Pathology of the Endocrine System 1 Flashcards

1
Q

what is the function of the endocrine system?

A

Integrated network of GLANDS - secrete chemical messengers – hormones - directly into bloodstream

HORMONES act on target cells distant from site of synthesis - bind to receptors – change cell activity

REGULATION of metabolism, growth and development, tissue function

maintain functional balance

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2
Q

what are the kind of hormones synthesised and stored in glands?

A

packets of cells with secretory granules
vascular
ductless

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3
Q

what are the contents of the classical endocrine system?

A
pineal gland
hypothalamus
pituitary gland
thyroid gland
parathyroid gland
adrenal gland
pancreas
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4
Q

what is hyperplasia?

A

increased number and secretory activity of cells

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5
Q

what is atrophy

A

diminution of cells due to lack of stimulation

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6
Q

what is tissue damage?

A

inflammation, autoimmune disease, compression, trauma, infarction

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7
Q

what are the two types of neoplasia?

A

adenoma

carcinoma

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8
Q

whats the difference between adenoma and carcinoma

A

adenoma- functioning or non functioning

carcinoma- 1ry or metastatoc

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9
Q

how would you determine the cause of congenital abnormality?

A

morphologic findings

biochemical measurements of hormone levels, regulators and metabolites.

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10
Q

what is the function of synthesis, storage, release of thyroxine T4 and triiodothyronine T3?

A

regulated basal metabolic rate

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11
Q

whats the function of calcitonin?

A

regulates calcium homeostasis

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12
Q

what is the histology of thyroid gland?

A

Follicles

Colloid-contains thyroglobulin

Epithelial cells – TG synthesis, iodination, resorption & release of T4 and T3

C-cells – secrete calcitonin (not visible)

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13
Q

what is the manifestation of thyroid diseases?

A

Hyperthyroidism
Thyrotoxicosis*

Hypothyroidism
Myxoedema, Cretinism
Subclinical

Thyroid enlargement
Goitre
Isolated nodule/mass

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14
Q

what are the causes of thyroid diseases?

A

Thyroiditis
Autoimmune
Others

Gland destruction

Multinodular goitre
Tumours
Benign
Malignant

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15
Q

what are the causes of hyperthyroidism?

A

Diffuse toxic hyperplasia (Graves disease) – 70%

Toxic multinodular goitre – 20%

Toxic adenoma

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16
Q

whos more likely to get graves disease?

A

females
peak- 20-40 years
genetic predisposition

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17
Q

what happens to the histology in graves disease?

A

cell activity increases and cell numbers increase

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18
Q

what are the causes of hypothyroidism?

A

Hashimoto’s thyroiditis
(auto-immune destruction)

Iatrogenic – surgery drugs

Iodine deficiency

Congenital hypothyroidism

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19
Q

whos more likely to get hashimotos thyroiditis?

A

females

45-65 yrs

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20
Q

what is graves disease?

A

Autoimmune production of anti- TSH receptor antibodies
stimulate activity, growth, inhibit TSH binding
ophthalmopathy immune mediated – ocular fibroblasts have TSH receptor

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21
Q

what is hashimotos thyroiditis?

A

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

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22
Q

what happens to the thyroid in hashimotos thyroiditis?

A

Diffuse enlargement gradual failure

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23
Q

what is the histology of hashimotos thyroiditis?

A

hurthle cell change
intense infiltrate of plasma cells
lymphocytes

crowded follicles
distended colloid filled follicles
haemorrhage, fibrosis, cycstic change

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24
Q

what is goitre?

A

enlarged thyroid

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25
Q

what is the pathway to multinodular goitre?

A

iodine deficiency, goitrogens –> impaired synthesis of T3 and T4 –> increase of TSH –> hypertrophy and hyperplasia of epithelium

goes from simple to multi nodular

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26
Q

what is a thyroid nodule?

A

dominant nodule in multinodular goitre
cysts
follicular adenoma
carcinoma

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27
Q

how would you investigate a thyroid nodule?

