Endocrinology Flashcards
Diabetes Type 1 & 2 , DKA, HHS, Hypo/ Hyperglycaemia, Hypo/ Hyperthyroidism, Graves, Thyroid cancer, Hashimoto's, Cushing's syndrome /disease, Acromegaly, Prolactinoma, Conn's Syndrome, Addisons 1° &2° ,SIADH, Hypo/ Hyperkalaemia, Diabetes Insipidus, Hypo/ Hyperparathyroidism, Pheochromocytoma, Diabetes meds, Thyroid drugs, Steroids, Pituitary gland drugs
1
Q
What is Type 1 Diabetes?
A
This is insulin deficiency due to an autoimmune destruction of pancreatic B-cells
– The disease usually manifests in adolescence, sometimes after a viral infection.
2
Q
Symptoms of Type 1 Diabetes?
A
– Hyperglycemia – low insulin leads to decreased glucose uptake by fat and muscle
– Weight loss, low muscle mass – unopposed glucagon leads to lipolysis and glycogenolysis
– Polyuria, polydipsia and glycosuria
3
Q
Treatment of Type 1 Diabetes?
A
1) Insulin therapy – twice-daily insulin detemir is a common regime, but depends on patient’s diet and compliance
2) Monitor HbA1c every 3-6months
4
Q
Diagnosis for Type 1 Diabetes?
A
The diagnosis of diabetes mellitus can be made using plasma glucose or a HbA1c sample[1].
– Plasma glucose or HbA1c must show evidence of diabetes of two separate occasions if asymptomatic:
Fasting glucose > 7.0 mmol/L
Random glucose/OGTT > 11.1mmol/L
HbA1c > 48mmol/mol (6.5%)
5
Q
Acute Complication for Type 1 Diabetes?
A
Diabetic Ketoacidosis
6
Q
What is Type 2 Diabetes and causes
A
This is non- insulin dependent/ resistant
– Arises in middle aged, obese adults due to decreased number insulin receptors due to failed secretion from pancreatic B- cells
– Progresses from impaired glucose tolerance
7
Q
Risk of Type 2 Diabetes?
A
Obesity, lack of excercise + alcohol excess
– Stronger genetic influence than type 1 – high in Asians, men and the elderly
8
Q
Diagnosis for Type 2 Diabetes?
A
The diagnosis of diabetes mellitus can be made using plasma glucose or a HbA1c sample[1].
Fasting glucose > 7.0 mmol/L
Random glucose/OGTT > 11.1mmol/L
HbA1c > 48mmol/mol (6.5%)
9
Q
Treatment for Type 2 Diabetes
A
1) If HbA1c rises to 48mM
– Lifestyle modifications – diet, weight control + exercise
2) If HbA1c stays above 48mM
– Commence Metformin – aim for HbA1c < 48mM
3) If HbA1c rises >58mM …Dual, Triple therapy
– Add sulphonylurea or Pioglitazone or DPP -4 inhibitor or SGLT-2 inhibitor or insulin
10
Q
Acute Complication for Type 2 Diabetes?
A
HHS
11
Q
What is DKA?
A
This is an emergency which is characterized by severe hyperglycaemia and severe acidosis, due to lack of insulin.
– Due to the body being in starvation like state and excessive ketone body production.
12
Q
Symptoms of DKA?
A
– Triad of drowsiness + dehydration + Unexplained vomiting
– Ketotic/ fruity breath, coma
– Deep breathing (Kussmaul hyperventilation)
- Tachycardia
- Weight loss
- Potassium imbalance
13
Q
Diagnosis for DKA?
A
– Acidaemia (Venous pH <7.3 or HCO3– >15mM)
– Hyperglycaemia (glucose >11mM) or known diabetic
– Ketones >3mmol/L on a urine dipstick
- Serum U + E = Increase urea, creatinine, Decrease total and serum K+
14
Q
Management for DKA?
A
Use the ABC approach
F = Fluids - IV Fluid resuscitation with saline
I = Insulin - Insulin infusion
G = Glucose - Dextrose infusion if < 14 mmol / L
P = Potassium - monitor serum k+
I = Infection - Treat underlying cause
c = Chart - fluid balance
k = ketones - monitor blood ketones/ bicarb.
15
Q
Complications for DKA?
