Endocrine Flashcards
1
Q
Features of water soluble hormones?
A
- transported unbound
- bind to cell surface receptors
- short half-life
- cleared fast
- stored in vesicles before secretion
2
Q
Example of water-soluble hormones?
A
- peptides
- monoamines
3
Q
Features of fat soluble hormones?
A
- transported bound to protein
- diffuse into cells
- long half-life
- cleared slowly
- synthesised on demand
4
Q
Examples of fat-soluble hormones?
A
- thyroid hormone
- steroids
5
Q
What is the main example of a peptide hormone?
A
Insulin
6
Q
How are peptide hormones stored?
A
Stored in secretory granules.
7
Q
How are peptide hormones released? (Timing)
A
Pulses / bursts
8
Q
How are peptide hormones cleared?
A
Tissue enzymes / circulating enzymes.
9
Q
How does insulin cause glucose uptake?
A
- binds to insulin receptors
- results in phosphorylation of the receptor
- this activates tyrosine kinase (secondary messenger)
- causing phosphorylation of signal cascade molecules
- results in glucose uptake (via GLUT4 channels)
10
Q
Examples of amine hormones?
A
- dopamine
- adrenaline
- noradrenaline
11
Q
What is the adrenaline (amine) synthesis pathway?
A
Phenylalanine > L-tyrosine > L-dopa > dopamine > noradrenaline > adrenaline
12
Q
Which enzyme breaks down noradrenaline / adrenaline?
A
COMT (Catechol-O-methyl transferase)
13
Q
What are the breakdown products of noradrenaline/ adrenaline?
A
Noradrenaline > normetanephrine
Adrenaline > metanephrine
14
Q
What does binding of nor(adrenaline) to alpha receptors cause?
A
- vasoconstriction
- bowel muscle contraction
- sweating
- anxiety
15
Q
What does binding of nor(adrenaline) to beta receptors cause?
A
- vasodilation
- increased HR
- increased force of contractility
- relaxation of bronchial smooth muscles
16
Q
What are iodothyronines (T3/T4) bound to?
A
Thyroid-binding globulin (TBG)
17
Q
Which is more active, T3 or T4?
A
T3
T4 is a reservoir for additional T3.
18
Q
Which hormone is produced more, T3 or T4?
A
T4
19
Q
How are T3/T4 synthesised?
A
- iodine binds to tyrosine on thyroglobulin
- this forms iodothyrosines (MIT / DIT)
- conjugation of MIT / DIT forms T3 / T4
20
Q
How are T3 / T4 stored?
A
Stored in colloid of thyroid follicular cells (bound to thyroglobulin).
21
Q
Thyroglobulin vs TBG?
A
Thyroglobulin binds T3/T4 in colloid of thyroid follicular cells.
TBG binds T3/T4 in the bloodstream.
22
Q
What does TSH stimulate?
A
Movement of colloid into secretory cell, where T4 and T3 are cleaved from thyroglobulin.
23
Q
Where does breakdown of T4 > T3 occur?
A
Outside the thyroid gland.
24
Q
How does vitamin D act on a cell?
A
- enters cell directly (lipid soluble)
- binds to nucleus to stimulate mRNA production
25
How is vitamin D transported?
Vitamin D binding protein
26
Adrenal cortex vs adrenal medulla?
Adrenal cortex - GFR makes good sex.
| Adrenal medulla - fight/flight (catecholamines, adrenaline)
27
How does oestrogen act on a cell?
Enters cell and acts directly on the nucleus.
28
How do cortisol, aldosterone, progesterone & testosterone act on a cell?
- enters cell and binds to cytoplasmic receptor
- receptor-hormone complex enters nucleus
- complex binds to glucocorticoid response element (GRE)
- binding initiates transcription
29
Which hormone receptors are located on the cell surface membrane?
Insulin
30
Which hormone receptors are located in the cytoplasm?
Steroids:
- glucocorticoids (cortisol)
- mineralocorticoids (aldosterone)
- androgens (testosterone)
- progesterone
31
Which hormone receptors are nuclear?
- thyroid hormones
- oestrogen
- vitamin D
32
Which hormones follow circadian rhythm?
- ACTH
- prolactin
- GH
- TSH
- cortisol
33
Which hormone inhibits prolactin?
Dopamine
34
Example of hormone receptor induction?
Induction of LH receptors by FSH.
35
What type of hormone are LH and FSH?
Peptide hormones.
36
Example of hormone synergism?
Glucagon + adrenaline.
| Released when hypoglycaemic.
37
How are the hypothalamus and pituitary connected?
By the infundibulum (pituitary stalk).
| Contains axons from hypothalamic neurones and small blood vessels.
38
Examples of hypophysiotropic hormones?
- CRH
- GHRH
- TRH
- GnRH
- dopamine
39
How does hypothalamus-anterior pituitary regulation work?
