FYI: Thyroid Function, Bile Flow, Sphincter of Oddi Tone

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Neurogastroenterology and Motility

Volume 14 Issue 2 Page 183 - April 2002

doi:10.1046/j.1365-2982.2002.00316.x

Bile flow to the duodenum is reduced in hypothyreosis and enhanced

in hyperthyreosis

J. LAUKKARINEN1, P. K™™BI2, J. KALLIOVALKAMA2,3, J. SAND1, J.

MATTILA4, V. TURJANMAA5, I. P™RSTI6 & I. NORDBACK1

Disturbances in sphincter of Oddi (SO) function may prevent normal

bile flow and thus enhance probability of common bile duct stone

(CBDS) formation. We have previously shown increased prevalence of

diagnosed hypothyroidism in CBDS patients, which may be explained

by thyroxine-induced inhibition of SO contractility, in addition

to previously suggested changes in bile composition and

hepatocytic excretion. The aim of this study was to investigate

biliary dynamics in relation to altered thyroid gland function in

rat, a rodent without a gallbladder. Euthyroid, hypothyroid or

hyperthyroid Spraque-Dawley rats were anaesthetized with i.p.

urethane, and exsanguinated at 15, 45, or 60 min after intravenous

99mTc HIDA injection. At these timepoints, the bile flow to

intestine was determined by measuring the relative intestine vs.

liver radioactivity. At 45 min this was 44% lower in hypothyroid

rats and at 60 min 73% higher in hyperthyroid rats compared to

euthyroid rats, while hepatic radioactivity at 15 min and blood

pressure at injection were similar in the groups. We conclude that

the bile flow to duodenum is reduced in hypothyreosis and enhanced

in hyperthyreosis.

To cite this article

LAUKKARINEN, J. , K™™BI, P. , KALLIOVALKAMA, J. , SAND, J. ,

MATTILA, J. , TURJANMAA, V. , P™RSTI, I. & NORDBACK, I. (2002)

Bile flow to the duodenum is reduced in hypothyreosis and enhanced

in hyperthyreosis. Neurogastroenterology and Motility 14 (2),

183-188. doi: 10.1046/j.1365-2982.2002.00316.x

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http://granum.uta.fi/english/kirjanTiedot.php?tuote_id=6169

Laukkarinen Johanna

The Effect of Thyroxine on Biliary Motility

Acta Universitatis Tamperensis; 850

Acta Electronica Universitatis Tamperensis; 154

157 p.

2002

ISBN:951-44-5265-8

951-44-5266-6

Language: eng

Publisher: Tampereen yliopisto

Here you can read the book in pdf format

In the present study the association between common bile duct

(CBD) stones and hypothyroidism was investigated, the finding

leading to further studies regarding the effect of thyroxine (T4)

on the human and pig sphincter of Oddi (SO) and the specificity

and the mechanisms of this effect. The net impact of altered

thyroid function on bile flow was studied both in the rat and in

human subjects. The study consisted of two clinical and three

experimental investigations.

In the retrospective study the CBD patients had significantly more

diagnosed hypothyroidism compared to the gallbladder stone

patients or to the age-, sex- and hospital admission-adjusted

controls. The higher prevalence of hypothyroidism in the CBD stone

patients compared to the gallbladder stone patients suggested that

also factors other than merely changes in the cholesterol

metabolism, or bile excretion rate, e.g. changes in the function

of the SO, may be behind the association between CBD stones and

hypothyroidism.

Ex vivo experiments with SO-rings were carried out in organ bath

chambers. In the pig T4 did not affect on unspecific, high

concentration KCl-induced SO contraction but did reduce the

receptor-mediated ACh- and Hist-induced SO contraction, which

suggested a direct effect of T4 on the control mechanisms of SO

motility. Because the effect of T4 on the SO appeared to be

prorelaxing, the absence of T4 might result in an increased

tension in the SO. A similar prorelaxing effect of T4 on the SO

contractility observed in the pig was found also in human SO

specimens. This observation is thus not " pig-specific " , but may

also be of clinical significance, as suggested by the association

between diagnosed hypothyroidism and CBD stones. T4 had a direct

prorelaxing effect on pig SO contractility also in physiological

concentrations, and might thus influence SO tone also in vivo. In

Western Blotting, the human SO expressed TR beta1 and beta2. The

prorelaxing effect of T4 was mediated via a mechanism, which

requires new mRNA and protein synthesis and subsequently leads to

the activation of K+ channels.

The net impact of altered thyroid function on bile flow was

studied both in the rat and in human. In rats net bile flow was

studied by counting the relative intestine v. liver 99mTecnetium

(Tc) HIDA activity of organs removed at various time points after

99mTc HIDA i.v. injection. The net bile flow to the duodenum was

reduced in hypothyroidism and enhanced in hyperthyroidism. In

patients 99mTc HIDA cholescintigraphy was performed in hypothyroid

and euthyroid stage. The hepatic clearance was decreased and the

hilum-duodenal transit time tended to be increased in the

hypothyroid stage in the study patients, the appearance of

radioactivity in the large bile ducts at the hilum, and hepatic

maximal uptake being the same in the hypothyroid and the euthyroid

stage. These findings further support the other findings that

hypothyroidism might decrease bile flow into the duodenum.

