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PENYAKIT ENDOKRIN

Suatu penyakit Hiperglikemi kronis dari


metabolik yang ditandai DM dihubungkan
oleh hiperglikemia yang dengan kerusakan
merupakan hasil dari jangka panjang, disfungsi,
gangguan pada sekresi dan kegagalan berbagai
insulin, kerja insulin atau macam organ, terutama
keduanya. mata, ginjal, syaraf,
jantung, dan pembuluh
darah.
Tabel 1. Daftar negara dengan jumlah perkiraan kasus DM terbanyak
untuk tahun 2000 dan 2030
Kerja hormon insulin

GLUKOSA GLIKOGEN
INSULIN
Darah Otot
Liver
Insulin affects many organs: protein
amino acids
uptake synthesis
It stimulates skeletal muscle fibers.

It stimulates liver cells. glycogen


glucose
synthesis
uptake

It acts on fat cells


fat
synthesis
It inhibits production of certain
enzyme.
enzyme glycogen
In each case, insulin triggers production breaking
these effects by binding to the
insulin receptor.
SlametS

9 PATOFISIOLOGI DMT2

Genetic susceptibility,
obesity, Western lifestyle

Insulin
IR -cell
resistance dysfunction

Type 2 diabetes
RESISTENSI INSULIN

RI : ketidak mampuan insulin untuk meningkatkan ambilan dan


pembuangan glukosa di otot,
RI di perifer : defek reseptor, post reseptor (translokasi dan
sintesis GLUT), produksi gula hati berlebihan
Kelainan yang memperberat : Faktor genetik, obesitas dan
inaktivitas fisik

IR
Disfungsi sel

Defek utama pada DMT2 bersama dengan resistensi insulin


Berkurangnya kemampuan sel beta untuk mensekresi insulin
sebagai respon terhadap hiperglikemi


1. Diabetes tipe 1
- kerusakan sel mengarah kepada defisiensi insulin absolut
A. Imun
B. Idiopatik
2. Diabetes tipe 2 (80%)
- defisiensi insulin relatif sampai defek sekresi
3. Tipe spesifik lainnya
A. Defek genetik dari fungsi sel
B. Defek genetik pada kerja insulin
C. Penyakit pankreas eksokrin
D. Endokrinopati
E. Induksi obat atau bahan kimiawi
F. Infeksi
G. Bentuk tidak umum dari diabetes dimediasi imun
H. Sindroma genetik lainnya
4. DM kehamilan (Gestational DM)
KELUHAN

Keluhan Klasik : Poliuria, polidpsia, polifagia, pean BB yg tidak jelas


sebabnya
Keluhan lain : lemah badan, kesemutan, gatal, mata kabur, DE, pruritus
vagina
KRITERIA DIAGNOSIS DM

Gejala klasik DM + GD sewaktu 200 mg/dl


Atau
Gejala klasik DM + GDP 126 mg/dl
Atau
GD 2 jam pada TTGO 200 mg/dl
Atau
HBA1c 6.5%
PREDIABETES

GDPT
GDP 100-125 mg/dl dan GD 2J setelah TTGO < 140 mg/dl
TGT
GD2J setelah TTGO 140 199 mg/dl dan GDP < 100 mg/dl
Bersama sama didapatkan GDPT dan TGT
HBA1c 5.7 6.4%
At 24-28 weeks gestation in women not previously
dxd with overt diabetes
75-g OGTT; Measure plasma glucose at fasting and
at 1 and 2 hours.
GDM dxd when plasma glucose exceeds:
Fasting: 92 mg/dL (5.1 mmol/L)
1 h: 180 mg/dL (10.0 mmol/L)
2 h: 153 mg/dL (8.5 mmol/L)
1. Usia 45 tahun, pemeriksaan diulang setiap 3 tahun.
2. Pemeriksaan seharusnya dipertimbangkan pada usia lebih
muda atau dilakukan lebih sering pada individu dengan:
Overweight (BMI 25 kg/m2)
Ada riwayat DM pada saudara tingkat pertama
Populasi etnis risiko tinggi (orang Amerika-Afrika, Amerika-
Hispanik, penduduk asli Amerika/Indian, Amerika-Asia,
Penduduk Kepulauan Pasifik)
Pernah melahirkan bayi dengan BBL > 9 lb ( 4 kg) atau
didiagnosis GDM
Hipertensi ( 140/90)
Kadar Kolesterol HDL 35 mg/dl (0,90 mmol/l) dan/atau
kadar trigliserida 250 mmol/dl (2,82 mmol/l)
Tes sebelumnya mempunyai IGT atau IFG.
Therapeutic Lifestyle Changes
Short-term use:
Acute illness, surgery, stress and emergencies
Pregnancy
Breast-feeding
Insulin may be used as initial therapy in type 2 diabetes
in marked hyperglycaemia
Severe metabolic decompensation (diabetic ketoacidosis, hyperosmolar
nonketotic coma, lactic acidosis, severe hypertriglyceridaemia)

