Tahapan hormonogenesis

 6 tahap :

 trapping
 yodinasi tirosil di tiroglobulin
 coupling residu iodotirosil di tiroglobulin
 proteolisis tiroglobulin dan sekresi hormon tiroid,
 deiodinasi iodotirosine dalam sel tiroid, konservasi Yodium
 5”-deiodinasi T4 menjadi T3 intratiroidal
 Yang berperan penting : TSH, glikoprotein tiroglobulin,
ensim esensial TPO ( tiroid peroksidase), sistem deiodinasi
dan sistem transpor.
 Tugas : buat esai pendek mengenai tahapan hormonogenesis
hormon tiroid dan efek TSH pada tiroid. Tulisan tangan. 1
lembar A4
Physiologic effects of Disorders of thyroid function ( disease)
Thyroid hormones Hyperthyroid Hypothyroid
Fetal development : brain development and Abortus , premature, BBLR Intelectual disorder to
skeletal maturation Thyroid Cretinism
↑O2 consumption, heat production, free radical Increase BMR & sensitivity to heat (reverse)


formation
Cardiovascular : positive inotropic and Increase HR, contractilyti, lower (reverse)
chronotropic, heightened adrenergic sensitivity peripheral vascular resistance, increase
Cardiac output
Sympathetic : ↑ β adrenergic receptors, ↑ sensitivity to catech. : sympathomimetic (reverse)
amplify postreceptor catecholamine actions. manif.
Pulmonary : brain stem’s ventilatory responses ( reverse) hypoventilation
to hypoxia & hypercapnia, respiratory muscle
f/
Hematopoietic ↑ prod. Of erythropoetin, erythropoesis, ( reverse)
red cell turn over
Gastrointestinal : promote gut motility ↑ formed bowel movement ( reverse)

Skeletal : stimulate bone turn over esp. bone
resorption
Neuromuscular : maintain protein
turnover&skeletal muscle
Lipid & Carbohydrate metabolism
Endocrine : alter prod., responsiv., metab.
Clearance of a number hormones.
Hypercalciuria, hypercalcemia, ↓ bone
density
Proxymal myopathy, hyperreflexia, distal ↓deep tendon reflex
hand tremor, hyperactivity relaxation, hypoactivity
↑ hepatic gluconeogenesis, ↑ total and LDL cholesterol
glycogenolysis, glucose absorption,
cholesterol synthesis and degradation.
Precox pubert, gynecomastia Delay puberty,
hyperprolactinemia
 Disorders of Thyroid

1. Thyroid enlargement: Diffuse , Nodular : uni ,
multi.
2. Thyroid function dis. : hyper , hypo
3. Specific form : Graves opthalmopathy, thyroid
dermopathy
 Paschke 1997

Thyrotropin receptor

G proteins

cAMP pathway

function ↑ Iodine ↓ Proliferation

IGF-1 ↑
↓ EGF ↑
TGF-β ↓
Expression of Tg gene Expression of c-fos and
and TPO gene c-myc

Hyperthyroidism Adenoma

Konsekuensi aktifasi disproposional terhadap Thyrotropin receptor

 
Hyperthyroid
 Causes of
Hyperthyroidism

Most common causes Rarer causes
 Graves disease  Thyroiditis or other causes
 Toxic multinodular of destruction
goiter  Thyrotoxicosis factitia
 Iodine excess (Jod-
 Autonomously
Basedow phenomenon)
functioning nodule
 Struma ovarii
 Secondary causes (TSH or
ßHCG)
 Graves Disease

 Most common cause of endogenous hyperthyroidism

 Characterized by hyperthyroidism, ophthalmopathy with

exophthalmos and dermopathy (pretibial myxedema)

