Endocrine Flashcards

Question

What is pseudo cushings?

Answer 1

Mimics cushings syndrome Due to alcohol excess or severe depression. Resolves in 1-3 weeks

Answer 2

where the adrenal glands do not produce enough steroid hormones, particularly cortisol and aldosterone

Answer 3

refers to the specific condition where the adrenal glands have been damaged, resulting in a reduction in the secretion of cortisol and aldosterone. This is also called Primary Adrenal Insufficiency

Answer 4

Autoimmune destruction of the adrenal gland

Answer 5

Hypopituitarism A result of inadequate ACTH stimulating the adrenal glands, resulting in low cortisol release. This is the result of loss or damage to the pituitary gland. Most commonly due to long term steroids Also can be due to surgery to remove a pituitary tumour, infection, loss of blood flow or radiotherapy.

Answer 6

Tertiary Adrenal Insufficiency is the result of inadequate CRH release by the hypothalamus. This is usually the result of patients being on long term oral steroids (for more than 3 weeks) causing suppression of the hypothalamus and then suddenly stopping the steroids causing the HPA axis to not wake up properly

Answer 7

Fatigue Nausea Cramps Abdominal pain Reduced libido

Answer 8

Bronze hyperpigmentation to skin (ACTH stimulates melanocytes to produce melanin) Hypotension (particularly postural hypotension)

Answer 9

This is primary adrenal insufficiency and therefore the Hypothalamus and Ant. pit are still working. These are releasing CRH and ACTH to increase the levels or cortisol but the adrenals are not responding. High levels of ACTH are not seen in 2' or 3' adrenal insufficiency

Answer 10

Early Morning cortisol (measured at 9am) ACTH blood test: 1' - ACTH is High 2' / 3' - ACTH is Low GS - Short Corticotrophin (Synacthen) Test Hyponatraemia - Low aldosterone Hyperkalaemia - Low aldosterone

Answer 11

The test involves giving synacthen, which is synthetic ACTH. The blood cortisol is measured at baseline, 30 and 60 minutes after administration. Synacthen will stimulate healthy adrenal glands to produce cortisol and the cortisol level should at least double. A failure of cortisol to rise (less than double the baseline) indicates primary adrenal insufficiency (Addison’s disease).

Answer 12

Adrenal autoantibodies (80% of autoimmune adrenal insufficiency) 21-hydroxylase antibodies 17alpha hydroxylase antibodies

Answer 13

Replace steroids titrated to signs. Hydrocortisone - replace cortisol Fludrocortisone - replace aldosterone

Answer 14

Describes acute presentation of severe Addisons disease where the absence of hormones leads to a life threatening presentation. often occurs from suddenly stopping long term steroids Present with: (4 Hs) Reduced consciousness Hypotension Hypoglycaemia, Hyponatraemia Hyperkalaemia

Answer 15

- Immediate parenteral hydrocortisone (100mg IV, IM) then100mg every 6hrs - Fluid resuscitation (1L N/saline 1 hour) - Correct hypoglycaemia - If the patient has primary adrenal insufficiency, give fludocortisone (100-200µg)

Answer 16

10x 10mg Tablets Hydrocortisone

Answer 17

Cannot harm the patient and can be life saving

Answer 18

- 3-5mg/d orally once or twice a day - Patients with reduced compliance to hydrocortisone

Answer 19

Developed - Addison's disease Developing - TB (+Sarcoidosis)

Answer 20

Addison's disease - High ACTH, Low Adrenal hormones 2' Cause - HPA suppression - Low ACTH, Low adrenal hormones (no hyperpigmentation)

Answer 21

Hyperthyroidism: TSH - Low (except in a pituitary adenoma) T3/T4 - High Primary Hypothyroidism: TSH - High T3/T4 - Low Secondary Hypothyroidism: TSH - Low T3/T4 - Low

Answer 22

Anti-thyroid Peroxidase antibodies (Anti-TPO) - Graves disease and Hashimoto's Thyroiditis Antithyroglobulin antibodies - Graves disease, Hashimoto's Thyroiditis and thyroid cancer TSH Receptor antibodies (IgG) - Graves disease

Answer 23

Thyroid Ultrasound for Nodules Radioisotope Scan with radioactive iodine: Diffuse high uptake - Graves disease Focal high uptake - TMG/adenoma Cold areas (low uptake) - Thyroid cancer

Answer 24

Over production of Thyroid hormone from the thyroid gland

Answer 25

Abnormal/excessive quantity of thyroid hormone in the body.

Answer 26

An autoimmune condition where TSH receptor autoantibodies stimulate the TSH-R leading to increased production of T3/T4. Most common cause of hyperthyroidism (80-90% primary cause)

Answer 27

Nodules develop in the thyroid gland that act independently of the normal negative feedback system and therefore result in over production of T3/T4

Answer 28

Grave’s disease Toxic multinodular goitre Benign Adenoma (Solitary toxic thyroid nodule) Thyroiditis (e.g. De Quervain’s, Hashimoto’s, postpartum and drug-induced thyroiditis)

Answer 29

(EVERYTHING FAST) Sweating and heat intolerance Tachycardia Weight loss Fatigue Frequent loose stools Sexual dysfunction Anxiety and irritability

Answer 30

Diffuse goitre (without nodules) Graves eye disease Bilateral exophthalmos Pretibial myxoedema Acropachy All relate to the presence of TSH Receptor antibodies

Answer 31

bulging of eyeball out of the socket caused by Graves Disease. This is due to inflammation, swelling and hypertrophy of the tissue behind the eyeball that forces the eyeball forward.

Answer 32

Deposits of mucin under the skin on the anterior aspect of the leg (the pre-tibial area). This gives a discoloured, waxy, oedematous appearance to the skin over this area. It is specific to Grave’s disease and is a reaction to the TSH receptor antibodies.

Answer 33

Goitre with firm nodules Most patients are aged over 50 Second most common cause of thyrotoxicosis (after Grave’s)

Answer 34

A rare presentation of hyperthyroidism. It is also known as “thyrotoxic crisis”. It is a more severe presentation of hyperthyroidism with pyrexia, tachycardia and delirium.

Answer 35

Transient form of thyrotoxicosis caused by excessive stimulation of thyroid gland by hCG. This leads to raise free T4 but low TSH. Usually limited to the first 12-16 weeks of pregnancy

Answer 36

Transplacental transfer of thyroid stimulating autoantibodies from mother to fetus. These autoantibodies bind to the fetal thyroid stimulating hormone (TSH) receptors and increase the secretion of the thyroid hormones.

Answer 37

Carbimazole: Prevent thyroid peroxidase enzyme coupling and iodinating tyrosine residues on thyroglobulin → reduce T3 and T4

Answer 38

Propylthiouracil (PTU): inhibits the conversion of T4 to T3

Answer 39

PTU has high risks of severe hepatic reactions

Answer 40

Carbimazole Propylthiouracil Radioactive iodine Beta-Blockers Surgery

Answer 41

Drinking a single dose of radioactive iodine. This is taken up by the thyroid gland and the emitted radiation destroys a proportion of the thyroid cells. This reduction in functioning cells results in a decrease of thyroid hormone production and thus remission from the hyperthyroidism Patients are then on Levothyroxine replacement

Answer 42

Pregnant women

Answer 43

Used to block the adrenaline related symptoms Typically Propranolol (non-selective) would be used

Answer 44

To removed toxic nodules/adenomas The patient would likely be on Levothyroxine permanently

Answer 45

Graves Disease symptoms predate pregnancy (and are more prominent during pregnancy) N&V is greater in Gestational Thyrotoxicosis Graves disease will present with Goitres Graves disease ill have TSH-R antibodies

Answer 46

Inadequate output of thyroid hormones by the thyroid gland.