A
– Arrhythmias secondary to hyperkalaemia/iatrogenic hypokalaemia
– Cerebral oedema –> seen more in children/young adults, occurs 4-12 hours usually after treatment
–> Gives headache, confusion, visual disturbances due to raised ICP
16
Q
Chronic complication for DM?
A
Microvascular = Retinopathy, Nephropathy, Erectile dysfunction, Neuropathy
Macrovascular = Atherosclerosis, Stable angina, ACS, stroke
17
Q
What is HHS?
A
- Marked hyperglycaemia
- Hyperosmolality
- No ketosis
18
Q
HHS Pathophysiology?
A
- Low insulin -> Increased gluconeogenesis -> hyperglycaemia but not enough to inhibit ketoneogenesis.
- Hyperglycaemia -> Osmotic diuresis -> Dehydration
19
Q
DKA pathophysiology?
A
- Peripheral lipolysis -> Increase in free fatty acids -> oxidised to Acetyl CoA -> Ketone bodies = Acidosis
20
Q
HHS Symptoms?
A
Diabetes +…
- Confusion
- Lethargy
- Deydration
21
Q
Hyperglycaemia pathophysiology?
A
- Absence of insulin -> more catabolism -> more gluconeogenesis & decreased peripheral glucose uptake -> Hyperglycaemia
22
Q
HHS diagnosis?
A
- Random plasma glucose = >11mmol/L
- Urine dipstick = glycosuria
- U+E = Decrease total K+, Increase serum K+
23
Q
HHS treatment?
A
- Replace fluid
- Insulin
- Restore electrolytes e.g. K+
- Low molecular weight heparin
24
Q
Hyperthyroidism
A
increased levels of circulating thyroid hormone.
– It leads to increase in basal metabolic rate (due to increased synthesis of Na/K-ATPase)
– Increased sympathetic nervous system activity (due to increased B1-adrenergic receptors)
25
Hyperthyroidism symptoms?
– Weight loss despite increase appetite
– Heat intolerance and sweating
– Tachycardia + palpitations
– Tremor/anxiety
– Decreased muscle mass with weakness
– Bone resorption with hypercalcemia
– Hyperglycaemia
26
Hyperthyroidism signs
```
– Fast pulse/atrial fibrillation
– Warm moist skin
– Thin hair
- Goitre
- Menorrhagia
```
27
Hyperthyroidism diagnosis
– TFT shows high T4, low TSH. High glucose and hypocholesterolaemia
28
Hyperthyroidism treatment
i) Beta-blockers – Propranolol gives control of symptoms due to high sympathetic activity
Propranolol + Carbimazole + Iodine
2nd line - Propylthiouracil
iii) Radioiodine
iv) Thyroidectomy – risk of recurrent laryngeal nerve injury + people become hypothyroid after
29
Graves disease
This is an autoimmune condition which is the most common cause of hyperthyroidism
– Autoimmune IgG antibody stimulates the TSH receptor antibodies increasing thyroid release
30
Graves disease symptoms
– Diffuse goitre as constant TSH stimulate leads to thyroid hyperplasia
– Pretibial myxoedema – shin fibroblasts express TSH receptor causing inflammation
– Exophthalmos (bulging of eyes) – fibroblasts behind orbit express the TSH receptor
31
Hashimoto thyroiditis
most common cause in regions where iodine levels are adequate
– Due to autoimmune destruction of thyroid gland by anti- TPO & Antithyroglobulin antibodies
- associated with Type I diabetes, Addison’s
- High TSH, Low T4
32
Hypothyroidism
- marked by a lack of thyroid hormone
| - based on decreased BMR and decreased sympathetic activity
33
Hypothyroidism symptoms
```
– Increased weight with normal appetite
– Cold intolerance with no sweating
– Bradycardia
– Decreased mood
– Constipation
– lethargic
```
34
Hypothyroidism signs
– Slow reflexes and ataxia
– Cold dry hands
– Ascites/oedema
– Hypercholesterolemia
35
Hypothyroidism diagnosis
- Primary = High TSH, Low T4
| - Secondary = Low TSH, Low T4
36
Hypothyroidism treatment
Levothyroxine (T4)
37
Subclinical hypothyroidism
High TSH, Normal T4
