Endocrine Flashcards
(145 cards)
1
Q
What hormones are released from the anterior pituitary?
A
ACTH
TSH
LH/FSH
GH
2
Q
What hormones are released from the posterior pituitary?
A
Prolactin
ADH
3
Q
What visual disturbance is caused by compression of the optic chiasm?
A
Bitemporal hemianopia
4
Q
What are the different types of pituitary tumours?
A
Non-functional
Functional
Other
5
Q
What are the effects of functional pituitary tumours?
A
Prolactin - prolactinoma
GH - acromegaly
ACTH - Cushing’s disease
TSH - TSHoma
6
Q
Give three examples of ‘other’ pituitary tumours
A
Craniopharyngioma
Pituitary cancer
Rathke’s cyst
7
Q
Describe non-functional pituitary tumours
A
Most common (25%) No hormonal releases Mass effects - visual field defects - headache - stops other pituitary hormones working - eye movement problems due to involvement of cranial nerves --> blurred vision
8
Q
How should non-functioning pituitary tumours be investigated?
A
Imaging - MRI
Visual field assessment
Measure pituitary hormones
9
Q
How should non-functioning pituitary tumours be managed?
A
Surgery - protection of vision
Radiotherapy
10
Q
Describe hypopituitarism
A
Failure of the (anterior) pituitary
Can affect a single hormonal axis or all hormones (panhypopituitarism)
Leads to secondary gonadal/thyroid/adrenal failure
Need multiple hormone replacement
11
Q
In hypopituitarism, what hormonal replacement therapy should always be started first?
A
Hydrocortisone
12
Q
Give some potential causes of hypopituitarism
A
Tumours Radiotherapy Infarction/haemorrhage (apoplexy) Infiltrate (sarcoid) Trauma Lymphocytic hypophysitis
13
Q
What are potential causes of high prolactin?
A
Prolactinomas
Physiological - pregnancy, breast feeding
Drugs that block dopamine
Stalk effect - loss of inhibitory dopamine
14
Q
Give examples of drugs that block dopamine
A
Tricyclics
Antiemetics
Antipsychotics
15
Q
What is a prolactinoma?
A
Pituitary tumour that secretes prolactin
16
Q
What are the clinical features of a prolactinoma?
A
Galactorrhoea Headaches Mass effects Visual field defects Amenorrhoea/erectile dysfunction
17
Q
Describe the diagnosis of prolactinoma
A
Serum prolactin (>6000) MRI pituitary Test remaining pituitary function
18
Q
Describe the treatment of a prolactinoma
A
Medical:
Dopamine agonist - cabergoline, bromocriptine
Surgical:
VF compromised
Failure of medical therapy
19
Q
Describe the association of prolactinomas and pregnancy
A
Pituitary gland get bigger in pregnancy - increase in prolactin production
Dopamine agonists are contraindicated
[Prolactin] is unhelpful
Monitor visual fields if macroprolactinoma
20
Q
Describe acromegaly
A
Pituitary tumour secreting growth hormone post puberty
21
Q
What are the clinical features of acromegaly?
A
Sweats and headaches Alteration of facial features Increased hand/feet size Visual impairment Cardiomegaly
22
Q
Describe the diagnosis of acromegaly
A
Glucose tolerance test (glucose should suppress GH)
Measure IGF-1 (GH stimulates liver to produce IGF-1)
MRI
23
Q
Describe the management of acromegaly
A
Surgery - first line to debulk tumour
Drugs:
Somatostatin analogue - octreotide (before and after surgery)
Dopamine agonist
GH receptor antagonist (Pegvisomant)
Radiotherapy - residual tumour/ongoing symptoms
24
Q
Describe Cushing’s disease
A
Pituitary tumour secreting ACTH
25
What are the symptoms of Cushing's disease?
```
Weight gain
Thin skin
Easy bruising
Hypertension
Osteoporosis
```
26
How can Cushing's disease be diagnosed?
Try to suppress ACTH by dexamethasone suppression therapy
27
Describe the management of Cushing's disease
Surgery first line
If fails or inappropriate:
Bilateral adrenalectomy
Medical therapy - metyrapone, ketoconazole
Radiotherapy
28
Describe TSHoma
Rare pituitary tumour releasing TSH
29
What TFT results are associated with TSHoma?
High TSH
| High fT4
30
What are the two types of Diabetes Inspidus?
Central
| Nephrogenic
31
What are potential central causes of diabetes insidius?
```
Idiopathic
Trauma
Pituitary tumour
Pituitary surgery
Pregnancy
```
32
What are the clinical features of diabetes inspidus?
