1955_snow_pjd_4015_1.pdf

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II BCL NOo4 (§ 91e)

Gy NOo946 (§75d)

LSD N0oI30 (§].02a)

serotonin _ 90a)

Z 250 metas%: _<ising carc.i_oid

tumours

sNow, PoJ_Do, LENNARD_JONES,

3oEo (Manchester)_

CURZONs

STACEY, RoS, (London)

Humoral effects of metastasisij/g ca_cinoid tumo._.s

Lancet

2_9_

1004 (195§)

Go_

PROBLEM: In some patients with malignant caroinoid tumours the

most constant feature is a peculiar type of flushing, but diar _

rhoea

and right=sided val_ular lesions of the heart may be pre-

sent° It has been suggested that the symptoms may be due to the

s_cretion of 5_hydroxytryptamine

(5_HT)o This paper contains

clinical, pharmacological

and biochemical

findings

in 3

such cases.

Clinical findings: All 3 patients exhibited flushing associated

with abdominal carcinomatosis

and. liver metastases.

In the 2 ca-

ses from which material for histological examination was obtai=

ned, the tumours proved to be malignant carcinoidso

Pharmacological

and biochemical

findin_s" Acetone extracts of

tissue, plasma, serum, urine

ind

cerebrospinal

fluid were assay-

ed on the atropinised rat uterus against a standard solution of

5_HT, and the 5=HT concentration

in whole blood was calculated°

The active substance in all these extracts was completely anta=

gonized by LSD, with the exception of that from the plasma and

tumour tissue of one patient. All 3 patients had considerable

a_ounts of 5=HT in the urine and all exhibited abnormally high

Urinary excretion

of 5=hydro_indole=acetic-acid

(5o_HIAA), the

output corresponding

to the clinic.,alseverity of the disease

and the blood 5_HT level° Chromatography

was used to confirm and

extend the quantitative estimates of 5_HT and 5_oHIAA_ No increase

_ the histamine content of blood and

urine

was noted°

"_l°fects of treatment_ In view of the possible

role

of 5o_HT in

the pathogenesis

of the syndrome,

t_he effects of various 5_.HT

antagonists

were studied_

I)_

Two doses of 002.5 and 0o5 mg were given iov_ to the first

patient., but without effect on the flush o The second patient re _

celved 0°25 mg SoCo on 2 occasions before a mea/_ but the flush

was not prevented°

2) LSD

given to the first patient on 2 successive days _n

doses of 5 and lO_g

_rally.Jcaused

an unpleasant

throbbing

noise in the head for several days, which precluded

furthez in _-,

crease in dosage° No effect was noted on the flushing or the

dia_ _hoea

3) BO_ was given to the 2nd patient in a dose of O, 5 mg [orally._J

daily, working ap to 7_5 mg daily ove_ a period, of 3 weeks.

There was no reductionin

the n_mber of flushes, but the pa-

tient th0ug_t t_&t they wereless

severe° During treatment one

severe attack occurredl The dailyexcretionof

5_HIAA was un-

alteredo The 3rd-pa_leht was given 0_5 mg every 2 hours for 4

doses, afterw_ic_ IO ml_ of 10% alcohol was given, causing a

flush which wis_

intense and prolonged as previously°

4) anthihist_!nos: mepyramine and promethazine had no effect

on the symptoms°

It is concluded that the 5-HT antagonists and antihistamines

were without benefit°

Surgery: In neither of the two patients who came to laparotomy

was a large-scale resection possible. Resection of the primary

tumour in the 3rd patient was not followed by any immediate

change in the flushing, but the liver became smaller°

COMMENT: Although the results of this investigation werenega-

tire with regard to the effect of our preparations i they are

nevertheless of interest with regard to antagonismto 5-HTo

(Humorale Wirkungen

von metastasierenden

carcinoiden

Tumoren)

Bei einigen Patient_n mit malignen carcinoiden Tum0ren bestand

ein eigenartiges Syndrom mit Wallungen nach dem Kopf, Durch-

f_llen und Klappenfehlern amrechtenHerzen_

Beschreibung der

klinische_, pharmakologische_

und biochemischen Befunde bei 3

derartigen F_lleno In der Annahme, dass die Symptome durch 5_

Hydroxytryptamin (5_HT) Verursacht seien, wurde die Wirkuhg von

5_HT_Antagonisten unte_chtQ Gy (2 FKlle) beeinflusste die Wal-

lungen nichto LSD (1 Fall) hatte keinen_Einfluss aufWallun_

oder

Durchf_lleo

BOL

verminderte

die

HMufigkeit

der

Wallung

in 1 Falle nicht, doch gab der Patient an, dass ihre IntensitEt

nachgelassen h_tteo Bei einem anderen Pat. hatte BOL keine

prophylaktische Wirkung auf die durch Alkohol provozierteGe-

sichtsrSteo Antihistamine waren ebenfalls wirkungsloso

_9 (EDSI3S)

_T/OroSpi/mb 156 @_

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