• Pituitary disorders

• Adrenal disorders
• Thyroid diseases

Harsinen Sanusi
ACTH
GH
PITUITARY ADENOMA
 Pituitary tumors
• Pituitary tumors are the most common
diseases of the pituitary gland

• Benign and monoclonal - arise from single

type of anterior pituitary cells

• Variable presentation
 Pituitary tumors
Hypersecretion

Function
Insufficiency

Microadenoma

Size
Macroadenoma
 Classification of pituitary tumors according to
size,invasiveness and expansion

Microadenomas Macroadenomas
(D < 10 mm) (D > 10 mm)

Intrasellar Extra sellar

Non invasive

Invasive
Excessive pituitary GH-Secretion Normal pituitary GH-Secretion
 Pituitary Adenomas
Commonnest causes
Majority are hypersecreting

Endocrinologic abnormality
Pituitary Hypersecretion
• PRL  most commonly
secreted by adenoma 
hyperprolactinemia
• GH  Acromegaly
• ACTH  Cushing’s disease
 ACROMEGALY
• GH-secreting pituitary adenoma 2nd
frequency
• Clinical manifestations :
Chronic GH hypersecretion  overgrowth
of bone is the classic feature particularly of
the skull and mandible
• Adults : linear growth does not occur,
because of prior fusion of the epiphyses of
long bones
• Childhood & adoloscence  Gigantism
 ACROMEGALY
• Etiology: excessive pituitary GH secretion
• Sex incidence equal
• Mean age at diagnosis is approximately
40 years
• Duration of symptoms usually 5-10 years
before the diagnosis established
• Increased late morbidity and mortality if
untreated  slowly progressive and
spontaneous remission
 Clinical manifestations of
acromegaly
• Manifestation of GH Excess
• Disturbance of other endocrine
function
• Local manifestation
 Clinical manifestations of
acromegaly
Manifestation of GH Excess
Acral enlargement, soft tissue
overgrowth, hyperhydrosis, lethargy
or fatigue, weight gain, paresthesis,
joint pain, hypertrichosis, goiter,
hypertension
Adults : linear growth does not occur, because of prior fusion of the
epiphyses of long bones. Childhood & adoloscence  Gigantism
 Clinical manifestations of
acromegaly
Disturbance of other endocrine function:
hyperinsulinemia,
glucose intolerance,
irregular or absent menses,
decreased libido,
hypothyroidism,
galactorrhea,
gynaecomastia,
hyperadrenalism
 Clinical manifestations of
acromegaly
Local manifestations
Enlarged sella
Head ache
Visual deficit
Laboratory finding
GH hypersecretion > 10 ng /mL

postprandial hyperglycemia,
serum insulin is increased,
elevated serum phosphorus,
hypercalciuria
Initial steps diagnosis :
Neuro-opthalmologic
evaluation
and
Neuro-radiologic studies with
MRI
 Imaging study
• Plain films:
Sellar enlargement (90% cases),
Enlargement of the frontal, maxillary
sinuses and the jaw
Thickening of the calvarium
Increased thickness of the heel pad
• MRI
Increase in hell pad thickness
Visual Field Defects
• Bitemporal hemianopsia
• Visual loss
• Large tumor  diplopia,
cranial nerve dysfunction
(NIII,IV,VI)
Effects of pituitary
tumors on the
visual apparatyus
 Diagnostics
• Laboratory findings:
GH increase 10 ng/mL (N= 1-5 ng/mL), pp
plasma glucose, serum insulin, serum
phosphor , hypercalciuria
• Imaging studies:
Plain film  90% casessellar
enlargement
Enlargement of jaw, maxillary sinuses,
increased soft tissue bulk
Treatment
• Removal or destruction of pituitary tumor
• Reversal of GH hypersecretion
• Maintenance of normal pituitary function
• Criteria for adequate respons GH< 5 ng/mL
Remission< 2 ng/mL
• Initial therapy  transphenoidal micro surgery.
• Radiation th/ reserved for patients w/ inadequat
responses to surgery & medical therapy
 Treatment
• Surgical treatment : for small or moderate –size
tumors (< 2cm) transphenoidale Surgery is
the treatment of choice for microadenomas (90%
cure)
• Medical treatment:
Somatostatin analog
Octreotide acetate (Sandostatin) & Lanreotide
(Somat uline)  the therapy of choice with
residual GH hypersecr. Following surgery
• Radiotherapy
 HIPOTHALAMUS

GHRH SOMATOSTATIN

PITUITARY SOMATOSTATIN
DOPAMINE-AGONIST AGONIST :
DRUGS:BROMOCRIP OCTREOTIDE
TINE,CABERGOLINE GH
GH-RECEPTOR
ANTAGONIST:
PEGVISOMANT
GH-RECEPTOR

IGF-1 GH

IGF-1 :Insulin like growth factor

 ACTH Secreting Pituitary
Adenoma
(Cushing Disease)

