Idiopathic Retroperitoneal Fibrosis: Diagnostic Enigma: Report of a Case Simulating Diabetes Insipidus and a Review of the Literature

Vol. 96, Nov. Printed in U.S.A.

THE JOURNAL OF UROLOGY

Copyright © 1966 by The Williams & Wilkins Co.

IDIOPATHIC RETROPERITONEAL FIBROSIS: DIAGNOSTIC ENIGlVIA: REPORT OF A CASE SIMULATING DIABETES INSIPIDUS AND A REVIEW OF THE LITERATURE WILLIAM T. LEMMON, JR.*

AND

WILLIAM S. KISER t

From the Surgery Branch of the National Cancer Institute, National Inslilules of Health, United Stales Pitblic Health Service, Department of Health, Education and Welfare, Bethesda, Maryland

Although more than 200 cases of retroperitoneal fibrosis have appeared in the English literature, only five have simulated diabetes insipidus. The case reported by Mees demonstrated an abrupt onset of polyuria, polydipsia, uremia and hypertension which responded to surgical release of the ureteral obstruction. 1 Francke and Wiggers described a patient symptomatic for months until the onset of thirst, edema and hyposthenuria led to the discovery of advanced bilateral hydronephrosis.2 The patients reported by Tulloch 3 and by Goldberg4 underwent extensive diagnostic investigations for prolonged vague symptoms until anuria, followed by spontaneous isosthenuric diuresis, directed attention to the presence of bilateral ureteral obstruction. The patient described by Knowlan and associates experienced the sudden onset of hypertension, polydipsia and isosthenuric polyuria unresponsive to dehydration. 5 As in the case to be presented, a diagnosis of diabetes insipidus was made because no premonitory symptoms preceded the abrupt appearance of altered water regulation. Both of these patients had only one effectively functioning kidney so that compensation by the contralateral Accepted for publication November 3, 1965. Read at annual meeting of Mid-Atlantic Section, American Urological Association, Inc., Washington, D. C., November 3-6, 1965. * Present address: The Jefferson Hospital, Philadelphia, Pennsylvania 19107. t Present address: Cleveland Clinic Foundation, Cleveland, Ohio 44106. 1 Mees, E. J. D.: Reversible water losing state, caused by incomplete ureteric obstruction. Acta Med. Scand., 168: 193, 1960. 2 Francke, C. and Wiggers, K.: Bilateral idiopathic peri-ureteric fibrosis. Arch. Chir. N eerl., 10: 165, 1958. 3 Tulloch, W. S.: Idiopathic retroperitoneal fibrosis. J. Roy. Coll. Surg., 5: 142, 1960. 4 Goldberg, W. M.: Idiopathic periureteral fibrosis demonstrating a marked polyuric phase. Canad. Med. Ass. J., 87: (HS, 1962. 5 Knowlan, D., Corrado, M., Schreiner, G. E. and Baker, R.: Periureteral fibrosis, with a diabetes insipidus-like syndrome occurring with progressive partial obstruction of a ureter unilaterally. Amer. J. Med., 28: 22, 1960.

kidney did not obscure the dramatic effects of ureteral obstruction caused by retroperitoneal fibrosis. The purpose of this report is to document an additional case of retroperitoneal fibrosis which presented clinical manifestations initially suggesting diabetes insipidus. A review of 124 verified cases of idiopathic retroperitoneal fibrosis emphasizes the protean symptomatology of this condition which too often results in delayed diagnosis and serious impairment of renal function. CASE REPORT

A 45-year-old construction supervisor had been aware of mild non-progressive ankle edema for 5 months. He remained otherwise asymptomatic until 6 weeks prior to hospitalization at the National Institutes of Health when upper respiratory symptoms, treated with ornade spansule capsules,* were followed by sudden craving for iced fluids and associated frequency of urination (6 or 7 times during his work-day). The only physical abnormality was hypertension in a previously normotensive patient. Skull and chest roentgenograms were unremarkable, but excretory urography revealed poor concentration of the contrast material in both kidneys and right hydronephrosis. Repeated urinalyses showed no specific gravity exceeding 1.004. Blood urea nitrogen was 37 mg. per 100 ml.; serum sodium, 150; potassium, 5.3; chloride, 101 meq per L; and carbon dioxide content, 63 volumes per 100 ml. The hemogram revealed an elevated erythrocyte sedimentation rate. Twenty-four hour fluid restriction failed to elevate the urinary specific gravity above 1.005; a Hickey-Hare test infusing 900 ml. 2.5 per cent saline over 45 minutes, and 4 days of intramuscular pitressin tannate in oil (1.0 ml.) were also unsuccessful in concentrating the urine.

