You are on page 1of 70

THYROID GLAND DISORDERS

Download this presentation for FREE at:

www.Examville.com

THYROID GLAND DISORDERS


GENERAL ASPECTS OF THYROID GLAND

Anatomy: weight range from 12 to 30g Located in the neck, anterior to the traquea Produces: T4 & T3 (active hormone) Regulation: negative Feed-back axis

THYROID GLAND DISORDERS


THYROID GLAND REGULATION negative Feed-back axis

(negative effect)

Hypothalamus
(TRH positive effect)

Pituitary gland
(TSH, positive effect)

Thyroid gland
T3 & T4

THYROID GLAND DISORDERS


Thyroid hormones:
T4: (Thyroxine) is made exclusively in thyroid gland
Ratio of T4 to T3 ;
Potency of T4 to T3;

5::1
1::10

T4 is the most important source of T3 by peripheral tissue deiodination T4 to T3

THYROID GLAND DISORDERS


Thyroid hormones:
T3: (Triiodothyronine) main source is peripheral deiodination:
Ratio of T3 to T4 ; Potency of T3 to T4; 1::5 10::1

T3 is the most important because more than 90% of the thyroid hormones physiological effects are due to the binding of T3 to Thyroid receptors in peripheral tissues.

THYROID GLAND DISORDERS

PHYSIOLOGY EFFECTS

OF THYROID HORMONES

THEY ARE NOT ESSENTIAL

FOR LIFE, BUT ARE EXTREMELY HELPFUL

THYROID GLAND DISORDERS


THYROID HORMONE EFFECTS:
Affects every single cell in the body
Modulates:
Oxygen consumption Growth rate Maturation and cell differentiation Turnover of Vitamins, Hormones, Proteins, Fat, CHO

THYROID GLAND DISORDERS


MECHANISMS OF THYROID

HORMONE ACTION

Act by binding to Nuclear receptors, termed Thyroid Hormone Receptors (TRs), Increasing synthesis of proteins At mitochondrial level increases number and activity to increasing ATP production At Cell membrane increases ions and substrates transmembrane flux

THYROID GLAND DISORDERS


THYROID HORMONE EFFECTS
CALORIGENESIS GROWTH & MATURATION RATE C.N.S. DEVELOPMENT & FUNCTION CHO, FAT & PROTEIN METABOLISM MUSCLE METABOLISM ELECTROLYTE BALANCE VITAMIN METABOLISM CARDIOVASCULAR SYSTEM HEMATOPOIETIC SYSTEM GASTROINTESTINAL SYSTEM ENDOCRINE SYSTEM PREGNANCY

THYROID GLAND DISORDERS


THYROID HORMONE EFFECTS
CALORIGENESIS
Controls the Basal Metabolic Rate (BMR)

CHO METABOLISM
Increases:
Glucose absorption of the GI tract Glucose consumption by peripheral tissues Glucose uptake by the cells Glycolysis Gluconeogenesis Insulin secretion

THYROID GLAND DISORDERS


THYROID HORMONE EFFECTS
GROWTH & MATURATION RATE C.N.S. DEVELOPMENT & FUNTION
ESSENTIAL in the newborn to prevent development of CRETINISMS & to a normal IQ

Modulation of brain cerebration


Mood modulation

THYROID GLAND DISORDERS


THYROID HORMONE EFFECTS
- FAT & PROTEIN METABOLISM
Increase lipolysis and lipid mobilization with:
Cholesterol Triglicerides Free fatty acids

MUSCLE METABOLISM
Modulates;
Strength & velocity of contraction

THYROID GLAND DISORDERS


THYROID HORMONE EFFECTS
ELECTROLYTE BALANCE
Low Thyroid hormones could induce hyponatremia

VITAMIN METABOLISM
Modulates vitamin consumption

HEMATOPOIETIC SYSTEM
Could induce anemia

THYROID GLAND DISORDERS


THYROID HORMONE EFFECTS
CARDIOVASCULAR SYSTEM
Hyperthyroidism, increases:
Heart rate & myocardial strenght Cardiac output Peripheral resistances (Vasodilatation) Oxygen consumption Arterial pressure

Hypothyroidism, reduces:
Heart rate & myocardial strenght Cardiac output Peripheral resistances (Vasodilatation) Oxygen consumption Arterial pressure

THYROID GLAND DISORDERS


THYROID HORMONE EFFECTS
GASTROINTESTINAL SYSTEM
Modulate bowel movements and absorption

