ENDOCRINOLOGY Flashcards
1
Q
What does diabetes predispose you to?
A
Atheroscerlosis which leads to CVD
2
Q
How does diabetes affect your chance of getting renal disease?
A
1 in 3 T2Dm develops overt kidney disease and diabetes is the most common causes of ESRD.
3
Q
What is the risk of amputation in a patient with diabetes?
A
15% lifetime risk of amputation
4
Q
How is the life expectancy affected by diabetes?
A
Reduced by 5-10 years
5
Q
What is the normal plasma glucose concentration?
A
4-6 mmol/l
6
Q
How do you define diabetes?
A
Abnormally elevated plasma glucose concentration
7
Q
How do you diagnose diabetes?
A
Symptoms + one abnormal result OR 2 abnormal results of ideally the same (but can be different) tests at least week apart.
Fasting glucose greater than or equal to 7mmol/l and/or
OGTT of 75g glucose, 2 hours after greater than or equal to 11.1mmol/l
Hba1c greater than or equal 6.5%
8
Q
If the patient is asymptomatic, how far apart do diagnostic tests for diabetes have to be?
A
1 week
9
Q
What is the classic triad of symptoms for diabetes
A
polyuria, polydipsia and weight loss
10
Q
What is the treatment basis for T1DM?
A
ALWAYS be treated with insulin, always need insulin cover
11
Q
What other diseases is T1DM associated with?
A
Thyroid disease and adrenal insufficiency, due to its autoimmune nature
12
Q
What is LADA syndrome?
A
Latent autoimmune diabetes adult, patient who has positive antibodies to beta cell function, indicative of T1DM, but insidious presentation with mild hyperglycaemia
13
Q
Why don’t healthy people have ketone production?
A
It is suppressed by insulin, absence of insulin leads to gluconeogenesis and fat breakdown—> free fatty acid
14
Q
What is the mechanism of ketone production in T1DM?
A
No insulin, therefore production of ketones by beta oxidation of free fatty acids.
15
Q
What is the relevance of a diabetic patient with ketones in their urine?
A
Immediate insulin therapy needs to be started NOW
16
Q
How is T1DM managed?
A
Insulin- SC injection–> different types of insulin available
Patient education
Lifestyle–> accurate carbohydrate counting -DAFNE course
Home blood glucose monitoring
Regular HbA1c testing and complications- foot check, renal assessment and retinal screening assessment
17
Q
How is T2DM managed?
A
Lifestyle Anti-obesity drugs Oral hypoglycaemic drugs GLP 1 agonists Insulins SGLT2s
18
Q
What is first line therapy for T2DM?
A
Metformin
19
Q
What is the main contraindication of metformin?
A
eGFR<30mL/min
20
Q
How does metformin work?
A
Decrease hepatic glucose production by inhibiting gluconeogenesis
21
Q
What are the ADRs of metformin?
A
GI upset, nausea, vomitting, diarrhoea
22
Q
What are the drug-drug interactions with metformin?
A
ACEi, diuretics, NSAIDs- drugs that may impair renal function
loop and thiazide like diuretics- increase glucose so can reduce metformin action
23
Q
A patient complains of diarrhoea with metformin, what would you suggest?
A
modified release preparations or temporarily decrease the dose.
24
Q
How do sulphonylureas work?
A
Stimulate the beta cells to release insulin by blocking ATP dependent K+ channels
25
What are the side effects of sulphonylureas?
Weight gai, mild GI upset, hypoglycaemia
26
What is GLP-1?
incretin hormone
27
What are the effects of GLP-1
Pancreas- Increase insulin secretion, decrease glucagon secretion, increase insulin biosynthesis
Liver- decrease glucose production
Stomach- decreases gastric emptying
Muscle- increase glucose uptake
Brain- increase satiety
28
When is GLP-1 release?
From the intestinal L cells, during meals
29
When do you use GLP-1 agonists?
NICE suggest add-on if triple therapy is ineffective, but evidence for their use is vey strong
30
What are the benefits of GLP-1 agonists?
Weight loss
31
When is using GLP-1 agonists contraindicated?
Renal impairment
32
When do you use sulphonyureas in diabetes management?
Used less now, but often used if patient with T2DM has low weight, to increase their weight.
33
What are DPP-4 inhibitors?
They inhibit DPP-4 activity which increases GLP-1 concentrations
34
What are the side effects of DPP-4 inhibitors?
GI symptoms, but quite well tolerated
Acute pancreatitis
Hypoglycaemia when prescribed with other hypoglycaemic drugs - SU, insulin
35
When are SGLT-2 inhibitors used?
In diabetes but also people who have comorbities such as congestive cardiac failure and CKD
36
What are the acute complications of type 1 DM?
DKA
37
How is DKA defined?
Hyperglycaemia, ketonaemia and acidosis
38
How is DKA diagnosed ?
```
Needs to have
Ketonaemia greater than or equal to 3 mmol/L
Blood glucose > 11mmol/L
Bicarb < 15mmol/L
and/or pH<7.3
```
39
What are the key issues in DKA?
```
Hyperglycaemia
Acidosis
Dehydration due to osmotic diuresis and vomitting
Electrolyte loss
Cerebral oedema
Hyperkalaemia
```
40
How do you manage DKA?