* Chlorpheniramine maleate, phenylpropanolamine HCl, and isopropamide iodide; Smith, Kline & French, Philadelphia, Pennsylvania. 658

G~n

IDIOPATHIC RETRO PERITONEAL FIBROSIS

TABLE 1. Laboratory dala ---

~----------·--

: Date

BU1'

Crea iinine

I

mg.%

nrg.%

926-G3 10-2-63 10-4-63 10-8-63 HHl-63 10-10-63 10-11-6::l 10

rn

5;:;

10--19-63 10-25-63 10 31-63 ll-G-63 11-2063 11-25-G:3

37 47 49 4,5 __

47 48 ,54 50 2H

22 20 23 21

Carbon Dioxide Content

Uric Acid

mg.?la

7-13-64 7-18-Cii

Potassium

meq/L

mcq/L

meq/L

141 141 141 140

tncq/L

28 _, Opemtion -----------------t 5.6 24 84 5.0 8.1 21 2n 7.0 25 2.9 6.8 5.4 3.0 5.0 2.0 5. ;3 27 5. 8 3 1.4 6.4

21 18 19 _,

Sodium

!st ilclmission---~------__, 4.8 7.1 30 101 (i.O 7.2 26 101

.'i!ncl A.clm.iss-ion

]-13-64 1-20-(]4

Chloride

------

I

l .5

7.4

6.5 ---

- - - - - - - - --------

99 98

1:17

phorus

Total Proi-ein

mg.%

mg-0;{;

-mg.(¼

pn.%

4.5 5.3 4.3

5.60

l.87 2.06

4.6

5.75

5.2

8.6

5.0

3.9

4.4 3.2 7.1 7.3

102

137

3.9

.5.40 7.5 1.45

7

----------;<

22

1.5 I 6.7 I 3rd A. dmissfon

1.7 1.G

128 1:35

89

Phos--

Magnesium

Calcium

I

I

108 I

--

144

4.4

5.25

140

4.6

.5.00 i 1 . .50

:i 2

G.8

I

. ---·"·----j

30

--- ------

I

101

--

I

- · - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - -- -

Physical exarnination in September 1963 revealed a well-nourished man with no lymphadenopathy, no surgical sears, no abdominal or flank tenderness, no abdominal mas.oes or organomcgaly and blood pressure of 140/98 mm. Hg. Laboratory studies indicated reduced renal function with phenolsulfonphthalein excretion 2 per cent in 30 minutes and creatinine 4.8 mg. per 100 ml. (tables l-3). Fa.sting blood glucose was 108; cholesterol, 255 a.nd calcium, 5.6 mg. per 100 ml. Alkaline phosphatase wa.s 10 King-Armstrong units a.nd thymol turbidity 5 units. Lupus erythematosus preparations, VDRL serology and C-rcactiyc protein titer., were normal. The antistreptolysin-0 titer wa.s greater than 500 units. Febrile agglutinins to Proteus OX-K, Proteus OX-19, tula.rensis and Drucella abortus were not elevated. The bentonitc flocculation test was negative and serum protein electrophoresis dcmomtratcd no abnormalities. Skin tests for blastomycosis, histoplasmosis a.nd coccidioidomycosis were negativr but an intermediate strength purified protein drriva.tive (PPD) was positive at 48 homs. Acid-fast bacilli were not found in the urine. Repeated urine cultures were sterile; the spe

cific gravity varied between l.004 and 1.010 and the pH 5 to 8, with no proteinuria or cellular sediment. Bence Jones proteinuria was absent. A 24hour dehydration test produced a l. 10 kg. weighl loss, an increase in Rerum osmolality from 267 to 293 mOsm per kg. and urine osmola.lity of 804 mOsm per kg. Excretory urography revealed striking disparity in renal sizes and the presencP of right hydroureteronephrosis (fig. 1, A. radioisotope renograrn demonstrated marked delay in tubular secretion and excretion of -1::ll hippura.n from the right kidney c:mrnistent with urinary outflow obstruction, while no significant left renal function was demonstrable. Retrogracfo pyelography demonstrated an unobstrnctec! plastic left kidney and marked hydronephrcmi::; of the right kidney with medial deviation and obstruction of its ureter at the level of the iliac vessels (fig. 1, B). At exploratory laparotomy, the dilated right ureter was traced caudally to the common iliac vessels where it entered a hard, white fibrotin plaque. The plaque extended across the sacral promontory and 2 cm. above the aortic bifurcation, lying predominately to Lhe right of the great. vessels. The serosal and muscular of the

660

LEMMON AND KISER

2. Laboratory clata (continued)

TABLE

Phenosulfonphthalein Excretion

I Erythrocyte

Date

Sedimentation Rate

Urine Specific Gravity

Urine Culture

1s·

%

mm./hr.

