1. The endocrine systemic disease
Li xiao yun 李晓昀

2. Thyroid gland disease

3. A. Introduction Hypothalamus (TRF) + - Pituitary (TSH)
Pituitary (TSH)
Thyroid gland (T3,T4)

4. 1. Anatomy and histology of thyroid gland
Thyroid consists of two bulky lobes.
Weight: 15~20 gram; color: red-brown.
Histologic basic unite is thyroid follicle lined by single layer of cuboidal epithelial cells.
Follicular lumina contain colloid ,which is accumulating thyroglobulins(TG) secreted by follicular cells.

5. Follicular cells produce and secrete the thyroid hormone.
Parafollicular cells ,located between follicles or between follicular cells, secrete calcitonin.

8. 2. Physiologic function of thyroid hormone—T3 and T4
Enhancement of basal metabolic rate and the nervous system excitability.
Promotion of growth and development.
Great influence on growth of skeleton and central nervous system especially in the fetal and infant period.

9. 3. Classification of thyroid gland diseases
Most of thyroid gland diseases are usually more common in women than in men
Thyroid tumor
Goiter
Thyroid inflammation

10. B. Thyroid tumor 1. Thyroid adenoma
Benigh tumor derived from thyroid follicular epithelium
Grossly:
Solitary,spherical nodule with intact capsule,and 1~10 cm in diameter.
The nodule may compress adjacent thyroid tissue.

11. The cut surface is gray–white or red-brown,depending on the colloid content of adenoma .
The tumor lesion may have hemmorage,fibrosis, calcification ,and cystic change.

12. Slide 26.13

13. Microscopy:
(1). Embryonal adenoma:Tumor cells are small and closely packed to form cords or trabeculae,while follicles are seldom formed.
(2). Fetal adenoma : Tumor tissue resembles fetal thyroid tissue. Tumor lesion is mainly composed of small and uniform-appearing follicles with a tiny amount of colloid. Follicular cells are cuboidal

14. (3). Simple adenoma: Tumor mainly consists of follicles
(3). Simple adenoma: Tumor mainly consists of follicles.The size and colloid content of follicles are similar to those of normal thyroid follicles.
(4). Colloid adenoma: Tumor mainly consists of large,colloid-rich follicles lined by flattened epithelial cells.Follicles may be not the same in size,sometimes merge into cystides.

16. Slide 26.14

19. (5). Acidophilic cell adenoma: Seldom.
Tumor cells are large, polygonal, eosinophilic, and contain abundant cytoplasm.There are eosinophilic granules within cytoplasm.Cells form cords or sheets,while follicle are seldom formed.

21. 2. Thyroid carcinoma
Malignant tumor derived from thyroid follicular epithelial cells or parafollicular cells,often accompanied by hemmorage, necrosis,fibrosis,calcification or cystis formation.

22. Pathologic classification
Papillary carcinoma:60-70%
Follicular carcinoma:20%
Medullary carcinoma:5%
Undifferentiated carcinoma:15%

23. (1) Papillary carcinoma
Grossly:
Tumors are usually solitary,spherical and firm lesions with 2~3cm in diameter.
The cut surface is gray-white,and sometimes papillary foci may be seen.
Most tumors have no capsules,but their circumscriptions are still recognizable.

24. Microscopy:
Tumors mainly consists of a large number of papillae with many branches.
There is fibrovascular stalk within papilla.
Tumor nuclei are ground-glass:
loose chromatins,unclear nucleolus,big and empty nucleus.
A single to multiple layers of cuboidal epithelial cells covering the papillae arrange disorderly, and are obviously atypical.
Calcified structures termed psammoma bodies are often present within tumor stroma,especially within the stalks of papillae.

27. Slide 26.16

28. Behavior:
slow growth,
low grade malignant
good prognosis
regional lymphoid nodule metastasis
5-year survival rate:90%
10 -year survival rate:85%

29. (2)Follicular carcinoma
Grossly:
Most tumors are single, well circumscribed nodules,and capsules are usually not intact.The cut surface is gray-white.

30. Slide 26.17

31. Microscopy:
The tumor lesions have different differentiation degree of follicles,but no papillae.The nuclei lack ground-glass features.

32. Well-differentiated carcinoma
It resembles thyroid adenoma,but capsules and blood vessels have been invaded by tumor cells.
Tumor cells form many follicles,cell atypia is relatively less obvious.

34. Slide 26.18

35. Poor-differentiated carcinoma
Tumor cells are apparently atypical and form solid nests or sheets,while follicles are less seen and usually not intact.

38. Behavior: Middle grade malignant Early bloodstream metastasis
5-year survival rate: 30-40%

39. (3). Medullary carcinoma:
Malignant tumors derived from parafollicular cells, APUD tumor.Tumor cells secrete calcitonin and other hormones.

