PATHOLOGY- Endocrine disorders Flashcards
1
Q
Define cell-signalling
A
Cells communicating in the body to co-ordinate/integrate functions
2
Q
How are signalling molecules, produced by one cell type, detected by another
A
Via receptors
3
Q
Where are the receptors used to detect signalling molecules found
A
Cell surface
Inter-cellular
4
Q
What are the 2 purposes of the receptors
A
Alter gene expression
Alter cell behaviour/function
5
Q
What 3 mechanisms can signalling occur via
A
Autocrine
Paracrine
Endocrine
6
Q
What is autocrine signalling
A
Signalling molecule acts on the same cell
7
Q
What is paracrine signalling
A
Signalling molecule secreted into interstitial fluid, acting on nearby cells
8
Q
What is endocrine signalling
A
Signalling molecule secreted into blood stream, acting on distant cells throughout the body
9
Q
How are body-wide metabolic processes maintained
A
Via regulatory molecules
10
Q
What are endocrine glands
A
Hormone-secreting specialised tissues
11
Q
What is the endocrine system
A
System of hormone-secreting specialised tissues
12
Q
How do hormones travel to target cells distant to site of production
A
Usually via blood
13
Q
Explain the general process of the hypothalamic-pituatry axis
A
- Hypothalamus produces releasing hormones which act on the pituitary gland
- Pituitary gland produces trophic hormones which are released in to the blood stream and can act on specific target glands
- Endocrine glands receives signal from the trophic hormones. It then produces its end product OR acts directly on the cell themselves e.g growth hormone
14
Q
Most hormones are produced by what
A
Hypothalamus
15
Q
What is the pituitary known as
A
Conductor of endocrine orchestra
16
Q
What is the pituitary
Where is it
How much does it weigh
What is its role
A
Small organ
Base of the brain
0.5-1g
Essential control over endocrine system
17
Q
What are the 2 distinct parts of the pituitary
A
Anterior pituitary (adenohypophysis, 75-80%)
Posterior pituitary (neurohypophysis)
18
Q
What is the anterior pituitary (adenohypophysis)
A
- Stimulated by hypothalamic ‘releasing hormones’
- Releasing hormones pass via “portal” circulation to anterior pituitary
- Secretes six trophic hormones into systemic bloodstream
19
Q
What is the Posterior pituitary (neurohypophysis)
A
Neural structures directly from hypothalamus which release 2 trophic hormones, ADH and oxytocin
20
Q
What is the difference between the anterior and posterior pituitary
A
In posterior, the signal comes through modified neurons
In anterior, the signal is mediated through the blood stream
21
Q
What 2 ways is the endocrine system regulated
A
Hormones (produced in specific circumstances)
Negative feedback
22
Q
What is negative feedback
A
Produced hormones ‘feedback’ onto pituitary / hypothalamus to regulate secreting / trophic hormone production, therefore precisely control hormone production
23
Q
List pituitary dysfunctions
A
Hyperpituitarism
Hypopituitarism
Local mass effects
24
Q
What is hyperpituitarism caused by
A
Excess production of trophic hormones
25
List examples of where you can see hyperpituitarism
Hyperplasias
Adenomas,
Carcinomas
Secretion of pituitary-like hormones from non-pituitary tumours
Hypothalamus disorders
26
What is hypopituitarism caused by
Deficient production of trophic hormones
27
List examples of where hypopituitarism Is present
Ischaemia
Surgery
Radiation
Inflammatory disorders
Mass effect of non-functional pituitary tumours
Post-partum ischaemic necrosis (Sheehan syndrome)
28
Examples of how local mass effects can case pituitary dysfunction
- Optic nerve (chiasm) - visual field defects
- Raised intra-cranial pressure (^ICP)
- Pituitary apoplexy = haemorrhage causing sudden enlargement = emergency!
