ENDOCRINE Flashcards

Question

What are the side effects of insulin?

Answer 1

hypoglycaemia, weight gain, lipodystrophy Lipodystrophy - where you loose fat in some regions, but gain it in others, like on Organs like the Liver

Answer 2

**Measure HbA1c** levels every 3 months in children and every 3-6 months in adults Make sure level is under **6.5% (48 mmol/mol)** Also monitor; **Blood Pressure** **Kidney function**

Answer 3

Death due to ketoacidosis

Answer 4

- Microvascular: retinopathy, peripheral or autonomic neuropathy - Cardiovascular disease, diabetic kidney disease. - Potential for depression and eating disorder# - Foot amputations - Blindness

Answer 5

A progressive disorder defined by deficits in insulin secretion and insulin resistance that lead to abnormal metabolism and related metabolic derangements

Answer 6

Basal - One long acting dose in the morning Bolus: Givng a dose before each meal in order to miminc the effect of insulin released So three times a day *eg. Insulin Inspiro, or Insulin Aspart*

Answer 7

Just once a day, (Basal) sometimes twice (BD)

Answer 8

OLDER! >30 years of age. Often overweight around the abdomen - More prevalent in South Asian, African and Caribbean ancestry Common is all populations enjoying an affluent lifestyle More common in males

Answer 9

**Decreased insulin secretion and/or increased insulin resistance** Associated with obesity, lack of exercise, calorie and alcohol excess No immune disturbance Also a genetic link

Answer 10

Glucose levels, in general, are far higher than normal. When you eat a meal with T2DM, it takes alot longer for your blood sugar levels to come down again like in normal physiology.

Answer 11

Family History of it - genetics Obesity and poor exercise - Ageing and being overweight (body mass index [BMI] 25.0 to 29.9 kg/m²), and obesity (BMI >30 kg/m²) Age ***Low birth weight has been shown to predisposose***

Answer 12

Repeated exposure to high levels of Glucose and insulin makes the cells in the body come resistant to insulin. Over time, the pancreas (specifically the beta cells) becomes fatigued and damaged by producing so much insulin and they start to produce less. Fasting glucose levels increases

Answer 13

Having the risk factors eg Older age Overweight/obese Being of a certain ethnic groups inc Black, south asiain, And coming in with: Fatigue Polydipsia and polyuria (thirsty and urinating a lot) ***Unintentional weight loss Opportunistic infections Slow healing***

Answer 14

Polyphasia - Eating lots, Polydipsia, Drink, Polyuria - wee lots, unexplained weight loss

Answer 15

Fasting plasma glucose - **Order after a minimum 8-hour fast.** Positive result is ≥7.0 mmol/L (≥126 mg/dL) 2 hour post load glucose test after 75g oral glucose - Plasma glucose is measured 2 hours after 75 g oral glucose load Positive result is ≥11.1 mmol/L (≥200 mg/dL) Random Plasma glucose - positive test is >11mmol/L ***Bear in mind that a repeat confirmatory test is required for diagnosis in most cases.***

Answer 16

HbA1c glycated haemoglobin how much glucose is attached to the haemoglobin molecule, shows blood glucose levels over the past 3 months - HbA1c > 6.5% normal (48mmol/mol) = DIABETES DIAGNOSIS

Answer 17

Urine ketones, fasting lipid profile (high LDL), **Albumin to creatine ratio***

Answer 18

Non-diabetic hyperglycaemia (pre-diabetes) Diabetes mellitus, type 1 Latent autoimmune diabetes in adults (LADA) Diabetes, gestational

Answer 19

Patient education about their condition and the lifestyle changes, advise that there is a possible cure. Exercise and weight loss, stop smoking Regarding food: - Include **high-fibre, low-glycaemic-index** sources of carbohydrate in their diet, such as fruit, vegetables, wholegrains, and pulses - Eat **low-fat dairy products and oily fish** - Limit their intake of foods containing saturated and trans fatty acids. **Needs annual reinforcement and review** Optimise treatment for other illnesses, eg hypertension