Answer 47

Hashimoto's Thyroiditis

Answer 48

Autoimmune destruction of the thyroid gland associated with anti-TPO antibodies and Anti thyroglobulin antibodies. It initially causes a goitre when then leads to atrophy of the gland

Answer 49

Iodine deficiency

Answer 50

Hashimoto's Thyroiditis (autoimmune) Iodine deficiency Secondary to Hyperthyroid treatment Medications - lithium, Amiodarone

Answer 51

Tumours Infection Vascular (Sheehan Syndrome) Radiation

Answer 52

Where the pituitary gland is failing to produce enough TSH. This is often associated with a lack of other pituitary hormones such as ACTH. This is called hypopituitarism

Answer 53

(EVERYTHING SLOW) Cold Intolerance Weight gain Fatigue Dry skin Coarse hair and hair loss Fluid retention (oedema, pleural effusions, ascites) Heavy or irregular periods Constipation

Answer 54

TSH and Thyroid hormone blood tests TSH & T3/T4: Primary Hypothyroidism: TSH - High T3/T4 - Low Secondary Hypothyroidism: TSH - Low T3/T4 - Low

Answer 55

Replacement of thyroid hormone - Levothyroxine Dose is titrated until TSH becomes normal

Answer 56

Post partum Thyroiditis De Quervain's thyroiditis

Answer 57

Inhibits the production of thyroid hormones in the thyroid gland Can cause a goitre and hypothyroidism

Answer 58

Interferes with thyroid hormone production and metabolism. Can lead to hypothyroidism. Can also cause destruction of the thyroid leading to acute release of thyroid hormone and transient thyrotoxicosis

Answer 59

Agranulocytosis Presents as a sore throat

Answer 60

Agranulocytosis Presents as a sore throat

Answer 61

Myxoedema coma - usually infection precipitated Rapid loss of T4 Hypothermia, loss of consciousness, heart failure

Answer 62

Papillary - (70%) has Orphan Annie Eyes Follicular (25%) Medullary (5%) MEN-2 associated. Secretes Calcitonin Anaplastic (1%) - worst prognosis

Answer 63

Presents as Thyroid Nodules - hard and irregular May have local compression on the recurrent laryngeal nerve - hoarse voice

Answer 64

Fine needle aspriation biopsy TFTs Thyroid ultrasound

Answer 65

LLBB Lung Liver Bone Brain

Answer 66

Papillary / Follicular - Thyroidectomy / radioiodine Anaplastic - palliative care

Answer 67

ABCDE and fluids to correct volume 1st Line: Using Propylthiouracil AND hydrocortisone AND propranolol GS: Thyroidectomy Can also give Hydrocortisone

Answer 68

between 4.4-6.1 mmol/l

Answer 69

Liver - breakdown of glycogen -gluconeogenesis

Answer 70

Low - there is less glucose in the blood so insulin is low because it does not need to stimulate glucose storage

Answer 71

Free fatty acids

Answer 72

Inhibition of glucagon secretion Stimulation of insulin Glucose is taken up by the liver (40%) and peripheral tissues (60%)

Answer 73

Inhibition of lipolysis reduced levels of free fatty acids

Answer 74

Islets of langerhans of the pancrease Alpha cells - glucagon Beta cells - Insulin

Answer 75

The release of insulin from beta cells acts on the alpha cells of the pancreas to inhibit further glucagon release. In diabetes the insulin is lost and therefore you lose the alpha cell inhibition mechanism leading to excess glucagon and increased levels of glucose and free fatty acids in the blood.

Answer 76

Glucose is taken into the pancreas via GLUT2 transporters Once in the pancreas glucose is metabolised by glucokinase which forms ATP ATP then acts on the SUR1 potassium channels to close the K+ channels This leads to depolarisation of the cell membrane and thus the opening of Ca channels Calcium influx stimulates exocytosis of insulin secretory granules Insulin is released

Answer 77

Stimulates the metabolism of GLUT4 channels to the cell membrane Allows for the entry of glucose into the cell increases peripheral uptake

Answer 78

Suppresses hepatic glucose output - Decrease glycogenolysis, Decrease gluconeogenesis. Increase glucose uptake into insulin sensitive tissues - fat and muscle. Suppresses lipolysis and muscle breakdown

Answer 79

Increases hepatic glucose output - increase glycogenolysis, increased gluconeogenesis Reduces peripheral glucose uptake - keeps glucose in the blood stimulates peripheral release of gluconeogenic precursors - glycerol and amino acids, lipolysis, muscle glycogenolysis and breakdown.

Answer 80

Occurs when there is insufficient glucose supply and glycogen stores are exhausted (prolonged fasting) There is lipolysis, liver converts FFAs to Ketones. This are normally buffered by HCO3 from the kidneys preventing acidosis.

Answer 81

Lack of insulin and therefore no peripheral uptake of glucose into fat and muscle cells They believe they are starving - therefore undergo lipolysis and proteolysis. Increased FFAs, and krebs is saturated (due to hyperglycaemia) so ketogenesis occurs. Extreme hyperglycaemic ketosis occurs and the bicarbonate is used up. Blood becomes acidic leading to ketoacidosis

Answer 82

A disorder of carbohydrate metabolism characterised by hyperglycaemia

Answer 83

Acute hyperglycaemia if untreated leads to diabetic ketoacidosis (DKA) and hyperosmolar hyperglycaemic states (HHS) Chronic hyperglycaemia leads to tissue complications (macro and microvascular) Side effects of treatment - hypoglycaemia

Answer 84

Type 1 DM - Insulin dependent Type 2 DM - Insulin Independent - Maybe be gestational or medication induced) MODY Pancreatic diabetes Endocrine diabetes - Acromegaly, Cushing's Malnutrition related diabetes

Answer 85

Maturity onset diabetes of youth

Answer 86

Type 1 diabetes mellitus (T1DM) is a metabolic disorder characterised by hyperglycaemia due to an absolute deficiency of insulin. This is caused by an autoimmune destruction of beta cells of the pancreas. May have a genetic component, may be triggered by a certain event. Type 4 hypersensitivity reaction

Answer 87

Beta cells express HLA antigens ( HLA DR3 and HLA DR4) on MHC in response to an environmental event Activates chronic cell mediated immune response leading to chronic insulitis Islet cell autoantibodies Glutamic acid decarboxylase Insulin Autoantibodies Protein tyrosine phosphatase

Answer 88

Loss of beta cells - Loss of insulin secretion Leads to: unrestricted hepatic glucose output: Continued glycogenolysis in the liver + gluconeogenesis. Impaired peripheral glucose uptake - cells believe they are starving and so need to obtain energy from: Unrestricted lipolysis and skeletal muscle breakdown for gluconeogenesis Increased Ketone Production leading to DKA Glucose concentration rises lead to excretion of glucose in urine as renal reuptake routes are saturated (glycosuria). This also draws other essential electrolytes into the blood causing polyuria and polydipsia

Answer 89

Ketoacidosis: Can cause nausea and vomiting due to acidosis Dehydration: Hyperglycaemia overwhelms the kidneys - glucose is filtered into urine Osmotic diuresis draws water into urine Causes polyuria and polydipsia Potassium Imbalance: No insulin so K is not driven into cells. - Low cellular K but high/normal serum K Total body K is low as there is no K stored in cells. When insulin treatment is given this causes K influx into cells Low serum K Can lead to hypokalaemia and fatal arrhythmias.

Answer 90

Insulin increases the number of Na/K/ATPases present on cell membranes which leads to K influx into cells and removes K from circulation.