ENDOCRINE SYSTEM
Modulates pituitary axis, affecting GH, ACTH, FSH, LH, so-on

PREGNANCY
Modulates growth rate and affects lactation

THYROID GLAND DISORDERS


DIVIDED INTO:

THYROTOXICOSIS (Hyperthyroidism) Overproduction of thyroid hormones

HYPOTHYROIDISM (Gland destruction) Underproduction of thyroid hormones NEOPLASTIC PROCESSES Beningn Malignant

LABORATORY EVALUATION

THYROID GLAND DISORDERS


TSH normal, practically excludes abnormality

If TSH is abnormal, next step: Total & Free T4 & T3


- TSI (Thyroid Stimulating Ig) - TPO (Thyroid Peroxidase Ab) - Antimitochondrial Ab - Serum Tg (Thyroglobulin)

- Radioiodine uptake & Thyroid scaning


- FNA, Fine-needle aspiration - Thyroid ultrasound

THYROID GLAND DISORDERS


TSH High usually means Hypothyroidism
Rare causes: TSH-secreting pituitary tumor Thyroid hormone resistance Assay artifact

TSH low usually indicates Thyrotoxicosis


Other causes First trimester of pregnancy After treatment of hyperthyroidism Some medications (Esteroids-dopamine)

THYROID GLAND DISORDERS

THYROTOXICOSIS: is defined as the state of thyroid hormone excesss HYPERTHYROIDISM: is the result of excessive thyroid gland function

THYROID GLAND DISORDERS


Abnormalities of Thyroid Hormones

Thyrotoxicosis Primary Secondary Without Hyperthyroidism Exogenous or factitious


Hypothyroidism Primary Secondary Peripheral

THYROID GLAND DISORDERS


Causes of Thyrotoxicosis:
Primary Hyperthyroidism Graves disease Toxic Multinodular Goiter Toxic adenoma Functioning thyroid carcinoma metastases Activating mutation of TSH receptor Struma ovary Drugs: Iodine excess

THYROID GLAND DISORDERS


Causes of Thyrotoxicosis: Thyrotoxicosis without hyperthyroidism
Subacute thyroiditis Silent thyroiditis Other causes of thyroid destruction:
Amiodarone, radiation, infarction of an adenoma

Exogenous/Factitia

Secondary Hyperthyroidism
TSH-secreting pituitary adenoma Thyroid hormone resistance syndrome Chorionic Gonadotropin-secreting tumor Gestational thyrotoxicosis

THYROTOXICOSIS
Symptoms:

Signs:

Hyperactivity Irritability Dysphoria Heat intolerance & sweating Palpitations Fatigue & weakness Weight loss with increased appetite Diarrhea Polyuria Sexual dysfunction

Tachycardia Atrial fibrillation Tremor Goiter Warm, moist skin Muscle weakness, myopathy Lid retraction or lag Gynecomastia * Exophtalmus * Pretibial myxedema

THYROID GLAND DISORDERS


Differential diagnosis: Panic attacks
Psychosis

Mania
Pheochromocytoma

Hypoglycemia
Occult malignancy

THYROID GLAND DISORDERS


Treatment:
Reducing thyroid hormone synthesis: Antithyroid drugs (Methimazole, Propylthyouracil) Radioiodine (131I) Subtotal thyroidectomy Reducing Thyroid hormone effects: Propranolol Glucocorticoids Benzodiazepines Reducing peripheral conversion of T4 to T3 Propylthyouracil Glucocorticoids Iodide (Large oral or IV dosage) (Wolf-Chaikoff effect)

THYROID GLAND DISORDERS


Treatment: Special considerations:
Thyrotoxic crisis or Thyroid storm:
Its a life-threatening exacervation of thyrotoxicosis, acompanied by fever, delirium, seizures, coma, vomiting, diarrhea, jaundice. Mortality rate reachs 30% even with treatment

Its usually precipitated by acute illness, such as:


Stroke, infection,trauma, diabeic ketoacidosis, surgery, radioiodine treatment

Propylthyouracil IV or Nasogastric tube Radioiodine (131I) Propranolol Glucocorticoids Benzodiazepines Iodide (Large oral or IV dosage) (Wolf-Chaikoff effect)

THYROID GLAND DISORDERS


HYPOTHYROIDISM

Primary
Autoimmune (Hashimotos) Iatrogenic Surgery or 131I Drugs: amiodarone, lithium Congenital (1 in 3000 to 4000) Iodine defficiency Infiltrative disorders

THYROID GLAND DISORDERS


Hashimotos Thyroiditis or

Goitrous thyroiditis

Mean anual incidence:


