• Pituitary disorders• Adrenal disorders• Thyroid diseases

Harsinen Sanusi

ACTHGH

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

Function

Hypersecretion

Insufficiency

Size

Microadenoma

Macroadenoma

Pituitary tumors

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

• 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 ExcessAcral 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% casessellar 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) transphenoidal-Surgery is the treatment of choice for microadenomas (90% cure)

• Medical treatment: Somatostatin analogOctreotide acetate (Sandostatin) & Lanreotide (Somat uline) the therapy of choice with residual GH hypersecr. Following surgery

• Radiotherapy

HIPOTHALAMUS

PITUITARY

SOMATOSTATINGHRH

DOPAMINE-AGONIST DRUGS:BROMOCRIPTINE,CABERGOLINE

SOMATOSTATIN AGONIST : OCTREOTIDE

IGF-1

GH-RECEPTOR

GH-RECEPTOR ANTAGONIST: PEGVISOMANT

GH

IGF-1 :Insulin like growth factor

GH

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

Pit

uit

ary

Insu

ffic

ien

cy

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 vaasopressin (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 LHypernatremia weakness,altered mentaal status,

coma, seizuresSigns: Physical examination is` usually normal

Laboratory Evaluation:Spesific gravity <1.010Urine osmolality <300 m Osm/kgHypernatremia

Diagnosis• HighPlasma 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

Treatment2 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)

EtiologyMalignant lung disease, TBC, lymphoma, CNS trauma, drugs (clofibrat, chlorpropamide, HCT), HIV infection, Endocrine diseases ( adrenal insuff, myxedema)

TreatmentFluid restriction Diuretics

Disorders of adrenocortical function

Adrenocortical hyperfunction

Glucocorticoids

Aldosteronism Mineralocorticoids

Virilizing tumors Androgens

Feminizing tumors Estrogens

Adrenocortical hypofunction

Hypopituitarism Glucocorticoids

Hypoaldosteronism Mineralocorticoids

Hypopituitarism Androgens

Estrogens

Cushing’s syndrome

Addison’s disease

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 carcinomametastatic neoplasmlymphoma

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 excesssymptoms & Physical features CS

Iatrogenic CS ( Chronic glucocorticoid therapy): most commonly

Spontaneous CS : Pituitary (Cushing disease)AdrenalACTH 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

Indicative of Cushing

Syndrome

CUSHING’S SYNDROMECushing’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 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, metyraponeIATROGENIK (CUSHINGOID)

Tapering of Alternate day regimen

CUSHING’S SYNDROME

PSEUDO CUSHING’s SYNDROME

• Obesity • Chronic alcoholism• Depresion

Post adrenalectomyHirsutism

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

• DiagnosisBasal adrenokortical steroid Normal

Rapid ACTH stimulation test

ACTH plasma • Treatment:

Replacement therapy cortisol

ACTH

Aldosterone

Renin substrate

Renin

Angiotensin I

Angiotensin II K

EBV

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

PheochromocytomaPheochromocytomas 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

Common Symptoms in Patients with Hypertension Due to Pheochromocytoma.

Symptoms during or following paroxysms 

  Headache

  Sweating

  Forceful heartbeat with or without tachycardia

  Anxiety or fear of impending death

  Tremor

  Fatigue or exhaustion

  Nausea and vomiting

  Abdominal or chest pain

  Visual disturbances

  Dyspnea

Symptoms between paroxysms 

  Increased sweating

  Cold hands and feet

  Weight loss

  Constipation

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

• 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

• Treatment

Pheochromocytoma

• Treatment Laparoscopic removal of the tumor treatment of choice, open laparatomy

• Prognosis

Depends early diagnosis is made

Pheochromocytoma

HARSINEN SANUSI

THE THYROID GLAND

Pyramidal lobe

Left lobe

Right lobe

Isthmus

Internal jugular vein

Thyroid cartilago

External carored arteri

http://arbl.cvmbs.colostate.edu/hbooks/pathphys/endocrine/thyroid/anatomy.html

THYROID GLAND HISTOLOGY

Thyroid hormone synthesis, storage and release

CAPILLARY FOLLICULAR CELL COLLOID

TRAPPING

DEIODINATION

PROTEOLYSIS

STORAGECOUPLING

ORGANIFICATION

I PEROXIDASE

H2O2OXIDIZED

IODIDE

MIT DIT

TGB

MIT DIT T3

TGB TGB

T3 --TGB

T4 --TGBT3T3

T4

DIT DIT T4

TGB TGB

Tyr Tyr

AA TGB Tyrosine

Protease

MIT DIT

Iodinase

Tyrosine?