I 30' I 60' %

Urine

Blood

Urine Sediment

pH

Pressure

) 120·

%

%

mni. Hg

1st Admission-------> 75 Neg. 9-26-63 1 1 Neg. 10-2-63 82 Neg. 10-4-63 82 Neg. 10-8-63 10--9-63 - - - Operation - - - - - - > 10-10-63 10--11-63 10-16-63 10--19-63 10-25-63 16 9 10 1 10-31-63 11-6-63 Pseudomonas >10' 11-20-63 117 11 13 14 8 Pseudomonas 6 X 10 6 11-25-63 66 Pseudomonas <1 X 104 ,____ 2nd Admission - - - - - - > 1-13-64 28 Neg. 11 10 1-20-64 34 1~1~1 1 - - - - - > 3rd Admission------> ------->

1.004

5

Rare RBC

140/98 160/100 134/98

138/94 132/98 138/86 110/60 108/78

1.012

6 6

1.015

6

2-3 WBC Innum. WBC Innum. WBC

110/70

1.017

1

1

-

8

1.010 1.015

1- - - -

~=i~=~! I

1.006

i

126116114111 I Neg.

1.015 1.007

i:~i~

100/60

I

I

40-50 WBC

6 6

I 10-15 WBC

~

I

1120/80

120/80

~~:r;~~C

--~---------~-----------------------~--TABLE

3. H emalologic data

I

Differential

Date

Hema-

REC

globin

X 10 6

~1-9-27-63 10--4-63 10-9-63* 10-10--63 10-16-63 10-25-63 10-31-63 11-20-63 11-25-63 11-27-63

Platelets

Hematocrit

Total WEC

Reticu locytes

X 10'

~

""

},

0.

E

Lym- l\!lono- Eosm- Basapho cytes cytes ophils phils

~

z

-- -- -- --

I 12.4

-

-

12.8

-

0.2

----

:Mean Corpus cular Volume

:J\1ean Corpuscular Remoglobin

I

:lYiean Corpuscular

Bemoglobin Concentration

--

%

gm.%

39 4.25 40 - - - - - > Operation 13.4 43 11.8 37.5 12.0 38 11.3 36 10.9 33 10.9 35

-

7900 6900

I

-

-

-

-

-

-

-

94

30

32

-->

0.6 0.8 7800 538 1.5 8300 590 9100 395 500 8100 475 7800 - - - - - > 2nd Admission 0.3 1-13-64 13.4 4.34 42 253 5300 - - - - - > 3rd Admission - - - - - - - > 7-13-64 14.5 I I 45.5 j 183 I o.6 I 5100 I

I

REC Indices

I

I

I

43 60 61

40 31 29

10 1 5

6 8 4

I 43

46

7

4

97

31

32

54

I 38

5

3

93

29

32

* Estimated blood loss-600. ml.; replaced with 1000 ml. whole blood.

1

lDIOPA'l'HIC RE'l'ROPERITONEAL FIBR08IS

GGl

FrG. 1. ~-1, excretory urogram. Line drawing illustrates right hydronephrosis and tortuou;; ureter which is dilated to L5-81 level. Hight kidney measured 15 by 8.5 cm.; hypoplastic left kidney mcmmred 8 by 4.5 cm. J-J, retrograde pyelogram demonstrntes 2 cm. ureteral obstruction at L5-81 level with proximal hydroureteronephroses. Medial ureteral deviation, characteristic of retropcrito11cal fibrosis, is shown

stenotic ureteral segment were invaded by the fibrosis but the ureter could be freed for lateral mobilization. Right ureterojysis and neµhrostomy were performed after renal and rn.ultiplc retroperitoneal biopsies hacl been obtained. Ristopathologic interpretation of the retroperitoneal biopsies reported dense fibrornllagenous tissue containing proliferative fibroblasts and chronic inflammatory cells. Rcual biopsy demorn,trated focal scarring, chronic interstitial inflammation and both hyalinized and hypcrtrophic glomeruli. Progressive improvement in renal function ensued and the nephrostomy tube was removed 6 ,veeks after surgery (table 1). A Pseudomonas aeruginosa urinary tract infection responded to colistin sulfate and mandelamine therapy. Readmission in .January 1964 disclosed the onset of flank pains during the preceding 6 weeb. Thirst, polydipHia, polyuria, urinary frequency, weight loss and decreased libido were denied. Ko abdominal masses nm flank tenderness were present, although slight bilateral prctibial edema remained. Four per cent eosinophilia (table 2) and a sedimentation rate of 28 mm. per hour were present. Quantitative urine culture revealed les,; than 10,000 Pseudomonas aeruginosa colonies. Fishberg concentrations werr l.012, 1.013 and 1.015. Radioisotope renogram showed norm.al right and insignificant left renal function. Excretory urography demonstrated a marked decrease

