Endocrine Flashcards
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clinical features of Diabetes Mellitus
-
“Honeymoon period”: First 1-2 years after
manifestation of overt type 1 diabetes - Hyperglycaemia
- Glycosuria –> Osmotic Diuresis –> Polyuria
- Polydipsia (increased thirst)
- Polyphagia (excessive hunger)
- Ketoacidosis (severe cases) [type 1 DM]
- Hyperosmolar non-ketotic coma (sever dehydration) [type 2 DM]
- Weight loss [type 1 DM]
- Obesity [type 2 DM]
honeymoon : pancreas is still able to produce small amounts of insulin
Histology of Type 1 vs Type 2 diabtes Mellitus
Type 1: “insulitis” ; Islets lymphocytic infiltrates (made up of macrophages and lymphocytes)
Type 2: Islet Amyloid polypeptide (IAPP) deposists
Type 1 vs Type 2 diabetes
Explain the Pathology of how islets are replaced by Amyloid in Type 2 DM
1) inadequate compensation for peripheral resiatnce –> Hyperglycaemia + loss of β-cell mass
2) Excess FFAs and glucose –> lymphocytic infiltration (Recruitment of macrophages and T cells) –> Cytokine production –> Beta cell dysfunction and death
3) Replacement of islets by amyloid
list 4 Diabetic Macrovascular diseases
1) MI
2) Atherosclerosis of the aorta and large/medium-sized arteries
3) Gangrene of the lowere extremities
4) Hylaine Arteriosclerosis [associated with hypertension]
list 3 complications of Diabetic Microangiopathy
1) Diabetic Nephropathy (Glomerulosclerosis, Pyelonephritis, Hylaine Arteriolosclerosis)
2) Retinopathy (cataracts, Galucoma)
3) Neuropathy (nerve injury in the legs and feet)
Diabetic Nephropathy
poorly controlled diabetes can cause damage to blood vessel clusters , leading to Glomerular lesions –> kidney damage. Explain how this happens
Changes in the apperance of the glomerulus due to lesions:
GBM thickening –> Mesangial expansion (Diffuse mesangial sclerosis) –> Nodular glomerulo-sclerosis (Kimmelstiel-Wilson lesions) –> Diffuse glomeurlosclerosis (chronic)–> kidney damage due to Ischaemia
* GBM : Glomerular Basement Membrane
Non-proliferative vs Proliferative Diabetic Retionopathy
Non-proliferative
–> Microangiopathy,retinal haemorrhages and exudates (“soft” = microinfarcts, “hard” = deposits of plasma proteins and lipids), micro-aneurysms and oedema
Proliferative:
–> Process of neovascularisation and fibrosis; Vitreous haemorrhages, due to rupture of newly formed vessels –> Organisation of the haemorrhage –> Retinal detachment
*Vitreous Haemorrhage : presence of blood in the vitreous humor
The 2 PanNETs associated with MEN-1 syndrom (mutation)
*PanNETs: Pancreatic Neuro-Endocrine Tumours
1) Insulinomas (in the pancerase)
2) Zollinger-Ellison Syndrome (Gastrinomas)
primary causes of Thyrotoxicoses associated w/ Hyperthyrodism
1) Diffuse toxic hyperplasia (Grave’s disease)
2) Hyper-functioning (“toxic”) multi-nodular goiter
3) Hyper-functioning (“toxic”) adenoma
4) Iodine-induced hyperthyroidism
diagnostic tests for Hyperthyroidism
- increased T3/T4
- Decreased TSH (if Primary)
Measurement of radioactive iodine uptake by the
thyroid gland
* Diffusely [increased/decreased] uptake in Grave’s disease
* [Increased/decreased]uptake in a solitary nodule in toxic adenoma
* [Increased /decreased] uptake in thyroiditis
- Diffusely increased uptake in Grave’s disease
- Increaseduptake in a solitary nodule in toxic adenoma
- [decreased] uptake in thyroiditis
LABs of Primary vs secondary Hypothyroidism
Primary Hypothyroidism:
* Increased TSH
* Decreased serum T4
Secondary Hypothyroidism:
* Not increased TSH
* Decreased serum T4
Types of Thyroiditis
Chronic Lymphocytic (or Hashimoto) Thyroiditis
Granulomatous (de Quervain) Thyroiditis
Subacute Lymphocytic Thyroiditis
Riedel (Fibrous or Invasive) Thyroiditis
Chronic Lymphocytic (Hashimoto) Thyroiditis.
Linkage to ————— gene cytotoxic
Cytotoxic T-lymphocyte-associated Ag-4
gene (CTLA4)
Microscopic Findings:
* Inflammatory infiltrates (lymphocytes, plasma cells) + Germinal centers
* Atrophic thyroid follicles, lined by Hürthle or Oxyphil cells (marked eosinophil., granular cytopl.)
features of?
Chronic Lymphocytic
(Hashimoto) Thyroiditis
CF of Hashimoto Thyroiditis
Painless, symmetric and diffuse enlargement of the thyroid
complications of Chronic Lymphocytic
(Hashimoto) Thyroiditis
Increased risk for development of B-cell non -Hodgkin lymphomas, within the thyroid gland
causes of Subacute Granulomatous
(de Quervain) Thyroiditis
- Viral infection
- Inflammatory process triggered by viral infections;
commonly, history of upper respiratory tract
infection
Microscopic Findings:
* Disruption of thyroid follicles –> Extravasation of
colloid –> Polymorphonuclear infiltrate –>
Lymphocytes, plasma cells and macrophages
* Development of a granulomatous reaction with
giant cells –> Granulomatous inflammation
* Healing: Resolution of inflammation and fibrosis
Macroscopic features :
- firm gland
- Intact capsule
Features of?
SubacuteGranulomatous
(de Quervain) Thyroiditis
CF of Subacute Granulomatous
(de Quervain) Thyroiditis
- Neck pain (particularly with swallowing)
- Fever
- Malaise
- Transient Hyperthyroidism –> Transient
Hypothyroidism –> Euthyroid state
(within 6-8 weeks)
Macroscopic Features:
* Mild symmetric enlargement of the thyroid gland
Microscopic Findings:
* Lymphocytic infiltrates and hyperplastic germinal centers
Features of?
Subacute Lymphocytic Thyroiditis (aka silent or painless Thyroiditi)
CF of Riedel Thyroiditis (Fibrous/Invasive Thyroiditis)
- Hard and fixed thyroid mass
Microscopic findings:
* Thyroid replaced by fibrous tissue and inflammatory infiltrate (plasma cells , lymphocytes, macrophages)
Features of?
Riedel Thyroiditis
most common casue of Hyperthyroidism?
Grave’s disease
Garve’s diseases coexists with what diseases?
SLE, Pernicious Anaemia (Autoimmune gastritis), DM-t1 and Addison’s disease
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
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
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
Toxic Multi-Nodular Goiter is aka?
Plummer Syndrome
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)
Imaging findings of thyroid Follicular Adenomas
1) “warm” or “hot” thyroid nodule –> toxic adenoma
or
2) “Cold” nodules
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)
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)
Histo of Hürthle Cell Adenoma (follicular) vs. Carcinoma
Follicular adenoma: intact capsule
Follicular Carcinoma: invades thyroid capsule and vasculature
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
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
*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 Calcitonin
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
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