- hypothalamus is stimulated to release hypophysiotropic hormones by other areas of the CNS
- hormones reach the anterior pituitary via the hypothalamo-hypophyseal portal vessels
- hormones stimulate the release of hormones from the anterior pituitary
40
What is the blood supply to the anterior pituitary gland?
- no arterial supply
| - portal venous circulation (hypothalamo-hypophyseal vessels)
41
What are the 6 hormones secreted by the pituitary?
- FSH
- LH
- ACTH
- TSH
- prolactin
- GH
42
Name of cells where FSH is produced?
Gonadotrophs
43
Name of cells where LH is produced?
Gonadotrophs
44
Name of cell where ACTH is produced?
Corticotrophs
45
Name of cell where TSH is produced?
Thyrotrophs
46
Name of cell where prolactin is produced?
Lactotrophs
47
Name of cell where GH is produced?
Somatotrophs
48
What is the function of FSH?
- stimulates germ cell development (ovum / sperm)
| - stimulates oestrogen release (in females)
49
What does the release of oestrogen stimulate in the menstrual cycle?
Release of LH.
50
What is the function of LH?
- in females: stimulates the release of the egg, which stimulates progesterone release and causes thickening of the uterine wall
- in males: acts on leydig cells, stimulating testosterone release
51
What is the function of GH?
- stimulates gluconeogenesis and inhibits insulin (causing increased glucose)
- breaks down fat in adipose tissue
- acts on liver to increase protein synthesis
- stimulates IGF-1 which acts to increase cartilage proliferation
52
What is the function of ACTH?
- stimulates adrenal cortex to secrete cortisol (from zona fasiculata)
- stimulates androgen release (from zona reticularis)
- stimulates adrenaline release (from the adrenal medulla)
53
What is the function of cortisol?
- regulating & breaking down proteins, fats and carbohydrates
- anti-inflammatory effect (resulting in a lowered immune response)
- helps the body overcome stress (avoiding adrenal crisis)
54
What is the function of TSH?
- stimulates the release of thyroid hormone
55
What is the function of thyroid hormone?
- controls rate of metabolic reactions
- accelerates food metabolism
- increases protein synthesis
- stimulates carbohydrate metabolism
- enhances fat metabolism
- increases ventilation rate
- increases CO and HR
- brain development (foetal & post-natal)
- accelerates growth rate
56
What are the half lives of T3 and T4?
T3 - 1 day
| T4 - 5-7 days
57
What is the function of prolactin?
- stimulates breasts to produce milk
| - helps breast development
58
How does negative feedback work with prolactin?
Short-loop mechanism.
| Prolactin acts on the hypothalamus to stimulate dopamine. Dopamine inhibits the secretion of prolactin.
59
What tissue type is the posterior pituitary?
- many glial-type cells present
| - originates from neuronal tissue (extension of the hypothalamus)
60
What are glial cells?
Non-neuronal cells in the CNS that provide physical and metabolic support to neurons. (Like a Schwann cell but for the CNS).
61
Does the posterior pituitary synthesise hormones?
No, the hormones are synthesised in the hypothalamus and stored in the posterior pituitary.
62
Where is vasopressin synthesised?
Supraoptic nucleus.
63
Where is oxytocin synthesised?
Paraventricular nucleus.
64
How do vasopressin / oxytocin reach the posterior pituitary from the hypothalamus?
- axons of the supraoptic / paraventricular nuclei pass down the pituitary stalk and terminate in the posterior pituitary
- hormones move down the axons enclosed in vesicles and accumulate at the axon terminal in the posterior pituitary
65
What is the function of vasopressin?
- decreases water secretion in urine (helps maintain blood volume)
- acts on smooth muscle cells of blood vessels to cause vasoconstriction and increase BP (e.g. in response to low BP due to blood loss)
- stimulates ACTH release to increase aldosterone release
66
What stimulates vasopressin release?
- decreased blood volume
- trauma
- stress
- increased blood CO2 / decreased blood O2
- increased osmotic pressure of blood
67
What is the function of oxytocin?
- ejection of milk in response to mammary gland stimulation during breast feeding
- promotes the onset of labour and stimulates uterine smooth muscle contraction
68
What is the half life of vasopressin / oxytocin?
Very short, they are released on a minute to minute basis.
69
What receptors do all pituitary and hypothalamic hormones act on?
G-protein coupled receptors. (Cell-surface membrane receptors).
All are peptide hormones.
70
What are 6 main diseases of the pituitary?
- benign pituitary adenoma
- craniopharyngioma
- trauma
- Sheehan’s syndrome (pituitary infarction after labour)
- sarcoidosis (development of granulomas)
- TB
71
What are three main effects of pituitary tumours?
- pressure on local structures
- pressure on normal pituitary (hypopituitarism)
- functioning tumour (hyperpituitarism)
72
What might result from a tumour causing pressure on local structures?
- bitemporal hemianopia (pressure on optic chiasm)
- hydrocephalus (pressure on ventricles)
- CSF leak
73
What can result from a tumour causing pressure on the pituitary?