in the right hyclronephrosis with straightening of the upper ureter. Inferior vena cavography rPvealed stenosis of both common iliac veins and the distal vena cava with many collateral vessels (fig. 2, . Amtography defined no aorto-iliac obstruction, a normal right and a hypoplastie left renal vascular system (fig. 2, B). Lymph angiography showed delayed filling of the uppcl' µara-aortic nodes, mesenteric lymph node opacification and a convex displacement of the paraaortic nodal chain toward the right (fig. 3). Fifteen months after surgery, the patient was asymptomatic and normotensive. The erythroeyte sedimentation rate was 20 mm. per hour and the urinary specific gravity reached l.024. Overnight fluid restriction produced a serum osmoJality of 312 and a urine osmolality of 1056 mOsm pl'r kg. The radioisotope re11ogram and excretory urogram were unchanged. DI.':\CUS,'ilON

Diabetes insipidus, a symptom complex resulting from insufficient antidiuretir hormone (vasopres,~in), is characterized by the passage of large volumes of hyposthenuric urine, pernistent thirst and compensatory polydipsia. The persistently low urinary specific gravity does not respond to increased serum. osmolarity, induced by dehydration or hypertonic saline administration, but does respond clramatically to vasopres-

662

LEMMON AND KISER

sin replacement therapy. The differential diagnosis includes: 1) psychogenic polydipsia, in which increasing the serum osmolarity increases the urine osmolarity; 2) polyuria associated with

various metabolic states including diabetes mellitus, amino-aciduria, hypercalcemia and potassium depletion; 3) nephrogenic diabetes insipidus, an inherited disease symptomatic in the neonatal

Fm. 2. A, inferior vena-cavogram. Constriction, narrowing and irregularity of proximal right common iliac vein and distal vena cava as well as stenosis of left common iliac vein are demonstrated. Reflux flow into dilated lateral sacral and iliolumbar veins is seen on right while large ascending lumbar vein scallops cephalad to left of vertebral column. B, aortogram. Note hypoplastic left renal artery. No compression of iliac arteries is demonstrable.

Fm. 3. Lymphangiogram. A, 2-hour film reveals no opacification of upper para-aortic lymph nodes. Dilated right iliac collateral vessels are shown. B, 24-hour film illustrates opacification of mesenteric lymph nodes and convex curvature of para-aortic nodal chain to right. Plain ethiodol was utilized as contrast agent.

IDIOPATHIC RETROPERITONEAL FIBROSIS TABLE

4. Case material

Total cases reviewed: Unsuitable for analysis: Insufficient data Previously reported Periureteritis plastica variant Malignancy in biopsy material Other cause for fibrosis Un biopsied Total Total cases analyzed:

663

REVIEW OF REPORTED CASES OF IDIOPATHIC RETROPERITONEAL FIBROSIS

215 56 13 7 6

5 4

91 124

period, unresponsive to both dehydration and vasopressin administration; and 4) water-losing nephritis, 6 an acquired reversible renal lesion resulting from obstructive uropathy, again unresponsive to both dehydration and vasopressin.1 ·5-8 The cases of idiopathic retroperitoneal fibrosis simulating diabetes insipidus are included within this last classification. The sudden onset of thirst, polyuria and hyposthenuria may result from urinary outflow obstruction, as demonstrated by the case reported, and should be differentiated from the more common isosthenuric osmotic diuresis of chronic renal failure. 1 Zetterstri:im and associa,tes demonstrated with split renal function studies that the hydronephrotic kidney has a diminished or absent response to both dehydration and vasopressin and produces a larger urine volume than the normal unobstructed kidney. 9 Obstruction to the only effectively functioning kidney in Mees',' Knowlan's 5 and the authors' cases resulted in a dramatic demonstration of this concentrating defect and led to the initial diagnosis of diabetes insipidus. The nature of this vasopressin-resistant concentrating defect is not clearly understood but the available evidence suggests a dysfunction of the distal tubular and/or collecting duct epithelium. 9 6 Roussak, N. J. and Oleesky, S.: Water-losing nephritis, syndrome simulating diabetes insipidus. Quart. J. Med., 23: 147, 1954. 7 Bricker, N. S.: Obstructive uropathy. In: Diseases of the Kidney. Edited by M. B. Strauss and L. E. Welt. Boston: Little, Brown, & Co., 1963, pp. 747-748. 8 Early, L. E.: Extreme polyuria in obstructive uropathy; report of a case of "water-losing nephritis" in an infant, with a discussion of polyuria. New Engl. J. Med., 255: 600, 1956. 9 Zetterstri:im, R., Ericsson, N. 0. and Winberg, J.: Separate renal function studies in predominantly unilateral hydronephrosis. Acta Paediat., 47: 540, 1958.