40. Grossly :
Tumors can arise as solitary nodules or multiple lesions and may have fake capsules.The cut surface is gray-white or tan, and the consistency is soft.

41. Slide 26.19

42. Microscopy:
Tumors are composed of round, polygonal or spindle cells,which may form solid nests or sheets. Pink amyloid deposits are often present in tumor stroma.Electron microscopy reveals variable number of nervous endocrine granules within cytoplasm.

43. Slide 26.20

46. Slide 26.21

47. Behavior:
Middle grade malignant
5-year survival rate:50%

48. (4)Undifferentiated carcinoma:
Grossly:
Tumors are massive,ill-circumscribed nodules without capsules,and surrounding tissues are invaded by tumor cells. The cut surface is gray-white. Hemorrhage and necrosis often occur in tumor lesions.

49. Microscopy:
Tumors mainly consist of highly anaplastic cells,including 3 types of pathological classification.
(Anaplasia: malignant tumor cells lack differentiation and show high atypia.)

50. Small cell type:
Tumor cells are small and similar to lymphocytes,closely arranging to form nests or cords with some abortive follicles.

52. Spindle cell type :
Tumor cells are spindle and resemble fibrosarcoma cells , so this type should be distinguished from sarcomas.

54. Giant cell type:
Tumor cells are giant and often multinuclear.

56. Behavior: High grade malignant Rapid growth
Early infiltration and metastasis
Most cases die within 2 years.

57. C . Goiter
Thyroid enlargement due to non-tumor hyperplasia

58. Nontoxic goiter (Endemic goiter)
Definition :
The deficient secretion of thyroid hormone leads to a compensatory rise in serum TSH level,which ,in turn,causes hyperplasia of thyroid follicular epithelia and colloid accumulation,and ultimately gross enlargement of the thyroid gland,usually without hyperthyroidism.

59. Clinical symptom: The enlargement of thyroid gland in neck.
Excessive enlargement may compress surrounding structures of thyroid gland and cause the difficulties in swallow and breath.

60. Etiology and pathogenesis
(1) Iodine deficiency .
TSH epithelium hyperplasia
thyroid hormone
Iodine gland
Deficiency enlargement
thyroglobulin within
follicular lumina can’t iodinate
and then can’t be resorbed by
epithelia colloid accumulation within follicles

61. (2) goitrogenic factions:
(3) Heredity and immunology

62. Pathologic changes:
(1) Hyperplastic stage (diffuse hyperplastic goiter)
Grossly:
The thyroid gland is diffusely, bilaterally,symmetrically and moderately enlarged,the gland rarely exceeds 150 gram,and the surface is smooth.

63. Microscopy:
Follicular epithelial cells proliferate and become cuboidal or low and columnar, sometimes forming small follicles and fake papillae.
Follicular lumina contain less colloid,and stroma shows hyperemia.

64. (2)Colloid accumulation stage (diffuse colloid goiter)
Involution occurs in this stage.
Grossly:
The gland is diffusely, bilaterally , symmetrically , and conspicuously enlarged ,and the weight is approximately gram.
The surface of gland is smooth,and the cut surface is brown,somewhat glassy, translucent, and colloidal.

66. Microscopy:
The majority of follicular lumina are highly enlarged, containing abundant colloid,and the epithelial cells involute and become flattened.

68. (3) Nodular stage (Nodular goiter)
The recurrent hyperplasia and involution of follicular cells
The formation of fibre interval and nodules

69. Grossly:
Nodular goiters are multinodular, bilaterally, asymmetrically enlarged,which may achieve a weight of more than 2000 gram.
Nodules are not uniform in size and are well-circumscribed, without capsules or with incomplete capsules.
On cut section , hemorrhage, fibrosis, calcification, and cystic change are often seen.

72. Slide 26.12

73. Microscopy: Follicles are not uniform in size.
Partial follicles are highly enlarged and colloid-rich,and the epithelial cells involute and become flattened.
Partial follicular cells proliferate and become columnar or form fake papillae or small follicles.
The hyperplastic connective tissue divide and enclose thyroid tissue to result in the formation of irregular nodules.

75. Results:
Hypofunction of thyroid
Malignant change :1-5%.

76. 2. Diffuse toxic goiter Definition :
Hyperthyroidism: Hyperthyroidism is a clinical syndrome caused by excessive thyroid hormone in serum acting on tissue of the whole body, manifesting the rise of basal metabolic rate and the nervous system excitability.