- cortisol deficiency - can be fatal
- presentation in males: pale, no body hair, central obesity, effeminate skin
- presentation in females: loose body hair, sallow complexion
74
What are the features of a prolactinoma?
- common in young women
- increased milk production in breast and galactorrhea)
- reduced fertility
- amenorrhoea
75
Treatment for prolactinoma?
Dopamine agonist to inhibit prolactin release. E.g. cabergoline.
76
What are some features of acromegaly?
- thick, greasy, sweaty skin
- large hands and feet
- enlarged organs (increased risk of heart disease)
- large brow and nose
77
What are some features of Cushing’s disease?
- central obesity
- bruising
- thin skin
- osteoporosis
- ulcers
- purple stretch marks
78
How does glucose uptake by the brain work?
- uptake independent of insulin
| - brain cannot use FFAs as an energy source as they cannot cross the BBB
79
What happens during biphasic insulin release?
- initially there is a rapid release of stored insulin
| - more insulin is synthesised and release if glucose levels remain high
80
What are some other counter-regulatory hormones of glucose (opposing insulin)?
- adrenaline, cortisol, GH
- increase glucose production in the liver
- reduce glucose utilisation in fat and muscle
81
Proinsulin vs insulin?
Proinsulin - contains alpha and beta insulin chains joined by C peptide.
Insulin - C peptide has been cleaved from alpha and beta chains.
82
Function of GLUT-1?
Enables basal, non-insulin stimulated glucose uptake into cells.
83
Function of GLUT-2?
- found in beta cells of pancreas (also renal tubules and hepatocytes)
- enables cells to sense glucose levels, by transporting glucose into the beta cell
- low affinity transporter: only allows glucose in when glucose concentration is high
84
Function of GLUT-3?
Enables non-insulin mediated glucose uptake into brain neurones and placenta.
85
Function of GLUT-4?
Channel in muscle and adipose
| cell surface membranes for glucose uptake stimulated by insulin.
86
Examples of when diabetes is secondary to another condition?
- pancreatic pathology (total pancreatectomy, chronic pancreatitis, haemochromatosis)
- endocrine disease (acromegaly, Cushing’s disease)
- drug-induced (thiazide diuretics, corticosteroids)
- MODY
87
Where is the most common place for carcinoid tumours to metastasise to?
Liver
88
What are some side effects of metformin?
- GI disturbances
- peripheral neuropathy due to decreased absorption of B12
- lactic acidosis
89
What is the mechanism of action of metformin?
Decreases gluconeogenesis and encourages insulin sensitivity.
90
What is the risk of metformin in patients with renal impairment?
Lactic acidosis.
91
What is the mechanism of action of sulphonylureas?
Act on beta cells to promote insulin secretion.
92
Side effects of sulphonylureas?
- GI disturbances
- frequent hypoglycaemia
- weight gain
93
Mechanism of action of pioglitazone?
Reduces peripheral insulin resistance.
94
Side effects of pioglitazone?
- bone fractures
- weight gain
- bladder cancer
95
Mechanism of action of DPP-4 inhibitors?
Inhibition of DPP-4 increases insulin secretion and lowers glucagon secretion.
96
Side effects of DPP-4 inhibitors?
- headache
| - acute pancreatitis
97
Mechanism of action of SGLT-2 inhibitors?
Inhibition of sodium-glucose co-transporter 2 results in reduced glucose reabsorption and increased urinary glucose excretion.
98
Side effects of SGLT-2 inhibitors?
- UTI
- genital pruritus
- DKA
99
What nerve roots are associated with carpal tunnel syndrome?
Median nerve (C5/6 - T1).
100
Diagnostic criteria for DKA?
- ketones >= 3.0 mmol/L
- glucose > 11.0 mmol/L
- pH < 7.3
101
What is the management of acromegaly?
1. Transphenoidal surgery.
2. Somatostatin analogue (ocreotide) +/- dopamine agonist.
3. GH-receptor antagonist (pegvisomant).
4. Radiotherapy
102
Non-diabetic HbA1c?
Less than 42 mmol/mol
103
Pre-diabetic HbA1c?
42 mmol/mol < HbA1c < 48 mmol/mol
104
Diabetic HbA1c?
> 48 mmol/mol
105
What is the cause of Cushing’s disease?
ACTH-secreting pituitary adenoma.
106
First line treatments for DKA?
```
IV fluids (0.9% sodium chloride).
IV insulin +/- potassium.
```
107
Which arrhythmia is a consequence of untreated hyperkalaemia?
Ventricular tachycardia
108
Gold standard test for acromegaly?
Oral glucose tolerance test.
109
Treatment of hypercalcaemia?
- fluids
| - bisphosphonates with calcitonin
110
Potassium in DKA?
Hyperkalaemia
111
Immediate management for carcinoid syndrome?
Somatostatin analogue (octreotide).
112
What is the definition of type 1 diabetes?
Autoimmune destruction of pancreatic beta cells leading to complete insulin deficiency.