• Harvey Cushing 1932

• ACTH Hypersecretion bilateral
adrenal hyperplasia
• Spontaneous hypercorticolism (Cushing
syndrome).
• DD: Adrenocorticosteroid excess-
Ectopic ACTH syndrome and adrenal
tumors
 Clinical Features
• Onset insidious, usual 20-40 y, F:M :8:1,
Ectopic ACTH M:F:3:1
• Central Obesity, hypertension, glucose
intolerance, gonadal disfunction, moon
facies, plethora osteopenia, muscle
weakness, violaceous striae, hirsutism,
acne,poor wound healing, fungal infection,
 Diagnosis & Treatment
• Basal plasma ACTH
• Treatment :
Surgical treatment: microsurgery
Radiotherapy: Conventional radiotherapy
Medical therapy: no drugs supresses pituitary
ACTH secretion.
* Ketoconazole to inhibit adrenal steroid biosynthesis,
* Metyrapone, aminoglutethimide  reduce cortisol
hypersecretion
EMPTY SELLA SYNDROME
• Etiology
Congenital  Subarachnoid space
extends into the sellaturcica with
cerebrospinal fluid  enlargement,
remodelling (Congenital ,after pituitary
surgery or radiation therapy, postpartum
pituitary infarctin (sheehan syndrome)
 Clinical features and Diagnosis
• Midlle aged, obese women
• Hypertension, rhinorrhea, visual field
impairment
• Diagnosis: MRI
 CRANIOPHARYNGIOMA
• Children and adolescence
• >80% hypothalamic-pituitary deficiencies
 GH deficiency most common, growth
retardation, gonadotropin deficiency
• Symptom: intracranii pressure, decreased
visual acuity
• Diagnose:MRI
Pituitay Insufficiency
 Pituitay Insufficiency
• Panhypopituitarism 
classic manifestation
of pituitary adenomas;
Hypogonadism c/
GnRH  screened
FSH/LH to exclude
primary gonadal failure
• TSH or ACTH
deficiency is relatively
unusual
 Posterior Pituitary
Antidiuretic hormon (ADH; Vasopressin )

Diabetes Insipidus : Deficient ADH

action
Synd Inappropriate ADH : High plasma
ADH concentration
 DIABETES INSIPIDUS
• Is disorder of water balance caused by
nonsmotic renal losses of water
• Etiology : deficient argenine vasopressin
(AVP=ADH) secretion (central) or end organ
unresponsivenes to AVP (nephrogenic)
• AVP is released from cells in the posterior
pituitary gland  increase water permeability at
the distal tubule and collecting duct of the
nephron
 DIABETES INSIPIDUS

• Classification
Central DI: Hypophysectomy, idiopathic,
familial, tumor/cyst, granuloma,
autoimmune
Nephrogenic DI: chronic renal disease,
hypokalemia, hypercalcemia, familial, etc

DD: Primary polydipsy (Psychogenic,

compulsive water drinking)
 DIABETES INSIPIDUS
Symptoms:
Thirst, polyurea, daily urine volume >3 L
Hypernatremia weakness, altered mental status,
coma, seizures Signs: Physical examination is
usually normal
Laboratory Evaluation:
Spesific gravity <1.010
Urine osmolality <300 m Osm/kg
Hypernatremia
 Diagnosis
• High Plasma osmolality
• Urine osmolality reduced
• Water Deprivation; Spesific-Gravity <1.005
(200mosm/Kg of water)
• Plasma Vasopressin low in Neurogenic
DI and N/high in nephrogenic DI, low in
psychogenic polydipsia
• ADH Radioimmunoassays
 Treatment
2 goals: replace the water deficit & treat
underlying abnormality
• Central DI
Desmopressin acetat = AVP analog DDAVP)
• Nephrogenic DI
Underlying disorder should be treated if
possible, diuretic, prostaglandin synthesis
inhibitors, amiloride
 Syndrome of inappropriate
secretion of ADH (SIADH)
Etiology
Malignant lung disease, TBC, lymphoma, CNS trauma, drugs
(clofibrat, chlorpropamide, HCT), HIV infection, Endocrine
diseases ( adrenal insuff, myxedema)

Clinical Manifestation
Hyponatremia: GI :diarrhea, nausea, vomiting, neuropsychiatric
signs, muscular weakness, headache, lethargy,cerebral edema

Treatment
Fluid restriction
Diuretics
 Disorders of adrenocortical function

Adrenocortical hyperfunction
Glucocorticoids
Aldosteronism  Mineralocorticoids
Virilizing tumors  Androgens
Cushing’s syndrome
Feminizing tumors  Estrogens
Adrenocortical hypofunction
Hypopituitarism  Glucocorticoids
Hypoaldosteronism  Mineralocorticoids
Addison’s disease
Hypopituitarism  Androgens
Estrogens
ADRENAL INCIDENTALOMAS
• Masses found incidentally during
radiographic imaging of the abdomen
• Incidence : 0.35-4.36% in general
population
In Evaluation such mass:
• Is the mass benign or malignant?
• Does the mass secrete hormones or mass
disfunction
 DD ADRENAL INCIDENTALOMA
• Benign:
Non hormone secreting (lipoma,cyst,
ganglioneuroma, adenoma)
Hormone secreting (pheochromocytoma,
aldosteronism, subclinical Cushing’s syndrome
• Malignant
Adrenocortical carcinoma
Metastatic neoplasm
Lymphoma
ADRENAL INCIDENTALOMAS
• Size is important:
Adrenal masses >4cm  more likely
malignant  surgical resection should
be consideration
• The great majority (+ 89%) are benign,
non functioning masses
• A full biochemical workup should be
completed before surgery is done
 CUSHING’S SYNDROME
• Chronic glucocorticoid excess Symptoms &
Physical features  CS
Iatrogenic CS ( Chronic glucocorticoid
therapy): most commonly
Spontaneous CS :
Pituitary (Cushing disease)
Adrenal
ACTH secretion non pituitary tumor (ectopic
ACTH Syndrome)
CUSHING’S SYNDROME
Classification
ACTH-dependent
Pituitary adenoma (Cushing disease) 70%
Nonpituitary neoplasma (ectopic ACTH)
ACTH-independent
Iatrogenic (glucocorticoid, megestrol acetat)
Adrenal neoplasma (adenoma, carcinoma),
Hyperplasia
Factitious
 CUSHING’S SYNDROME
Cushing’s syndrome suspected

