 2), by contrast, was operated upon in 1952, and bilatera1 splanchnicectomy was performed without exploration of the adrenal glands. Hypertension was not affected and persisted despite the use of various combinations of antihypertensive drugs, She was readmitted to the hospital five years later folIowing a cerebra1 hemorrhage which proved fatal. The eIectro1yte pattern at that time was
typical of primary aIdosteronism as were urinary and electrocardiographic findings. At autopsy a benign cortical adenoma, measuring 3 cm. in diameter, was found arising from the right adrenal gIand. Only one patient (Case B, Tables IA and IB) who had biIatera1 adenomas had a larger tumor, which measured 7.2 cm. in diameter. The incidence of cortica1 adenomas is much higher among hypertensive than among normotensive persons. They are a11 simiIar in appearance and coIor and most are thought to be unreIated to hypertension. The microscopic appearance of the tumors causing aIdosteronism apparentIy has not been found to differ significantIy from that of cortical adenomas found at autopsy in normotensive persons. One patient (Case 3) aIso underwent splanchnicectomy in 1932. The adrena gIands were expIored but no tumor was found. Hypertension persisted and was refractory to al1 antihypertensive drugs. In 1936 the patient was studied in detai1 with the possibility of aIdosteronism in mind. The findings were typica1. (Tables IA and IB.) The adrena glands were re-explored and a cortical adenoma was found on the right side. It was diffrcuIt to fee1 because, aIthough it was 2 cm. in largest diameter, it was buried in the center of the gIand and was ffat rather than round or ova1 in shape. (Fig. 2.) It, undoubtedly, was present at the time of the original operation. Because many of the tumors causing primary aIdosteronism are Iess than 2 cm. in diameter, 184
Treatment
of AIdosteronism
exposure of the adrenal glands must be exceIlent and exploration thorough. Another patient (Case C), for instance, underwent bilateral adrena exploration elsewhere four years before a 1.8 cm. adenoma was removed. The tumor was undoubtedly present at the first operation and was overlooked. Two patients (Cases 6 and IO) had tumors which measured Iess than I cm. in diameter. Figure 3 is a photograph of the specimen from Case 6. A preoperative diagnosis of aldosteronism was made in Cases 4 through C, and splanchnicectomies were not performed in these ten patients. COICGENITAL
AND
ACQUIRED
ALDOSTERONISM
The diagnosis of primary aldosteronism has been reserved by Conn for patients having hypertension associated with other findings which we have just commented upon and who have adrenal cortical adenomas. For patients who do not have adenomas, but who otherwise have identical findings, he has suggested the diagnosis of congenital aldosteronism for a group of 1.ounger patients, aged nine to twentythree years, whose symptoms can be traced back to very early chiIdhood. We have added the diagnosis of acquired aldosteronism because it wouId seem most unlikely that any of the five patients listed in TabIes IIA and IIB had congenita1 aldosteronism because of their age or known duration of hypertension. Prior to expIoration it is not possibIe to differentiate between the various forms of aldosteronism with certainty. However, the marked preponderance of woman (eleven of thirteen) among our patients having primary ardosteronism is in sharp contrast to marked preponderance of men (four of five) among patients having acquired aldosteronism. One must, therefore, suspect that male patients are much less IikeIy to have tumors and are more likely to have nodular hyperplasia, hypertrophy or norma adrena glands. Hypertension may be rapidly progressive or of the malignant variety in contrast to that in patients having primary aldosteronism. Absence of evidence of renaI hypertension or the effects of diuretic antihypertensive drug treatment is, however, necessary for the diagnosis of congenita1 or acquired aldosteronism. Of the five patients listed in TabIes IIA and IIB, two were found to have noduIar hyperplasia of both adrena glands. One patient (Case 12)
had nodu1a.r hyperpIasia of the left and hypertrophy of the right adrenal gIand. One (Case I 3) appeared to have norma glands; however, since the weight of the one which was removed was the glands probably were slightly 7.7 w., hypertrophied. No nodules were present. One patient (Case E) had normal adrenal gIands. When both adrenal gIands show nodular hyperplasia, biIatera1 total aclrenalectomy wouId appear to be indicated. The three patients treated in this fashion did weI1. One (Case I I) died thirteen months after operation of a CerebrovascuIar accident even though the bIood pressure was normal. He had been operated upon in 1946 for hypertensive cardiovascuIar disease, and biIatera1 splanchnicetomy was performed. Hypertension persisted despite antihypertensive drug treatment. In 1959 a diagnosis of aldosteronism was made. Expioratory surgery reveaIed bilatera1 noduIar hyperpIasia, and both adrena gIands were removed. BIood pressure became norma and was 140/85 mm. Hg eight months later. AI1 other stigmas of aIdosteronism also disappeared. One patient (Case 12) aIso has done we11 although there have been probIems reIated to the need for repIacement therapy which must be faced whenever totaI adrenalectomy is performed. An attempt was made in th’is patient to avoid total repIacement therapy by removing al1 of the Ieft adrenal gland which showed
Smithwick,
Harrison,
Unger
FIG. 4. The adrenal gIands of a patient (Case 12) with acquired aldosteronism. (TabIes IIA and IIB.) There was no tumor. The gIand on the Ieft side of the photograph showed noduIar hyperpIasia and on the right, hypertrophy.
noduIar hyperpIasia, and an estimated 60 per cent of the right adrena gIand, which was hypertrophied but contained no noduIes. (Fig. 4.) However, adrenalectomy was physioIogicaIIy compIete. Some of the probIems which may resuh from tota adrenaIectomy are we11 described in a Ietter from the patient’s physician written one year and eight months after operation in repIy to a request for foIIow-up information. The folIowing is a quotation from his Ietter. “At his Iast examination the bIood pressure was zoo/130 sitting, 190/126 standing -paroxysmaI auricuIar fibrihation-marked Addisonian pigmentation. It is quite a task to maintain Mr. M. A. (Tables IIA and IIB) between the ScyIIa of hypertension and congestive failure and the Charybdis of adrenocortica1 faiIure.” As you know, these are dangerous cIiffs between Italy and SiciIy. Guarding the ItaIian shore is ScyIIa, a 12 footed, six headed she-monster with three rows of teeth. On the Sicilian side is Charybdis, another femaIe creature who three times a day swahows up the waves and three times a day Iets them out. If one is Iured by ScyIIa, one wiI1 go on the rocks; whiIe if persuaded by Charybdis, one will be enguIfed by a whirIpoo1, a most unsatisfactory outcome in either case. It wouId, therefore, appear that biIatera1 total adrenaIectomy shouId not be performed without good and sufficient reason. The most recent check-up information 186
and WhiteIaw
was received three and a haIf years after operation in response to a foIIow-up Ietter. The patient had moved to CaIifornia, was retired, feIt very we11 and was extremeIy gratefu1 that his Iife had been saved by the operation. His genera1 condition was satisfactory and the most recent blood pressure readings were in the range of 130/90 to 144/94 mm. Hg. One patient (Case D, TabIes IIA and IIB) likewise underwent biIatera1 total adrenaIectomies for noduIar hyperpIasia and has been we11for two and a haIf years. Two patients (Cases I 3 and E, TabIes IIA and IIB) are of particmar interest. The first was a forty-two year old surgeon with a difhcuh personaIity. He had rapidly progressive symptomatic hypertensive cardiovascuIar disease of four months’ duration, with retinitis, an abnorma1 eIectrocardiogram and norma renaI function. He had not been on thiazide drugs. The findings, otherwise, were typica of primary aIdosteronism; however, because of the progressive nature of hypertension, its short duration and the fact that he was a maIe, the presumption was that he wouId not have a cortica1 adenoma. At expIoration, the adrena gIands appeared to be normaI. There was considerabIe argument about what should be done. BiIateraI tota adrenaIectomy was favored by most. UniIateraI adrenaIectomy was performed combined with a conservative spIanchnicectomy. His course has been satisfactory (Fig. 5) and bIood pressure was 120/80 mm. Hg four years after operation, Since the adrena gIand which was removed weighed 7.7 gm., it probabIy was sIightIy hypertrophied. No nodules were found. AI1 other evidences of aIdosteronism have disappeared. He, of course, has not required adrena repIacement therapy which wouId have been a rea1 probIem in this particular patient. It is, of course, impossibIe to teI1 whether adrenaIectomy, spIanchnicectomy or both procedures pIayed a roIe in the resuIt. It would seem worth whiIe to try this combination of procedures again under simiIar circumstances. A forty-three year old man (Case E) with hypertension of three weeks’ known duration aIso has done weI1. His adrena gIands were normal. Blood pressure was 130/70 mm. Hg four years after biIatera1 tota adrenaIectomy. He, of course, is being given adrena repIacement therapy. Most surgeons like to avoid removing both adrena gIands whenever possible. Most internists, who speciaIize in endocrine problems,
Treatment
Splanchnicect. m: e-12
of Aldosteronisnr
Encephalopathy 3 c--Abn. 38-75 3.4t------33.1 -
I I LD:S-12
L.Mmmlect.
