Endocrinology Flashcards
1
Q
At what eGFR is metformin contraindicated?
A
<30
2
Q
What is phaeochromocytoma?
A
A rare catecholamine secreting tumour of the adrenal medulla
3
Q
What are the two parts of the adrenal gland?
A
Outer cortex
Inner adrenal medulla
4
Q
What does the adrenal cortex produce?
A
Mineralocorticoids - e.g. aldosterone
Glucocorticoids - mainly cortisol
Androgens - mainly dehydroepiandrosterone (DHEA) and testosterone
5
Q
Where is ACTH made/secreted from?
A
Anterior pituitary gland
6
Q
What does the adrenal medulla produce?
A
Catecholamines - e.g. adrenaline, noradrenaline and dopamine.
7
Q
Describe the HPA axis
A
Hypothalamus produces CRH
CRH activates the anterior pituitary
Ant. pituitary releases ACTH which stimulates the cortex of the medulla
8
Q
What is Cushing’s syndrome?
A
This is a disorder in which the body produces too much cortisol (glucocorticoid)
9
Q
What is more common, exogenous or endogenous Cushing’s?
A
Exogenous is far more common
10
Q
What is an exogenous cause of Cushing’s?
A
Steroid therapy e.g. for eczema, asthma, RA etc
11
Q
How can we split endogenous causes of Cushing’s?
A
ACTH dependent
ACTH independent
12
Q
What are some ACTH dependent causes of Cushing’s?
A
Cushing’s disease (80%) - pituitary tumour secreting ACTH resulting in adrenal hyperplasia
Ectopic ACTH production (5-10%) - e.g. small cell lung cancer
13
Q
What are some ACTH independent causes of Cushing’s syndrome?
A
Adrenal adenoma
Adrenal carcinoma
Carney complex
Micronodular adrenal dysplasia
14
Q
What are signs/symptoms of Cushing’s syndrome?
A
Central obesity (but thin arms/legs) Round moon-like face Fat deposition above collar bone, behind neck Thin skin Muscle weakness High BP High blood sugar Reduced libido/ED
15
Q
What are some causes of pseudo-Cushing’s?
A
Alcohol excess
Severe depression
16
Q
How can we differentiate pseudo-cushing’s from cushing’s?
A
Insulin stress test
17
Q
What might you see on an ABG in Cushing’s?
A
A hypokalaemic metabolic alkalosis
18
Q
What two tests do we commonly do to diagnose Cushing’s?
A
Overnight dexamethasone suppression test (most sensitive)
24 hr urinary free cortisol
19
Q
Dexamethasone suppression results interpretation
A
Cortisol not suppressed by low dose - Cushing’s syndrome
Suppressed by high dose - Cushing’s disease (pituitary adenoma)
Not suppressed by low or high dose - ectopic ACTH syndrome likely
High dose suppresses ACTH but not cortisol - adrenal tumour
20
Q
What is primary adrenal failure?
A
Atrophy/destruction of the adrenal gland
21
Q
What is secondary adrenal failure?
A
Inadequate ACTH production
Most commonly from acute steroid withdrawal
22
Q
Symptoms/features of primary adrenal failure?
A
Lethargy Weakness Anorexia Nausea + vomiting Weight loss Hyperpigmentation (particularly palmar creases) Loss of pubic hair Hypotension (hypovolaemic shock is commonly how acute adrenal insufficiency presents) Hypoglycaemia Hyponatraemia Hyperkalaemia
23
Q
Is ACTH high or low in primary adrenal failure?
A
High
24
Q
What is the common cause of primary adrenal failure?
A
Addison’s disease - autoimmune destruction of the adrenal glands
25
What is reduced in adrenal failure?
Cortisol (and aldosterone)
26
How can we temporarily lower cortisol before surgery/other curative treatment for cushing's syndrome?
Metyrapone (inhib. cortisol synth.) or ketoconazole (p450 inhibition)
27
What is Addison's disease associated with?
