MEDICINE - ENDOCRINOLOGY Flashcards
(277 cards)
1
Q
What does hypothalamus stimulate?
A
Pituitary gland
2
Q
Anterior pituitary gland hormones release
A
- Thyroid-stimulating hormone (TSH)
- Adrenocorticotropic hormone (ACTH)
- Follicle-stimulating hormone (FSH)
- luteinising hormone (LH)
- Growth hormone (GH)
- Prolactin
3
Q
Posterior pituitary hormones release
A
- Oxytocin
- Antidiuretic hormone (ADH)
4
Q
Thyroid axis
A
Hypothalamus releases TRH
TRH stimulates Anterior pituitary to release TSH
TSH stimulates thyroid to release T3 and T4
T3 and T4 suppress the release of TRH and TSH by acting on hypothalamus and pituitary
5
Q
Adrenal axis
A
Hypothalamus releases corticotropin-releasing hormone.
CRH stimulates anterior pituitary to release ACTH
ACTH stimulates adrenals to release cortisol
* Cortisol supresses release of CRH and ACTH (in hypothalamus and anterior pituitary)
6
Q
Which hormone has diurnal variation?
A
- Cortisol (peaks in the morning, lowest in the evening)
7
Q
Actions of cortisol
A
- Increases alertness
- Inhibits the immune system
- Inhibits bone formation
- Raises blood glucose
- Increases metabolism
8
Q
Growth hormone axis
A
Hypothalamus produces GHRH
GHRH stimulates anterior pituitary to release GH
GH stimulates the release of IGF-1 from the liver
9
Q
Growth hormone actions
A
- Stimulates muscle growth
- Increases bone density and strength
- Stimulates cell regeneration and reproduction
- Stimulates growth of internal organs
10
Q
Parathyroid axis
A
PTH is released from four PTH glands (in response to low Ca/ low Mg/ low phosphate)
PTH increases serum calcium concentration
1) PTH increases activity and numbers of osteoclasts in bone (resorption of Ca from bone into blood)
2) PTH stimulates calcium reabsorption in the kidneys
3) PTH stimulates kidneys to convert D3 into calcitriol (Active form of vit D)
* If serum Ca is high, PTH is suppressed
11
Q
Role of Vit D
A
Hormone that promotes calcium absorption from food in the intestine
12
Q
The renin-angiotensin-aldosterone system
A
Renin is released in the kidney
Blood vessels secrete more Renin in low BP/ less Renin in high BP
Renin converts Angiotensinogen (released in liver) into Angiotensin I
ACE converts Angiotensin I into Angiotensin II (in the lungs)
Angiotensin II stimulates the release of Aldosterone (from adrenals)
* Aldosterone increases sodium and water reabsorption, increasing BP
13
Q
Main role of renin-angiotensin-aldosterone
A
Regulate the BP
14
Q
What is renin?
A
Enzyme released by juxtraglomerular cells in afferent arterioles in kidney
15
Q
What is aldosterone?
A
Mineralcorticoid steroid hormone, acts on nephrons to:
* Increase sodium reabsorption from the distal tubule
* Increase potassium secretion from the distal tubule
* Increase hydrogen secretion from the collecting ducts
16
Q
2 groups of corticosteroid hormones
A
- Glucocorticoids (e.g., cortisol)
- Mineralocorticoids (e.g., aldosterone)
17
Q
Primary glucocorticoid hormone
A
Cortisol, produced by adrenal glands
18
Q
Cushing’s syndrome
A
Prolonged high levels of glucocorticoids in the body [Cushing disease + Alternative cause: use of exogenous corticosteroids (dexamethasone or prednisolone)]
19
Q
Cushing’s disease
A
Pituitary adenoma secreting excess ACTH
* This stimulates excess cortisol release from adrenals
20
Q
Features of Cushing’s syndrome
A
- Round, moon face
- Central obesity
- Abdominal striae (stretch marks)
- Enlarged fat pad on the upper back (buffalo hump)
- Proximal limb muscle wasting (with difficulty standing from a sitting position without using their arms)
- hirsutism
- Easy bruising and poor skin healing
- Hyperpigmentation
21
Q
Hyperpigmentation in Cushing’s cause
A
High ACTH levels
22
Q
Metabolic effects of Cushing’s syndrome
A
- Hypertension
- Cardiac hypertrophy
- Type 2 diabetes
- Dyslipidaemia (raised cholesterol and triglycerides)
- Osteoporosis
23
Q
Causes of Cushing’s syndrome
A
- Cushing disease (pituitary adenoma releasing ACTH)
- Adrenal adenoma (adrenal tumour secreting excess cortisol)
- Paraneoplastic syndrome
- Exogenous steroids
24
Q
Paraneoplastic Cushing’s syndrome
A
ACTH is released from a tumour other than pituitary gland (ectopic ACTH)
* Eg. small cell lung cancer
25
Dexamethasone suppression tests
Used to diagnose Cushing’s syndrome caused by endogenous problem (not used to look for exogenous steroids cause)
26
Normal dexamethasone response
Supressed cortisol due to negative feedback (dexamethasone negatively acts on hypothalamus, which reduces CRH – this causes negative feedback on pituitary, then reduces ACTH. Low CRH and ACTH result in low cortisol release from adrenals. – lack of cortisol suppression is cushings syndrome.
