The document provides information on the thyroid gland, including its anatomy, histology, physiology, pathology, and disorders. Some key points: - The thyroid is one of the earliest endocrine organs to develop. It is located in the neck and weighs 15-25 grams. - Graves' disease is the most common cause of hyperthyroidism. It is characterized by the triad of thyrotoxicosis, ophthalmopathy, and dermopathy due to autoantibodies that mimic TSH. - Hypothyroidism is most commonly caused by Hashimoto's thyroiditis, an autoimmune disorder characterized by lymphocytic infiltration and antibody production. Clinical manifestations range from mild to

1. APRIL. 19. 2015
Thyroid Gland

2. Thyroid gland
• Anatomy
• Histology
• Physiology
• Pathology
• Hyperthyroidism
• Hypothyroidism
• Tumors
April . 12. 2015

3. 15-25
grams

4. Earliest endocrine organs to
differentiate
• Thyroid; 1st ph. Pouch
• Thymus & Inf. Para. G; 3rd
ph. Pouch
• Sup. Para. G; 4th ph.pouch
• Remnants;
• Arrested descent
• Thyroglossal duct – cyst
• Inferior part – pyramidal
lobe
Foramen Caecum
Lingual thyroid
Tongue
Thyroglossal duct
Hyoid boneThyrohoid
membrane
Thyroid cartilage
Cricoid cartilage
?
Thyroid gland

7. Arteries; Superior and inferior thyroid arteries
Veins; Superior, middle, and inferior thyroid veins
Lymphatics; Periglandular, prelaryngeal, pretracheal,
paratracheal lymph nodes (level VI)
Nerves; Sympathetic: Superior, middle sympathetic ganglia
Parasympathetic: Vagus nerves
Recurrent laryngeal nerve. External laryngeal nerve
Thyroid gland

9. High mag of thyroid follicles – note Parafollicular or C-Cells (arrows)

10. Examples of results of thyroid function tests
Free T3Free T4TSHThyroid functional state
Euthyroid
Thyrotoxicosis
Myxoedema
Suppressive T4 therapy
T3 toxicity

11. Developmental Abnormalities
Lingual Thyroid;
Midline mass at the base
of tongue
THYROGLOSSAL DUCT CYST

12. Many vegetables are goiterogens, fruits are NOT
Goitrogens; chemical agents
inhibit function of the thyroid
gland.
Suppress T3 and T4 synthesis,
so the level of TSH increases,
&t hyperplastic enlargement of
the gland (goiter) follows.

13. Anti-thyroid autoantibodies
 Anti-thyroid peroxidase Abs; Hashimoto`s thyroiditis &
Grave’s disease.
 TSH receptor Abs; (two forms)
• 1. An activating Abs “TSI” (associated with
hyperthyroidism); TSH receptor activating Abs are
characteristic of Graves Disease (in 90% of patients).
• 2. A blocking antibody (associated with thyroiditis);
These competitively inhibit the binding of TSH to its
receptor.
 Anti-Thyroglobulin Abs; found in most people with
Grave’s disease and nearly all with Hashimoto’s
thyroiditis).
• They are commonly used to monitoring thyroid cancer
following thyroidectomy.

14. Tests of Thyroid Function
1. Serum Thyroid-Stimulating Hormone (TSH) (Normal 0.5–5
U/mL)
2. Total T4 (55–150 nmol/L) & T3 (1.5–3.5 nmol/L)
3. Free T4 (12–28 pmol/L) & Free T3 (3–9 pmol/L)
4. Thyroid Antibodies:
5. Thyroid antibodies include: antibodies against thyroid
peroxidase (TPO), anti-thyroglobulin antibodies & TSH
receptor antibodies
6. Serum Thyroglobulin: The most important use is in
monitoring patients with differentiated thyroid cancer for
recurrence, particularly after total thyroidectomy & RAI
ablation.
7. Serum Calcitonin (0–4 pg/mL Basal): It is also a sensitive
marker of Medullary Thyroid Carcinoma.

