Endocrinology Flashcards
1
Q
What are the properties of peptide hormones? How do they work?
A
Made from short-chain amino acids (size is anything from few AAs to small protein) - Pre-Made and stored in cell, released and dissolved into blood when needed - Large, hydrophilic, charged molecules - cannot diffuse through a plasma membrane - Bind to receptors on cell membranes, triggering a second messenger to be released within cell - very quick - Examples: Insulin, growth hormone, TSH, ADH
2
Q
What are the properties of steroid hormones? How do they work?
A
Synthesised from cholesterol - Not stored in cell, released as soon as they are Made - Not water soluble - must be bound to transport proteins to travel in blood - Lipid soluble - can cross plasma membrane and Bind to receptor inside cell - slow response - Examples: Testosterone, oestrogen, cortisol
3
Q
Tell me about catecholamine hormones (amino acid derived)
A
Synthesised from the amino acid tyrosine - Acts same way as peptide hormone - Large, hydrophilic, charged molecules - cannot diffuse through a plasma membrane, so released via exocytosis - Examples: Adrenaline, thyroxine
4
Q
What are the cell types and their functions within the islets of langerhans in the pancreas?
A
Alpha cells - produce glucagon Beta cells - produce insulin and amylin Delta/D cells - produce somatostatin PP cells - produce pancreatic polypeptide
5
Q
What are the classes of hormones?
A
Steroids - Peptides - Thyroid hormones - Catecholamines
6
Q
Tell me about thyroid hormones 😎
A
released via proteolysis - T3 = triiodothyronine, T4 = thyroxine - Take a day to act - in blood bound to thyroglobulin binding protein (produced by liver)
7
Q
What is the blood supply to the thyroid gland?
A
Superior Thyroid artery - off thyrocervical trunk (subclavian) - Inferior Thyroid artery - off external carotid artery
8
Q
Where are the thyroid and parathyroid glands located?
A
- Thyroid gland sits at C5-T1 - Two lobes connected by an isthmus - Parathyroid is 4 glands on the posterior surface of thyroid glands
9
Q
What effect does parathyroid hormone have on the kidneys?
A
- Increased conversion of 25-hydroxyvitamin D (inactive) to 1,25-dihydroxyvitamin D(active) - At the DCT: Increased Ca2+ reuptake and PO43- excretion
10
Q
What effect does parathyroid hormone have on the gut?
A
Increased Ca2+ and PO43- absoroption
11
Q
What hormones does the adrenal gland produce?
A
Adrenal cortex: - Zona glomerulosa - mineralocorticoids (eg: aldosterone) - Zona fasciculata - glucocorticoids (eg: cortisol) - Zona reticularis - adrenal androgens Adrenal medulla: - Catecholamines (eg: adrenaline)
12
Q
Pathophysiology of T2DM
A
Peripheral Insulin resistance with partial Insulin deficiency - Decreased GLUT4 expression - impaired Insulin secretion - Lipid and beta amyloid deposits in pancreas, progressive b cell damage
13
Q
Epidemiology of T2DM
A
Presents later on in life (usually 30+ years) - Males > females - People of Asian, African and Afro-Carribean ethnicity are 2-4x more likely to develop T2DM than white people
14
Q
Clinical presentation of T2DM
A
Obese hypertensive older patient - Polydipsia - Nocturia - Polyuria - Glycosuria - Recurrent thrush
15
Q
Diagnosis of T2DM
A
same as T1DM - Prediabetes exists this time
16
Q
Risk factors for T2DM
A
Genetic link (stronger than T1DM) - Obesity - Alcohol excess - Hypertension - Gestational diabetes - PCOS - Drugs: corticosteroids, thiazides
17
Q
Last line of treatment for T2DM if all else fails
A
Insulin treatment
18
Q
Treatment for T2DM
A
Initial: Biguanide (metformin) Second line: Carry on Metformin and add either: - DPP-4 inhibitor - Pioglitazone - Sulfonylurea - SGLT-2 inhibitor
19
Q
Epidemiology of Diabetic Ketoacidosis
A
4% of T1DM patients develop each year
20
Q
Risk factors for DKA
A
- Poorly managed/undiagnosed T1DM - Infection/illness - Characteristic in patients around 20 years old
21
Q
Pathophysiology of DKA
A
Absolute immune deficiency = unrestrained lipolysis and gluconeogenesis and Decreased Peripheral glucose uptake - Not all glucose from gluconeogenesis is usable so converted to ketone bodies, which is acidic
22
Q
Describe Kussmaul’s breathing
A
Deep and rapid breathing in acidosis to expel acidic carbon dioxide
23
Q
Signs of DKA
A
- Kussmaul’s breathing - Pear drop breath - Reduced tissue turgar (hypotension + tachycardia)
24
Q
How to investigate DKA
A
- Ketones > 3mmol/L - RPG > 11.1mmol/L (hyperglycemic) - pH < 7.3 or HCO3- < 15mmol - Urine dipstick glyosuria/ketonuria
25
What are common differentials of DKA?
HHS - Lactic acidosis - identical presentation, normal serum glucose and Ketones - Starvation ketosis - physiologically appropriate lipolysis
26
Treatment for DKA (in order)
- ABCDE - IV fluids FIRST 0.9% saline - IV insulin 0.1units/kg/hour - once glucose level <14mmol add 10% glucose - Restore electrolytes, eg: K+
27
Symptoms of HHS
Generalised weakness and leg cramps - Confusion, lethargy, hallucinations, headaches - Visual disturbance - Polyuria and Polydipsia - Nausea, vomiting and abdo pain (more common in DKA)
28
Epidemiology of HHS
- Less than 1% of diabetes admissions - 5-15% mortality Risk factors: - Infection - MI - Poor medication compliance
29
Pathophysiology of HHS
- Rise in counter-regulatory hormones (glucagon, Ad, cortisol, GH) - Causes hyperglycaemia ans hyperosmolality - Electrolytes in blood overflow into urine -> excessive loss of water and electrolytes
30
Characteristics of HHS
Marked hyperglycaemia - hyperosmolality - Profound dehydration - Electrolyte abnormalities
31
Diagnosis of HHS
Diagnostic: - Hyperglycaemia ≥30mmol/L without a metabolic acidosis or significant ketonaemia - Hyperosmolality ≥320mOsmol/kg - Hypovolaemia Other tests: - Urine dipstick: heavy glycosuria - U+E: low total body K+, high serum K+
32
How can HHS be differentiated from Diabetic ketoacidosis?