Answer 91

Polyuria Polydipsia Nausea and vomiting Acetone smell to their breath Kussmaul Respiration - Deep laboured breathing to reverse acidosis Dehydration and subsequent hypotension Altered Consciousness They may have symptoms of an underlying trigger (i.e. sepsis)

Answer 92

Hyperglycaemia (i.e. blood glucose > 11 mmol/l) Ketosis (i.e. blood ketones > 3 mmol/l) Acidosis on VBG/ABG (i.e. pH < 7.3)

Answer 93

FIG-PICK: ABCs F – Fluids – IV fluid resuscitation with normal saline I – Insulin – Add an insulin infusion G – Glucose – Closely monitor blood glucose and add a dextrose infusion if below a certain level P – Potassium – Closely monitor serum potassium (e.g. 4 hourly) and correct as required I – Infection – Treat underlying triggers such as infection C – Chart fluid balance K – Ketones – Monitor blood ketones

Answer 94

Younger onset (<30yrs) Usually lean North European Associated with other Autoimmune Disorders

Answer 95

Onset older (>30 years). Usually overweight. More common in African/Asian. More common in general.

Answer 96

2-6 week history of: (shorter history and more severe symptoms) Polyuria Polydipsia Weight loss Over longer periods of time may have: Lethargy eye problems Neuropathy - glove/stocking

Answer 97

Patient education is essential: - Monitoring dietary carbohydrate intake - Monitoring blood sugar levels on waking, at each meal and before bed - Monitoring for and managing complications, both short and long term Insulin is prescribed.

Answer 98

1st Line: Basal-Bolus Regimen - Log acting Insulin (levemir) + rapid acting insulin before meals (Humalog) (Short acting insulin - 30mins prior to CHO intake) Other: Mixed insulin - Mix of short/rapid + intermediate given 2x daily Continuous - If Px has disabling hypoglycaemia or persistent hyperglycaemia

Answer 99

May occur when a patient injects insulin into the same spot causing the subcutaneous fat to harden. This can lead to poorer absorption of insulin

Answer 100

Hypoglycaemia Patients may inject insulin and become hypoglycaemic which can cause death.

Answer 101

PISTD Pallor Irritability Sweating Tremor Dizziness

Answer 102

Reduced consciousness Coma Death

Answer 103

Levothyroxine Hydrocortisone until adrenal insufficiency has been ruled out

Answer 104

Low levels of insulin are still produced Low levels of insulin enough to prevent muscle catabolism and ketogenesis so muscle breakdown and ketone production rarely excessive In chronic T2DM the beta cells may be destroyed and very little insulin is produced which can result in DKA.

Answer 105

Control glucose between meals and at night. Adjusted to maintain fasting blood glucose between 5-7mmol/L

Answer 106

Low plasma glucose causing impaired brain function

Answer 107

<3.9 mmol/L

Answer 108

The higher the HbA1c levels, the higher the glucose levels can be when the patient experiences a hypoglycaemic episode In DM a patient will have higher HbA1c levels and therefore the threshold of the secretion of counter-regulatory hormones is lower

Answer 109

- History of severe episodes - HbA1c > 48 mmol/l (6.5%) - Long duration of diabetes - Renal impairment - Impaired awareness of hypoglycaemia - Extremes of age

Answer 110

- Advancing age - Cognitive impairment - Depression - Aggressive treatment of glycaemia - Impaired awareness of hypoglycaemia - Duration of multi dose insulin therapy - Renal impairment and other comorbidities

Answer 111

- Counter-regulatory hormones - Glucagon - Adrenaline

Answer 112

1. Recognise symptoms 2. Confirm the need for treatment with plasma glucose test 3. Treat with 15g fast-acting carbohydrate to relieve symptoms (lucozade) 4. Retest in 15 minutes to ensure blood glucose > 4 mmol/l and re-treat if needed 5. Eat a long-acting carb to prevent recurrence of symptoms (toast, biscuit)

Answer 113

Repeated glucose and insulin exposure leads to cellular resistance to the effects of insulin. Overtime the pancreas becomes fatigued and damaged from the over production of insulin leading to cell destruction (50% of beta cell loss) Reduced insulin effects leads to hyperglycaemia

Answer 114

Microvascular Macrovascular Infection complications.

Answer 115

Older age Male Ethnicity (Black, Chinese, South Asian) Family history

Answer 116

Obesity Sedentary lifestyles High carbohydrate (particularly refined carbohydrate) diet

Answer 117

Fatigue Polydipsia and polyuria (thirsty and urinating a lot) Unintentional weight loss Opportunistic infections Slow healing Glucose in urine (on dipstick)

Answer 118

performed in the morning prior to having breakfast. It involves taking a baseline fasting plasma glucose giving a 75g glucose drink measuring plasma glucose 2 hours later. If >11mmol/L then Diabetes It tests the ability of the body to cope with a carbohydrate meal.

Answer 119

The body struggles to get their blood glucose levels in to normal range, even after a prolonged period without eating carbohydrates. But glucose levels are not high enough to be diagnosed with DM

Answer 120

HbA1c – 42-47 mmol/mol Fasting plasma glucose 6.1 – 6.9 mmol/l OGTT - plasma glucose at 2 hours 7.8 – 11.1 mmol/l on an OGTT

Answer 121

HbA1c > 48 mmol/mol Random Glucose > 11 mmol/l Fasting Glucose > 7 mmol/l OGTT 2 hour result > 11 mmol/l

Answer 122

Patient education about condition and their lifestyle Dietary modification Exercise and weight loss Smoking Cessation Monitor for DM complications

Answer 123

Metformin (biguanide) to keep HbA1C <48mmol/mol Increases insulin sensitivity and decreases liver production of glucose Does not alter weight

Answer 124

If HbA1c rises above 58 mmol/mol Dual therapy of Metformin + one of: Sulfonylurea Pioglitazone DPP4 inhibitor SGLT2 inhibitor GLP-1 analogues

Answer 125

If HbA1c still >58 mmol/mol on dual therapy then: Triple Therapy - Metformin + 2 of the second line medications OR Metformin + insulin

Answer 126

Preferentially in patients with CVD

Answer 127

Increases insulin sensitivity and decreases liver production of glucose

Answer 128

Diarrhoea and abdominal pain - dose dependent Lactic acidosis Does NOT typically cause hypoglycaemia

Answer 129

A Thiazolidinedione acts on the PPAR-y receptor to Increases insulin sensitivity and decreases liver production of glucose

Answer 130

Weight gain Fluid retention Anaemia Heart failure Extended use may increase the risk of bladder cancer Does NOT typically cause hypoglycaemia

Answer 131

Gliclazide Stimulate insulin release from the pancreas acting on the SUR1 receptor

Answer 132

Weight gain Hypoglycaemia Increased risk of cardiovascular disease and myocardial infarction when used as monotherapy

Answer 133

Hormones produced by the GI Tract (GLP-1 and GIP) They act in response to large meals and reduce blood sugar.

Answer 134

Increase insulin secretions Inhibit glucagon production Slow absorption by the GI tract

Answer 135

Sitagliptin Inhibit the DPP4 which breaks down incretins. Therefore there is increased activity of GLP-1 and GIP

Answer 136

GI tract upset Symptoms of upper respiratory tract infection Pancreatitis

Answer 137

Exenatide/liraglutide Mimic GLP-1

Answer 138

In combination with Metformin and a Sulfonylurea in overweight patients

Answer 139

GI tract upset Weight loss Dizziness Low risk of hypoglycaemia

Answer 140

Empagliflozin, Canagliflozin, Dapaglifozin Inhibit SGLT2 from reabsorbing glucose in the PCT in the kidneys. They cause glucose to be excreted in the urine.

Answer 141

Glucosuria Increased rate of urinary tract infections Weight loss Diabetic ketoacidosis, notably with only moderately raised glucose (rare)

Answer 142

48 mmol/mol for new type 2 diabetics 53 mmol/mol for diabetics that have moved beyond metformin alone

Answer 143

Glycated haemoglobin This is an average glucose level over the last 3 months (due to lifespan of an RBC) it is measured every 3-6 months in diabetics.

Answer 144

Macrovascular Microvascular Infection related

Answer 145

hyperglycaemia causes damage to the endothelial cells of blood vessels. This leads to leaky, malfunctioning vessels that are unable to regenerate. High levels of sugar in the blood also causes suppression of the immune system, and provides an optimal environment for infectious organisms to thrive.