15. Tests of Thyroid Function
• Images techniques:
X – Ray
U/S
CT Scan
MRI
PET
RAI uptake (Scan), (I-123) or technetium (99mTc)
• FNA
• Biopsy

16. • The thyroid scan is used to determine the size, shape & position of the thyroid
gland
• A whole-body thyroid scan is typically performed on people who have had
thyroid Ca. It detects the recurrence & spread of thyroid Ca.

17. Normal Thyroid Scan Cold nodule in left lobe

19. PET/CT scan of the neck. Axial
images through the thyroid
gland on
A) A CT-scan
B) A 18F-FDG PET scan &
C) A fused 18F-FDG PET & CT
scan.
A heterogeneous thyroid
(arrows) is located in a CT scan
in panel. A.
Diffuse accumulation of 18F-
FDG (arrows) is seen
throughout the thyroid in panel.
B.
Fusion of the CT scan & 18F-FDG
PET scan confirms that the
entire thyroid is
hypermetabolic.

20. Disorders Associated with Thyrotoxicosis
Associated with Hyperthyroidism
Primary
• Diffuse hyperplasia (Graves disease)
• Hyperfunctioning (“toxic”) multinodular goiter
• Hyperfunctioning (“toxic”) adenoma
• Iodine-induced hyperthyroidism
• Neonatal thyrotoxicosis associated with maternal Graves disease
Secondary
TSH-secreting pituitary adenoma (rare)
Not Associated with Hyperthyroidism
Granulomatous (de Quervain) thyroiditis (painful)
Subacute lymphocytic thyroiditis (painless)
Struma ovarii (ovarian teratoma with ectopic thyroid)
Factitious thyrotoxicosis (exogenous thyroxine intake)

21. Hyperthyroidism
Clinical Course.
 Hypermetabolic state.
 Overactivity of the SNS
(increase in the β-adrenergic “tone”).

22. Hyperthyroidism
 Increase BMR
• The skin
• Sweating
• Weight loss despite increased appetite.

23. Hyperthyroidism
• Cardiac manifestations
• Elevated cardiac contractility and cardiac output, in
response to increased peripheral O2 requirements.
• Tachycardia, palpitations.
• Arrhythmias, particularly Atrial fibrillation.
• Congestive HF.
• Cardiomegaly

24. Hyperthyroidism
Over activity of Sympathetic Nervous System;
• Tremor, hyperactivity, emotional labile, anxiety,
inability to concentrate, insomnia.
• Thyroid myopathy; Muscle weakness and decreased
muscle mass.
• GIT, hypermotility, diarrhea, & malabsorption

25. Hyperthyroidism
• Ocular changes;
• Staring gaze
• lid lag
• Proptosis (only in Graves
Dis)

26. Hyperthyroidism
• The skeletal system.
• Increased bone resorption & risk of Osteoporosis & fractures
• Atrophy of skeletal M.
• Minimal liver enlargement due to fatty changes in the hepatocytes;
• generalized lymphoid hyperplasia & lymphadenopathy in Graves disease.
 Thyroid storm
 Apathetic hyperthyroidism

27. Diagnosis of hyperthyroidism
• Both Clinical and laboratory findings.
• A low TSH value
• High free T4.
• RAI uptake by the thyroid gland.

28. Graves disease
• The most common cause of endogenous
hyperthyroidism.
• Characterized by a triad of clinical findings:
• • Hyperthyroidism associated with diffuse
enlargement of the gland
• • Infiltrative ophthalmopathy with resultant
exophthalmos
• • Localized, infiltrative dermopathy, (pretibial
myxedema, which is present in a minority of
patients

29. Pathogenesis of Graves disease
• Autoantibodies against multiple thyroid
proteins, most importantly the TSH
receptor.
• Thyroid stimulating immunoglobulin
(TSI) Abs, in 90% of patients.

30. Graves ophthalmopathy
• Exopthalmos, protrusion of the eyeball is associated with;
increased Vo. Of retroorbital CT & extraocular M., for several
reasons;
• (1) infiltration of retroorbital space by mononuclear cells;
• (2) inflammation, edema and swelling of extraocular M;
• (3) accumulation of ECM, glycosaminoglycans such as
hyaluronic acid and chondroitin sulfate;
• (4) increased numbers of adipocytes (fatty infiltration).
• These changes displace the eyeball forward and can interfere
with the function of the extraocular muscles.