Long-term use:
If targets have not been reached after optimal dose of combination
therapy or BIDS, consider change to multi-dose insulin therapy. When
initiating this,insulin secretagogues should be stopped and insulin
sensitisers e.g. Metformin or TZDs, can be continued.
HIPOGLIKEMIA

HIPOGLIKEMIA DITANDAI MENURUNNYA


KADAR GD < 70 mg/dl

Diagnosis (TRIAS WHIPPLE) :


1. gx klinis hipoglikemia
2. kadar glukosa plasma rendah
3. keadaan klinis membaik setelah kadar glukosa
normal setelah pemberian glukosa
GEJALA KLINIS HIPOGLIKEMIA

KARENA 2 PENYEBAB:

1. Terpacunya sistem saraf otonom (simpatis)


2. Tidak adekuatnya suplai glukosa ke jaringan serebral
(neuroglikopenia)
Tahap awal hipoglikemia krn respon tubuh thd peningkatan hormon
adrenalin, gx seperti:
Gemetaran
Kulit lembab dan pucat
Rasa cemas
Keringat berlebihan
Mudah lapar
Penglihatan kabur
Pada tahap lanjut, terjadi neuroglikopenia:
Sulit berpikir
Bingung
Sakit kepala
Kejang-kejang
Koma
Treatment of Hypoglycemia
Hypoglycemia symptoms
(BG <70 mg/dL)

Patient severely confused or


Patient conscious and alert
unconscious (requires help)