29
What is the most common cause of hyperpituitarism
Pituitary adenomas (most commonly anterior lobe tumours)
30
What are pituitary adenomas classified by
Cell type
Hormones produced (if functional)
31
Whe do non-functional tumours tend to present and what size are they
Present later and are usually larger
32
Why do non functional tumours present later and are usually larger
Functional tumours will be producing abnormal amounts of their trophic hormones so they will be causing some biochemical abnormality, this will give some clinical manifestation when the tumour is much smaller but still producing these chemicals. Whereas nonfunctional tumours have to produce their symptoms by effects of their size
33
Who do pituitary adenomas usually present in
Most commonly adults, 35-60 years
34
What do the signs/symptoms of pituitary adenomas depend on
Hormones produced and/ or mass effect
35
What is the most common pituitary adenoma
Lactotroph pituitary adenoma (30%)
36
What are lactotroph pituitary adenomas
Prolactin producing tumours
37
What are lactotroph pituitary adenomas also known as
Prolactinomas
38
What symptoms does Lactotroph pituitary adenoma cause
Amenorrhea, galactorrhoea, loss of libido, infertility
39
Is lactotroph pituitary adenoma more easily diagnosed in men or women
Women
40
What is the second most common pituitary adenoma
Somatotroph pituitary adenoma
41
What are Somatotroph pituitary adenoma
Growth-hormone producing tumours
42
what symptoms do somatotroph pituitary adenomas cause
Gigantism in children
Acromegaly in adults
43
What is corticotroph pituitary tumours
Adrenocorticotrophic hormone (ACTH) producing tumours
44
What do corticotroph pituitary adenomas cause
Adrenal hypersecretion of cortisol
Hypercortisolism (Cushings syndrome)
45
What is the thyroid
Where is is located
What level is it on the vertebra
Bi-lobed organ with isthmus
Below, anterior to larynx, close to the trachea
Level of 5th to 7th vertebra
46
How does the thyroid work
What does this process need to work
1. Hypothalamus send a signal via TRH through to the anterior pituitary which acts on the thyrotrophic cells which produces thyrotropin/TSH
2. TSH passes into bloodstream and interacts with receptors on thyroid follicular cells/FCs
3. This signals thyroid follicular cells to produce the thyroid hormones T3/T4
Iodine
4. Thyroid hormones stored by TG in colloid
5. When needed and released in to the blood stream by follicular cells, T4 is converted in to T3 (T3 much more active)
6. Thyroid hormones binds nuclear thyroid receptor in variety of tissues
7. This increases carbohydrate/lipid catabolism
8. Also increases protein synthesis which in turn increases basal metabolic rate (BMR)
47
What is TRH
Thyrotropin releasing hormone
48
What is thyrotropin also known as
Thyroid stimulating hormone
49
Where are thyroid hormones such as T3/T4 stored
Stored by thyroid glands in colloid
50
How are thyroid hormones released from the glands in to the blood stream
Colloid is broken down
51
List the CLINICAL implications of thyroid disorders and what they are caused by
- Hyperfunction (hyperthyroidism)
* Graves disease, toxic nodules, toxic adenoma
- Hypofunction (hypothyroidism)
* Hashimotos, endemic goitre, iatrogenic (surgery/drugs)
- Structural change (entire gland)
* Graves disease, diffuse / nodular goitre
- Structural change (nodules)
* Dominant nodule in MNG, tumours
52
List the aetiology of thyroid disorders and what they’re caused by
Autoimmune
* Graves, Hashimotos
- latrogenic
* Surgery, radiation, drugs
- Metabolic
* Endemic goitre, diffuse / nodular goitre
- Neoplastic
* Tumours (adenoma, carcinomas)
53
Similar aetiologies can cause different what
Clinical features
54
What are the clinical features of hypothyroidism
Weight gain
Muscle weakness
