Paraneoplastic Syndromes

syndromes.114 Paraneoplastic endocrine syn-

the nonmetastatic hypercalcemia seen in RCC

dromes are very common in patients with Renal

patients either by distinct mechanisms or by

Cell Carcinoma (RCC). However, they have been

augmenting the actions of PTHrP.120 Clinically,

described in patients with other urological

hypercalcemia presents a wide range of signs

malignances as well.

and symptoms affecting numerous organ sys-

tems. Patients may complain of lethargy, nau-

sea, fatigue, confusion, weakness and

Paraneoplastic Endocrine Syndromes

constipation. Physical examination may reveal

decreased deep tendon reflexes and an impaired

Associated with RCC

level of consciousness. Signs of dehydration

Nearly one third of patients affected by RCC

may also be present secondary to loss of renal

concentrating ability and subsequent polyuria.

show signs and symptoms of a paraneoplastic

Electrocardiogram

(ECG)

findings

include

syndrome which may be both endocrine or non-

increased PR and QT intervals with eventual

endocrine in nature.115 The presence of a para-

bradyarrhythmias and asystole. Nephrectomy

neoplastic syndrome in a patient with RCC is

is the most effective way of treating the non-

neither a marker of metastatic disease nor nec-

metastatic hypercalcemia

observed

in RCC

essarily indicative of a poor prognosis. However,

patients.

121

a paraneoplastic syndrome may be the initial

clinical presentation of RCC in a significant

number of patients and recognition of these

Hypertension

syndromes may facilitate early diagnosis. Most

paraneoplastic syndromes are associated with

Potential mechanisms of hypertension in RCC

RCC remission after resection of the primary

patients include increased renin secretion, ure-

tumor or treatment of metastatic sites. RCC

teral or parenchymal compression, presence of

tumor cells may elaborate a number of proteins

an arteriovenous

fistula

and polycythemia.

that serve as mediators of endocrine paraneo-

Elevated serum rennin levels have been found in

plastic syndromes such as parathyroid hor-

37% of patients with RCC.122,123 Renin may be

mone-related peptide (PTHrP), erythropoietin

secreted either by neoplastic proximal tubular

(EPO), insulin, glucagon, or renin.

cells or by local renal parenchymal which may

be compressed by a subcapsular hematoma or

by a large tumor leading to intrarenal ischemia

Hypercalcemia

with subsequent increase of rennin excretion by

the juxtaglomerular apparatus.Ureteral obstruc-

Hypercalcemia is the most common paraneo-

tion may cause renin secretion by a similar

plastic syndrome in patients with RCC affecting

mechanism.124

from 13% to 20% of RCC patients.116,117 Neither

the presence nor the degree of hypercalcemia,

have been shown to have a significant correla-

Polycythemia

tion with tumor grade or survival.118

Polycythemia has been reported in a percentage

Hypercalcemia secondary to bony metastatic

disease is not a true paraneoplastic syndrome.

of patients with RCC ranging from 1% to 8%.

Non metastatic hypercalcemia in patients with

Elevated serum red blood cell concentrations

RCC is thought to be mainly the consequence of

are believed to be mediated by ectopic secretion

the secretion of PTHrP by RCC cells.119 PTHrP

of EPO by tumor cells.125 Ectopic EPO produc-

binds to the PTH receptor in both the bone and

tion is found in 66% of RCC cases making this

renal tissue leading to increased bone re-

neoplasm the leading cause of ectopic EPO pro-

absorption and decreased renal clearance of

duction. Moreover, perineoplastic cells in RCC

calcium as well as increased phosphorus excre-

may also contribute to total EPO levels second-

tion. Additional factors such as transforming

ary to local tumor compression and resultant

growth factors alpha and beta, the osteoclast

tissue hypoxia. Although two thirds of RCC

activating factor, interleukin 1 and tumor

patients have elevated EPO levels, only 8% expe-

necrosis factor are also believed to exacerbate

rience erythrocytosis.