Rapid fluid administration 0.9% NaCl and insulin
Restoration of circulatory volume
Clearance of ketones
Correct any electrolyte imbalance using crystalloids
41
What insulin therapy do you use for DKA?
Fixed rate IV infusion 0.1 units per kilo body weight per hour
42
What are your metabolic treatment targets for DKA?
Reduce ketones by 0.5mmol/l/hour
Increase venous bicarb by 3.0mmol/l/hour
Maintain potassium between 4-5.5mmol/l
If blood glucose falls below 14mmol/l introduce dextrose with N saline until patient is eating
43
What do you measure hourly in patients admitted with DKA?
Blood glucose
| Hourly ketones
44
What initial investigations should you do for a patient with DKA?
```
Blood ketones
Cap blood glucose
Venous plasma glucose
Urea and electrolytes
VBG
FBC
Blood cultures
ECG
continuous cardiac monitoring
Urianalysis and culture
```
45
How many mmol/L in the blood do you start potassium therapy in patients with DKA?
Between 3.5-5.5mmol/L you add 40mmol/L of potassium into the infusion, any less than 3.5mmol/L need senior review
46
What must be done/considered in the first 6 hours of DKA treatment?
```
At least hourly review
Clear blood of ketones and surprise ketogenesis, reduce at rate of 0.5mmol/l/hour
Avoid hypoglycaemia
Consider catheterisation
Consider NG tubing
Continuous cardiac monitoring
Treat co-morbities
```
47
When can you stop the fixed rate insulin infusion (FRII) and convert back to subcut insulin in a patient with DKA?
Ketones <0.6mmol/L and ready to eat
| No evidence of acidosis
48
What is hyperosmolar hyperglycaemic syndrome?
Marked water loss due to hyperglycaemia, without ketonaemia or acidosis.
High osmolality--> v dehydrated
Usually you get a mixed picture of both HHS and DKA
49
How do you diagnose HHS?
Hypovolaemia
Marked hyperglycaemia (30mmol/L or more) with significant hyperkenonaemia (<3mmol/L) or without acidosis
Osmolality usually 320 mosmol/kg or more
50
Who is most affected by HHS?
Elderly and frail people
51
What can trigger HHS?
Usually precipitated by something e.g. infection
52
How can you calculate plasma osmolality?
2Na + glucose +urea
53
What are the treatment goals for HHS?
Normalise osmolality
Replace fluid and electrolyte losses
Normalise blood glucose
We also want to prevent
Arterial or venous thrombosis
Other potential complications e.g. Cerebral oedema, central pontine mylinolysis
Foot ulceration
54
How do you treat HHS?
```
Crystalloids
Aim to replace 50% of loss within first 12 hours
FRIII 0.05units/Kg/hour
Monitor potassium and renal function
Glucose fall 4-6mmol/hour
Co-morbities
Anticoagulation
```
55
Name 5 RF for hypoglycaemia?
* Increased exercise (relative to usual),
* renal failure,
* strict glycemic control,
* previous hx of severe hypoglycaemia,
* long duration of type 1 diabetes,
* food malabsorption,
* inadequate glucose monitoring
56
What are the causes of inpatient hypoglycaemia?
acute discontinuation of long term steroid therapy, recovery from acute illness, mobilisation after illness, missed or delayed meals, less carbs than normal, reduced appetite
57
How do you treat hypoglycaemia in an adult who is conscious, orientated and able to swallow?
15-20g quick acting carbohydrate of patients choice e.g. 90-120ml go original lucozade, 3-4 heaped teaspoons of sugar dissolved in water, 150-200ml pure fruit juice
58
How do you treat hypoglycaemia in a patient who is confused but able to swallow?
1.5-2 tubes glycogen/dextrogel squeezed between teeth and gum OR give glucagon IM (less effective in pts prescribed sulfonylurea therapy or under influence of alcohol)
59
What are the chronic complications of diabetes?
neuropathy
nephropathy
retinopathy
CVS
60
What 3 groups can the symptoms of hypoglycaemia be divided into?
Autonomic
Neuroglycopenic
General malaise
61
What are some autonomic symptoms of hypoglycaemia?
Sweating
palpitations
shaking
hunger
62
What are some neuroglycopenic symptoms of hypoglycaemia?
Confusion
Drowsiness
Odd behaviour
Speech difficulty
63
What are some general malaise symptoms related to hypoglycaemia?
Headache and nausea
64
What is charcots foot?
Osteoarthropathy associated with neuropathy
65
A patient with T2DM has a dusky and painful foot, what are you thinking?
Peripheral vascular disease associated with diabetes- not neuropathic but ischaemic, referral to the vascular surgeons
66
What are the physiological effects of thyroid hormone?
```
Increase HR and CO
Increase bone resorption
increases gut motility
Increases gluconeogenesis
Maintains normal hypoxic and hypercapnic drive
```
67
Outline the normal thyroid hormone axis?
TRH released from hypothalamus--> TSH secreted from ant pit--> thyroid to release T3 and T4
68
What is Graves disease?
A type of HYPERthryoidism where TSH-receptor stimulating antibodies cause excess T3/T4
69
Apart from Graves disease, outline another autoimmune cause of thyrotoxicosis?
Nodular, either toxic nodule on the thyroid or a multiple nodules, secreting T3/T4
70
What is thyroiditis?
Inflammation of the thyroid gland causing release of thyroxine (T4)
71
What can cause thyroiditis?