Of the 215 cases of idiopathic retroperitoneal fibrosis found in the English literature, 124 presented sufficient data for review purposes (table 4). Periureteritis plastica may be a variant of idiopathic retroperitoneal fibrosis but is not consideredin this review. 10 , 11 Etiology. Although retroperitoneal fibrosis has been recognized for almost 2 decades, it remains idiopathic because no adequately encompassing etiology has been discovered. Forgotten trauma, 12 vasculitis, 13 distant infections, 14 • 15 urinary tract infections, 16 periureteral lymphangitis, 11 Gerota's fasciitis 17 and hyper-allergenic states18 have all been proposed as possible causes in some cases. Houston suggested that the disease resulted from inadequate antibiotic therapy because most cases were reported following the introduction and widespread utilization of antibiotic therapy. 19 The most recent consideration concerns the development of retroperitoneal fibrosis in some patients receiving prolonged courses of sansert*, an anti-serotonin drug useful in preventing migraine headaches. 20 , 21 In some cases, the cessa10 Ormond, J. K.: Idiopathic retroperitoneal fibrosis; an established clinical entity. J.A.M.A., 174: 1561, 1960. 11 Vest, S. A. and Barelare, B., Jr.: Peri-ureteritis plastica: A report of four cases. J. Urol., 70:

38, 1953. 12 Hackett, E.: Idiopathic retroperitoneal fibroiss. Brit. J. Surg., 46: 3, 1958. 13 Raper, F. P.: Idiopathic retroperitoneal fibrosis involving the ureters. Brit. J. Urol., 28: 436,

1956. 14 Harlin, H. C. and Hamm, F. C.: Urologic disease re&ulting from non-specific inflammatory conditions of the bowel. J. Urol., 68: 383, 1952. 15 Stueber, P. J., Jr.: Primary retroperitoneal inflammatory process with ureteral obstruction. J. Urol., 82: 41, 1959. 16 McMillan, J.C., Swarts, C. J. and Knudtson, K. P.: Idiopathic fibrous retroperitonitis. Report of ten new cases. Northwest. Med., 63: 605, 1964. 17 Hutch, J. A., Atkinson, R. C. and Loquvam, G. S.: Perirenal (Gerota's) fascitis. J. Urol., 81:

76, 1959.

18 Hoffman, W. W. and Trippel, 0. H.: Retroperitoneal fibrosis: Etiologic considerations. J. Urol., 86: 222, 1961. 19 Houston, W .: Periureteritis plastica: A report of a case, with indications of the probable pathology. Brit. J. Urol., 29: 38, 1957. * Methysergide maleate, Sandoz Pharmaceuticals, Hanover, New Jersey. 20 Suby, H. I., Kerr, W. S., Jr., Graham, J. R. and Fraley, E.: Retroperitoneal fibrosis: A missing link in the chain. J. Urol., 93: 144, 1965. 21 Utz, D. C., Rooke, E. D., Spittell, J. A., Jr. and Bartholomew, L. G.: Retroperitoneal fibrosis in patients taking methysergide. J.A.M.A., 191:

983, 1965.

664

LElVIMON AND KISER

8

Total Cases (male and female) • Bilateral [ §s Unilateral I ~ Unilateral-Bilateral No gu involvement

7 6

=

U)

w

'fd_ 5 u

LJ.._

0

4

0:::

w

O'.l

~

3-

?l 0

11.~~ Il.II 20

10

40

30

I 1111__L

50

AGE (years)

60

I

70

80

FIG. 4. Incidence by age and ureteral involvement TABLE

5. Anatomical

Anatomy

-·

involvement*

A~u, ;: 52

Females (30) Total' (124) Males (9.1) -- ------ - - - - ~ - - - - - - ?so.

Bilateral Right Left Right, became bilateral Left, became bilateral Ureters not invalved

iireteral

Time for obstruction following negative pyelogrom

OUniloterol II Bilateral

No. F No. % % --- -- - - -- --

43 12 13 7

46.3 12.9 14.0 7.5

19 4 3 3

63.4 13.3 10.0 10.0

62 16 16

50.0 12.9 12.9 11 * 8.9

14

15.0

1

3.3

15

12.1

4

4.3

0

0.0

4

3.2

* No sex stated for 64-year-old patient.