Constipation
55
What are the clinical features of hyperthyroidism
Weight loss
Tachycardia
Anxiety
56
What diseases cause hypothyroidism
Hashimotos thyroiditis
Endemic goitre (I dericiency)
Iatrogenic
57
What diseases cause hyperthyroidism
Graves disease
Toxic nodules / tumours
58
What does goitre mean
Enlarged thyroid
59
What are the effects of euthyroid
Diffuse / nodular hyperplasia (goltre)
Tumours
60
What is euthyroid
Thyroid levels are normal but structural changes caused
61
What is Graves’ disease also known as
Diffuse hyperplasia
62
What is the most common cause of hyperthyroidism
Graves’ disease
63
What is graves diseases
What does it cause
Autoimmune disorder
Autoantibodies against multiple proteins especially TSH receptor in the thyroid. This activates TSH receptor on thyroid stimulating T3/T4 production. This causes T3/T4 levels to be high with low TSH levels (negative feedback on HPA)
64
Whta is the most common autoantibody inn Graves’ disease
Thyroid-stimulating immunoglobulin (TS|)
65
What are the clinical manifestations of Graves’ disease
Symmetrically diffusely enlarged thyroid
Follicles hyperplasticity causing papillary projections
Pale colloid
66
What are the clinical features of Graves’ disease
- Hyperthyroidism (as above)
- Enlargement of thyroid
- Infiltrative ophthalmopathy (characteristic for Graves)
* Activated T cells cytokines -> fibroblast proliferation, secretion of ECM
* Infiltration of retro-orbital space - protrusion of eyeball (exophthalmos)
67
How do you diagnose Graves’ disease
High T3/T4, low TSH, autoantibodies
68
How do you treat Graves’ disease
- Radioactive iodine
- Drugs
- Surgery
69
What is the most common cause of hypothyroidism
Chronic lymphocytic thyroiditis / Hashimotos
70
What is Chronic lymphocytic thyroiditis / Hashimotos
What does it cause
Autoimmune disorder
Autoantibodies against thyroglobulin / thyroid peroxidase (diagnostic)
71
What are the effects of Chronic lymphocytic thyroiditis / Hashimotos
Glands usually enlarged
Lymphocytic infiltration with germinal centre formation
Destruction of thyroid follicular epithelial cells
"Hurthle cell change" - reactive metaplasia due to chronic injury
72
What are the clinical features of Chronic lymphocytic thyroiditis / Hashimotos
- Hypothyroidism
- † risk of lymphoma / papillary carcinoma
73
How do you diagnose Chronic lymphocytic thyroiditis / Hashimotos
Low T3/T4, high TSH, TPO autoantibodies
74
What is the treatment for Chronic lymphocytic thyroiditis / Hashimotos
- T3/Т4 supplement
- Some have surgery if atypical features
75
What is diffuse and modular hyperplasia/goitre
Result of long term proliferative stimuli e.g. iodine deficiency, genetics, idiopathic
76
What causes thyroid hyperplasia
High TSH due to low T3/74
77
Initially what happens in diffuse and modular hyperplasia
What happens later
What is the theory that causes these changes
Initially diffuse enlargement (goitre)
Enlargement of thyroid leading to variable degrees of nodularity (multinodular goitre)
Variable responses in thyroid follicular epithelial cells
78
Why are most patients initially euthyroid
Result of hyperplasia
79
What can large dominant nodules be mistaken for clinically
Thyroid carcinoma
80
What can happen to nodules in nodular hyperplasia
May become active/hyper secretory
81
What may develop with large nodules
How is this treated
Tracheal compression or dysphasia
Surgery
82
Who do the majority of thyroid tumours affect
Women
83
The majority of thyroid tumours are what type
Papillary carcinoma
84
Give an example of a brining thyroid tumour
follicular adenoma
85
Give 4 examples of malignant thyroid tumours
- Papillary carcinoma (85%)
- Follicular carcinoma (5-10%)
- Medullary carcinoma (<5%) - rare = don't worry!
- Anaplastic carcinoma (<5%) - rare = don't worry!