).-
N I N . 24-62 + 4.6 )* 26.0
Br~iii Eyes ECG PSP K cot
T.E. No-35ImEq/Kg T.E.
0
4
K - 20.6
8
01
16
12
16
20
24
28
<
MONTHS
FIG. 5. Surgical treatment of hypertension (aidosteronisnb-normal adrenal gIands). (Case 13, Tables 11.4 and B.) Blood pressure and :IectroIyte pattern returned to normal promptly with reversa1 of CardiovasclIar changes after uniIatera1 adrenalectomy combined with a conservative splanchnicectomy. This patient had rapidly progressive hypertension. The allrena gIands were normaI. The aIternative wouId have been bilateraf adrenaIe*:tomy with permanent replacement therapy, a much Iess desirabIe soluticn. BIood pressure continues to be norma four years after operation. ChoIecystectomy was performed twenty-eight months after the original oper:.tion for acquired aldosteronism.
vascular disease of two months’ duration. She complained of indigestion, constipation, nervousness, weakr ess, headaches and convulsions. Six weeks prior to admission, she had an attack of right costovertebral angle pain. In addition to encephalopa thy, she had retinitis with hemorrhages and exudate but without papilledema and an abnorn al electrocardiogram. Her heart was normal in size and blood urea nitrogen was within normal limits. The intravenous pyelogram revealed no function on the right side and a slightly enl: rged normally functioning left kidney. The 1131 renogram confirmed these findings. An alrtogram showed a normal left renal artery ar d obstruction of the right renal artery near its origin from the aorta. (Fig. 6.) Blood volume was goo cc. less than the estimated value. !;he had marked postural hypotension even when sitting. Standing blood pressure was virttially unobtainable. Horizontal
do not hesitate to recommend total adrenalectomy when they believe it is indicated. On the whole, the results in the five patients contained in Tables IIA and IIB were satisfactory. SECONDARY
ALDOSTERONISM
Two patients (Cases 14 and F, Tables IIA and IIB) had aldosteronism which was secondary to renal disease. One (Case F) was in the terminal stage of long-standing hypertensive cardiovascular disease with nitrogen retention. Many such patients have aldosteronism; however, bilateral total adrenalectomy has not been helpful under these circumstances and was not in this case despite the presence of nodular hyperplasia of both adrenal glands. Case 14 is a typical exampIe of a correctable form of aldosteronism secondary to renaI disease. This fifty-two year old woman had a rapidly progressive form of hypertensive cardio187
Smithwick,
Harrison,
FIG. 6. This retrograde femora1 arteriogram shows occIusion of right renal artery near aortic ostium with norma vasculature of the Iarge hypertrophied Ieft kidney. (Case 14, Tables IIA and IIB.) The eIectroIyte pattern was typica of aIdosteronism secondary to renaI disease. FoIIowing right nephrectomy the bIood pressure and eIectroIyte changes returned to norma promptIy.
blood pressure was 160/120 mm. Hg. She had not been treated with antihypertensive drugs. As shown in Tables IIA and IIB, serum potassium, sodium and chIoride IeveIs were persistently Iow. The low sodium IeveI is in contrast with the norma or eIevated IeveIs which occur in the other forms of aIdosteronism which have been discussed. The CO2 values were consistentIy elevated. The right kidney was removed. It weighed 64 gm. The renaI artery was obstructed by an arterioscIerotic pIaque. The parenchyma showed infarction, marked ischemic tubuIar astrophy and extensive chronic pyeIonephritis. Serum eIectroIyte vaIues returned to norma in the course of ten days. BIood pressure, Iikewise, feI1to norma promptIy and was I r4/g4 mm. Hg fourteen months after operation. At that time she was symptomaticahy improved as was her genera1 CardiovascuIar status. SURGICAL
CONSIDERATIONS
With regard to surgical technic, it is essentia1 that the exposure of the adrena gIands is adequate so that smal1 tumors will not be over-
Urger
and WhiteIaw
Iooked. AIso, it is best to empIoy an approach which provides for the inspection of both adrena gIands. It wouId appear from our own experiences and from the data which Conn, Knopf and Nesbit have accumujated from the Iiterature that under certain circumstances one can be almost certain that only one adrenal gland is invoIved. For instance, if the preoperative findings make the diagnosis of primary aIdosteronism highIy probable, one then expects to find a cortical adenoma. Of our eIeven female patients, a11had a singIe adenoma. Of two maIe patients, one had a singIe adenoma and one had a tumor on both sides. According to the coIIected statistics of Conn, Knopf and Nesbit, there was a marked preponderance of tumors on the Ieft side; the ratio was more than 2: I in femaIe patients while for male patients, both sides were invoIved with equal frequency. More than one tumor was present in 9 per cent of the cohected series of Conn, Knopf and Nesbit; however, in a11 but two patients, the tumors were on the same side. FemaIe patients aIso appeared to be much more Iikely to have more than one tumor on one side than maIe patients. Of 138 cases of primary aIdosteronism which they reviewed, only two patients, one maIe and one femaIe, had an adenoma on both sides. Among our thirteen patients, one of two maIe patients had a singIe tumor on both sides. Since the incidence of tumors on the left side has been so much higher among women and the same for men, it would seem best routineIy to expIore the Ieft side first. If the patient is femaIe and one or more tumors are found on the left side, one may be justified in not expIoring the other side. It has been our custom to expIore both sides, however. With male patients, both sides shouId aIways be expIored. In cases of congenita1 or acquired aldosteronism, both sides shouId be expIored since one wiI1 be deaIing with biIatera1 noduIar hyperplasia, hypertrophy or norma adrena gIands. Here again, the chances of a form of aIdosteronism without an adenoma appear to be much more IikeIy among maIe patients. The exposure aIso shotrId ideaIIy permit the performance of a conservative type of spIanchnicectomy in the occasiona case in which this might be thought to be indicated, specificaIIy in the case of normaI or hypertrophied adrena gIands as in Case 13 (TabIes IIA and IIB) in which uniIateraI adrenaIectomy was combined successfuhy with a conservative spIanchnicectomy, thus avoiding permanent
Treatment
of AIdosteronism
FIN:. 7. A posterior cxtrapIeura1, transdiaphragmatic retroperitoneal approach is idealIy suited for biIatera1 exploration of the adrenal glands and kidneys. (From: GIBBON, J. II. (Ed.) Surgery of the Chest, p. 902. PhiIadeIphia, 1963. U’. B. Saunders Co.)