Viral infection, medication (amiodarone) or following pregnancy
72
What is Addisons disease?
Primary adrenal insufficiency. Destruction of the adrenal gland or genetic defects in steroid production
73
What are the symptoms of Addison's disease?
```
Very non-specific:
Nausea
Abdo pain
Weight loss
Fatigue
Weakness
Cramps
Reduced libido
```
Dizziness and hypotension due to mineralocorticoid deficiency (aldosterone)
Hypoglycaemia due to glucocorticoid deficiency
Pigmentation due to ACTH excess from reduced cortisol
74
How do you treat an Addisonian Crisis?
IV fluids and hydrocortisone
75
What is the relevance of hyponatraemia?
Very commonly affects hospital patients, up to 30% of hosp patients will have hyponatraemia
76
What are the symptoms of hyponatraemia?
```
Early symptoms:
headache
nausea
vomitting
general malaise
```
Later signs:
confusion
agitation
drowsiness
77
What serious symptoms can acute severe hyponatraemia cause?
Seizures
Resp depression
Coma
Death
78
What common medication can cause hyponatraemia?
thiazide like diuretics
79
What is osmolality?
How salty the blood is, low osmolality means less salt
80
What is a complication of acute severe hyponatraemia?
cerebral oedema
81
In patient with severe acute hyponatraemia what would always prescribe?
Hypertonic saline
82
What is the most common cause of Addison's disease in the UK?
Autoimmune
83
What is the relevance of TB to Addison's disease?
TB can cause Addison's- most common cause in developing countries
84
What is a known medication that can worsen blood sugar levels?
Bendroflumethiazide
85
What are the symptoms of hypothyroidism?
```
dry thick skin
brittle hair
macroglossia
puffy face
loss of lateral 1/3 eyebrow
weight gain
carpal tunnel syndrome
peripheral neuropathy
bradycardia
```
86
What is the first line investigation for Addison's disease?
Morning cortisol
87
What is a thyroid storm?
Severe form of thyroid disease.
| Can occur in thyroxic patients who experience an acute stressor e.g. illness, trauma, surgery
88
How do you treat a thyroid storm?
```
symptomatic treatment e.g. paracetamol
treatment of underlying precipitating event
HDU
Strong dose of anti-thyroid medication e.g methimazole or propylthiouracil
Beta blockers (IV propranolol)
Potassium iodide aka Lugol's iodine (to inhibit production of anymore thyroid hormone)
High dose steroids: dexamethasone - e.g. 4mg IV qds - blocks the conversion of T4 to T3
```
89
What is the pathological mechanism that leads to peripheral neuropathy in diabetes?
Hyperglycaemia leads to advanced glycation end products- these act on specific cells such as endothelial cells and monocytes, this leads to increased production of cytokines and adhesion molecules. This has been shown to have an effect on matrix metalloproteinases, which damaged nerve fibres
90
What are the effects of a prolactinoma in a) women and b) men
a) Women- amenorrhea, galactorrhea and infertility
| b) Men- erectile dysfunction, gynocomastia, reduced sex drive and less body hair
91
What are the risk factors of osteomyelitis?
```
DM
Peripheral vascular disease
Malnutrition
Immunosuppression
Malignancy
```
92
What is the most common cause of primary adrenal failure?
Autoimmune, usually have positive adrenal antibodies present
93
What are the hallmark biochemical features of primary adrenal failure?
Hyperkalaemia, hyponatraemia, raised urea and mild anaemia, hypoglycaemia
94
What biochemical investigations would you do in a patient with hyponatraemia?
Serum osmolality, urine osmolality, urine sodium, thyroid function and assessment of cortisol response
95
What is the first thing to do if a patient presents with low serum osmolality?
Rule out non-hypo- osmolar hyponatraemia e.g. hyperglycaemia
96
What would a low serum osmolality and urine osmolality of less than 100mosmol/kg indicate?
primary polydipsia or inappropriate IV fluid administration
97
What is the next steps in investigation if a patient has low serum osmolality and a urine osmolality of greater than 100mosmol/kg?
You need to measure their urine sodium
98
What would a low serum osmolality and a urine osmolality of greater than 100mosmol/kg (100= concentrated) and urine sodium of less than 30mmol/kg?
True dehydration e.g. GI salt loss
OR
clinically overloaded but intravascular depletion e.g. in congestive cardiac failure, cirrhosis or nephrotic syndrome
Urine sodium of <30 mmol/L suggests low effective arterial volume
99
What would a patient with SIADH look like biochemically (serum osmolality, urine osmolality, urine sodium and their fluid balance)
Low serum osmolality
Urine osmolality> 100mosmol/kg
Urine sodium> 30mmol/L
Euvolaemic
100
What is the next steps in investigation if a patient has low serum osmolality and a urine osmolality of greater than 100mosmol/kg and urine sodium of greater than 30mmol/kg?
Need to work out - are they EUVOLAEMIC or DEHYDRATED?
101
A patient low serum osmolality and a urine osmolality of greater than 100mosmol/kg and urine sodium of greater than 30mmol/kg and they are dehydrated, what do you need to consider?
Addison's disease, renal or cerebral salt wasting or does the patient have a history of vomitting
102
What do you need to rule out before you make a diagnosis of SIADH?