38
De Quervian Thyroiditis
granulomatous thyroiditis after a viral infection
39
Thyroid Storm + Treatment
biggest complications of hyperthyroidism due to trauma
| IV propranolol + Propylthiouracil + Dexamethasone (stops T4 –> T3) + Iodine solution
40
Cushing’s syndrome and disease
Syndrome = chronic cortisol excess
Disease = Caused by an ACTH secreting pituitary adenoma
More ACTH -> Adrenal cortex especially zona fasciculata stimulated -> More cortisol
41
Cushing’s syndrome causes
ACTH-independent causes: (gives low ACTH –> adrenal atrophy)
- steroids, adenoma
ACTH-dependent causes: (gives high ACTH –> adrenal hyperplasia)
- Cushing’s disease, Ectopic ACTH production from small cell lung cancer
42
Cushing’s syndrome symptoms
– Muscle weakness and breakdown
– Osteoporosis
– Immune suppression
– Hypertension
43
Cushing’s syndrome signs
– Abdominal striae- thinning of skin
– Poor wound healing
– Central obesity, buffalo hump
– Moon faced shape
44
Cushing’s syndrome diagnosis
– 1st line: Overnight dexamethasone test (48hr)
Normally cortisol is suppressed
low Dose Test - High cortisol = Cushing's Syndrome
High Dose test - Low Cortisol = Cushing's Disease
- High Cortisol - ACTH High= Ectopic ACTH
- ACTH low = Adrenal adenoma
-2nd line: 24-hour urinary free cortisol
45
Cushing’s syndrome Treatment
Stop steroids if iatrogenic, Transsphenoidal surgery, adrenalectomy
46
Pheochromocytoma
adrenaline producing tumour of the chromaffin cells
47
Pheochromocytoma symptoms
Triad of episodic headache, sweating and tachycardia (palpitations), with hypertension
48
Pheochromocytoma diagnosis
Increased plasma Metanephrine level
– Increased 24-hr Urine Catecholamines
– Abdominal CT/MRI scan to locate tumour
49
Pheochromocytoma treatment
– 1st line = alpha-blocker - phenoxybenzamine
- 2nd line = beta - blocker - Atenolol / Metoprolol
– Surgical excision to remove tumour
50
Conn's syndrome
primary hyperaldosteronism due to an aldosterone producing adenoma
Secondary hyperaldosteronism = excess renin causing more Aldosterone - serum renin will be high
Big cause in 2° hypertension
51
Conn's syndrome pathophysiology
excess production of aldosterone independent of the renin-angiotensin, causing increased sodium and water retention.
– It is characterized by high aldosterone and low renin (as high BP inhibits renin)
52
Conn's syndrome symptoms
- hypertension
- hypokalaemia
- Hypernatraemia
- nocturia
- polyuria
- headache, anxiety
- atrial fib.
53
Conn's syndrome investigations
Aldosterone - Renin Ratio blood test -
High aldosterone , Low renin = 1°
High aldosterone , High renin = 2°
Plasma potassium - low
54
Conn's syndrome Treatment
– Conn’s syndrome –> laparoscopic surgery to remove adenoma
| – Hyperplasia –> K+ sparing diuretics e.g. spironolactone
55
Addison's disease/ Primary insufficiency
(increased ACTH)
failure of adrenal gland to produce cortisol and aldosterone
- caused by TB, autoimmune disease
56
Secondary adrenal insufficiency
(decreased ACTH)
caused by a factor extrinsic to the adrenal glands
– Most common cause is iatrogenic due to long term steroid therapy and adrenal suppression
57
Addison's disease symptoms
– Lack of cortisol –> hypotension, muscle weakness
– Lack of aldosterone –> dehydration, hypovolemia, hyponatremia, hyperkalaemia
– Metabolic acidosis
– Increased ACTH –> causes hyperpigmentation due to increase melanocyte stimulating hormone
58
Addison's disease Diagnosis
```
1st line ACTH stimulation test
(Short Synacthen test - No rise= Primary A.l)
( Long Synacthen test - No change
Primary = High ACTH level