replacement therapy. The aIternative is bilatera adrenaIectomy. This shouId certainIy he performed for noduIar hyperpIasia. One can approach the adrena gIands through the abdomen. Many prefer this method. A Iong transverse incision usuaIIy gives a good exposure. It can be extended upwards in the midIine if necessary. This is a much more diffIcuIt procedure, especially in obese patients, than the posterior extrapIeura1 retroperitonea1 technic. This is simiIar to the method one of us (R. H. S.) has used in performing spIanchnicectomies during the course of which the adrena gIands, kidneys and renaI arteries are carefuIIy expIored. The patient is pIaced in the prone position with the chest and peIvis supported by firm hair mattresses so that there is no pressure on the abdomen. The tabIe is broken to fIatten the Iumbar spine. IntratracheaI anesthesia is used. BiIateraI paravertebra1 incisions are made over the IateraI portion of the sacrospinaIis muscIes centered over the tweIfth rib. (Fig. 7.) The dissection is then carried downward, eIevating the sacrospinalis muscIe and resecting the tweIfth rib. The pIeura is separated from the
FIG. 8. This extrapIeura1 retroperitoneal technic nIso gives exceIIent exposure of the spIanchnic innervation, thus, adrenalectomy or nephrectomy or splanchniccctomy or various combinations thereof can be performed with faciIitg as indicated. (From: GIBBON, J. I-I. (Ed.) Surgery of the Chest, p. 902. PhiIadcIphia, 1963. W. B. Saunders Co.)
Iower portion of the thoracic cage, the diaphragm is divided and renaI fascia incisecl. The upper poIe of the kidney is mobilized and retracted downward. This gives excellent exposure of the adrena gland as we11 as the kidney and spIanchnic bed. As a rule the left side is expIored first in the case of aldosteronism. If one is very familiar with this region, a smal1 incision can be made beneath both tweIfth ribs and the adrena gIands expIored with a forefinger to get a preIiminary idea of their size and whether a tumor is present on one or both sides before performing extensive dissection on either side. This extrapIeura1 extraperitonea1 technic is particularly usefu1 in obese or muscuIar persons, since an unfavorabIe body buiId does not make the operation more diffIcuIt as when the transperitonea1 approach is empIoyed. Having obtained the necessary exposure of the adrenal gland, whatever needs to be done can be performed with facility. This is also an excellent exposure for performing nephrectomy or conservative splanchnicectomy. The diaphragm is resutured (Fig. S), and the deeper layers are
Smithwick, TABLE ADRENACORTICAL BILATERAL
TOTAL
I
THERAPY
The foIIowing pIan of management is recommended for such patients. Cortisone acetate, I00 mg. intramuscuIarIy, is given the night before surgery and repeated at 7 A.M. the next morning. It is pIanned to give 300 mg. of hydrocortisone intravenousIy on the day of, and the day folIowing, biIatera1 total adrenaIectomy. During the ensuing ten days, the dose is graduaIIy reduced to 50 mg. per day. The fina maintenance daiIy dose is 37 to 50 mg. of cortisone acetate accompanied by 0.1 mg. of g-cY-ffuorohydrocortisone. The minima1 cortisone requirement as we11as that of sodium chIoride is greatIy increased in hot humid weather and under circumstances of stress, febriIe episodes or intercurrent infections. Careful education of the patient with Addison’s disease is a Iifesaving measure for today adequate substitution therapy is aIways avaiIabIe. TabIe IIC outIines an aIternative method of pre- and postoperative hormona1 therapy.
AFTER
ADRENALECTOMY
Days
*
Unger and WhiteIaw
IIC
SUBSTITUTION
Therapy
Postoperative
Day of surgery
Harrison,
Intravenous infusion started after induction anesthesia with hydrocortisone at rate of 100 mg. each eight hours during the twenty-four hour period 300 mg. of hydrocortisone intravenously. continued during twenty-four hour period zoo mg. of hydrocortisone continued by intravenous infusion 150--200 mg. of hydrocortisone continued by intravenous infusion roe-15~1 mg. of hydrocortisone intravenousIy or orally as indicated loo-,50 mg. hydrocortisone intravenously or orally as indicated 1oo mg. hydrocortisone orally 100 mg. hydrocortisone orally 75 mg. hydrocortisone oralIy 75 mg. hydrocortisone orally; start Ruorohydrocortisone postoperatively, 0.1 mg. daily 50 mg. hydrocortisone orally; Ruorohydrocortisone
postoperatively,
0.1 mg.
cIosed with interrupted catgut sutures and the skin with siIk sutures. A catheter is pIaced in the extrapIeura1 space and brought out through the incision. It is a.sDirated whiIe the Iung is exDanded with posi&e Dressure after the incision is closed -and is thkn removed. If the pIeura is opened, no attempt is made to cIose it. A second catheter is pIaced intrapIeuraIIy, aspirated and removed in a simiIar fashion after the incision is closed. If indicated, the operation is then repeated on the opposite side. As a ruIe. the biIatera1 Drocedure can be comDIeted in one to one and a haIf hours. This approach has been used aIso by the Brigham group in thin patients and especiaIIy in those having no roentgenographic evidence of tumor on either side. BiIateraI exDIoration has been performed most frequently at the Brigham (J. H. H. and others) via a Ieft transcosta1 (tweIfth rib) approach, both subdiaphragmatic and extrapIeura1, foIIowed by right posteroIateraI expIoration usuaIIy resecting two thirds of the eIeventh rib or just the tweIfth if the patient is not heaviIy muscIed. This approach has been described in detai1 [J]. ApproximateIy thirty minutes is added to the operating time to permit turning of the patient, preparing the new operative fieId and redraping. Preoperative, operative and postoperative management present no serious probIems in patients operated upon for aIdosteronism except when tota biIatera1 adrenaIectomy is necessary. 1
SUMMARY
Experiences with the management of twenty patients with aIdosteronism at the Massachusetts MemoriaI and the Peter Bent Brigham HospitaIs are reviewed with particuIar reference to the basis for diagnosis and the resuIts. IIIustrative case reports are presented and surgica1 technic, preoperative preparation, operative and postoperative management are commented upon brieff y. Thirteen patients had primary aIdosteronism. One patient died of a cerebra1 hemorrhage. The tumor was not removed but was discovered at autopsy. The other tweIve patients are Iiving and weI1, and have norma or near norma bIood pressures foIIowing remova of their tumors. OnIy one of these patients required biIatera1 tota adrenaIectomies with repIacement therapy. Five patients are cIassified as having acquired aIdosteronism. The preoperative findings were the same in these patients as in those having primary aIdosteronism. They did not have tumors. The adrena gIands showed noduIar hyperpIasia or hypertrophy, or were normaI. BiIateraI tota adrenaIectomies were performed in four. BIood pressures and eIectroIytes became normaI but one died of a cerebra1 accident thirteen months after operation. RepIacement therapy was necessary in these cases. This was diffIcuIt to manage in the earIy postoperative years in one patient. One patient is Iiving and we11 with norma bIood pressure and eIectro-
190
Treatment
of Aldosteronism ation. The diagnosis in the cast I’~~ll~~~vcdt’rjr fifteen years was made in retrospect. A regimen for the management of patients requiring biIatera1 tota adrenaIectomies is outlined.