Polydipsia
| Polyuria (>3L/d urine output)
33
Describe the diagnosis of diabetes inspidus
Try to stimulate the release
Water deprivation test
Assess ability to concentrate urine with ADH (nephrogenic won't)
34
What is diabetes inspidus?
ADH deficiency
35
Describe the treatment of diabetes inspidus
Treat underlying cause
| ddAVP (spray, tablets, injection)
36
What are the layers of the adrenal cortex, and what does each layer produce?
Zona Glomerulosa = aldosterone
Zona Fasciculata = cortisol
Zona Reticularis = androgens
37
What cells are located in the adrenal medulla, and what do they produce?
Chromograffin cells
| Catecholamines
38
What features are commonly associated with primary aldosteronism (Conn's syndrome)?
Hypertension
| Hypokalaemia
39
What biochemistry is associated with primary aldosteronism (Conn's syndrome)?
High aldosterone
Low renin
Very high aldosterone:renin ratio
40
What medications should be stopped if a patient is thought to have primary aldosteronism (Conn's syndrome)?
Beta blockers
41
What medications can be used in patients who have primary aldosteronism (Conn's syndrome)?
Alpha blockers
Verapamil
Hydralazine
42
How is primary aldosteronism (Conn's syndrome) diagnosed?
Saline suppression test
2L of saline over 4 hours (should suppress aldosterone production)
4h aldosterone >470pmol/l = highly suspicious
43
Describe the management of primary aldosteronism (Conn's syndrome)
Surgical:
Unilateral laparoscopic adrenalectomy - if adrenal adenoma
Cures hypokalaemia
Cures HTN in 30-70%
```
Medical:
MR antagonist (spironolactone/eplerenone)
```
44
What are the clinical features associated with Cushing's syndrome?
```
Hirsutism
Striae
Proximal myopathy
Plethora
Easy bruising
HTN
```
45
Describe the diagnosis of Cushing's syndrome
24h urinary free cortisol
Dexamethasone suppression testing
Late night salivary cortisol (cortisol should be at its lowest levels during the night)
46
What are the causes of Cushing's syndrome?
ACTH dependent:
Pituitary adenoma = Cushing's disease
Ectopic ACTH
Ectopic CRH
ACTH independent:
Adrenal adenoma
Adrenal carcinoma
Nodular hyperplasia
47
What is the mode of inheritance of congenital adrenal hyperplasia?
Autosomal recessive
48
Define congenital adrenal hyperplasia
Range of genetic disorders relating to defects in steroidogenic genes
49
What is the most common gene which is mutated in congenital adrenal hyperplasia?
CYP21 (21 hydroxylase)
50
What happens to hormone levels in congenital adrenal hyperplasia?
Aldosterone and cortisol not produced
| Increased androgen and 17-OH progesterone
51
What are the effects on males and females in congenital adrenal hyperplasia?
Males: adrenal crisis (hypotension, hyponatraemia), early virilization
Females: ambiguous genitals
52
What is the management of congenital adrenal hyperplasia?
Mineralocorticoid and glucocorticoid replacement
53
What are the signs and symptoms of phaechromocytoma?
HTN
Episodes of headaches, palpitations, pallor, sweating
Tremor, anxiety, N&V, chest/adbo pain
Crisis last ~15 mins
Generally otherwise well
54
What are the causes of phaechromocytoma?
Genetics - 25%
Malignancy - 15-20%
Benign - 80-85%
55
What genetics are associated with phaechromocytoma?
MEN, VHL, SDHB & SDHD mutations,
| Neurofibromatosis
56
Describe the pre-operative treatment of phaechromocytoma
Alpha blockers initially
(Phenoxybenzamine/doxazosin)
Aim for SBP <120mmHg
Beta blockers if tachycardic
Labetolol, bisopropol
Encourage salt intake (maintain fluid status)
57
Define adrenal insufficiency
Inadequate adrenocortical function
58
What are the clinical features of adrenal insufficiency?
```
Anorexia, weight loss
Fatigue, lethargy
Dizziness, hypotension
Abdo pain, vomiting, diarrhoea
Skin pigmentation
```
59
What is the 'suspicious biochemistry' associated with adrenal insufficiency?
Low Na
High K
Hypoglycaemia
60
What test can be used to assess whether a patient has adrenal insufficiency?
Short SynACTHen test
Measure plasma cortisol levels before and 30m after IV ACTH injection
Normal: baseline >250nmol/L, post ACTH >480nmol/L
61
What ACTH, renin and aldosterone levels are associated with adrenal insufficiency?