Vitiligo
Premature ovarian failure
Hypothyroidism
Female gender
28
What is the mechanism of pathology in secondary adrenal failure?
Chronic steroid use lowers ACTH levels
This causes adrenal cortex atrophy
If suddenly stopped can provoke adrenal failure
29
How do we investigate adrenal failure?
Short synacthen test (measure cortisol, give them ACTH and then measure cortisol again)
Can also measure adrenal autoantibidoies (e.g. anti-21-hydroxylase)
30
How do we manage adrenal failure?
Chronic
Hydrocortisone (20mg/day), double during infection
Can give fludrocortisone as well but only in primary adrenal failure (because then mineralocorticoids are affected as well)
Acute
Medical emergency - resus + hydrocortisone
Address precipitating factor (e.g. infection)
31
What is congenital adrenal hyperplasia?
A group of autosomal recessive disorders that affect adrenal steroid biosynthesis
32
Is ACTH high or low in congenital adrenal hyperplasia?
ACTH is high in response to low cortisol levels
33
What can high ACTH cause in female infants?
Adrenal androgens that may virilise them
34
What deficiencies cause congenital adrenal hyperplasia?
21-hydroxylase (90%)
11-beta hydroxylase (5%)
17-hydroxylase (v. rare)
35
Features of congenital adrenal hyperplasia?
Virilization of female genitalia
Precocious puberty in males
Salt losing crisis
36
Treatment of CAH?
Dexamethasone (I think)
37
What is Conn's syndrome and what does it cause?
Benign adrenal adenoma causing primary hyperaldosteronism
38
Features of hyperaldosteronism
HTN
Hypokalaemia (muscle weakness)
Alkalosis
39
How to diagnose hyperaldosteronism?
Aldosterone/reniin ratio (should show high aldosterone levels alongside low renin levels - due to negative feedback from sodium retention by aldosterone)
CT
40
How do we treat hyperladosteronism?
```
Surgical removal
Aldosterone antagonist (e.g. spironolactone)
```
41
What are features of phaeochromocytoma?
```
Usually episodic, brought on by exercise etc.)
HTN (90%)
Headaches
Palpitations
Sweating
Anxiety
```
42
How do we test for phaeochromocytoma?
24 hour urinary collection of metanephrines (metabolites of catecholamines)
MRI
43
Treatment of phaeochromocytoma?
Initial:
Alpha blockade - phenoxybenzamine
Beta blockade - propanolol
Definitive:
Adrenalectomy
44
What is Addisonian crisis?
A severe adrenal insufficiency that is life threatening
45
What causes Addisonian crisis?
Sepsis/surgery exacerbating the chronic insufficiency from Addison's/hypopituitarism
Adrenal haemorrhage (e.g. Waterhouse-Friderichsen syndrome)
Steroid withdrawal
46
How do we manage addisonian crisis?
Hydrocortisone (100mg im/iv), then continue 6 hourly till patient is stable
1 litre normal saline infused over 30-60 mins (or with dextrose)
Oral replacement after 24 hours, reduced to maintenance after 3 days
47
What are features of addisonian crisis?
```
Sudden penetrating pain in legs/lower back/abdomen
Confusion/psychosis, slurred speech
Severe lethargy
Convulsions
Fever
Hyperkalaemia
Hypercalcaemia
Hypot./hypon./hypogly.
Syncope
```
48
Control of thyroid hormone secretion
Hypothalamus produces thyrotropin-releasing hormone (TRH)
TRH stimulates the anterior pituitary to release thyroid-stimulating hormone (TSH)
TSH stimulates the thyroid to release thyroxine (T4) and triiodothyronine (T3)
49
What do T3/T4 do?
They act on a wide variety of tissues helping the regulation of energy sources, protein synthesis and also affects their sensitivity to other hormones
50
Which is active, T3 or T4?
T3. T4 is converted peripherally into T3 which is 4x more potent.