1~tc5 I.our vearh after unilateral total adrenalcctom v corn bincd with a bilateral conservative sl,lanchnicectonl~. T\vo patients had aldosteronism secondaq to renal disease. One of these, who was in renal f;Lilurc a\ a result of long-standing hypertensive cardiovascular disease, died three weeks after bilateral total adrenalectomy. The other is living and well with norma blood pressure and electrolytes fourteen months after uniIatera1 neDhrectomv. eventeen of the twenty patients are living and welt and have norma or near norma bIood pressures and norma eIectroIytes for varying periods of time up to fifteen years after oper-
REFERENCES
CON-S, J. ui. Presidential address: painting background: primary aldosteronism, new clinical syndrome. J. Lab. F Clin. Med., 45: 3, 1955. 2. CONN, J. 1%‘. Aldosteronism in man. Somr clinic:rI and climatological aspects. Part II. J. A. M. A., 183: 871, 1963. 3. HARRISON, J. II. Surgery of the adrenals. In: Encyclopedia of Urology, vo1. 13. p. 298. Berlin, I.
s
1961. Springer.
191
Treatment
EXPERIENCES PETER
of Aldosteronism
AT THE MASSACHUSETTS MEMORIAL BENT BRIGHAM HOSPITALS
AND
THE
REGINALDH. SMITHWICK,M.D., J. HARTWELLHARRISON,M.D., LAURENCEUNGER, M.D. AND GEORGEP. WHITELAW, M.D., Boston, Massachusetts From tbe Departments of Surgery, Massachusetts Memorial Hospitals and Boston University School of Medicine, Boston University Medical Center, and tbe Department of Urology, Peter Bent Brigbam Hospital and Harvard Medical School, Boston, Massachusetts. Tbis work was supported in part by Research Grant H-4631. (Cr) from tbe National Institutes of Healtb. United States Public Healtb Service, Wasbinglbn, D. 6., and by a grant from tbe trustees under tbe wills of Cbarles A. King and Marjorie King.
HIS report deaIs with twenty patients who T were operated upon at the Massachusetts
MemoriaI or the Peter Bent Brigham Hospitals for aIdosteronism. Thirteen of these patients had cortica1 adenomas and appear to conform with the diagnostic criteria which Conn [x,2] has estabhshed for patients having primary aIdosteronism. Data concerning each of these patients are summarized in TabIes IA and IB. Five patients are Iisted under the heading, acquired aldosteronism. They did not have tumors, but otherwise had findings comparable to patients having primary aIdosteronism. The data for these patients are summarized in TabIes IIA and IIB. These tabIes aIso contain information regarding two patients with aIdosteronism secondary to renaI disease. In another articIe in this Symposium Conn, Knopf and Nesbit have analyzed their own experiences with eighteen cases of primary aIdosteronism and have reviewed and tabuIated the data which they were abIe to obtain from a review of 145 cases which had been reported in the Iiterature up to JuIy 1962. They have summarized the symptoms and physical findings in a Iarge number of cases; therefore, it seems unnecessary to persue these aspects of the matter further. Our report is concerned mainIy with the data upon which the diagnoses were based, results, iIIustrative case reports, American
Journal
o/ Surgery.
Volume
107, January
1964
surgica1 technic and certain aspects of preoperative preparation and operative and postoperative management. PRIMARYALDOSTERONISM There were thirteen patients in this group. (Tables IA and IB.) EIeven were women. TweIve had a single cortica1 adenoma, six of which were on the right and six on the left side. EIeven of the tweIve singIe tumors were benign, one was maIignant. The other patient had biIatera1 tumors which were maIignant. The tumors varied in size from 0.9 to 7.2 cm., the great majority being Iess than 3 cm. in diameter. Six of the fourteen tumors were less than 2 cm. in Iargest diameter and often much Iess than 2 cm. in cross section, so that they may be quite ffat and easy to overIook, especially if they are centraIIy Iocated in the substance of the gIand. The age of the patients varied from thirtyone to sixty years, and the known duration of hypertension from one and a haIf to eighteen years. Thus, primary aIdosteronism occurs preponderateIy in middIe aged or oIder women with elevated bIood pressure of several to many years ’ duration, and the cortica1 adenomas are smaI1, uniIatera1 and benign in the great majority of patients. The diagnosis shouId be suspected whenever hypertension is associated with a Iow IeveI of serum potassium. These two findings should be supported by further evidence. Table IA contains additiona preoperative information about these thirteen patients. In addition to the bIood pressure and serum potassium IeveIs, the vaIues for serum sodium, carbon dioxide and chIoride are aIso given. The sodium IeveI is typicaIIy norma or eIevated. The CO* vaIue 178
Treatment
of AIdosteronrsm
f .:.
z
2 m
%
2.0
Right
Right Left Right Left
E. H.
2.2
0.9 1.3
-
Grade 2
Grade 3
... I.1
Benign
Benign MaIignani MaIignant
Benign
Benign Benign Benign
Ietters
...
...
Negative
Negative
VacuoIar nephropathy Grade z Negative Grade 3 Negative Grade 2 Negative
Benign
Grade I
Grade z
Negative
Negative
..,
VacuoIar nephropathy
-__-
TubuIes
IB
I
Norma1
I
Normal
I
r4o/78
r 28/94 I 80/90 115/80
Normal Normal Norma1
Normal
Normal Normal Normal
Normal
Norma1 Normal Norma1
Norma1 = Peter Bent Brigham
Hospita
r35/8o
Normal Norma1 Normal
Excision of right corticai adenoma Right adrenaIect.omy Left adrenaIectomy BiIateraI tota adrenaIectomy
IO6/60
r 3o/7o 1466190 17O/IZO
Norma1 Normal Normal Norma1 Norma1 Normal Norma1 Norma1 NormaI
Left adrenalectomy Left adrenahzctomy Right adrenaIectomy
-
26/88 I
Norma1
Norma1
97/7x
Norma1
NormaI
r3o/9o
Normal
Norma1
Normat
Normal
Left adrenaIectomy
Post-
15
(yr.)
IntervaI
,operativt
I
_
-
2%
6 wk. 12 mo. 3
r
~
Carcinoma Left side explored first; carcinoma of Ieft adrenaf gland
...
..
Cerebrovascular accident preoperatively. Slight improvement without drugs
.
. .
2
I
...
3 3
eIetumor
CerebrovascuIar accident preoperativeiy
Blood pressure vated unti1 removed
Diagnosis based on urine pH, eIectrocardiogram and renal biopsy Tumor found at autopsy
Comment
2%
4%
5
BP. . ref ‘ractory to drugs; died five years postoper cident atively of cerebr O\
Norma1
Blood Pressure (mm. Hg)
Norma1
BiIateraI splanchnicectomy pIus excision of right cortical adenoma BiIateraI spIanchnicectomy in 1952; adrenaIs not expIored Bilateral splanchnicectomy in 1952; right adrenaIectomy in 1956 Excision of left corticai adenoma Excision of Ieft cortical adenoma
EIectrocardiogram?
ADENOMAS)
Urine
_--~
-
CORTICAL
EIectroIytes
(ADRENAL.
TABLE
Operation
ALDOSTERONISM
Benign
Grade I
Benign
Grade 3
...
,
Benign
Benign
L-
Arterioles
Renal Biopsy
Memorial HospitaIs; 11 lsetts * Numbers = I f Normal as regards e vi dence of hypokalemia.
C. E. C.
‘fl;.. :*I?.
Left
Right
9. 1M. P.
.
0.9 4.0 I.3 7.2
Left Left Right
6. A. H. 7. B. G. 8. C. B.
IO.
2.2
Left
5. D. G.
2.Y
Left
4. L. B.
2.5
5.0
Right
M.DeS.
2.
3. M-C.
1.0
Right
ccm.)
C.W.
_
Side
PathoIogic Condition
Adenomas
Size
I.
Case* and Patient
Cortical
PRIMARY
Treatment
of Atdosteronrsnl
-I
normal
plasia
plas,a
was normai
8s t0 evidence
of IwpokaIemia.
subtotal
adrenalectomy
adrenalectomy
adre-
Brigham
total
Hospital.
adrenaIectomy
Normal
-
Norma I
Norma I
Norma I
1
Norma I
~
Urine
-
-
I
rr4/94
f 30/70
140/w
I 20/80
I44/94
I 40/85
i
I
es=
-
I
YT.
comatose
14 mo.
4 yr.
yr.
4 Yr.
3%
8 mo.
2%
y
Interval
ative
I ‘ostoper-
in shock,
11 Negative
1Negative
’Negative
1Negative
-
i mm.
gram?