Women 4:1000 Men 1:1000 Risk factors; TPO antibodies (90%) Japanese, previous history, high I intake Average age: 60 Frequently associated to other autoimmune disorders such as: AR, SLE, Sjogrens so-on. Treatment: Levothyroxine

THYROID GLAND DISORDERS


CONGENITAL HYPOTHYROIDISM Prevalence: 1 in 3000 to 4000 newborns

Cause: Dysgenesis 85% Dx: Blood screning (TSH &/or T4)


Treatment:

Supplemental Tx. With Levothyroxine is essential for a normal C.N.S. Development and prevention of mental retardation

THYROID GLAND DISORDERS


HYPOTHYROIDISM

Secondary
Pituitary gland destruction Isolated TSH deficiency Bexarotene treatment Hypothalamic disorders

Peripheral:
Rare, familial tendency

HYPOTHYROIDISM
Symptoms: Tiredness Weakness Dry skin Sexual dysfunction Dry skin Hair loss Difficulty concentrating
Signs:
Bradycardia Dry coarse skin Puffy face, hands and feet Diffuse alopecia Peripheral edema Delayed tendon reflex relaxation Carpal tunel syndrome Serous cavity effusions.

THYROID GLAND DISORDERS


SPECIAL TREATMENT CONSIDERATIONS Myxedema coma

Reduced level of consciousness, seizures Hypotension/shock Hypothermia Hyponatremia

Usually in elderly hypothyroid pts. Usually precipitated by intercurrent illnesses that

impairs ventilation

Its an Emergency with a high mortality rate Treatment: Lyotironine(T3) or T4, Hydrocortisone,

external warming, IV fluids

THYROID GLAND DISORDERS


SPECIAL TREATMENT CONSIDERATIONS Elderly patients Coronary Artery Disease

Poor adrenal gland reserve


Childrens

Pregnancy
Emergency surgery (Non thyroid related)

THYROID

Hyperthyroidism

Thyrotoxicosis (most common cause) a) T3 and T4 3 most common causes: a) diffuse hyperplasia i) Graves disease (~ 85% of cases) b) hyperfunctional multinodular goiter c) multifunctional adenoma of thyroid

Clinical a) hypermetabolic state i) skin warm, soft and flushed ii) heat intolerant iii) sweating iv) weight loss (despite appetite) v) cardiac earliest S & S HR, contractility, CO, cardiomegaly, arrhythmias ( A fib in older patients) vi) neuromuscular overactivity of SNS causes tremors, anxiety, inability to concentrate, muscle weakness with muscle mass (thyroid myopathy)

vii) Ocular wide, staring gaze and lid lag - SNS overstimulation of levator palpebrae superiosis - ptosis - true thyroid opthalmopathy seen only in Graves disease viii) GI SNS hypermotility, malabsorption and diarrhea ix) Skeletal system bone resorption, osteoporosis b) thyroid storm i) abrupt onset of severe hyperthyroidism (Graves & SNS)

ii) febrile, HR (out of proportion to febrile response) iii) is a medical emergency - death from cardiac arrhythmias c) apathetic hyperthyroidism i) seen in elderly ii) age and other comorbidities blunt effects of excess thyroid hormone excess - diagnosis during work up for unexplained weight loss or worsening CV disease

d) Diagnosis i) measurement of serum TSH () in 1O - in 2O TSH may be or - TRH stimulation test excludes secondary hyperthyroidism ii) T4 (sometimes T3) - in some cases, T4 may be - T3 may therefore be useful

Thyrotoxicosis results in an increase in metabolic rate. This may result in: Smooth, moist, warm skin Flushing of face and hands Overgrown nails (acropachy, clubbing), which may lift off the nail bed (onycholysis) Fine soft thinned scalp hair Generalized itching (pruritus) Urticaria Increased skin pigmentation Pretibial myxedema

Hypothyroidism any defect causing thyroid hormone production a) anywhere in hypothalamic-pituitarythyroid axis b) 1o are most common cause i) thyroprivic (loss of parenchyma) ii) goitrous (due to TSH) Causes a) large surgical resection b) ablation (radiation) of hyperthyroidism ! c) autoimmune i) most common cause of goitrous hypothyroidism

ii) most are due to Hashimoto thyroiditis (later) d) drugs i) to thyroid secretion ii) non thyroid conditions (lithium, -aminosalicylic acid) e) inborn errors of thyroid metabolism i) uncommon ii) any step of thyroid hormone synthesis may be involved - e.g., Pendred syndrome failure of binding iodine in thyroglobulin

f) thyroid hormone resistance i) receptor mutations g) 2O hypothyroidism i) TSH deficiency ii) any of causes of hypopituitarism (frequently tumor). Other causes include: postpartum pituitary necrosis, trauma, nonpituitary tumors h) 3O (central) hypothyroidism i) anything that interfere with hypothalamic-portal system ii) inadequate TRH delivery

