Thyroid , antithyroid , parathyroid &

Calcium metabolism
Suharti K Suherman
Dept. of Pharmacology & Therapeutic
Medical Faculty, Univ. of Indonesia

Thyroid h secreted by thyroid gland source

of 2 different types of hormones :

a. tetraiodothyronine (T4) &

triidothyronine (T3) essential for normal
growth &

b. calcitonin secreted by parafollicular

cells
Synthesis unique & complex
- synthesized & stored as AA residues
of thyroglobulin = a protein component of
thyroid follicular colloid

Thyroid H the only hormone that

contains iodine & need exogenous I for
its synthesize , has 2 important
functions
:
** in developing phase determinants
of normal development espscl
CNS
devepl.
** in adult it maintains metabolic
homeostasis affecting the functions of
all organs

Biosynthesis thyroid hormones

Uptake of iodide ion (I- )by the gland
Oxidation of iodide & the iodination of
tyrosyl groups of thyroglobulin
Coupling of iodothyronines residues by ether
linkage to generate the iodothyronines
Resorption of the thyroglobulin colloid from the
lumen into the cell
Proteolysis of thyroglobulin & the release of
thyroxine & triiodothyronine into the
blood

 Normal daily production of thyroxine is

80 100 ug & T3 : 30 40 ug
Under normal condition 40% of T4 is
coverted to T3

** thyroid h is bound in TBG major

carrier of TH , T4 is also bound to
TB prealbumin & a small number
is bound to albumin or free
** eliminated slowly t 6 8 d
hyperthyroidism shortened to 3 4 d
hypothyroidis 9 10 d
pregnancy binding to TBG
retarded clearence
** metabolism liver

Grugs that alter binding of thyroid to TBG

binding
estrogen
clofibrate
5fluorouracil
tamoxifen
SERM
carbarmazepin
methadon
heroin

binding
glucocort
androgen
salicylates
mefenanic acid
phenytoin,
furosemide

Actions of thyroid hormones

mediated by nuclear TRs
T3 binds to high-affinity TRs then bind
to specific DNA sequences (TREs
= thyroid hormone response
elements) in the promoter regions
of target genes to modulate gene
transcrptn protein synthesis
T4 hasnt been shown to alter gene
transcrpt , it must be converted to
T3

 Indications : hormone replacement th/ in

hypothyroidism or cretinism;
for TSH suppression th/ in nontoxic
goiter or after th/ for thyroid cancer
Preparations :
* thyroxine Na tab 50100 ug/d or
* levothyroxine Na (L-T4) tab 25 - 50
ug/d or lyophilized powder for inject
= drug of choice for replace ment th/ due
to its consistent potency &
prolonged duration of action

 Average daily adult replacement dose of

levoth is 1.7 ug/kg BW
The goal of th/ is to normalize the serum
TSH ( in primary hypothyroidism)
or free T4 ( in secondary
hypothyroidism) ; and to relieve
symptoms of hypothyroidism

 Liothyronine Na (L-T3) tab & injectable

form mixture of L-T4 & L-T3 =
Liotrix, 0.05 0.1 mg/d (tab 100ug)

 L-T4 prefer for thyroid replacement

longer duration of action, 50 80%
of the dose is absorbed
blood level is easily monitored by FT4 &
TSH serum level
T1/2 7 days once daily
Side effects : allergic reactions, signs of
hyperthyroidis

 Drugs interactions:
# cholestyramin,iron,calcium,Al (OH)3
& soy product interfere L-T4
absorption
# phenytoin, carbamezepin & rifampin
biliary excretion of L-T4
often necessary the dose
# pregnant woman/ on OC
the dose of levothyroxine need to
be due to serum TBG induced
by estrogen

Hyperthyroidism antithyroid
propylthiouracil ( PTU), methimazole &
carbimazol (a carbethoxy derivative of
methimazole it inhibits
thyroglobulin to form T4 & T3
within the thyroid gland
PTU , but not methimazole, block
peripheral conversion T4 to T3

PTU

Methim

plasma prot binding ..75%........nil

plasma t1/2 .75 min.4 6 hrs
concentrated in thyroid.yesyes
metab in severe
liver disease..normal.
kidney disease..normal.normal
dosing frequency.1- 4 x/d..1 2 x/d
transplacental/
breast milklow..