Answer 20

Medical management: First line: metformin titrated from initially 500mg once daily as tolerated. Metformin is a “biguanide”. It **increases insulin sensitivity and decreases liver production of glucose.** It is considered to be “weight neutral” and does not increase or decrease body weight. Management cardiovascular risks: An ACE inhibitor or an angiotensin-II receptor antagonist If an ACE inhibitor is not tolerated, use an angiotensin-II receptor antagonist instead *because metformin only increases insulin sensitivity instead of stimulating more insulin, it'll rarely cause hypoglycaemia*

Answer 21

If HbA1c rises to 58mmol/mol, consider dual therapy or metformin and one of either a sulfonylurea, - **(Gliclazide)** DPP-4 inhibitor **(Sitagliptin)** or SGLT-2 inhibitor **(Dapagliflozin)**, or Glitazone. **(Pioglitazone)** The decision should be based on individual factors and drug tolerance. **Most commonly metformin and an SU**

Answer 22

Gliclazide Sitagliptin Dapagliflozin Pioglitazone

Answer 23

***Eg - Gliclazide*** stimulate insulin release by **binding to Beta-cell receptors** Improve glycaemic control (1-2% in HbA1c) ***give beta cells an extra kick to promote insulin*** Increase weight Increase the risk of heart failure Increase the risk of fractures CI: Pregnancy & breastfeeding (can cross placenta & enter breast milk) (May cause hypoglycaemia in newborns)

Answer 24

They block the reabsorption of glucose in the kidney, increase glucose excretion, and lower blood glucose levels Make you pee lots of glucose out =UTI and Thrush Peeing out glucose can make your body think you're in a fasting state - leading lipid break down - KETOACIDOSIS ***euglycaemic ketoacidosis***

Answer 25

Inhibit DPP4 (so increase effect of incretins (GLP-1 and GIP) which stimulates insulin secretion Incretin = A group of hormones released after eating & augment secretion on insulin (inhibited by DPP4) DOES NOT CAUSE weight gain or weight loss Sitagliptin

Answer 26

If HbA1c still 58mml/mol, consider triple therapy with: Metformin + SU + DPP4 inhibitor Metformin + SU + pioglitazone Metformin + SU/pioglitazone + SGLT-2i Insulin-based therapy

Answer 27

Insulin. Start with Basal Dose

Answer 28

Take HbA1c every 3 to 6 months. Measure blood pressure once a year, to look out for hypertension. Monitor for complications

Answer 29

“Maturity-onset diabetes of the young” Commonest type of monogenic diabetes (~1% diabetes) Diagnosed <25y Autosomal dominant Non-insulin dependent **Single gene defect** altering beta cell function Tend to be non-obese **Monogenic - caused a mutation of one gene only**

Answer 30

Parent affected with diabetes **Absence of islet autoantibodies** Measurable C - Peptide - NOT SEEN ON SYNTHETIC INSULIN

Answer 31

Glucocorticoids increase insulin resistance Thiazides / protease inhibitors (HIV) / antipsychotics – mechanisms not clearly understood

Answer 32

Diagnosed <6 months (usually de novo): Signs: Small babies, epilepsy, muscle weakness

Answer 33

* Diabetic retinopathy * Kidney disease Diabetic foot - due to neuropathy Cardiovascular disease - atherosclerosis, stroke TIA, CHD Glucose sticks in the vessels everywhere - eyes, brains, Kidney,

Answer 34

Ketoacidosis is High levels of ketones in the blood due to cells in the body initiating the process of ketogenesis for fuel. The **ketone acids use up the bicarbonate buffer and the blood starts to become acidic.**

Answer 35

***Inadequate supply of insulin*** ***New onset of diabetes/ Uncontrolled diabetes*** ***Infection*** Myocardial Infarction

Answer 36

Seen in TYPE 1 DM Won't get it in early TYPE 2 DM, but is possible later on 10 years In Type 2, you do have some insulin, so some glucose can go in the cell

Answer 37

***Infection (pneumonia, UTI)*** ==> due to the systemic response that it causes in the body **(eg adrenaline release leads to increased lipolysis, ketogenesis)** Myocardial Infarction (provoke the release of counter-regulatory hormones likely to result in DKA in patients with diabetes.)

