Transcript THYROID GLAND DISORDERS

THYROID GLAND
DISORDERS
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
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
 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
• 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
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 (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:
• 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)
THYROID GLAND DISORDERS
 HYPOTHYROIDISM
– Primary
• Autoimmune (Hashimoto´s)
• Iatrogenic Surgery or 131I
• 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
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
 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
Endocrine System
 Hormones
– Internal secretions
 Produced by ductless glands
 Secrete directly into bloodstream
 Drugs
– Natural or synthetic
Copyright © 2007 by
Thomson Delmar
Learning. ALL
RIGHTS RESERVED.
37
Categories
 Pituitary hormones
 Adrenal corticosteroids
 Thyroid agents
 Antidiabetic agents
Copyright © 2007 by
Thomson Delmar
Learning. ALL
RIGHTS RESERVED.
38
Pituitary
 Located at the base of the brain
 Master gland
 Secretes four hormones
Copyright © 2007 by
Thomson Delmar
Learning. ALL
RIGHTS RESERVED.
39
Somatotropin
 Anterior pituitary lobe hormone
 Human growth hormone (HGH)
 Regulates growth
 Treated by an endocrinologist
Copyright © 2007 by
Thomson Delmar
Learning. ALL
RIGHTS RESERVED.
40
Adrenocorticotropic Hormone
 ACTH
 Parenteral use
– Corticotropin
 Used for diagnosis of adrenocortical
insufficiency
Copyright © 2007 by
Thomson Delmar
Learning. ALL
RIGHTS RESERVED.
41
Adrenal Corticosteroids
 Adrenal glands adjacent to kidneys
 Secrete corticosteroids
 Act on the immune system
 Uses
– Replacement therapy
– Anti-inflammatory
– Immunosuppressent properties
Copyright © 2007 by
Thomson Delmar
Learning. ALL
RIGHTS RESERVED.
42
Corticosteroid Therapy
 Not curative
 Supportive therapy
 Conditions treated with corticosteroids
 Effects of prolonged administration
 Alternate-day therapy
Copyright © 2007 by
Thomson Delmar
Learning. ALL
RIGHTS RESERVED.
43
Corticosteroid Therapy
 Withdrawal of therapy
 Side effects
 Contraindications or extreme caution
 Interactions
 Patient education
Copyright © 2007 by
Thomson Delmar
Learning. ALL
RIGHTS RESERVED.
44
Thyroid Agents
 Natural or synthetic
 Replacement therapy
 Conditions requiring treatment
 Diagnosis with blood tests
 If patient euthyroid
– Treatment contraindicated
Copyright © 2007 by
Thomson Delmar
Learning. ALL
RIGHTS RESERVED.
45
Thyroid Agents
 Treatment required for life
 Periodic lab tests recommended
 Toxic effects
 Contraindications or extreme precautions
 Interactions
 Patient education
Copyright © 2007 by
Thomson Delmar
Learning. ALL
RIGHTS RESERVED.
46
Antithyroid Agents
 Relieve symptoms of hyperthyroidism
 Used in preparation for surgical or
radioactive iodine therapy
 Side effects
 Contraindication or caution
 Interactions
 Patient education
Copyright © 2007 by
Thomson Delmar
Learning. ALL
RIGHTS RESERVED.
47
Antidiabetic Agents
 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)
Copyright © 2007 by
Thomson Delmar
Learning. ALL
RIGHTS RESERVED.
48
Insulin
 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
Copyright © 2007 by
Thomson Delmar
Learning. ALL
RIGHTS RESERVED.
49
Insulin
 U-100
 Insulin syringes
 Doses must be double-checked before
administration
 Differ in onset, peak, and duration of action
Copyright © 2007 by
Thomson Delmar
Learning. ALL
RIGHTS RESERVED.
50
Insulin Types
 Rapid
 Short
 Intermediate
 Long
 Mixtures
Copyright © 2007 by
Thomson Delmar
Learning. ALL
RIGHTS RESERVED.
51
Insulin Administration
Copyright © 2007 by
Thomson Delmar
Learning. ALL
RIGHTS RESERVED.
52
Regular Insulin
 Rapid action and short duration
 Can be administered IV or SC
 Drawn up first when mixed with other
insulins
 Sliding scale varies with individual
Copyright © 2007 by
Thomson Delmar
Learning. ALL
RIGHTS RESERVED.
53
Hyperglycemia
 Causes
 Symptoms
 Treatment of acute hyperglycemia
 Insulin interactions
Copyright © 2007 by
Thomson Delmar
Learning. ALL
RIGHTS RESERVED.
54
Hypoglycemia
 Causes
 Symptoms
 Treatment
Copyright © 2007 by
Thomson Delmar
Learning. ALL
RIGHTS RESERVED.
55
Oral Antidiabetic Agents
 Type II diabetes
 How administered
 Weight reduction and modified diets
 Symptoms of Type II diabetes
Copyright © 2007 by
Thomson Delmar
Learning. ALL
RIGHTS RESERVED.
56
Sulfonylureas
 First-generation agents
 Second-generation agents
 Increase insulin production from the
pancreas
 Improve peripheral insulin activity
Copyright © 2007 by
Thomson Delmar
Learning. ALL
RIGHTS RESERVED.
57
Sulfonylureas
 Side effects
 Contraindications or extreme caution
 Interactions
Copyright © 2007 by
Thomson Delmar
Learning. ALL
RIGHTS RESERVED.
58
Alpha-Glucosidase Inhibitors
 Delay digestion of complex CHO and
glucose absorption
 Used with sulfonylurea medications
 Side effects
 Contraindications or extreme precautions
 Drug interactions
Copyright © 2007 by
Thomson Delmar
Learning. ALL
RIGHTS RESERVED.
59
Biguanides
 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
Copyright © 2007 by
Thomson Delmar
Learning. ALL
RIGHTS RESERVED.
60
Meglitinides
 Stimulate beta cells of pancreas to produce
insulin
 Used as monotherapy or with metformin
 Side effects
 Contraindication or extreme caution
 Drug interactions
Copyright © 2007 by
Thomson Delmar
Learning. ALL
RIGHTS RESERVED.
61
Thiazolidinediones
 Decrease insulin resistance
 Improve sensitivity to insulin in muscle and
adipose tissue
 Used as monotherapy or with sulonylurea,
insulin, or metformin
Copyright © 2007 by
Thomson Delmar
Learning. ALL
RIGHTS RESERVED.
62
Thiazolidinediones
 Side effects
 Contraindications or extreme caution
 Drug interactions
 Patient education
Copyright © 2007 by
Thomson Delmar
Learning. ALL
RIGHTS RESERVED.
63