27
3 types of dexamethasone suppression test
- Low dose overnight test
- Low dose 48h test
- High dose 48h test
28
Low dose overnight test
1mg dexa is given at night, cortisol checked in the morning; normal result is cortisol suppression
29
Low dose 48h test
0.5mg dexa is taken every 6h for 8 doses, starting at 9am.
Cortisol is checked at 0h and 48h later
Normal result: suppressed cortisol (abnormal is cushing syndrome)
30
High dose 48h test
2mg dexa taken every 6h for 8 doses starting at 9am.
Cortisol checked at 0h and 48h later
High dose supresses cortisol in cushing syndrome by pituitary adenoma (Cushing disease) but NOT in adrenal adenoma or ectopic ACTH
31
When is ACTH low?
When excess cortisol comes from adrenal tumour
32
When is ACTH high?
When it is produced by pituitary tumour or ectopic ACTH (small cell lung cancer)
33
high dose 48h test – cortisol supressed cause?
Cushing disease due to pituitary adenoma
34
High dose 48h test – cortisol not suppressed cause?
Adrenal adenoma or ectopic ACTH
35
Low dose dexa test/ high dose/ ACTH – normal pt
Cortisol low/ cortisol low/ ACTH high
36
Low dose dexa test/ high dose/ ACTH – adrenal adenoma
Not suppressed cortisol/ not suppressed/ low ACTH
37
Low dose dexa test/ high dose/ ACTH – pituitary adenoma
Not suppressed/ low cortisol/ high ACTH
38
Low dose dexa test/ high dose/ ACTH – ectopic ACTH
Not suppressed/ not suppressed/ high ACTH
39
Treatment in cushing syndrome
- Trans-sphenoidal removal of pituitary adenoma
- Surgical removal of adrenal tumour
- Surgical removal of ectopic ACTH tumour
40
Nelson’s syndrome
ACTH producing pituitary tumour develops post surgical removal of adrenals and lack of cortisol (lack of negative suppression)
41
Metyrapone
Reduces production of cortisol in the adrenals, might be used in treating Cushing’s
42
Primary hyperthyroidism
Thyroid abnormal – produces excessive thyroid hormones. TSH is suppressed by high T3 and T4 causing a low TSH level.
43
Secondary hyperthyroidism
Pituitary abnormal – produces excessive TSH (pituitary adenoma), stimulating excess production of TSH from thyroid, and hence T3 T4 are raised
44
Primary hypothyroidism
Thyroid abnormal – increased thyroid hormone produced, hence TSH is raised, T3 and T4 are low.
45
Secondary hypothyroidism
Pituitary produces inadequate TSH (eg post surgical removal of pituitary), understimulation of thyroid, hence TSH, T3, T4 all low
46
Primary hyperthyroidisim tsh, t3/4 levels
TSH low, T3/4 high
47
Secondary hyperthyroidism
TSH high, T3/4 high
48
Primary hypothyroidism
TSH high, T3/4 low
49
Secondary hypothyroidism
TSH low, T3/4 low
50
Anti-thyroid perioxidase antibodies
Antibodies against the thyroid gland (most relevant thyroid autoantibody in autoimmune thyroid disease); Graves disease and Hashimoto thyroidits
51
Anti-thyroglobulin antibodies (anti-Tg)
Antibodies against thyroglobulin (protein produced in the thyroid). Might be present in healthy individuals but raised in Grave’s disease, Hashmioto’s thyroiditis, and thyroid cancer
52
TSH receptor antibodies
Autoantibodies that mimic TSH and bind to the TSH receptor – they stimulate thyroid hormone release and cause Grave’s disease.