113
What proportion of diabetes is type 1?
10%
114
Pathophysiology of T1D?
Autoantibodies attack beta cells in the islets of Langerhans, leading to insulin deficiency and hyperglycaemia. There is continuous breakdown of glycogen from the liver.
115
Risk factors for T1D?
- other autoimmune diseases
- HLA DR3-DQ2 or HLA DR4-DQ8
- northern european ancestry
116
Classic presentation of T1D?
- polydipsia
- polyuria
- weight loss
- ketosis
Usually short history of severe symptoms.
117
Diagnosis of T1D?
- random plasma glucose > 11 mmol/L
- fasting plasma glucose > 7 mmol/L
- HbA1c > 48 mmol/mol
118
Treatment of T1D?
Insulin therapy:
- quick-acting insulin given at mealtimes
- long-acting insulin given once or twice daily
119
Definition of type 2 diabetes?
Progressive disorder defined by deficits in insulin secretion and increased insulin resistance, leading to abnormal glucose metabolism and hyperglycaemia.
120
Secondary causes of type 2 diabetes?
- corticosteroid therapy (long term)
- Cushing's disease
- chronic pancreatitis
121
Risk factors for T2D?
- obesity
- physical inactivity
- aged > 40
122
Signs and symptoms of T2D?
- polydipsia
- polyuria
- central obesity
- blurred vision
123
Investigations for T2D?
- fasting plasma glucose > 7 mmol/L
- random plasma glucose > 11 mmol/L
- HbA1c > 48 mmol/mol
124
T2D management summary?
1. Lifestyle changes.
2. Metformin
3. Dual therapy with metformin + DPP4 inhibitor / sulphonylurea / pioglitiazone
4. Triple therapy.
5. Insulin therapy.
125
What is diabetic ketoacidosis?
Acute complication of T1D characterised by hyperglycaemia, ketonaemia and metabolic acidosis.
126
Causes of DKA?
- untreated T1D
- inadequate insulin therapy
- infection
- acute illness (MI, pancreatitis)
127
Pathophysiology of DKA?
- reduced insulin and increased insulin counter-regulatory hormones
- increased gluconeogenesis and glycogenolysis, with impaired glucose uptake in peripheral tissues
- this results in hyperglycaemia and hyperosmolality
- insulin deficiency leads to lipolysis and ketogenesis, resulting in metabolic acidosis
- osmotic diuresis results in severe dehydration and hypovolaemia
128
Why does hyperkalaemia occur in DKA?
- insulin normally drives potassium uptake into cells
- insulin deficiency increases serum potassium
- eventually total body potassium becomes low due to increased urinary excretion
129
What is the risk when correcting dehydration and hyperglycaemia in DKA?
Cerebral oedema - due to rapid shift in water from the extracellular space to the intracellular space in brain tissues.
130
Signs and symptoms of DKA?
- polydipsia and polyuria
- nausea & vomiting
- weight loss
- acetone smell on breath
- dehydration
- confusion / lethargy
- Kussmaul breathing (acidosis)
- tachycardia and hypotension
131
Investigations for DKA?
- random plasma glucose > 11 mmol/L
- plasma ketones > 3 mmol/L
- venous / arterial blood gas - pH < 7.35
- urine dipstick - glycosuria, ketouria
- raised urea and creatinine
- low total K+, elevated serum K+
132
Management of DKA?
ABCDE approach:
- IV fluids (0.9% saline) for rehydration
- IV insulin
- correct hypokalaemia
133
What is hyperosmolar hyperglycaemic state?
Serious complication of T2D - characterised by hyperglycaemia, hyperosmolality, and volume depletion in the absence of ketoacidosis.
134
Causes of HHS?
- infection (UTI, pneumonia)
- untreated T2D
- acute illness (MI, stroke)
135
Pathophysiology of HHS?
- relative insulin deficiency results in hyperglycaemia and hyperosmolality
- there may also be increased insulin counter regulatory hormones due to infection
- insulin concentration is sufficient to suppress lipolysis and ketogenesis, but insufficient to promoto glucose uptake and regulate gluconeogenesis and glycogenolysis
- osmotic diuresis results in hypovolaemia
136
What are insulin counter regulatory hormones?
- catecholamines (adrenaline)
- glucagon
- cortisol
- growth hormone
137
Signs and symptoms of HHS?
- nausea & vomiting
- weight loss
- polydipsia and polyuria
- dehydration
- confusion and lethargy
138
Investigations for HHS?
- random plasma glucose > 11 mmol/L
- urine dipstick - glycosuria
- plasma osmolality elevated
- raised creatinine
- raised serum K+, low total K+
139
Management of HHS?
- IV fluids (0.9% saline)
- IV insulin
- correct potassium
140
Causes of primary hyperthyroidism?
- Grave's disease
| - toxic multinodular goitre
141
Cause of secondary hyperthyroidism?
TSH-secreting pituitary adenoma
142
Most common cause of hyperthyroidism?