RELEASE

I

Cryer PE. Diagnostic endocrinology 1976:35

T4

Basic elements in regulation of thyroid function

THYROID

TISSUE

TRH

HYPOTHALAMUS

PORTAL SYSTEM

TSH

ANTERIORPITUITARY

“FREE”

T3

T3

T4

T4

I

I

_

T4

+

T3

+

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

Diffuse goiter• Simple diffus goiter• Hypertiroidism• Hashimoto thyroiditis

Nodular goiter 1. Thyroid nodul 2. Thyroid cyst

3. Adenomatosa goiter 4. Subacut /chronis thyroiditis 5. Plummer thyroiditis

THYROID DISEASES

HYPERTHYROIDISMHYPOTHYROIDISM

THYROIDITISTHYROID NODUL

THYROID DYSFUNCTION PREVALENCE

• Hypothyroidism 2 %

• Subclinical hypothyroidism 5-7 %

• Hyperthyroidism 0,2 %

• Subclinical hyperthyroidism 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. THYROTOXICOSIS2. GOITER3.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

Ophtalmopathy Graves disease

• Infiltrative sympathetic overstimulationLid retraction (Dalrymphe’s sign)Van Graves sign late palpebra supStellwat’s sign the wink eyes lateJefroy’s sign fold of forehead not seeMobius’sign convergention of the eyes

late • Infiltratif autoimmune

Exophthalmus, oculopathy congestif: cheimosis, conjunctivitis, periorbital edemaUlcerasi Cornea , neuritis optica, atrophi n opticus

The Eye signs of Graves’Disease (ATA )

0 No signs no symptoms

1 Only signs, no symptoms, (signs limited

to upper lid retraction, stare,lid lag)

2 Soft tissue involvement (symptom & signs)

3 Proptosis (measured with Hertel

exophthalmometer)

4 Extraocular muscle involvement

5 Corneal involvement

6 Sight loss (optic nerve involvement)

Class Definition

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 EXOPHTHALMOMETEREXOPHTHALMOS : >18 MM

Computerised Axial Tomography

Thyroid Dermopathy

• Thickening of the skin,over the lower tibia due to accumulation glycosaminoglicans , rare (2-3%)

• TSH-R Ab high titer• Osteopathy in the metacarpal

bones

Non Pitting oedema

Suspected hyperthyroidism

TSH &FT4

Normal FT4 &TSH

Hyperthyroidism excluded

Low TSH & Normal

FT4

Measure FT3

Normal FT3 High FT3

Subclinical hyperthyroidismEvolving Graves’ diseaseOr toxic nodular goiter

Excess thyroxine replacementNon thyroidal illness

Repeat tests in 2-3 months: annual follow-up if no progression

T3 Hyperthyroidism

Low TSH & high FT4

Normal / high TSH &

high FT4

TSH- secreting pituitary adenoma.

Thyroid hormone-resistance syndrome

Hyperthyroidism

Graves’diseaseToxic nodular goiterThyroiditisGestational HyperthyroidismFactitious or iatrogenic hyperthyroidismThyroid CarcinomaStruma OvariiTumor secreting Chorionic gonadotropinFamilial nonautoimmun hyperthyroidism

Laboratoy tests useful in DD of 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 T4T3, 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)

• 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’ diseae

Treatment of Graves’ disease

• Radioactive iodine therapy

USA NaI 131I euthyroid over 6-12 weeks, Complication hypothyroidism

• 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

Treatment of Graves’ disease

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.

Complication

• 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

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)

HYPOTHYROIDISM

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 reflexesCardiovascular sign: bradycardia, diminished CO, low voltage QRS, cardiac enlargementPulmonary function: Respiratory failureIntestinal paralysis slowed , chronic constipation, ileusRenal function. Decresed GFR, renal impairementAnemia, Severe muscle cramp, parestesias, muscle weaknesCNS symptoms: fatigue, inability to concentrate

HYPOTIROIDISM

Pituitary- thyroid relationships in primary hypothyroidism

TRH

TSH

THYROID

Tissues

T3, T4

Hypothalamus

Pituitary

Dopamine

Somatostatin

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

www.hsc.missouri.edu/~daveg/thyroid/thy_dis.html

EXAMPLES OF THYROID DISEASES

1° Hypothyroidism Hyperthyroidism

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

I. Autoimmune thyroiditisChronic autoimune thyroiditis

Hashimoto’s thyroiditisAtrophic thyroiditisFocal thyroiditisJuvenile thyroiditis

Silent thyroiditis / Postpartum thyroiditis II. Subacute thyroiditis III. Acute suppurative thyroiditisIV. Riedel’s thyroiditis