Secondary = low ACTH level
```
- CT/ MRI of adrenals & Pituitary
59
Addison's disease Treatment
– Replace cortisol – hydrocortisone (glucocorticoid)
| – Replace aldosterone – fludrocortisone (mineralocorticoid)
60
Acromegaly
increased secretion of growth hormone from the anterior pituitary
– Most often due to a pituitary adenoma
61
Acromegaly Symptoms
- enlarged hands, tongue, jaw and feet
- prominent forehead
- profuse sweating
- bitemporal hemianopia
62
Acromegaly investigations
– 1st line is to check if Serum IGF-1 level is raised
- Oral glucose tolerance test
- MRI scan of pituitary fossa
63
Acromegaly Treatment
– 1st line is transphenoidal surgery
– Octreotide – somatostatin analogue
– Pegvisomant – GH receptor antagonist
- Bromocriptine - Dopamine agonist
64
Acromegaly complications
- Secondary diabetes mellitus as GH induces gluconeogenesis
| - Erectile dysfunction
65
Prolactinoma
pituitary adenoma producing excess prolactin
66
Prolactinoma causes
- dopamine antagonists (reduce inhibition of prolactin)
| - Primary hypothyroidism (TRH stimulates prolactin release)
67
Prolactinoma symptoms
Women = Galactorrhoea, Amenorrhoea, Infertility
-> Raised prolactin inhibits GnRH which decreases LH, FSH, oestrogen and testosterone
Men = Erectile dysfuction, Less libido
68
Prolactinoma Diagnosis
- Prolactin levels
| - MRI of pituitary gland
69
Prolactinoma Treatment
– 1st choice is dopamine agonists to reduce prolactin secretion e.g. Bromocriptine/Cabergoline
- 2nd line = Transsphenoidal Resection Surgery of pit. gland
70
SIADH
excessive ADH secretion - causing water to be reabsorbed in collecting duct
71
SIADH Causes
ectopic ADH production (e.g. small cell lung carcinoma)
| – CNS trauma + Drugs (Thiazide diuretics, SSRIs (Sertraline), NSAIDs)
72
SIADH Symptoms
– Hyponatremia
- Low osmolaIity
- Muscle aches & cramps
- neuronal swelling and cerebral oedema
- Seizures & Headaches
73
SIADH Diagnosis
- Urine sodium = high
- Urine osmolality = high
- Euvolemic
- Low Na+
74
SIADH Treatment
– Water restriction
| – ADH receptor antagonists [Tolvaptan]
75
Diabetic Insipidus
Production of too much dilute urine due to poor water reabsorption from kidneys due to lack of ADH.
Split into Cranial and Nephrogenic
76
Diabetic Insipidus Pathophysiology
- > Large volumes of dilute urine due to reduced ADH
- > Less Secretion from posterior pituitary [Cranial]
- > Impaired response of kidneys to ADH [Nephrogenic]
77
Cranial causes
- Idiopathic
- Neurosurgery
- Tumour/ Trauma
- Infection (Encephalitis)
78
Nephrogenic causes of Dl
- Inherited
- Metabolic [Low K+, High Ca2+]
- Drugs [Lithium]
79
Diabetic Insipidus Symptoms
- Polyuria
- Polydipsia
- Dehydration
- Dilute urine
80
Diabetic Insipidus Diagnosis
– Water deprivation test or Desmopressin Stimulation test - assess urine Osmolality
Cranial (Neurogenic) Dl = After Desmopressin - level is high, After fluid depriv. - level is low
Nephrogernic DI = After Desmopressin & Fluid deprive - level is low
81
Diabetic Insipidus Treatment
- Rehydration
– Cranial DI –> Desmopressin - replace ADH
– Nephrogenic DI –> Bendroflumethiazide – acts as an anti-diuretic
82
Hyperkalaemia
> 5.5 mmol/L
83
Hyperkalaemia Aetiology
- > Impaired excretion: - AKI / - Drugs (NSAIDs, ACE-I, Beta- blockers) / - Addison's
- > Increased Intake: - IV K+ therapy / - Increased dietary intake
- > Shift to extracellular: - Metabolic acidosis (Rhabdomyolysis) /
- Decreased insulin
84
Hyperkalaemia Symptoms
- Fatigue
- Light- headedness
- Weakness
- Chest pain
- Palpitations
85
Hyperkalaemia Signs