I

~

: 5 0 1 2 3 4 5 6 / f - 20 11 11 23 14 25 26 17

28

lL

0 0:

w

:1;·~"i:~I:":"·: ~~~ 0

I

2 3

4

5

6 8 9 IQ

12 14

16 12 14

35 37 39 41

MONTHS

tion of therapy with this drug resulted in regression of all manifestations of retroperitoneal fibrosis within a 3 to 6-week period. The possibility of allergy to sansert and other drugs in sensitive persons has been raised as another possible etiologic mechanism. 20 Incidence. Male patients were affected 3 times as often as female patients. Although the age span was from 8 to 75 years, more than 60 per cent occurred during the fourth and fifth decades (fig. 4). When first discovered, bilateral ureteral obstruction was present in 50 per cent of the cases; a further 20 per cent became bilateral while under medical supervision (table 5), usually within 6 m.onths of the diagnosis of the initial

FIG. 5. Time for nreteral obstruction following negative pyelograms. A, ureteral involvement is difficult to demonstrate early in symptomatic phase of retroperitoneal fibrosis. Repeated urograms or renograms may be necessary despite earlier normal studies. B, unilateral ureteral obstruction may rapidly progress to involve second side. This complication should be expected and sought for following release of initial ureteral obstruction for symptoms may not be apparent in immediate postoperative period.

ureteral obstruction (fig. 5). Because silent progression occurred as early as 1 week or as late as 41 months after treatment of the initial obstruction, it appears that frequent excretory urograms or radioisotope renograms should be obtained

IDIOPATHIC RETROPERITONEAL FIBROSIS TABLE

I

6. Symptoms Present

I

TABLE

Absent

II 1-N--]-°' 11 B-ac_k_,_a_b__---;I I~ u!~:-:n:~I1~t Symptom

I,I "o.

Oi

/o

o. .

71.8

1

pain ::~:tt\o::akAnuria Claudication

73159. l . 29

10

Not Stated

N-

l

o.

24

7

I ~~::

21 19.3 100 5.6

16.9 80.7

22

17. 7

~~

Hypertension CVA sign Fever Mass Edema

No.

%

;'\o.

%

No.

%

49 40 26 24 24

39.5 32.2 21.0 Hl.3 19.3

l(j

40 51 68 40

12.9 32.2 ,11.0 54.9 32.2

59 44 48 32 60

47.6 35.6 39.0 25.8 48.

:::~ TABLE

1117

8. Laboratory values

94.6 Absent

Present

Finding

during the first 6 months after surgery with semiannual urograms or renograms thereafter to adequately follow these patients. Symptoms. The symptoms produced by retroperitoneal fibrosis depended on the anatomic structures involved. The ureters were the most frequently (97 per cent) and most seriously inobstructed and volved because they are unable to develop collateral pathways. The venous and arterial systems were less often obstructed and were usually able to function by way of collateral channels. Occasionally the rectum,22 duodenum16 •23 •24 and even the biliary tree 13 • 16 • 23 - 25 were obstructed. The commonest complaint was persistent backache, which was often severe (table 6). A retroperitoneal pain source was suggested when spinal extension aggravated and spinal flexion eased the back pain. Spinal myelography and intervertebral disk surgery may have been recently contemplated or performed in an attempt to alleviate this back pain. Sixty per cent of patients described other pain recognizable as renal or ureteral in origin by its character and anatomic radiation. Half the 22 Popham, B. I. and Stevenson, T. D.: Idiopathic retroperitoneal fibrosis associated with a coagulation defect (factor VII deficiency): Report of a case and review of the literature. Ann. Int. Med., 52: 894, 1960. 23 Bartholomew, L. G., Cain, J. C., Woolner, L. B., Utz, D. C. and Ferris, D. 0.: Sclerosing cholangitis: Its possible association with Riedel's struma and fibrous retroperitonitis. Report of two cases. New Engl. J. Med., 269: 8, 1963. 24 Schneider, C. F.: Idiopathic retroperitoneal fibrosis producing vena caval, biliary, ureteral, and duodenal obstructions. Ann. Surg., 159: 316,

1964.

Not Stated -·-··--·-------

07 10

I

~~

Absent

Present

Finding

12.1 - ; ; - ~ 23. 2

7. Physical findings

25 Hardy, J. D.: Some lesions of the biliary tract: Idiopathic retroperitoneal fibrosis and other problems. Amer. J. Surg., 103: 457, 1962.

I

Not Stated

,----1----i---. ----Xo. I

%

No.

I

%

I N"o. !

%

Urem_ra____ ,I_-6-8 54.81-~l-27_4-1-;1~~; II

Anemia Abnormal urine ESR elevation Low specific gravity Ba(:~~l:~:~; Eosinophilia

r:i1

46.0

149

I 39.5

I

133126.5 26 , 21. 0 I

29 I 23.4 I 38 '130.6 49 i 39.5 26 21.0 i

5 19

I

! 16112.8 1 7 1 5. 6

1

4.3 86 15 4 I 79

69. 63

I 55 ! 44.415:3

42 . 8 1

23

i

18 5

94 _l_75 :~.