Glucagon injection, delivered by


Consume glucose-containing foods (fruit
juice, soft drink, crackers, milk, glucose another person
tablets); avoid foods also containing fat Patient should be taken to
Repeat glucose intake if SMBG result hospital for evaluation and
remains low after 15 minutes treatment after any severe
Consume meal or snack after SMBG has episode
returned to normal to avoid recurrence
Normal Thyroid State
Synthesis and release of thyroid hormone is
controlled by TSH relaesed form the anterior
pituitary
TSH is controlled by the release of thyroid
releasing hormone (TRH) from the
hypothalmus and a negative feedback loop to
the pituitary
Thyroid hormone productions dependent on
adequate iodine intake
Normal Thyroid State
Thyroid hormone is reversible bound to
various proteins including thyronine-binding
globulin (TBG)
Free unbound portions are biologically active
T4 is the predominant circulating hormone
T4 is deiodinated to t3
T3 is biologically more active than T4 but has a
shorter half-life
Clinical Exam. of Thyroid
Have patient seated on a stool / chair
Inspect neck before & after swallowing
Examine with neck in relaxed position
Palpate from behind the patient
Remember the rule of finger tips
Use the tips of fingers for palpation
Palpate firmly down to trache
Where to look for Thyroid ?
Clinical Anatomy of Thyroid
Clinical Exam of Thyroid
Causes of Hyperthyroidism
Most common causes Rarer causes
Graves disease Thyroiditis or other causes
of destruction
Toxic multinodular
Thyrotoxicosis factitia
goiter
Iodine excess (Jod-Basedow
Autonomously phenomenon)
functioning nodule Struma ovarii
Secondary causes (TSH or
HCG)
Hyperthyroidism
Occurs in in all ages
Uncommon under the age of 15
10 xs more common in women (1/10,000)
Graves disease is the most common etiology
80% of cases in the U.S.
Common in the 3rd and 4th decades
Caused by autoimmune thyroid-stimulating antibodies
Associated with diffuse goiter, opthalmopathy, and local
dermopathy
Hyperthyroidism
Toxic multinodular and toxic nodular goiters
are the next most common etiologies
Usually occurs in older populations
Commonly with previous history of goiter
Often with milder symptoms of thyrotoxicosis
Hyperthyroidism
Amiodarone-induced thyrotoxicosis (AIT)
Amiodarone is iodine rich and may cause both
hyper and hypothyroidism
Difficult to treat because of incomplete
understanding of mechanism
Two major forms exists
Type 1 occurs with a normal thyroid
Type 2 occurs with a abnormal thyroid
Tx.Varies based on the the type
Hyperthyroidism
Confirmed by thyroid function test
Elevated free T4 and Low TSH
In some cases of graves disease T4 may be normal
and TSH decreased but the patient appears
thyrotoxic
T3 level should be done to rule out T3 toxicosis
Hypothyroidism secondary to pituitary adenoma
will have elevated TSH levels
Hyperthyroidism
Graves Disease Eye Signs
N - no signs or symptoms
O only signs (lid retraction or lag)
no symptoms
S soft tissue involvement (peri-
orbital oedema)
P proptosis (>22 mm)(Hertls
test)
E extra ocular muscle
involvement (diplopia)
C corneal involvement (keratitis)
S sight loss (compression of the
optic nerve)
Graves Disease Other
Manifestations
Pretibial mixoedema
Thyroid acropachy
Onycholysis
Thyroid enlargement with
a bruit frequently audible
over the thyroid
Diagnosis of Graves Disease
TSH , free T4
Thyroid auto antibodies
Nuclear thyroid
scintigraphy (I123, Te99)
Treatment of Graves Disease
Reduce thyroid hormone production or reduce the
amount of thyroid tissue
Antithyroid drugs: propyl-thiouracil, carbimazole
Radioiodine
Subtotal thyroidectomy relapse after antithyroid therapy,
pregnancy, young people?
Simptomatic treatment
Propranolol
Obat Mekanisme kerja Indikasi
Beta blocker Inhibisi efek adrenergik Mengontrol gejala
Iodida Blok konversi T4 Menurunkan kadar hormon tiroid secara cepat
menjadi T3
Inhibisi sekresi hormon
PTU Memblok konversi T4 First line terapi jangka panjang pada graves
menjadi T3 dalam disease
jumlah besar di perifer
Radioaktif Terkonsentrasi pada Memiliki high cure rate pada terapi single dose
jaringa tiroid dan Pilihan terapi pada graves disease, multinoduler
menghancurkan goiter, nodul toksik
jaringan tiroid Pasien usia > 40 tahun
Relaps dengan terapi obat antitiroid
Pembedahan (subtotal Mengurangi massa Terapi pilihan pada pasien hamil, anak-anak yang
tiroidektomi) tiroid timbul efek samping dalam penggunaan obat
antitiroid
Nodul toksika pada pasien usia > 40 tahun
Goiter besar dengan gejala hebat
Terapi pilihan pada pasien yang menolak
radioaktif, gagal dalam terapi antitiroid
Indikasi kosmetik
Hypothyroidism