Hypothyroidism - elevated ADH due to decreased Cardiac output
Total salt depletion
ACTH deficiency- check serum cortisol as low cortisol causes less -ve feedback on CRH and Cortisol directly suppresses ADH secretion )
103
Why does ACTH deficiency present like SIADH?
Cortisol deficiency leads to increased ADH secretion
104
What are the causes of SIADH?
Underlying malignancy
Resp/CNS pathology- CXR to rule out any lung pathology needs to be done
Drugs e.g. anticonvulsants
105
What malignancy is know to cause SIADH?
small cell lung cancer
106
How do you treat SIADH?
Fluid restriction- however in practice this is quite poorly tolerated
ADH antagonists- Tolvaptan
Demeclocycine- tetracycline antibiotic that inhibits ADH
107
How do you treat hyponatraemia?
Hypovolaemic hyponatraemia- normal saline
Hypervolaemic hyponatraemia- needs specialist treatment to treat the underlying cause of CCF, nephrotic syndrome or cirrhosis
108
What is diabetes insipidus caused by?
Vasopressin deficiency - cranial DI,
| or vasopressin resistance - nephrogenic DI.
109
What is seen in biochemistry of DI?
High serum osmolality, low urine osmolality and high urine volume
110
What is cranial DI caused by?
```
Pituitary disease
Brain tumours
Head injury
Brain malformation
Brain infections
Genetic causes - strong FHx
```
111
What is nephrogenic DI caused by?
Metabolic and electrolyte disturbance
Renal disease
Drugs affecting the kidney e.g. lithium
112
What values of urine volume confirm DI?
>3L in 24hrs in the presence of high serum osmolality and low urine osmolality
113
What values of serum osmolality and urine osmolality confirm DI?
serum osmolality >295mosmol/kg and urine osmolality <300mosmol/kg
114
What value of urine osmolality or serum osmolality can exclude diagnosis of DI?
Urine osmolality >600mosmol/kg
| Double serum osmolality
115
What investigation might you do for suspected DI?
Water deprivation test
116
How do you conduct the water deprivation test?
Patient fluid deprived for 8 hours
Then urine osmolality is measured
Synthetic ADH is administered
8 Hours later urine osmolality is measure again
117
What results would you expect on the water depravation test for cranial DI?
Initially low urine osmolality, then post-ADH administration high urine osmolality as cells of collecting duct are responding to the synthetic ADH
118
What results would you expect on the water depravation test for nephrogneic DI
Low urine osmolality both pre and post ADH, due to the cells of the collecting duct not being able to respond to ADH
119
How is cranial DI managed?
Investigate for pituitary disease
| Give synthetic vasopressin - desmopressin
120
How does overtreatment of DI with desmopressin present?
Get dilutional hyponatrameia - so get headaches, reduced cognitive ability, seizures
N.B.desmopressin= synthetic ADH, overtreatment leads to increased reabsorption of water therefore leading to the dilutional hyponatraemia
121
How does undertreatment of DI with desmopressin present?
Excessive thirst, polyuria
122
How is nephrogenic DI managed?
Find cause and reverse if possible.
Use of low salt, low protein diet, diuretics, NSAIDs
Keep on top of the thirst and replace water lost
123
Where is the pituitary gland situated?
In pituitary fossa at the base of the brain
124
What anatomy lies a) superior and b) laterally to the pituitary gland?
a) Superior - optic chiasm. b) Laterally - cavernous sinus
125
What nerves/ blood vessels are in the cavernous sinus?
Occulomotor, Trochlear , trigeminal Va, Vb, abducens, internal carotid artery.
126
How is growth hormone secreted?
Pulsatile manner. Peak pulses during REM sleep
127
Name the hormones positively and negatively controlling GH
Positive = GHRH. Negative = somatostatin
128
Describe the adrenal axis
CRH stimulates ACTH release. ACTH release is circadian - peak pulses early in the morning and lowest at midnight. ACTH stimulates cortisol release. Cortisol has negative feedback on ACTH
129
What are LH and FSH stimulated by and inhibited by?
Pulsatile GnRH stimulates. Testosterone and oestrogen inhibit
130
What hormones does prolactin inhibit?
LH and FSH - directly inhibit.
131
What are the 2 ways that pituitary tumours can present?
Compressive - compress surrounding structures - vision, cranial nerves, all hormones can be reduced. (non-functional pituitary tumour).
Excessive hormone production (functional pituitary tumours).
132
How is prolactin predominantly controlled?
Mostly under negative control by dopamine and weak stimulatory control by TRH
133
How can functional pituitary tumours present?
Acromegaly. Cushing’s disease. Prolactinoma. TSHoma.
134
Pituitary tumours compressing optic chiasm cause which visual defect?
Bi-temporal hemianopia
135
What should be assessed in pt with suspected pituitary tumour?
Assessment of visual fields
Biochemical assessment- divided into basal (prolactin, TSH, LH and FSH) and dynamic tests (synacthen test and insulin tolerance test)
136
What time of day should LH, FSH and basal testosterone be checked in men?
0900 when deficiency is suspected.
137
When should LH, FSH be tested in women?
Measured within 1st 5 days of the menstrual cycle
138
IGF-1 is a marker of GH. What do a) low levels and b) high levels of IGF-1 show?
a) low levels - GH deficiency
| b) high levels - excess GH.
139
What is synacthen test?
Give synthetic ACTH to assess primary adrenal failure. Test how well adrenal glands work by measuring cortisol.