High ACTH
High Renin
Low Aldosterone
62
Give three functions of Ca
```
Muscle contraction
Bone growth and remodelling
Second messenger signalling
Stabilising of membranes
Enzyme co-factor
Secretion of hormones (insulin)
```
63
What is the normal total calcium range?
2.2-2.6mmol/L
64
Describe the position of the parathyroid glands
Usually 4 glands on the posterior aspect of the thyroid gland
2 at superior poles; 2 at inferior poles
Supplied by the inferior thyroid artery
10% of people have ectopic parathyroid glands
65
What effect does PTH have on blood calcium levels?
Increases
66
What are the actions of PTH in the kidneys?
Reabsorption of calcium at DCT
Internalisation of Na/PO4- co-transporter at PCT (hypophosphataemia and hypercalcaemia)
Inhibits N/H exchanger --> bicarbonate wasting (mild acidosis)
67
What are the actions of PTH on the bones?
Continuous PTH = increased number and activity of osteoclasts
Intermittent PTH = increased number of osteoblasts
68
What are the actions of PTH in the gut?
Stimulates the synthesis of active form of VIT D in the kidney (1,25-dihydroxycholecalciferol) --> increases Ca absorption in gut
69
Where is PTH stored?
Chief cells in parathyroid gland
70
What controls the secretion of PTH?
Ca Sensing Receptors (CaSR)
71
Where are CaSR located?
Parathyroid gland
Thyroid
Kidney
72
Describe what happens when CaSR are activated in the parathyroid gland
Rising Ca --> activates CaSR
Inhibits translation of PTH gene
PTH secretion inhibited
(Rising Ca --> activates calcium sensing proteases --> degrade PTH)
73
What familial condition is associated with loss of function of the CaSR?
Familial hypocalciruric hypercalcaemia
74
Describe what happens when CaSR are activated in the kidney
Increases urinary Ca and Mg excretion
| Increases Na, K, Cl excretion
75
Describe what happens when CaSR are activated in the thyroid
Stimulates the release of calcitonin from C cells --> lowers serum Ca
76
Describe the process by which Vit D is activated
Cholecalciferol (UV light) and Ergocalciferol (diet) are inactivated
Hydroxylated in liver to 25-hydroxycholecalciferol (storage form)
Hydroxylated in kidneys to 1,25-dihydroxycholecalciferol (active form)
77
Give three actions of Vit D
Increases calcium and phosphate absorption from gut
Bone mineralisation and mobiles Ca stores
Immunomodulation
Increases bone strength
Reduces insulin resistance
Interaction with RAAS
78
Give the assay results associated with 25-hydroxycholecalciferol
```
<15nmol/l = severe deficiency
15-30nmol/l = deficiency
>50nmom/l = adequate
```
79
What is the normal range for 1,25-dihydroxycholecalciferol?
50-125pmol/L
80
If a patient has a raised serum Ca, what should always be measured?
PTH
81
When do symptoms of hypercalcaemia generally arise?
Serum Ca >3mmol/L
82
Give some symptoms associated with hypercalcaemia
Confusion, depression, fatigue, coma
Shortening of QTc, bradycardia, HTN
Polyuria, nephrogenic DI, stones, nephrocalcinosis
Anorexia, constipation, nausea, pancreatitis
Muscle weakness, bone pain, osteoporosis
83
Give DDx if Calcium and PTH are both raised?
Parathyroid overactivity
Familial hypocalciuric hypercalcaemia
Lithium
84
Give DDx if Calcium is raised and PTH is normal?
Parathyroid overactivity
Familial hypocalciuric hypercalcaemia
Lithium
85
Give DDx if Calcium is raised and PTH is undetectable?
Malignancy
Drugs (thiazide, lithium, calcium supplements)
Granulomatous disease
86
What investigations are needed if a patient has hypercalcaemia?
```
Hx and examination
CXR (signs of malignancy, hilar lymphadenopathy - signs of sarcoidosis)
FBC, ESR
TFTs
Myeloma screen
Short SynACTHen test
Vit D
```
87
What are the ways in which malignancies can cause hypercalcaemia?
Osteolytic metastases and myeloma
Tumour secretes PTHrP
Tumour produces 1,25-dihydroxycholecalciferol
88
What tumours are most likely to secrete PTHrP?
Squamous cell lung cancer
Oesophageal cancer
Renal cell carcinoma
Breast cancer
89
What type of tumour is most likely to produce 1,25-dihydroxycholecalciferol?
Lymphoma (activated macrophages)
90
Give examples of conditions which can produce endogenous 1,25-dihydoxycholecalciferol
Lymphoma
Sarcoid
Wegner's granulomatosis
(usually responds to steroids)
91
Why does adrenal insufficiency cause hypercalcaemia?
