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
– Hypothalamus
(negative effect)
(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 ; 5::1
• Potency of T4 to T3; 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 ; 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.

THYROID GLAND DISORDERS



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


THYROID GLAND DISORDERS
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

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

– is defined as the state of thyroid hormone excesss

– 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
• Grave´s 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

 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

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 ( 131 I)
• 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:
• 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 ( 131 I)
• Propranolol
• Glucocorticoids
• Benzodiazepines
• Iodide (Large oral or IV dosage) (Wolf-Chaikoff effect)

THYROID GLAND DISORDERS
 HYPOTHYROIDISM
– Primary
• Autoimmune (Hashimoto´s)
• Iatrogenic Surgery or 131 I
• Drugs: amiodarone, lithium
• Congenital (1 in 3000 to 4000)
• Iodine defficiency
• Infiltrative disorders

THYROID GLAND 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

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

 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
 It´s 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 GLAND DISORDERS
 THYROID GLAND NEOPLASIAS
 Out of the focus of this lecture


Hormones
– Internal secretions

Produced by ductless glands

Secrete directly into bloodstream

Drugs
– Natural or synthetic
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
Pituitary hormones

Adrenal corticosteroids

Thyroid agents

Antidiabetic agents
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
Located at the base of the brain

Master gland

Secretes four hormones
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
Anterior pituitary lobe hormone

Human growth hormone (HGH)

Regulates growth

Treated by an endocrinologist
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
ACTH

Parenteral use
– Corticotropin

Used for diagnosis of adrenocortical insufficiency
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
Adrenal glands adjacent to kidneys

Secrete corticosteroids

Act on the immune system

Uses
– Replacement therapy
– Anti-inflammatory
– Immunosuppressent properties
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
Not curative

Supportive therapy

Conditions treated with corticosteroids

Effects of prolonged administration

Alternate-day therapy
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
Withdrawal of therapy

Side effects

Contraindications or extreme caution

Interactions

Patient education
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
Natural or synthetic

Replacement therapy

Conditions requiring treatment

Diagnosis with blood tests

If patient euthyroid
– Treatment contraindicated
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
Treatment required for life

Periodic lab tests recommended

Toxic effects

Contraindications or extreme precautions

Interactions

Patient education
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
Relieve symptoms of hyperthyroidism

Used in preparation for surgical or radioactive iodine therapy

Side effects

Contraindication or caution

Interactions

Patient education
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
Administered to lower blood glucose levels

Impaired metabolism of CHO, fats, and proteins

Diabetes mellitus
– Insulin dependent (Type I, IDDM)
– Non-insulin dependent (Type II, NIDDM)
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
Used in Type I

Sometimes used in Type II

Must be administered parenterally

Other forms in clinical trials

Made from pork, beef-pork, biosynthetic human, or analogue
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
U-100

Insulin syringes

Doses must be double-checked before administration

Differ in onset, peak, and duration of action
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
Rapid

Short

Intermediate

Long

Mixtures
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
Rapid action and short duration

Can be administered IV or SC

Drawn up first when mixed with other insulins

Sliding scale varies with individual
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
Causes

Symptoms

Treatment of acute hyperglycemia

Insulin interactions
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
Causes

Symptoms

Treatment
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
Type II diabetes

How administered

Weight reduction and modified diets

Symptoms of Type II diabetes
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
First-generation agents

Second-generation agents

Increase insulin production from the pancreas

Improve peripheral insulin activity
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
Side effects

Contraindications or extreme caution

Interactions
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
Delay digestion of complex CHO and glucose absorption

Used with sulfonylurea medications

Side effects

Contraindications or extreme precautions

Drug interactions
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
Decrease hepatic glucose output and enhance insulin sensitivity in muscle

Can be used as monotherapy or with sulonylureas

Side effects

Contraindications or extreme precautions

Drug interactions
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
Stimulate beta cells of pancreas to produce insulin

Used as monotherapy or with metformin

Side effects

Contraindication or extreme caution

Drug interactions
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
Decrease insulin resistance

Improve sensitivity to insulin in muscle and adipose tissue

Used as monotherapy or with sulonylurea, insulin, or metformin
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
Side effects

Contraindications or extreme caution

Drug interactions

Patient education
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