Overnight 1 mg DST

AM cortisol > 1.8 ug/dl AM cortisol <1.8 ug/dl  Normal

24 hours urine free cortisol

Normal Elevated

Repeat if high Endocrinology

index of suspicion consultation
 CUSHING’S SYNDROME
Cushing’s syndrome established
ACTH IRMA

<5 pg/mL >10 ug/mL

CT adrenals MRI pituitary

Unilateral mass Bilateral enlargement IPSS Normal Abnormal

CRH test

Peak ACTH Peak ACTH IPS:P<1.8 IPS:P>2.0

<10pg/ml >20 ug/dL

Adrenal surgery Ectopic ACTH Pituitary Surgery

 CUSHING’S SYNDROME

Treatment:
CUSHING’disease
Microsurgery, Radiation therapy,
Adrenal tumors
Unilateral adrenalectomy
Ectopic ACTH syndrome
Benign  surgical treatment
Malignant : Ketokonazole, metyrapone
IATROGENIK (CUSHINGOID)
Tapering of
Alternate day regimen
 PSEUDO CUSHING’s
SYNDROME

• Obesity
• Chronic alcoholism
• Depresion
Hirsutism Post adrenalectomy
 Disorders of adrenocortical
insufficiency
• Deficient adrenalproduction of
glucocorticoid and mineralocorticoid 
Adrenocortical insufficiency
@ Primary adrenocortical insufficiency
(Addison’s disease)
@ Secondary : deficient pituitary ACTH
secretion, glucocorticoid therapy
(most common)
 Addison’s Disease
• Etiologi: tbc (prior 1920), Autoimmune
adrenalitis  adrenal atrophy (80%)
Associated other immunologic and
autoimmune endocrine disorders, AIDS,
malignant disease
• Rare, female >>, 30-50 year
• Clinical features: weakness, fatigue,
anorexia, weight loss, hyperpegmentasi,
hypotension,
 Addison’s disease
• Laboratorium :
Hiponatrimia- hiperkalemia (classic)
Radiologis /CT Scan
• Diagnosis
Basal adrenokortical steroid Normal
Rapid ACTH stimulation test
ACTH plasma
• Treatment:
Replacement therapy cortisol
 ACTH

Aldosterone

K Angiotensin II

EBV Angiotensin I
Renin

Renin substrate

Major factors regulating aldosterone secretion; EBF(Effective Blood Volume)

 Primary Hyperaldosteronism
• Accounts for about 0.7% of cases of
hypertension, Women >>, unilateral
adrenocortical adenoma (Conn’s
syndrome, 73%), 27% bilateral
• Hyperaldosteronism: hypertension,
hypokalemia, alkalosis
 Primary Hyperaldosteronism

Clinical finding: Hypertension, muscular

weakness, paresthesias, headache,
polydipsia, polyuria, moderate
hypertension (malignant is rare)
Laboratory finding: Serum potassium low, 24
hours urine collection aldosterone
Imaging: CT-scan
 Primary Hyperaldosteronsm

Treatment: Laparoscopic
adrenalectomy, Spironolactone,
antihypertensive agent
Complication: Renal damage
Prognosis: Improved by early
diagnosis and treatment, only 2%
malignant
 Diseases of adrenal medulla
Pheochromocytoma
Pheochromocytomas are rare (<0,2% of
hypertensive), cathecolamine-producing tumor
of neurochromaffin cells. Extraadrenal Ph 
sympathetic ganglia are called Paraganggliomas
Incidence 3-4th
decades,autosomal dominat hereditary,
malignant 10-15% cases Hypertension is
caused by excessive plasma level epinephrine
by tumor located either or both adrenals &
anywhere along sympathetic nervus chain
( 90% adrenal)
 Pheochromocytoma
• Symptoms and Signs
Usually lethal unless diagnosed and treated
severe headache, perspiration, palpitation,
anxiety, tremor, tachycardia
Attack  cyanosis, facial pallor
Classical symptomatic triad: headache,
sweating, palpitations
• Laboratory finding
Urinary cathecolamines, metanephrine,
creatinine, Urinary VMA
 Pheochromocytoma
Localisation
• CT scanning
– Overall accuracy 90%-95% for adrenal tumours
– Less accurate for extra adrenal tumours
• Isotope scintigraphy (MIBG scanning)
– 131I-MIBG stored in chromaffin granule
– Sensitivity 99%
– False negative 11%
– False positive 2%
Blood and Urine analysis
– Plasma catecholamine levels > 1000micrograms
– Urinary VMA and Metanephrine levels
 Pheochromocytoma
• Treatment
• Surgery  Preoperative preparation
• To control hypertension & prevent CVS
complications.
• Alpha adrenergic blockade
– Phenoxybenzamine 10 mg qds 1-2 weeks before surgery
– Beta blockade propanolol 10 mg qds 2-3 days
• Intraoperatively
• Phentolamine
• Sodium nitroprusside
 Pheochromocytoma
• Treatment Laparoscopic removal of the
tumor  treatment of choice, open
laparatomy
• Prognosis
Depends early diagnosis is made
HARSINEN SANUSI
THE THYROID GLAND

