Internal Medicine Al Azhar university Faculty of Oral and Dental Medicine Lama El Banna

1. Dr. Suhail S. Kishawi
Consultant in Endocrinology and Diabetes
Consultant Internist
DISEASES OF THYROID GLAND

2. THE THYROID GLAND
 Named after the thyroid cartilage
(Greek: Shield-shaped)
 Wharton 1656: “glandulae thyroidaeae”
“whose purpose is to….. beautify the neck….
particularly in females to whom for this reason a
larger gland has been assigned”
 Vercelloni 1711: “a bag of worms” whose eggs
pass into the esophagus for digestive purposes
 Parry 1825: “a vascular shunt” to cushion the
brain from sudden increases in blood flow

4. ANATOMY OF THYROID GLAND
• The thyroid gland lies over the
thyroid cartilage and upper
trachea.
• It is attached to these
structures by the pretracheal
fascia, which explains why it
moves on swallowing.
• The gland is H-shaped with two
lateral lobes and an isthmus
joining them.
• In about 15% of people there is
a small pyramidal lobe arising
out of the upper margin of the
isthmus

5. THYROID ANATOMY
• Largest endocrineLargest endocrine
gland (20 - 25 g)gland (20 - 25 g)
• Fills the tracheo-Fills the tracheo-
esophageal spaceesophageal space
• Overlies RLNOverlies RLN
bilaterallybilaterally
• Parathyroids lie atParathyroids lie at
each pole (usually!)each pole (usually!)

6. HISTOLOGY OF THYROID GLAND
• The structural unit of the
thyroid is the follicle containing
colloid, surrounded by a layer
of cuboidal epithelium. Groups
of 20-40 follicles by connective
tissue to form lobules, groups
of which are, in turn,
incorporated to form lobes.
• In addition, small groups of
cells, the parafollicular cells or
C-cells, with different
histological appearance, are
found scattered throughout the
gland. They secret the calcium-
lowering hormone calcitonin.

7. Thyroid Follicles
C cell
(parafollicular)
Follicular cell
Lumen
(colloid)
Apical membrane
Basolateral (Basal)
membrane

8. HISTOLOGY OF THYROID GLAND
• The parathyroid glands may
be sometimes embedded in
the thyroid tissue,
particularly the lower ones.
• The structure of a
parathyroid gland is
distinctly different from a
thyroid gland. The cells that
synthesize and secrete
parathyroid hormone
(parathormone) are arranged
in rather dense cords or
nests around abundant
capillaries.

9. SYNTHESIS AND SECRETION OF THYROID
HORMONES
1. IODINE TRAPPING
2. ORGANIFICATION
3. COUPLING
4. SECRETION

10. SYNTHESIS AND SECRETION OF THYROID HORMONES
(1)TRAPING
(2)ORGANIFICATION
(3)COUPLING
(4)SECRETION

11. CHEMISTRY OF THYROID HORMONES

12. Thyroglobulin
 Major protein product of follicular cells
 Released into circulation with thyroid hormone
 “Catalyst” as well as storage role in the thyroid
 Native structure essential for T4 production

13. Thyroid Binding Proteins
 Thyroid hormones are highly lipophilic
 Majority (>99%) circulate bound to proteins
 Thyroid binding globulin (TBG) ~70%
 Albumin ~15 - 20%
 Transthyretin (TTR) ~10%
 Lipoproteins ~2 - 5%

14. Thyroid Hormones
• Transported through the bloodstream bound
to carrier proteins (most important: TBG)
• T4 is predominant circulating hormone
• Converted to active T3 in cytoplasm of target
cells before binding thyroid hormone
receptor

15. Binding Protein Abnormalities
Increased binding capacity
 Dysalbuminemic
 Increased hepatic synthesis
of TBG
 - Estrogens
 - Pregnancy
 - Hyperthyroidism
Decreased binding capacity
 TBG deficiency (inherited)
 Decreased hepatic synthesis of
TBG
 - Malnutrition
 - Severe illness
 - Hepatic failure
 - Hypothyroidism
 Protein wasting states

16. Functions of Thyroid Hormone
1. Metabolic: increases cellular oxygen consumption and heat
production in part by stimulating Na+/K+ ATPase
2. Cardiovascular: marked positive inotropic and chronotropic effects
on heart
3. Sympathetic: increases number of alpha and beta-adrenergic
receptors in heart muscle and beta receptors in skeletal muscle,
adipose tissue, and lymphocytes
4. Respiratory: maintains normal hypoxic and hypercapneic
drive in medullary respiratory center
5. Hematopoietic effects: stimulates secretion of Epo to
increase RBC synthesis