Cretinism a) hypothyroidism developing in infancy/early childhood i) severe mental retardation ii) occurs in iodine deficient areas of world (i.e., Himalayas, inland China, Africa) iii) may also be sporadic, owing to enzyme deficiencies thyroid hormone synthesis

b) clinical: i) impaired skeletal development ii) impaired CNS development - inadequate maternal thyroid hormone prior to fetal thyroid gland formation SEVERE mental retardation - normal brain development if maternal thyroid deficiency occurs after fetal thyroid gland development

Myxedema (i.e., Gull disease) a) hypothyroidism developing in older b) slowing of physical and mental activity i) generalized fatigue ii) apathy iii) cold-intolerant iv) overweight v) CO - shortness of breath - exercise capacity vi) SNS activity - constipation - sweating

child/adult

vii) skin pale, cool ( blood flow) viii) edema, puffy face, coarse hair ix) broadening of facial features x) enlarged tongue xi) deepening of voice c) clinical: i) TSH level most sensitive screening - in 1O (due to loss of feedback inhibition of TRH release) - normal or not elevated in 2O or 3O hypothyroidism - T4 in all forms of hypothyroidism

test

Thyroiditis

inflammation of thyroid a) acute illness with thyroid pain b) may not significantly affect thyroid Types: a) Hashimoto thyroiditis (chronic lymphocytic thyroiditis) i) gradual thyroid failure due to autoimmune destruction of thyroid ii) 45-65 yrs iii) 10:1 female predominance iv) major cause of non endemic goiter in children

function

v) genetic component - patients with Turner syndrome have circulating antithyroid Ab vi) Clinical: 1) progressive depletion of thyroid epithelial cells 2) replaced with mononuclear cells and fibrosis 3) comes to clinical attention as enlargement of thyroid with some degree of hypothyroidism 4) hypothyroidism progresses slowly 5) can be preceeded by hashitoxicosis 6) patients at risk in developing other autoimmune diseases 7) no CA risk

painless

b) Subacute (granulomatous) thyroiditis [aka De Quervain thyroiditis] i) occurs less often than Hashimoto ii) 30-50 yrs iii) female preponderance 5:1 iv) caused by viral infection v) history of upper respiratory infection just prior to onset of thyroiditis vi) seasonal incidence (summer peak) vii) acute or gradual viii) painful presentation, radiating to jaw, throat, ears: especially when swallowing !!

ix) inflammation and hyperthyroidism

are transient
- followed by transient period of asymptomatic hypothyroidism x) self limited disease c) subacute lymphocytic (painless) i) uncommon ii) hyperthyroid presentation - may present with any of signs of hyperthyroidism (no opthalmopathy, as in Graves disease)

thyroiditis

d) Riedel thyroiditis i) fibrosis of thyroid and neighboring structures ii) presents as hard and fixed thyroid which clinically is similar to CA e) Palpation thyroiditis i) vigorous clinical palpation ii) thyroid function not affected iii) usually an incidental finding.

Graves disease Most common cause of endogenous hyperthyroidism Characteristics: a) hyperthyroidism i) diffuse enlargement of thyroid ii) lymphocytic infiltration b) infiltrative ophthalmopathy i) with resultant exophthalmos c) localized infiltrative dermopathy i) pretibial myxedema - present in minority of cases !

Thyrotoxicosis results in an increase in metabolic rate. This may result in: Smooth, moist, warm skin Flushing of face and hands Overgrown nails (acropachy, clubbing), which may lift off the nail bed (onycholysis) Fine soft thinned scalp hair Generalised itching (pruritus) Urticaria Increased skin pigmentation