Thyroid
cartilago
Pyramidal
lobe
Left lobe

Isthmus
Right lobe

Internal
jugular vein
External
carored arteri
THYROID GLAND HISTOLOGY

http://arbl.cvmbs.colostate.edu/hbooks/pathphys/endocrine/thyroid/anatomy.html
 Thyroid hormone synthesis, storage and release

TRAPPING ORGANIFICATION
I I PEROXIDASE
OXIDIZED
H2O2 IODIDE MIT DIT T3
TGB TGB
COUPLING STORAGE
Tyrosine?
Tyr Tyr
DIT DIT T4
Iodinase
AA TGB TGB TGB
Tyrosine

MIT MIT DIT

DEIODINATION DIT

RELEASE TGB
PROTEOLYSIS
T3 T3 T3 --TGB
Protease
T4 T4 T4 --TGB

CAPILLARY FOLLICULAR CELL COLLOID

Cryer PE. Diagnostic endocrinology 1976:35
 HYPOTHALAMUS
Basic elements in regulation TRH
of thyroid function

T3

PORTAL SYSTEM
I

ANTERIOR
PITUITARY
T4
+
“FREE” T3 _ TSH
T4 T3

TISSUE

+
I
THYROID
T4
 Usually Complain thyroid
disease
• Thyroid enlargement which
may be diffuse or nodular
• Symptom of thyroid deficiency
or Hypothyroidism
• Symptoms of thyroid hormon
excess, or Hyperthyroidism
 Usually Complain thyroid
disease
Complications of a Spesific form
hyperthyroidism: Graves’ disease
which may present which prominence
of the eyes or exophthalmos and

Thickening of the skin over the lower

legs (rare) or thyroid dermopathy
 Physical Examination
• Inspection : Good light coming
from behind the examiner, The
patient is instructed to swallow a
sip of water, Observe the gland as
it moves up and down.
Enlargement and nodularity can
often be noted.
 Physical Examination
• Palpate the gland from
behind the patient with the
middle threes fingers on
each lobe while the patients
swallows. Nodules can be
measured in a similar way.
 Physical Examination
• On physical examination the normal
thyroid gland about 2cm in vertical
dimension and about 1cm in horizontal
dimention above the isthmus
• Enlarged thyroid gland is called Goiter
• The generalized enlargement is termed
diffuse goiter, irreguler or lumpy
enlargement is called nodular goiter
THYROID DISEASES
HYPERTHYROIDISM
HYPOTHYROIDISM
THYROIDITIS
THYROID NODUL
THYROID DYSFUNCTION PREVALENCE

• Hypothyroidism 2%
• Sublinical hypothyroidism 5-7 %
• Hyperthyroidism 0,2
%
• Subclinical hypothyroidism 0,1-6,0%
 Hyperthyroidism & Thyrotoxicosis

• Thyrotoxicosis is the clinical syndrome that

results when tissues are exposed to high levels
of circulating thyroid hormone.
• Thyroxicosis is due to hyperactivity of the
thyroid gland or hyperthyroidism
• Occasionally, thyrotoxicosis may be due to
other causes such us excessive ingestion of
the thyroid hormone or excessive thyroid
hormon from ectopis site
 Conditions asscosiated with
thyrotoxicosis
• Diffuse toxic goiter (Graves’ disease)
• Toxic adenoma (Plummer’s disease)
• Toxic multinodular goiter
• Subacute thyroiditis
• Hyperthyroid phase of Hashimoto’s thyroiditis
• Thyrotoxicosis factitia
• Rare: Ovarian struma, metastatic thyroid
carcinoma, hydatiform mole,
 GRAVES’ DISEASE (DIFFUSE
TOXIC GOITER)
• GD is the most common form of thyrotoxicosis,
may occur at any age, more commonly in
females than in males (5X)
• The syndrome consist one or more of the
following features:
1. THYROTOXICOSIS
2. GOITER
3.OPHTHALMOPATHY(Exophthalmos)
4. DERMOPATHY (Pretibial myxedema)
 ETIOLOGY & PATHOGENESIS
• GD is currently viewed as an
autoimmun disease of unknown cause
• Ther is a strong familial predisposition
in that about 15%. 50% GD have
circulating thyroid autoantibodies
• Peak incidence 20-40-year
• T-lymphocytes sensitized to antigen
within thyroid gland and stimulate B
lymphocyte  antibodies
 Clinical features
Graves’s disease
• Symptoms: in younger patients: palpitation,
nervousness, easy fatigability, hyperkinesia,
diarhhea, excessive sweating, intolerance to
heat, weight loss, without loss appetite
• Signs: Thyroid enlargement, exophthalmos,
tachycardia, muscle weakness, tremor Older
patients cardiovascular & myopatic predominate
clinical manifestation  palpitatation, dyspnea
on exersice, tremor, nervousness, weight loss
Ophtamopathy Graves disease
• Infitratif  sympathetic overstimulation
Lid retraction (Dalrymphe’s sign)
Van Graves sign late palpebra sup
Stellwat’s sign the wink eyes late
Jefroy’s sign  fold of forehead not see
Mobius’sign  convergention of the eyes late
• Infiltratif  autoimmune
Exophthalmus, oculopathy congestif: cheimosis,
conjunctivitis, periorbital edema
Ulcerasi Cornea , neuritis optica, atrophi n
opticus
 DISEASE SEVERITY