Hg)
Blood Pressure
cardio-
r_=
-
GLANDS)
Electro-
ADRENAL
Died three weeks postoperatively,
-7
NORMAL
Normal
Secondary Aldosteronism
total
total
adrenalectomy
splanchnicectomy;
OR
in
adrenal-
(60 per cent)
right
nephrectomy
Bilateral
Right
B&tend
Bilaterd
left total
BiIateraI
nalectomy,
in 1959
total
spIanchnicectomy
Operation
IXB
ALDOSTERONISM
TABLE HYPERTR~PHY
biIatera1
Left tot&
Peter Bent
Normal
Grade 3
=
atrophy
tubular
letters
pyelone(marked),
phritis
athy
nephrop
VZXCU&I
Negative
Negative
Chronic
Grade z
Hospital;
hyper-
Memorial
Nodular
hyper-
hyper-
hyper-
Nodular
Nodular
Nodular
Massachusetts
f Electrocardiogram
* Numbers
F. N. L.
=
Grossly
normal
M. M.
Grossly
rq.
plasia N0iXlal
plasia
NClrmZll
4.0
E. T. D.
5.8
9.4
J. C.
trophy
hyper-
? slight
Grade 2
athy
plasia Normal
nephrop
hyper-
D.
trophy
VXUOhr
ectomy Grade 2
plasia Nodular
plasia
Hyper-
1946;
Negative Bilateral
hyper-
2
-
Nodular
Grade
-_
Tub&s
Biopsy
hyper-
Left
Renal
Arteride5
I
HYPERPLASIA,
Nodular
Right
. ~
II .2
Left
PathoIogy
~3. S. G.
S.
(pm.)
- ~
7.5
J.
-
Right
Weight
Giands
12. M. A.
,I.
p
and
Patient
Case*
Adrenai
-
(NODULAR
ACQUIRED
j
mo.
both
and uremic
pyeionephritis
artery
of renal
struction chronic
arteriosclerotic
and
ob-
nonfunctioning
giands
kidney;
(64 sm.)
adrenal
Patient cured without
reremoving
requiring
was physiologi-
accident
w.
o
8
2
?” i;’ 0
3
“*
_i g 4 postoperatively
therapy
complete placement
tally
Adrenalectomy
SmalI
I
13
-. from cerebrovascular
Died
__
comments
Treatment
ot’ Aldosteronism hypertension is characteristicall> not rapid13 progressive, excessively severe or of the malignant variety (papilledema). In summary, we would believe that in the absence of renal disease or diuretic treatment the following findings justify the diagnosis of primary aldosteronism and expIoration of the adrenal gIands: (I ) hypertension: mild to severe; (2) plasma K, persistently low; (3) plasma C02, norma or elevated; (4) plasma Na, normal or elevated; (5) urine K, high when serum K low; (6) urine, often high pH, Iow specific gravity; (7) eIectrocardiogram, usuaIIy shows evidence of hypokalemia. IdeaIIy, the folIowing information should be obtained if possibIe: (I) norma1 urinary I 7-hydroxycorticosteroids always, and (2) a t- urinary aldosterone IeveI. If no tumor is found, the diagnosis w&d be congenital or acquired aIdosteronism. The resuIts of operation were good as regards the effect on blood pressure levels, the carcIiovascuIar system in general and the eIectroIyte pattern. As shown in TabIe IB, the bIood pressure return.ed to norma or near norma in twelve patients. In one, the diagnosis was made at autopsy. In four patients, the cortical adenoma was removed and the rest of the adrena gland was preserved. In seven, uniIateraI total adrenaIectomy incIuding removal of the adenoma was performed. In one patient, bilatera1 total adrenalectomy with remova of the adenomas was performed. This was the onIy patient who required repIacement therapy. This possibility must be anticipated, although it wiI1 rarely be necessary in patients with primary aIdosteronism. The electrocardiograms reverted to normal so far as evidence of hypokalemia was concerned as did urinary pH, specific gravity and potassium content. Several patients will be commentecl upon briefly. One patient (Case I) was a forty-six year old woman with hypertension of eighteen years’ known duration at the time of operation fifteen years ago. BiIateraI splanchnicectomy was performed. On exploration of the adrenal glands, a I cm. cortical adenoma of the right adrenal gland was found and removed. Renal biopsy specimens were also obtained. The patient has been weI1. BIood pressure was 140/78 mm. Hg fifteen years later and her genera1 CardiovascuIar status was exceIIent. This patient was operated upon long before Conn described the entity of aldosteronism and is one of many who have undergone
1s high or norma I. Only about half the CO, determinations lvere elevated so that it is not necessary to have persistent evidence of nlkalosis to make the diagnosis. By contrast, it is very unusual to find the potassium level anything but reduced. When normal, which it may I e occasionally, it is usuaIIy at the Iolyer range of normal. In this connection, it is important to know whether the patient has been taking any of the thiazide derivatives, since they cause a depression of the serum potassium and elevation of CO, IeveIs. In this case the drug shouId be eIiminated and the K and CO, values repeated at frequent intervaIs for atl!east one month. If the potassium vaIues are persistently Iow and the CO, vaIues norma or eIevated, the presumptive diagnosis is primary aIdosteronism in the absence of evidence of a renaI factor. The serum chloride is generaIIy normal or occasionally a little below normal. The urinary specific gravity and pH vary, but the specific gravity wil1 often be Iow and the pH high. The evidence so far referred to makes the diagnosis almost certain. However, an additional finding which virtuaIIy clinches the diagnosis is a persistentlv high urinary potassium excretion. As sholvn in TabIe IA, this was found to be the case in a11 ten patients in whom this observation was made. The excretion of more than 30 mEq. of sodium and at Ieast 35 mEq. of potassium is typical of primary aIdosteronism. Since this determination is available to most its importance as a diagnostic physicians, criterion is emphasized. Also important, but not widely available, are determinations of serum or urinary aIdosterone Ievels. They may be normal or elevated and probabIy are eIevated in a11 patients at some time. OnIy a few laboratories are capabIe of performing this analysis accurately at the present time. In only two of our thirteen patients was the IeveI of aldosterone excretion known. Patients with primary aIdosteronism excrete normal amounts of I 7-hydroxycorticosteroids in the urine, so that if possibIe, this determination should be made. This information was rareIy avaiIabIe in our cases. FinaIIy, the electrocardiogram usuaIIy shows evidence of hypokaIemia and did so in eIeven of our thirteen patients. The various diagnostic criteria are discussed in much greater detai1 in the papers by Conn, Knopf and Nesbit, and ReIman in this Symposium. Both emphasize that the ‘83
Smithwick,
Harrison,
Unger and Whitelaw
FIG. z.. Right adrenal gland (Case 3, Tables IA and IB), a flat inconspicuous adenoma measuring z. cm. can be seen in the Iower left portion of the gland. The rest of the gland shows nodular hyperplasia.