53
Radioisotope scans – diffuse high uptake
Grave’s disease
54
Radioisotope scans – focal high uptake
Toxic multinodular goitre and adenomas
55
Radioisotope scans – cold areas, abnormally low uptake
Thyroid cancer
56
Hyperthyroidism
Over production of thyroid hormones, T3 and T4
57
Thyrotoxicosis
Abnormal and excessive quantity of thyroid hormones
58
Primary hyperthyroidism
Thyroid pathology, thyroid produces excessive thyroid hormones
59
Secondary hyperthyroidism
Due to pathology in hypothalamus or pituitary when pituitary produces too much TSH, stimulating thyroid to produce excessive thyroid hormone
60
Subclinical hyperthyroidism
Thyroid hormones are normal but TSH is suppressed
61
Grave’s disease
Autoimmune condition of primary hyperthyroidism, as TSH receptor antibodies stimulate TSH receptors to produce thyroid hormones
62
Toxic multinodular goitre (Plummer’s disease)
Nodules develop on thyroid and produce excessive thyroid hormones
63
Exophthalmos
Proptosis – bulging of eyes due to Grave’s (due to presence of TSH receptor antibodies behind eyes, that swell)
64
Pretibial myxodema
Deposits of glycosaminoglycans/mucin under skin, specific to Grave’s disease, due to TSH receptor antibodies
65
Causes of hyperthyroidism
* G – Graves’ disease
* I – Inflammation (thyroiditis)
* S – Solitary toxic thyroid nodule
* T – Toxic multinodular goitre
66
Thyroiditis
Initial hyperthyroid then hypothyroid
67
Causes of thyroiditis
* De Quervain’s thyroiditis
* Hashimoto’s thyroiditis
* Postpartum thyroiditis
* Drug-induced thyroiditis
68
Features of hyperthyroidism
* Anxiety and irritability
* Sweating and heat intolerance
* Tachycardia
* Weight loss
* Fatigue
* Insomnia
* Frequent loose stools
* Sexual dysfunction
* Brisk reflexes on examination
69
Grave’s specific features
(due to presence of TSH receptor antibodies)
* Diffuse goitre (without nodules)
* Graves’ eye disease, including exophthalmos
* Pretibial myxoedema
* Thyroid acropachy (hand swelling and finger clubbing)
70
Solitary toxic thyroid nodule
Benign adenoma; Tx is surgical removal
71
De Quervain’s Thyroiditis
* Thyrotoxicosis (excess T3/4, thyroid swelling, flu-like ilnness, raised ESR and CRP)
* Hypothyroidism
* Return to normal
72
What is a long term rish of De Quervain’s thyroiditis
<10% of pts remain hypothyroid
73
Tx for De Quervain’s Thyroiditis
* NSAIDs for symptoms of pain and inflammation
* Beta blockers for the symptoms of hyperthyroidism
* Levothyroxine for the symptoms of hypothyroidism
74
Thyroid storm
/thyrotoxic crisis/ Rare representation of hyperthyroidism
More severe presentation of hyperthyroidism (fever, tachy, delirium) – might need fluid resuscitation, anti-arrhythmic, and b blockers
75
Mx of thyroid storm
Carbimazole – 1st line, anti-thyroid, taken 12-18months
Propylthiouracil – 2nd line
Radioactive iodine
B blockers
surgery
76
Maintenance dose of carbimazole
- Titrated to maintain normal thyroid levels
- Higher dose of carbimazole to block all production and levothyroxine to replace thyroid hormones
77
SE of carbimazole
Pancreatitis
78
SE of propylthiouracil
Liver reactions and death
79
SE of anti-thyroid medications
(propylthiouracil, carbimazole) – agranulocytosis (v low WBC) – low immunity, presenting with sore throat
80
Radioactive iodine treatment
Drinking a single dose of radioactive iodine, proportion of thyroid cells is destroyed and there is a reduction in thyroid hormone production – remission is 6 months and thyroid is then ofter underactive requiring levothyroxine treatment
81
Rules of tx with radioactive iodine
- No pregnancy or breastfeeding
- No pregnancy within the next 6 months
- No fathering within 4 months (men)
- Limit contact with people afterward (especially pregnant and children)
82
B Blockers in thyroid storm
Block the adrenalin-related symptoms of hypothyroidism (propranolol)
83
Surgery in thyroid storm
Thyroidectomy; definitive treatment; pt then requires life long levothyroxine
84
Primary hypothyroidism
Thyroid produces inadequate t3 and t4 (thyroid hormones); low t3/4 cause no negative feedback so TSH raises.
85
Secondary hypothyroidism
Pituitary gland produces too little TSH which causes understimulation of t3/4 production. All 3 are low.
86
Most common cause for hypothyroidism
Hashimoto’s thyroiditis
87
Hashimoto’s thyroiditis
Autoimmune condition causing inflammation of the thyroid.
88
What antibodies are present in Hashimoto?
Anti TPO, anti Tg
89
Hyperthyroidism treatment
- Carbimazole
- Prophylthiouracil
- Radioactive iodine
- Thyroid surgery
90
Lithium and thyroid
Lithium inhibits the production of thyroid hormone; causing goitre and hypothyroidism
91
Amiodarone and thyroid
Causes hypothyroidism and thyrotoxicosis
92
Secondary hypothyroidism causes
Tumours (pituitary adenoma)
Surgery to pituitary
Sheehan’s syndrome
Trauma
radiotherapy
93
Symptoms of hypothyroidism
- Weight gain
- Fatigue
- Dry skin
- Hair loss
- Fluid retention
- Heavy or irregular periods
- Constipation
94
What causes goitre?
Iodine deficiency
95
Hashimoto thyroiditis and thyroid structure
Initially causes a goitre, then atrophy of thyroid
96
Mx of hypothyroidism
Oral levothyroxine (synthetic t4), titrated every 4 weeks
97
Alternative drug to levothyroxine
Liothyronine sodium (synthetic t3) when levothyroxine is not tolerated.