Thyroid eye disease can be divided into

MILD disease

MODERATE disease

SEVERE disease
 MILD DISEASE

• Usually young patient

• Dry eyes---->lubricants
• Lid retraction
• Lid malposition-entropion
• Mild proptosis
 MODERATE DISEASE

™ Thyroid myopathy

™ asymmetric involvement

™ tends to involve vertical

muscles in Asians
LID RETRACTION
HERTEL EXOPHTHALMOMETER
EXOPHTHALMOS : >18 MM
Computerised Axial
Tomography
Thyroid Dermopathy
• Thickening of the skin,over the
lower tibia due to accumulation
glycosaminglicans , rare (2-3%)
• TSH-R Ab high titer
• Osteopathy in the metacarpal
bones
Non Pitting oedema
 Suspected hyperthyroidism

TSH &FT4

Low TSH Low TSH & Normal /

Normal & Normal high FT4 high TSH &
FT4 &TSH FT4 high FT4

Hyperthyroidism Measure FT3

excluded TSH- secreting
pituitary adenoma.
Normal FT3 High FT3 Hyperthyroidism Thyroid hormone-
resistance syndrome
Subclinical hyperthyroidism
Evolving Graves’ disease T3 Hyperthyroidism
Or toxic nodular goiter
Excess thyroxine replacement
Non thyroidal illness
Graves’disease
Toxic nodular goiter
Thyroiditis
Repeat tests in 2-3 months: annual Gestational Hyperthyroidism
follow-up if no progression Factitious or iatrogenic hyperthyroidism
Thyroid Carcinoma
Struma Ovarii
Tumor secreting Chorionic gonadotropin
Laboratoy tests useful in DD of hyperthyroidism
Familial nonautoimmun hyperthyroidism
 Atypical fashion Graves’
Disease
• Thyrotoxic periodic paralysis: usually
Asian males, sudden attack flacid
paralysis, hypokalemia, usualy subsides
spontaneously. Prevention: K+ supplement
& Betablockers
• Thyrocardiac disease:
primarily with symptoms of heart
involvement: refrsctory AF insensitif
digoxin or high output heart failure, no
evidence underlying heart disease (50%).
Treatment of thyrotoxicosis  cure
Atypical fashion Graves’ Disease

• Apethetic hyperthyroidism:
Older patients: weight loss,
small goiter, slow AF, severe
depression with none clinical
features
 Treatment of Graves’ Disease
1. Antithyroid drug therapy:
Young pts, small glands, mild disease
Propylthiouracil, methimazole (6m-15 y),
relaps 50-60%. PTU inhibits the
conversion T4T3, effect more quickly compare
Methimazole : longer duration of action,
Single dose
Therapy 3-6 months  tapering dose and
combination levothyroxin 0.1 mg/d 12-24
months
Allergic reaction (rash, agranulocytosis)
 Treatment of Graves’ diseae
• Surgical treatment
Surgical subtotal thyroidectomy 
treatment of choice for very large
glands, or multinodular goiter,
prepared wth anti thyroid drug (about 6
months)
Complication:Hypothyroidism,recurent
laryngeal nerve injury
 Treatment of Graves’ disease