Answer 146

Coronary artery disease Peripheral ischaemia/peripheral vascular disease - leads to diabetic foot Stroke Hypertension

Answer 147

Peripheral neuropathy Diabetic retinopathy Peripheral nephropathy - glomerulosclerosis

Answer 148

UTI Pneumonia Skin and soft tissue infections - often feet Fungal infections - oral/vaginal candidiasis

Answer 149

- Steroids - Tacrolimus - Thiazides - Protease inhibitors (HIV) - Antipsychotics

Answer 150

Pain: Allodynia Paraesthesia Burning Hyperaethesia Autonomic: Gastroparesis Diarrhoea/Constipation Incontinence Orthostatic Hypotension - Postural hypotension Insensitvity: Foot ulceration Infection amputation Charcot foot

Answer 151

Abnormal sensation (normally tingling or pins and needles) due to peripheral nerve damage

Answer 152

pain response to normally non-painful stimulus

Answer 153

Weakening of the bones of the foot, they are more prone to fractures and the stress of walking leads to deformity of the foot

Answer 154

Non-reversible condition Treatment is only symptomatic management

Answer 155

- gloves and stocking sensory loss - Starts in tips of fingers and toes and works its way up

Answer 156

- Hypertension - Smoking - Poor glycaemic control - Diabetic duration - BMI - Triglycerides - Total cholesterol

Answer 157

- Test sensation - Vibration perception - Ankle Reflexes

Answer 158

Amputation

Answer 159

Quit smoking Walk through the pain Surgical Intervention

Answer 160

- Hyperglycaemia induces apoptosis of perictyes (which causes micro-aneurysms) and endothelial cells (which increases permeability of capillaries, proteins leak into retina) - It does this by increasing blood flow to the retinal capillaries and inducing abnormal metabolism - Loss of pericytes cause endothelial cells to respond by increasing turnover, which cause thickening of the capillary wall and cause ischaemia - Vascular growth factors are released in response to ischaemia, which cause the growth of new, fragile blood vessels which are prone to bursting

Answer 161

- R0 - None detected - R1 - Background changes; screened once a year - R2 - Pre-proliferative; early changes screened 6-monthly - R3 - Proliferative; called into eye clinic to look at interventions to protect vision - M - Maculopathy; changes that happen close to the fovea - P - Photocoagulation; laser treatment has been done - U - Unclassifiable

Answer 162

- Laser therapy - Aim is to stabilise the changes - Target abnormal blood vessels to stop them bleeding - Does not improve sight

Answer 163

Proteinuria

Answer 164

Poor blood pressure and blood glucose control

Answer 165

- Hyperglycaemia leads to RBCs becomming sticky and can cause occlusion of the efferent arteriole. - Efferent arteriole is blocked leading to a build up of pressure and Hyperfiltration. - The hyperfiltration damages the filtration barrier and stimulates mesangial cells to secrete extracellular matrix - This leads to sclerosis and scarring (glomerulosclerosis) and subsequent nephropathy

Answer 166

T1DM - Around 10 years after diagnosis T2DM - Can be present at diagnosis

Answer 167

Clinical manifestation of excessive growth hormone (GH). Growth hormone is produced by the anterior pituitary gland. This drives increased bone and muscle growth, increased protein synthesis

Answer 168

Pituitary Adenoma secreting excess GH Account for >90% of causes

Answer 169

Growth hormone

Answer 170

Acromegaly occurs in adults - after growth plates are fused. Gigantism occurs in children - prior to epiphyseal fusion caused by a pituitary tumour causing increased GH release however the tumour also presses on the pituitary so you get hypopituitarism which means the other hormones do not work and therefore they don't go through puberty as no testosterone is being produced

Answer 171

44 years old; mean duration of symptoms is 8 years

Answer 172

excess secretion of GH from an ectopic source: e.g. lung/adrenal tumours that produce GHRH or GH Hypothalamic dysfunction e.g. hypothalamic tumours

Answer 173

Slow gradual changes: Space Occupying Lesion: Headaches Visual field defect (“bitemporal hemianopia”) Overgrowth of tissues: Prominent forehead and brow (“frontal bossing”) Large nose Large tongue (“macroglossia”) Large hands and feet Large protruding jaw (”prognathism”) Arthritis from imbalanced growth of joints GH can cause organ dysfunction: Hypertrophic heart Hypertension Type 2 diabetes Colorectal cancer Symptoms suggesting active raised growth hormone: Development of new skin tags Profuse sweating

Answer 174

Bitemporal hemianopia: A pituitary tumour of sufficient size will start to press on the optic chiasm that lies just above. Pressure on the optic chiasm will lead to a stereotypical “bitemporal hemianopia” visual field defect. This describes loss of vision on the outer half of both eyes.

Answer 175

Insulin-like Growth Factor 1 (IGF-1) is the initial screening test (raised) Oral glucose tolerance test whilst measuring growth hormone (high glucose normally suppresses growth hormone) MRI brain for the pituitary tumour Refer to ophthalmology for formal visual field testing

Answer 176

Hypertension and heart disease Diabetes Cerebrovascular events and headache Arthritis Insulin resistant Diabetes Sleep Apnoea

Answer 177

Often caused by pituitary adenoma: Therefore Trans-sphenoidal surgery is first line treatment If ectopic GH is the cause then surgical removal of these cancers is also treatment.

Answer 178

2nd Line: Somatostatin analogues - Block GH release (Ocreotide) 3rd Line: Pegvisomant - GH antagonist OR Dopamine agonists - Block GH release (Bromocriptine/Cabergoline) 1st line Tx = transsphenoidal surgery

Answer 179

GH Antagonist used to treat acromegaly

Answer 180

Somatostatin analogue used to treat acromegaly as this blocks the Growth Hormone axis

Answer 181

A dopamine agonist used to treat acromegaly as this blocks the growth Hormone axis

Answer 182

The development hypopituitarism; therefore, it is generally avoided in those of reproductive age.

Answer 183

Renal STONES Painful BONES Abdominal GROANS - Constipation, nausea, vomiting Psychiatric MOANS - Fatigue, depression, psychosis THRONES - Polyuria, Polydipsia

Answer 184

Short QT interval Shortening of the ST segment - faster ventricular repolarisation as a result of increased calcium entering the cell through L type calcium channels

Answer 185

90% of the time caused; - Malignancies - Hyperparathyroidism - primary and tertiary

Answer 186

Myeloma Bone metastases Lymphoma PTH related tumour.

Answer 187

Uncontrolled parathyroid hormone produced directly by a tumour of the parathyroid glands. This leads hypercalcaemia: an abnormally high level of calcium in the blood. This is treated by surgically removing the tumour.

Answer 188

This is where insufficient vitamin D or chronic renal failure leads to low absorption of calcium from the intestines, kidneys and bones. This causes hypocalcaemia: a low level of calcium in the blood. The parathyroid will react to the chronically low serum Ca and secrete excessive PTH.

Answer 189

Parathyroid undergoes hyperplasia due to overactivation from chronic hypocalcaemia. This results in serum calcium being low/normal but PTH being high

Answer 190

When 2' hyperparathyroidism continues for a long time it leads to hyperplasia of the gland and the baseline PTH increases drastically. If the 2' Hyperparathyroid cause is treated then there is high PTH in the absence of pathology leading to hypercalcaemia

Answer 191

High PTH due to hyperplasia and increased baseline levels High serum calcium due to high PTH in the absence of pathology.

