Thyroid, parathyroid, pituitary Flashcards
Causes of primary hyperthyroidism
- Diffuse enlargement of thyroid
- Toxic multinodular goitre
- Toxic adenoma
Grave’s disease
basics,, antibodies involved
M/C cause of endogenous hyperthyroidism 👱🏽♀️ > 👨🦰 20-40 year olds Type II hypersensitivity reaction Antibody mediated: 1. Anti-thyroid stimulating immunoglobulin 2. LATS (long acting thyroid simulator)
Grave’s disease
Associated with genes
Autoimmune etiology CTLA4 PTPN 22 HLA DR3 HLA B8
Grave’s disease
Clinical triad
- Hyperthyroidism
- Infiltrative ophthalmopathy
- Infiltrative dermopathy
Grave’s disease
Gross and microscopic features
Gross: symmetrically enlarged meaty/beefy red
H&E:
1. Hyperplastic follicles
2. Formation of papillae (absence of core)
3. Scalloping of colloid (whitish area along the cuboidal epithelium where it takes the shape of epithelium)
Multinodular goitre
Gross: multiple nodules filled with colloid HPE: 1. Follicles of various sizes 2. Filled with colloid 3. Degenerative changes: • calcification • hemosiderin laden macrophages • cystic changes
Hypothyroidism
Basics
Two types:
1. Primary
2. Secondary
M/C cause of hypothyroidism: iodine deficiency
M/C of hypothyroidism in iodine sufficient areas of the world: Hashimoto’s thyroiditis
Hashimoto’s thyroiditis
pathogenesis
Autoimmune etiology Genetic: • CTLA 4 • PTPN 22 Antibody mediated: • anti TPO Ab • anti microsomal Ab • anti- thyroglobulin Ab Clinically: Hashitoxicosis ➡️ hypothyroidism
Hashimoto’s thyroiditis
gross & microscopic features
Diffuse enlargement of thyroid gland
HPE:
1. Lymphoid follicles with terminal centers:
Struma lymphomatosum
2. Hurthle cell/ oncocytic change:
• Cells with abundant granular, eosinophilic cytoplasm
• Excess of mitochondria
Complications of Hashimoto’s disease
🔼 risk of developing:
- Papillary carcinoma of thyroid
- Extranodal marginal B cell lymphoma
Subacute lymphocytic thyroiditis
Occurs in 🤰 Self limiting HPE: 1. Predominance of lymphocytes 2. Absence of Hurthle cell change
De Quervain’s thyroiditis
or
Granulomatous thyroiditis
Painful thyroid
Following viral infections
Self limiting
HPE: granulomas & lymphocytes
Reidel’s thyroiditis
Sony hard thyroid gland due to fibrosis
D/D for thyroid malignancy
Thyroid tumors
types
1. Benign: Follicular adenoma 2. Malignancy: • papillary • follicular • medullary • anaplastic 3. Lymphoma
Criteria to predict malignancy in a thyroid nodule
- Solitary
- Solid
- Young male
- Cold nodule
- Previous history of radiation ☢️ exposure
Follicular adenoma
Benign thyroid tumor
HPE: large no of follicles with scanty colloid
Papillary malignant thyroid carcinoma
basic features
M/C thyroid malignancy Best prognosis From follicular cells Metastasis: lymphatic Genetics: 1. BRAF: M/C 2. RET-PTC
Risk factors for papillary thyroid carcinoma
- Radiation ☢️ exposure
- Thyroglossal cyst
- Hashimoto’s thyroiditis
Papillary carcinoma of thyroid
microscopic features
- Papillae with fibrovascular core
- Lined by cells with orphan Annie eye nucleus (optically clear nuclei)
- Nuclear pseudoinclusions
- Nuclear grooves: coffee ☕️ bean nuclei
- Psamomma bodies
Tumour that show nuclear grooves
- Papillary carcinoma of thyroid
- Granulosa cell tumour
- Brenner’s tumour
- Langerhan’s cell histiocytosis
Variants of papillary carcinoma of thyroid
1. Follicular variant: Cells arranged in follicles but nuclear features are those of papillary carcinoma 2. Tall cell variant 3. Columnar cell variant 4. Papillary microcarcinoma 5. Dense sclerosing variant
Follicular carcinoma of thyroid
basics
From follicular cells Hematogenous metastasis Genetics: 1. K-RAS 2. P13K Risk factors: 1. Iodine deficiency 2. Multinodular goitre
Follicular carcinoma of thyroid
microscopy
Cells arranged in follicles
📝: Capsular/ vascular invasion is useful in differentiating follicular adenoma from carcinoma ➡️
FNAC is not useful for diagnosis (capsule/ blood vessel specimen not taken)
H&E: gold standard for diagnosis
Medullary carcinoma of thyroid
cells, metastasis
From para follicular cells/ C cells of thyroid
Both hematogenous & lymphatic metastasis