• Radioactive iodine
therapy
USA  NaI 131I 
euthyroid over 6-
12 weeks,
Complication
hypothyroidism
Treatment of Graves’ disease
• Other medical measures:
Beta-adrenergic blocking agents
Propranolol 10-40 mg every 6
hours, multivitamin supplements,
phenobarbital as sedative + to
lower T4 levels
Cholestyramine, 4 gr orally 3X
daily lower T4
 Complication of Graves’
Disease
Thyrotoxic crisis (thyroid storm)
Acute exacerbation symptoms
thyrotoxicosis. May be mild & febrile until
life threatning. Etiology : after thyroid
surgery in patients who has been
inadequatlely prepared, RAI131, parturition
in adequately controlled thyrotoxicosis or
stressfull illnes.
• Thyrotoxic crisis(thyroid
“storm”):
Clinical manifestation:Fever,Sweating,
flushing, tachycardia/AF, heart failure,
agitation,delirium, coma, jaundice,
nausea vomiting and diarhea.
Treatment: Propranolol 1-2 mg IV, PTU
250 mg every 6 hours. Hydrocortison,
supportive therapy
• Clinical manifestation  marked
hypermetabolism, excessive
adrenergic response, fever, flushing,
sweating, tachicardia, AF, heart
failure, delirium , coma, GI
Symptoms
HYPOTHYROIDISM
 HYPOTHYROIDISM
Etiology
• Primary:Hashimoto thyroiditis, Radio
active iodine therapy for Graves’ disease,
Subtotal thyroidectomy, Excesive iodide
intake, subacute thyyroiditis, Iodide
deficiency
• Secondary :
Hypopituitarism due to pituitary adenoma
• Tertiary :
Hypothalamic disfunction (rare)
 HYPOTIROIDISM
Clinical finding
• Incidence : Various causes depending
geographic & enviromental factors
• Hashimoto thyroiditis the most common
cause of hyperthyroidism
• Newborn infants (Cretinism)
• Fatigue, coldness, weight gain, constipation,
menstrual irregularities, muscle cramps
 HYPOTIROIDISM
• Physical findings:
Cool,rough, dry skin, puffy face and hands,
ahoarse voice, slow reflexes
Cardiovascular sign: bradycardia, diminished CO,
low voltage QRS, cardiac enlargement
Pulmonary function: Respiratory failure
Intestinal paralysis slowed , chronic constipation,
ileus
Renal function. Decresed GFR, renal impairement
Anemia, Severe muscle cramp, parestesias,
muscle weaknes
CNS symptoms: fatigue, inability to concentrate
 Pituitary- thyroid relationships in primary
hypothyroidism
TRH Hypothalamus

Dopamine Somatostatin

Pituitary

TSH
Tissues

T3, T4

THYROID
 Complication
• Myxedema coma  end stage of
untreated hypothyroidism, Cause
Radiotherapy in Graves’ Disease
• Myxedema & Heart disease  CAD
• Hypothyroidism Neuropsychiatric
disease  depression, confuse,
paranoid, manic
Treatment Hypothyroidism
• Levothyroxine (T4), not liothyronine (T3)
because rapid absorption, short half life,
transient effect. Dosis T4, 1X in the morning
to avoid insomnia 0.05 mg-0.2 mg/d
• Mixedema coma ICU, intubation &
mechanical ventilation, Treat infection, heart
failure, IV drips with caution, levothyroxin IV
EXAMPLES OF THYROID DISEASES

1° Hypothyroidism Hyperthyroidism
www.hsc.missouri.edu/~daveg/thyroid/thy_dis.html
Complication
• Myxedema coma  end stage of
untreated hypothyroidism, Cause
Radiotherapy in Graves’ Disease
• Myxedema & Heart disease  CAD
• Hypothyroidism Neuropsychiatric
disease  depression, confuse,
paranoid, manic
 Definition
• Thyroiditis  heterogenous group of
inflamatory disorders the thyroid gland
• Etiologies range from autoimmune to
infectious origins
• Clinical course  Acute, subacute, or
chronic. Can be euthyroid, transient phase
thyrotoxicosis and / or hypothyroidism.
Painless or painfull
 Classification of thyroiditis
I. Autoimmune thyroiditis
Chronic autoimune thyroiditis
Hashimoto’s thyroiditis
Atrophic thyroiditis
Focal thyroiditis
Juvenile thyroiditis
Silent thyroiditis / Postpartum thyroiditis
II. Subacute thyroiditis
III. Acute suppurative thyroiditis
IV. Riedel’s thyroiditis
 Classification of thyroiditis
Hystologic classification Synonims
Chronic lymphocytic Chronic lymphocytic thyroiditis,
Hashimoto’s thyroiditis
Subacut lymphocytic thyroiditis,
Subacute lymphocytic Postpartum thyroiditis,
Granulomatous Sporadic painless thyroiditis
Subacut granulomatous thyroiditis
De Quervains thyroiditis
Suppurative thyroiditis
Microbial inflamatory Acut thyroiditis
Riedel’s struma
Invasive fibrosis Riedel’s thyroiditis
Terminology for Thyroiditis.

Type Synonim
Hashimoto’s thyroiditis Chronic lymphocytic thyroiditis
Chronic autoimmune
thyroiditis Lymphadenoid
goiter
Painlesspostpartum thyroiditis Postpartum thyroiditis
Subacute lymphocytic thyroiditis
Painless sporadic thyroiditis Silent sporadic thyroiditis
Subacute lymphocytic thyroiditis
Painful subacute thyroiditis Subacute thyroiditis
de Quervain’s thyroiditis
Giant-cell thyroiditis
Subacute granulomatous

thyroiditis
Pseudogranulomatous thyroiditis
Terminology for Thyroiditis.