FIG. I. Low and high power views of renal showing vacuolar nephropathy of the tubules, of hypokaIemia. (Case I, Tables IA and IB.)
tubules typical
removal of a cortical adenoma at spIanchnicectomy. Among these patients there are undoubtedly others who had primary aldosteronism. Potassium and sodium determinations were not obtained routinely in these patients as the flame photometer was not in use. The diagnosis of primary aIdosteronism seems warranted in retrospect in this patient, since the pH of the urinary specimen was uniformly high and the specific gravity low. The electrocardiogram had changes typical of hypokaIemia. The renal biopsy showed tubuIar vacuolar nephropathy, typica of that which may be noted when hypokaIemia is present. (Fig. I .) Another patient (Case 2), by contrast, was operated upon in 1952, and bilatera1 splanchnicectomy was performed without exploration of the adrenal glands. Hypertension was not affected and persisted despite the use of various combinations of antihypertensive drugs, She was readmitted to the hospital five years later folIowing a cerebra1 hemorrhage which proved fatal. The eIectro1yte pattern at that time was
typical of primary aIdosteronism as were urinary and electrocardiographic findings. At autopsy a benign cortical adenoma, measuring 3 cm. in diameter, was found arising from the right adrenal gIand. Only one patient (Case B, Tables IA and IB) who had biIatera1 adenomas had a larger tumor, which measured 7.2 cm. in diameter. The incidence of cortica1 adenomas is much higher among hypertensive than among normotensive persons. They are a11 simiIar in appearance and coIor and most are thought to be unreIated to hypertension. The microscopic appearance of the tumors causing aIdosteronism apparentIy has not been found to differ significantIy from that of cortical adenomas found at autopsy in normotensive persons. One patient (Case 3) aIso underwent splanchnicectomy in 1932. The adrena gIands were expIored but no tumor was found. Hypertension persisted and was refractory to al1 antihypertensive drugs. In 1936 the patient was studied in detai1 with the possibility of aIdosteronism in mind. The findings were typica1. (Tables IA and IB.) The adrena glands were re-explored and a cortical adenoma was found on the right side. It was diffrcuIt to fee1 because, aIthough it was 2 cm. in largest diameter, it was buried in the center of the gIand and was ffat rather than round or ova1 in shape. (Fig. 2.) It, undoubtedly, was present at the time of the original operation. Because many of the tumors causing primary aIdosteronism are Iess than 2 cm. in diameter, 184
Treatment
of AIdosteronism
exposure of the adrenal glands must be exceIlent and exploration thorough. Another patient (Case C), for instance, underwent bilateral adrena exploration elsewhere four years before a 1.8 cm. adenoma was removed. The tumor was undoubtedly present at the first operation and was overlooked. Two patients (Cases 6 and IO) had tumors which measured Iess than I cm. in diameter. Figure 3 is a photograph of the specimen from Case 6. A preoperative diagnosis of aldosteronism was made in Cases 4 through C, and splanchnicectomies were not performed in these ten patients. COICGENITAL
AND
ACQUIRED
ALDOSTERONISM
The diagnosis of primary aldosteronism has been reserved by Conn for patients having hypertension associated with other findings which we have just commented upon and who have adrenal cortical adenomas. For patients who do not have adenomas, but who otherwise have identical findings, he has suggested the diagnosis of congenital aldosteronism for a group of 1.ounger patients, aged nine to twentythree years, whose symptoms can be traced back to very early chiIdhood. We have added the diagnosis of acquired aldosteronism because it wouId seem most unlikely that any of the five patients listed in TabIes IIA and IIB had congenita1 aldosteronism because of their age or known duration of hypertension. Prior to expIoration it is not possibIe to differentiate between the various forms of aldosteronism with certainty. However, the marked preponderance of woman (eleven of thirteen) among our patients having primary ardosteronism is in sharp contrast to marked preponderance of men (four of five) among patients having acquired aldosteronism. One must, therefore, suspect that male patients are much less IikeIy to have tumors and are more likely to have nodular hyperplasia, hypertrophy or norma adrena glands. Hypertension may be rapidly progressive or of the malignant variety in contrast to that in patients having primary aldosteronism. Absence of evidence of renaI hypertension or the effects of diuretic antihypertensive drug treatment is, however, necessary for the diagnosis of congenita1 or acquired aldosteronism. Of the five patients listed in TabIes IIA and IIB, two were found to have noduIar hyperplasia of both adrena glands. One patient (Case 12)
had nodu1a.r hyperpIasia of the left and hypertrophy of the right adrenal gIand. One (Case I 3) appeared to have norma glands; however, since the weight of the one which was removed was the glands probably were slightly 7.7 w., hypertrophied. No nodules were present. One patient (Case E) had normal adrenal gIands. When both adrenal gIands show nodular hyperplasia, biIatera1 total aclrenalectomy wouId appear to be indicated. The three patients treated in this fashion did weI1. One (Case I I) died thirteen months after operation of a CerebrovascuIar accident even though the bIood pressure was normal. He had been operated upon in 1946 for hypertensive cardiovascuIar disease, and biIatera1 splanchnicetomy was performed. Hypertension persisted despite antihypertensive drug treatment. In 1959 a diagnosis of aldosteronism was made. Expioratory surgery reveaIed bilatera1 noduIar hyperpIasia, and both adrena gIands were removed. BIood pressure became norma and was 140/85 mm. Hg eight months later. AI1 other stigmas of aIdosteronism also disappeared. One patient (Case 12) aIso has done we11 although there have been probIems reIated to the need for repIacement therapy which must be faced whenever totaI adrenalectomy is performed. An attempt was made in th’is patient to avoid total repIacement therapy by removing al1 of the Ieft adrenal gland which showed
Smithwick,
Harrison,
Unger
FIG. 4. The adrenal gIands of a patient (Case 12) with acquired aldosteronism. (TabIes IIA and IIB.) There was no tumor. The gIand on the Ieft side of the photograph showed noduIar hyperpIasia and on the right, hypertrophy.
noduIar hyperpIasia, and an estimated 60 per cent of the right adrena gIand, which was hypertrophied but contained no noduIes. (Fig. 4.) However, adrenalectomy was physioIogicaIIy compIete. Some of the probIems which may resuh from tota adrenaIectomy are we11 described in a Ietter from the patient’s physician written one year and eight months after operation in repIy to a request for foIIow-up information. The folIowing is a quotation from his Ietter. “At his Iast examination the bIood pressure was zoo/130 sitting, 190/126 standing -paroxysmaI auricuIar fibrihation-marked Addisonian pigmentation. It is quite a task to maintain Mr. M. A. (Tables IIA and IIB) between the ScyIIa of hypertension and congestive failure and the Charybdis of adrenocortica1 faiIure.” As you know, these are dangerous cIiffs between Italy and SiciIy. Guarding the ItaIian shore is ScyIIa, a 12 footed, six headed she-monster with three rows of teeth. On the Sicilian side is Charybdis, another femaIe creature who three times a day swahows up the waves and three times a day Iets them out. If one is Iured by ScyIIa, one wiI1 go on the rocks; whiIe if persuaded by Charybdis, one will be enguIfed by a whirIpoo1, a most unsatisfactory outcome in either case. It wouId, therefore, appear that biIatera1 total adrenaIectomy shouId not be performed without good and sufficient reason. The most recent check-up information 186
and WhiteIaw
was received three and a haIf years after operation in response to a foIIow-up Ietter. The patient had moved to CaIifornia, was retired, feIt very we11 and was extremeIy gratefu1 that his Iife had been saved by the operation. His genera1 condition was satisfactory and the most recent blood pressure readings were in the range of 130/90 to 144/94 mm. Hg. One patient (Case D, TabIes IIA and IIB) likewise underwent biIatera1 total adrenaIectomies for noduIar hyperpIasia and has been we11for two and a haIf years. Two patients (Cases I 3 and E, TabIes IIA and IIB) are of particmar interest. The first was a forty-two year old surgeon with a difhcuh personaIity. He had rapidly progressive symptomatic hypertensive cardiovascuIar disease of four months’ duration, with retinitis, an abnorma1 eIectrocardiogram and norma renaI function. He had not been on thiazide drugs. The findings, otherwise, were typica of primary aIdosteronism; however, because of the progressive nature of hypertension, its short duration and the fact that he was a maIe, the presumption was that he wouId not have a cortica1 adenoma. At expIoration, the adrena gIands appeared to be normaI. There was considerabIe argument about what should be done. BiIateraI tota adrenaIectomy was favored by most. UniIateraI adrenaIectomy was performed combined with a conservative spIanchnicectomy. His course has been satisfactory (Fig. 5) and bIood pressure was 120/80 mm. Hg four years after operation, Since the adrena gIand which was removed weighed 7.7 gm., it probabIy was sIightIy hypertrophied. No nodules were found. AI1 other evidences of aIdosteronism have disappeared. He, of course, has not required adrena repIacement therapy which wouId have been a rea1 probIem in this particular patient. It is, of course, impossibIe to teI1 whether adrenaIectomy, spIanchnicectomy or both procedures pIayed a roIe in the resuIt. It would seem worth whiIe to try this combination of procedures again under simiIar circumstances. A forty-three year old man (Case E) with hypertension of three weeks’ known duration aIso has done weI1. His adrena gIands were normal. Blood pressure was 130/70 mm. Hg four years after biIatera1 tota adrenaIectomy. He, of course, is being given adrena repIacement therapy. Most surgeons like to avoid removing both adrena gIands whenever possible. Most internists, who speciaIize in endocrine problems,
Treatment
Splanchnicect. m: e-12
of Aldosteronisnr
Encephalopathy 3 c--Abn. 38-75 3.4t------33.1 -
I I LD:S-12
L.Mmmlect.