17. Functions of Thyroid Hormone
6. Bone: stimulates increased bone turnover (resorption
>formation)
7. Muscle: increases speed of muscle contraction and
relaxation; normally stimulate increased protein synthesis but
at high levels cause protein turnover and loss of muscle tissue
8. Neuro: necessary for normal development and CNS
functioning
9. G.I.: stimulates gut motility

18. Thyroid Hormone Receptor
 High lipid solubility ensures
easy passage across cell
membrane
 Action is principally within
the nucleus, altering gene
regulation
T3

19. Regulation of secretion : negative feed back
Thyroid
Pituitary
Hypothalamus
TRH (+)
TSH (+)
T3, T4 (-)
T3, T4 (-)

20. METHODS OF INVESTIGATION
• MEASUREMENT OF THYROID HORMONE CONCENTRATIONS
• TESTS OF THYROID DYNAMICS
• TESTS OF METABOLIC FUNCTION
• TESTS TO KNOW THE CAUSE OF THYROID DYSFUNCTION

21. MEASUREMENT OF THYROID HORMONE
CONCENTRATIONS
1. Total Thyroxine ( Total T4 )
• Provides a sensitive indicator of thyroid function.
• In people with normal thyroid function concentrations may be:
 Raised because of increased TBG
 Pregnancy,
 Estrogen administration
 Congenital anomaly.
 Diminished because of decreased TBG
 Due to nephrotic syndrome, androgen therapy, liver failure,
 Inherited TBG deficiency.
 TBG may appear to be low if binding sites are saturated with
drugs such as salicylates, phenylbutazone, sulphonylureas
and phenytoin.

22. MEASUREMENT OF THYROID HORMONE
CONCENTRATIONS
2. Free Thyroxine ( FT4 )
 In most circumstances the level is normal
when the above alterations of protein binding
are present.
3. Total Tri-iodothyronine (Total T3)
 This can be measured by radioimmunoassay.
 It is useful in clinically thyrotoxic patients with
normal T4 levels 'T3-toxicosis'.
 But is of less value in hypothyroidism where
T3 levels may be in the low normal range.

23. MEASUREMENT OF THYROID HORMONE
CONCENTRATIONS
4. FreeT3
 It is of value in diagnosing thyrotoxicosis.
5. Thyrotrophin (TSH)
 Patients with hyperthyroidism have TSH levels of <0.05
mU/l
 Normal subjects are in the range of 0.4-4.0 mU/l
 Patients with hypothyroidism have elevated
concentrations of TSH.

24. • Thyroid Scintigraphy (“Scans”)
– 99m
Tc
– 131
I
• Thyroid Ultrasound
– May be useful to accurately determine size for
purposes of documenting therapeutic efficacy
TESTS OF THYROID DYNAMICS
Normal
Thyroid
Graves’
Thyroid
Multinodular
Goiter

25. normal scan cold nodule

26. Thyroid Scan – Multinodular Goiter

27. TESTS FOR THE CAUSE OF THYROID DYSFUNCTION
THYROID ANTIBODIES
1. Thyroglobulin antibodies:
 A titre of > 1: 100 suggests significant thyroiditis.
2. Microsomal (TPO) antibodies:
 A titre of > 1:40 indicates significant thyroiditis.
 Microsomal antibodies correlate better than
thyroglobulin antibodies with the degree of
thyroiditis and the impairment of thyroid function.

28. TESTS FOR THE CAUSE OF THYROID DYSFUNCTION
THYROID ULTRASOUND
 Ultrasound is a useful technique for
deciding whether a nodule, which is non-
functioning on isotope scanning, is cystic
or solid.
 If it is cystic, aspiration and cytological
studies may cancel the necessity for
operation.

29. Sonogram of the left lobe of the thyroid gland in the
transverse plane showing a rounded lobe of a goiter.
• L : enlarged lobe,
• I : widened isthmus
• T : trachea,
• C : carotid artery
• J : jugular vein,
• S : Sternocleidomastoid
muscle,
• M : strap muscles,
• E : esophagus.

30. TESTS FOR THE CAUSE OF THYROID
DYSFUNCTION
NEEDLE BIOPSY (FNAB)
 In patients with non-functioning nodules,
determined by isotope scanning, which are
shown by ultrasound to be solid, fine needle
aspiration biopsy can be carried out with or
without local anesthesia.
 It carries a diagnostic accuracy of more than
80%.

32. (A) Benign epithelial cells, colloid, and occasional
macrophages, typical of a "colloid nodule"
(B) Epithelial cells in a follicular arrangement suggesting
adenoma, but which could be from a follicular carcinoma.
(C) Epithelial cells in a pappilary formation from a papillary
thyroid carcinoma. Nuclear grooves are also apparent.

