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Endocrine System > Pathology of the Endocrine System 1 & 2 > Flashcards

Pathology of the Endocrine System 1 & 2 Flashcards

1
Q

the endocrine system:

uIntegrated network of ______ - secrete chemical messengers – hormones - directly into bloodstream

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

___________ of metabolism, growth and development, tissue function

maintain functional balance __________

A

glands

hormones - by binding to receptors which change cell activity, differentiation, mitosis. It is instrumental in regulating metabolism, growth, development and puberty and tissue/organ function

regulation

homeostasis

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2
Q

Hormones synthesised and stored in glands, what are the features of a gland?

A

packets of cells with secretory granules

vascular

ductless

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3
Q

balance of hormones is maintained by

A

feedback inhibition

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4
Q

what makes up the endocrine system?

A

Pineal gland - produces melatonin - regulates circadian rhythm

Hypothalamus

Pituitary gland

Thyroid gland

Parathyroid gland

Adrenal glands

Pancreas

other organs (ovary, testes, kidney)

diffuse endocrine cells (lung, GIT)

Often two - in - one (endocrine organ often does more than one thing)

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5
Q

example of major system pathways:

A

TRH – TSH – T3/T4

GnRH – LH/FSH – sex hormones

CRH – ACTH – cortisol

Renin – angiotensin – aldosterone

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6
Q

what is endocrine disease?

A

Disease processes lead to changes in function and/or structure

Dysregulated hormone release -HYPERFUNCTION and HYPOFUNCTION

Effect of a MASS lesion (tumour – may secrete a hormone or have an effect of being a mass and compressing things nearby)

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7
Q

Disease Processes in Endocrine Organs:

what is hyperplasia?

A

increased number and secretory activity of cells

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8
Q

Disease Processes in Endocrine Organs:

what is atrophy?

A

shrinking of an organ

diminution of cells due to lack of stimulation

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9
Q

Disease Processes in Endocrine Organs:

what can cause tissue damage?

A

inflammation, autoimmune disease, compression, trauma, infarction

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10
Q

Disease Processes in Endocrine Organs:

what are examples of neoplasia (unregulated growth)

A

Adenoma – functioning or non functioning

Carcinoma – 1ry or metastatic

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11
Q

Disease Processes in Endocrine Organs:

what is it called when something is wrong form birth

A

congenital abnormality

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12
Q

what are the properies of benign neoplasia in endocrine organs?

A

Often circumscribed, localised, cannot invade, don’t usually transform

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13
Q

what are the properies of malignant neoplasia in endocrine organs?

A

Synonymous with cancer, invades, metastasises, if untreated, will often prove fatal

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14
Q

Disease in one endocrine gland may have __________ clinical effects

__________ effects may cause endocrine gland changes

Endocrine organs have high _______ capacity

A

multiorgan

feedback

reserve

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15
Q

what does thyroid gland secrete and what are its functions?

A

Synthesis, storage, release of thyroxine (T4), triiodothyronine (T3) - Regulates basal metabolic rate

calcitonin - Regulates calcium homeostasis

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16
Q

describe the histology of the thyroid gland

A

Thyroid epithelial cells are arranged in follicles filled with colloid –thyroglobulin.

Synthesis in colloid of thyroglobulin

Roles of iodine and tyrosine in T3/T4 synthesis

Involved in synthesise thyroglobulin – this requires iodine tyrosine

Cells reabsorb thyroglobulin and convert it to T3 and T4

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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17
Q

decsribe the hypothalamus - pituitary- thyroid axis

A
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18
Q

what is a manifestation of hyperthyroidism and what causes hyperthyroidism?

A

Thyrotoxicosis

Thyroiditis, Autoimmune, Others

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19
Q

what are manifestations of hypothyroidism and what are the causes hypothyroidism?

A

Myxoedema, Cretinism (a condition characterized by physical deformity and learning difficulties that is caused by congenital thyroid deficiency), Subclinical

Gland destruction

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20
Q

what are the manifestations of thyroid enlargement and what causes thyroid enlargement?

A

Goitre, Isolated nodule/mass

Multinodular goitre

Tumours - Benign or Malignant

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21
Q

what are the causes of hyperthyroidism?