Pretibial myxedema

peak incidence 20-40 female preponderance (7:1) familial link Pathogenesis: a) autoimmune disorder b) Ab against TSH receptor is central to process c) retro-orbital connective tissue and ocular increased i) inflammatory edema ii) T-cell infiltration iii) fatty infiltration iv) ECM accumulation v) these cause eye to bulge outward

disease
muscles are

d) Clinical: i) T3 and T4 ii) TSH Goiter Diffuse and multinodular enlargement of the thyroid a) most common manifestation of thyroid disease b) most often caused by dietary iodine deficiency (i.e., impaired synthesis of thyroid hormone) i) compensatory rise in TSH

ii) hyperplasia and hypertrophy compensates for hormone deficiency (via TSH) - result is euthyroid state iii) if response is inadequate goitrous hypothyroid - enlargement is proportional to degree and duration of thyroid hormone deficiency Diffuse nontoxic goiter a) diffuse goiter without nodules b) thyroid follicles filled with colloid i) colloid goiter

c) two types: i) endemic ii) sporadic d) endemic goiter (<10% population) i) geographic area deficient in iodine ii) mountainous areas of world - Alps, Himalayas, Andes. iii) TSH iv) can result from ingestion of certain goitrogens - cabbage, cauliflower, Brussels sprouts, turnips, cassava - excessive calcium

e) Sporadic goiter i) less frequent than endemic ii) female preponderance iii) peak incidence near puberty

Multinodular goiter a) recurrent hyperplasia/hypertrophy b) all simple nontoxic goiters evolve into goiters c) produce the most extreme thyroid i) often mistaken for neoplasm d) asymmetrically enlarged thyroid

multinodular

enlargements

e) small % of patients may develop a hyperfunctioning thyroid (nodule) resulting in a toxic multinodular goiter i) Plummer syndrome is example - without dermopathy nor ophthalmopathy (as in Graves) all goiters may cause Mass Effects a) dysphagia b) compression of large vessels c) airway obstruction

Thyroid Neoplasms

Adenomas discrete solitary masses derived from follicular epithelium (i.e., follicular adenomas) a) difficult to differentiate from a dominant follicular hyperplasia b) NOT predecessors of malignancy c) mostly nonfunctional i) small % produce hormones (thyrotoxicosis) ii) hormones independent of TSH (thyroid autonomy). Similar to multinodular toxic goiter

nodule of

Pathogenesis: a) toxic adenoma i) TSH receptor pathway is important signaling for hormone production - overproduction of cAMP ii) hot nodules iodine uptake b) usually present as unilateral painless mass c) take up less radioactive iodine compared to normal thyroid parenchymal cells i) cold nodules ii) ~10% of cold nodules malignant iii) hot nodules rarely malignant d) biopsy is gold standard for diagnosis

e) do not recur nor metastasize other benign tumors a) cysts i) usually represent cystic degeneration thyroid follicular adenoma b) lipomas c) hemangiomas d) dermoid cysts e) teratomas (mainly in infants)

of

Thyroid Carcinomas

relatively uncommon in USA most appear in adults a) papillary CA may present in childhood female predominance (early and middle adult) a) childhood and late adulthood have equal gender distribution most CA are well differentiated: a) papillary CA (~80% of cases) b) follicular CA ( ~15% of cases) c) medullary CA (~5% of cases) d) anaplastic CA (< 5% of cases)

genetic and environmental factors implicated a) genetic factors seen in both familial and nonfamilial (sporadic) forms of CA i) familial medullary CA most inherited of thyroid CA ii) papillary and follicular familial CA are very rare !! b) exposure to ionizing radiation during first 2 decades of life is one of the most important factors predisposing one to thyroid cancer

i) in past, radiation of head and neck in children for a variety of problems has led to ~ 10% developing thyroid carcinoma ii) atomic bomb survivors as well as those survivors following Chernobyl incident have thyroid carcinoma - type is papillary carcinoma c) pre-existing thyroid disease i) multi-nodular goiter have predisposition to develop carcinoma due to areas of iodine - type is follicular carcinoma

Papillary Carcinoma a) most common of thyroid carcinoma b) any age c) vast majority of carcinoma associated radiation exposure d) solitary or multi-focal nodules e) are non-functional tumors i) painless masses ii) within thyroid or metastasis to cervical lymph nodes

with ionizing

Follicular Carcinoma a) second most common form of thyroid b) incidence in areas of dietary iodine c) do not arise from pre-existing adenomas d) present most often as solitary nodules uptake (cold nodules) e) metastasize via blood to lungs, bone and f) unlike papillary carcinoma, regional nodal involvement is uncommon

carcinoma deficiency
with no iodine liver

Medullary Carcinoma a) secrete calcitonin from C cells i) calcitonin important diagnostic measurement as well as a follow-up following treatment b) may arise as solitary nodule or multiple lesions c) C cell hyperplasia Anaplastic Carcinoma a) most aggressive thyroid neoplasms b) predominantly in elderly patients i) areas with endemic goiter c) death in < 1 year ( compromise of neck) d) distant metastasis is common

Join now for FREE!

www.Facebook.com/Ex