 Autoimmune disease with genetic susceptibility associated with

HLA-B8 and DR3, Female:Male = 7:1, 3rd to 4th decades

 Diffuse enlargement with audible bruit

 Wide,staring gaze,lid lag,exophthalmos,pretibial myxedema

 ↑ levels of free T4 & T3 and ↓ levels of TSH in blood

 ↑ uptake of radioactive iodine

Table 1. Antibodies in Graves’ Disease
Elevated levels of TSAb, TSBAb ( thyrotrophin receptor
antibodies (TRAb) exist as stimulating or blocking ) and
antibodies TBII (thyroid binding inhibiting
immunoglobulins )
• Elevated levels of anti-TPOAb ( 80%)
• Elevated levels of anti-TGAb ( 50%)
• Antibodies reacting to the Iodide Symporter and
Pendrin protein
• Antibodies recognizing components of eye muscle
and/or fibroblasts
• Antibodies to DNA
• Antibodies to Parietal Cells (infrequent)
• Antibodies binding to platelets
Graves Disease
Symmetrical
enlargement of
thyroid gland
Cut-surface is
homogenous, soft
and appear meaty
Hyperplasia and
hypertrophy of
follicular cells
Figure 2. Extreme thyroid hyperplasia in Graves' Disease, with tall cells,
small follicles, scant and "scalloped" colloid. Figure kindly provided by Dr.
Francis Straus
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)(Hertl’s test)
E – extra ocular muscle
involvement (diplopia)
C – corneal involvement (keratitis)
S – sight loss (compression of the
optic nerve)
Table 4. Ocular Signs and Symptoms in Graves’ Disease ( source : thyroid manager)

Ophthalmic phenomena reflecting thyrotoxicosis per se and apparently resulting from

sympathetic overactivity :
Lid reaction
• Wide palpebral aperture (Dalrymple’s sign), Lid lag (von Graefe’s sign)
• Staring or frightened expression, Infrequent blinking (Stellwag’s sign)
• Absence of forehead wrinkling on upward gaze (Joffroy’s sign)
Ophthalmic phenomena unique for Graves’ disease and caused by specific pathologic changes in
the orbit:
• Inability to keep the eyeballs converged (Mobius’ sign)
• Limitation of movement of the eyeballs, especially upward, Diplopia
• Blurred vision due to inadequate convergence and accommodation
• Swelling of orbital contents and puffiness of the lids, Chemosis, corneal injection, or ulceration
• Irritation of the eye or pain in the globe, Exophthalmos (also produces mechanically a wide
palpebral fissure), Visible and palpable enlargement of the lacrimal glands
• Visible swelling of lateral rectus muscles as they insert into the globe, and injection of the
overlying vessels, Decreased visual acuity due to papilledema, retinal edema, retinal hemorrhages,
or optic nerve damage
HR, contractility CO
O2 consumption, CO2
production Vt, RR

/ PTH levels

bone turnover (i.e.
formation/ catabolism)

Vasodilation
Blood flow
Figure 9. Congestive
heart failure induced
in an otherwise
healthy young
woman
(a), which receded
(b), and returned to
normal
(c), during and after
therapy.
Figure 7. Plummer's nail changes, showing
thinning of the nail and marked posterior erosion
of the hyponychium.

Figure 8. Remarkable "pretibial

myxedema", also present on feet and
hands, of a patient with Graves' disease
and exophthalmos.
Graves Disease Other
Manifestations
Pretibial mixoedema
Thyroid acropachy
Onycholysis
Thyroid enlargement
with a bruit frequently
audible over the thyroid
GRAVES’ DISEASE SYMPTOMS

• Preference for cool temperature, Weight loss with increased appetite

•Prominence of eyes, puffiness of lids, Pain or irritation of eyes
•Blurred or double vision, decreasing acuity,↓motility
•Goiter, Dyspnea, Palpitations or pounding of the heart
•Ankle edema (without cardiac disease)
•Less frequently, orthopnea, paroxysmal tachycardia, anginal pain, and CHF
•↑ frequency of stools, Polyuria
•↓ in menstrual flow; menstrual irregularity or amenorrhea, ↓ fertility
•Fatigue, Weakness, Tremor, Occasional bursitis, Rarely periodic paralysis
•Nervousness, irritability, Emotional lability, Insomnia or decreased sleep requirement
•Thinning of hair, Loss of curl in hair, Increased perspiration
•Change in texture of skin and nails, Increased pigmentation, Vitiligo
•Swelling over out surface of shin
• Family history of any thyroid disease, especially Graves’ disease
Table 5. Neuromuscular Manifestations of Thyrotoxicosis
Tremor
• Hyperactive reflexes
• Accelerated reflex relaxation
• Anxiety
• Disorientation
• Psychosis
• Thyrotoxic neuropathy (rare)
• Acute thyrotoxic encephalopathy (very rare)
• Seizures (with or without an underlying abnormality)
• Neuropathy secondary to nerve entrapment by lesions of
pretibial myxedema
• Corticospinal tract disease with pyramidal tract damage
(rare)
• Chorea and athetoid movements (rare)
• Hypokalemic periodic paralysis
• Myopathy
• (Myasthenia gravis — associated)
Table 6. Cardiac Manifestation of Graves’ Disease