DKA - T1DM - Patients younger and leaner - Ketoacidosis - Develops over hours to a day HHS - T2DM - No ketoacidosis - Significantly higher mortality rate - Develops over a longer time - days to a week
33
Treatment of HHS
- IV fluid 0.9% saline - IV insulin only if there is ketonaemia or IV fluids aren't working - LMWH to anticoagulate patient as they have thicker blood - Electrolyte loss (K+)
34
What are complications of HHS treatment with insulin?
Insulin-related hypoglycaemia - Hypokalaemia
35
Draw out the process of phosphate regulation physiology
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36
What can pituitary tumours do?
- Press local structures - eg: optic chiasm -> bitemporal hemianopia - Hypopituitism - Hyperpituitarism - acromegaly, Cushing's disease, prolactinoma
37
Hormones secreted by the hypothalamus and what they stimulate from the anterior pituitary
- GnRH -> FSH and LH - CRH -> ACTH - GHRH -> GH - TRH -> TSH - DA -> Prolactin
38
What is always given to unresponsive hypoglcyemic patients?
IM glucagon
39
Role of insulin
- Increase peripheral glucose uptake - Glucose -> glycogen
40
Biphasic release of insulin
1. Glucose binds to GLUT2 receptors of pancreas on b cells, stimulating insulin release 2. Insulin binds to peripheral insulin receptors: - Activates intracellular tyrosine kinases + cascane - Increase of Glut-4 channel expression on CSM
41
Posterior pituitary hormones
Oxytocin (paracentricular nucleus) - milk ejection + labour induction - Vasopressin (supraorbital nucleus)
42
What does vasopressin do?
Vasoconstricts blood vessels - Increased APO II expression in collecting duct - Increased aldosterone
43
Functions of cortisol
- Increases protein and carb breakdown - Upregulates alpha 1 receptors on arterioles -> increased BP - Suppresses immune response - Increased osteoclast activity (osteoporotic) - Increased insulin resistance
44
Prediabetic states
FBG: 6.1-6.9 2nd post prandial: 7.8-11.0 HbA1c: 42-47 (6.0-6.4%)
45
First treatment for Type 2 diabetes and prediabetes before drugs
Lifestyle change - diet, exercise, modify RFs
46
Main complication of T2DM
Hyperosmolar hyperglycaemic state
47
Define T1DM
- Absolute insulin deficiency, usually resulting from autoimmune destruction of the insulin-producing beta islet cells in the pancreas - Type 4 hypersensitivity
48
Which genes are linked with increased risk of developing T1DM?
HLA-DR2 and HLA-DQ3 or HLA-DR4 and HLA-DQ8
49
Environmental factors that can increase the risk of developing T1DM
Diet - Vitamin D deficiency - Early-life exposure to viruses associated with islet inflammation (eg: enteroviruses) - Decreased gut-microbiome diversity
50
Epidemiology of T1DM
- Young (usually between 5-15 years) - Lean - North European descent - 10% of diabetes is type 1
51
Macrovascular complications of T1DM
Atherosclerosis, which leads to: - CVD - Stroke - Peripheral arterial disease
52
Microvascular complications of T1DM
- Nephropathy - Retinopathy -> glaucoma, cataracts - Neuropathy -> diabetic foot disease
53
Other autoimmune conditions that can result from T1DM (most to least common)
- Thyroid disease - Autoimmune gastritis - Pernicious anemia - Coeliac diease - Vitiligo - Addison's disease
54
Psychological complications of T1DM
- Anxiety - Depression - Eating disorders Also in children: - Behavioural and conduct disorders - Family/relationship difficulties - Risk-taking behaviour
55
Signs of T1DM
- BMI < 25kg/m2 - Failure to thrive in children - Glove and stocking sensory loss - Reduced visual acuity - Diabetic retinopathy - Diabetic foot disease
56
Symptoms of T1DM
Polyuria - Polydipsia - Weigt loss - lethargy - Recurrent infections - Evidence of complications - eg: blurred vision or parasthesia
57
At what level of blood glucose can it no longer be absorbed?
10mmol/L Thirsty and develop polyuria - body attempts to remove excess glucose
58
At what level of Beta cell destruction does hyperglycaemia develop?
80-90%
59
Diagnosis of T1DM
Random blood glucose ≥11mmol/L Fasting blood glucose ≥7mmol/L - One abnormal value diagnostic in symptomatic patients - Two abnormal values diagnostic in asymptomatic patients
60
What is the most accurate test for T1DM?
HbA1C - measures glycated haemoglobin >48 mmol/mol or >6.5% suggest hyperglycaemia over 3 months
61
Optimal targets for glucose self monitoring
- FBG: 5-7mmol/L on waking - Plasma glucose 4-7mmol/L before meals at other times of the day - If testing after meals: 5-9mmol/L at least 90 minutes after
62
How can T1DM be differentiated from Latent Autoimmine Diabetes in Adults (LADA)?
- In LADA age of onset is >30 yrs - Low to normal C-peptide
63
How can T1DM be differentiated from Neonatal diabetes?
In neonatal diabetes: Genetic testing shows mutation in genes coding ATP K+ channel and insulin gene
64
How can T1DM be differentiated from Monogenic diabetes?