98
T1D
Pancreas is unable to produce adequate insulin (hence body cells can’t absorb glucose) -> hyperglycaemia
99
What viruses may trigger T1D
Coxsackie B
Enterovirus
100
Hyperglycaemia symptoms
* Polyuria (excessive urine)
* Polydipsia (excessive thirst)
* Weight loss (mainly through dehydration)
Or diabetic ketoacidosis
101
Where are carbohydrates absorbed?
Small intestine
102
Ideal blood glucose concentration
4.4-6.1 mmol/L
103
Where is insulin produced?
Beta cells in Islets of Langerhans in pancreas
104
What kind of hormone is insulin?
Anabolic hormone (building hormone)
105
Actions of insulin
Reduces blood sugar:
- Absorbs glucose into the cells
- Causes muscle and liver to absorb glucose and store it as glycogen (glycogenesis)
106
Where is glucagon produced
By alpha cells in the Islets of Langerhans in the pancreas
107
Actions of glucagon
Responds to low blood sugar levels and stress and works to increase blood sugar levels – by acting on liver to break down the stored glycogen into glucose (glycogenolysis)
- Also acts of liver to convert protein and fat into glucose (gluconeogenesis)
108
Ketogenesis
Production of ketones in event on insufficient glucose and exhausted glycogen stores (in fasting)
- Liver takes fatty acids and converts them to ketones
109
Ketones
Water soluble fatty acids, they can cross blood prain barrier
110
Ketosis symptom
Acetone smell to breath
111
Pathophysiology of DKA
Consequence of inadequate insulin
- T1D not adhering to insulin regime
- T1D unwell with infection
- Pt presenting with T1D for the first time
112
Key features of DKA
* Ketoacidosis
* Dehydration
* Potassium imbalance
113
Ketoacidosis process
Liver produces ketone in low insulin state; levels of glucose and ketones increase and kidneys produce bicarbonate to counteract ketone acids. Over time blood becomes acidic (ketoacidosis)
114
Dehydration in DKA
Glucose leaks into urine, then glucose in the urine draws more water by osmotic diuresis – this causes polyuria and severe dehydration +there is polydipsia.
115
Potassium imbalance in DKA
Insulin drives potassium into cells – in DKA serum potassium may be high, bu total body potassium is low because no potassium is stored in cells – once insulin treatment starts, pts develop hypokalemia and arrythmia
116
Presentation of DKA
* Hyperglycaemia
* Dehydration
* Ketosis
* Metabolic acidosis (with a low bicarbonate)
* Potassium imbalance
* Polyuria
* Polydipsia
* Nausea and vomiting
* Acetone smell to their breath
* Dehydration
* Weight loss
* Hypotension (low blood pressure)
* Altered consciousness
117
Diagnosing DKA
* Hyperglycaemia (e.g., blood glucose above 11 mmol/L)
* Ketosis (e.g., blood ketones above 3 mmol/L)
* Acidosis (e.g., pH below 7.3)
118
Mx of DKA
* F – Fluids – IV fluid resuscitation with normal saline (e.g., 1 litre in the first hour, followed by 1 litre every 2 hours)
* I – Insulin – fixed rate insulin infusion (e.g., Actrapid at 0.1 units/kg/hour)
* G – Glucose – closely monitor blood glucose and add a glucose infusion when it is less than 14 mmol/L
* P – Potassium – add potassium to IV fluids and monitor closely (e.g., every hour initially)
* I – Infection – treat underlying triggers such as infection
* C – Chart fluid balance
* K – Ketones – monitor blood ketones, pH and bicarbonate
119
Before stopping insulin and fluid in DKA
* Ketosis and acidosis should have resolved
* They should be eating and drinking
* They should have started their regular subcutaneous insulin
120
What is max rate of potassium infusion in normal circumstances?
10 mmol/h (risk of arrhythmia and cardiac arrest)
121
What are the key complications in DKA treatment?
* Hypoglycaemia (low blood sugar)
* Hypokalaemia (low potassium)
* Cerebral oedema, particularly in children
* Pulmonary oedema secondary to fluid overload or acute respiratory distress syndrome
122
How is insulin given in DKA?
Up to 20 mmol/h with central line
123
Serum C peptide
Measure of insulin production
124
Low serum C peptide
Low insulin production
125
High serum C peptide
High insulin production
126
Autoantibodies in T1D
* Anti-islet cell antibodies
* Anti-GAD antibodies
* Anti-insulin antibodies
127
Long term management
* Subcutaneous insulin
* Monitoring dietary carbohydrate intake
* Monitoring blood sugar levels upon waking, at each meal and before bed
128
Basal-bolus regime
* Background, long-acting insulin injected once a day
* Short-acting insulin injected 30 minutes before consuming carbohydrates (e.g., at meals)
129
Lipodystrophy
Subcut fat hardens due to injections and can’t absorb insulin (must circulate injection sites)
130
Insulin pump
Device that continuously infuses insulin (canula and site are rotated every 2-3 days)
131
Advantage of insulin pump
Good at sugar control and more flexibility with eating and less injections
132
Disadvantage of insulin pump
* Difficulties learning to use the pump
* Having it attached at all times
* Blockages in the infusion set
* A small risk of infection
133
Tethered pumps
Devices with replaceable infusion sets and insulin
134
Patch pumps
Sit directly on the skin without visible tubes, - when finished, entire pump is disposed and new one attached.