Grave's disease
143
Pathophysiology of hyperthyroidism?
Increased thyroid hormone increases metabolic rate, cardiac output, bone resorption, and activates the sympathetic nervous system.
144
Signs and symptoms of hyperthyroidism?
- hot and sweaty
- diarrhoea
- weight loss
- palpitations
- tremor
- irritability
- anxiety
- oligomenorrhoea
- goitre
145
Pathophysiology of Grave's disease?
TSH receptor autoantibodies cause thyroid hormone hyper-production, thyroid hypertrophy, and hyperplasia of thyroid follicular cells.
146
What causes extra-thyroidal manifestations of Grave's disease?
TSH receptors are also found in retro-orbital and dermal tissue. Autoantibodies stimulate fibroblasts, resulting in retro-orbital tissue expansion.
147
Signs and symptoms of Grave's disease?
- signs and symptoms of hyperthyroidism
- diffuse goitre
- orbitopathy (upper eyelid retraction, exophthalmos)
- pretibial myxoedema
- thyroid acropachy (digital clubbing)
148
Investigations for Grave's disease?
- serum T3 and T4 - elevated
- serum TSH - low
- serum TSH-R autoantibodies
- ultrasound neck
- CT head and neck
149
Management of Grave's disease?
- beta blockers to reduce sympathetic activity
- carbimazole / propylthiouracil in pregnancy
- radioiodine therapy
- thyroidectomy
150
Treatment of Grave's dermopathy?
Topical corticosteroid
151
Treatment of Grave's orbitopathy?
- eye drops
| - high dose corticosteroids if sight-threatening
152
Complications of thyroidectomy?
- laryngeal nerve damage
| - parathyroid damage
153
Complications of hyperthyroidism?
- AF
- congestive heart failure
- vision loss
154
What is Hashimoto's thyroiditis?
Autoimmune-mediated inflammation of the thyroid, usually resulting in hypothyroidism due to destruction of thyroid cells.
155
Causes of primary hypothyroidism?
- Hashimoto's thyroiditis
- primary atrophic hypothyroidism
- iodine deficiency
- post-thyroidectomy
156
Cause of secondary hypothyroidism?
Hypopituitarism
157
Signs and symptoms of hypothyroidism?
- fatigue & lethargy
- weight gain
- cold intolerance
- constipation
- depression
- menorrhagia
- goitre
158
Investigations for hypothyroidism?
- serum T3 and T4 - decreased
- TSH elevated if primary, decreased if secondary
- autoantibodies (thyroid peroxidase)
159
Treatment of hypothyroidism?
Thyroid replacement therapy with levothyroxine.
160
What is post-partum thyroiditis?
Autoimmune inflammation of the thyroid occurring within 12 months of delivery. May involve hyperthyroidism and / or hypothyroidism followed by a return to euthyroid.
161
What is the most common endocrine malignancy?
Thyroid cancer.
162
Risk factors for thyroid cancer?
- head and neck irradiation
| - family Hx
163
Clinical presentation of thyroid cancer?
- palpable thyroid nodule
- hoarseness due to laryngeal nerve involvement
- dysphagia
- cervical lymphadenopathy
164
Gold standard investigation for thyroid cancer?
Thyroid biopsy
165
Investigations for thyroid cancer?
- biopsy
| - ultrasound
166
Management of thyroid cancer?
- thyroidectomy
- radioactive iodine ablation
- chemotherapy / radiotherapy
167
What is Cushing's syndrome?
The clinical manifestation of pathological hypercortisolism from any cause.
168
What is Cushing's disease?
Pituitary adenoma secretes excessive ACTH, causing Cushing's syndrome.
169
Causes of Cushing's syndrome?
- exogenous corticosteroid exposure
- ACTH-secreting pituitary adenoma
- adrenal adenoma / carcinoma
- small cell lung cancer
170
Most common cause of Cushing's syndrome?
Exogenous corticosteroid exposure.
171
Clinical manifestations of Cushing's syndrome?
- facial rounding
- violaceous abdominal striae
- weight gain and central obesity
- acne
- depression
- proximal muscle wasting and weakness
- dorsal hump
- hypertension
- easy bruising
172
Which causes of Cushing's syndrome are ACTH dependent?
- pituitary adenoma
| - small cell lung cancer
173
Which causes of Cushing's syndrome are not ACTH dependent?
- adrenal adenoma
| - exogenous corticosteroid exposure
174
Gold standard investigation for Cushing's syndrome?
Dexamethasone suppression test.
175
Initial investigation for Cushing's syndrome?
Random plasma cortisol.
176
What do the results of the high-dose dexamethasone suppression test indicate?
Pituitary adenoma - high dose is sufficient to suppress cortisol.
Adrenal adenoma - high dose suppresses ACTH but not cortisol.
Small cell lung cancer - high dose does not suppress ACTH or cortisol.
177
Management of Cushing's syndrome?