Classification of thyroiditis

Classification of thyroiditis

Hystologic classification

Chronic lymphocytic

Subacute lymphocyticGranulomatous

Microbial inflamatory

Invasive fibrosis

Synonims

Chronic lymphocytic thyroiditis,Hashimoto’s thyroiditisSubacut lymphocytic thyroiditis,Postpartum thyroiditis,Sporadic painless thyroiditisSubacut granulomatous thyroiditisDe Quervains thyroiditisSuppurative thyroiditisAcut thyroiditisRiedel’s strumaRiedel’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

Hakaru Hashimoto (1912) 4 patients chronic disorder of the thyroid diffuse lymphocytic infiltration, fibrosis, parenchymal atrophy, and eosinophilic change in some acinar cells

Hashimoto’s thyroiditis(Chronic thyroiditis)

Dr Hakaru Hashimoto

Hashimoto thyroiditisis the most common

cause of hypothyroidism &

goiter

in the United States

Hashimoto’s thyroiditis

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

Hashimoto’s thyroiditis

Etiology & pathogenesisHT is immunologic disorder which lymphocytes become sensitized to thyroidal antigens and auto antibodies 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 & SignsHT 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 thyroiditisTgAb 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

Diffuse goiter

Anti microsomal (or TPO) antibody Anti-thyroglobulin antibody Positive

Hashimoto’s thyroiditis

PositiveUS Biopsy

Other diseases*Negative

Negative

Sign symptom of hypothyroidism

*Simple goiter, adenomatous goiter etc

Diagnosis of Hashimoto’s thyroiditis

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

20

0

15

10

5

1Eu Hypo EuHyper4 11 -

Phase :Weeks:

0

30

20

10

40

24-hour 131 I

uptake %T4

ug/dL

T4

131 I

Changes in serum T4 & Radiactive iodine uptake in patients with subacute Thyroiditis

Woolf PD, Daly R :Am J Med 197;60:73

Laboratory findings during different phases of subacute thyroiditis

Phase

Thyrotoxicosis

Hypothyroid

Recovery

T4 &/T3 Level

High

Low

Normal

TSH level

Low

Normal,or high

High to normal

RAIU value

<5%

Normal to high

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%)

• Antibioticsno value

• Thyroidectomy rarely

NECK PAIN

RAIU

PRESENTING SYMPTOMS

YES N0

INCREASED

RAIU

SUBACUTE GRANULOMATOUS

THYROIDITIS

MICROBIAL INFLAMMATORY

THYROIDITIS

HYPERTHYROIDISMDECREASED HYPOTHYROIDISM

CHRONIC LYMPHOCYTIC THYROIDITIS

GRAVES DISEASE SUBACUT LYMPHOCYTIC THYROIDITIS

Clinical Differentiating of the Subtype 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

• 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

Symptoms & signs

• 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

Acute suppurative thyroiditis

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 surgery95% 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 missedhot 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

Calcitoninvery high results diagnostic for MTCrisk of borderline false positivesnot for routine use

Thyroglobulinnot helpful for exclusion of carcinoma: overlap with benign diseasebest 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

N o

W atch ?

B en ig n

S u rg ery

M alig n an t

In d e te rm in a te

S u rg ery

R ep eat F N A C

In d e te rm in a te

S u rg ery

F o llicu la r

F N A C

Y es

Tru e so lita ry n od u le?

Treatment• Thyroidectomi• Jodium 131Radioactive• Thyroxine supression

Differenteated Undifferenteated

Local removal to prevent obstruction (palliative

therapy)

Positive scan

Scan with 2-5 mCi 131 I

Near total thyroidectomy and modified neck dissection

Levothyroxine for life

Lobectomy and isthmusectomy

Under 2cm, no invasion

Over 2cm, or multicentric, or invasive

Negatitive scan

X-ray therapy or chemotherapy (or both)

plus levothyroxine replacement therapy

Liothyronine, 75-100 mcg/d for 3 mos,

discontinue 2 week. Low iodine diet

FNA POSITIF MALIGNANCY

Repeat after 12 months

Levothyroxine for life

50-150 mCi131 I (therapeutic dose)

No recurence Recurrence + - Scan X Ray therapy or chemo therapy (or both) 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