2. THYROID GLAND DISORDERS

3. 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

4. THYROID GLAND DISORDERS
THYROID GLAND REGULATION
“negative Feed-back” axis
Hypothalamus
(TRH positive effect)
Pituitary gland
(TSH, positive effect)
Thyroid gland
T3 & T4
(negative effect)

5. THYROID GLAND DISORDERS
Thyroid hormones:
T4: (Thyroxine) is made exclusively in thyroid gland
Ratio of T4 to T3 ; ::1
Potency of T4 to T3; 1::10
T4 is the most important source of T3 by peripheral tissue deiodination “ T4 to T3 “

6. THYROID GLAND DISORDERS
Thyroid hormones:
T3: (Triiodothyronine) main source is peripheral deiodination:
Ratio of T3 to T4 ; ::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.

7. THYROID GLAND DISORDERS
PHYSIOLOGY EFFECTS OF THYROID HORMONES
THEY ARE NOT ESSENTIAL FOR LIFE, BUT ARE EXTREMELY HELPFUL

8. 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

9. 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

10. 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

11. 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

12. 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

13. 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

14. THYROID GLAND DISORDERS
THYROID HORMONE EFFECTS
ELECTROLYTE BALANCE
Low Thyroid hormones could induce hyponatremia
VITAMIN METABOLISM
Modulates vitamin consumption
HEMATOPOIETIC SYSTEM
Could induce anemia

15. 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:

16. 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

17. THYROID GLAND DISORDERS
DIVIDED INTO:
THYROTOXICOSIS (Hyperthyroidism)
Overproduction of thyroid hormones
HYPOTHYROIDISM (Gland destruction)
Underproduction of thyroid hormones
NEOPLASTIC PROCESSES
Beningn
Malignant

18. 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

19. 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)

20. THYROID GLAND DISORDERS
THYROTOXICOSIS:
is defined as the state of thyroid hormone excesss
HYPERTHYROIDISM:
is the result of excessive thyroid gland function

21. THYROID GLAND DISORDERS
Abnormalities of Thyroid Hormones
Thyrotoxicosis
Primary
Secondary
Without Hyperthyroidism
Exogenous or factitious
Hypothyroidism
Peripheral

22. 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

23. 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

25. THYROTOXICOSIS Symptoms: Signs: 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

26. THYROID GLAND DISORDERS
Differential diagnosis:
Panic attacks
Psychosis
Mania
Pheochromocytoma
Hypoglycemia
Occult malignancy

27. 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
Iodide (Large oral or IV dosage) (Wolf-Chaikoff effect)

28. 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)

29. 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

30. 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

31. 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

32. THYROID GLAND DISORDERS
HYPOTHYROIDISM
Secondary
Pituitary gland destruction
Isolated TSH deficiency
Bexarotene treatment
Hypothalamic disorders
Peripheral:
Rare, familial tendency

33. HYPOTHYROIDISM Symptoms: Signs: 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.

34. 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

35. THYROID GLAND DISORDERS
SPECIAL TREATMENT CONSIDERATIONS
Elderly patients
Coronary Artery Disease
Poor adrenal gland reserve
Childrens
Pregnancy
Emergency surgery (Non thyroid related)

36. THYROID GLAND DISORDERS
THYROID GLAND NEOPLASIAS
Out of the focus of this lecture

37. Endocrine System Hormones Produced by ductless glands
Internal secretions
Produced by ductless glands
Secrete directly into bloodstream
Drugs
Natural or synthetic
Copyright © 2007 by Thomson Delmar Learning. ALL RIGHTS RESERVED.

38. Categories Pituitary hormones Adrenal corticosteroids Thyroid agents
Antidiabetic agents
Copyright © 2007 by Thomson Delmar Learning. ALL RIGHTS RESERVED.

39. Pituitary Located at the base of the brain Master gland
Secretes four hormones
Copyright © 2007 by Thomson Delmar Learning. ALL RIGHTS RESERVED.

40. Somatotropin Anterior pituitary lobe hormone
Human growth hormone (HGH)
Regulates growth
Treated by an endocrinologist
Copyright © 2007 by Thomson Delmar Learning. ALL RIGHTS RESERVED.

41. Adrenocorticotropic Hormone
ACTH
Parenteral use
Corticotropin
Used for diagnosis of adrenocortical insufficiency
Copyright © 2007 by Thomson Delmar Learning. ALL RIGHTS RESERVED.

42. 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.

43. 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.

44. Corticosteroid Therapy
Withdrawal of therapy
Side effects
Contraindications or extreme caution
Interactions
Patient education
Copyright © 2007 by Thomson Delmar Learning. ALL RIGHTS RESERVED.

45. 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.

46. 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.

47. 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.

48. 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.

49. 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.

50. 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.

51. Insulin Types Rapid Short Intermediate Long Mixtures
Copyright © 2007 by Thomson Delmar Learning. ALL RIGHTS RESERVED.

52. Insulin Administration
Copyright © 2007 by Thomson Delmar Learning. ALL RIGHTS RESERVED.

53. 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.

54. Hyperglycemia Causes Symptoms Treatment of acute hyperglycemia
Insulin interactions
Copyright © 2007 by Thomson Delmar Learning. ALL RIGHTS RESERVED.

55. Hypoglycemia Causes Symptoms Treatment
Copyright © 2007 by Thomson Delmar Learning. ALL RIGHTS RESERVED.

56. 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.

57. 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.

58. Sulfonylureas Side effects Contraindications or extreme caution
Interactions
Copyright © 2007 by Thomson Delmar Learning. ALL RIGHTS RESERVED.

59. 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.

60. 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.

61. 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.

62. 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.

63. Thiazolidinediones Side effects Contraindications or extreme caution
Drug interactions
Patient education
Copyright © 2007 by Thomson Delmar Learning. ALL RIGHTS RESERVED.