- stop corticosteroid medication if possible
- trans-sphenoidal removal of pituitary adenoma
- adrenalectomy for adrenal adenoma
178
Complications of Cushing's syndrome?
- hypertension
- diabetes mellitus
- osteoporosis
- thrombosis
179
What is acromegaly?
Release of excess growth hormone, causing overgrowth of all systems.
180
Most common cause of acromegaly?
Pituitary adenoma.
181
Physiology of growth hormone?
- GH stimulates the release of IGF-1 from the liver
- IGF-1 causes widespread promotion of growth
- GH may also directly act on tissues to promote their growth
182
What hormone is a negative regulator of GH?
Somatostatin
183
Signs and symptoms of acromegaly?
- prominent forehead (frontal bossing)
- large protruding jaw (prognathism)
- large hands, nose, tongue, feet
- bitemporal hemianopia
- sweating
- lower pitch of voice
- obstructive sleep apnoea
- polydipsia and polyuria
- organomegaly
184
First line investigation for acromegaly?
Serum IGF-1 - elevated.
185
Gold standard investigation for acromegaly?
Oral glucose tolerance test.
186
Management of acromegaly?
1. Trans-sphenoidal resection of pituitary adenoma.
2. Somatostatin analogue (octreotide).
3. GH receptor antagonist (pegvisomant).
4. Dopamine agonist.
187
What is a prolactinoma?
Benign pituitary adenoma producing excess prolactin.
188
Signs and symptoms of prolactinoma?
- visual field defect (bitemporal hemianopia)
- headache
- menstrual irregularity
- infertility
- galactorrhoea
189
Why does a prolactinoma cause infertility?
Inhibition of FSH and LH.
190
Investigations for prolactinoma?
- pituitary MRI
| - serum prolactin
191
Management of prolactinoma?
1. Trans-sphenoidal resection of prolactinoma.
| 2. Dopamine agonists.
192
Dopamine agonist example?
Cabergoline
193
What is Conn's syndrome?
Primary hyperaldosteronism (i.e. due to adrenal adenoma).
194
Pathophysiology of Conn's syndrome?
Excess aldosterone production leads to:
- increased sodium and water retention
- increased renal potassium excretion
- hypertension
- metabolic acidosis
- low renin (negative feedback)
195
Signs and symptoms of Conn's syndrome?
- hypertension
- hypokalaemia
- polyuria, polydipsia
- mood and concentration disturbance
- muscle cramps
- arrhythmia (AF)
196
What cells does aldosterone act on?
```
Principle cells (sodium-potassium transporters) in the DCT.
Intercalated cells in the DCT (acid-base balance).
```
197
Investigations for Conn's syndrome?
- aldosterone / renin ratio - increased
| - serum potassium - low
198
Management of Conn's syndrome?
- spironalactone
| - laparoscopic adrenalectomy
199
What is Addison's disease?
Primary adrenal insufficiency, resulting in impaired synthesis and secretion of all steroids (glucocorticoids and mineralocorticoids).
200
Causes of Addison's disease?
- autoimmune
- infection (TB, pseudomonas, meningococcal)
- infiltrative disease (amyloidosis, sarcoidosis, haemochromatosis)
- metastasis
- bilateral adrenalectomy
- adrenal infarct
201
What causes skin hyperpigmentation in Addison's disease?
Increased synthesis of ACTH precursor proopiomelanocortin, also a precursor of melanocyte-stimulating hormone.
202
Signs and symptoms of Addison's disease?
- weight loss
- abdominal pain
- bronze hyperpigmentation
- fatigue
- postural hypotension
203
First line investigations for Addison's disease?
- U&Es - hyponatraemia, hyperkalaemia
| - blood glucose (hypoglycaemia)
204
Gold standard investigation for Addison's disease?
Short synACTHen test.
205
Serum renin and aldosterone in Addison's disease?
Renin - high
| Aldosterone - low
206
Serum cortisol and ACTH in Addison's disease?
Cortisol - low
| ACTH - high
207
What autoantibodies may be seen in Addison's disease?
21-hydroxylase antibodies
208
Summary of Addison's disease investigations?
```
1. U&Es
Gold standard - short synACTHen test.
- serum renin & aldosterone
- serum cortisol & ACTH
- 21-hydroxylase antibodies
- adrenal CT / MRI
```
209
Management of Addison's disease?
- hydrocortisone to replace cortisol
- fludrocortisone to replace aldosterone
- treat underlying cause
- warn against suddenly stopping steroids (emergency ID tag)
210
What is Addisonian (adrenal) crisis?
Emergency presenting with hypotension and tachycardia due to lack of cortisol.
211
Management of adrenal crisis?
- IV fluids
- IV hydrocortisone
- correct hypoglycaemia
- correct electrolytes
212
Causes of secondary adrenal insufficiency?
- cessation of long term corticosteroid usage
| - hypopituitarism
213
What is SIADH?
Syndrome of inappropriate ADH - characterised by hypotonic hyponatraemia, concentrated urine, and a euvolaemic state.
