Endocrine system I (b) Flashcards by Elyaa Saleh

Genetic association of Grave’s diseases?

Association with HLA-DR3 and polymorphisms in genes encoding CTLA-4 and PTPN22

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most common casue of Hyperthyroidism?

Grave’s disease

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Garve’s diseases coexists with what diseases?

SLE, Pernicious Anaemia (Autoimmune gastritis), DM-t1 and Addison’s disease

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Pathogensis of Grave’s disease

caused by the production of IgG autoantibodies directed against the TSH receptor. These antibodies bind to and activate the receptor, causing the autonomous production of thyroid hormones

IgG: Thyroid stimulating immunoglobulin

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Pathogenesis of Graves Opthalamopathy

Infiltrative Ophthalmopathy, due to:
1. T-cell activation –> lymphocytic infiltration in the retro-orbital space
2. ↑ cytokines (e.g, TNF-α, IFN-γ) –>Inflammatory oedema and swelling of extra-ocular muscles
3. Accumulation of extra-cellular matrix components
4. ↑ numbers of adipocytes

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LAB findings of Grave’s disease + raido-iodine scan

1) ↑ serum free T4 and T3
2) ↓ TSH
Radio-iodine scan: increased diffuse radioactive iodine uptake

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Macroscopic Features:
* Symmetrical, Diffuse enlargement of the thyroid gland
* Smooth and soft organ
* Intact capsule

Microscopic Findings:
* Diffuse hypertrophy and hyperplasia of the thyroid follicular epithelial cells
* Tall, columnar and crowded epithelial cells
* Small papillae, without fibrovascular cores
* Pale colloid with scalloped margins within the follicular lumen
* Lymphocytes and plasma cells, and germinal
centers

Features of?

Grave’s disease

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CF of Grave’s disease

Triad of Manifestations
1) Thyrotoxicosis (all cases)
2) Infiltrative Ophthalmopathy –> Exophthalmos
(40% of cases)
3) Localised Infiltrative Dermopathy or Pretibial
Myxoedema (minority of cases): Scaly thickening and induration of the skin

*Exophthalamos : protruding eyes

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cause of Diffuse & Multi-Nodular Goiter

Dietary iodine deficiency

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casues of Sporadic Goiter

Intake of excessive calcium and vegetables
of the Cruciferae family
Hereditary enzymatic defects –> Dyshormogenetic goiter

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Pathogenesis of Diffuse Goiter

TSH-induced hypertrophy and hyperplasia of thyroid follicular cells –> Diffuse, symmetric enlargement of the gland (Diffuse Goiter)

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Pathogenesis of Colloid Goiter

Increase in dietary iodine or decrease in
thyroid hormone demands –> Enlarged colloid-rich
gland (Colloid Goiter)

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Toxic Multi-Nodular Goiter is aka?

Plummer Syndrome

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CF of Plummer Syndrome (Toxic Multi-Nodular Goiter)

1) Airway obstruction
2) Dysphagia (difficulty swallowing)
3) Compression of large vessels in the neck and
upper thorax (Superior Vena Cava Syndrome)

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Progression of Toxic Multi-Nodular Goiter

Rarely malignant (5% of cases)

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Epi of Toxic Multi-Nodular Goiter (Plumer syndrome

females > 60yrs

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cause of Toxic Multi-Nodular Goiter (PLummer Syndrome)

Development of autonomous nodules

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Non-functioning Follicualr Adenomas are asociated with mutations of?

RAS or PIK3CA, or presence of
PAX8/PPARG fusion gene

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Imaging findings of thyroid Follicular Adenomas

1) “warm” or “hot” thyroid nodule –> toxic adenoma
or
2) “Cold” nodules

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Macroscopic Features:
* Solitary, spherical lesion
* Well-defined, intact capsule

Microscopic Findings:
* Uniform follicles, containing colloid
* Occasionally, cells with brightly eosinophilic
granular cytoplasm
* Hallmark –> Intact well-formed capsule;

features of?

Follicular Adenoma (aka Hürthle Cell Adenoma)

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Macroscopic Features:
cut surface: glassy-appearing, Irregular nodules with variable amounts of brown gelatinous colloid; Areas of fibrosis, haemorrhages, calcification and cystic changes

Microscopic Findings:
* Hyperplastic epithelium (early stages)
* Flattened and cuboidal epithelium with
abundant colloid (periods of involution)

features of?