Answer 192

Primary: Cause - Tumour PTH - High Calcium - High Phosphate - Low Secondary: Cause - Low Vitamin D / CKD PTH - High Calcium - Low/Normal Phosphate - High Tertiary: Cause - Hyperplasia PTH - High Calcium - High Phosphate - High

Answer 193

Mild/moderate Hypocalcaemia: 1.9-2.2 mmol/l Sever Hypocalcaemia: <1.9 mmol/l Normal Serum level: 2.2-2.6 mmol/l Mild Hypercalcaemia: 2.7 - 2.9 mmol/l Moderate Hypercalcaemia: 3.0-3.4 mmol/l Severe Hypercalcaemia: >3.4 mmol/l

Answer 194

Primary: Surgical removal of adenoma. Potentially bisphosphonates. Secondary: Calcium correction. Treat underlying condition Tertiary: Calcium mimetic (Cinacalcet), total or subtotal parathyroidectomy

Answer 195

Primary: Surgical removal of adenoma. Potentially bisphosphonates. Secondary: Calcium correction. Treat underlying condition Tertiary: Calcium mimetic (Cinacalcet), total or subtotal parathyroidectomy

Answer 196

CATS go Numb Convulsions Arrhythmias Tetany Spasm Numbness

Answer 197

QT prolongation Prolongation of the ST segment due to slower ventricular repolarisation as there is less calcium entering myocardial cells.

Answer 198

Chvostek: Facial nerve spasm when tapped Trousseau: Carpopedal

Answer 199

Vit D Deficiency CKD Hyperphosphatemia Diuretics Hypoparathyroidism Pseudohypoparathyroidism Critical illness - sepsis

Answer 200

Primary: gland failure - autoimmune destruction Congenital - Di George Syndrome Secondary Surgery/radiation therapy

Answer 201

PTH stimulates the activation of vitamin D, which facilitates intestinal calcium absorption, renal reabsorption of calcium as well as calcium release from bone. Phosphate reabsorption is inhibited by PTH. In Hypoparathyroidism, these processes do not occur as PTH is not produced

Answer 202

Hypocalcaemia Hyperphosphatemia

Answer 203

Acute: IV calcium gluconate Persistent: Vitamin D analogue/supplementation

Answer 204

CKD Increased phosphate Microprecipitation of calcium phosphate in tissues Low serum level of calcium. CKD Inadequate production of active vitamin D.

Answer 205

An adrenal adenoma secreting Aldosterone leading to hyperaldosteronism independent of the RAAS

Answer 206

When the adrenal glands are directly responsible for producing too much aldosterone Serum renin will be low as it is suppressed by the high blood pressure

Answer 207

Bilateral adrenal hyperplasia (most common) An adrenal adenoma secreting aldosterone (known as Conn’s Syndrome) Familial hyperaldosteronism type 1 and type 2 (rare) Adrenal carcinoma (rare)

Answer 208

Where excessive renin stimulates the adrenal glands to produce more aldosterone Serum renin will be high

Answer 209

Renal artery stenosis Renal artery obstruction Renin secreting tumours Heart failure

Answer 210

1st Line: FBC/U&E Check Renin : Aldosterone ratio: High aldosterone and low renin indicates primary hyperaldosteronism High aldosterone and high renin indicates secondary hyperaldosteronism GS- Selective adrenal venous sampling CT / MRI to look for an adrenal tumour Renal doppler ultrasound, CT angiogram or MRA for renal artery stenosis or obstruction

Answer 211

Hypertension (most common cause of secondary hypertension) Hypokalaemia Hypernatraemia Alkalosis

Answer 212

Aldosterone antagonists: Spironolactone/Eplerenone Treat underlying cause: Surgical removal of tumour Renal artery angioplasty

Answer 213

Hyperaldosteronism

Answer 214

Resistant HTN (unfixable with ACEi / Bb) Hypokalaemia Muscle weakness Paraesthesia Polydipsia Polyuria and nocturia Mood Disturbance

Answer 215

Where there is inappropriately large amounts of ADH release

Answer 216

Idiopathic CNS disorders Head Injury Tumours - Pituitary or Ectopic ADH production pneumonia Respiratory causes Drugs

Answer 217

Excess ADH secreted Excessive water reabsorption in CD of nephron Water dilutes Na in the blood so low serum Na concentration (hyponatraemia) Water reabsorption does not normally cause fluid overload so euvolemia Euvolemic Hyponatraemia Urine is more concentrated - less water is excreted SIADH patients high High urine osmolality and High urine Sodium

Answer 218

Non-specific Headache Fatigue Muscle aches/cramps Confusion Severe Hyponatraemia - can cause seizures and reduced consciousness

Answer 219

In a way, SIADH is a diagnosis of exclusion as we do not have a reliable test to directly measure ADH activity. Clinical examination will show euvolaemia. U+Es will show a hyponatraemia. Urine sodium and osmolality will be high.

Answer 220

Negative short synacthen test to exclude adrenal insufficiency No history of diuretic use No diarrhoea, vomiting, burns, fistula or excessive sweating No excessive water intake No chronic kidney disease or acute kidney injury

Answer 221

Establish and treat the cause Correct sodium levels - must be done slowly to prevent CPM Fluid restriction Tolvaptan - ADH receptor blockers (V2 receptors) Demeclocycline - tetracycline antibiotic that inhibits ADH

Answer 222

Central Pontine Myelinolysis (Osmotic Demyelination Syndrome) Usually caused by treating severe hyponatraemia too quickly

Answer 223

SIADH will release more ADH Will increase water retention but have compensatory Na excretion to maintain euvolemia Therefore SIADH presents as Euvolemia and Hyponatraemia Other Hyponatraemia causes can be fluid overload (Liver failure) or dehydration

Answer 224

Arginine Vasopressin Deficiency (AVP Deficiency) - Cranial Diabetes Insipidus Arginine Vasopressin Resistance (AVP Resistance) - Nephrogenic Diabetes Insipidus

Answer 225

A lack of ADH or a lack of response to ADH. This prevents the kidneys from being able to concentrate the urine leading to polyuria and polydipsia.

Answer 226

A lack of ADH production

Answer 227

Although ADH is produced, it is not able to bind to receptors to induce a response and hence ADH does not function.

Answer 228

When the patient has normally functioning ADH system but they are drinking excessive quantities of water leading to excessive urine production.

Answer 229

Drugs, particularly lithium used in bipolar affective disorder Mutations in the AVPR2 gene on the X chromosome that codes for the ADH receptor Intrinsic kidney disease Electrolyte disturbance (hypokalaemia and hypercalcaemia)

Answer 230

Can be idiopathic - no clear cause Brain tumours Head injury Brain malformations Brain infections (meningitis, encephalitis and tuberculosis) Brain surgery or radiotherapy

Answer 231

Polyuria (excessive urine production) Polydipsia (excessive thirst) Dehydration Postural hypotension Hypernatraemia No Glycosuria

Answer 232

Low urine osmolality High serum osmolality Water deprivation test Desmopressin suppression test

Answer 233

Also known as desmopressin stimulation test: Initially the patient should avoid taking in any fluids for 8 hours (This is referred to as fluid deprivation) Then, urine osmolality is measured and synthetic ADH (desmopressin) is administered. 8 hours later urine osmolality is measured again.