A

Diffuse toxic hyperplasia (Graves disease) – 70%

Toxic multinodular goitre – 20%

Toxic adenoma

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22
Q

who is graves disease common in?

A

F>M

peak 20-40 yrs

genetic predisposition

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23
Q

what happens in graves disease?

A

Autoimmune production of anti- TSH receptor antibodies:

stimulate activity, growth, inhibit TSH binding

ophthalmopathy immune mediated - ocular fibroblasts have TSH receptor

Thyroid - diffuse hyperplasia and hyperfunction

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24
Q

what does the histology of a thyroid gland look like in graves disease?

A

increased cell activity

increased cell numbers

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25
Q

what are causes of hypothyroidism?

A

Hashimoto’s thyroiditis (auto-immune destruction)

Iatrogenic – surgery, drugs

Iodine deficiency

Congenital hypothyroidism

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26
Q

who is at risk of hashimotos thyroiditis

A

F>M , 45-65yrs

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27
Q

how does hashimotos thyroiditis occur?

A

Autoimune destruction of thyroid epithelial cells

Cytotoxic T cells, cytokine and antibody mediated destruction

Circulating autoantibodies to thyroglobulin, thyroid peroxidase

Thyroid - Diffuse enlargement gradual failure

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28
Q

what is the histology of hashimotos thyroiditis?

A
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29
Q

goite is

A

an enlarged thyroid

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30
Q

what are the causes of multinodular goitre?

A

Physiological - Puberty, Pregnancy

Autoimmune - Graves’ disease, Hashimoto’s disease

Thyroiditis - Acute (de Quervain’s ), Chronic fibrotic (Reidel’s)

Iodine deficiency (endemic goitre)

Dyshormogenesis

Goitrogens

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31
Q

describe the process of multinodular goitre

A

Iodine deficiency, goitrogens

↓

Impaired synthesis of T3,T4

↓

↑TSH

↓

Hypertrophy and hyperplasia of thyroid epithelium

Simple → → multinodular

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32
Q

describe the histology of multinodular goite

A

Distended colloid filled follicles

Haemorrhage, fibrosis, cystic change

Nodular appearance

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33
Q

what is the cause of a dominant nodule in multinodular goitre?

A

Follicular adenoma

Carcinoma (5% of nodules)

Differentiated thyroid carcinoma

Papillary carcinoma 75-85%

Follicular carcinoma 10-20%

Anaplastic carcinoma <5%

Medullary carcinoma 5%

(lymphoma)

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34
Q

how do you investigate a thyroid nodule?

A

TFTs

Ultrasound

FNA - cytology

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35
Q

how is thyroid carcinoma normally detected?

A

Often incidentally detected

36
Q

what are the risk factors of a thyroid carcinoma?

A

Family Hx

Chronic inflammatory conditions

Radiation exposure

Obesity

37
Q

what is a Follicular adenoma?

A

a benign encapsulated tumor of the thyroid gland

Most non-functioning

Circumscribed, encapsulated tumour

Histology often small microfollicles

38
Q

desribe the featurrs of a follicular carcinoma

A

Rare, usually solitary

Malignant cells breach capsule

uMetastases – blood, bones

39
Q

what are the features of a papilllary carcinoma?

A

Papillary carcinoma (PTC) is the most common form of well-differentiated thyroid cancer, and the most common form of thyroid cancer to result from exposure to radiation. Papillary carcinoma appears as an irregular solid or cystic mass or nodule in a normal thyroid parenchyma

Usually <50yrs

BRAF mutation or RET/PTC gene rearrangement

Associated with exposure to ionizing radiation

Spreads via lymphatics…but

Excellent prognosis - 85% survival 10 yrs (esp <55yrs)

40
Q

describe the histology of a papillary carcinoma

A

Papillary projections

Empty nuclei

Psammoma bodies

May be cystic

41
Q

what are the featrues of thyroid medullary carcinoma

A

Malignant tumour of C – cells

produces calcitonin (+/- other polypeptides)

70% sporadic

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

42
Q

what is the treatment of thyroid carcinoma?

A

Surgery (no surgical option in anaplastic)

Radioactive iodine - gets rid of any bits that are left

External radiotherapy

Chemotherapy

43
Q

what are the parathyroid glands and their function?