135
Pancreas transplant
Implanting donor pancreas to produce insulin, original pancreas left in place to produce digestive enzymes
136
Islet transplantation
Inserting donor islets into pt’s liver. Islet cells produce insulin; pt often still needs insulin therapy.
137
Flash glucose monitor
FreeStyle Libre 2 – senson on the skin to measure glucose levels in the interstitial fluid in the subcut tissue. Pt swipes mobile phone over the sensor to collect reading. Sensors need replacing every 2 weeks.
138
What is the issue with Flash glucose monitor
There is a 5 min delay which means capillary blood glucose is required if hypoglycaemia is suspected.
139
Continuous glucose monitors
Similar to flash glucose, sensor on the skin monitors sugar levels, sends reading over bluetooth, no need to scan the sensor
140
Closed-loop system
Called artificial pancreas. Combination of continuous glucose monitor and insulin pump. The system automatically adjusts itself.
141
Short term complications of T1D
* Hypoglycaemia
* Hyperglycaemia (and diabetic ketoacidosis)
142
Tx of hypoglycaemia
Rapid acting glucose (high sugar drink), then slower-acting carbohydrates to prevent sugar dropping. In severe cases: IV dextrose or IM glucagon.
143
Long term complications of T1D
Chronic damage to endothelial cells of blood vessels, vessels are leaky and unable to regenerate. High glucose levels also cause immune dysfunction.
144
Macrovascular complications of T1D
* Coronary artery disease is a significant cause of death in diabetics
* Peripheral ischaemia causes poor skin healing and diabetic foot ulcers
* Stroke
* Hypertension
145
Microvascular complications of T1D
* Peripheral neuropathy
* Retinopathy
* Kidney disease, particularly glomerulosclerosis
146
Infection-related complications of T1D
* Urinary tract infections
* Pneumonia
* Skin and soft tissue infections, particularly in the feet
* Fungal infections, particularly oral and vaginal candidiasis
147
T2D
Insulin resistance and reduced insulin production (+pancreas is fatigued over time)
148
Complications of chronic hyperglycaemia
- Microvascular
- Macrovascular
- Infectious complications
149
Non modifiable risk factors for T2D
* Older age
* Ethnicity (Black African or Caribbean and South Asian)
* Family history
150
Modifiable risk factors for T2D
* Obesity
* Sedentary lifestyle
* High carbohydrate (particularly sugar) diet
151
Presenting features of T2D
* Tiredness
* Polyuria and polydipsia
* Unintentional weight loss
* Opportunistic infections (e.g., oral thrush)
* Slow wound healing
* Glucose in urine (on a dipstick)
152
Acanthosis nigricans
Thickening and darkening of the skin (neck, axilla, groin), velvety appearance; present in insulin resistance
153
Pre diabetes HbA1c
42-47 mmol/mol
154
Type 2 diabetes HbA1c
>48 mmol/mol (sample retaken 1 month later to confirm diagnosis)
155
HbA1c targets in diabetics
* 48 mmol/mol for new T2D
* 53 mmol/mol for pts on >1 antidiabetic medication
156
How often is HbA1c measured in a newly diagnosed pt
Every 3 to 6 months
157
1st line Tx for T2D
Metformin
158
Which pts need additional SGLT-2 inhibitor (dapagliflozin) after metformin?
- If they have CVD or heart failure
- QRISK >10%
159
2nd line Tx for T2D
Sulfonylurea, pioglitazone, DPP4 inhibitor, SGLT2 inhibitor
160
3rd line Tx for T2D
Either:
- Metformin + 2nd line
- Insulin
161
When is GLP-1 mimetic (liraglutide) used?
When Triple therapy fails and BMI >35
162
Metformin MOA
(biguanide)
Increases insulin sensitivity
Decreases glucose production by the liver
No weight gain, No hypoglycaemia
163
SE of metformin
GI symptoms (nausea and diarrhoea)
Lactic acidosis 2ndary to AKI
164
SE on standard release metformin
Try modified release metformin
165
SGLT-2 inhibitors
-GLIFLOZIN (empagliflozin, canagliflozin, dapagliflozin, ertugliflozin)
Blocks sodium glucose co transporter 2 protein in the proximal tubules so glucose is not reabsorbed from the urine and is excreted.