In monogenic diabetes: - C-peptide present - Autoantibodies absent
65
First line treatment for T1DM
Basal-Bollus regimen Basal - Long acting (either given twice or once daily) Bollus - Short before meals
66
Types of Insulin
Rapid: aspart, lisporo, novorapid, glulisine - short: regular Insulin - Intermediate: NPH (half a day) - Long: detemir, lantus, glargine
67
Pathophysiology of T1DM
- Beta islet cell destruction - Hyperglycemia - Low cellular glucose (increased lypolysis and gluconeogenesis) - Hyperkalemia even though there is a low body K+ (enters cells via Na+/K+ ATPases)
68
Complications of DKA
Coma - Cerebral oedema - Thromboembolism - Aspiration pneumonia - Death - dehydration - MI
69
Presentation of hypokalaemia
Hypotonia - Hyporeflexia - Arrhythmias (especially AF) - Muscle paralysis and rhabdomyolysis
70
Aetiology of hypokalaemia
Decreased intake of potassium Increased excretion of potassium - Thiazides + loop diuretics - Renal disease - GI loss - Increased aldosterone (Conn's syndrome) Potassium shifted to intracellular - Insulin - Salbutamol - (other drugs)
71
Treatment for hypokalaemia
K+ replacement - aldosterone antagonist (spironolactone) - Treat underlying cause - Other Electrolyte defficiencies
72
Diagnosis of hypokalaemia
- Low K+ in U+E ECG: - Small inverted T waves - Prominent U waves - ST depression - PR prolongation
73
Definition of hyperkalaemia and hypokalaemia
Hyper ≥ 5mmol/L Emergency hyper = ≥ 6.5mmol/L Hypo < 3.5mmol/L
74
Presentation of hyperkalaemia
Muscle weakness and cramps - parasthesia - Palpitations - Tachycardia (Arrhythmias)
75
Aetiology of hyperkalaemia
Increased intake of potassium - IV therapy - Increased dietary intake Decreased excretion of potassium - AKI and CKD - Drugs (NSAIDs, spironolactone, ACE inhibitors) - Renal tubular acidosis (T4) - Addison's disease Potassium shifted to extracellular - Metabolic acidosis/DKA - Rhabdomyolysis Other: trauma and burns
76
Effect of hyperkalaemia on types of muscle
Smooth Muscle cramping - Skeletal mucle weakness due to overcontraction - Cardiac arrythmias and arrest
77
Effect of hypokalaemia on types of muscle
Smooth Muscle constipation - Skeletal Muscle weakness and cramps - Cardiac arrythmias and Palpitations
78
Effect of hyperkalaemia on Insulin, pH and Beta 2 receptors
- Insulin deficiency as not enough K+ flows into the cell - Acidosis (H+ in and K+ out) - Beta blocker - inhibits pumping of K+ into cell
79
Effect of hypokalaemia on insulin, pH and beta 2 receptors
- Excess insulin as too much K+ flows into cell - Alkalosis (H+ out and K+ in) - B2 agonist - Increase B2 pumping of K+ into cell
80
Complications of hyperkalaemia
Cardiac arrhythmias and arrest - Hyperkalaemia is associated with broadening QRS complex
81
Aetiology of hypercalcaemia (90% of cases)
90%: - Hyperparathyroidism - Malignancy: bone mets, myeloma, PTHrP, lymphoma
82
ECG in hypercalcaemia
Short QTc
83
Symptoms of hypercalcaemia and hyperparathyroidism
Bones - excess resorption, ostopoenia - Stones - kidney - Groans - abdominal pain, constipation - Psychedelic moans - Confusion, Depression, Anxiety - Thrones - Polyuria and Polydipsia
84
How does hypercalcaemia affect muscles
Low muscle tone and contractions as Ca2+ inhibits fast Na+ influx
85
What happens to PTH in hypercalcaemia
It will decrease due to negative feedback (except in hyperparathyroidism)
86
Aetiology of hypocalcaemia
CKD (due to Decreased Vit D activation) - Severe Vit D deficiency - Primary hypoparathyroidism - Acute pancreatitis
87
Symptoms of hypocalcaemia and hypoparathyroidism
parasthesia - Tetany (involuntary Muscle contractions) - Chvostek sign - Trousseau sign
88
How does hypocalcaemia affect muscle?
Muscle spasms: hands, feet, larynx, premature labour
89
How does hypocalcaemia affect PTH?
Always Increases - Except in hypoparathyroidism
90
Difference between primary and secondary hyperthyroidism?
Primary: Pathology is in the Thyroid - Secondary: Pathology is in the hypothalamus/pituitary
91
TFTs for hyperthyroidism
- Low TSH, high T4 = primary hyperthyroidism (Graves') - High TSH, high T4 = secondary hyperthyroidism OR thyroid hormone resistance
92
Graves' specific hyperthyroid signs
Exophithalmos or ephthalmoplegia - Pretibial myxedema due to deposits of mucin under the skin (may Also be seen in Hashimoto’s) - Thyroid acropachy
93
Epidemiology and risk factors of hyperthyroidism
Middle aged women - Family history - autoimmune diseases
94
De Quervain's thyroiditis
Follows a viral prodrome and can Also present with a transient thyrotoxic state - Painful goitre with raised inflammatory markers. usually self limiting
95
Pathophysiology of Graves' disease
immune system produces TSH receptor antibodies that mimic TSH and stimulate the TSH receptors on the Thyroid - Increased T3 Increases metabolic rate, CO, bone resorption and activates the sympathetic nervous system
96
Symptoms of hyperthyroidism
Heat intolerance and sweating - Weight loss - Palpitations - Oligomenorrhoea
97
What is toxic multinodular goitre? (also known as Plummer's disease)
Nodules develop on the thyroid gland and produce excessive thyroid hormone
98
Symptoms of thyroid storm
NDV - abdo pain - Jaundice - Confusion, delirium or Coma
99
Diagnosis of hyperthyroidism
First line: TFT (thyroid function test) - Anti-TSH receptor antibodies positive in Graves' - Anti TPO antibodies in 80% of cases (but much more in hypo) - Thyroid ultrasound
100
First line treatment for hyperthyroidism
- Carbimazole - Blocks synthesis of T4 - Normal thyroid function after 4-8 weeks (euthyroidism) - SE: agranulocytosis, presents as sore throat/mouth ulcers - + beta blocker (eg: propanolol) alongside for rapid symptom relief
101
Second line treatment for hyperthyroidism