Answer 234

AVP Deficiency (Cranial DI): After Deprivation - Urine osmolality is Low After ADH (desmopressin) - Urine osmolality is High AVP Resistance (Nephrogenic DI): After Deprivation - Urine osmolality is Low After ADH (desmopressin) - Urine osmolality is Low Primary Polydipsia: After Deprivation - Urine osmolality is High After ADH (desmopressin) - Urine osmolality is High

Answer 235

Desmopressin - Synthetic ADH to replace normal ADH

Answer 236

Adequate fluid intake to match output and insensible losses Thiazide Diuretics - increase sodium excretion to reduce blood osmolality and therefore reduce stimulation of thirst centres in the hypothalamus

Answer 237

135-145mmol/l

Answer 238

- Mild130-135mmol/l - Moderate 125-129mmol/L - Severe <125mmol/l

Answer 239

- Headache - Lethargy - Anorexia and abdominal pain - Weakness - Confusion/hallucinations - Agitation - Decreased consciousness level - Fitting - Coma

Answer 240

- Acute - 48 hours - Rapid correction safer and may be necessary - Chronic - CNS adapts - Correction must be slow - <8mmol/24hr

Answer 241

Severe Hyponatraemia Water moves by osmosis across BBB into the cells of the brain (from low solute conc to high solute conc) Causes the brain to swell. Brain adapts by reducing solutes in brain cells so water is balanced across BBB preventing oedema. This process is protective and takes a few days to adapt Therefore in chronic hyponatraemia, brain cells will also have low osmolality (after adaptation) If Hyponatraemia treated too quickly: Serum Na levels rise Water rapidly shifts out of brain cells into blood leads to demyelination of neurones

Answer 242

A tumour of the chromaffin cells in the adrenal medulla that secrete unregulated amounts of adrenaline. This leads to episodic activation of the sympathetic nervous system

Answer 243

25% are familial associated with Multiple Endocrine Neoplasia Type 2 (MEN2) 10% rule for patterns of tumour: 10% bilateral 10% malignant 10% outside of adrenal gland

Answer 244

Signs and symptoms fluctuate with peaks and troughs relating to when the tumour is secreting adrenaline. Anxiety Sweating Headache Hypertension Palpitations, tachycardia and paroxysmal atrial fibrillation

Answer 245

24 hour urine Catecholamines Plasma free Metanephrines

Answer 246

They are the breakdown product of adrenaline which have a much longer half life Therefore they are less prone to dramatic fluctuations like adrenaline is

Answer 247

Alpha blockers - Phenoxybenazmine Beta-blockers - Once established on alpha blockers Adrenalectomy to remove the tumour - definitive management.

Answer 248

Hypertenstion crisis (>180/120 BP) Treatment is Phentolamine

Answer 249

Benign adenoma of the pituitary gland secreted Prolactin

Answer 250

Females: Amenorrhoea/oligorrhoea Low Libido Galactorrhoea Infertility. Men: Low testosterone ED Reduced facial hair Low Libido

Answer 251

Dopamine agonist (e.g. Cabergoline or Bromocriptine) - produces prolactin-reducing feedback Surgery possibly

Answer 252

Lactotroph

Answer 253

- Hypothalamic-pituitary stalk damage - Drug induced e.g. anti-psychotics which block dopamine - Pregnancy and lactation - Systemic disorders e.g. CKD or cirrhosis

Answer 254

- MRI scan - Prolactin levels in the blood

Answer 255

HLA DR3 HLA DR4

Answer 256

Defective enzymes mediating the production of adrenal cortex products

Answer 257

In severe forms; salt loss. Female: Ambiguous genitalia with common urogenital sinus. Male: no signs at birth, bar subtle hyperpigmentation and possible penile enlargement.

Answer 258

Low cortisol, maybe low aldosterone, high androgen

Answer 259

Defective 21-hydroxylase -> disruption of cortisol biosynthesis. This causes cortisol deficiency, with or without aldosterone deficiency and androgen excess. In severe forms, aldosterone deficiency -> salt loss

Answer 260

Genetic 21-hydroxylase deficiency is the cause of about 95% of cases.

Answer 261

Serum 17-hydroxyprogesterone (precursor to cortisol) levels: high

Answer 262

Glucocorticoids: Hydrocortisone Mineralocorticoids: Fludrocortisone Control electrolytes If salt loss: Sodium chloride supplement

Answer 263

Excess potassium in the blood more than 5.5mmol/L

Answer 264

Impaired excretion: - CKD/AKI. - Potassium Sparing Diuretics - Adrenal Insufficiency/Addisonian Crisis Increased Intake - dietary/IV Shift to extracellular - rhabdomyolysis

Answer 265

Impaired muscular transmission: Fatigue Generalised weakness Chest pain cramps diarrhoea dyspnoea Palpitations Signs: hyperreflexia Arrythmias Reduced power Can cause MI

Answer 266

Tall tented T Waves Reduced/small P wave Prolonged PR Widened QRS

Answer 267

Myocardial Infarction Leads to Death

Answer 268

- Myocardial protection - IV Calcium gluconate - Drive K intracellularly - insulin w/dextrose AND Nebulised salbutamol - Dietary potassium restriction and loop diuretic

Answer 269

Low serum Potassium < 3.5mmol/L

Answer 270

Usually asymptomatic, Hypotonia Hyporeflexia Muscle cramps and pain possibly muscle weakness. Increased risk of cardiac arrhythmias. Tetany Palpitations

Answer 271

T wave Inversion or Flat T waves ST Depression Prolonged PR Prominent U waves

Answer 272

Excessive loss of potassium through the kidneys in response to aldosterone or diuretic therapy. GI fluid loss -> less chloride -> increase in aldosterone -> Decreased potassium reabsorption

Answer 273

Hypokalaemia w/ alkalosis: Vomiting, thiazides, loop diuretics, cushings, Conns Hypokalaemia w/ Acidosis: Diarrhoea, Rental tubular acidosis, acetazolamide, DKA partially treated

Answer 274

Mild/ASx (3-3.4mmol/l) Oral replacement/IV Severe (<2.5mmol/l) IV replacement 40mmol KCL in 1L 0.9 NaCl

Answer 275

Cardiac Arrythmias Sudden death

Answer 276

Describes the physiological, morphological, and behavioural changes as the gonads switch from infantile to adult forms

Answer 277

- Girls - menarche - First menstrual bleed - Boys - first ejaculation - Often nocturnal

Answer 278

- Girls - Ovarian oestrogens - Growth of breasts and female genitalia - Ovarian and adrenal androgens - Control pubic and axillary hair - Boys - Testicular androgens - External genitalia and pubic hair growth - Enlargement of larynx and laryngeal muscles - Deepening of the voice

Answer 279

Scale of physical development through puberty

Answer 280

Orchidometer

Answer 281

Girls: Lack of breast development by 13yrs More than 5yrs between breast development and menarche Lack of pubic hair by age 14yrs Absent menarche by 15-16yrs Boys: Lack of testicular enlargement by age 14yrs Lack of pubic hair by age 15yrs More than 5 years to complete genital enlargement

Answer 282

Chronic Renal disease / Chronic lung disease Chronic GI disease/malnutrition Sickle cell disease Anorexia nervosa/Bulimia Psychosocial stress Extreme exercise Drugs Poorly controlled T1DM Hypothyroidism Cushing's Syndrome Hyperprolactinaemia

Answer 283

- Issue with the gonads - Also known as hypergonadotropic hypogonadism

Answer 284

- Gonads not responding to stimulus so hypothalamus and pituitary more stimulated - FHS/LH will both be high - Sex hormones will be low

Answer 285

Also known as Hypogonadotrophic Hypogonadism Secondary - Issue with Pituitary Tertiary - Issue with Hypothalamus

Answer 286

CNS disorders - tumours Kallmanns' Syndrome - Gonadotrophin deficiency Prader willi syndrome sickle cell CF AIDS

Answer 287

Mainly Males 4:1 M:F

Answer 288

Anosmia delayed puberty

Answer 289

Hypogonadotrophic hypogonadism - Failure of migration of GNRH neurones from hypothalamus to pituitary - X-linked, autosomal recessive or dominant

Answer 290

Klinefelters - Males Turners Syndrome - Females

Answer 291

45 XO Loss of an X chromosome

Answer 292

Primary Hypogonadism Webbing of neck Short stature recurrent Otitis media Small mandible

Answer 293

47 XXY Primary hypogonadism

Answer 294

- Azoospermia - Gynaecomastia - Reduced secondary sexual hair - Osteoporisis - Tall stature - Reduced IQ

Answer 295

20-fold increased risk of breast cancer

Answer 296

- GnRH therapy - Pituitary must be intact - Parenteral combination of gonadotropin therapy - LH/hCG and FSH