140
What is the Insulin Tolerance Test?
Gold standard to test ACTH and GH reserve.
| Cause insulin - induced hypoglycaemia. Should see ACTH and GH rise (from the reserve).
141
Which patients should you NOT do insulin tolerance test for?
Pt with IHD - can triggery coronary ischemia
| Pt with epilepsy - can trigger seizures
142
What imaging would you order for pathology of pituitary gland?
MRI
| CT if unable to have MRI
143
Distinguish between micro and macro adenomas
Micro - less than a cm. More common in women
| Macro - more than a cm. More common in men
144
Name ddx for a finding of hyperprolactinaemia
```
Pregnancy - needs to be excluded first
Medications - antiemetics, anti-psychotics
Hypothyroidism (rare)
PCOS
Large pituitary tumour
Stress
Renal failure, adrenal insufficiency.
```
145
How do micro-prolactinomas present?
Menstrual disturbance
Hypogonadism in men
Galactorrhoea
Infertility
146
How is PCOS distinguished from prolactinoma?
The presence of androgenic symptoms
Less elevated prolactin (<1,000 miU/L)
Absence of pituitary lesion on MRI
147
How are prolactinomas treated?
Dopamine D2 agonists
148
Name a D2 agonist
Cabergoline- given once or twice weekly, and better tolerated than bromocriptine
Bromocriptine- given daily
149
Name common side effects of cabergoline
Nausea, postural hypotension
| Rare - psych disturbance
150
What is risk associated to reducing size of lesion/ tumour bulk of prolactinoma?
When size reduces rapidly, can get CSF leak which gives potential risk of meningitis
151
What causes acromegaly?
Excessive growth hormone.
Most common cause if unregulated GH secretion by pituitary adenoma
Can also be secondary to malignancy elsewhere e.g lung or pancreatic cancer secreting ectopic GHRH or GH
152
What can untreated acromegaly lead to?
Disfiguring features
CVD → premature death
Increased risk of bowel cancer
153
How does acromegaly present?
Increased size of hands and feet
Frontal bossing of forehead
Protrusion of chin
Widely spaced teeth
Enlargement of tongue and soft palate due to soft tissue swelling - sleep apnoea, snoring
Puffiness of hands - carpal tunnel syndrome
154
Name specific features of active GH hypersecretion
Sweating, headaches, HTN, DM
155
What investigation would you do for suspected acromegaly? And what would you see?
Oral glucose tolerance test. Failure to supress GH after OGTT ad elevated IGF-1.
156
List management options available for acromegaly
Surgery - remove adenoma
Medical - somatostain analogue or dopamine agonist.
External beam or stereotactic radiotherapy- stereotactic radiotherapy only suitable for lesions well away from the optic chiasm
157
How does the chance of remission differ between patients with pituitary micro-adenomas vs macro-adenoma
Micro-adenoma, high chance of remission
| Macro-adenoma- only achieved in 60% of patients
158
How is acromegaly monitored?
Repeat OGTT after surgery
Long term follow up needed - to control GH and IGF-1 levels.
Periodic screening colonoscopy as there is risk of neoplasia.
Assess for sleep apnoea, DM, CVD risk, symptoms of recurrance
159
What are Non-functioning pituitary adenomas (NFPA)?
Biochemically inactive tumours
160
How do non-functioning pituitary adenoma present?
Visual field loss, headache, hypopituitarism
161
How does hypopituitarism present?
Non specific - lethargy, weight gain, sexual dysfunction
Can present with hypo-adrenal crisis - hyponatraemia, hypotension - MEDICAL EMERGENCY
Short stature in children
162
How is hypopituitarism investigated?
Exclusion of adrenal insufficiency
Investigate levels of all hormones.
MRI could show empty fossa or pituitary tumour
163
How is hypopituitarism treated?
Depends on the deficiency - ACTH-hydrocortisone replacement
TSH-thyroxine replacement
gonadotropin- Men- testosterone via gel or injection
Women- oestrogen and progesterone via COCP or HRT
GH- daily subcut injection
164
Differentiate between Cushings syndrome and Cushing's disease
Cushing's syndrome- collection of symptoms
| Cushing's disease- excessive ACTH secretion from a PITUIATARY adenoma, can cause cushings syndrome
165
How does Cushing’s syndrome present?
Central obesity
Dorso-cervical fat pad
Increased roundness of the face
Pt has red face, thin skin, proximal myopathy
May be HTN, premature osteoporosis, DM, depression, cardiac hypertrophy (due to too much stress hormone)
166
Why is it dangerous to leave Cushing’s syndrome untreated?
Significant morbidity. 5-yr mortality approaching 50%
167
What are the causes of Cushing's syndrome?
Exogenous steroids
Cushing's disease
Adrenal adenoma
Paraneoplastic Cushing's (ectopic ACTH secretion e.g. small cell lung cancer)
168
What investigations would you do for suspected Cushing’s syndrome?
24hr urine free cortisol, low dose dexamethasone suppression test, overnight dexamethasone suppression test.
Screening tests - alcoholism and severe depression can make pts look like they have cushings syndrome but tests come back as normal
169
Explain the dexamethasone supression tests.