- Ventricular Tachycardia
86
Hyperkalaemia ECG
- > No P waves
- > Prolonged PR interval
- > Wide QRS interval
- > Tall tented T waves
87
Hyperkalaemia Diagnosis
- ECG
| - Bloods -> FBC, U+E
88
Hyperkalaemia Treatment
- ABC
- Cardiac monitoring
- Calcium Gluconate
- Insulin + Dextrose or Nebulised salbutamol
89
Hypokalaemia
< 3.5 mmol/L
90
Hypokalaemia Aetiology
- > Increased Excretion: - Renal disease / - Drugs (Thiazide, Loop diuretics, Laxatives) / - GI Loss /
- Conn's syndrome
- > Decreased Intake: - Dietary deficiency
- > Shift to intracellular: - Metabolic alkalosis / - Drugs (B2 agonist = SABA & LABA)
91
Hypokalaemia symptoms
Asymptomatic
92
Hypokalaemia signs
Rhabdomyolysis
93
Hypokalaemia ECG
- > Prolonged PR interval
- > ST depression
- > Flat T wave inversion
- > Prominent U waves
94
Hypokalaemia Treatment
- Potassium - IV
95
Hyperparathyroidism
Primary Hyperparathyroidism - excess PTH due to a disorder of the parathyroid gland itself e,g. tumour
Secondary Hyperparathyroidism - excess PTH due to a disease extrinsic to gland - low vit D → less Ca2 + absorption → more PTH
Tertiary hyperparathyroidism - prolonged secondary hyperparathyroidism, causing glands to act autonomously
96
Hyperparathyroidism Causes
Primary Hyperparathyroidism = parathyroid adenoma, parathyroid hyperplasia
Secondary Hyperparathyroidism = chronic kidney disease / Low Vit. D
– Renal failure → decreased phosphate excretion →Phosphate binds serum Ca2+
– Less free calcium stimulates parathyroid glands to secrete excess PTH
Tertiary hyperparathyroidism = – Leads to increased Calcium from high PTH secretion → leads to hyperplasia of gland
– Decreased Phopshate and Vitamin D
97
Hyperparathyroidism Symptoms
- >Bone pain
- > Renal stone
- > Physic Moans
- > Abdominal Groans
- > Hypercalcaemia
98
Hyperparathyroidism Diagnosis
```
- PTH/ blood test : High PTH...
Primary = + High Ca2+
Secondary = + Low Ca2+
Tertiary = + High Ca2+
LOW phosphates, Low Vit D
```
99
Hyperparathyroidism Treatment
Primary = Surgical removal , Bisphosphonates
Secondary = Calcium correction
Tertiary = Cinacalcet
100
Hypoparathyroidism
Primary = Gland failure
- > Autoimmune
- > Congenital (DiGeaorge syndrome)
Secondary = Pituitary gland dysfunction
-> Low Mg (required for PTH secretion)
Tertiary = Hypothalamic dysfunction
101
Hypoparathyroidism Signs & Symptoms
- > Chvostek's sign = Facial nerve tap induces spasm
- > Trousseau's sign = BP cuff causes wrist flexion
- Convulsions
- Arrhythmias
- Tetany
- Spasms
- Numbness
102
Hypoparathyroidism Investigations
Bloods =
- > Low PTH
- > Low Ca2+
- > High Phosphate
103
Hypoparathyroidism Treatment
- IV Calcium
| - AdCal D3 - Calcitriol
104
Type 1 Diabetes pathophysiology
– T lymphocytes attack B - cells in islets of langerhans, with autoantibodies against insulin present -> Hyperglycaemia
- Continuous breakdown of glycogen from liver -> glycosuria
– It is associated with HLA-DR3 and HLA-DR4
105
What are the normal glucose levels?
4.4 - 6.1 mmol/ L
106
Where is insulin produced?
By Beta cells in the Islets of Langerhans in the pancreas
107
Two ways insulin reduces the blood sugar?
1) causes cells to absorb glucose from blood and uses it as fuel
2) causes muscle and liver cells to absorb glucose from blood and stores it as glycogen
108
Where is glucagon produced?
Produced by alpha cells in the Islets of langerhans in the pancreas
109
What does glucagon do?
Tells liver to break down glycogen into glucose (glycogenolysis).
Also tells liver to convert Proteins and fats to glucose (gluconeogenesis).
110
Ketogenesis?