Side effects
Skin rash ( 3% & 7%)
Agranulocytosis ( 0.44 & 0.12% )
Tremor, tachycardia, palpitation, flushing,
headache
Interactions
Anticoagulants, digitalis, amiodarone,
cholestyramine

Parathyroid H & vit D

importance role in calcium metabolism
secreted by parathyroid gland Ca++
plasma = the most powerful
regulator for its secretion
Ca++ plasma is low PTH secretion , if
the hypocalcemia is sustained
hypertrophy & hyperplasia of the
gland

Whole body daily turnover of calcium

Calcium homeostasis & its regulation by PTH & 1.25dihydroxyvitamin D.

Other factor to bone strength : bone

turn
over
Bone
remodeling sequence in healthy subjects

Faaltirotoksikosis
--------hipotiroidism
*Kulit: panas,lembab -------------pucat,dingin,kering
*mata: retraksi kelopak-----------kelopak terjatuh
periorbital edema-------------( lidah besar )
exopthalmus
*jantung : freq & CO ------------ freq jatng,nadi,CO
*resp : dyspnoe -------------------- hipoventilasi
* GI : nafsu makan ------------------ peristaltik
*otot: lemah, lelah ---------------------kaku , lelah

 Primary target cell PTH is osteoblast ,

although some PTH receptors has
been found in osteocytes
PTH also recruits osteoclast precursor
cells to form new bone remodeling
units
Sustained increases in circulating PTH
increase in the prevalence of
osteoclasts resorption sites
PTH increase total number of osteoblast
initiation of bone remodeling

 PTH stimulates cyclic AMP production in

osteoblast
Teriparatide for severe osteoporosis
20 ug SQ/daily serum PTH increase to
peak concen within 30 min after
the inj & decline within 3 hrs,
serum Ca increase to peak
concent at 4 6 hrs

 Preparat: l-tiroksin (T4) 75-100ug atau

1-1.5ug/kg/h, Liotironon (T3) --25-50ug
Liotrix (T3 : T4=4:1) 60-80ug

Biosintesis H tiroid
Iodide trapping = transport iodida ke kel
tiroid
di oksidasi - thyroidal peroxidase
iodium iodinasi residu tirosin di
molekul tiroglobulin monoiodoti rosin
(MIT) & diiodotirosin (DIT)
2 mol DIT bergab diantara mol tiroglo
bulin L-tiroksin (T4)
1 mol MIT+1mol DIT T3

 Stimulasi TSH T3 ,T4 darah , Proses ini

tehambat bila iodium berlebihan.
T4 > T3 , potensi ikatannya dg reseptor T3
10 x > T4 .
Dlm darah , hepar & organ lain T4 diubah
T3 , dihambat oleh obat anti- tiroid
T3 & T4 terikat : TBG , album , prealbum
TBG dibentuk hepar dibawah pengaruh :
estrog , androg, glukokort

ANTI-TIROID
Gol.tioamida , iodida, radioactive
Iodium.
Indikasi : hipertiroidism
Sering: propiltiourasil , metimazol,
karbimasol , atau iodium radioaktiv
Kerja: menghambat sintesis tiroksin
peroksidase
oral

Calcitonin
hormone produced by parafollicular C cells
A single chain peptide hormone IM /
nasal spray
Postmenopausal oeteoporosis calcitonin
inhibit osteoclast activity in bone
resorption osteoklast
BMD = Bone Mineral Density)

 enough intake Calcium & vit D

Preparations : synthetic salmon
calcitonin nasal spray 50 IU 2x/
day or injection ampul 50 IU 1 x /
2 days
Adverse reactions : nausea,
flushing,
dose-dependent

Calcitriol
Metabolit aktif vit. D3
Normal dibentuk ginjal dari
prekursornya 25-OH
cholecalciferol (25-HCl)
Produksi sehari : 0,5---1,0 gme
pada masa pembentukan tulang
(masa kehamilan)
Normal : peran me absorpsi
Ca++ di usus & meregulasi
mineralisasi tulang

 Postmenopausal osteoporosis
calcitriol resorpsi tulang prevention
of lost bone mass
Dosage : 0,25 ug 1 x / 2 x / d risk of &
hyper - calemia / siuria

OK dosis awal dimulai 0.25mg/h -setelah itu dapat di 0.5 mg/h

monitor kadar Ca++
Adverse reactions : hypersens,
hypercalcemia

 Preparat Iodida u/ hipertiroidism

kurang memuaskan, krn setelah
th/ sering terjd hipertiroidism yg >
hebat