).-
N I N . 24-62 + 4.6 )* 26.0
Br~iii Eyes ECG PSP K cot
T.E. No-35ImEq/Kg T.E.
0
4
K - 20.6
8
01
16
12
16
20
24
28
<
MONTHS
FIG. 5. Surgical treatment of hypertension (aidosteronisnb-normal adrenal gIands). (Case 13, Tables 11.4 and B.) Blood pressure and :IectroIyte pattern returned to normal promptly with reversa1 of CardiovasclIar changes after uniIatera1 adrenalectomy combined with a conservative splanchnicectomy. This patient had rapidly progressive hypertension. The allrena gIands were normaI. The aIternative wouId have been bilateraf adrenaIe*:tomy with permanent replacement therapy, a much Iess desirabIe soluticn. BIood pressure continues to be norma four years after operation. ChoIecystectomy was performed twenty-eight months after the original oper:.tion for acquired aldosteronism.
vascular disease of two months’ duration. She complained of indigestion, constipation, nervousness, weakr ess, headaches and convulsions. Six weeks prior to admission, she had an attack of right costovertebral angle pain. In addition to encephalopa thy, she had retinitis with hemorrhages and exudate but without papilledema and an abnorn al electrocardiogram. Her heart was normal in size and blood urea nitrogen was within normal limits. The intravenous pyelogram revealed no function on the right side and a slightly enl: rged normally functioning left kidney. The 1131 renogram confirmed these findings. An alrtogram showed a normal left renal artery ar d obstruction of the right renal artery near its origin from the aorta. (Fig. 6.) Blood volume was goo cc. less than the estimated value. !;he had marked postural hypotension even when sitting. Standing blood pressure was virttially unobtainable. Horizontal
do not hesitate to recommend total adrenalectomy when they believe it is indicated. On the whole, the results in the five patients contained in Tables IIA and IIB were satisfactory. SECONDARY
ALDOSTERONISM
Two patients (Cases 14 and F, Tables IIA and IIB) had aldosteronism which was secondary to renal disease. One (Case F) was in the terminal stage of long-standing hypertensive cardiovascular disease with nitrogen retention. Many such patients have aldosteronism; however, bilateral total adrenalectomy has not been helpful under these circumstances and was not in this case despite the presence of nodular hyperplasia of both adrenal glands. Case 14 is a typical exampIe of a correctable form of aldosteronism secondary to renaI disease. This fifty-two year old woman had a rapidly progressive form of hypertensive cardio187
Smithwick,
Harrison,
FIG. 6. This retrograde femora1 arteriogram shows occIusion of right renal artery near aortic ostium with norma vasculature of the Iarge hypertrophied Ieft kidney. (Case 14, Tables IIA and IIB.) The eIectroIyte pattern was typica of aIdosteronism secondary to renaI disease. FoIIowing right nephrectomy the bIood pressure and eIectroIyte changes returned to norma promptIy.
blood pressure was 160/120 mm. Hg. She had not been treated with antihypertensive drugs. As shown in Tables IIA and IIB, serum potassium, sodium and chIoride IeveIs were persistently Iow. The low sodium IeveI is in contrast with the norma or eIevated IeveIs which occur in the other forms of aIdosteronism which have been discussed. The CO2 values were consistentIy elevated. The right kidney was removed. It weighed 64 gm. The renaI artery was obstructed by an arterioscIerotic pIaque. The parenchyma showed infarction, marked ischemic tubuIar astrophy and extensive chronic pyeIonephritis. Serum eIectroIyte vaIues returned to norma in the course of ten days. BIood pressure, Iikewise, feI1to norma promptIy and was I r4/g4 mm. Hg fourteen months after operation. At that time she was symptomaticahy improved as was her genera1 CardiovascuIar status. SURGICAL
CONSIDERATIONS
With regard to surgical technic, it is essentia1 that the exposure of the adrena gIands is adequate so that smal1 tumors will not be over-
Urger
and WhiteIaw
Iooked. AIso, it is best to empIoy an approach which provides for the inspection of both adrena gIands. It wouId appear from our own experiences and from the data which Conn, Knopf and Nesbit have accumujated from the Iiterature that under certain circumstances one can be almost certain that only one adrenal gland is invoIved. For instance, if the preoperative findings make the diagnosis of primary aIdosteronism highIy probable, one then expects to find a cortical adenoma. Of our eIeven female patients, a11had a singIe adenoma. Of two maIe patients, one had a singIe adenoma and one had a tumor on both sides. According to the coIIected statistics of Conn, Knopf and Nesbit, there was a marked preponderance of tumors on the Ieft side; the ratio was more than 2: I in femaIe patients while for male patients, both sides were invoIved with equal frequency. More than one tumor was present in 9 per cent of the cohected series of Conn, Knopf and Nesbit; however, in a11 but two patients, the tumors were on the same side. FemaIe patients aIso appeared to be much more Iikely to have more than one tumor on one side than maIe patients. Of 138 cases of primary aIdosteronism which they reviewed, only two patients, one maIe and one femaIe, had an adenoma on both sides. Among our thirteen patients, one of two maIe patients had a singIe tumor on both sides. Since the incidence of tumors on the left side has been so much higher among women and the same for men, it would seem best routineIy to expIore the Ieft side first. If the patient is femaIe and one or more tumors are found on the left side, one may be justified in not expIoring the other side. It has been our custom to expIore both sides, however. With male patients, both sides shouId aIways be expIored. In cases of congenita1 or acquired aldosteronism, both sides shouId be expIored since one wiI1 be deaIing with biIatera1 noduIar hyperplasia, hypertrophy or norma adrena gIands. Here again, the chances of a form of aIdosteronism without an adenoma appear to be much more IikeIy among maIe patients. The exposure aIso shotrId ideaIIy permit the performance of a conservative type of spIanchnicectomy in the occasiona case in which this might be thought to be indicated, specificaIIy in the case of normaI or hypertrophied adrena gIands as in Case 13 (TabIes IIA and IIB) in which uniIateraI adrenaIectomy was combined successfuhy with a conservative spIanchnicectomy, thus avoiding permanent
Treatment
of AIdosteronism
FIN:. 7. A posterior cxtrapIeura1, transdiaphragmatic retroperitoneal approach is idealIy suited for biIatera1 exploration of the adrenal glands and kidneys. (From: GIBBON, J. II. (Ed.) Surgery of the Chest, p. 902. PhiIadeIphia, 1963. U’. B. Saunders Co.)
replacement therapy. The aIternative is bilatera adrenaIectomy. This shouId certainIy he performed for noduIar hyperpIasia. One can approach the adrena gIands through the abdomen. Many prefer this method. A Iong transverse incision usuaIIy gives a good exposure. It can be extended upwards in the midIine if necessary. This is a much more diffIcuIt procedure, especially in obese patients, than the posterior extrapIeura1 retroperitonea1 technic. This is simiIar to the method one of us (R. H. S.) has used in performing spIanchnicectomies during the course of which the adrena gIands, kidneys and renaI arteries are carefuIIy expIored. The patient is pIaced in the prone position with the chest and peIvis supported by firm hair mattresses so that there is no pressure on the abdomen. The tabIe is broken to fIatten the Iumbar spine. IntratracheaI anesthesia is used. BiIateraI paravertebra1 incisions are made over the IateraI portion of the sacrospinaIis muscIes centered over the tweIfth rib. (Fig. 7.) The dissection is then carried downward, eIevating the sacrospinalis muscIe and resecting the tweIfth rib. The pIeura is separated from the
FIG. 8. This extrapIeura1 retroperitoneal technic nIso gives exceIIent exposure of the spIanchnic innervation, thus, adrenalectomy or nephrectomy or splanchniccctomy or various combinations thereof can be performed with faciIitg as indicated. (From: GIBBON, J. I-I. (Ed.) Surgery of the Chest, p. 902. PhiIadcIphia, 1963. W. B. Saunders Co.)