31. The thyroid gland is symmetrically enlarged due
to diffuse hypertrophy and hyperplasia of thyroid
follicular epithelial cells
Graves disease

34. Graves disease

35. Graves Disease
• SUMMARY:
■ Graves disease, the most common cause of endogenous
hyperthyroidism,
• characterized by the triad of thyrotoxicosis, ophthalmopathy,
and dermopathy.
• ■ It is an autoimmune disorder caused by activation of thyroid
epithelial cells by autoantibodies to the TSH receptor that
mimic TSH action (thyroid-stimulating immunoglobulins).
• ■ The thyroid in Graves disease is characterized by diffuse
hypertrophy and hyperplasia of follicles and lymphoid
infiltrates;
• glycosaminoglycan deposition and lymphoid infiltrates are
responsible for the ophthalmopathy and dermopathy.
• ■ Laboratory features include elevations in serum free T3 and
T4 and decreased serum TSH.

36. G
O
I
T
E
R

37. Causes of Hypothyroidism
Primary
Iodine deficiency*
Autoimmune hypothyroidism
Hashimoto thyroiditis*
Postablative
Surgery, radioiodine therapy, or external irradiation
Genetic defects in thyroid development (PAX8, FOXE1, TSH receptor
mutations) (rare)
Thyroid hormone resistance syndrome (THRB mutations) (rare)
Drugs (lithium, iodides, p-aminosalicylic acid)*
Congenital biosynthetic defect (dyshormonogenetic goiter) (rare) *
Secondary (Central)
Pituitary failure (rare)
Hypothalamic failure (rare)

38. Autoimmune hypothyroidism
• The most common cause of hypothyroidism in
iodine-sufficient areas of the world.
• The majority are due to Hashimoto thyroiditis.
• antimicrosomal, antithyroid peroxidase, and
antithyroglobulin antibodies,
• goitrous
• can occur in isolation or in conjunction with
autoimmune polyendocrine syndrome.

39. • Myxedema is applied to hypothyroidism developing
in the older child or adult.
• Early symptoms; Dry skin, brittle hair, depression,
wt. gain, constipation, increased sensitivity to cold ,
weakness, Heavy menstruation, joint & M. pain.
• Late symptoms;, Puffy face, hands & feet, Slow
speech, Thickening of the skin.
• Myxedema coma; medical emergency, thyroid
hormones becomes very low.
Hypothyroidism

40. Cretinism

43. THYROIDITIS
• Hashimoto (Auto-Immune) (Lymphoid follicles
with germinal centers), MOST COMMON cause
of acquired hypothyroidism in USA
• Subacute Granulomatous (DeQuervain)
• Subacute Lymphocytic (just like Hashimoto’s but
NO fibrosis and no germinal centers), often
post-partum

44. Hashimoto thyroiditis. The thyroid parenchyma contains a dense
lymphocytic infiltrate with germinal centers. Residual thyroid follicles lined
by deeply eosinophilic Hürthle cells are also seen.

48. G
O
I
T
E
R

49. GOITERS
(diffuse or nodular)
• IODINE deficiency**
• Associated with HYPO thyroidism**
eventually, NOT hyperthyroidism
• Increased TSH
• Goitrogens vegetables.

50. Etiology of Nontoxic Goiter
ClassificationSpecific etiology
Iodine deficiency, dietary goitrogens
(cassava, cabbage)
Endemic
Iodide, amiodarone, lithiumMedications
Subacute, chronic (Hashimoto's)Thyroiditis
Dyshormonogenesis - genetic defect. (Impaired
hormone synthesis from enzyme defects)
Familial
Adenoma, carcinomaNeoplasm
Goiter

51. Physiological goiter:
Endemic goiter; The occurrence of a goiter in a significant
proportion of individuals in a particular geographic regions
due to dietary iodine deficiency.
Goiter

52. Goiter
Colloid goitre; A colloid goitre is a late stage of diffuse hyperplasia
when TSH stimulation has fallen off & when the follicles are
inactive & full of colloid