33. Disorders of the Thyroid Gland
• Abnormal thyroid function
– Hypothyroidism
– Hyperthyroidism
• Thyroid enlargement
– Goiter
– Thyroid nodules
– Thyroid tumors

34. Disorders of the Thyroid Gland
Physical Examination of the Thyroid Gland
 Inspection
 Glass of water for swallowing
 Palpation
 Anteriorly
 From behind
Each lobe measures : vertical dimension – 2 cm
horizontal dimension – 1 cm

35. Thyroid Palpation
Texture – soft / firm / hard
Surface – smooth / seedy / lumpy
Shape – diffuse / nodular
Presence of regional adenopathy

38. Hypothyroidism
• Definition: Deficiency of thyroid hormone
• Causes:
– Primary (TSH high) ~95%
– Secondary (TSH low) ~5%
• Pituitary disease
• Hypothalamic disease
– Thyroid Hormone Resistance (rare)
• Relatively common:
– 2% adult women, 0.2% adult men
– >60: 6% adult women; 2% adult men

39. Wide Range of Hypothyroidism
• Asymptomatic to Severe:
– Biochemical: Very common; TSH 6-10 IU/ml, with normal T4, T3.
Treatment is controversial & should be correlated with
improvement in symptoms
– Myxedema Coma: Profound, severe hypothyroidism
• Onset: Usually Gradual
• ± Goiter
• Risk Factors: Age >60, female, history of thyroid
disease, history of radiotherapy to head/neck, family
history of thyroid disease, lithium or amiodarone
therapy.

40. Clinical Features: Hypothyroidism
• Constitutional Symptoms :
– Cold Intolerance
– Fatigue, Lethargy
– Hoarseness of voice
• skin :
– Thickened/yellowed, Dry, Non-pitting Edema
(=“Myxedema”) of hands/feet/periorbital region, Cool, ↓
Perspiration, Alopecia.
• Cardiovascular:
↓ contractility, ↓ rate, ↓ cardiac output, pericardial/pleural
effusions, ↑ peripheral vascular resistance. CHF rare.

41. Clinical Features: Hypothyroidism
• Gastrointestinal:
↓ Appetite, Constipation, Weight Gain (5-10% increase)
• Gynecologic:
– Menorrhagia, Menstrual Irregularities
• Musculoskeletal:
– Myalgias, Arthralgias
• Hematologic:
– Anemia
• Neurologic:
– Delayed relaxation phase of DTRs, Difficulty Concentrating, Poor
Memory, Somnolence, Depression, Headache, Paresthesia

42. Myxedema

43. Hypothyroidism

44. Laboratory Diagnosis: Hypothyroidism
TSH Free T4 T3
Primary Hypothyroidism:
Subclinical Hypothyroidism ↑ N N
Mild Hypothyroidism ↑ N/↓
N/↓
Overt Hypothyroidism ↑ ↓
N/↓

45. Etiologies of Primary Hypothyroidism
• Loss of Functional Thyroid Tissue
– Chronic/Autoimmune thyroiditis (Hashimoto’s thyroiditis)
– Transient Thyroiditis (post-partum, silent, painful)
– Transient or Permanent Iatrogenic hypothyroidism, 2º to
surgery or following
131
I thyroid ablation therapy
– Congenital Thyroid Agenesis/Dysgenesis
• Interference with T4/T3 Production
– Drug-Induced Defects in T4 Biosynthesis
• Anti-thyroid drugs, lithium, iodide, amiodarone
– Iodine Deficiency (rare in US, common in 3rd world)
– Congenital Defects in Thyroid Hormone Production (rare)

46. Autoimmune Thyroiditis (Hashimoto’s, Chronic
Lymphocytic)
• Autoimmune destruction of thyroid tissue
– High titers of anti-thyroid antibodies
– Lymphocytic Infiltration of thyroid gland, fibrosis
• Firm, non-tender diffuse goiter
• #1 cause of hypothyroidism (70%)
• Usually permanent

47. Hypothyroidism in Infants
• Delayed Growth & Development
• Poor Feeding
• Prolonged Neonatal Jaundice
• Umbilical Hernia
• Protruding Tongue
• Delayed Bone Age

48. Hypothyroidism in Infants
Age: 6 mos 4 mos after L-T4

49. Hypothyroidism in Children
• Short Stature, Delayed
Bone Age
• Increased Wt for Ht Age
• School performance
often does not suffer
• Other symptoms/signs
similar to adults
• Pituitary enlargement
may occur
Fisher, D., Hypothyroidism, Rudolph’s Pediatrics, 21st
Ed, 2002

