HUMORAl HYPERCAlCEMIA OF

MAlIGNANCY
ECTOPIC VASOPRESSIN:
TUMOR-ASSOCIATED SIADH
Most patients with ectopic vasopressi n prod uction develop hypo
natremia over several wee ks or months. The d isorder s h o u l d be
corrected g ra d u a l ly u n less mental status is a ltered or there is risk
of seizu res. Treatment of the u n d erlyi ng m a l i g n a ncy may red uce
ectopic vasopressi n production but this response is s l ow if it occ u rs
at a l l . F l u i d restriction to less than u r i n e output p l u s insensible
l osses is often sufficient to correct hyponatremia partial ly. However
strict mon itori ng of the a m o u nt a n d types of l i q u i d s consu med
or a d m i n i stered intravenously is req u i red for fl u i d restriction to
be effective. Salt ta b l ets a n d sa l i n e are not h e l pfu l u n less vo l u me
depletion is a l s o present. Demecl ocyc l i n e ( 1 5 0-300 mg o ra l ly th ree
to fou r times d a i ly) ca n be used to i n h i bit va sopressin action on
the ren a l d ista l t u b u l e but its o nset of action i s relatively s l ow ( 1 -2
weeks). on iva pta n a non peptide V2-receptor a ntagon ist can be
a d m i n i stered either PO (20 1 20 mg bid) or IV ( 1 0-40 mg) and is
particu la rly effective when used i n combi nation with fl u i d restric
tion i n euvo l e m i c hyponatremia. To lva ptan ( 1 5 mg PO d a i ly) is
a n other vasopressi n antagonist. The dose ca n be i n c reased to 3 0-60
mg/d based on res ponse. Severe hyponatremia (Na < 1 1 5 meq/L)
or menta l status chan ges may req u i re treatment with hyperto n i c
(3%) or norma l sa l i n e i nfu sion together w i t h fu rose m i d e to e n h a nce
free water cleara n ce. The rate of sod i u m correction s h o u l d be s l ow

(0.5 - 1 meq/L per h o u r) to prevent ra pid fl u i d s h ifts a n d the poss i b l e

d evelopment o f centra l ponti ne mye l i n olysis.
The ma nagement of HHM beg i n s with remova l of excess ca l c i u m
i n the d i et medications o r IV sol utions. S a l i n e rehyd ration (typically
200-500 m L/h) is used to d i l ute serum ca l c i u m and promote
c a l c i u resis; exe rcise caution i n patients with ca rd iac hepatic or
ren a l insufficiency. Forced d i u resis with fu rose m i d e (20-80 mg IV i n
esca lating d oses) or other l o o p d i u retics ca n e n h a nce c a l c i u m excre
tion but provides relatively l ittl e va l u e except i n l ife-th reaten i n g
hyperca lcemia. W h e n used l o o p d i u retics s h o u l d be a d m i n istered
o n ly after com p l ete rehyd ration and with ca refu l m o n itoring of fl u i d
bala nce. Ora l phosphorus (e.g . 250 mg N eutra-Phos 3 - 4 t i m e s d a i ly)
s h o u l d be given u n t i l seru m phosphorus is > 1 m m o l/L (>3 mg/d L) .
Bisphosphonates such as p a m i d ronate (60-90 mg IV) zo ledron ate
(4-8 mg IV) and etidronate (7.5 mg/kg per day PO for 3-7 consecu
tive days) ca n red uce serum c a l c i u m wit h i n 1 -2 days and s u p p ress
I c i u m release for severa l weeks. Bisphospho nate infusions ca n be
repeated or ora l bisphosphonates ca n be used for c h ro n i c treatment.
Dia lysis s h o u l d be considered in severe hyperca lcemia when
sa l i n e hyd ration a n d bisphosphonate treatments a re not poss i b l e
or a re t o o s l ow i n o nset. Previously u s e d ag ents such as ca lciton i n
a n d mithra myci n have l ittl e util ity n o w t h a t bisphosphor tes a re
ava i lable. Calcito n i n (2-8 U/kg SC every 6 1 2 h) s h o u l d be considered
when ra pid correction of severe hyperca lcemia is needed.
Hype rca lcemia associated with Iym p h omas m u ltiple myeloma or
l e u kemia may respond to g l u cocorticoid treatment (e.g. pred nisone

40- 1 00 mg PO i n fou r d ivided doses).