A

4 small glands -120mg

Produce PTH - regulates plasma Ca2+

thyroid Calcitonin opposes PTH (Calcitonin promotes bony absorption of calcium and prevents bone resorption)

44
Q

if someone has got a parathyroid adenoma they will often present __________

A

hypercalcaemic

45
Q

Primary hyperparathyroidism often asymptomatic _____________

A

hypercalcaemia

46
Q

what are the causes of primary hyperparathyroidism?

A

Sporadic or familial (MEN-1)

  • Adenoma (85-95%)
  • Hyperplasia (5-10%)
  • Carcinoma (rare)
47
Q

What is secondary hyperparathyroidism due to?

A

Physiological response to ↓Ca2+ renal failure

48
Q

where and what is the role of the hypothalamus and the pituitary gland?

A

Small gland, located in sella turcica

Connected to hypothalamus by pituitary stalk

Critical role in regulating other endocrine glands

49
Q

what does the the anterior pituitary secrete, what is its blood supply and what is it controlled by?

(adenohypophysis 80%)

A

secretes - ACTH, TSH, GH, PROLACTIN, FSH/LH

blood supply from hypothalamus

controlled by release factors from hypothalamus

50
Q

where is the posterior pituitary and what does it secrete?

(neurohypophysis)

A

downgrowth of hypothalamus

Secretes ADH, OXYTOCIN

51
Q

what is the most common cause of pituitary hyperfunction?

A

pituitary adenoma (not all secrete so may just cause a mass effect)

(pituitary carcinomas v rare and some hypothalamic disorders)

52
Q

what people are pituitary adenomas common in?

A

uusually adults, 35 to 60 yrs

most sporadic; 5% inherited eg MEN1

53
Q

pituitary adenomas are macroscopic, what do they look like?

A

soft, well-circumscribed lesion

small microadenomas may be incidental eg at post mortem

54
Q

what are the effects of a pituitary adenoma?

A

If functioning - hormone excess

Prolactinoma - 20-30% - galactorrhoea, menstrual disorders

GH secreting - acromegaly, gigantism

ACTH secreting - Cushing’s disease

Non-functioning - 25-30% of detected tumours - immunohistochemical demonstration (mostly prolactin)

55
Q

what is the difference between cushings syndrome and cushings disease?

A

Cushing’s syndrome refers to the condition caused by excess cortisol in the body, regardless of the cause

When Cushing’s syndrome is caused by a pituitary tumor, it is called Cushing’s disease

56
Q

what happens if a pituitary adenoma is large, what are some mass pressure effects?

A

radiographic abnormalities

visual field abnormalities

elevated intracranial pressure

compression damage – hypopituitarism

57
Q

how much function needs to be lost for someone to have pituitary hypofunction?

A

75%

58
Q

what are the causes of pituitary hypofunction?

A

Compression by tumours (most common) – craniopharyngioma metastatic

Trauma

Infection (rare)

TB

Sarcoidosis

Post partum ischaemic necrosis - Sheehan’s syndrome - pituitary gland is damaged during childbirth. It’s caused by excess blood loss (hemorrhage) or extremely low blood pressure during or after labor. A lack of blood deprives the pituitary of the oxygen it needs to work properly

59
Q

what is the weight of the adrenal glands

A

12g combined

60
Q

what does the cortex and medulla of the adrenal gland do?

A

cortex - Steroid hormones

medulla:

Neuroendocrine (chromaffin) cells

Adrenaline/noradrenaline response to stress maintain BP

Extra adrenal paraganglia similar

61
Q

what does each layer of the cortex of the adrenal gland secrete?

A

zona glomerulosa - mineralocorticoids - aldosterone

zona fasciculata glucocorticoids - cortisol

zona reticularis - sex steroids, oestrogen, androgens

62
Q

what are different adrenal pathologies?

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

63
Q

what are 3 syndromes caused by adrenal cortical hyperfunction?

A

Hypercortisolism (cushings syndrome)

Hyperaldosteronism (Conn’s syndrome)

Adrenogenital syndormes

64
Q

what are the cuases of cushings syndrome?

A

Exogenous -Iatrogenic steroids

Endogenous:

ACTH dependent - pituitary adenoma Cushings disease – 70%, ectopic ACTH

ACTH independent - functioning adrenal adenoma 10%

65
Q

how do you diagnose cushings syndrome?