- Propylthiouracil - Prevents T4->T3 conversion - Small risk of severe hepatic reaction, including death
102
Radioactive iodine treatment for hyperthyroidism
- First line definitive treatment for Grave’s disease and toxic multinodulae goitre - Destroys excess thyroid tissue - Remission can take 6 months - Patient must not be pregnant or planning to get pregnant within 6 months, must also avoid close contact with children and pregnant women for 3 weeks - Also limit contact with anyone for several days after receiving the dose
103
Last resort treatment for hyperthyroidism
Surgery or radioactive iodine
104
How to stop patients from becoming hypothyroid after hyperthyroidism treatment
Give them levothyroxine
105
Most common cause of hypothyroidism in the developed world
- Hashimoto's thyroiditis - Autoimmune inflammation of the thyroid gland - initially cause a goitre - Associated with anti-TPO antibodies and antithyroglobulin antibodies
106
Most common cause of hypothyroidism in the developing world
Iodine deficiency
107
What is postpartum thyroiditis
- Same mechanism as Hashimoto's - Acute: presents during pregnancy - Resolves by itself within 1 year of symptoms
108
Other causes of hypothyroidism
- DeQuervain’s thyroiditis - Post-thyroidectomy or post-radioiodine - Drugs; amiodarone, lithium, carbimazole
109
Causes of secondary hypothyroidism (pathology at pituitary gland)
Compression from a pituitary tumour - Sheehan syndrome - Drug: cocaine, Steroids, dopamime (all inhibit TSH secretion)
110
Symptoms of hypothyroidism
Cold intolerance - constipation - Weight gain - lethargy - Menorrhagia
111
Signs of hypothyroidism
Hair loss, dry and Cold skin- Bradycardia - goitre - Decreased deep tendon reflexes - Carpal tunnel syndrome
112
Diagnosis of hypothyroidism
TFT (Thyroid function test) - Anti-TPO antibodies high - Tyically anaemic (any Type)
113
TFTs for hypothyroidism
high TSH, Low T4 = Primary hypothyroid - Low TSH, Low T4 = Secondary hypothyroid - normal/Low TSH, Low T4 = hypopituitarism
114
Treatment for hypothyroidism
Levothyroxine (T4) - Titrate dose so you don't induce iatrogenic hyperthyroidism
115
Complication of hypothyroidism
Myxedema coma - Often infection precipitated - Rapidly drops T4 - Loss of consciousness, heart failure
116
Treatment for myxedema coma
Levothyroxine - antibodies - Hydrocortisone
117
Types of thyroid carcinoma
Papillary - 70% - Follicular - 25% - Anaplastic (worst prognosisas as it metastasises the most) - Lymphoma - Medullary cell
118
Most common metastasis sites for thyroid carcinoma
Lung - 50% - bone - 30% - liver - 10% - Brain - 5%
119
How does thyroid carcinoma usually present?
as hard and irregular Thyroid nodules - may have local Compression (eg: hoarse voice)
120
Diagnosis of thyroid carcinoma
Fine needle Aspiration biopsy - TFTs - Thyroid ultrasound
121
Treatment for thyroid carcinoma
- Papillary and follicular = thyroidectomy or radioactive iodine - Anaplastic = mostly palliative :(
122
Pathophysiology of Cushing's syndrome
Chronic excess of cortisol released by the adrenal glands
123
Aetiology of Cushing's syndrome
ACTH dependent causes - Cushing's disease - Ectopic ACTH production - ACTH treatment ACTH independent causes - Iatrogenic (steroid use) - mc - Adrenal adenoma
124
What is Cushing's disease?
Pituitary adenoma secreting excess ACTH
125
Signs of Cushing's syndrome
Hypertension - Moon face - Central Obesity - abdominal striae - Buffalo hump (fat pad on upper back) - Proximal limb Muscle wasting - Ecchymoses and fragile skin
126
Symptoms of Cushing's syndrome
Bloating and Weight gain - Mood change - Increased susceptibility to Infection - Menstrual irregularity - Reduced libido - hyperglycaemia
127
Pseudo-Cushing's
Cushingoid features and abnormal cortisol levels, but not associated with HPA pathology - Common causes: alcohol excess, severe depression, obesity, pregnancy - Results in a false positive dexamethasone suppression test and 24hr free cortisol - Differentiated using an insulin stress test
128
Diagnosis of Cushing's syndrome
Dexamethasone suppression test or midnight salivary cortisol - If positive, test plasma ACTH to see If ACTH dependent - If independent, see If it is pituitary or ectopic GH release
129
How to do dexamethasone suppression test
- Measure cortisol at 12am, before giving dexamethasone - Measure cortisol 8 hours later, at 8am - Non-Cushing's -> suppression >50nmol/L - Cushing's -> little/no suppression
130
Plasma ACTH test
- Test at 9am - High = ACTH dependent cause -> Do high dose dexamethasone suppression test - Low = ACTH independent cause -> CT adrenals to look for pathology
131
Treatment for Cushing's syndrome caused by Cushing's disease
Transsphenoidal resection or bilateral adrenalectomy
132
Complication of bilateral adrenalectomy
Nelson's syndrome - Pituitary tumour will continue to enlarge with no negative feedback from adrenals - High ACTH and skin hyperpigmentation
133
Treatment for Cushing's syndrome caused by adrenal adenoma
Tumour resection or unilateral adrenalectomy
134
Treatment for Cushing's syndrome caused by ectopic ACTH
Treatment of underlying cancer, such as surgical removal of SCLC
135
Complications of Cushing's syndrome
Osteoporosis - T2DM - Hypertension and ischaemic heart disease
136
Primary adrenal insufficiency
- Addison's disease - Pathology is at the adrenal glands - Decreased producion of adrenocortical hormones (cortisol and aldosterone) - High ACTH, low adrenocortical hormones
137
Secondary adrenal insufficiency
Pathology is in the pituitary - Inadequate ACTH released from pituitary - Leading to Low release of adrenocortical hormones from the adrenal gland - Low ACTH, Low adrenocortical hormones
138
Why do patients with primary adrenal sufficiency present with bronzed skin?