Answer 297

- Breast development - Oestrogen

Answer 298

- Prolactin - Glucocorticoids - Insulin

Answer 299

- Maturation process of the adrenal gland - Specialised subset of cells arises forming the androgen producing zona reticularis

Answer 300

- Peri-puberty - Premature or exaggerated adrenarche can occur up to 2 years prior to puberty, especially in obese children

Answer 301

- Mild advance in bone age - Axillary hair growth - Mild acne - Body odor

Answer 302

Early puberty

Answer 303

- Up to 80% female - If male patients present with precocious puberty, differentials should be ruled out before a diagnosis of idiopathic puberty is given - Brain tumour may be highly likely or some other significant pathology

Answer 304

Resembles puberty, but not from normal hypothalamus activation

Answer 305

- Adrenal sex hormones excess - Congenital adrenal hyperplasia - hCG Secreting Tumours - Gonads - Brain - Liver - Retroperiteneum - Mediastinum

Answer 306

- Use of GnRH super-agonist suppresses pulsatility of normal physiology - Stops the process

Answer 307

- Idiopathic Hypogonadotropic Or hypergonadotropic hypogonadism

Answer 308

Girls: Lack of breast development by 13yrs More than 5yrs between breast development and menarche Lack of pubic hair by age 14yrs Absent menarche by 15-16yrs Boys: Lack of testicular enlargement by age 14yrs Lack of pubic hair by age 15yrs More than 5 years to complete genital enlargement

Answer 309

Hyperosmolar Hyperglycaemic State (HHS)

Answer 310

Hyperosmolar Hyperglycaemic State: Profound Hyperglycaemia and Hyperosmolality in the absence of ketoacidosis Occurs when the blood glucose levels go really high ( >33.3 mmol/l) Results in a blood osmolality of >320 mOsm/kg The hyperosmolar state draws water out of cells and into the blood This leads to polyuria and severe dehydration

Answer 311

Polyuria Extreme thirst Dehydration - Can lead to neurological symptoms Reduced GCS Poor capillary refill Hypotension Tachycardia

Answer 312

History and physical exam Blood tests and U&Es: Severe hyperglycaemia - >30mmol/l High blood osmolality >320mOsm/kg Hypotension No/minimal urinary ketones ABG - No acidosis

Answer 313

ABCs IV Fluids Electrolyte Replacement IV Insulin VTE prophylaxis

Answer 314

Transport: Water - unbound Fat - Protein bound Cell interaction: Water - Bind to surface receptor Fat - diffuse into cell Half life: Water - short Fat - long Clearance: Water - Fast Fat - Long

Answer 315

Peptide hormones Monoamines

Answer 316

Thyroid hormones Steroid Hormones

Answer 317

In vesicles

Answer 318

Typically not stored They are synthesised on demand

Answer 319

Secretions go directly into the bloodstream/lymph to act at distant sites

Answer 320

Glandular secretions poured into a duct to the site of action Typically will act locally

Answer 321

Cellular secretions/signals that act on adjacent cells

Answer 322

Cellular secretions/signals that feedback on the same cell that secreted the hormone.

Answer 323

- Initial stimulus causes response - Response feedback to stimulus to reduce - Response loop shuts off

Answer 324

- Initial stimulus causes response - Response causes stimulus to increase - Response continues to increase - Outside factor required to shut off feedback cycle

Answer 325

- Hydrophilic and water soluble - Usually stored in secretory granules; released in bursts or as part of a rhythmic cycle

Answer 326

- Translocation of Glut-4 transporter to the plasma membrane and influx of glucose - Glycogen synthesis (liver) - Glycolysis - Fatty acid synthesis (live and adipose tissue)

Answer 327

Tryptophan derived amines Tyrosine Derived amines

Answer 328

Catecholamines - Dopamine, noradrenaline, adrenaline Thyroid Hormones - T3 and T4

Answer 329

Adrenaline and noradrenaline from the adrenal medulla Dopamine from the hypothalamus

Answer 330

Both play a role in the body's sympathetic nervous system; - Adrenaline has slightly more of an effect on the heart - Noradrenaline has slightly more of an effect on blood vessels

Answer 331

Hydrophobic

Answer 332

Triiodothyronine (T3) Thyroxine (T4)

Answer 333

T4 produced by the thyroid gland - more abundant T3 is produced by the conversion of T4 to T3 in the periphery - more active

Answer 334

1. *Thyroglobulin* (T4 precursor) is synthesised in cells of thyroid gland and discharged into follicle lumen 2. *Iodide* is actively transported inside the follicular cell 3. Iodide is oxidised to *iodine*. 4. Iodine is attached to tyrosine in colloid, forming *Diiodotyrosine* (DIT) and *Monoiodotyrosine* (MIT). 5. DIT and MIT join together to form T3 and T4; - MIT + DIT = T3 - DIT + DIT = T4 6. T3 and T4 are stored in follicular cell 7. lysosomal enzymes cleave T4 and T3 from thyroglobulin and hormones diffuse into bloodstream

Answer 335

Iodothyronine deiodinase

Answer 336

Corticosteroids (Adrenocorticoids) sex steroids (Gonadal)

Answer 337

It is based upon the receptor that they bind to!

Answer 338

Corticosteroids

Answer 339

Sex steroids

Answer 340

Cholesterol

Answer 341

- Cholesterol is converted to Pregnenolone - Pregnenolone converted to **Progesterone** - In adrenal glands, progesterone changed to **Cortisol** - In ovaries or testes, progesterone converted to **Androstenedione** which is converted to **Testosterone** - Testosterone converted to **Estradiol** in the ovaries

Answer 342

Lipid soluble

Answer 343

- Humoral stimulus; released as result of change in environment (e.g. low calcium causes release of PTH) - Neural stimulus; sympathetic nervous system stimulates adrenal gland to release adrenaline - Hormone stimulus; hypothalamus releases hormone which stimulates pituitary gland which releases further hormones to stimulate other glands.

Answer 344

Pituitary gland Thyroid Gland Parathyroid Gland Adrenal Gland Pancreas Gonads - Ovary / Testes

Answer 345

Adrenal Cortex: Zona Glomerulosa - Mineralocorticoids - Aldosterone Zona Fasciculata - Glucocorticoids - Cortisol/cortisone Zona Reticularis - Androgens - Oestrogen / Testosterone Adrenal Medulla: Catecholamines - Adrenaline, Noradrenaline

Answer 346

The desire to eat food

Answer 347

The feeling of fullness Disappearance of appetite after a meal

Answer 348

Lack of Appetite

Answer 349

The need to eat

Answer 350

Weight (kg) / Height (m^2)

Answer 351

<18.5 underweight 18.5-24.9 normal 25-29.9 overweight 30-39.9 obese >40 morbidly obese

Answer 352

Internal Physiological drive - a feeling that prompts the thought of food and motivates food consumption External Psychological drive - Explains why we eat in the absence of hunger (eg. at a buffet)

Answer 353

The Hypothalamus Lateral Hypothalamus - Hunger centre Ventromedial Hypothalamic Nucleus - Satiety centre

Answer 354

Lateral Hypothalamus

Answer 355

Ventromedial Hypothalamic Nucleus

Answer 356

NPY - Neuropeptide Y MCH - Melanin concentrating Hormone AgRP - Agouti related peptide Orexin Endocannabinoid

Answer 357

- α-MSH: alpha melanocyte stimulating hormone from POMC - CART: cocaine and amphetamine regulated transcript - GLP-1: glucagon like peptide 1 - Serotonin - Peptide YY (PYY) - CCK

Answer 358

NPY POMC - α-MSH

Answer 359

Proopiomelanocortins Precursor polypeptides that are cleaved into 3 main hormones ATCH MSH Endorphins

Answer 360

Induces satiety by binding to the MCR3 and MCR4 receptors in the brain

Answer 361

Expressed in adipose tissue Switches off appetite and is immunostimulatory Leptin is sensed by the arcuate nucleus of the hypothalamus where it stimulates the release of anti-appetie factors (POMC; CART) and inhibits the release of pro-apeptite factors (NPY; AgRP).