86
What is a follicular adenoma
How do they usually present
Who do they mostly affect
Are they functional/nonfunctional
Benign tumour if follicular epithelial cells
Usually solitary
Women
Non-functional with a small proportion being functional/toxic
87
List the pathological features of a follicular adenoma
Solitary lesion
Small thyroid follicles (microfollicles)
Surrounded by thick capsule
88
How do you know whether a follicular adenoma is benign
Only if there is no invasion of capsule or blood vessels
Hence can only call FA if lesion completely examined
89
What are the clinical features of follicular adenomas
- Solitary painless nodule
- Incidental on examination or radiology
- Toxic nodules (rarely) produce thyroid hormones
- Defined by radioactive iodine uptake
90
What is the treatment for follicular adenomas
- Excision (needed to exclude carcinoma)
- Carcinoma looks similar but defined by invasion through capsule / BVs
91
What is the most common form of thyroid cancer
Papillary thyroid carcinoma
92
What is the ratio of females to males that have papillary thyroid carcinoma
2.5:1
93
What age are people affected by papillary thyroid carcinoma
Wide age range
Mean 43 years
94
what is the prognosis for papillary thyroid carcinoma
Generally good prognosis (5 year survival 85-95%)
95
What is the underlying cause of papillary thyroid carcinoma
Radiation exposure
Mutations of RAS or BRAF
96
What does papillary thyroid carcinoma look like
* Ill defined, infiltrative
* Some circumscribed / encapsulated
* May be cystic
* Characteristic nuclear features - diagnostic
97
To make a diagnosis of papillary thyroid carcinoma what do you need
Nuclear features
- tightly packed cells
- very open clear nuclei
- wrinkled and irregular membranes
- pseudo inclusions
98
What different patterns may be seen in papillary thyroid carcinoma
- "Papillary" structures = "classical" variant
- Lots of small follicles = follicular variant
99
What are the clinical features of papillary thyroid carcinoma
- Painless mass
- Incidental on examination or radiology
- May present with LN mets
- Hoarse voice / dysphagia if RLN involved
100
What is the treatment of papillary thyroid carcinoma
- Excision
- Radio-iodine (e.g. large tumour, mets, invasion outside thyroid)
101
What is follicular thyroid carcinoma
Malignant tumour of thyroid epithelial cells showing NO PTC NUCLEAR FEATURES
102
which is more common papillary or follicular thyroid carcinoma
Papillary thyroid carcinoma
103
who does follicular thyroid carincoma affect
Women 3:1
104
What age does follicular thyroid carcinoma affect people
Older onset (40-60yrs)
V rare in children
105
what are the risk factors for follicular thyroid carcinoma
Radiation
Iodine deficiency
106
what does the prognosis of follicular thyroid carcinoma depend on
Presence/extent of vascular invasion
107
What is the effect if there is and isn’t vascular invasion in follicular thyroid carcinoma
No vi= excellent prognosis
Vi= prone to metastases
108
What causes follicular thyroid carcinoma
RAS gene mutations
109
What is the difference between a follicular adenoma and follicular thyroid carcinoma
Follicular adenoma
- micro follicular lesion
- has capsule
- no invasion beyond capsule or blood vessel invasion
Follicular thyroid carcinoma
- microfollicular lesion
- capsular invasion and or vascular invasion => malignant
110
What are the clinical features of follicular thyroid carcinoma
- Painless mass
- Incidental on examination or radiology
- Hoarse voice / dysphagia if RLN involved
- LN mets very rare (contrast PTC)
- Can present with distant mets (bone #, lung nodule)
111
What is the treatment for follicular thyroid carcinoma
Excision
Radio-iodine (e.g. large tumour, mets, invasion outside thyroid)
112
How many parathyroid glands are there and where are they
Four
One on upper / lower poles of each thyroid lobe (usually)