High ACTH stimulates melanocytes, resulting in hyperpigmentation
139
Aetiology of primary adrenal insufficiency
- Developed world: Autoimmune adrenal destruction (21-hydroxylase present in 60-90% of people) - Developing world: TB (+ sarcoidosis)
140
Risk factors for adrenal insufficiency
Female - adrenocortical antibodies - Other autoimmune disease
141
Other causes of adrenal insufficiency
adrenal metastasis (Lung, liver, breast) - adrenal haemorrhage (eg: meningococcal septicaemia)
142
Symptoms of adrenal insufficiency
Weight loss - Nausea and vomiting - lethargy and Generalised weakeness - Salt cravings
143
Signs of adrenal insufficiency
- Bronze hyperpigmented skin, particularly in palms (only in Addison's) - Postural hypotension - Hypoglycaemia - Change in body hair distribution - Loss of pubic hair in women - Associated autoimmune condition
144
Signs of adrenal crisis
Hyponatraemia - Hyperkalaemia - Profound fatigue - dehydration - Vascular collapse (Low BP)
145
Treatment of Addisonian/adrenal crisis
- Immediate 100mg hydrocortisone - IV solve + dextrose (if hypoglycaemia) - Without cortisol, you will die from adrenal crisis if you have an infection
146
Diagnosis of adrenal insufficiency
- First line: 8-9am cortisol - Gold standard: ACTH stimulation test (short Synacthen test) RESULTS - Low cortisol, high ACTH, poor response to synacthen = Primary adrenal insufficiency - Low cortisol, low/normal ACTH, poor response to synacthen = Secondary adrenal insufficiency OR hypopituitarism
147
Other investigations for adrenal insufficiency
- U+E to test for hyponatraemia and hyperkalaemia - Aldosterone:renin ratio - Adrenal CT or MRI - Test bloods for 21-hydrolase adrenal antibodies
148
Treatment for Adrenal insufficiency
Hydrocortisone - glucocorticoid to replace cortisol - Fludrocortisone - mineralocorticioid to replace aldosterone If necessary - Double the dose of Hydrocortisone in trauma/Infection
149
Tertiary adrenal insuffiiency
Caused by Inadequate CRH released by the hypothalamus - usually a result of Long term oral Steroids
150
Acromegaly in children
Called gigantism - Occurs before epiphyseal fusion - hypopituitarism Causes inhibition of puberty as gonadotrophs cannot be released
151
Aetiology of acromegaly
Functional pituitary adenoma
152
Pathophysiology of acromegaly
- Excess GHRH - GHRH -> GH -> High IGF-1 (produced by liver)
153
Signs of acromegaly caused by space occupying lesion
Bitemporal hemianopia - headaches
154
Signs of acromegaly to do with overgrowth of tissues
Prominent forhead and brow - Large nose, tongue, hands and feet - Large, protruding jaw - Arthritis
155
Signs of acromegaly to do with GH causing organ dysfunction
Hypertrophic heart - Hypertension - impaired glucose tolerance - Colorectal cancer
156
Other symptoms suggesting active raised growth hormone
Development of new skin tags - Profuse sweating
157
Diagnosis of acromegaly
- 1st line: IGF-1 serum levels (high) - Gold standard: OGTT: Oral glucose tolerance test (failure of GH suppression 2 hours post 75g glucose load)
158
First line treatment for acromegaly
Transsphenoidal resection of pituitary adenoma
159
Other treatments for acromegaly
Somatostatin analogue to block GH (eg: ocreotide) - Dopamine agonist (eg: bromocriptine) - GH antagonist (eg: pegvisomant) - Radiotherapy
160
Complications of acromegaly
T2DM Caused by impaired glucose tolerance - Obstructive sleep apnoea - Cardiomyopathy - Hypertension - Arthropathy - Carpal tunnel syndrome
161
Risk factors for hyperprolactinaemia
Females - high serum prolactin (released from lactotrophs in the ant. pituitary)
162
Aetiology of hyperprolactinemia
Prolactinoma - Drugs (ecstacy)
163
Symptoms of hyperprolactinoma
Secondary amenorrhoea - Galactorrhoea 🪐🌌 - Sexual dysfunction (M+F) - Gynecomastia, low testosterone
164
Diagnosis of hyperprolactinemia
- High serum prolactin - >1000mIU/L - or 500-1000mIU/L on two occasions
165
Best treatment for hyperprolactinemia
Dopamine agonists - eg: cabergoline or bromocriptine - Massively shrinks Prolactinoma (tumour) as Dopamine is an inhibitor of prolactin
166
Primary hyperparathyroidism
usually Caused by a Parathyroid adenoma - Causes hypercalcaemia
167
Secondary hyperparathyroidism
Caused by Parathyroid hyperplasia - Secondary to CKD + Vit D deficiency
168
Tertiary hyperparathyroidism
after many years of Secondary - most common cause is CKD - Glands act autonomously and release PTH regardless of Ca conc.
169
Malignant causes of hyperparathyroidism
Neoplasms - (Squamous cell Lung cancer, breast, renal) - Secrete PTHrP, ectopically mimics PTH
170
Diagnosis of primary hyperparathyroidism
high PTH - very high calcium - Low phosphate - high ALP
171
Diagnosis of secondary hyperparathyroidism
high PTH - Low calcium - high phosphate - high ALP
172
Diagnosis of tertiary hyperparathyroidism
high PTH - high calcium - high phosphate - high ALP
173
Other tests for hyperparathyroidism
Xr KUB for kidney Stones - DEXA scan for bone density - U+E to assess renal function - short QT on ECG
174
Treatment for hyperparathyroidism
- Primary: Removal of PTH adenoma/parathyroidectomy of all 4 glands :( (most definitive) - Secondary and tertiary: Treat cause - Tertiary: Removal of parathyroid glands - Malignant: Remove tumour!
175
Complication of hyperparathyroidism
Acute Severe hypercalcaemia - Give IV fluids + bisphosphonates
176
Primary vs secondary hypoparathyroidism
Primary: PTH gland failure, a number of causes Secondary: After surgery (parathyroid/thyroid ectomy)
177
Causes of primary hypoparathyroidism
Di George syndrome - Genetic - Radiation - autoimmune - Infiltration - Magnesium deficiency
178
Pseudohypoparathyroidism
- Very rare - End-organ PTH resistance due to defect in G protein signalling Associated with: - Low IQ - Short stature - Small 4th/5th metacarpals - Obesity
179
What is the Chvostek sign?
Twitching of facial muscles when facial nerve is trapped over parotid
180
What is the Trousseau sign?