Multi-Nodular Goiter (Plummer syndrome)

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Histo of Hürthle Cell Adenoma (follicular) vs. Carcinoma

Follicular adenoma: intact capsule
Follicular Carcinoma: invades thyroid capsule and vasculature

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CF of Follicular Adenomas (Hurthel cell Adenoma)

Painless nodules
Difficulty in swallowing (larger masses)
Thyrotoxicosis (toxic adenomas)

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prognosis of Follicular Adenomas

good prognosis
(Excellent, with no recurrence or
metastatic potential)

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The 4 major subtypes of Thyroid Carciomas

1) Papillary Carcinoma (**>85%**) 2) Follicular Carcinoma (5-15%) 3) Anaplastic (Undifferentiated) Carcinoma (<5%) 4) Medullary Carcinoma (5%)

Macroscopic Features: * Solitary or multifocal lesions * Variable appearance: **Either well-circumscribed and encapsulated or infiltrative tumors with ill-defined margins** * Possible, areas of fibrosis, calcifications and cystic changes * Cut surface: Granular, sometimes with **distinct papillary foci** Microscopic Findings: * Ground glass or **“Orphan Annie eye” nuclei** * Invaginations of the cytoplasm --> Pseudo-inclusions * Papillary architecture; papillae with dense fibrovascular cores * Presence of **“psammoma bodies”** * Foci of lymphatic invasion features of? | (**Papi** and **Moma** adopted **Orphan Annie**

Papillary carcinoma

CF of Papillary Carcinoma

Painless, palpable mass in the neck (lymph node/thyroid)

Prognosis of Papillary Carcinoma?

Good prognosis (10-year survival --> 95%)

Microscopic Findings: * **Unifrom**, small **follicles** Macroscopic features: * **Invasion of the thyroid capsule** and vasculature * Possible **Hemotogenous spread** features of?

Follicular Carcinoma

Epi of Anaplastic/Undifferentiated carcinomas

Older patients > 65yrs Quarter of patients --> Past history of a well-differentiated carcinoma (**folliclar carcinoma**)

Macroscopic Features: * Bulky mass * **Rapidly enlarging neck mass** --> growth beyond thyroid capsule -> Invasion into adjacent neck structures Microscopic Findings: * Populations of highly anaplastic cells: * Large, pleomorphic giant cells or * **Spindle cells with a sarcomatous appearance** or * **Mixed spindle and giant cell lesions** * Foci of papillary or follicular differentiation features of?

Anaplastic Carcinoma

CF of Follicular Carcinoma

* presentation as **solitary cold thyroid nodules** * **Haematogenous dissemination** to the lungs, bones and liver

Prognosis of Anaplastic Carcinoma

poor prognosis

# *important Medullary Carcinoma are associated with (Type of mutation)?

MEN 2A and 2B (RET mutations)

pathogenesis of Medullary Carcinoma

Neuro-Endocrine Neoplasm --> from Parafollicular "**C** cells" of the thyroid | * "**C** cells" --> produce **C**alcitonin

Macroscopic Features: * Solitary nodule or multiple lesions in both lobes * **Multicentricity**, common in familial cases * Areas of necrosis and haemorrhage and extrathyroidal extension (larger tumours) Microscopic Findings: * **Sheets of Polygonal cells in the Amyloid stroma** * Multi-centric **C cell hyperplasia**, in familial cases features of?

Medullary Carcinoma

Immunohistochemistry of Medullary Carcinoma

Intracytoplasmic **Calcitonin** positivity

CF of Medullary Carcinoma

1) **Mass in the neck**; possible **dysphagia or hoarseness** (sporadic cases) 2) **Diarrhoea**, caused by the secretion of VIP | *VIP : Vasoactive intestinal Peptide

Diagnosis of Familial cases of Medullary Carcinoma

elevated Calcitonin levels or RET mutations

causes of Primary Hyperparathyroidism

* Adenoma [85%-95%] * Primary Hyperplasia (diffuse or nodular) [5%-10%] * Parathyroid Carcinoma [1%]

Genetic predispostion of Primary Hyperparathyroidism

**MEN-1 and MEN-2A**; Germ-line **mutations of MEN-1 and RET**, respectively

cause of Hypercalcaemia

1) **Hyperparthyroidism** (primary, 2,3) 2) Familial Hypercalcaemia 3) Vitamine D toxicity 4) Drugs (Thiazide diuretics) 5) Hypercalcaemia malignancies (**Osteolytic metastases**, PTH related protein mendiated) 6) **Sarcoidosis** 7) Immobilisation

genetic predispostion of Familial Hypocalciuric Hypercalcaemia

Inactivating mutations in the **Calcium-Sensing Receptor Gene (CSRG)** (CSRG)

Macroscopic Features: * **Well-circumscribed**, soft, **tan nodule** * **Delicate capsule** * ***Localisation: Confined to a single gland** * Microscopic Findings: * Composed predominantly of **chief cells** * Rim of compressed, **non-neoplastic parathyroid tissue**, at the **edge**s * Cells with bizarre and **pleomorphic nuclei** (endocrine atypia) * **Absence of adipose tissue** Features of?