A

measuring cortisol, ACTH and response to ACTH suppression

66
Q

what are the causes of conns syndrome?

A

Bilateral idiopathic hyperplasia

Functioning adrenal adenoma

(2ry hyperaldosteronism – physiological due to ↓renal perfusion ↑renin-angiotensin)

67
Q

conns syndrome causes increased _____ retention in the nephron

A

sodium

To much aldosterone = hypertension

68
Q

what are the causes of adrenogenital syndromes?

A

Functioning adrenal tumour

Pituitary tumour Cushings disease

Congenital adrenal hyperplasia – steroid enzyme deficiency

69
Q

what are the symptoms of adrenogenital syndromes?

A

Symptoms are variable

Ambiguous genetalia, precocious puberty, failure of puberty, virilisation, infertility, undervirilisation

70
Q

Adrenal Insufficiency - destruction of glands, can either by _____ or ______

A

acute

chronic

71
Q

what is chronic adrenal insufficiency?

A

1 year - addisons

2 year - pituitary failure

72
Q

what are the causes of addisons disease?

A
  • Autoimmune: autoimmune polyendocrine syndromes – spare medulla
  • Infections: TB, fungus HIV-related infections
  • Replacement: metastatic carcinoma amyloidosis
  • Atrophy: prolonged steroid therapy
  • Congenital hypoplasia
73
Q

what are the effects of adrencortical tumours?

A

Functioning – hyperadrenal syndromes, atrophy of adjacent cortex

Non functioning – often incidental - imaging/autopsy

Yellow-brown circumscribed

Most 2-3cm <30g

74
Q

describe the histology of adrenocortical tumours

A

Cells similar to those of normal cortex

nuclei small

Some pleomorphism (“endocrine atypia”).

Cytoplasm eosinophilic to vacuolated, depends on lipid

Mitoses inconspicuous

75
Q

What are the features 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

76
Q

are metastatic adrenal carcinoma more common? and where do they come from?

A

More common

lung, breast

77
Q

name an adrenal medullary tumour?

A

PHAEOCHROMOCYTOMA

Adrenal medulla neuroendocrine cells

78
Q

what does a phaeochromocytoma secrete?

A

secrete catecholamines → hypertension

79
Q

Is a phaeochromocytoma benign or malignant? and is it inherited?

A

Usually benign behaviour, can be bilateral

Up to 30% inherited – eg MEN 2, SDH

10% extra adrenal (paraganglioma)

80
Q

describe the histology of a phaeochromocytoma?

A

Nests “Zellballen” of polygonal cells in vascular network

Granular cytoplasm containing catecholamines

81
Q

What is multiple endocrine neoplasia?

A

Inherited disorders with underlying genetic mutation

Hyperplasia/neoplasms of endocrine organs -

younger age, multifocal

Several distinct syndromes

82
Q

what is MEN 1 (Wermer syndrome)?

A

MEN 1 tumour suppressor gene mutation - defect in menin protein involved in regulating cell growth

Parathyroid hyperplasia and adenomas

Pancreatic and duodenal endocrine tumours (hypoglycaemia and ulcers)

Pituitary adenoma (prolactinoma)

83
Q

what is MEN 2?

A

RET proto-ongogene mutations

Medullary carcinoma of thyroid

Phaeochromocytoma

84
Q

What is MEN 2A (Sipple syndrome)?

A

+ Parathyroid hyperplasia

Extracellular domain auto dimerisation of RET receptor

85
Q

what is MEN 2B

A

+ Neuromas of skin & mucous membrane, skeletal abnormalities

+ Younger patients, aggressive

Autoactivation of tyrosine kinase pathway

86
Q

Disease in one endocrine gland may have _________ clinical effects

Disease in one endocrine gland may lead to altered activity of another __________ _____

________ effects may cause changes in endocrine glands

Endocrine organs have high _______ capacity

nb - ectopic hormone production by other organs

A

Disease in one endocrine gland may have multiorgan clinical effects

Disease in one endocrine gland may lead to altered activity of another endocrine gland

Feedback effects may cause changes in endocrine glands

Endocrine organs have high reserve capacity

nb - ectopic hormone production by other organs

Endocrine System (90 decks)

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