Low dose 1mg- give dexamethasone at 10pm, check free cortisol at 9am. NORMALLY, should be suppressed, in Cushing's SYNDROME, it will not be suppressed, therefore you now do the HIGH dose to find out the underlying cause
High dose dexamethasone supression test 8mg. Process is same as above:
Cortisol is surpressed- cushing's disease- pit adenoma
Cortisol is NOT supressed but ACTH is surpressed- adrenal adenoma (secreting cortisol independently)
Neither cortisol or ACTH surpressed- ectopic ACTH
170
Name differential for Cushings syndrome
Pituitary, adrenal or ectopic ACTH
171
What may be in pt’s Hx to point towards them having ectopic ACTH secretion, causing Cushings syndrome?
Hypokalaemia
SMoking Hx
Weight loss
By lung cancer or other malignancy.
172
What presenting complaint directly points towards adrenal tumour?
Significant, accelerated hirsutism
173
How is adrenal tumour managed?
Adrenalectomy
174
How is cushings disease managed?
Trans-sphenoidal removal of pit adenoma
175
What is Trousseau's sign? What is relevance?
Due to Hypocalcaemia
When inflate BP cuff above systolic pressure. Brachial artery is occluded. Causes carpal spasm (e.g. wrist flexing and fingers abducting)
176
What is Chvostek's sign? What is its relevance?
Due to hypocalcaemia.
Tapping over parotid (CN7) causes facial muscles to twitch
177
Briefly describe hypoparathyroidism
decrease PTH secretion
e.g. secondary to thyroid surgery*
low calcium, high phosphate
treated with alfacalcidol
178
What are the main symptoms of hypoparathyroidism?
The main symptoms of hypoparathyroidism are secondary to hypocalcaemia:
tetany: muscle twitching, cramping and spasm
perioral paraesthesia
Trousseau's sign: carpal spasm if the brachial artery occluded by inflating the blood pressure cuff and maintaining pressure above systolic
Chvostek's sign: tapping over parotid causes facial muscles to twitch
if chronic: depression, cataracts
ECG: prolonged QT interval
179
What is myxoedemic coma? How would it present? How treated?
WHAT? Potentially fatal complication of undiagnosed hypothyroidism or poor adherence to levothyroxine therapy
Present: overweight pt, dry skin, thinning hair, hypotensive, bradycardia, hypothermic
Treat:
IV Thyroxine
IV hydrocortisone - for possibility of adrenal insufficiency
ITU for support
180
What are some side effects of long term steroid use - many think of a few from different systems
```
endocrine:
impaired glucose regulation
increased appetite/weight gain
hirsutism
hyperlipidaemia
```
Cushing's syndrome:
moon face
buffalo hump
striae
musculoskeletal:
osteoporosis
proximal myopathy
avascular necrosis of the femoral head
immunosuppression:
increased susceptibility to severe infection
reactivation of tuberculosis
```
psychiatric:
insomnia
mania
depression
psychosis
```
gastrointestinal:
peptic ulceration
acute pancreatitis
ophthalmic:
glaucoma
cataracts
suppression of growth in children
intracranial hypertension
neutrophilia
181
What is Sheenhan's syndrome? What causes it?
What?
Ischaemia of pituitary gland causes necrosis of secretory cells - get panhypopituitarism.
Leads to : amenorrhea, failure to lactate and death
Cause?
Hypotension/ hypovolaemia due to obstetric haemorrhage. Pituitary gland becomes large and vascular during pregnancy so is vulnerable to hypotension and hypoxia.
182
What is a pituitary apoplexy? What causes it? What is commonly lost? Tests?
What?
Endocrine Emergency ----> Haemorrhage / infarction of a pituitary tumour
Cause?
Commonly hypertension or surgery
Commonly lost?
Anterior pituitary hormones- especially ACTH.
Causes 2ndary Adrenal Insufficiency
Tests: Electrolytes / Pit hormones / Glucose / MRI or CT if none
183
How would a patient with pituitary apoplexy present?
Sudden onset severe headache (thunderclap) retro-orbital
Nausea, vomiting, reduced consciousness
Opthalmoplegia (paralysis / weakness of 1 or more extraocular muscles)
Visual disturbance - bitemporal hemianopia most common
+ deficiency in Ant Pit hormones - especially ACTH
184
Most common functioning tumour of the anterior pituitary gland?
Prolactinoma
185
What causes hypopituitaism vs hyper
186
What investigations would you do if suspect hypopituitasm
187
How large is a macroadenoma of the pituitary? what sign might a patient have ?
>10mm
Bitemporal hemianopia due to compression of optic chiasm
188
What is 1st line treatment for Prolactinomas in men and women? 2nd line?
1st line:
Dopamine agonist - Cabgergoline reduce tumour size and prolactin level
2nd line: Trans sphenoidal surgery if medical treatment not tolerated or unsuccessful
189
How does Prolactinoma present in men vs women
```
Men:
Loss of libido
Lethargy
Galactorrhea
impotence
hypogonadism (small testes)
```
Women:
1. Menstrual disturbance: Amenorrhea/Oligomenorrhea/Menorrhagia
2. Infertility
3. Galactorrhea
190
How does hypercalcaemia present?
Non-specific symptoms - tiredness, aches, pains
Specific symptoms - polyuria, polydipsia (nephrogenic DI)
Abdominal pain, constipation. Psychiatric symptoms present. Kidney stones.
191
How might a non-functioning adenoma present?