• Tachycardia
• LVH and strain on EKG
• Premature atrial and ventricular contractions
• Atrial fibrillation
• Congestive heart failure
• Angina with (or without) coronary artery disease
• Myocardial infarction
• Systemic embolization
• Death from cardiovascular collapse
• Resistance to some drug effects (digoxin, coumadin)
• Residual cardiomegaly
Diagnosis of Graves Disease

Examination of the thyroid

•Have patient sit on chair
•Look at neck before and after swallowing
•Examine patient in relaxed position
•Palpate firmly
Diagnosis of Graves Disease
Ultrasonography thyroid
 Diagnosis of Graves Disease

Nuclear thyroid scintigraphy (I123, Te99)

Diagnosis of Graves Disease
Blood analysis :

TSH  , free T4 
Thyroid auto antibodies : TRAb, anti
TPO
 Treatment of Graves
Disease

Reduce thyroid hormone production or
reduce the amount of thyroid tissue
 Antithyroid drugs: propyl-thiouracil,
carbimazole/metimazol
 Radioiodine
 Subtotal thyroidectomy – relapse after antithyroid
therapy, pregnancy, young people?
Symptomatic treatment
 Propranolol
Figure 2. Comparison of outcome of treatment of thyrotoxicosis by 131-I (left upper
panel); 131-I plus ATD + KI (right upper panel); surgery (left lower panel); and ATD
(right lower panel); over ten years follow-up. Surgery produced the highest final
percentage of euthyroidism without therapy, followed by ATD and 131-I.
Table 5. Iodine-131 Therapy for Graves’ Disease
Indications

•Any patients above a preselected age limit

•Patients who fail to respond to antithyroid drugs
•Prior thyroid or other neck surgery Contraindications to surgery, such as
severe heart, lung,or renal disease

General Contraindications

•Pregnancy or lactation
•Insufficient 131-I uptake due to prior medication or disease
•Question of malignant thyroid tumor
•Age below a preselected age limit, such as (possibly) age 15-18
•Patient concerns regarding radiation exposure

Other Contraindications

•Unusually large glands

•Active exophthalmos
 Wayne's Index

The score ranges from + 45 to -25. > 19 implies toxic hyperthyroidism, < 11
euthyroidism, 11 - 19 is equivocal. Diagnostic accuracy of 85%.
HYPOTHYROID

Dr. Hakaru Hashimoto

Figure 7. Diagnosis of Hashimoto’s thyroiditis (chronic thyroiditis)
Figure 2. Electron microscopy image of thyroid
tissue from a patient with Hashimoto's thyroiditis,
showing electron dense deposits of IgG and TG
along the basement membrane of follicular cells
Figure 3. Pathology of Hashimoto's thyroiditis. In this typical view of severe
Hashimoto's thyroiditis, the normal thyroid follicles are small and greatly
reduced in number, and with the hematoxylin and eosin stain are seen to be
eosinophilic. There is marked fibrosis. The dominant feature is a profuse
mononuclear lymphocytic infiltrate and lymphoid germinal center
formation.
Incidence and Distribution
• Unknown, roughly equal to that of Graves’ disease (0.3 – 1.5 cases 0/ 00 )
• 15 – 20 X frequent in women as in men
• Especially 30 to 50 y.o, but may be seen in any age group, including children.
• Much higher frequency than is diagnosed clinically.
• Family : a number of relatives with moderate enlargement of the thyroid gland
suggestive of Hashimoto’s thyroiditis. Many of these persons have TG and
TPO antibodies, and most are entirely asymptomatic.
• In most instances, biopsy revealed focal rather than diffuse thyroiditis.
• Roughly 10% of most populations have positive TG and TPO antibody test
results in the apparent absence of thyroid disease by physical examination.
Figure 4. Fluorescent thyroid scan in thyroiditis. The normal thyroid scan
(left) allows identification of a thyroid with normal stable (127I) stores
throughout both lobes. A marked reduction in 127I content is apparent
throughout the entire gland involved with Hashimoto's thyroiditis (right).
 Billewicz diagnostic index

A score of +25 or more suggests hypothyroidism, while a score of -30 or less

excludes the disease. Counting the pulse for a 30-s period, and report bradycardia
of the pulse <75/min
Zulewski's clinical
score for
hypothyroidism

>5 points :
hypothyroidism,
0-2 points : euthyroidism