50. Treatment of Hypothyroidism
Replace with levo-thyroxine (L-T4)
(Example Brands: Eltroxin ®, Euthyrox®,)
Monitor thyroid function tests every 6-8
weeks until steady dose is achieved; goal is
to normalize TSH in most cases

51. Figure 15-12. Ten year old female with severe 1° hypothyroidism due to primary myxedema before (A) and after
(B) treatment. Presenting complaint was poor growth. Note the dull facies, relative obesity and immature body
proportions prior to treatment. At age 10 years she had not lost a single deciduous tooth. After treatment was
initiated (indicated by the arrow in Panel C), she lost 6 teeth in 10 months and had striking catch up growth. Bone
age was 5 years at a chronologic age of 10 years. TSH receptor blocking antibodies were negative.
A B

52. Hyperthyroidism: Clinical Features
– Cardiac
• Sinus Tachycardia/Atrial Fibrillation
• Congestive heart failure (high-output)
• Angina
• Increased pulse pressure
– Musculoskeletal
• Tremor
• Proximal Muscle Weakness (Myopathy)
– Neurologic/Psychiatric
• Anxiety, Hyperactivity, Mania
• Disorientation, Coma
• Rarely, seizures/convulsions

53. Diagnosis of Hyperthyroidism
• Physical Examination
• Laboratory Tests

54. Laboratory Diagnosis: Hyperthyroidism
TSH T4 Free T4 T3
Primary:
Subclinical Hyperthyroidism ↓ N N N
Hyperthyroidism ↓ ↑ ↑ ↑
T3 thyrotoxicosis ↓ N N ↑
Secondary Hyperthyroidism ↑ ↑ ↑ ↑
(TSH Secreting Adenoma-Rare!)

55. Causes of Hyperthyroidism
• Toxic Diffuse Goiter (Grave’s) ~70%
• Multinodular Goiter ~20%
• Toxic Adenoma (nodule) ~ 5%
• Non Goitrous causes:
– Thyroiditis
– Thyroid hormone use

56. Graves’ Disease
(Toxic Diffuse Goiter)

57. Toxic Multinodular Goiter
Hormone secretion by
normal follicles
Thyroid Gland
Euthyroid State Hyperthyroidism
Hormone secretion
by Autonomous Follicles
TSH
Normal Range
of T4/T3

58. Toxic Adenoma (Nodule(
• Clinical Features & Diagnosis
– Solitary nodule on exam, usually >2.5 cm
– Other stigmata of Grave’s Disease absent
– No lab test is specific for toxic adenoma goiter
– RAIU usually elevated (4 / 24 hour uptake %(
– Thyroid Scintigraphy reveals a solitary hot nodule
– Thyroid Ultrasound reveals a solitary nodule

59. Treatment of Hyperthyroidism
• Anti-thyroid Drugs
– Methimazole
– Propylthiouracil
• Radioactive Iodine
• Surgery

60. Cervical Mass

61. Non-thyroidal Cervical Masses
• Lymphadenopathy
• Thyroglossal duct cyst
• Brachial cleft cyst
• Metastatic or locally invasive malignant tumors
• Lymphoma
• Teratoma
• Sarcoma

62. Enlarged Thyroid Gland - Goiter
Diffuse
– Autoimmune disease
– Simple/Colloid goiter
– Iodine deficiency
– Endemic – > 5% of the population in the endemic region
(iodine deficiency or exposure to environmental goitrogens)
– Biosynthetic defects
Multinodular (up to 12% of adults)
– Nontoxic
– Toxic
Single nodule

63. Thyroid Nodule
• The main concern is to exclude the possibility of
thyroid cancer even though the vast majority of
nodules are benign
• In patients less than 20 years old, and in cases of a
high clinical suspicion for cancer the patients
should be offered hemi-thyroidectomy regardless of
the results of FNA

64. Thyroid Tumor
• Tumors of the Follicular Epithelium 96%
– Follicular adenoma 2%
– Papillary carcinoma 75%
– Follicular carcinoma 16%
– Anaplastic carcinoma 3%
• Tumors of Nonfollicular Origin 4%
– Medullary carcinoma 3%
– Metastatic or locally invasive malignant tumors
– Lymphoma
– Histiocytoma

65. Thyroid Tumor
Treatment
• Extensive surgery (near-total thyroidectomy)
• (Selective lymph node dissection)

66. Thyroid Disorders - Summary
• Patients with thyroid disease are usually referred for
evaluation because of abnormal thyroid function
tests.
• Disorders of thyroid gland function result primarily
from autoimmune processes.
• Thyroid nodules are relatively common; although
most of them are benign, a thorough evaluation
should be carried out in order to rule out
malignancy.

67. THANK YOUTHANK YOU