- Improve heart failure, cause weight loss, reduces BP, lowers HbA1c
166
Alternative action of SGLT-2 inhibitors
Reduces risk of CVD
167
SGLT-2 inhibitors licenced for heart failure
Empagliflozin and dapagliflozin
168
SGLT-2 inhibitors licensed for CKD
Dapagliflozin
169
SE of SGLT-2 inhibitors
* Glycosuria
* Increased urine output and frequency
* Genital and urinary tract infections (e.g., thrush)
* Weight loss
* Diabetic ketoacidosis,
* Lower-limb amputation may be more common in patients on canagliflozin (unclear if this applies to the others)
* Fournier’s gangrene (rare but severe infection of the genitals or perineum)
170
Pioglitazone
thiazolidinedione.
increases insulin sensitivity and decreases liver production of glucose.
does not cause hypoglycaemia.
171
Pioglitazone SE
* Weight gain
* Heart failure
* Increased risk of bone fractures
* A small increase in the risk of bladder cancer
172
Sulfonylureas
Gliclazide
Stimulates insulin release from the pancreas
173
SE of sulfonylureas
- Weight gain
- Hypoglycaemia
174
Glucagon like peptide 1
Glucagon like peptide 1
175
What inhibits incretins?
Enzymes called dipeptidyl peptidase-4 DPP4
176
Incretins
Hormones produced in the GI
* Increasing insulin secretion
* Inhibiting glucagon production
* Slowing absorption by the gastrointestinal tract
177
DPP4 inhibitors
Sitagliptin and alogliptin
178
SE of DPP4 inhibitors
Headache
Acute pancreatitis
179
GLP 1 mimetics
Imitate GLP 1; exenatide, liraglutide
180
SE of GLP 1 mimetics
* Reduced appetite
* Weight loss
* Gastrointestinal symptoms, including discomfort, nausea and diarrhoea
181
Rapid acting insulin
NovoRapid; start working after 10 min; last 4h
182
Short acting insuling
Actrapid; start working in 30 mins and last 8h
183
Intermediate acting insulins
Humulin I – start working in 1h and last 16h
184
Long acting insulin
Levemir, Lantus – start working 1h and last 24h
185
Combinations insulin
Contain rapid and intermediate acting (ratio of rapid to intermediate)
* Humalog 25 (25:75)
* Humalog 50 (50:50)
* Novomix 30 (30:70)
186
Complications of T2D
* Infections (e.g., periodontitis, thrush and infected ulcers)
* Diabetic retinopathy
* Peripheral neuropathy
* Autonomic neuropathy
* Chronic kidney disease
* Diabetic foot
* Gastroparesis (slow emptying of the stomach)
* Hyperosmolar hyperglycemic state
186
T2D 1st line HTN tx
Ace inhibitor
187
T2D with CKD and ACR >3mg/mmol
Start ACE inhibitor
188
T2D with CKD and ACR >30mg/mmol
Start SGLT2 inhibitor on top off ACEi
188
Erectile dysfunction in T2D
Give Phosphodiesterase 5 inhibitors (e.g., sildenafil or tadalafil)
189
Gastroparesis in T2D tx
Prokinetic drugs (e.g., domperidone or metoclopramide)
190
Tx For diabetic neuropathy (neuropathic pain)
* Amitriptyline – a tricyclic antidepressant
* Duloxetine – an SNRI antidepressant
* Gabapentin – an anticonvulsant
* Pregabalin – an anticonvulsant
191
Hyperosmolar Hyperglycaemic State
Hyperosmolality (water loss), hyperglycaemia, and absence of ketones
192
Tx of HSS
IV fluids
193
Acromegaly
Excessive Growth hormone
194
Where is Growth hormone produced?
By anterior pituitary
194
Most common cause of growth hormone upregulation?
Pituitary adenoma (microscopic or macroscopic), lung or pancreatic cancer which secretes growth hormone releasing hormone or growth hormone
194
Pituitary tumour pressing on optic chiasm
Bitemporal hemianopia
195
Presentation of pituitary tumour
Space-occupying:
* Headaches
* Visual field defect (bitemporal hemianopia)
196
How to diagnose acromegaly?
Test insulin-like growth-factor 1 (IGF1) – raised, means raised GH
196
Additional features of excess growth hormone/acromegaly
* Hypertrophic heart
* Hypertension
* Type 2 diabetes
* Carpal tunnel syndrome
* Arthritis
* Colorectal cancer
196
Excess growth hormone body features:
* Prominent forehead and brow (frontal bossing)
* Coarse, sweaty skin
* Large nose
* Large tongue (macroglossia)
* Large hands and feet
* Large protruding jaw (prognathism)
196
How to diagnose pituitary adenoma?
MRI of the pituitary
196
GH suppression test
Consume 75g glucose drink, GH tested at baseline and at 2h – the glucose should suppress the growth hormone – failure to suppress means Acromegaly
197
Tx of pituitary tumour
Trans-sphenoidal surgery (through nose and sphenoid bone) to remove the tumour +- radiotherapy
197
Why is testing GH unreliable?
Fluctuates throughout the day
197
Somatostatin
Growth hormone-inhibiting hormone
197
Medical options for reducing growth hormone
* Pegvisomant is a growth hormone receptor antagonist given daily by a subcutaneous injection
* Somatostatin analogues (e.g., octreotide) block growth hormone release
* Dopamine agonists (e.g., bromocriptine) block growth hormone release
197
Where is parathyroid hormone produced?