Iower portion of the thoracic cage, the diaphragm is divided and renaI fascia incisecl. The upper poIe of the kidney is mobilized and retracted downward. This gives excellent exposure of the adrena gland as we11 as the kidney and spIanchnic bed. As a rule the left side is expIored first in the case of aldosteronism. If one is very familiar with this region, a smal1 incision can be made beneath both tweIfth ribs and the adrena gIands expIored with a forefinger to get a preIiminary idea of their size and whether a tumor is present on one or both sides before performing extensive dissection on either side. This extrapIeura1 extraperitonea1 technic is particularly usefu1 in obese or muscuIar persons, since an unfavorabIe body buiId does not make the operation more diffIcuIt as when the transperitonea1 approach is empIoyed. Having obtained the necessary exposure of the adrenal gland, whatever needs to be done can be performed with facility. This is also an excellent exposure for performing nephrectomy or conservative splanchnicectomy. The diaphragm is resutured (Fig. S), and the deeper layers are
Smithwick, TABLE ADRENACORTICAL BILATERAL
TOTAL
I
THERAPY
The foIIowing pIan of management is recommended for such patients. Cortisone acetate, I00 mg. intramuscuIarIy, is given the night before surgery and repeated at 7 A.M. the next morning. It is pIanned to give 300 mg. of hydrocortisone intravenousIy on the day of, and the day folIowing, biIatera1 total adrenaIectomy. During the ensuing ten days, the dose is graduaIIy reduced to 50 mg. per day. The fina maintenance daiIy dose is 37 to 50 mg. of cortisone acetate accompanied by 0.1 mg. of g-cY-ffuorohydrocortisone. The minima1 cortisone requirement as we11as that of sodium chIoride is greatIy increased in hot humid weather and under circumstances of stress, febriIe episodes or intercurrent infections. Careful education of the patient with Addison’s disease is a Iifesaving measure for today adequate substitution therapy is aIways avaiIabIe. TabIe IIC outIines an aIternative method of pre- and postoperative hormona1 therapy.
AFTER
ADRENALECTOMY
Days
*
Unger and WhiteIaw
IIC
SUBSTITUTION
Therapy
Postoperative
Day of surgery
Harrison,
Intravenous infusion started after induction anesthesia with hydrocortisone at rate of 100 mg. each eight hours during the twenty-four hour period 300 mg. of hydrocortisone intravenously. continued during twenty-four hour period zoo mg. of hydrocortisone continued by intravenous infusion 150--200 mg. of hydrocortisone continued by intravenous infusion roe-15~1 mg. of hydrocortisone intravenousIy or orally as indicated loo-,50 mg. hydrocortisone intravenously or orally as indicated 1oo mg. hydrocortisone orally 100 mg. hydrocortisone orally 75 mg. hydrocortisone oralIy 75 mg. hydrocortisone orally; start Ruorohydrocortisone postoperatively, 0.1 mg. daily 50 mg. hydrocortisone orally; Ruorohydrocortisone
postoperatively,
0.1 mg.
cIosed with interrupted catgut sutures and the skin with siIk sutures. A catheter is pIaced in the extrapIeura1 space and brought out through the incision. It is a.sDirated whiIe the Iung is exDanded with posi&e Dressure after the incision is closed -and is thkn removed. If the pIeura is opened, no attempt is made to cIose it. A second catheter is pIaced intrapIeuraIIy, aspirated and removed in a simiIar fashion after the incision is closed. If indicated, the operation is then repeated on the opposite side. As a ruIe. the biIatera1 Drocedure can be comDIeted in one to one and a haIf hours. This approach has been used aIso by the Brigham group in thin patients and especiaIIy in those having no roentgenographic evidence of tumor on either side. BiIateraI exDIoration has been performed most frequently at the Brigham (J. H. H. and others) via a Ieft transcosta1 (tweIfth rib) approach, both subdiaphragmatic and extrapIeura1, foIIowed by right posteroIateraI expIoration usuaIIy resecting two thirds of the eIeventh rib or just the tweIfth if the patient is not heaviIy muscIed. This approach has been described in detai1 [J]. ApproximateIy thirty minutes is added to the operating time to permit turning of the patient, preparing the new operative fieId and redraping. Preoperative, operative and postoperative management present no serious probIems in patients operated upon for aIdosteronism except when tota biIatera1 adrenaIectomy is necessary. 1
SUMMARY
Experiences with the management of twenty patients with aIdosteronism at the Massachusetts MemoriaI and the Peter Bent Brigham HospitaIs are reviewed with particuIar reference to the basis for diagnosis and the resuIts. IIIustrative case reports are presented and surgica1 technic, preoperative preparation, operative and postoperative management are commented upon brieff y. Thirteen patients had primary aIdosteronism. One patient died of a cerebra1 hemorrhage. The tumor was not removed but was discovered at autopsy. The other tweIve patients are Iiving and weI1, and have norma or near norma bIood pressures foIIowing remova of their tumors. OnIy one of these patients required biIatera1 tota adrenaIectomies with repIacement therapy. Five patients are cIassified as having acquired aIdosteronism. The preoperative findings were the same in these patients as in those having primary aIdosteronism. They did not have tumors. The adrena gIands showed noduIar hyperpIasia or hypertrophy, or were normaI. BiIateraI tota adrenaIectomies were performed in four. BIood pressures and eIectroIytes became normaI but one died of a cerebra1 accident thirteen months after operation. RepIacement therapy was necessary in these cases. This was diffIcuIt to manage in the earIy postoperative years in one patient. One patient is Iiving and we11 with norma bIood pressure and eIectro-
190
Treatment
of Aldosteronism ation. The diagnosis in the cast I’~~ll~~~vcdt’rjr fifteen years was made in retrospect. A regimen for the management of patients requiring biIatera1 tota adrenaIectomies is outlined.
1~tc5 I.our vearh after unilateral total adrenalcctom v corn bincd with a bilateral conservative sl,lanchnicectonl~. T\vo patients had aldosteronism secondaq to renal disease. One of these, who was in renal f;Lilurc a\ a result of long-standing hypertensive cardiovascular disease, died three weeks after bilateral total adrenalectomy. The other is living and well with norma blood pressure and electrolytes fourteen months after uniIatera1 neDhrectomv. eventeen of the twenty patients are living and welt and have norma or near norma bIood pressures and norma eIectroIytes for varying periods of time up to fifteen years after oper-
REFERENCES
CON-S, J. ui. Presidential address: painting background: primary aldosteronism, new clinical syndrome. J. Lab. F Clin. Med., 45: 3, 1955. 2. CONN, J. 1%‘. Aldosteronism in man. Somr clinic:rI and climatological aspects. Part II. J. A. M. A., 183: 871, 1963. 3. HARRISON, J. II. Surgery of the adrenals. In: Encyclopedia of Urology, vo1. 13. p. 298. Berlin, I.
s
1961. Springer.
191