Occurs when there is insufficient hormone


production or secretion
Occurs more frequently in women (0.6 to 5.9 %)
May be transient
Pathophysiology is unclear but may be viral in nature
Etiologies of Hypothyroidism
Primary
Autoimmune etiologies
Hashimotos is the most common
Idopathic
Post ablation (surgical, radioiodine)
Post external radiation
Thryoiditis (subacute, silent, postpartum)
Postpartum thyroiditis occurs within 3-6 months and occurs in 2- 16
% of women
Self limited etiologies, often prededed by hyperthroid phase
Infiltrative disease (lymphoma, sarcoid, amyloidosis, Tuberculosis
Congenital
Etiologies of Hypothyroidism
Post Partum
Occurs 3-6 months post partum and occurs in 2-16% of women
Secondary (pituitary)
Neoplasm
Infiltrative Dz.
Hemorrhage
Tertiary (hypothalamic)
Neoplasm
Infiltrative Dz.
Hypothyroidism
Etiologies of Hypothyroidism
Drugs
Amiodarone
Occurs in 1-32% of patients
Most likely due to the large amount of iodine released in the
metabolism of the drug which inhibits thyroid hormone synthesis,
release, and conversion of T4 to T3
Lithium
Acts similarly to iodine and inhibit thyroid hormone release
Antithyroid medication
Hypothyroidism Symptoms
Tiredness and Weight gain with poor
weakness appetite
Dry skin Hoarse voice
Feeling cold Menorrhagia, later oligo
Hair loss and amenorrhoea
Difficulty in Paresthesias
concentrating and poor
memory Impaired hearing
Constipation
Hypothyroidism Signs
Dry skin, cool extremities
Puffy face, hands and feet
Delayed tendon reflex relaxation
Carpal tunnel syndrome
Bradycardia
Diffuse alopecia
Serous cavity effusions
Lab Investigations of
Hypothyroidism
TSH , free T4
Ultrasound of thyroid little value
Thyroid scintigraphy little value
Anti thyroid antibodies anti-TPO
S-CK , s-Chol , s-Trigliseride
Normochromic or macrocytic anemia
ECG: Bradycardia with small QRS complexes
Treatment
Most patient with uncomplicated symptomatic
Hypothyroidism may be referred to the primary
physician for further evaluation and initiation of
treatment
If hypothyroidism is due to a secondary etiology
initiation of thyroid hormone therapy may
exacerbate preexisting adrenal insufficiency
Treatment of Hypothyroidism
Levothyroxine
If no residual thyroid function 1.5 g/kg/day
Patients under age 60, without cardiac disease can be
started on 50 100 g/day. Dose adjusted according to
TSH levels
In elderly especially those with CAD the starting dose
should be much less (12.5 25 g/day)
Thyroiditis
The most common form of thyroiditis is
Hashimoto thyroiditis, this is also the most
common cause of long term hypothyroidism
The outcome of all other types of thyroiditis
is good with eventual return to normal
thyroid function
Thyroiditis
Acute: rare and due to suppurative
infection of the thyroid
Sub acute: also termed de Quervains
thyroiditis/ granulomatous thyroiditis mostly
viral origin
Chronic thyroiditis: mostly autoimmune
(Hashimotos)
Acute Thyroiditis
Bacterial Staph, Strep
Fungal Aspergillus, Candida, Histoplasma,
Pneumocystis
Radiation thyroiditis
Amiodarone (acute/ sub acute)
Painful thyroid, ESR usually elevated, thyroid
function normal
Sub Acute Thyroiditis
Viral (granulomatous) Mumps, coxsackie,
influenza, adeno and echoviruses
Mostly affects middle aged women, Three
phases, painful enlarged thyroid, usually
complete resolution
Rx: NSAIDS and glucocorticoids if necessary
Sub Acute Thyroiditis (cont)
Silent thyroiditis
No tenderness of thyroid
Occur mostly 3 6 months after pregnancy
3 phases: hyperhyporesolution, last 12 to
20 weeks
ESR normal, TPO Abs present
Usually no treatment necessary
Clinical Course of Sub Acute
Thyroiditis
Chronic Thyroiditis
Hashimotos
Autoimmune
Initially goiter later very little
thyroid tissue
Rarely associated with pain
Insidious onset and
progression
Most common cause of
hypothyroidism
TPO abs present (90 95%)
Chronic Thyroiditis
Reidels
Rare
Middle aged women