Increases PCT Ca reabsorption
| Increases bone resorption
92
Describe Milk-Alkali syndrome
Hypercalcaemia
Metabolic acidosis
Renal insufficiency
(ingestion of calcium and antacids - rare with PPI)
93
What is the management of PTH independent hypercalcaemia?
Stop offending/contributing medications
Rehydrate (3-4L normal saline in 24h)
±loop diuretics - promotes calciuria
Bisphosphonates (inhibits bone reabsorption)
Steroids (haematological malignancy, vit D intoxication, granulomatous disease)
94
Who is most likely to have primary hyperparathyroidism?
Postmenopausal women
95
What are the causes of primary hyperparathyroidism?
85% isolated parathyroid adenoma
14% parathyroid hyperplasia
<1% parathyroid carcinoma
96
What end organ damage is associated with primary hyperparathyroidism?
Bone:
Osteoporosis
Bone cysts, subperiosteal resorption
Brown tumours (collections of osteoclasts, mineralised bone and fibrous tissue)
Kidney:
Renal calculi
Nephrocalcinosis - calcium deposits in kidney
Renal impairment
Pancreatitis
97
What investigations should be arranged to confirm diagnosis of primary hyperparathyroidism?
```
DHx
U&Es
PTH
Urine calcium:creatinine ratio
Vit D
```
98
What investigations should be arranged to assess end organ damage in primary hyperparathyroidism?
DEXA
| Renal USS
99
When should MEN-1/2 be considered as a potential cause of primary hyperparathyroidism?
<40yr
| Hx of hyperparathyroidism in 1st degree relative
100
What investigations are needed if surgery is indicated in the management of primary hyperparathyroidims?
Sestamibi - radio labelled isotope --> taken up by parathyroid gland
Neck USS
101
What are the indications for parathyroidectomy?
Calcium >3mmol/L
Hypercalciuria
Osteoporosis
Renal stones
102
What complications are associated with parathyroidectomy?
Vocal cord paresis, haematoma causing tracheal compression
Transient hypocalcaemia,
"Hungry bones"
103
If someone has no-end organ damage or is unfit for surgery for management of their primary hyperparathyroidism, what surveillance should they have?
Annual bone profile, renal function and urinary calcium
DEXA and renal USS every 3y
104
Describe the medical RRx for primary hyperparathyroidism
Only if not fit for surgery
Bisphosphonates - preserve bone mass but little effect on calcium
Calcium sensing agonists (cinacalcet)
Reduces serum calcium but doesn't prevent end-organ damage
105
Give three causes of vitamin D deficiency
```
Poor sunlight exposure
Malabsorption
Gastrectomy
Enzyme inducing drugs - anticonvulsants
Renal disease
```
106
Define osteomalacia
Failure to ossify bones in adulthood as a result of Vit D deficiency leading to hypo-mineralisation of trabecular and cortical bone
107
How does osteomalacia present?
Bone pain
Proximal myopathy
Hypocalcaemia
108
What biochemistry results are suggestive of osteomalacia?
```
Low calcium
Low phosphate
High Alk Phos
Low Vit D
Elevated PTH
```
109
What radiological appearances are associated with osteomalacia?
Looser zone - pseudo-fractures commonly occur in femur/pelvis
Osteopenia - areas of low bone density
110
How can Vit D deficiency be managed?
Cholecalciferol (D3) = restores body stored, corrects metabolic disturbances
Alfacalidol (active Vit D) - in renal impairment, heal bony abnormalities
111
Define diabetes
A metabolic disorder of multiple aetiology characterised by chronic hyperglycaemia with disturbance of carbohydrate, protein and fat metabolism resulting in defects in insulin secretion, insulin action or both
112
Describe and explain the symptoms of diabetes
Glycosuria --> depletion of energy stores
(Tired, weak, weight loss, difficulty concentrating, irritability)
Glycosuria --> osmotic diuresis
(Polyuria, polydipsia, thirst, dry mucous membranes, reduced skin turgor, postural hypotension)
Glucose shifts --> swollen ocular lenses
(Blurred vision)
113
Describe and explain the presentation of insulin deficiency
```
Ketone production
(N&V, abdo pain, heavy/rapid breathing, acetone breath, drowsiness, coma)
```
Depletion of energy stores
(Weakness, polyphagia, weight loss, growth retardation in young)
Complications (T2DM)
(Microvascular, macrovascular, neuropathy, infection)
114
What are the diagnostic values for diabetes in a fasting glucose test?
Normal: <7.0
| Diabetes >7.0
115
What are the diagnostic values for diabetes in a OGTT?