Carpopedal spasm when tourniquet is applied to forearm
181
Diagnosis of hypoparathyroidism
Low PTH - Low calcium - high phosphate - ECG = longer QTc
182
Treatment for hypoparathyroidism
Calcium and Vitamin D suppements (AdCalD3)
183
GH/IGF-I axis
img
184
Insulin secretion by the beta cell
glucose enters via GLUT2 transporter - K+ channels close and depolarise cell membrane - calcium channels open and CA2+ enters cell and stimulates Insulin secretory granules - Insulin secreted
185
Insulin action in muscle and fat cells
Insulin enters via Insulin receptors - Intracellular signalling cascades cause GLUT4 vesicles to integrate into plasma membrane - glucose enters cell via GLUT4 transporter
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Alpha vs beta islet of Langerhans cells
Alpha cells: glucagon - Increases hepatic glucose by increasing glycogenolysis and gluconeogenesis - Stimulates lipolysis and muscle breakdown - Reduces peripheral glucose output Beta cells: insulin - Suppresses hepatic glucose by decreasing glycogenolysis and gluconeogenesis - Suppresses lipolysis and breakdown of muscle - Increases glucose uptake into insulin sensitive tissues
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How can you get ketoacidosis in T2DM?
Happens later on in the disease - Because initially, micro secretions of Insulin are sometimes still present, inhibiting glucagon
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Symptoms of DKA
Nausea and vomiting - Weight loss - Drowsy/confused - abdominal pain
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Why are thiazolidinediones (pioglitazone) not commonly given as a diabetic drug?
Increase Weight - Increase risk of heart failure - Increase risk of fractures
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Advantages of basal insulin in T2DM
patient adjusts Insulin themselves, based on fasting glucose measurements - Carries on with oral therapy, combination therapy is common - Less risk of hypoglycaemia at night
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Advantages of premixed insulin in diabetes
Both basal and prandial together - can cover Insulin requirements though most of the day
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Disadvantages of pre-mixed insulin
Requires consistent meal and exercise pattern - cannot seperately Titrate individual Insulin components - Increased risk of nocturnal and fasting hypoglycaemia
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Causes of hypoglycaemia
Diabetic drugs: sulfonylureas or insulin - Non diabetic: oral, liver failure, Addison's, increasing age
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Symptoms of hypoglycaemia on the brain
Cognitive dysfunction - Blackouts - Seizures - Comas - Psychological effects
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Treatment for hypoglycaemia
If not serious, food to release blood sugars - IV glucose or oral glucose gel - If no access, IM glucagon (only if alpha cells are working) - Check BM after 5 mins and if it’s increased give food
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Symptoms of hypoglycaemia on the heart
Increased risk of MI - Cardiac Arrhythmias
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Symptoms of hypoglycaemia on the musculoskeletal system
Falls - Accidents (inc. driving) - fractures - Dislocations
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Symptoms of hypoglycaemia on circulation
inflammation - blood coagulation abnormalities - Haemodynamic changes - Endothelial dysfunction
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Blood glucose of patient with hypoglycaemia
<3.5mmol/L
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Thyroid axis
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Diagnosis of pseudohyperparathyroidism
high PTH - Low calcium - high phosphate
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What does hypercalcaemia of malignancy do to PTH and phosphate levels?
PTH levels decrease - phosphate levels stay the same
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Other causes of hypercalcaemia (other than top 90%)
Multiple myeloma - Granulomatous diseases (eg: TB and sarcoidosis) - dehydration - Drugs
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How to calculate corrected calcium levels
total serum calcium + (0.02* (40-serum albumin))
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Why may serum calcium levels be inaccurate?
Low serum albumin Causes a Low total serum calcium - but this is Not a Low ionised calcium - Need to do corrected calcium equation
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Physiology of thyroid hormone production
iodine diffuses from Follicular Thyroid cells into the colloid (fatty empty space inbetween Follicular cells) - iodine binds to tyrosine residues on molecule thyroglobulin - Cleaved from Long chains to form T3 or T4(active)
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Physiology of thyroid hormone release
Supraventricular nucleus of hypothalamus releases TRH - TSH released from thyrotrophs in anterior pituitary - binds to TSH-receptors on Thyroid - Causes T3/T4 to diffuse from colloid to Follicular cells then to the bloodstream
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PTH regulation
- Tightly regulated by body Ca2+ to prevent hyper/hypocalcaemia - Directly inhibited by calcitonin - from parafollicular C cells fo the thyroid
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Who would you not want to give carbimazole to?
Women wanting to get pregnant as it’s teratogenic (causes fetal abnormalities)
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Pathophysiology of hyperkalaemia
high K+ decreases action potential - Easier depolarisation - abnormal heart rhythms
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Diagnosis of hyperkalaemia
- High K+ on U+Es ECG: - Absent P waves - Prolonged PR - Tall tented T waves - Wide QRS - Bradycardia
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Treatment for hyperkalaemia
If urgent: Calcium gluconate to stabilise cardiac membrane if there are heart problems, then insulin dextrose Non-urgent: Insulin (+dextrose)
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Aetiology of hyperaldosteronism
2/3 - Adrenal adenoma (Conn's) 1/3 - Bilateral adrenal hyperplasia Also (rare): - Familial hyperaldosteronism type 1 and 2 - Adrenal carcinoma
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Secondary hyperaldosteronism
Excessive renin stimulates the adrenal glands to produce more aldosterone Causes: - Renovascular disease - Renin-secreting tumour
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Pathophysiology of hyperaldosteronism
excess aldosterone(😱) - Increased sodium and water reabsorption and potassium excretion in kidneys - Hypertension and Hypokalaemia
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Symptoms of hyperaldosteronism
Resistant Hypertension (unfixable with ACE inhibitors or beta blockers) - Hypokalaemia (lethargy Mood disturbance, parasthesia, Muscle cramps) - Polydipsia + Polyuria
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Diagnosis of hyperaldosteronism
1st line: Aldosterone:renin ratio High ratio = Primary (do CT) Low rato = Secondary Diagnostic: High serum aldosterone not suppressed with 0.9% IV saline or fludrocortisone Also: Hypokalaemic on U+E and ECG
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Treatment of hyperaldosteronism
- Single benign adrenal tumour -> unilateral adrenalectomy - Bilateral adrenal hyperplasia -> Aldosterone antagonist (spironolactone)
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Two types of diabetes insipidus
Cranial - Low ADH secretion - Nephrogenic - Low response to ADH
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Aetiology of cranial diabetes insipidus
ADH gene mutation - pituitary adenomas - Brain infections - Idiopathic
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Aetiology of nephrogenic diabetes insipidus
- Renal tubular acidosis - ADH-R mutation - Drugs (lithium) - Electrolyte disturbance
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Presentation of diabetes insipidus
Polyuria - Polydipsia - Hypernatremia - lethargy Confusion Coma - Severe dehydration
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How much urine a day will make you suspect diabetes insipidus?