In chief cells in the parathyroid glands (in 4 corners of the thyroid), - produced in response to hypocalcaemia
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Dopamine
Where is parathyroid hormone produces?
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3 ways of PTH raising the blood calcium
* Increasing osteoclast activity in bones (reabsorbing calcium from bones)
* Increasing calcium reabsorption in the kidneys (less calcium is lost in urine)
* Increasing vitamin D activity, resulting in increased calcium absorption in the intestines
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PTH and vit D
PTH acts on vit D to convert it to active form and absorb more calcium from the intestines
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Symptoms of hypercalcemia mnemonic
Stones, bones, groans, moans
* Kidney stones
* Painful bones
* Abdominal groans (constipation, nausea and vomiting)
* Psychiatric moans (fatigue, depression and psychosis)
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Primary hyperparathyroidism
Uncontrolled PTH production by parathyroid tumour – leads to increase in blood calcium
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Conn’s syndrome
Adrenal adenoma producing too much aldosterone
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Tertiary hyperparathyroidism
Occurs as a result of 2nd hyperparathyroidism – hyperplasia of the gland – when initial problem is corrected but still v high PTH produced – high PTH and hypercalcaemia
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High PTH and low/normal Ca
Secondary hyperparathyroidism
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High PTH and high Calcium
Primary hyperparathyroidism
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Key presenting feature of hyperaldosteronism
Hypertension
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Secondary hyperparathyroidism
Insufficient vit D or CKD reduce calcium absorption and cause hypocalcaemia. -> Hence more PTH is released.
High PTH and low/normal serum Ca
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Where is renin released?
Juxtraglomerular cells in the afferent arterioles of the kidney
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What does ACE do ?
Converts angiotensin I to angiotensin II
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What is the role of Angiotensin II
Stimulates release of aldosterone from adrenal glands
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What is the role of juxtraglomerular cells?
Sense the blood pressure and release renin in response (low bp, more renin released; high bp , moless renin released)
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What does renin do?
Converts angiotensinogen (released by liver) to angiotensin I
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High PTH and high Ca
Tertiary hyperparathyroidism
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Causes of primary hyperaldosteronism
* Bilateral adrenal hyperplasia (most common)
* An adrenal adenoma secreting aldosterone (known as Conn’s syndrome)
* Familial hyperaldosteronism (rare)
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Actions of aldosterone
* Increase sodium reabsorption from the distal tubule
* Increase potassium secretion from the distal tubule
* Increase hydrogen secretion from the collecting ducts
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Secondary hyperaldosteronism
Due to excessive renin stimulating excessive aldosterone release
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How is renal artery stenosis confirmed?
* Doppler ultrasound
* CT angiogram
* Magnetic resonance angiography (MRA)
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Primary hyperaldosteronism
Adrenal glands produce too much aldosterone
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Primary hyperaldosteronism blood test
High aldosterone and low renin
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What causes excessive renin?
Dispropitionaly lower pressure in the kidneys due to:
* Renal artery stenosis
* Heart failure
* Liver cirrhosis and ascites
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How to check for primary/secondary hyperaldosteronism?
Aldosterone-to-renin ratio
203
Ix on the effect of hyperaldosteronism
* Raised blood pressure (hypertension)
* Low potassium (hypokalaemia)
* Blood gas analysis (alkalosis)
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Secondary hyperaldosteronism blood test
High aldosterone and high renin
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Ix for underlying cause of hyperaldosteronism
* CT or MRI to look for an adrenal tumour or adrenal hyperplasia
* Renal artery imaging for renal artery stenosis (Doppler, CT angiogram or MR angiography)
* Adrenal vein sampling of blood from both adrenal veins to locate which gland is producing more aldosterone
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Mx of hyperaldosteronism
* Eplerenone
* Spironolactone
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Treating the underlying cause of hyperaldosteronism
* Surgical removal of the adrenal adenoma
* Percutaneous renal artery angioplasty via the femoral artery to treat renal artery stenosis
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Where is ADH secreted?
Posterior pituitary gland
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SIADH
Increased release of antidiuretic hormone from the posterior pituitary – it increases water reabsorption from urine, diluting blood and leading to hyponatremia
204
Where does ADH work?
Collecting ducts in the kidneys
204
Presentation of SIADH
Low sodium
* Headache
* Fatigue
* Muscle aches and cramps
* Confusion
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Where is ADH produced
Hypothalamus
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2 sources of too much ADH
* Increased secretion by the posterior pituitary
* Ectopic ADH, most commonly by small cell lung cancer
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What does SIADH result in?
Euvolaemic hyponatraemia
More concentrated urine – high urine osmolality and high urine sodium
205
How is diagnosis of SIADH made?