Type Synonim
Suppurative thyroiditis Infectious thyroiditis
Acute suppurative thyroiditis
Pyogenic thyroiditis
Bacterial thyroiditis
Drug-induced thyroiditis -
(amiodarone, lithium, interferon
alfa, interleukin-2)
Riedel’s thyroiditis Fibrous thyroiditis
 Hashimoto’s thyroiditis
(Chronic thyroiditis)
Hakaru Hashimoto (1912)
 4 patients chronic
disorder of the thyroid
diffuse lymphocytic
infiltration, fibrosis,
parenchymal atrophy, and
eosinophilic change in
some acinar cells

Dr Hakaru Hashimoto
 Hashimoto’s thyroiditis
Hashimoto thyroiditis
is the most common
cause of hypothyroidism
& goiter
in the United States
Statosky J et al. Am Acad of Family physicians 2000;61:1054
 Hashimoto’s thyroiditis

Etiology & pathogenesis

HT is immunologic disorder which
lymphocytes become sensitized to
thyroidal antigens and autoantibodies are
performed.
Thyroid antibodies in HT are:
1.Thyroglobulin antibody (Tg Ab)
2. Thyroid peroxidase antibody (TPO Ab)
= Microsomal antibody) 3. TSH
Receptor blocking antibody (TSH- R Ab
block)
 Clinical Manifestation
Hashimoto’s Thyroiditis

Symptom & Signs

HT usually presents with
goiter , euthyroid or mild
hypothyroidism.
Sex distribution : F/M 4:1
Painless & patients may be
anware of the goiter
 Laboratory findings

• T4 N/ low, TSH will be elevated.

RAIU may be high, normal or
low
• Tg Ab & TPO Ab positif
• Fine needle aspiration biopsy
 large infiltration lymphocytes
 Hurttle cells
Diagnostic procedures
• Test of thyroid autoimmunity:
TPOAb  95% + in Hashimoto
thyroiditis & 90% Atrophic thyroiditis
TgAb  less frequently +
Diagnostic specificity of thyroid
antibody tests is not absolute.
• Test for thyroid function TSH, fT4
• RAIU: normal, low or high.
• USG:diffusely reduced echogenecity.
• FNAB not necessary,excep. rapidly
enlarging goiter
Diagnosis of Hashimoto’s thyroiditis
Diffuse goiter
Anti microsomal (or TPO) antibody
Anti-thyroglobulin antibody Positive

Sign symptom of
hypothyroidism
Hashimoto’s
Negative thyroiditis

US Biopsy Positive
*Simple goiter,
adenomatous goiter etc

Negative Other diseases*

Treatment Hashimotos
thyroiditis
 Treatment
• Goiter small & asymptomatic not
require therapy
• Levo-thyroxine is given over
hypothyroidism to supress TSH &
decreased serum thyroid antibody.
Levo-thyroxine in euthyroid, still
controversial
 Treatment
• Corticosteroids : regression pain,
reduction in size of the goiter,
thyroid antibody, not
recommended in benign disease.
• Surgery indicated pain,
cosmetic, or pressure
symptoms after levothyroxine
and corticosteroid therapy.
 Riedel’s thyroiditis
• Rare 1,06/100.000, middle age or elderly
women
• Etiology unknown (autoimmune
process or primary fibrotic disorder)
• Characterized  fibrosis replaces
normal thyroid parenchyma,1/3 cases
multifocal fibrosclerosis
 Riedel’s thyroiditis
• Thyroid fibrosis (stony hard,woody),
painless, progressive anterior neck mass,
• Generalized fibrosing (1/3 patients), pressure
symptoms  laryngeal nerve paralysis or
hypoparathyroidism (rare)
• Usually euthyroidism, hypothyroidism (30%)
• Laboratorium : non spesific
• USG/CT-Scan inconclusive
• Difinitive diagnosis  open Biopsy
 Riedel’s thyroiditis
• Treatment:
Corticosteroids  medical treatment of choice
Tamoxipen, methotrexate  inhibitor fibroblast
proliferation ( early stages)
Levothyroxine  hypothyroidism
Surgical care  diagnosis, relieving tracheal
compression
• Mortality  asphyxia (6-10%), extrathyroidal
fibrotic lesions may complicate the prognosis
 Subacute thyroiditis
• Cause unknown ( viral infection
(?) preceded URT infection,
coincidence viral disease (mumps,
measles, Echo virus, adeno virus,
epst. Barr virus, influenza)
• Women : Men (3-5:1)
• Onset: 20-60 yr
• Summer
 Subacute thyroiditis
• Palpation thyroid: enlarged, asymetrical,
nodul, firm, tender & painful.
• Thyrotoxicosis during inflamatory phase
 euthyroidism hypothyroidism
euthyroidism (4th phases)
• Laboratorium: ESR increase, leukocyt N/
increase, fT4,,TSH, RAIU
• Recovery 4-6 months, spontaneous
remitting
 Changes in serum T4 & Radiactive iodine uptake in
patients with subacute Thyroiditis 24-hour
T4 131 I
ug/dL uptake %

20 T4 40

15 30

10 20

5 10

0 131 I 0
Phase : Hyper Eu Hypo Eu
Weeks: 1 4 11 -
Woolf PD, Daly R :Am J Med 197;60:73
Laboratory findings during different phases of subacute thyroiditis

Phase T4 &/T3 Level TSH level RAIU value

Thyrotoxicosis High Low <5%

Hypothyroid Low Normal,or high Normal to high

Recovery Normal High to normal High to normal

 Treatment Subacute
thyroiditis
• Symptomatic: Acetaminophen 4X 0,5g, NSAID or
glucocorticoid (prednison 3 X 20 mg (7-10 days)
• Betablockers  symptoms of thyrotoxicosis
• L-thyroxine 0.1-0.15 mg /daily  hypothyroid
phase. Long-term L-thyroxine  permanent
hypothyroidism (10%)
• Antibioticsno value
• Thyroidectomy  rarely
 Clinical Differentiating of the Subtype Thyroiditis