Parathyroid Adenoma (caused by primary Hyperparathyroidisim)

Microscopic Findings: * **Chief cell hyperplasia** * Diffuse or multinodular pattern * **Absence of adipose tissue within hyperplastic foci** * **“Salt and pepper"** like chromatin of the nuclei Features of?

Parathyroid Hyperplasia (caused by Primary Hyperparathyroidism)

Macroscopic Features: * **Gray-white**, homogenous appearnace Microscopic Findings: * Usually **uniform; Pleomorphism** may be noted * **Nodular or trabecular patterns** * Dense **fibrous capsule**, around the tumour * Prominent cellular Atypia Definitive Criteria for Diagnosis: * **Invasion of surrounding tissues and metastasis** features of?

Parathyroid Carcinoma (caused by Primary Hyperparathyroidism)

Lab findings of Primary Hyperparathyroidism

1) Increased serum ionized calcium (**Hypercalcemia**) 2) **Hypophosphataemia** 3) Increased urinary excretion of calcium and phosphate (**Hypercalciuria**)

CF of Primary Hyperparathyroidism

* Painful **bones** * Renal **stones** * Abdominal **groans** * Psychic **moans** | * Stones, Bones, Groans, Psychiatric overtones"

what is Osteitis Fibrosa Cystica

Cystic **bone** spaces filled w/ Brown fibrous tissue (**"Brown tumour"**)

Osteitis Fibrosa Cystica is composed of?

"Brown tumour": --> osteoclasts, reactive giant cells and haemorrhagic debris

Osteitis Fibrosa Cystica is assciated with?

primary Hyperparathyroidism

causes of Secondary Hyperparathyroidism

Renal failure

patho of Secondary Hyperparathyroidism

Chronic renal insufficiency --> Decreased phosphate excretion --> **Hyperphosphataemia (↑PO-3)** --> **Declined serum calcium levels (↓ Ca+2)** --> Stimulation of parathyroid gland activity

Macroscopic Features: * Hyperplastic parathyroid glands Microscopic Findings: * **Increased number of chief cells**, in a diffuse or multinodular pattern * **Decreased number of fat cells (Adipose cells)** * **Metastatic calcification** in many tissues (e.g. lungs, heart, stomach, blood vessels) features of ?

Secondary Hyperparathyroidism

Lab findings of Secondary Hyperparathyroidism

Near normal serum calcium levels

CF of Secondary Hyperparathyroidism

1) Manifestations of **Chronic renal failure** 2) Metastatic calcification of blood vessels --> Ischaemic damage to skin and other organs (**Calciphylaxis**)

causes of Tertiary Hyperparathyroidism

Secondary Hyperparathyroidism -> **increased PTH and Ca+2** (HYpercalcemia)

casuses of **Hypoparathyroidism**

* **Surgically removed parathyroids** during thyroidectomy * Congenital absence of parathyroid glands, in conjunction with **thymic aplasia (DiGeorge Syndrome)**

CF of Hypoparathyroidism

1) **Tetany** [Chvostek’s sign and Trousseau’s sign] 2) Cardiac arrhythmias w/ and characteristic **prolonged QT interval** in the ECG 3) Increased intracranial pressure 4) **Seizures**

Morphologic Changes in Hypoparathyroidism

* Cataracts * Calcifications of the cerebral basal ganglia * Dental abnormalities

**Pseudo-Hypoparathyroidism** is aka?

Martin-Albright Syndrome

casuses of Martin-Albright Syndrome (Pseudo-Hypoparathyroidism)

Hereditary disorder, inherited through: * X-linked dominant genes * Autosomal dominant genes

Lab findings of Pseudo-Hypoparathyroidism (**Martin-Albright Syndrome**)

* low calcium levels * Elevated levels of phosphate and PTH

CF of **Pseudo-Hypoparathyroidism**(Martin-Albright Syndrome)

* Unusual sensations * Weakness * Easy fatigue

Signs and symptoms of Pseudo-Hypoparathyroidism (**Martin-Albright Syndrome**

* Short stature * Round face * Short neck * Shortened bones in the hands and feet