Where there's less glucose supply and glycogen stores (eg. fasting), liver converts fatty acids to ketones
111
Macrovascular complications of Diabetes Type 1
CAD, Hypertension, Stroke
112
Microvascular complications of T1 DM
- Retinopathy
- Neuropathy
- Nephropathy
113
Type 2 DM Presentation
- Fatigue
- Polydipsia
- Polyuria
- Glycosuria
- Weight loss
114
Cause of hypothyroidism
- Lithium
| - Amiodarone drug
115
Primary Hyper/ Hypo thyroidism pathology
Due to thyroid itself producing high / low thyroid hormone
116
Secondary Hyper /Hypo thyroidism
Disorder with pituitary gland causing over/ under Stimulation of TSH causing high/ low thyroid hormone
117
Where is adrenaline made?
by Chromaffin cells in the adrenal medulla
118
Ca2 + levels in Hyperparathyroidism
1° = High
2° = low/ Normal
3° = High
119
Renin - Angiotensin system
- Juxtaglomerular cells in afferent arterioles of kidneys sense BP levels
In low BP = they secrete renin
Liver secretes Angiotensinogen
- Renin converts Angiotensinogen → Angiotensin 1
- Angiotensin 1 turns to Angiotensin 2 in the lungs with the help of Angiotensin converting enzymes (ACE)
- Angiotensin 2 Stimulates release of aldosterone from Zona Glomerulusa in the adrenal glands
120
Functions of cortisol?
- Inhibits immune system
- Inhibits bone formation
- Raises blood glucose
- Increases metabolism
- increases alertness
121
In Diabetes What is the
plasma glucose - Random & Fasting?
HbA1c?
Oral glucose tolerance test?
Plasma glucose:
Random: > 11 mmol/L
Fasting: >7 mmol/ L
HbA1c : >48 mmol/ L
Oral glucose test: give glucose drink, after 2 hrs plasma glucose: 11mmol/L
122
Pre -diabetic diagnosis- What is the:
HbA1c range?
Impaired fasting glucose?
Impaired glucose tolerance?
HbA1c = 42-47 mmol /mol
Impaired fasting Glucose - Fasting glucose: 6.1-6.9 mmol/L
Impaired glucose tolerance- take oral glucose tolerance test
Plasma glucose after 2 hours = 7.8-11.1mmol/L
123
BIGUANIDES
e.g. + What it does? + Side effects
e.g. Metformin
Prevents production of glucose in liver, increases insulin sensitivity.
S. E = Lactic acidosis , Gl disturbance
124
SULFONYLUREAS
e.g. + What it does? + Side effects
e.g. Glipizide
Cause insulin secretion by binding to ATP - sensitive Potassium channels.
S. E = Hypoglycaemia , Weight gain
125
THIAZOLIDINEDIONES (Glitazone)
e.g. + What it does? + Side Effects
e.g. Pioglitazone
Boosts insulin sensitivity.
S.E = Fluid retention, Weight gain, Worsening heart Failure
126
SGLT 2 inhibitors (Sodium -glucose co-transporter-2)
e.g. + What it does? + Side Effects
e.g. Dapagliflozin
Prevents kidneys from reabsorbing glucose back into blood.
S. E = Risk of UTIs , Diabetic Ketoacidosis when used with insulin
127
DPP 4 -inhibitors
e.g.+ What it does? + Side Effects
e.g. Sitagliptin
Blocks DPP4 enzymes → More incretin hormones → Stimulates insulin secretion.
S. E = Hypoglycaemia, Gl upset
128
GLP1 Analogues
e.g. + What it does? + Side Effects
e.g. Exenatide
Incretin hormone mimics.
S. E = Hypoglycaemia , Gl upset , Increased risk of pancreatitis if used with DPP-4 inhibitors
129
Hypercalcaemia
Causes
Diagnosis
Management
> 2.65 mmol/L
Causes = 1° & 3° Hyperpara., Vit.D&A, Osteolytic bone lesions
Ix = ECG (Shortened QT interval, J waves), Bone profile
Tx = IV Fluids, Bisphosphonates
130
Thyroid Function Test Diagnosis results
Hyper / Graves = Low TSH, High T4 - TSH receptors antibodies
I° Hypo. (Hash.) = High TSH, Low T4 - (Anti- TPO antibodies)
2° Hypo. = Low TSH, Low T4
131
Carbimazole
block thyroid Peroxidase
Adverse S. E = Agranulocytosis