Over 3L
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Water deprivation test for diabetes insipidus
- No fluid for 8 hours - Normally serum osmolality stays normal, urine osmolality increase - DI = serum osmolality rises while urine osmolality unchanged
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Desmopressin test for diabetes insipidus
Cranial urine osmolality: After deprivation: Low After desmopressin: High Nephrogenic urine osmolality: After deprivation: Low After desmopressin: Low Primary polydipsia After deprivation: High After ADH: High
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Treatment for diabetes insipidus
Cranial - Desmopressin Nephrogenic - Thiazides (+ treat underlying cause)
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What are carcinoid tumours?
- Poorly malignant tumours of enterochromaffin cells which produce 5-HT/serotonin - Mostly in the GI tract at the appendix and terminal ileum - Can also be in the lungs
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Carcinoid tumours vs syndrome
tumours - only the neoplastic cell, No/v little symptoms - syndrome - when tumour metastasises to the liver
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Presentation of carcinoid syndrome
Diarrhoea - Flushing - Tricuspid incompetence (valve lesion) - Right upper quadrant pain - Bronchospasm
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What does carcinoid syndrome tend to express?
Somatostatin receptors
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Diagnosis of carcinoid syndrome
- High volume of 5-hydroxyindoleacetic acid (breakdown of serotonin) in urine - Metabolic panel and LFTs - Liver ultrasound to confirm metastases - CT/MRI to locate primary tumour
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Treatment for carcinoid syndrome
Surgically excise Primary tumour - Peri-operative ocreotide (SST analogue) infusion to block tumour hormones - for metastases: above + radiofrequency ablation
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Carcinoid crisis
Lif threatening - Treated with high dose SST analogue (octeotride)
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What is a phaeochromocytoma?
An adrenal medullar tumour of chromaffin cells that secrete catecholamines (NAd, Ad)
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Aetiology of phaeochromocytomas
- 25% familial and associated with MEN 2a+2b - Neurofibromatosis 1 (tumours deposited along myelin sheath) - Von-Hippel Lindau disease
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Tumour patterns in phaeochromocytomas
- 10% bilateral - 10% cancerous - 10% familial - 10% extra-adrenal (mc location: organ of Zuckerkandl at aortic bifurcation)
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Signs of phaeochromocytomas
- Hypertension (90%) - Hypertensive retinopathy - Tachycardia
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Symptoms of phaeochromocytomas
Episodic headache - Profuse sweating - Palpitations - Anxiety
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Diagnosis of phaeochromocytoma
- 24 hour urine metanephrine collection - Plasma free metanephrines - CT abdomen and pelvis
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Why are metanephrines measured to diagnose pheochromocytoma?
Adrenaline has a very short half life in blood (only a few minutes) - Metanephrines are a breakdown product of Adrenaline and have a longer half life
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Treatment of phaeochromocytoma
Peri-operative - Alpha blocker first (eg: phenoxybenzamine) - Then beta blocker (eg: atenolol, propanolol) - This prevents reactive vascoconstriction Surgical - Laproscopic adrenalectomy
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Pheochromocytoma hypertensive crisis
- BP higher than 180/120 - Causes: XR contrast, TCA, opiates - First line treatment: phentolamine (alpha blocker)
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What is SIAD?
Overdiagnosed cause of hyponatremia - Inappropriately released ADH, dilute euvolemia - excess ADH = more water retention = compensatory Na+ excretion to maintain euvolemia
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Normal water sodium distribution vs SIADH
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Aetiology of SIAD
Cancers - SCLC and others - Infection/immunosuppression, eg: TB, pneumonia, meningitis - Abscesses - Drugs: SSRIs, carbamazepine, sulfonylureas - Head trauma
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Pathophysiology of SIAD
high ADH independent of RAAS - Increased vasoconstriction - APO-II expression of collecting duct - Lead to high BP - excess H2O retained means more dilute blood and more Na+ loss
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Symptoms of hyponatremia
vomiting - headache - Decreased GCS - Muscle weakness
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Symptoms of extreme hyponatremia
Seizures - Neurological complications - Brainstem herniation
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How can hyponatremia cause brain stem herniation?
Low Na+ means high compensatory H2O - enters skull, high ICP - Causes hyponatremic encephalopathy - risk of Brainstem herniating through foramen magnum (tentorial herniation)
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Diagnosis of SIAD
decrease in serum Na+ and normal serum K+ - high urine osmolality - skin turgor and jugular venous pressure test
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Differential diagnosis of SIAD
Na+ depletion - Give 0.9% saline - Na+ depletion -> serum will normalise - SIAD -> serum fails to normalise
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Treatment for hyponatraemia secondary to SIAD
- Asymptomatic/mild symptoms: Fluid restrict; vaptans (vasopressin antagonist) - Severe symptoms: 3% hypertonic saline to concentrate blood
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Pathophysiology of craniopharyngioma
- Squamous epithelial remnants of Rathke's pouch - Benign, slow growing tumour infiltrates to surrounding structures - Mixed solid and cystic parts - Doesn't spread to other parts of the body but puts pressure on suprasellar region of skull
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Adamantinous vs squamous papillary craniopharyngioma
Adamantinous: Cyst formation and calcification Squamous papillary: Well circumscribed
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Peak ages craniopharyngiomas occur
- 5 to 14 years - 50 to 74 years
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Presentation of craniopharyngioma
raised ICP - Visual disturbances (Bitemporal hemianopia) - growth failure - Pit. hormone deficiency - Weight Increase
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How common are meningiomas?