53. Multinodular goiter. A, Gross morphology nodular gland, containing areas of
fibrosis and cystic change. B, Photomicrograph of a hyperplastic nodule, with
compressed residual thyroid parenchyma on the periphery. Note absence of a
prominent capsule, a distinguishing feature from follicular neoplasms

54. “NODULES”
• Solitary vs. Multiple
• Younger vs. Older
• Male vs. Female
• Hx. neck radiation vs. NO Rx.
• “Cold” vs. HOT (really NOT-cold)

55. Thyroid Neoplasms
• “Nodules” vs. true neoplasms
• Adenomas vs. Carcinomas

56. NEOPLASMS
• ADENOMAS
– FOLLICULAR
– HÜRTHLE (oxyphilic)
• CARCINOMAS
– FOLLICULAR
– PAPILLARY
– MEDULLARY (AMYLOID)
– ANAPLASTIC (worst)

57. • Risk factors for malignancy;
• Ionizing radiation.
• Sex; women 3 times > than men.
A discrete swelling in male is much more likely to be
malignant than in a female.
• Family history;
Medullary (MEN2) syndromes) &
Non-medullary thyroid cancer (familial cancer
syndromes e.g. Cowden's syndrome; has high risk of
breast, thyroid, endometrium, colorectal & skin
tumors.
• Investigations; TFTs, Autoantibody titers, Isotope
scan, U/S & CT, MRI, FNA & Biopsy.

58. Hyperfunctional thyroid adenoma

59. Follicular adenoma of thyroid.
A, A solitary, well-circumscribed
nodule.
B, well-differentiated follicles
resembling normal thyroid
parenchyma

62. HÜRTHLE CELL ADENOMA, note “atypia”

63. CARCINOMAS
• Papillary carcinoma (>85% of cases)
• Follicular carcinoma (5% to 15% of cases)
• Anaplastic (undifferentiated) carcinoma (<5% of
cases)
• Medullary carcinoma (5% of cases)

64. Follicular carcinoma.
A, Cut surface of a follicular
carcinoma with substantial
replacement of the lobe of
the thyroid. The tumor has
a light tan appearance and
contains small foci of
hemorrhage.
B, A few of the glandular
lumens contain
recognizable colloid.

65. Capsular integrity in follicular neoplasms. adenomas (A),
follicular carcinomas demonstrate capsular invasion (B, arrows) that may be minimal, or wide
The presence of vascular invasion is another feature of follicular carcinomas

66. Thyroid; Follicular ca.
invasion or metastases is the only evidence of malignancy.

67. Papillary neoplasms do NOT usually look uniform on cut surface.

68. Papillary carcinoma of the thyroid

69. Papillary thyroid Ca.

71. ORPHAN ANNIE CELLS in PAPILLARY CARCINOMA

72. Anaplastic carcinoma of the thyroid

73. MEDULLARY CARCINOMA of the thyroid with “HYALINIZATION”, i.e., AMYLOID!!!

74. HYALINIZATION showing APPLE GREEN birefringence in CONGO RED stain, i.e., AMYLOID

75. Fine Needle Aspiration Cytology
•FNAC is a safe, sensitive & specific
technique.
•An excellent screening test for thyroid
swellings
•Diagnosis can be achieved in a majority
of cases.
•Thyroid papillary carcinoma ;
•(a) FNAC smear showing intra-
nuclear cytoplasmic inclusions
(black arrow) & nuclear grooves
(red arrow).
•(b) Histopathology section
showing intra-nuclear cytoplasmic
inclusions (black arrow) and
nuclear grooves (red arrow)
•© ground glass nuc. (blue arrow).

76. • A discrete swelling in an otherwise impalpable gland is termed
isolated or solitary. Conditions presenting as Solitary thyroid
nodule are;
1. Dominant nodule of multinodular goiter
2. Thyroid adenoma (30-40%)
3. Thyroid cyst
4. Thyroid carcinoma (10 - 15%)
5. Localised form of thyroiditis
6. Colloid nodule
• (Incidental nodules).
Solitary thyroid nodule