T3 is less tightly bound than T4 to plasma proteins
51
How do we classify hypothyroidism?
Primary - problem with the thyroid itself
Secondary - problem with the pituitary gland
Congenital
52
What are causes of primary hypothyroidism?
```
Hashimoto's thyroiditis (most common)
Subacute thyroiditis (De Quervain's)
Iodine deficiency
Drug therapy (e.g. lithium, carbimazole, amiodarone)
```
53
What are causes of secondary hypothyroidism?
Pituitary failure
Down's
Turner's
Coeliac's
54
What are features of hypothyroidism?
```
Weight gain
Lethargy
Cold intolerance
Dry, cold skin
Constipation
Menorrhagia
Decreased deep tendon reflexes
```
55
What is hashimoto's thyroiditis?
Autoimmune disease causing hypothyroidism, it is the most common cause of hypothyroidism
56
Features of hashimoto's thyroiditis
Associated with T1DM, Addison's/pernicious anaemia
Can cause transient thyrotoxicosis in the acute phase
5-10 times more common in women
57
What is de Quervain's thyroiditis?
Hypothyroidism that is usually triggered by a viral infection, it presents with a painful goitre/fever, and it causes a raised ESR
58
What is Riedel's thyroiditis?
When fibrous tissue replaces the normal thyroid parenchyma
| It causes a painless goitre
59
What are the TSH and free T4 levels in Hashimoto's thyroiditis?
High TSH
| Low T4
60
What is the TSH and T4 in secondary hypothyroidism?
Both are low
61
What would you see in TSH/T4 if compliance with thyroxine was bad?
High TSH
Normal T4
(Patient with poor compliance may just be taking thyroxine in the days before their blood test)
62
Which autoantibodies should be tested for in thyroid disorders?
Anti-thyroid peroxidase (anti-TPO)
TSH receptor antibodies
Thyroglobulin antibodies
TSH receptor antibodies are almost always present in Grave's disease
Anti-TPO antibodies are almost always present in Hashimoto's
63
What is subclinical hypothyroidism?
Where TSH is high and T4 is normal, basically they are on their way to developing hypothyroidism but still have normal thyroxine
64
What is the treatment for hypothyroidism?
Levothyroxine (25mcg if cardiac disease/over 50 as well, 50-100mcg otherwise)
65
Levothyroxine management of hypothyroid
Test thyroid function 8-12 weeks after levothyroxine change
Normal TSH of 0.5-2.5
If pregnant, levothyroxine should be increased by 25-50mcg
66
What are side effects of thyroxine?
Reduced bone mineral density
AF
Worsening of angina
Hyperthyroid
67
Symptoms of thyrotoxicosis?
```
Weight loss
Heat intolerance
Palpitations (tachycardia)
Diarrhoea
Oligomenorrhoea
Anxiety
Tremor
```
68
What are causes of thyrotoxicosis?
Graves' disease
Toxic nodular goitre
Acute phase of de Quervain's thyroiditis/Hashimoto's
Amiodarone therapy
69
What do you see on investigation in thyrotoxicosis?
TSH down
| T3/T4 up
70
What are features of graves' disease not present in other causes of thyrotoxicosis?
Exophthalmos
Ophthalmoplegia
Pretibial myxoedema
Thyroid acropachy
71
What is myxoedema?
A dermatological change commonly seen in severe hypothyroidism. Mucopolysaccharides are deposited in the dermis resulting in swelling of the area
72
What is pretibial myxoedema?
Myxoedema of the lower limb, seen in Graves' disease
73
What is the pathophysiology of thyroid eye disease?
Caused by an autoimmune response against an autoantigen (maybe TSH receptor?) causing retro-orbital inflammation
74
How can you prevent thyroid eye disease?
Smoking prevention
| Radioiodine treatment can increase the inflammatory symptoms of thyroid eye disease
75
What is exophthalmos?