NECK PAIN

YES N0

RAIU PRESENTING SYMPTOMS

INCREASED DECREASED HYPERTHYROIDISM HYPOTHYROIDISM

CHRONIC
MICROBIAL SUBACUTE RAIU LYMPHOCYTIC
INFLAMMATORY GRANULOMATOUS THYROIDITIS
THYROIDITIS THYROIDITIS

GRAVES DISEASE SUBACUT

LYMPHOCYTIC
THYROIDITIS

Statosky J et al. Am Acad of Family physicians 2000;61:1054

 Acute suppurative
thyroiditis
• Rare, serious, bacterial inflamatory
disease, children, 20-40 yr, sex ratio
1:1
• Etiologi: Infectious: Staph. aureus,
strep.pyogenes, strep. pneumonia,
esch.coli, pseudomonas aeruginosa
• Infection by hematogenous, direct
trauma
 Symptoms & signs
• Neck pain, warm, tenderness, the
neck unable to extend
• Dysphagia, dysphonia, referred to
ear, mandibula, lymphadenopathy
• Systemic manifestation: fever,
chills, tachycardia, malaise
• Palpation: unilateral, erythematous
 Acute suppurative
thyroiditis
• Thyroid function : Euthyroidism
• Laboratorium :TPO antibodies
absent, ESR high, PMN leukocytosis
• 24-hour 123I uptake normal
• FNA Biopsy: purulent material
• Treatment: antibiotics or surgical
drainage
 Chronic-pyogenic thyroiditis
• Etiology : Salmonella typhosa,
syphilis,
tuberculosis,echinococcus,
actinomyces
• Symptoms: Suppurative, non
suppurative
• Treatment: antibiotic, drainage
Thyroid nodules &

Thyroid cancer
Thyroid nodules - prevalence
• Thyroid nodules common, increase with
age

• 30-60% of thyroids have nodules at autopsy

• Palpation: 5-20% (>1cm)

• U/S: 15-50% (>2mm)

 Diagnostic approach
• Fine Needle Aspiration (FNA)
10-20% risk of suspicious cytology, therefore  thyroid
surgery
95% of histology will be benign, and surgery
“unnecessary
• Isotop Scann(CT)
rarely used for evaluation  80% of nodules are
“cold”
small cold nodules may be missed
hot nodules may be malignant
• Ultrasonography (USG)
Diagnostic approach - ultrasound
Identifies solid v. cystic nodules

Identifies MNG

May aid FNA

Does not exclude malignancy

Diagnostic approach - other tests

Calcitonin
very high results diagnostic for MTC
risk of borderline false positives
not for routine use
Thyroglobulin
not helpful for exclusion of carcinoma:
overlap with benign disease
best for follow-up after thyroidectomy
 Thyroid nodules & Thyroid cancer
• In 95% of cases , thyroid cancer
presents as a nodule or lump in the
thyroid nodul thyroid.
• Thyroid nodule extremely
common, particularly
women.Prevelance in USA 4% in
adult population. F:M ratio 4:1.
• Thyroid cancer rare. Incidence
0.004% per year
 Diffrentiation benign & Malignant
lesions
• History : Family history of goiter suggests
benign disease, endemic goiter
• Physical characteristics:
Benign: older age, woman, soft nodule, multi
nodular goiter.
Malignant: Children, young, male, solitary,
firm nodule, vocal cord paralysis, firm lymph
nodes, distant metastasis
 Malignant thyroid Carcinoma

• Papillary Carcinoma 75 %
• Folliculare Carcinoma 16 %
• Medullary Carcinoma 5%
• Anaplastic Carcinoma 3%
• Lymphoma 5 -10 %
Management of the solitary
nodule
T r u e s o lit a r y n o d u le ?

No Yes

FNAC

B e n ig n M a lig n a n t I n d e t e r m in a t e F o llic u la r

W a tc h ? S u rg e ry R epeat FN A C S u rg e ry

I n d e t e r m in a t e

S u rg e ry
 Treatment
• Thyroidectomi
• Jodium 131Radioactive
• Thyroxine supression
 FNA POSITIF
MALIGNANCY

Differenteated Undifferenteated
Over 2cm, or
Under 2cm, no invasion multicentric, or invasive
Local removal to prevent
obstruction (palliative
Lobectomy and Near total thyroidectomy and therapy)
isthmusectomy modified neck dissection
X-ray therapy or
Levothyroxine for life Liothyronine, 75-100 chemotherapy (or both)
mcg/d for 3 mos, plus levothyroxine
discontinue 2 week. replacement therapy
Low iodine diet

Scan with 2-5 mCi 131 I Repeat after 12 months

Negatitive scan Positive scan

Levothyroxine for 50-150 mCi131 I (therapeutic dose)

life

No recurence X Ray therapy or chemo therapy (or both)

Recurrence + - Scan
cure
Treatment of thyroid cancer
• Papillary cancer
– < 1.5 cms Lobectomy & isthmusectomy
– > 1.5 cms Total thyroidectomy

• Follicular cancer Total thyroidectomy

• Hurthle Total thyroidectomy

• Medullary Total thyroidectomy & central neck

dissection