77. Diffuse toxic goiter (Graves disease, Exophthalmic goiter) :
Conspicuous hyperplasia of thyroid follicular cells makes thyroid gland enlarged,accompanied by hyperthyroidism.
Clinical menifestation:
The enlargement of thyroid, exophthalmia, palpitation, rapid pulse, excitable, easily sweaty ,finger shake,eating too much,easily hungry, emaciated.

78. Pathologic changes: Grossly:
Thyroid gland is usually diffusely, bilaterally, symmetrically enlarged,and its surface is smooth.The cut surface is gray-red or brown and shows meaty appearance.The gland usually weigh more than 80 gram.

80. Slide 26.8

82. Microscopy:
a. Follicular epithelial cells diffusely proliferate and become tall and columnar.The hyperplasia of epithelial cells may result in the formation of fake papillae,small follicles ,or solid cell nests.

83. The colloid within follicular lumen is thin with scalloped margins.
In the interfollicular stroma,there are abundant blood vessels, hyperemia, the infiltration of lymphocytes and the formation of lymphoid follicles.

84. Slide 26.11

85. Etiology and pathogenesis:
An autoimmune disorder produced by autoantibodies to the TSH receptor.
Important Abs include:thyroid-stimulating immunoglobulin(TSI),thyroid growth-stimulating immunoglobulin(TGI).
The two Abs combine with TSH receptors to respectively stimulate excessive secretion of thyroid hormone and the hyperplasia of follicular epithelia.

86. D .Hypothyroidism Definition:
Hypothyroidism is a syndrome caused by deficiency in synthesis and release of thyroid hormone.

87. Classification 1. Cretinism:
Hypothyroidism developing in fetal period ,infancy ,or early childhood results in impaired development of the skeleton system and the central nervous system, characterized by mental retardation,low intelligence,dementia expression,stupid facial features,short stature,and dwarf,and so on.

90. 2. Myxedema:
Hypothyroidism developing in youth or adult results in the decrease of basal metabolic rate and the nervous system excitability and the accumulation of mucoid matrix in stroma.

91. The clinical manifestations include listlessness,fatigue,sleepiness,apathetic expression,mental retardation,intolerant cold,cool and coarse skin, edema,and other symptoms related to mucoid matrix deposition in other different organs.

94. Cause of hypothyroidism:
Thyroid injury: thyroiditis,
thyroid surgery or radiation
Suppressed synthesis of thyroid hormone.
Autoimmune disease
Pituitary or hypothalamus disease.

95. E .Thyroiditis 1. Subacute thyroiditis (Granulomatous thyroiditis):
A granulomatous inflammation usually caused by virus infection.

96. Grossly:
The gland is unilaterally or bilaterally, asymmetrically,lightly enlarged,and may be adherent to surrounding structures.
The cut surface is yellow-white and firm,and may contain areas of necrosis or fibrosis.

97. Microscopy :
Partial follicles are destroyed and then release colloid. Neutrophils, macrophages, lymphocytes,and plasma cells aggregate about collapsed follicles.Macrophages engulf released colloid and then convert into multinuclear giant cells,which results in the formation of granulomas similar to tuberculoma ,but without caseous necrosis.
In later stages, lesions have fibrosis or scar formation,and regeneration of follicular cells.

99. Slide 26.10

100. Clinical manifestation:
Thyroid gland is enlarged and pain.

101. 2. Chronic lymphocytic thyroiditis(Hashimoto’s thyroiditis):
Autoimmune disease.

102. Grossly:
Gland is diffusely enlarged and firm,the cut surface is gray-white or gray-yellow.
Microscopy:
Thyroid gland structure is extensively destroyed,and follicles atrophy and disappear .
In lesion,there are infiltration of a large number of lymphocytes,formation of lymphoid follicles,and hyperplasia of fibers.

103. Slide 26.9

104. Clinical manifestation:
Enlargement of gland
Hypothyroidism(usually in later stage)

105. 3. Fibrous thyroiditis (Chronic woody thyroiditis):
Grossly :
Gland is asymmetrically enlarged, hard as wood, and obviously adherent to surrounding structures.
The cut is pray-white,and show nodular appearance.

106. Microscopy: Atrophy and destruction of the majority of follicles.
Hyperplasia of a large amount of
fibre tissue.
Hyaline change
Scar formation
The infiltration of a tiny number
of lymphocytes

109. Clinical:
Enlargement of gland,hard consistency
Hypothyroidism
Compression symptoms

110. The distinction between adenoma and nodular goiter
Capsule
Intact
Not intact
Nodular number
Usually single
Multinodular,usually bilateral
Structure
Relatively uniform
Not uniform. Follicles of unequal size
Adjacent thyroid tissue
Follicles are compressed and deformed
There are pathologic changes similar to those of nodules,but no compression phenomenon