Bulging of the eye anteriorly (usually bilaterally in Graves') due to abnormal connective tissue deposition in the orbit/extraocular muscles
76
How do we treat thyroid eye disease?
Topical lubricants
Steroids
Radiotherapy
Surgery
77
What is ophthalmoplegia?
Paralysis of the muscles within the eye/surrounding the eye
78
What are the features of thyroid eye disease?
Exophthalmos
Conjunctival oedema
Optic disc swelling
Ophthalmoplegia
79
What is the treatment of Graves' disease?
Anti-thyroid drugs:
Carbimazole
Radioiodine treatment (can make thyroid eye disease worse)
80
What are the two ways you can give carbimazole in Graves'?
Anti-thyroid drug titration
Block and replace
81
What is the concerning side-effect of carbimazole therapy?
Agranulocytosis
82
What is thyroid storm?
A rare, life-threatening complication of thyrotoxicosis
83
What causes thyroid storm?
```
Usually has a precipitating event:
Surgery
Trauma
Infection
Acute iodine overload (e.g. from CT contrast)
```
84
Clinical features of thyroid storm?
```
Fever >38.5
Tachycardia
Confusion/agitation
Nausea and vomiting
HTN
Heart failure
Abnormal liver function (jaundice?)
```
85
How do we manage thyroid storm?
Paracetamol
Treat precipitating event
Beta blockers (IV propanolol)
Propylthiouracil/methimazole (anti-thyroid drugs)
Dexamethasone (blocks T4 conversion to T3)
86
What are the parathyroid glands?
Four tiny glands located in the neck that control the body's calcium levels
They do this via secretion of parathyroid hormone
87
How does PTH affect calcium?
3 ways:
Stimulates osteoblasts (and osteoclasts indirectly) to break down and release calcium
Stimulates GI calcium absorption by activating vitamin D
Promotes calcium conservation at the kidineys
88
What does PTH do to phosphate levels?
PTH is the major regulator of serum phosphate concentrations via the kidney. It inhibits its reabsorption and thus lowers the levels of phosphate
89
What are the features of hypercalcaemia?
'bones, stones, abdominal groans and psychic moans':
```
Polydipsia, polyuria
Peptic ulceration/constipation/pancreatitis
Renal stones
Depression
HTN
```
90
What are the findings in hyperparathyroidism investigations?
Raised calcium
Low phosphate
PTH may be raised
Pepperpot skull is characteristic on x-ray
91
Primary vs secondary hyperparathyroidism?
Primary:
Proliferation of chief cells in the parathyroid
Secondary:
Renal disease resulting in calcium loss/vit. D deficiency can result in compensation from the parathyroid (hypertrophy to synthesise more PTH)
92
Treatment of primary hyperparathyroidism?
Total parathyroidectomy
| Medical: Cinacalcet
93
What is the main cause of primary hyperparathyroidism?
80% are caused by a parathyroid adenoma
94
What is an adenoma?
A benign proliferation of glandular tissue
95
Primary hypoparathyroidism
Decreased PTH secretion
Can be caused by things like thyroid surgery
You get a low calcium and high phosphate
96
What are the symptoms of hypoparathyroidism?
```
Symptoms of hypocalcaemia:
Tetany (muscle twitching/cramping/spasm)
Perioral paraesthesia
Trousseau's sign (carpal spasm)
Chvostek's sign (tapping over parotid causes facial muscles to twitch)
ECG: prolonged QT interval
Chronic: depression/cataracts
```
97
What is pseudohypoparathyroidism?
Where the target cells are insensitive to PTH
This is due to an abnormality in a G protein
You get low calcium, high phosphate and high PTH
98
How do we treat hypoparathyroidism?
Alfacalcidol
99
What does the anterior pituitary produce?
```
ACTH
Growth hormone
Luteinising hormone and FSH
Prolactin
TSH
```
100
What does the posterior pituitary store and release (originally produced in hypothalamus)?