patients manifested weakne:.;s and weight loss was as great as GO pounds .. \.nuria occurred in 42.4 per cent of the cases reported prior to 1958 but in only 13 per cent thereafter because of increasing awareness of the disease and earlier diagnosis. Physical signs. Forty per cent of patients manifested hypertension with an equal incidence of systolic and diastolic elevations (table 7). Costovertebral angle percussion confirmed the sus pected renal tenderness in only a third of the cases, tending to absolve the urinary system 0£ its central role in symptom production. An ab. dominal mass was usually an enlarged nephrotic kidney rather than tJm.,mun, fibrous tissue. Fever, although reputedly uncommon in retroperitoneal fibrosis, was recorded in 20 per cent of the cases. The lower extremity edema was often brawny because of associated lympheclema. Laboratory tests. Of the reported sedimentation tests, 89 per cent were elevated (table 8); this simple but useful test, when obtained, tended to reflect the activity of the fibrotic process. Azotemia occurred in 55 per cent of these patients, approximately the incidence of 0

666

LEMMON AND KISER

bilateral ureteral obstruction. Urern.ia in the presence of a normal urinalysis was an e,;cellent diagnostic clue; however, 40 per cent of reported urinalyses were sufficiently abnormal to suggest a urinary system problem. Almost half the cases manifested unexpected anemia, usually in the range of 9 to 11 gm. hemoglobin. Mild to moderate eosinophilia was found in one quarter of the reported differential counts. Only 13 per cent presented positive pre-instrumentation urine cultures. Roentgenography. Although the clinical manifestations of retroperitoneal fibrosis were protean, almost every case presented sufficient diagnostic clues to suggest obtaining the urographic studies which demonstrated ureteral obstruction. The combination of hydronephrosis, extra-ureteral obstruction, and medial deviation of the ureter by urography suggested retroperitoneal fibrosis. The lymphangiograrn. in our case revealed collateral lymphatic filling, reflux into channels not usually visualized, irregular nodal filling defects and non-visualization of lymphatic channels above the fourth lumbar vertebra (fig. 3). Similar findings were previously reported by Clouse and associates 26 and utilized as a preoperative diagnostic test. 27 The increased transit time observed by Clouse is probably not due to diseaseinduced stasis, for our 24-hour films demonstrated the expected complete clearing of the lymphatic channels when plain ethiodol * was used. There is recent evidence that ethiodol containing chlorophyll,"! used by Clouse in his study, regularly causes prolonged lymphatic vessel dilatation and stasis when compared to plain ethiodol.28 Although Ormond believes that arteriography and cavography are of little value in the diagnosis of retroperitoneal fibrosis, they are often useful techniques for demonstrating the pathologic process.12, 29-32 Treatment. Adequate collateral channels often

* Ethyl ester of poppy seed oil containing 37 per cent iodine, E. Fougera & Co., Hicksville, New York. t Same compound with addition of oil soluble chlorophyll, E. Fougera & Co. 26 Clouse, M. E., Fraley, E. E. and Litwin, S. B.: Lymphangiographic criteria for diagnosis of retroperitoneal fibrosis. Radiology, 83: 1, 1964. 27 Clouse, M. E.: Bilateral ureteral obstruction. J.A.M.A., 188: 299, 1964. 28 Lemmon, W. T., Jr., Ketcham, A. S., MacLowry, J. D. and Herdt, J.: Surgical advantages and disadvantages of ethiodol with chlorophyll in lymphangiography. In preparation. 29 Ardagh, J. W. and Blake, G. B.: Idiopathic

n1.ade vascular surgery unnecessary but when the ureters became involved, progressive renal damage occurred. Surgical release of ureteral obstruction was then necessary for survival of the patient and preservation of remaining renal function. In all cases reviewed, the diagnosis was established by surgical exploration and adequate biopsy of the retroperitoneal mass. Lymphosarcoma, reticulum cell sarcoma, Hodgkin's disease and many carcinomas are able to incite a sclerotic reaction which may be mistaken for idiopathic retroperitoneal fibrosis. Careful surgical exploration revealed other possible sources of ureteral obstruction including aortic aneurysm, tubo-ovarian abscess, hematoma, ileitis and colitis. A transperitoneal surgical approach allowed bilateral ureteral exploration and more thorough abdominal exploration than retroperitoneal flank approaches. The ureter was completely liberated and displaced laterally or intraperitoneally, for the fibrosis seldom extended more than 2 cm. lateral to the normal anatomic location of the ureters. 12 · 33 The need for proximal nephrostomy or ureterostomy drainage depended on the degree of renal damage, the general status of the patient and whether the involved ureteral segment immediately regained its normal appearance and peristalsis after successful ureterolysis. This disease often resembled malignancy; a Whipple procedure23 and a left colectomy extended to include the spleen and parts of the diaphragm and pancreas34 were performed because of the gross resemblance to cancer. Tissue sections examined by frozen section techniques have been interpreted as malignancy in some cases. 16 • 18 •35 retroperitoneal fibrosis. New Zeal. M. J., 63: 362, 1964.