A

TFTs, ultrasound, FNA

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28
Q

name some thyroid tumours

A

Follicular adenoma

Carcinoma (5% of nodules)
Differentiated thyroid carcinoma (DTC)
Papillary carcinoma              75-85%
Follicular carcinoma             10-20%
Anaplastic carcinoma                5%
Medullary carcinoma                   5%
    (lymphoma)
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29
Q

what is the most non functioning thyroid neoplasm?

A

follicular adenoma

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30
Q

give some characteristics about follicular adenomas?

A

Most non-functioning
Circumscribed, encapsulated tumour
Histology often small microfollicles

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31
Q

how common are follicular carcinomas?

A

rare, usually solitary

32
Q

where are follicular carcinomas most likely to metastasise?

A

blood, bones

33
Q

what is the type of mutation in papillary carcinomas?

A

BRAF mutation or RET/PTC gene rearrangement

34
Q

what is papillary carcinoma associated with?

A

exposure to ionizing radiation

35
Q

where is papillary carcinoma most likely to spread?

A

lymphatics

36
Q

what is the histology of papillary carcinoma?

A

Papillary projections
Empty nuclei
Psammoma bodies
May be cystic

37
Q

what are some characteristics of thyroid medullary carcinomas?

A

Malignant tumour of C – cells

produces calcitonin (+/- other polypeptides)

70% sporadic

38
Q

what are the type of genes in thyroid medullary carcinomas?

A

30% MEN 2A, 2B, familial FMTC – mutations in RET proto-oncogene – prophylactic thyroidectomy

39
Q

how many glands are in the parathyroid gland?

A

4 small glands - 120mg

40
Q

what do parathyroid glands produce?

A

PTH- regulates plasma Ca

41
Q

what are the causes for parathyroid hyper function?

A

1ry hyperparathyroidism
often assymptomatic
hypercalcaemia

Sporadic or familial (MEN-1)
Adenoma (85-95%
Hyperplasia (5-10%)
Carcinoma (rare)

2ry hyperparathyroidism
Physiological response to ↓ Ca2+ renal failure

42
Q

what are the functions of the hypothalamus?

A

maintains homeostasis

governs emotional behaviour

links nervous system to endocrine system via the pituitary gland

43
Q

what is the function of pituitary gland?

A

small gland, located in sella turcica

connected to hypothalamus by pituitary stalk

critical role in regulating other endocrine glands

44
Q

what is the adenohypophysis

A

the anterior part of the pituitary gland that is derived from the embryonic pharynx and is primarily glandular in nature

45
Q

where is the blood that supplies the anterior pituitary from?

A

hypothalamus

46
Q

what does the anterior pituitary secrete?

A

ACTH, TSH, GH, PROLACTIN, FSH/LH

47
Q

how is the anterior pituitary controlled?

A

release factors from hypothalamus

48
Q

what is neurohypophysis?

A

that posterior part of the pituitary gland

49
Q

what does the posterior pituitary secrete?

A

ADH, OXYTOCIN

50
Q

what are the 3 major cell types of pituitary glands?

A

pink ACIDOPHILS secrete GH and PRL

dark purple BASOPHILS secrete ACTH, TSH, FSH, LH

pale CHROMOPHOBES

51
Q

what is the most common cause of pituitary hyper function?

A

pituitary adenoma

52
Q

what is the histology of pituitary adenoma?

A

cells of same appearance as normal gland

classified by hormone(s) produced by the neoplastic cells - detected by immunohistochemical stains

53
Q

whos most likely to get pituitary adenomas?

A

usually adults, 35 to 60 yrs

most sporadic;

54
Q

what are the effects of pituitary adenomas?

A

if functioning- hormone excess

55
Q

what effect does prolactiinoma have on pituitary adenomas?

A

galactorrhoea, menstrual disorders

56
Q

what effect does GH secreting have on pituitary adenoma?

A

acromegaly, gigantism

57
Q

what effect does ACTH secreting have on pituitary adeomas?