214
Causes of SIADH?
- small cell lung cancer
- CNS disorders (meningitis, encephalitis, trauma, multiple sclerosis, haemorrhage)
- anaesthesia and post-operative state
- nephrogenic (gain of function mutation in the vasopressin 2 receptor)
- medications (thiazide diuretics)
215
What is the most common cause of SIADH?
Medication (thiazide diuretics)
216
Signs and symptoms of SIADH?
- headache
- nausea
- fatigue
- muscle cramps
- confusion
217
Pathophysiology of SIADH?
- excessive ADH results in excessive water reabsorption in the collecting ducts
- water dilutes sodium in the blood, causing hyponatraemia
- increased extracellular volume results in RAA system suppression, and therefore increased naturesis
- euvolaemia as excessive water reabsorption is not enough to cause fluid overload
- high urine osmolality
218
Investigations for SIADH?
- hyponatraemia
- urine osmolality high
- urine sodium high
- exclude Addison's (short synACTHen test)
219
Causes of hyponatraemia?
- SIADH
- Addison's disease
- vomiting / diarrhoea
- diuretic use
- AKI / CKD
220
Management of SIADH?
- stop causative medication
- fluid restriction
- ADH receptor blocker (tolvaptan)
221
How should tolvaptan be used with caution?
ADH receptor blocker - don't let sodium rise too quickly (aim for increase of less than 10 mmol in 24 hours). Risk of osmotic demyelination syndrome.
222
What potassium level is considered hyperkalaemia?
> 5.5 mmol/L
223
Causes of hyperkalaemia?
- AKI / CKD
- ACE inhibitors
- Addison's disease
- decreased insulin
- IV K+ therapy
224
Signs and symptoms of hyperkalaemia?
- fatigue
- light-headedness
- chest pain
- palpitations (due to arrhythmia)
- reduced power and reflexes
- flaccid paralysis
225
Investigations for hyperkalaemia?
- ECG
- U&Es
- urine osmolality and electrolytes
226
Management of hyperkalaemia?
- cardiac monitoring and calcium gluconate to protect the myocardium
- insulin + dextrose
- nebulised salbutamol
- treat underlying cause
227
What potassium level is considered hypokalaemia?
< 3.5 mmol/L
228
Causes of hypokalaemia?
- thiazide and loop diuretics
- Conn's syndrome
- diarrhoea and vomiting
- fasting
- salbutamol
229
Symptoms of hypokalaemia?
- fatigue
- light-headedness
- cramps
- palpitations (due to arrhythmia)
- constipation
- hypotonia and hyporeflexia
- muscle paralysis
230
Severe complication of hypokalaemia?
Rhabdomyolysis
231
ECG signs of hypokalaemia?
- prolonged PR
- ST depression
- flat T waves
- prominent U waves
232
ECG signs of hyperkalaemia?
- tall tented T waves
- small / absent p waves
- prolonged PR
- wide QRS
233
Investigations for hypokalaemia?
- ECG
- U&Es
- urine osmolality and electrolytes
234
Management of hypokalaemia?
- potassium replacement (oral or IV)
| - treat underlying cause
235
What is diabetes insipidus?
Inadequate ADH secretion / inadequate renal response to ADH.
236
Subtypes of diabetes insipidus?
Central - abnormal ADH synthesis / secretion.
Nephrogenic - abnormal renal response to ADH.
Gestational - increased ADH metabolism.
237
Causes of central diabetes insipidus?
- brain tumours
- skull fracture
- surgical damage to hypothalamus / pituitary stalk
- CNS infection
- autoimmune disorders (Hashimoto's / T1D)
238
Causes of nephrogenic diabetes insipidus?
Congenital - X-linked mutation of vasopressin 2 receptors.
| Acquired - polycystic kidney disease, lithium.
239
Medication causing diabetes insipidus?
Lithium
240
Most common cause of nephrogenic diabetes insipidus?
Lithium
241
Where is vasopressin synthesised?
Supraoptic and paraventricular nuclei of the hypothalamus.
242
Signs and symptoms of DI?
- polyuria & polydipsia
- dehydration
- hypernatraemia (spasticity, hyper-reflexia, irritability)
243
Gold standard investigation for DI?
8 hour water deprivation test - no decrease in urine osmolality.
244
How is cranial DI distinguished from nephrogenic DI?
Desmopressin test following water deprivation test. If cranial, urine osmolality decreases. No decrease in urine osmolality if nephrogenic.
245
Management of DI?
- conservative management with rehydration in mild cases
- desmopressin to replace ADH in cranial DI
- bendroflumethiazide for nephrogenic DI if underlying cause cannot be resolved
246
What is primary hyperparathyroidism?
Parathyroid gland produces excess PTH.
247
What is secondary hyperparathyroidism?
Increased secretion of PTH to compensate for hypocalcaemia (e.g. due to kidney failure).
248
What is tertiary hyperparathyroidism?