Medullary thyroid carcinoma
🧬
Ret gene on chromosome 10: 1. Sporadic: Unilateral Adults Poor prognosis 2. Familial: Bilateral Multicentric MEN 2 syndrome
Medullary carcinoma of thyroid
Microscopy & tumour markers
H&E:
• spindle cells
• A cal amyloid
Tumour marker: calcitonin
CEA carcinoembyronic antigen: marker for calcitonin negative medullary carcinoma
To confirm diagnosis: Congo red stain for amyloid shows 🍏 birefringence
Anaplastic carcinoma of thyroid
basic features
Least common
Worst prognosis
From follicular cells
Both hematogenous and lymphatic metastasis
🧬 : p53
Usually, arises in the setting of papillary carcinoma
Anaplastic carcinoma of thyroid
microscopy
H&E: pleomorphic cells like
- Spindle cells
- Sarcomatoid cells
- Giant cells
Malignant lymphoma of thyroid
Elderly female
Cold nodule
Risk factor: Hashimoto’s thyroiditis
Eg. of MALToma
Water clear cells
Abundant glycogen deposition ➡️ produces clearing
Functions of parathyroid gland
Ca2+ homeostasis, 🔼
- Renal tubular reabsorption of Ca2+
- Conversion of vit D to active form in kidney
- Urinary PO4 excretion
- GIT Ca2+ abortion
Disorders of parathyroid
- Hyperparathyroidism
- Hypoparathyroidism
- Mass lesion
Causes of primary hyperparathyroidism
1. Parathyroid adenoma 85-90 % 2. Hyperplasia 5-10 % 3. Carcinoma <1 % Rare Criteria for diagnosis: metastasis
Primary hyperparathyroidism
pathology
- Cyclin D1 🧬 inversion
- 🔼 expression of cyclin D1
- 🔼 cellular proliferation
- Adenoma
OR - Mutation in MEN I 🧬
- 🔼 expression of menin
Difference between parathyroid adenoma and hyperplasia
Adenoma:
Solitary lesion involving single gland, but encapsulated
Hyperplasia:
Involves all 4 parathyroid glands, usually symmetrically.
Sometimes, 🔼 water clear cells
Microscopically, both are same
Microscopic features of parathyroid adenoma and hyperplasia
- Sheets/ cords of chief cells, central nuclei are round to polygonal
- Sometimes 🔼 in oxyphil cells ➡️:
Oxyphil adenoma/ Hurthle cell adenoma
Clinical features of hyperparathyroidism
- Painful 😣 bones 🦴
- Renal stones (➡️ pain)
- Abdominal groans
- Psychic moans: depression, anxiety, …
Bone manifestations of hyperparathyroidism
- Osteoporosis
- Osteitis fibrosa cystica
- Brown’s tumour
Brown’s tumour
Cortical bone in parathyroid disorders ➡️
osteoclasts move through medullary cavity ➡️
Rail Road lesion/ dissecting osteitis
Accumulation of hemosiderin laden macrophages ➡️ some reparative lesions/ reactive bone formation ➡️ brown’s tumor
Secondary hyperparathyroidism
Due to prolonged hypocalcemia
M/C cause chronic renal failure
Other causes: vit D deficiency, malabsorption
Reversible
Tertiary hyperparathyroidism
Parathyroid bd starts producing PTH even with hypocalcemia treatment autonomously ➡️ 🔼 PTH
Acidophils of pituitary
Somatotrophs
Lactotrophs
Basophils of pituitary
C. Corticotrophs
B. Basophilic cells
T. Thyrotrophs
Gonadotrophs
Pituitary adenoma
basics
M/C pituitary tumour
M/C type: prolactinemia (amenorrhea + galactorrhea)
Distinguished from carcinoma via metastasis only
Classification of pituitary adenomas based on cells involved
1. Corticotrophic: Cushing’s and Nelson’s syndrome 2. Somatotrophic: acromegaly, gigantism 3. Lactotrophic: prolactinemia 4. Mammosomatotrophic: acromegaly, gigantism, hyperprolactinemia 5. Thyrotrophic: hypo & hyperthyroidism 6. Gonadotrophic: hypogonadism, mass effect
Pituitary adenoma classification:
• radiologically
• functionally
Microadenoma: <1 cm
Macroadenoma: >1 cm
Functional
Non-functional
Microscopic and gross features of pituitary adenoma
- Round to polygonal monomorphic cells
- Sparse supportive connective tissue
- Cellular monomorphism
- Absence of significant reticulin network
Grossly: soft, well circumscribed
Craniopharyngioma
Arises from Rathke’s pouch 3-4 cm encapsulated tumour Pressure effects on optic chiasma Gross: cyst with yellow/ brown oil ‘machine oil’
Features of adenomatous craniopharyngioma absent in papillary craniopharyngioma
Adenomatous craniopharyngioma is seen in children unlike papillary (adults)
- Stratified squamous epithelium
- Wet keratin
- Calcitonin
- Cysts
- Reticulin