Normal: <7.8
IGT: 7.8-11.0
Diabetes: >11.1
116
What HbA1c value corresponds to diabetes?
6.5% (48mmol/L)
117
Describe T1DM
Chronic, progressive metabolic disorder characterised by hyperglycaemia and the absence of insulin secretion due to autoimmune destruction of beta cells in the Islets of Langerhans
118
Describe T2DM
Chronic, progressive metabolic disorder characterised by hyperglycaemia, insulin resistance and relative impairment of insulin deficiency
119
How is MODY inherited?
Autosomal dominant
120
How many genes cause MODY, and what is the most common?
6 genes
| HNF1-alpha 70%
121
What are the three main features of MODY?
Often <25y at onset
Runs in families - autosomal dominant
Managed by diet, OHAs, insulin
122
Define gestational diabetes
Carbohydrate intolerance with onset, or diagnosis, during pregnancy
123
What risk factors are associated with gestational diabetes?
High BMI
Previous macrosomic baby/gestational DM
FHx of diabetes
124
Who should be tested for gestational diagnosis, when and what is the criteria?
Women with risk factors
OGTT at 24-28 weeks
Fasting venous plasma glucose >/= 5.1mmol/L OR
1 hour value >/= 10.0mmol/L OR
Two hours after >/= 8.5mmol/L
125
Give potential causes of secondary DM
Disorders of exocrine pancreas (pancreatitis, carcinoma, CF, haemochromatosis)
Endocrinopathies (Acromegaly, Cushing's, phaechromocytoma)
Drug therapies (Immunosuppressive agents, anti-psychotics)
126
Under fasting conditions, what is the basal secretion of insulin per hour?
40ug/h
127
Describe the release of insulin
1st phase: stored insulin is released immediately due to increased plasma glucose levels
2nd phase: blood insulin levels starts to fall, the pancreas produces more insulin
128
Give an example of a short/rapid (bolus) insulin
Novorapid
129
Give an example of intermediate/long (basal) insulin
Determir
Degludec
Glargine
130
Give and example of a mixed insulin
Novomix 30
| Humalog Mix 25/50
131
What is Whipple's triad in regard to hypoglycaemia?
1. Symptom of low blood glucose
2. Measure low plasma glucose
3. Symptoms improve with glucose
132
At what concentration of blood glucose are counter-regulatory hormones released? What hormones are they? What is the effect?
3.8mmol/L
Glucagon and adrenaline
Sweating, palpitations, shaking, nausea, anxiety
133
What what blood glucose concentration is cognitive function impaired?
2.5-2.8mmol/L
134
How is mild hypoglycaemia treated in hospital?
Give 15-20g of quick acting carbohydrate
Test blood glucose after 15mins
If <4mmol/L repeat up to 3x
135
How is moderate hypoglycaemia treated in hospital?
If capable and cooperative, 15-20g of quick acting carbohydrate
If not, 1.5-2 tubes GlucoGel or 1mg Glucagon IM
Test blood glucose levels after 15mins
If <4mmol/L repeat up to 3 times
136
How is severe hypoglycaemia treated in hospital?
```
Check ABC
Stop IV insulin
Give IV glucose over 10 mins
Test blood glucose after 10 mins
If <4mmol/L repeat
```
137
How often does a person with diabetes need to check their blood glucose levels whilst driving?
Every 2 hours
138
What are the three aspects of DKA?
1. Metabolic acidosis (pH <7.3)
2. Plasma glucose (>13.9mmol/L)
3. Urinary/plasma ketones (++ on urine/ >3mmol/L in plasma)
139
What are some of the symptoms of DKA?
```
Breathlessness - Kussmaul's breathing
Abdominal pain
Leg cramps
N&V
Confusion
```
140
What are some of the precipitants of ketoacidosis?
```
New onset DM
Insulin omission
Acute illness
Steroids
Infections
```
141
What losses are associated with DKA?
Water: 6-8L (100ml/kg)
Sodium: 500-1000mmol/L
Chloride: 350mmol/L
Potassium: 300-1000ml/L
142
Describe the management of DKA
Treat the precipitant
Fluids
Potassium replacement
Insulin - with glucose once the blood glucose levels starts to fall
143
How high are the blood glucose levels in HHS?
>30mmol/L
144
What are precipitating factors of HHS?
Infection
Poor compliance
Drugs
145
Describe the management of HHS
Treat the precipitant
Fluids
0.9% saline
Rate of Na fall should not exceed 10mmol/24hr
Insulin
Rate of fall no more than 5mmol/L/hr
Other
LMWH
Foot protection