Most common tumour of region after pituitary adenoma
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Cause of meningiomas
Complication of radiotherapy
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Complications of meningioma
loss of Visual acuity - Visual field defects - Endocrine dysfunction
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Testing gonadal axis: men
- Low testosterone, high LH/FSH: Primary hypogonadism - Low testosterone, normal/low LH/FSH: Hypopituitarism - Low testosterone and low LH: Anabolic use Measure 9hr fasted testosterone (morning) and LH/FSH in pituitary disease
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Testing gonadal axis: women
Low oestradiol, high LH and FSH (FSH greater) = Pimary ovarian failure - Low oestradiol, normal/Low LH and FSH, oligo/amenorrhoea = hypopituitarism
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Normal gonadal levels in women
Before puberty: - Low oestradiol - Low LH/FSH Puberty: - Increased oestradiol - Increased pulsatile LH Post menarche: - Monthly menstrual cycle with LH/FSH - Mid-cycle surge in LH and FSH - Levels of oestradiol increases through cycle
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What to do after euthyroidism is achieved in hyperthyroid treatment
Maintenance carbimazole using either: - Titration block regimen - Block and replace regimen Complete remission achieved after 18 months of treatment (remission rate 50%)
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What does the pituitary gland control?
Thyroid - adrenal cortex - Testis - Ovary Not the adrenal medulla
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What hormones have a circadian rhythm
- Cortisol - Testosterone - DHEA - 17OH Progesterone Not T4
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Which conditions do you need to rule out before confirming SIAD?
Hypothyroidism - Hypervolaemia - adrenal insufficiency - Diuretic use
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Which hormones suppress appetite?
- Peptide YY - CCK - GLP 1 - Glucose
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What is the main adipose signal to the brain?
Leptin
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Treatment of chronic cases of SIAD
Furosemide - Vasopressin antagonist (tolvaptan) - Demeclocycline (inhibits ADH)
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Typical features of hypogonadism in males
Joint and muscular aches - Decreased sexual appetite - Decreased Hair growth - Asymptomatic
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What is satiety?
The physiological feeling of no hunger
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What does ghrelin do?
Stimulates hunger
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Risk factors of hyperthyroidism
- Smoking - Stress - HLA-DR3 - Female 20-40 years - Other autoimmune diseases
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Epidemiology of hypothyroidism
- Mainly >40 years - F>M 6:1
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High and low values for urine osmolality
< 300 = low >800 = high
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Cancers that can cause SIAD
SCLC (small cell carcinoma) - Prostate cancer - Pancreatic cancer - Lymphomas - cancer of the thymus
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What do long term corticosteroid medications lead to?
- Suppression of the adrenal glands - Long term atrophy of the adrenal glands - can't produce enough corticosteroids - Adrenal insufficiency if medication is stopped
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Differential diagnoses for presentation of polyuria and polydipsia
diabetes mellitus - diabetes insipidus - SIAD - Primary Polydipsia - hypercalcaemia
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Complications of adrenal insufficiency
- Addisonian crisis (experiences by 40% of patients) - Cushing's syndrome
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Signs of HHS
Reduced GCS - dehydration - Hemiparesis (can be confused for a stroke) - Seizures
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Why is there no acidosis in HHS?
- Small amounts of circulating insulin in T2DM - So lipolysis doesn't occur
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Complications of HHS
Cardiovascular - venous Thromboembolism, Arrhythmias, MI - Neuro - stroke and Seizures - AKI
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NICE diagnostic criteria for T1DM
- Clinical features and evidence of hyperglycaemia - Ketosis - Rapid weight loss - < 50 years - BMI < 25 kg/m2 - Personal and/or family history of autoimmune disease
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Other treatments for T1DM after basal-bollus
Mixed Insulin regimen - Continuous Insulin infusion
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Mixed insulin regimen
- A mixture of short or rapid acting and intermediate-acting insulin - Twice daily - For those who can't tolerate multiple injections for basal bollus
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Continuous insulin infusion
- If patient has disabling hypoglycaemia - or persistently hyperglycaemic (HbA1c > 69mmol/mol) on multiple injection insulin therapy
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Disadvantages of basal insulin in T2DM
- Doesn't cover meals - Best used with long-acting insulin analogues (expensive)
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Signs of T2DM
Acanthosis nigricans (fig.1) - Glove and stocking sensory loss - Diabetic Retinopathy - Diabetic foot disease
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Drugs that can cause hypercalcaemia
Thazides - Diuretics - Lithium - Excessive Vit D or a intake
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Treatment of hypercalcaemia
Aggressive IV fluids - Consider IV bisphosphonates If No response - Treat underlying cause
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Drugs that can cause hypocalcaemia
bisphosphonates - Phenytoin - Loop Diuretics - Cinacalcet
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Treatment of hypocalcaemia
oral calcium replacement or IV calcium gluconate - Treat the cause
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How to determine if hyperaldosteronism is unilateral or bilateral
Adrenal venous sampling - Measures the amount of corticosteroid secreted from each adrenal gland
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Epidemiology and risk factors of hyperparathyroidism
- Female - Radiation therapy to neck - Severe Vit D or Calcium deficiences - Familial rare conditions: MEN1 and 2A
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Diagnosis of pseudohypoparathyroidism
high PTH - Low calcium - high phosphate Pseudopseudohypoparathyroidism Also exists, but levels for everything are normal
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General signs of hyperthyroidism
Postural tremor - Palmar erythema - Hyperreflexia - goitre - Lid lag and retraction
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Signs of thyroid storm
- Hyperpyrexia, often >40°C - Tachycardia, often >140bpm, with or without atrial fib - Reduced GCS
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Diagnosis of thyroid storm
TFTs: high T3 and T4, suppressed TSH - ECG - blood glucose (perform in all patients with Reduced consciousness)
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Treatment of thyroid storm
High dose propylthiouracil and KI
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What is thyroid storm/thyrotoxic crisis?
- Endocrine emergency often seen in patients with Graves’ disease or toxic multinodular goitre - Secondary to precipitating factor such as infection or trauma - 10-20% mortality
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Treatment for DeQuervain’s thyroiditis
NSAIDs for pain and inflammation - beta blockers for symptomatic relief
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Side effects of dopamine agonists such as bromocriptine
Impulsiveness, so can lead to addictions
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Link between acromegaly and prolactinoma
50% of acromegaly tumours are associated with prolactinoma
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ECG in hypocalcaemia
Longer QTc and ST segment
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Why can acromegaly cause sleep apnoea?
Pressure around the neck due to enlargement
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Side effects of other diabetic medication
- SGLT-2 inhibitor - genitourinary infections - GLP-1 analogue - weight loss - Thiazide diuretics - weight gain