113
What are parathyroid glands made up of
Mixture of chief cells, oxyphil cells and fat (fat increases with age)
114
How is parathyroid gland function controlled
Function controlled by free calcium in blood (not via pituitary)
115
What happens when there is a decrease in calcium
1. Sensed by parathyroid
2. Increases PTH levels
3. Decreases osteoblast activity and increases osteoclast activity
4. This increases calcium levels
116
What else do the parathyroid glands act on
Kidneys
117
What do most parathyroid abnormalities result in
Hyperparathyroidism (increase in PTH)
118
What are the 3 forms of Hyperparathyroidism
1. Primary Hyperparathyroidism
2. Secondary Hyperparathyroidism
3. Tertiary Hyperparathyroidism
119
What is primary Hyperparathyroidism
autonomous overproduction of PTH, usually resulting from an adenoma or hyperplasia of parathyroid tissue
120
What is secondary Hyperparathyroidism
compensatory hypersecretion of PTH in response to prolonged hypocalcemia, most commonly from chronic renal failure, malabsorption, vitamin D deficiency
121
What is tertiary Hyperparathyroidism
persistent hypersecretion of PTH, even after the cause of prolonged hypocalcemia is corrected (e.g., after renal transplant)
122
What is one of the most common endocrine disorders
Primary Hyperparathyroidism
123
what is primary Hyperparathyroidism a cause of
Hypercalcaemia
124
What are the causes of primary Hyperparathyroidism
- Parathyroid adenoma (85-95%) - by far most common cause
- Primary hyperplasia (5-10%)
- Parathyroid carcinoma (rare ~1%)
125
Who does primary Hyperparathyroidism affect
Usually adults
Females 4:1
126
How is primary Hyperparathyroidism usually found
Incidentally by high calcium levels
127
What is the most common cause of primary hyperthyroidism
Parathyroid adenoma
128
What is the cause of parathyroid adenomas
Most sporadic, unknown cause
Molecular defects and mutations
Familial syndromes
129
What does parathyroid adenoma look like histopathalogically
* Usually solitary solid nodule of cells
* Commonly chief cells but can see oxyphil cells
* Well circumscribed, thin capsule, adjacent B/G parathyroid
* Remaining glands small / supressed
130
What are the clinical features of Hyperparathyroidism
- Most diagnosed incidentally by ^Ca on blood tests -> most asymptomatic
- Clinical manifestations of incPTH/ inc Ca -> "painful bones, renal stones, abdominal groans, and psychic moans"
- Classical symptoms rarely seen
131
What is the treatment for parathyroid adenomas
Extraction
132
What is parathyroid carcinoma
malignant tumour derived from parathyroid cells
133
What % of primary Hyperparathyroidism is caused by parathyroid carcinoma
1%
134
What are the symptoms of parathyroid carcinoma
Symptoms as per hypercalcamia
135
What are the features of parathyroid carcinoma
* Fibrous bands
* Vascular invasion
* Invasion of background tissue
136
How do you treat parathyroid carcinoma
Surgery
137
Where are the adrenal glands in the body
Just above both kidneys
138
What are the adrenal glands also known as
Suprarenal glands
139
what are the 2 regions of the adrenal glands
Outer cortex
Inner medulla
140
What does the cortex in adrenal glands produce
- Glucocorticoids (mainly cortisol)
- Mineralocoricoids (mainly aldosterone)
- Sex steroids (mainly ostrogens / androgens)
141
What does the medulla in adrenal glands produce
Catecholamines (mainly adrenaline/NA)
142
Most adrenal defects are…
Cortical
143
What is hypercortisolism also known as
Cushing’s syndrome
144
what is hypercortisolism
Syndrome (collection of signs and symptoms) due to increased levels of glucocorticoids which result in metabolic / abnormalities
145
What is the most common cause of hypercortisolism
Exogenous steroids administration
146
What is endogenous cushings
Cushings as a result of abnormalities in the endocrine system
147