ADH (vasopressin)
| Oxytocin
101
What does the intermediate pituitary gland produce?
Melanocyte-stimulating hormone
102
What is acromegaly
A condition caused by an excess of growth hormone secondary to a pituitary adenoma in 95% of cases
103
What are the features of acromegaly
```
Coarse facial appearance
Spade like hands
Large shoe size
Large tongue
Prognathism (outward jaw)
Excess sweating/oily skin
Pituitary tumour features (headache, bitemporal hemianopia)
Raised prolactin
```
104
What are complications of acromegaly
HTN
Diabetes
Cardiomyopathy
Colorectal cancer
105
How do we investigate acromegaly
Serum IGF-1 levels + OGTT
In normal patients growth hormone is suppressed to <2, there's no suppression in acromegaly
106
How do we manage acromegaly?
Trans-sphenoidal surgery is first line
Dopamine agonists (bromocriptine)
Somatostatin analogue (directly inhibits growth hormone release) - octreotide
107
What is a prolactinoma?
A tumour of the pituitary gland which produces high levels of prolactin
108
Features of hyperprolactinaemia
Infertility
Decreased sex drive
Bone loss
Women:
Vaginal dryness
Irregular periods
Production of milk when not pregnant/nursing
Men:
ED
Breast enlargement
Decreased muscle mass/body hair
109
How to diagnose hyperprolactinaemia?
Blood test
Thyroid tests too (rule out hypothyroidism as cause)
Pregnancy test
MRI head for prolactinoma
110
Treatment for hyperprolactinaemia
Surgery for tumour
Bromocriptine and cabergoline reduce prolactin production
Radiation
111
Causes of high prolactin
```
Prolactinoma
Hypothyroidism
Chest wall injuries/shingles
Chronic liver/kidney disease
Drugs
```
112
What causes hypopituitarism?
```
Tumours in or near the pituitary gland
Radiation treatment for a tumour
Chemo
Brain surgery
Traumatic bain injury
TB/meningitis
```
113
Symptoms of hypopituitarism?
```
Stomach pain, decreased appetite, nausea and vomiting, constipation
Excessive thirst/urination
Fatigue/weakness
Anaemia
Headache/dizziness
```
114
How do we treat hypopituitarism?
Replacement of the missing hormones
| Surgery to remove the tumour
115
What type of adenoma causes hypopituitarism?
Macroadenomas
116
How do we classify pituitary tumours?
By size:
Microadenoma - <1cm in diameter
Macroadenoma >1cm in diameter
Hormone status:
e.g. prolactinoma
117
What type of hemianopia can we get in pituitary adenomas with mass effect?
Bitemporal hemianopia due to compression of the optic chiasm
118
How do you investigate pituitary tumours?
Pituitary blood profile (prolactin, TFTs, ACTH, GH and FSH/LH)
Visual field testing
MRI brain with contrast
119
What is diabetes insipidus?
A disorder characterised by lack of ADH/or insensitivity to ADH
120
What are causes of cranial DI?
Idiopathic
Head injury
Pituitary surgery
Haemochromatosis
121
What are causes of nephrogenic DI?
Genetic (vasopressin receptor affected - aquaporin 2 channel)
Tubulo-interstitial disease - obstruction/pyelonephritis, sickle-cell
122
What are features of DI?
Polyuria
| Polydipsia
123
What is the difference between cranial and nephrogenic DI?
Deficiency to produce ADH (cranial)
| Insensitivity to ADH (nephro)
124
What are investigation findings in DI?
Urine osmolality of >700 excludes DI
| Water deprivation test
125
How do we treat DI?
Thiazides, low salt/protein diet (nephrogenic)
| Desmopressin (cranial)
126
What is Nelson’s syndrome?
This is where, say you removed the adrenal gland, that you then get zero negative feedback to the pituitary. It keeps producing ACTH and hypertrophies.
Symptoms include discolouration of skin, visual disturbance, headache