3 ° Furlong, J. H., Jr. and Connerty, H. V.: Compression of the aorta and ureters by a retroperitoneal inflammatory mass; case report. Delaware Med. J., 30: 63, 1958. 31 Perlow, S.: Obstruction of the iliac artery caused by retroperitoneal fibrosis. Amer. J. Surg.,

105: 285, 1963. 32 Olsson, S., Sjoberg, J.E., Wahlqvist, L. and Zederfeldt, B.: Idiopathic retroperitoneal fibrosis. Acta Chir. Scand., 123: 427, 1962. 33 Raper, F. P.: Idiopathic retroperitoneal fibrosis involving the ureters. Proc. Roy. Soc. Med., 53: 690, 1960. 34 Paull, D. P., Causey, J.C. and Hodges, C. V.: Perinephritis plastica. J. Urol., 73: 212, 1955. 35 Margoles, J. S. and McQueeney, A. J.: Ormond's syndrome: a discussion of the problem and a presentation of three cases. AMA Arch. Surg.,

81: 660, 1960.

IDIOPATHIC RETROPERI'l'ONEAL FIBROSIS

On occasion, radiation and antibiotics seemed

to produce dramatic responses but have been ineffective in most cases. Apparently successful results have been recorded using adrenal corticosteroids,32· 3 e- 39 although more authors reported no response 37 , 4 o- 45 or even progression of the disease2 , 15 · 23 , 29 during steroid therapy. Cessation of sansert therapy has resulted in return of excretory urograms to normal in sorn.e cases. 20 , 21 Because of the variable nature of idiopathic "'Reinhard, R. E. · Presumptive Ormond's disease: Remissiou following steroid therapy. Henry Ford Hosp. Med. Bull., 11: 313, 1963. " 7 Hawk, W. A. and Hazard, J. B.: Sclerosing retroperitonitis and sclerosing mediastinitis. Amer. J. Clin. Path., 32: 321, 1959. 38 Shaheen, D. J. and Johnston, A.: Bilateral ureteral obstruction due to envelopment and compression by an inflammatory retroperitoneal process; report of two cases. J. Urol., 82: 51, 1959. 39 O'Regan, R., Treahy, P. A, and Prior, I. A.: Idiopathic retroperitoneal fibrosis; a case presenting with renal failure, treated effectively with adrenal steroids. New Zeal. Med. J., 60: 518, 1961.

4 ° Charnock, D . A., Riddell, H. I. and Lombardo, L. ,J., Jr.: Retroperitoneal fibrosis producing ureteral obstruction. J. Urol., 85: 251, 1961. 41 Cameron, D. G., Ing, S. T., Boyle, M. and Mathews, W. H.: Idiopathic mediastinal and retroperitoneal fibrosis. Canad. Med. Ass. J., 85: '227, 1961. 42 Harrow, B. H. and Sloane, J. A.: Idiopathic retroperitoneal fibrosis. J.A.M.A., 182: 38, 1962. 43 Ross, J. A.: Peri-ureteritis fibrosa, with notes on three cases. J. Fae. Radio., 9: 142, 1958. 44 Que, G. S. and Mandema, E.: A case of idiopathic retroperitoneal fibrosis presenting as a systemic collagen disease. Amer. J. Med., 36: 320,

1964.

Var is, A.: Hetroperito11eal fibrosis. Ann. Chir. Gynaec. Fenn., 53: 56, 1904. 45

Gfi7

retroperitoneal fibrosi~ 20 • 46 and the small number of cases treated "·ith these non-surgical modalities, objective evaluation remains difficult .. Prognosis. l'rolonged followup studies have been reported in only a few cases. The morbidity following retroperitoneal fibrosis remains ,;ignificant, for delayed diagnosis or inadequate treat ment resulted in chronic renal impairment for 33 per cent of these patients. Twenty-one of the 124 patients included in this review have died. Four of these deaths ,vere unrelated to the clisea,:e or the therapy used, resulting in a mortality rate of 14 per cent. Death usually resulted from renal failure following late diagnosis or inadequate treatment. SUMMARY

The sixth case of idiopathic retroperitoneal fibrosis simulating diabetes insipidus is prnsented. A vasopressin-resistant concentrating defect resulting from urinary outflow obstruction seem.-:: responsible for the polyuria, polydipsia and hyposthenuria noted in these cases. A review of 124 cases of idiopathic retroperitoneal fibrosis demonstrates the protean clinical features of this disease which often resulted in delayed diagnosis. Late diagnosis caused per manent illness for 33 per cent and death for 14 per cent of these patients due to chronic renal impairment. Increased awareness of the manifestations of this disease may allow detection of nreteral obstruction before permanent renal damage has occurred. 46 Mahoney, E. M. and Edwards, E. A.: Spontaneous regression of leg edema and hydronephro-· sis following idiopathic retroperitoneal fibrosis. Amer. J. Surg., 103: 514, H)fi2.