Compression might cause:
Visual disturbance - bitemporal hemianopia
Headache / vomiting / papilloedema (ICP +)
Oligomenorrohea and amenorrhea in women
Reduced libido and fertility in men
Cranial nerve palsy
192
How might a non functioning pituitary adenoma cause hyperprolactineamia?
Non functioning can cause as it removes the dopaminergic inhibition of prolactin release
193
What investigations for Hyperpituitarism ? (4)
1. Visual
Optic chiasm - bitemporal hemianopia
Cavernous sinus - diplopia
```
2. Blood hormones (morning )
TSH / thyroxine
Prolactin
ILGF-1
FSH / LH / oestrogen / testosterone
ACTH / Cortisol
```
3. Imaging
MRI / CT
radio-labelled dopamine antag. can visualise prolactinoma
4. SUPPRESSION tests (reduced -ve feedback)
Oral glucose tolerance test - should normally suppress GH
ACTH in response to dexamethesone should suppress CRH and ACTH
194
What drugs can cause hyperprolactinaemia?
D2 antagonists
Antipsychotics 1st + 2nd:
Haloperidol 1st
Clazapine 2nd
Cyclic Antidepressants:
Amytryptilline
SSRIs:
Citalopram
Anti emetics:
Domperidone
Metoclopramide
195
How does a prolactinoma lead to infertility?
Prolactin interferes with GnRH release. This inhibits the release of LH and FSH causing hypogonadism
196
What outside of the pituitary gland in surrounding tissues could cause hypopituitarism?
Tumours of surrounding tissues that could compress.
Gliomas (in optic chiasm)
Meningiomas
Craniopharyngiomas
Mets - breast, bronchus, kidney
197
What is the medical treatment of hyperprituitarism? (4) Risk of treatment?
All risk of inducing hypopituitarism
Cabergoline - dopamine antagonist to reduce prolactin
Somatostatin analogue - Octreotide to reduce GH
Surgical removal
Irradiation to prevent recurrence
198
What is a microadenoma?
adenoma <10mm
| more common
199
Name causes of hypocalcemia?
Post - surgical hypoparathyroidism
Vitamin d deficiency
Hypomagnesaemia
200
What are the clinical features of acute severe hypocalcaemia?
Laryngospasm
Prolonged QT interval
Seizures
201
How does hypocalcemia present?
```
Muscle cramps
Carpo-pedal spasm
Perioral parasthesia
Peripheral parasthesia
Neuro-psychiatric symptoms
Positive Chvostek’s sign
Trousseau’s sign
```
202
What investigations needed to diagnose hypopituitarism?
Visual field assessment
Basal blood tests
MRI or CT
STIMULATION TESTS
GH - does GH rise in response to insulin tolerance test?
Cortisol - does it rise after ACTH (Synacthen)
LH / fSH in response to GnRH or clomifene (anti oestrogen)
203
What is Trousseau’s sign?
Carpo-pedal spasm induced after inflation of a sphygmomanometer cuff 20 mmHg over pts systolic BP for 3 mins. Positive when induces latent tetany (spasm) due to hypocalcaemia.
204
How is hypocalcaemia treated?
Calcium replacement
205
How is acute hypocalcaemia treated?
IV calcium
206
What is dosage given for severe vit d deficiency?
Loading dose of cholecalciferol - 20,000IU per week for 7 weeks then maintenance dose of 1-2000 IU per week
207
How is hypoparathyroidism treated?
Alfacalcidol or calcitriol - starting dose of 0.25mcg/day 1-alfacalcidol
208
What is the aim in treating hypocalcaemia?
Keep calcium levels at lower end of reference to reduce risk of nephrocalcinosis
209
What is pseudo-hypoparathyroidism?
Rare condition caused by mutation in G protein coupled to PTH receptor, leading to PTH resistance
210
How does pseudo-hypoparathyroidism present?
Bloods - Hypocalcaemia, High phosphate
| Signs - Short stature, round face, short 4th and 5th metacarpals
211
A 10 week pregnant patient comes in with heat intolerance and palpitation, upon further investigations it is found she has hyperthyroidism, what drug would you prescribe here?
Propylthiouracil as carbimazole crosses the placenta, therefore unable to use in first trimester of pregnancy
212
What is the treatment for Pituitary Apoplexy?
High dose IV hydrocortisone
Transsphenoidal surgical decompression w/in 1 week
( Surgery for pts with neuro-opthalmic signs / deteriorating consciousness)
213
Group the major disorders of the anterior pituitary into 2 main categories
1. Hormone excess due to functioning adenomas
e. g. GH- acromegaly, ACTH- Cushing's disease
2. Hormone deficiency due to non functioning adenoma (SOL). Present later as a macroadenoma - compress secretory cells or portal vessels
214
List 4 ways that pituitary tumours can present
1. Visual disturbance / headache
2. Inappropriate hormone excess ACTH- Cushing's disease, Prolactinaemia, GH- acromegaly
3. hormone hypo / hyper secretion due to compression
4. Amenorrhea or loss of libido
215
What are some infective / inflammatory cause of pituitary failure?
Infective:
TB / syphyllis
Inflammatory:
sarcoidosis
haemochromatosis
216
What investigations needed to diagnose hypopituitarism?
STIMULATION TESTS
217
What are the differentials of Diabetes Insipidus clinical presentation?
