THYROID GLAND DISORDERS

• GENERAL ASPECTS OF THYROID GLAND

– Anatomy: weight range from 12 to 30g

– Located in the neck, anterior to the trachea

– Produces: T4 & T3 (active hormone)

• Thyroid hormones:

– T4: (Thyroxine) is made exclusively in thyroid gland

• Ratio of T4 to T3 ; 5::1

• Potency of T4 to T3; 1::10

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

– T3: (Triiodothyronine) main source is peripheral deiodination:

• Ratio of T3 to T4 ; 1::5

• Potency of T3 to T4; 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.

• PHYSIOLOGY EFFECTS OF THYROID HORMONES

• THEY ARE NOT ESSENTIAL FOR LIFE, BUT ARE EXTREMELY HELPFUL

THYROID GLAND DISORDERS

– Affects every single cell in the body

• Modulates:

– Oxygen consumption

– Growth rate

– Maturation and cell differentiation

– Turnover of Vitamins, Hormones, Proteins, Fat, CHO

• 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 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

– 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

– 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

- FAT & PROTEIN METABOLISM

• Increase lipolysis and lipid mobilization with:

– Cholesterol

– Triglicerides

– Free fatty acids

– MUSCLE METABOLISM

• Modulates;

– Strength & velocity of contraction

– ELECTROLYTE BALANCE

• Low Thyroid hormones could induce hyponatremia

– VITAMIN METABOLISM

• Modulates vitamin consumption

– HEMATOPOIETIC SYSTEM

• Could induce anemia

– 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

• 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

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

• 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)

• THYROTOXICOSIS:

– is defined as the state of thyroid hormone excesss

• HYPERTHYROIDISM:

– is the result of excessive thyroid gland function

• Abnormalities of Thyroid Hormones

– Thyrotoxicosis

• Primary

• Secondary

• Without Hyperthyroidism

• Exogenous or factitious

– Hypothyroidism

• Primary

• Secondary

• Peripheral

• Causes of Thyrotoxicosis:

– Primary Hyperthyroidism

• Grave´s disease

• Toxic Multinodular Goiter

• Toxic adenoma

• Functioning thyroid carcinoma metastases

• Activating mutation of TSH receptor

• Struma ovary

• Drugs: Iodine excess

– 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

• Symptoms:

– Hyperactivity

– Irritability

– Dysphoria

– Heat intolerance & sweating

– Palpitations

– Fatigue & weakness

– Weight loss with increased appetite

– Diarrhea

– Polyuria

– Sexual dysfunction

• Signs:

– Tachycardia

– Atrial fibrillation

– Tremor

– Goiter

– Warm, moist skin

– Muscle weakness, myopathy

– Lid retraction or lag

– Gynecomastia

– * Exophtalmus

– * Pretibial myxedema

• Differential diagnosis:

– Panic attacks

– Psychosis

– Mania

– Pheochromocytoma

– Hypoglycemia

– Occult malignancy

• 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)

• Treatment: Special considerations:

– Thyrotoxic crisis or Thyroid storm:

• It´s a life-threatening exacervation of thyrotoxicosis, acompanied by fever, delirium, seizures, coma, vomiting, diarrhea, jaundice.

• Mortality rate reachs 30% even with treatment

• It´s 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)

• HYPOTHYROIDISM

– Primary

• Autoimmune (Hashimoto´s)

• Iatrogenic Surgery or 131I

• Drugs: amiodarone, lithium

• Congenital (1 in 3000 to 4000)

• Iodine defficiency

• Infiltrative disorders

• Hashimoto´s 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, Sjogren´s so-on.

• Treatment: Levothyroxine

• 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

HYPOTHYROIDISM

– Secondary

• Pituitary gland destruction

• Isolated TSH deficiency

• Bexarotene treatment

• Hypothalamic disorders

– Peripheral:

• Rare, familial tendency

• 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.

• 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

• It´s an Emergency with a high mortality rate

• Treatment: Lyotironine(T3) or T4, Hydrocortisone, external warming, IV fluids

• Elderly patients

• Coronary Artery Disease

• Poor adrenal gland reserve

• Childrens

• Pregnancy

• Emergency surgery (Non thyroid related)