A

Cushing’s disease

58
Q

what effect does non-functioningn pituitary have on pituitary adenomas

A

immunohistochemical demonstration (mostly prolactin)

59
Q

what is the result of a large pituitary adenoma?

A

radiographic abnormalities

visual field abnormalities

elevated intracranial pressure

compression damage – hypopituitarism

60
Q

what are the causes of pituitary hypofunction?

A

Compression by tumours – craniopharyngioma. metastatic

Trauma

Infection (rare)
TB
Sarcoidosis

Post partum ischaemic necrosis Sheehan’s syndrome

61
Q

what is the pathology of adrenal?

A

Hyperfunction
clinical syndromes depend on which adrenal hormones stimulated

Hypofunction

Mass lesion - effect late

Effect on adrenal gland –hyperplasia (diffuse or nodular), atrophy, mass lesion

62
Q

what are the three syndromes of adrenal cortical hyper function?

A

Hypercortisolism– CUSHING’S SYNDROME

Hyperaldosteronism (Conn’s syndrome)

Adrenoginital syndormes

63
Q

what are characteristics of hypercorticolism?

A

Exogenous -Iatrogenic steroids

Endogenous
ACTH dependent
pituitary adenoma Cushings disease – 70%
ectopic ACTH

ACTH independent
functioning adrenal adenoma 10%

64
Q

what are some characteristics of hyperaldosteronism?

A

Bilateral idiopathic hyperplasia
Functioning adrenal adenoma
(2ry hyperaldosteronism – physiological due to ↓renal perfusion ↑renin-angiotensin)

65
Q

what are characteristics of adrenogenital syndromes?

A

Functioning adrenal tumour
Pituitary tumour Cushings disease
Congenital adrenal hyperplasia – steroid enzyme deficiency

66
Q

what are the acute causes of adrenal insufficiency destruction of glands?

A

meningococcal septicaemia

waterhouse friderichsen

67
Q

what are the chronic causes of adrenal insufficiency destruction of glands?

A

1ry - Addison’s disease
Autoimmune : autoimmune polyendocrine syndromes – spare medulla
Infections: TB, fungus HIV-related infections
Replacement: metastatic carcinoma amyloidosis,
Atrophy: prolonged steroid therapy
Congenital hypoplasia

2ry - Pituitary failure

68
Q

what are the characteristics of adrenocortical tumours?

A

Functioning – hyperadrenal syndromes, atrophy of adjacent cortex
Non functioning – often incidental – imaging/autopsy
Yellow-brown circumscribed
Most 2-3cm <30g

69
Q

what are the characteristics of primary adrenocortical carcinoma?

A

rare, any age
More likely functional – virilising
Most large >20cm , haemorrhage and necrosis, cystic
Metastasises by lymphatics and blood – invades adrenal vein

70
Q

what are the characteristics of adrenal medullary tumour (phaeochromocytoma)

A
Adrenal medulla neuroendocrine cells  
secrete catecholamines → hypertension
Usually benign behaviour, can be bilateral
Up to 25% inherited – eg MEN 2
10% extra adrenal
71
Q

what is the histology of adrenal medullary tumour?

A

Nests “Zellballen” of polygonal cells in vascular network

Granular cytoplasm containing catecholamines

72
Q

what syndrome does MEN 1 cause?

A

wermer syndrome

73
Q

what does the MEN 1 tumour supressor gene mutation cause?

A

defect in menin protein involved in regulating cell growth

Parathyroid hyperplasia and adenomas

Pancreatic and duodenal endocrine tumours (hypoglycaemia and ulcers)

Pituitary adenoma (prolactinoma)

74
Q

what does MEN 2 cause?

A

Medullary carcinoma of thyroid

Phaeochromocytoma

75
Q

what does MEN2A cause?

A

sipple syndrome

parathyroid hyperplasia

76
Q

what does MEN 2B cause?

A

Neuromas of skin &mucous membrane, skeletal abnormalities
+ Younger patients, aggressive