Insidious painless

Symptoms due to compression

Dense fibrosis develop

Usually no thyroid function impairment


Thyroid Storm
A life threatening hypermetabolic state due to
hyperthyroidism
Mortality rate is high (10-75%) despite treatment
Usually occurs as a result of previously unrecognized
or poorly treated hyperthyroidism
Thyroid hormone levels do not help to differentiate
between uncomplicated hyperthyroidism and thyroid
storm
Thyroid Storm
Preciptants of Thyroid Storm
- Infection
- DKA
- CVA
- Surgery
- Iodine administration
- Ingestion of Thyroid hormone
- Trauma
- MI
- Withdrawal of thyroid medication
- Palpation of thyroid gland
- Unknown etiology (20-25%)
Thyroid Storm
Clinical features
The most common signs are fever, tachycardia
out of proportion to the fever, altered mental
status, and diaphoresis
Clues include a history of hyperthyroidism,
exophthalmoses, widened pulse pressure and a
palpable goiter
Patients may present with signs of CHF
Thyroid Storm
Clinical features cont.
Common GI symptoms include diarrhea and
hyperdefication
Apathetic thyrotoxicosis is a distinct presentation
seen in the elderly
Characteristic symptoms include lethargy, slowed
mentation, and apathetic facies
Goiter, weight loss , and proximal muscle weakness
also present
Thyroid Storm
Diagnosis
Thyroid storm is a clinical diagnosis based upon
suspicion and treated empirically
Lab work is non specific and may include
Leukocytosis, hyperglycemia, elevated
transaminase and elevated bilirubin

Diagnosis dengan penilaian skor Burch


&Wartofsky > 45 krisis tiroid
Tatalaksana krisis tiroid
Pengobatan harus segera diberikan
Bila memungkinkan perawatan dalam Intensive care unit (ICU)
1. Perawatan suportif
- Koreksi gangguan cairan dan elektrolit
- Kompres atau pemberian antipiretik
- Atasi gagal jantung
2. Koreksi hipertiroid secara cepat
- Memblok sintesis hormon baru : PTU dosis besar
- Memblok keluarnya cikal bakal hormon dengan solusio lugol
- Menghambat konversi perifer dari T4 menjadi T3 dengan
kortikosteroid, penghambat beta (propranolol)
3. Mengobati faktor pencetus
4. Respon klinis pasien dapat terlihat dalam 24 jam dapat berlanjut
hingga beberapi hari atau minggu
Thyroid Storm
Drug Treatment of Thyroid Storm (table 216-6)
Decrease de novo synthesis:
Porpythiouracil 600-1000mg PO initially, followed by 200-250 mg q 4 hrs
Methimazole 40 mg PO initial dose, then 25 mg PO q6h
Prevent relases of hormone (after synthesis blockade intiated)
Iodine Iaponoric acid (Telepaque) 1 gm IV q8h for the first 24 h, then
500 mg bid or Potassium iodide (SSKI) 5 drops PO q6h or Lugol
solution 8-10 drops PO q6h
Lithuim 800-1200 mg PO every day
Prevent peripheral effects:
B-Blocker Propanolol (IV) titrate 1-2 mg q 5min prn (may need 240-480mg
PO q day) or Esmolol (IV) 500 mcg/kg IV bolus, then 50-200
mcg/kg per min maintenance
Guanethidine 30-40 mg PO q 6 h
Reserpine 2.5-5 mg IM q4-6h
Other consideration:
Corticosteroids Hydrocortisone 100 mg IV q 8 h or
dexamethosone 2 mg IV q 6 hr
Antipyretics Cooling blanket
acteaminophen 650 mg PO q 4-6h
Thyroid Storm
Treatment cont
Propranolol has the additional effects or blocking
perpheral conversion of T4-T3
Avoid Salicylates because it may displace T4 from TBG
If the patient continues to deteriorate despite appropriate
therapy circulating thyroid hormone may be removed by
plasma transfusion, plasmapheresis, charchoal
plasmaperfusion
Remember you must not administer iodine until
the synthetic pathway has been blocked
Thyroid Storm
Disposition
Admit to the ICU