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creased erythropoietin

inhibited

formation

of erythropoietin

formation

by

hepatoma

by insulin-like

growth

factor

(38,

39). cells I (40).

However, in vitro Whether

is

in

erythropoietin

cytostatic

drugs

of

the peptide

or

concentration

in

is related

to de-

the initial patients creased

increased

synthe-

increase treated elimination

with

sis

is unknown Estrogens,

(41, 42). f3-adrenergic

blockers

(35),

plasma

viscosity

may

decrease

erythropoietin

(43), enalapril,

as

do

agents

that

an

inhibitor

increase

renal

blood

of

angiotensin-converting

and high formation flow, e.g.,

en-

zyme

(44). Drugs

tation

polycythemia

suggested by way

for treating of inhibiting

posttransplan- erythropoietin

formation

are

nist

theophylline

enalapril (45).

(44)

and

the

adenosine

antago-

Serum

erythropoietin

concentrations

show

a circa-

in hospitalized patients, with rhythm values higher relation and blood negative of overproduction Thus, there the logarithm and, on the or the than lowest 40% adult the and (21). concen- 0800 late and 1200, evening occurring between occurring in values the erythropoietin The tration classical eases ropoietin. one hand, tration hematocrit, Overproduction mors and some concentrations between serum of a dis- erythrocyte feedback, to be operates that in mass which seems also and underproduction of eryth- is an inverse of serum the relation erythropoietin erythrocyte between, concen- volume, the on other, blood hemoglobin of erythropoietin concentration in patients (15). tu- with disorders in erythropoietin high with renal that resul ts inappropriately are re-

poietin

concentrations

in

conditions

with

anemia

are

seen

in

renal failure

(46),

autonomic

neuropathy

(37),

spect

to

this

relationship.

Inappropriately

low

erythro-

acquired therapy

immunodeficiency (47), and durin

g

syndrome

before

zidovudine

weeks

3

and

4 after

bone mar-

row

transplantation

poorly

understood

(48).

However,

there

stifi are

exceptions

to the

rule that

anemia

otherwise

is accompanied

concentrations

(49),

mechanisms

to ensure

long-standing

anemia.

by

possibly oxygen

increased as a result delivery

to erythropoietin of adaptive tissues

in

In conclusion, determination fects by considered values erythrocyte should drugs when on blood should be interpreted mass. erythropoietin evaluating sampling times be standardized; the values in relation the formation for erythropoietin obtained; to indices possible should

ef- be and of the

Inappropriate Concentration

Increases

of Serum

Erythropoietin

of increased of se- affect the in oxygen production, This may formation be formation Some evidence in the liver Nontumoral rum erythropoietin. concentrations causes Intrarenal flow, causing masses that a reduction regional tension, sometim renal may blood cause to the increased extent of for increased erythropoietin polycythemia. erythropoietin be es mechanism one in polycystic disease; in the cyst in renal another walls may (50). formation interstitial indicates of patients cells increased with erythropoietin viral hepatitis.

2096

CLINICAL

CHEMISTRY,

Vol. 40, No. 11, 1994

of er-ythropoietin

by

or malignant

tumor,

Production

with

a

benign

inappropriately poietin may

result

high

concentrations from formation

tumors. In polycythemia

patien wil

of serum of erythropoietin

erythr’

I

in the activity latter othi Exan of ar be secondary tumor growth. described the cells biological ples of the chorionic observations (and from in whom tumor as a are to or may result of a recently case (51) gonadotropin-producing from patients seminoma pheochromocytoir with patients induced treated with renal ischemia 3-adrenergic has been agonist considered

importance

(14).

tumors

associated

be of etiological Of malignant

production,

by

far

renal

adenocarcinomas,

the

most

common

i.e.,

tumors

ones

seem

to I

arising

from

prox

with

erythropoieti

mal tubular erythropoietin

cells in the

kidney (52)

(Table

is produced

by only

a small

2). Howeve fraction

(I

5%) of such

tumors.

systematic

study of

The

165

greater

patients

fraction

with

renal

all patients,

38%

(53) might

reflect

mass, as

discussed

of patients

with

(33% disease) intrarenal o

f

the

additional above. This

noted carcinoni metastat:

in

effect

of

a

may

also

I

for the increased erythropoietin concentration true see The su serve as to cytokir (54). may in a case gestion of that juxtaglomerular erythropoietin cell tumor production prognosti therapy for a favorable marker c response is controversial. (55) tumors Other erythropoietin carcinoma pheochromoc and meningioni the tumor polycythemia ai (58 to produce hepatocellular reported (56,57), nephroblastoma (59), testicular toma carcinoma mammary malignant carcinoma production (60), (61), within Erythropoietin (62). bee an described in a few patients with only

leiomyoma

(63), indicating

factors

than

erythropoietin

patients

(64).

that may

other

hematopoiet

be

involved

in

thet

In vitro derived

formation from tumors

scribed

in a testicular

erythroid leukemic Hemangioblastoma

of erythropoietin,

listed

in

Table

cells

germ (66). is an uncommon cell line

apart

from

ceL

2, has

been

di

and

in huma

(65)

cause

of polyc

themia

with

of erythropoietin

inappropriately

(11,

67-74).

high About

serum

concentratio

one-fifth

of

the

p

tients have

with

hemangioblastoma

polycythemia.

This

tu

mor

frequently

found

in the cerebellum,

have may

been reported be solitary

but also

in the

(mol mi

I

dulla and associated

the with

spinal cord and retinal angiomatosis

at extraneural in the von

sites) Hippel

c

Lindau disea this syndrome hemangiomas chromocytoma;

se.

Other

lesions

are

multiple

of

the adrenals,

that renal may and lungs,

and

hypernephroma-like

renal be observed pancreatic and liver; cyst phe tumor:

i

The may ma(s), type

origin be the or the is responsible of the hemangioblastoma(s), tissue around the increased for the increased renal erythropoietin the renal masses. Which serum concentrt productio carcin

ce

tions

of erythropoietin

toma

needs

further

The

case

presented

mor

being

a metastasis

with

hemangiobla

(69,

70,

72).

in patients clarification no evidence

from

(e.g.)

of the

cerebellar

a

renal

carcinomi

tt

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