Answer 362

In adipose tissue

Answer 363

Through leptin gene deficiency Through Leptin receptor mutation

Answer 364

Expressed in adipose tissue Switches off appetite and is immunostimulatory Leptin is sensed by the arcuate nucleus of the hypothalamus where it stimulates the release of anti-appetite factors (POMC; CART) and inhibits the release of pro-appetite factors (NPY; AgRP).

Answer 365

Ghrelin PYY GLP-1 CCK

Answer 366

Stimulates GH release Stimulates appetite (orexigenic)

Answer 367

The stomach

Answer 368

Peptide YY Structurally similar to NPY - binds to NPY receptors

Answer 369

Inhibits gastric motility Reduces appetite

Answer 370

Neuroendocrine cells in the ileum, pancreas, colon in response to food

Answer 371

Cholecystokinin Delays gastric emptying time gallbladder contraction Insulin release Acts on the vagus nerve to stimulate satiety

Answer 372

In a similar way to Leptin It inhibits NPY/AgRP release It stimulates POMC/CART release Acts to decrease appetite

Answer 373

Leptin and Insulin: Stimulate POMC/CART neurones - increase CART and alpha-MSH levels Inhibit NPY/AgRP neurones - Decrease NYP/AgRP Overall will increase satiety and decrease appetite. Ghrelin: Stimulates NPY/AgRP neurone - their levels increase Increase appetite PYY: Binds to an inhibitory receptor on NPY/AgRP neurones - decrease their levels Decrease appetite

Answer 374

GPCR: V1a - in vasculature (similar to adrenoceptors) V2 - in collecting tubules of nephron - water reabsorption V1b - In pituitary in the brain

Answer 375

- Osmoreceptors in hypothalamus - Routine - Baroreceptors in brain stem and great vessels - Emergency

Answer 376

Concentration of a solute per KG of solution mOsmol/Kg

Answer 377

The number of molecules (concentration)

Answer 378

- Size is irrelevant - a molecule of sodium has the same effect as a molecule of albumin It is the number of particles (concentration) that makes a difference to the osmolality

Answer 379

- Sodium - Potassium - Chloride - Bicarbonate - Urea - Glucose

Answer 380

- Alcohol - Methanol - Polyethylene glycol - Manitol

Answer 381

282-295 mOsmol/kg

Answer 382

2x[Na] mmol/L + [Glucose] mmol/L + [urea] mmol/L

Answer 383

To account for the anion gap

Answer 384

- Acts on V2 receptors - Stimulates an intracellular cascade - Aquaporin-2 proteins are synthesised and inserted into the apical membrane - Permeability to water is increased - Increased reabsorption of water - Concentration of Urine

Answer 385

Non functioning pituitary adenoma A benign growth in the pituitary gland that does not produce excessive hormones into the blood

Answer 386

Rare type of brain tumour derived from pituitary gland embryonic tissue.

Answer 387

Squamous epithelial remnants of Rathke's pouch

Answer 388

- Adamantinous (classical) - Papillary

Answer 389

Tumour forming from the three membranous layers of the meninges

Answer 390

- On waking up - Lunchtime - Dinnertime

Answer 391

Carbimazole is teratogenic therefore give PTU

Answer 392

CORTICOSTEROIDS: Cushing's Syndrome Osteoporosis Reduced Growth Thin Skin Immunosuppression Cataracts Oedema Suppressed HPA axis Teratogenic Emotional/Mood Disturbances Rise in blood pressure Obesity Increased hair growth Diabetes + hyperglycaemia Striae

Answer 393

Graves' disease Hashimoto's disease Drugs (e.g. lithium, amiodarone) Iodine deficiency/excess De Quervain's thyroiditis (painful) Infiltration (e.g. sarcoid, haemochromatosis

Answer 394

Toxic solitary adenoma Non-functional thyroid adenoma Multinodular goitre Thyroid cyst Cancer

Answer 395

1st Line: Random Blood Glucose - >11mmol/L Fasting Blood Glucose - >7 mmol/L For Borderline cases: OGTT - >11mmol/L 2 hours after 75g oral glucose load HbA1c - >48mmol/L Ix to Consider: C-peptide Autoantibodies - Glutamic acid, insulin, islet cell

Answer 396

- Hypoglycaemia - most common (also caused by SULFONYLUREA - antidiabetic drug) - Injection site - lipohypertrophy - Insulin resistance - mild and associated with obesity - Weight gain - insulin makes people feel hungry

Answer 397

Undiagnosed T1DM (potentially also T2DM) Inadequate insulin / non-adherence to Insulin therapy

Answer 398

Usually triggered by an infection: - relative Lack of insulin coupled with a rise in counter regulatory Hormones (Cortisol, GH, glucagon) - Leads to profound rise in glucose (but insulin is adequate to prevent DKA) - Excessive glucose leads to osmotic diuresis as capacity for renal reabsorption is full. This also draws out other essential electrolytes. - As water is lost there is dehydration and reduced circulating volume. - Leading to hyperosmolarity with Hyperglycaemia - This can cause hypovolaemia and cause AKI. Hyperosmolarity also increases viscosity of blood increase risk of thrombotic events.

Answer 399

1st Line: Random Blood Glucose - >11mmol/L Fasting Blood Glucose - >7 mmol/L For Borderline cases: OGTT - >11mmol/L 2 hours after 75g oral glucose load HbA1c - >48mmol/L Ix to Consider: Fasting Lipids U&Es - if suggestive signs of Diabetic Nephropathy

Answer 400

Lower BP Decrease Aldosterone Resolve electrolyte imbalance

Answer 401

Subacute Granulomatous thyroiditis Self limited inflammation of the thyroid often following viral infection.

Answer 402

4 Phases: Phase 1 (3-6 weeks) Hyperthyroidism and painful goitre Phase 2 (1-3 weeks) Euthyroid - normal function Phase 3 (weeks-months) Hypothyroidism Phase 4 Thyroid structure and function return to normal

Answer 403

Neck pain (may radiate to jaw/ears) Difficulty eating Tender firm enlarged thyroid + goitre Fever Palpitations - often secondary to thyrotoxicosis

Answer 404

All elevated Total T4, T3, T3 resin uptake CRP elevated Often follows viral infection

Answer 405

Hyperthyroid Phase - NSAIDs and corticosteroids Hypothyroid Phase - No Tx usually

Answer 406

CHIMPANZEES: Calcium supplementation Hyperparathyroidism Iatrogenic immobilisation Multiple Myeloma Parathyroid Hyperplasia (3' Hyperparathyroidism) Alcohol Neoplasms Zollinger-ellison syndrome Excessive Vitamin D Excessive Vitamin A Sarcoidosis

Answer 407

Fasting Serum Calcium Serum PTH Ultrasound for Primary Parathyroidism 24hr urinary calcium

Answer 408

Rehydration with normal saline Bisphosphonates Loop Diuretics (furosemide)

Answer 409

Neuroendocrine tumour that mainly arises from GI tract, lungs, liver or ovaries. Secretes serotonin (5-hyroxytryptamine/ 5-HT) into systemic circulation.

Answer 410

If from GI tumour - ASx - serotonin is metabolised by liver and prevents Sx Other causes - Flushing, palpitations, diarrhoea (main three), cramps, abdo pain, bronchospasm,

Answer 411

Ix: 1st: Urinary 5-HT acid test. GS: Chromagranin-A + Octreoscan Then CXR/CAP MRI for tumours. Tx: Surgery is only cure. Ocreotide can help

Answer 412

Metformin + Sulfonylurea

Answer 413

Occasionally PTH can be normal if the calcium suppresses the PTH production. This is an inappropriate suppression

Answer 414

Hypothyroidism Cushing's Acromegaly

Answer 415

Small cell lung cancer Prostate Thymus Lymphomas