Psychogenic polydipsia, DM, Diuretic use, Hypercalcaemia ( as serum calcium is elevated)
218
Acid base balance in addisons/adrenal insufficiency?
Hyperkalaemic metabolic acidosis
219
Target HbA1c for patients on a drug the causes hypoglycaemia?
The Hba1c target for patients on a drug which may cause hypoglycaemia (eg sulfonylurea) is 53 mmol/mol
220
Causes of hypoglycaemia?
Insulinoma
Self-Administered insulin/sulfonyureas
Addisons disease
alcohol
221
Levothryroxine side effects?
hyperthyroidism: due to over treatment
reduced bone mineral density
worsening of angina
atrial fibrillation
222
Treatment for ectopic Cushing's syndrome?
Treat underlying malignancy
223
Why are ACTH levels low in an adrenal cause of Cushing's syndrome?
Increased cortisol causes negative feedback.
224
What are levels of ACTH in Cushing's syndrome caused by pituitary adenoma or paraneoplastic?
Normal or high
Pit adenoma= excessive ACTH secretion
Paraneoplastic= tumour secreting ACTH that is NOT pit adenoma
225
What are cortisol levels following high dose dexamethasone suppression test in a pituitary adenoma?
Reduced cortisol
226
What are cortisol levels following high dose dexamethasone suppression test in ectopic Cushing's syndrome?
No suppression - cortisol remains high.
227
Following High dose DST for pituitary adenoma secreting ACTH, what is next step in management ?
MRI of the pituitary gland.
228
If MRI of pituitary gland in Cushing's syndrome does not show pituitary adenoma, what is next step?
Inferior Petrosal Sinus Sampling = shows clear gradient between central and peripheral ACTH levels after an injection with CRH. (Sampling the veins that drain the pituitary gland)
229
In suspected ectopic ACTH in Cushing's syndrome, what is next step following High Dose DST?
Whole body CT scan or PET imaging - to find carcinoma.
| Note: common place = thorax.
230
Medical treatment options for Cushing's syndrome?
Metyrapone - block steroid synthesis pathway
Ketocanazole - adrenolytic agent
Radiotherapy - help reduce size of tumours before surgery. Or mainstay of treatment if tumours are unresectable.
231
What is myxoedema coma?
extreme form of hypothyroidism
high mortality
232
Clinical features of myxoedema coma?
stupor
hypothermia
respiratory failure
confusion
coma
dry skin
sparse hair
hoarse voice
periorbital oedema
CVS: non-pitting oedema of hands and feet, bradycardia, hypotension refractory to vasopressors, reduced contractility, pericardial effusion
RESP: respiratory depression, impaired respiratory muscle function, hypoxia and hypercapnia
RENAL: bladder atony, urinary retention, urinary Na+ normal or high
ELECTROLYTES: hyponatraemia from increased H2O reabsorption from high levels of ADH
GI: macroglossia, anorexia, abdominal pain, constipation, ileus
CNS: delayed tendon reflexes, slow mentation, depression -> psychosis, seizures
233
Risk factors for myxoedema coma?
* hypothermia
* CVACHF
* infections
* drugs: anaesthetics, sedatives, narcotics, amiodarone, lithium
* GIH
* trauma
* electrolytes: hypoglycaemia, hyponatraemia
* acidosis
* hypoxaemia
* hypercapnia
234
Inv and suspected findings in myxodema coma?
* TSH: markedly elevated in 95% of cases, 5% are caused by central TSH failure
* low free T4
* low T3
* hyponatraemia
* hypoglycaemia
* anaemia
* hypercholesterolaemia
* high LDH
* high CK
235
Management for myxoedema coma?
RESUSCITATION
* admit to ICU because if high mortality and multi-faceted therapy
* may require intubation for various reasons (respiratory failure, airway obstruction from macroglossia, coma)
* ventilation may be required for several days -> weeks
* IV fluid resuscitation and vasoactive agents until thyroid hormone action begins
* warm patient and pre-empt vasodilation and hypotension
Acid-base and Electrolytes
* supportive care
* glucose
* hyponatraemia: cautious correction over time (<10mmol/L day)
Specific Therapy
* hydrocortisone 100mg Q 6hourly if adrenal or pituitary insufficiency suspected
* replacement of thyroid hormones (T4 or T3 is controversial):
* (1) T4 – loading dose = 500mcg IV -> 50-100mcg OD IV or orally
* (2) T3 – loading dose = 10mcg IV -> 10mcg Q4 hrly for 24 hours then every 6 hours
Underlying Cause
treat precipitant (withdraw drugs, treat infection…)
236
Features of thyroid storm?
fever > 38.5ºC
tachycardia
confusion and agitation
nausea and vomiting
hypertension
heart failure
abnormal liver function test - jaundice may be seen clinically
237
What is pseudohypoparathryoidism?
due to abnormality in a G protein
associated with low IQ, short stature, shortened 4th and 5th metacarpals
238
Blood results for pseudohypoparathryoidism?
low calcium, high phosphate, high PTH
239
How is pseudohypothyroidism diagnosed?
diagnosis is made by measuring urinary cAMP and phosphate levels following an infusion of PTH. In hypoparathyroidism this will cause an increase in both cAMP and phosphate levels. In pseudohypoparathyroidism type I neither cAMP nor phosphate levels are increased whilst in pseudohypoparathyroidism type II only cAMP rises.
