Pathology of Endocrine System Flashcards by Graeme Miller

What is the definition of hyperplasia and atrophy?

Hyperplasia:

Increased number and secretory activity of cells

Atrophy:

Diminution of cells due to lack of stimulation

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What are important general considerations to make about disease in an endocrine gland?

May have multiorgan effects

May lead to altered activity of another endocrine gland

Feedback effects may cause changes in endocrine gland

Endocrine glands have high reserve capacity

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What hormones does the thyroid gland release?

Thyroxine (T4)

Triiodothyronine (T3)

Calcitonin

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What is the role of epithelial cells in the thyroid gland?

Thyroglobulin synthesis

Iodination

Resorption

Release of T4 and T3

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What is the histological findings of grave’s disease?

Increased cell activity

Increased cell numbers

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What mediates the destruction of the thyroid in hashimotos thyroiditis?

Autoimune destruction of thyroid epithelial cells

Cytotoxic T cells, cytokine and antibody mediated destruction
Circulating autoantibodies to thyroglobulin, thyroid peroxidase

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What are the histological findings of hashimotos hypothyroidism?

Hurthle cell change

Intense infiltrate of plasma cells

Lymphocytes

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What causes a goitre to become multinodular?

Something results to cause impaired synthesis of T3/T4 - (iodine deficiency or goitrogens)

To compensate the thyroid produces more TSH, this results in hypertrophy and hyperplasia of epithelium

Single becomes multi-nodular

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What are the features of multinodular goitre on histology?

Follicles are crowded and filled with colloid (distended)

Haemorrhage, fibrosis, cycstic change

Nodular appearance

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What might a dominant nodule be?

Cyst

Follicular Adenoma

Carcinoma (papillary, follicular, anaplastic, medullary)

Lymphoma (may result from hashimoto’s)

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What are the relevant investigations for thyroid nodule?

TFT’s

Ultrasound

FNA

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What are the features of a thyroid follicular adenoma?

Most are non-functioning

Encapsulated tumour

Circumscribed

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What are the features of follicular cell carcinoma?

Rare

Usually solitary

Malignant cells breach capsule

Mets - bone, blood (previous lecture also said lungs)

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Give an example of the cause of follicular cell carcinoma

RAS mutation

PAX8/PPARG transolcation

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What is the aetiology of papillary carcinoma?

BRAF mutation

RET/PTC gene rearrangement

Associated with exposure to ionizing radiation

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How does papillary carcinoma spread?

Via lymphatics

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What are the histological findings of papillary carcinoma?

Papillary projections

Empty nuclei

Psammoma bodies

May be cystic

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What cells does a thyroid medullary carcinoma arise from?

C- cells

What does a medullary carcinoma produce?

Calcitonin and maybe other peptides

What is medullary carcinoma associated with?

MEN 2A, 2B

Familial FMTC

Mutations in RET proto-oncogene

What are the histological findings of medullary carcinoma?

Amyloid deposits

What are causes of primary hyperparathyroidism?

Sporadic or Familial (MEN - 1)

Adenoma (common)

Hyperplasia

Carcinoma (rare)

What are causes of secondary parathyroidism?

Physiological response to reduced calcium - renal failure?

What is the role of the hypothalamus and the pituitary?

Hypothalamus - homeostasis and emotional behaviour

Pituitary gland - regulated other endocrine glands

What are acidophils and what do they secrete?

Stain pink! Acidophils exist in the anterior pituitary Secrete GH and PRL

What are basophils?

Found in the anterior pituitary Secrete ACTH, LH, FSH, TSH

What is the third type of cell found in the anterior pituitary?

Chromophobes

What is the most common cause of pituitary hyperfunction?

Pituitary adenoma Carcinomas are rare

What is the cause of pituitary adenoma?

5% are inherited (MEN1) Usually sporadic

What are the effects of pituitary adenoma?

Adenomas of the pituitary are classified according to the hormone produced by the neoplastic cells Prolactinoma (galactorrhoe and menstrual disorders) GH secreting (acromegaly or gigantism) ACTH secreting - cushing's disease Non-functioning - 25-30% of detected tumours If large - pressure effect - (radiographic abnormalities, visual field abnormalities, elevated intracranial pressure, compression damage - hypopituitarism)

What causes pituitary hypofunction?

Compression by tumours (craniopharyngioma - metastatic) Trauma Infection (rare) - TB sarcoidosis Post - partum ischaemic necrosis (sheehan's syndrome)

What do the following portions of the adrenal crotex secrete?

Zona glomerulosa: Mineralcorticoids aldosterone Zona fasciculata: Glucocorticoids cortisol Zona reticularis: sex steroids, oestrogen, androgens

What are the casues of conn's?

Bilateral idiopathic hyperplasia Functioning adrenal adenoma Secondary - Renovascular hypertension, diuretic use, renin-secreting tumour, malignant hypertension, coarctation of the aorta

What causes adrenogenital syndromes?

Functioning adrenal tumour Pituitary tumour (cushings) Congenital adrenal hyperplasia (steroid enzyme deficiency - 21-hydroxylase)

What causes acute adrenal insufficiency?

Meningococcal septicaemia

What are the causes of chronic adrenal insufficiency?

What is the result of a hyperadrenal syndrome (adenoma on cortex) on the adjacent cortex?

Causes atrophy

How does an adrenal adenoma compare to an adrenal carcinoma?

Adenoma - small (usually 2-3 cm), yellow-brown and circumscribed Carcinoma - more likely to be functional, usually large (over 20cm) = haemorrhage, necrosis, cystic

Describe the metastasis of adrenal carcinoma

By lymphatics and blood Invades adrenal vein Metastatic carcinoma to lung and breast

What is multiple endocrine neoplasia?

Inherited disorder with underlying genetic mutation Neoplasms or hyperplasia of endocrine organs

What causes MEN1?

Tumour suppressor gene mutation - defect in menin protein involved in regulating cell growth

What are the features of MEN1?

Parathyroid hyperplasia and adenomas Pancreatic and duodenal endocrine tumours (hypoglycaemia and ulcers) Pituitary adenoma (prolactinoma)

What causes MEN2?

RET proto-oncogene mutations

What are the features of MEN 2?

Medullary carcinoma of thyroid Phaeochromocytoma MEN 2A - Parathyroid hyperplasia MEN 2B - Neuromas of skin and mucous membrane, skeletal abnormalities - Younger patients, aggressive