In conclusion, the reduced prorelaxing effect of T4 on the SO in

hypothyroidism may result in delayed emptying of the biliary

tract, and, together with the possible cholesterol load in the

bile and decreased hepatocytic excretion rate composes an

important explanation for the increased association of CBD stones

and hypothyroidism

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Is bile flow reduced in patients with hypothyroidism?

Autor/-en: Laukkarinen J, Sand J, Saaristo R, Salmi J, Turjanmaa

V, Vehkalahti P, Nordback I

Quelle: Surgery 2003 Mar;133(3):288-293

Background. Disturbances in the sphincter of Oddi (SO) function

may prevent normal bile flow and thus enhance the probability of

common bile duct stone (CBDS) formation. We have previously shown

increased prevalence of diagnosed hypothyroidism in CBDS patients,

thyroxine (T-4)-induced inhibition of the SO contractility both in

animal and in human experiments ex vivo, and reduced bile flow to

duodenum in hypothyroid rats. The aim of the present study was to

investigate human biliary dynamics in relation to altered thyroid

gland function. Methods. Eight female patients, 1 with diagnosed

untreated hypothyroidism and 7 with total thyroidectomy performed

due to thyroid cancer, were studied in hypothyroid stage and again

after thyroxine replacement therapy in euthyroid stage, with

quantitative Tc-99m HIDA cholescintigraphy (QC), biliary

ultrasonography, and serum determinations. Each patient served as

her own control in the 2 stages of the study. Results. In QC,

maximal uptake of 99 7 HIDA was not changed in hypothyroidism

compared to euthyroidism. The first appearance of radioactivity to

large bile ducts, at the helium hilum remained,unchanged in the 2

stages of the study. Hepatic clearance of Tc-99m HIDA was

decreased at 45 minutes (28% [11-38] vs 50% [33-54]; P =.028;

median and range) and at 60 minutes (55% [28-80] vs 69% [61-79]; P

=. 028; median and range) and hilum-duodenal transit time

increased by 31% compared to euthyroid stage. In US no changes

were seen in gall bladder or bile ducts in the 2 stages of the

study. Serum hypercholesterolemia was observed in the hypothyroid

stage. Conclusions. We conclude that hypothyroidism may result in

delayed emptying of the biliary tract, as studied with QC. In

addition to the changes in bile composition and excretion rate

suggested before to take place in hypothyroidism, according to the

present study changes in biliary emptying also may be included in

the probable causes for the increased prevalence of CBDS in

hypothyroidism. This may be due to the absence of the prorelaxing

effect of thyroxine on SO, which we have shown before to exist ex

vivo.

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Mechanism of the prorelaxing effect of thyroxine on the sphincter

ofOddi

Autor/-en: Laukkarinen J , Sand J , Aittomaki S , Porsti I , Koobi

P , Kalliovalkama J , Silvennoinen O , Nordback I

Quelle: Scandinavian Journal of Gastroenterology 2002 Jun

1;37(6):667-673

Background: Disturbances in the function of sphincter of Oddi (SO)

may prevent normal bile flow and thus enhance the probability of

common bile duct stone (CBDS) formation. Previously, we have shown

increased prevalence of hypothyroidism in CBDS patients. Methods:

In animal (pig) experiments, thyroxine (T-4) and triiodothyronine

have a specific inhibitory effect on SO contractility, which

raises the possibility that the lack of this prorelaxing effect in

hypothyroidism could, at least in part, explain the increased

prevalence of CBDS. The aims of the present study were to

investigate, whether human SO reacts similarly to T-4, and to

study the mechanisms of the T-4 prorelaxin g effect. Results: We

found that T-4 had similar inhibitory effects on both human and

pig SO contractions. The T-4 effect was dose-dependent, and

maximum was observed in 30 min. The maximal prorelaxin g effect

was achieved with 0.1 nM T-4 concentration, the effect of the

physiologica l T-4 concentration (0.01 nM) being about half of the

maximal effect. Addition of alpha-adrenoceptor antagonist

phentolamine, beta-adrenoceptor antagonist propranolol, nitric

oxide (NO)-synthesis inhibitor L-NAME, nerve conductance blocker

tetrodotoxin, or cyclooxygenase inhibitor diclofenac did not

affect the T-4-induced inhibition of contraction. Addition of

transcription inhibitor actinomycin D or translation inhibitor

cyclophosphamide partially reversed the T-4-induced inhibition of

contraction. Addition of K+ channel blocker glibenclamide totally

reversed the T-4-induced inhibition of contraction. In Western

blotting, the thyroid hormone receptor (TR) antibody recognized 53

kDa and 58 kDa proteins, corresponding to beta1 and beta2 isoforms

of TR, in the human SO tissue. Conclusions: We conclude that T-4

has a direct prorelaxing effect on human SO that expresses TR

beta1 and beta2. This effect is mediated through a transcriptional

mechanism that requires new mRNA and protein synthesis and

subsequently leads to the activation of K+ channels.

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