Autonomous secretion of PTH even after correction of hypocalcaemia, due to CKD. Develops due to prolonged secondary hyperparathyroidism.
249
Causes of primary hyperparathyroidism?
- parathyroid adenoma (most common)
| - parathyroid hyperplasia
250
Causes of secondary hyperparathyroidism?
- CKD
| - low vitamin D
251
Signs and symptoms of hyperparathyroidism?
Hypercalcaemia
- bone pain
- renal stones
- psychiatric moans (depression)
- abdominal groans
252
Investigations for hyperparathyroidism?
- serum PTH
| - bone profile (high calcium, low phosphate)
253
Serum PTH and calcium in primary hyperPTH?
- normal / high PTH
| - high calcium
254
Serum PTH and calcium in secondary hyperPTH?
- low calcium
| - high PTH
255
Serum PTH and calcium in tertiary hyperPTH?
- high calcium
| - high PTH
256
Imaging for hyperPTH?
- DEXA scan
- X ray
- renal ultrasound for calculi
257
X ray signs in hyperPTH?
Salt and pepper degradation of bone.
258
Management of hyperPTH?
Mild - watchful waiting.
Primary: bisphosphonates, surgical removal of adenoma.
Secondary: correct calcium, treat underlying cause.
Tertiary: cinacalcet (calcium mimetic), parathyroidectomy.
259
Causes of primary hypoPTH?
- autoimmune destruction
| - congenital (DiGeorge syndrome)
260
Causes of secondary hypoPTH?
- surgical removal of parathyroid glands
| - damage during thyroidectomy
261
Pathophysiology of hypoPTH?
- hypocalcaemia and hyperphosphataemia
| - neurons become more excitable
262
Signs and symptoms of hypoPTH?
```
Hypocalcaemia (CATS go numb)
- convulsions
- arrhythmias
- tetany
- spasm
- numbness
Chvostek and Trousseau's signs.
```
263
Investigations for hypoPTH?
- bone profile (low calcium, high phosphate, low PTH)
| - ECG
264
ECG findings hypoPTH?
- prolonged QT
| - prolonged ST
265
Management of hypoPTH?
- IV calcium
- AdCal D3
- synthetic PTH
266
Risk factors for neuroendocrine tumours?
- multiple endocrine neoplasia
- neurofibromatosis type 1
- von hippel-lindau
267
Where are neuroendocrine tumours commonly located?
- stomach
- intestine
- pancreas
- lungs
268
Examples of neuroendocrine tumours?
- insulinoma
- gastrinoma
- small cell lung cancer
269
What is carcinoid syndrome?
Symptoms occurring due to the release of serotonin (5-HT) and other vasoactive peptides into the systemic circulation from a carcinoid (neuroendocrine) tumour.
270
Signs and symptoms of carcinoid syndrome?
- diarrhoea
- flushing
- palpitations
- abdominal cramps
- telangiectasia
- wheeze
271
Investigations for carcinoid syndrome?
- urinary 5-hydroxyindoleacetic acid (serotonin metabolite)
- CT chest, abdomen, pelvis
- bronchoscopy / endoscopy
272
Management of carcinoid syndrome?
- somatostatin analogue (octreotide)
| - surgical resection of tumour
273
What is a pheochromocytoma?
Tumour arising from catecholamine-producing chromaffin cells of the adrenal medulla.
274
Hereditary risk factors for pheochromocytoma?
- multiple endocrine neoplasia type 2
- von hippel-lindau
- neurofibromatosis type 1
275
Pathophysiology of pheochromocytoma?
- excess secretion of catecholamines
- activation of alpha and beta adrenergic receptors
- alpha receptors: increased BP, increased cardiac contractility
- beta receptors: increased HR and cardiac contractility
276
Pattern of symptoms in pheochromocytoma?
```
Usually paroxysmal (associated with periods when the tumour is secreting adrenaline).
Can be persistent / asymptomatic.
```
277
Classic triad of symptoms in pheochromocytoma?
- episodic headache
- sweating
- tachycardia
278
Symptoms of hypertensive crisis?
- hypertension
- hyperthermia
- confusion
- end-organ dysfunction
- hypotension due to circulatory collapse
279
Complication of pheochromocytoma?
Hypertensive crisis
280
Investigations for pheochromocytoma?
- plasma free metanephrines (if high probability)
- urinary fractionated metanephrines (if low probability)
- CT / MRI
281
Complications of hypertensive crisis?
- stroke
- cardiac failure
- seizure
282
Management of pheochromocytoma?
- adrenalectomy
| - alpha- and beta-blockers to control hypertension prior to surgery
283
Calcium in Addison's disease?
Raised due to volume depletion and increased release into extracellular space.
284
Addison's disease and blood volume?
Blood volume decreased due to naturesis.
285
Most common cause of Addisonian crisis?
Abrupt cessation of long term corticosteroid treatment.
286
Most important treatment for Addisonian crisis?
Hydrocortisone
287
What is pseudohypoPTH?
Peripheral resistance to PTH.