On clinical features:
* Euvolaemia
* Hyponatraemia
* Low serum osmolality
* High urine sodium
* High urine osmolality
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Primary polydipsia
Excessive water consumption but low urine sodium and low urine osmolality
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Mx of SIADH
* Admission if symptomatic or severe (e.g., sodium under 125 mmol/L)
* Treating the underlying cause (e.g., stopping causative medications or treating the infection)
* Fluid restriction
* Vasopressin receptor antagonists (e.g., tolvaptan)
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Severe hyponatremia presentation
seizures and reduced consciousness.
206
Why does Na need to be corrected slowly?
To prevent osmotic demyelination (Na concentration should not change more than 10 mmol/L in 24h)
206
Causes of SIADH
* Post-operative after major surgery
* Lung infection, particularly atypical pneumonia and lung abscesses
* Brain pathologies, such as a head injury, stroke, intracranial haemorrhage or meningitis
* Medications (e.g., SSRIs and carbamazepine)
* Malignancy, particularly small cell lung cancer
* Human immunodeficiency virus (HIV)
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What is the fluid restriction in SIADH
Limiting fluid intake to 750-1000 ml
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Osmotic demyelination syndrome symptoms
1st phase: electrolyte imbalance, encelopathy, confusion, headache, vomiting, seizures
2nd phase: demyelination, spastic quadriparesis, pseudobulbar palsy, cognitive and behavioural changes
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Osmotic demyelination syndrome
Central pontine myelinolysis – due to long term severe hyponatremia <120mmol/L treated too quickly
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2 causes of diabetes insipidus
* A lack of antidiuretic hormone (cranial diabetes insipidus)
* A lack of response to antidiuretic hormone (nephrogenic diabetes insipidus)
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What is diabetes insipidus
Kidneys are unable to reabsorb water and concentrate urine causing:
* Polyuria (excessive amounts of urine)
* Polydipsia (excessive thirst)
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Nephrogenic diabetes insipidus
Kidneys (collecting duct) does not respond to ADH
210
Causes for nephrogenic diabetes insipidus
* Medications, particularly lithium (used in bipolar affective disorder)
* Genetic mutations in the ADH receptor gene (X-linked recessive inheritance)
* Hypercalcaemia (high calcium)
* Hypokalaemia (low potassium)
* Kidney diseases (e.g., polycystic kidney disease)
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Cranial diabetes insipidus
Hypothalamus does not produce ADH for the pituitary gland to secrete
212
Causes of cranial diabetes insipidus
* Brain tumours
* Brain injury
* Brain surgery
* Brain infections (e.g., meningitis or encephalitis)
* Genetic mutations in the ADH gene (autosomal dominant inheritance)
* Wolfram syndrome (a genetic condition also causing optic atrophy, deafness and diabetes mellitus)
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Presenting features of diabetes insipidus
* Polyuria (producing more than 3 litres of urine per day)
* Polydipsia (excessive thirst)
* Dehydration
* Postural hypotension
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Ix in diabetes insipidus
* Low urine osmolality (lots of water diluting the urine)
* High/normal serum osmolality (water loss may be balanced by increased intake)
* More than 3 litres on a 24-hour urine collection
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Describe water deprivation test
Pt avoids all fluid for 8h; then urine osmolality is measured; if low then ADH/desmopressin is given and urine osmolality measured again after 4h
215
How to diagnose diabetes insipidus?
Water deprivation test / (desmopressin stimulation test)
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Primary polydipsia water deprivation test
Urine osmolality:
High after water deprivation; no desmopressin required
216
Cranial DI water deprivation test
Urine osmolality:
Low after water deprivation, high after desmopressin
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Mx of nephrogenic DI
* Ensuring access to plenty of water
* High-dose desmopressin
* Thiazide diuretics
* NSAIDs
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Phaeochromocytoma
Tumour of the adrenal glands that secretes unregulated amounts of catecholamines (Adrenaline) – tumour of chromaffin cells
216
Nephrogenic DI water deprivation test
Urine osmolality:
Low after water deprivation, low after desmopressin
216
Dx of phaeochromocytoma
* Plasma free metanephrines (have a longer half live than adrenaline)
* 24-hour urine catecholamines
* Ct or MRI to look at the tumour
* Genetic testing
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Mx of cranial DI
Desmopressin
216
What kind of hormone is adrenaline?
Catecholamine (stimulates sympathetic nervous system)
216
Where is adrenaline produced?
Chromaffin cells in the medulla (middle part) of the adrenal gland
216
Symptoms of phaeochromocytoma
* Anxiety
* Sweating
* Headache
* Tremor
* Palpitations
* Hypertension
* Tachycardia
Symptoms come in bursts when adrenaline is released
216
Mx of phaeochromocytoma
* Alpha blockers (e.g., phenoxybenzamine or doxazosin)
* Beta blockers, only when established on alpha blockers
* Surgical removal of the tumour
216
Which genetic conditions are related to phaeochromocytoma
* Multiple endocrine neoplasia type 2 (MEN 2)
* Neurofibromatosis type 1
* Von Hippel-Lindau disease