What are the 3 types of endogenous cushings and what are their effects
- Pituitary Cushings = Pituitary adenoma (70%) + †ACTH - †cortisol (Cushing's disease)
- Adrenal Cushings = Cortisol via adrenal adenoma / carcinoma, hyperplasia etc. -> dec in ACTH
- Paraneoplastic Cushings = †ACTH by tumours e.g. small cell lung cancer
148
What are the clinical features of Cushing’s syndrome due to
Glucocorticoid excess
149
What are the symptoms fo Cushing’s syndrome
Weight gain
Mental changes
150
How would you manage cushings if it was a pituitary cause
Surgery
Radiotherapy
151
How would you manage cushings if it was caused by other tumours
Surgery
152
what is the prognosis is cushings is left untreated and why
Poor prognosis due to hypertension
153
What is hypocortisolism known as
Addisons disease
154
what is hypocortisolism
Loss of entire adrenal cortex - inability to produce cortisol & aldosterone
155
What is affected by hypocortisolism
Blood pressure
Blood sugar regulation
Water/sodium balance
156
When is cortisol normally produced
During times of stress
157
How common is Addison’s disease and who does it affect more
Rare
Females
158
What is the vast majority of Addison’s caused by
Autoimmune disease
159
What are less common causes of addisons
TB
160
What is the classic triad seen in Addison’s disease
Triad of hyperpigmentation, postural hypotension and hyponatraemia.
161
How is Addisons disease treated
Long term steroid replacement
162
If Addisons is left undiagnosed what can happen
Can be fatal
163
Why is hyperpigmentation seen in Addisons disease
Decreased cortisol levels causes increases in CRH/ACTH
ACTH stimulates melanocytes to produce melanin causing hyperpigmentation
164
What occurs in 80-90% of cases with Addisons
postural hypotension
165
How is Addisons treated
Replacement steroids
166
Why may you need additional steroids during procedures in cases with Addisons
dental treatment -> hypotensive -> "Addisonian crisis" (medical emergency)
167
What is hyperaldosteronism
Excessive production of aldosterone which can result in hypertension
168
what are they 2 types of Hyperaldosteronism
primary and secondary
169
what is primary Hyperaldosteronism caused by
bilateral hyperplasia or solitary tumour "Conn's syndrome"
170
What is secondary Hyperaldosteronism caused by
due to RAS activation e.g. renal vascular disease (e.g. stenosis)
171
In Hyperaldosteronism, what is the effect of increased aldosterone levels
Na retention, K loss, H20 retention -> |[K] & hypertension
172
What does the management of Hyperaldosteronism depend on
depends on cause e.g. surgery for aldosterone secreting tumour
173
What are hyperplasias
Drugs
174
What is phaeochromocytoma
Rare tumour of catecholamine cells of adrenal medulla
175
Why is phaeochromocytoma clinically significant
As its a treatable cause of hypertension
176
What is hypertension a result of
Increased secretion of adrenaline/noradrenaline
177
What is the rule of 10 in regards to phaeochromocytoma
- 10% extra-adrenal
- 10% bilateral
- 10% malignant
178
What pattern does Phaeochromocytoma have
Nested ’zenballen’ pattern
179
How is Phaeochromocytoma treated
surgical excision
180
What are multiple endocrine neoplasia syndromes
* Inherited autosomal dominant diseases
* Proliferative / neoplastic diseases affecting multiple endocrine glands
181
What are the 3 forms of multiple endocrine neoplasia syndromes
MEN-1
MEN-2
182
What is MEN-1
What do pts with this present with
Mutation of MEN1 tumour suppressor gene
- Parathyroid hyperplasia / adenomas
- Pancreatic tumours (gastrin / insulin producing)
- Pituitary adenomas (most commonly prolactin)
183
What is MEN-2
What do pts with this present with
Gain of function of RET oncogene
- 2A = Medullary carcinoma, phaeochromocytoma, parathyroid hyperplasia
- 2B = As above but no parathyroid lesions, extra-endocrine lesions seen