Answer 38

nsulin deficiency leads to release of free fatty acids from adipose tissue (lipolysis), hepatic fatty acid oxidation, and formation of ketone bodies), which result in ketonaemia and acidosis, as the bicarbonate buffer from the kidneys is used up

Answer 39

he primary ketone body involved in diabetic ketoacidosis is **acetoacetate**

Answer 40

**Known to have diabetes, and are unwell** **Hyperkalaemia** Polydipsia polyuria, recent unexplained weight loss, or excessive tiredness, **Acetone smell on breath** Secondary: Nausea Abdominal pain[4][49] Hyperventilation Reduced consciousness.

Answer 41

**Venous blood gas (key)** Blood Glucose Blood ketones Urea and Electrolyte count Urine stick for ketones

Answer 42

Full blood count ECGs Pregnancy test

Answer 43

**Venous blood gas** of: pH ≥7.0 indicates mild or moderate DKA. pH <7.0 indicates severe DKA Diabetes - blood glucose is >11.0 mmol/L blood ketones are >3.0 mmol/L - Ketonemia ketonuria (2+ or more on standard urine sticks)

Answer 44

***(Insulin makes you hypokalaemic), as it move postassium into your cells*** Serum potassium can be high or normal in diabetic ketoacidosis, as the kidneys continue to balance blood potassium with the potassium excreted in the urine, however total body potassium is low because no potassium is stored in the cells.

Answer 45

Hyperosmolar hyperglycaemic state (HHS) Lactic acidosis Starvation ketosis Alcoholic ketoacidosis

Answer 46

IV fluids. 1. Give a fluid bolus of 500 mL of normal saline (0.9% sodium chloride) over 10 to 15 minutes if the initial systolic blood pressure (SBP) is <90 mmHg. If BP is >90mmHg, give 1L of normal saline over 60 minutes.

Answer 47

**Potassium and Insulin!!** 1. Add potassium to the **second litre of intravenous fluid** if serum potassium is ≤5.5 mmol/L ***(Insulin makes you hypokalaemic), as it move postassium into your cells *** 2. Start a fixed-rate intravenous insulin infusion (FRIII) according to local protocols; continue FRIII until DKA has resolved Ensure intravenous fluids have already been started before giving a FRIII.

Answer 48

Order hourly blood glucose and hourly blood ketones. Perform a venous blood gas (for pH, bicarb, K+) 60 minutes, 2 hours, and 2 hourly thereafter. * Maintain the potassium level between 4.0 and 5.0 mmol/L. * Maintain an accurate fluid balance chart. - Keep an eye on GCS

Answer 49

Hypokalaemia hypoglycaemia arterial or venous thromboembolic events cerebral oedema/brain injury

Answer 50

Prognosis is worsened at the extremes of age and in the presence of coma and hypotension Death is rarely caused by the metabolic complications of hyperglycaemia or ketoacidosis but *** rather relates to the underlying illness.*** Mortality rates have fallen significantly in the last 20 years from 7.96% to 0.67%.

Answer 51

Level 1 - Alert value Plasma glucose <3.9 mmol/l and no symptoms Level 2 - Serious biochemical Plasma glucose <3.0 mmol, patient has symptoms but can self treat, cognitive function is mildly impaired. Level 3 - Patient has impaired cognitive function sufficient to require external help to recover (Level 3)

Answer 52

Trembling Palpitations Sweating Anxiety Hunger Nausea and Headache are non specific

Answer 53

Difficulty concentrating Confusion Weakness Drowsiness, dizziness Vision changes Difficulty speaking Nausea and Headache are non specific

Answer 54

a) Stop secreting insulin b) starts secreting glucagon c) Adrenaline release - Causes neuroglypenic symptoms d) Cognitive dysfunction e) Reduced conscious level, convulsions, coma

Answer 55

Long duration of diabetes Use of drugs (prescribed or alcohol) Sleeping (not gonna notice) Increased physical activity Increasing age

Answer 56

§ Long duration of diabetes § previous hypoglycaemia § Impaired awareness of hypoglycaemia (IAH)* § Recent episodes of severe hypoglycaemia § Daily insulin dosage >0.85 U/kg/day § Physically active (e.g. athlete) Impaired renal and/or liver function

Answer 57

Recognise symptoms Confirm need for treatment Treat with 15g of fast acting carbohydrate ***RETEST*** in 15 mins to ensure blood glucose >4mmol/L Eat a long - acting carbohydrate to prevent the recurrence of symptoms - because after you've used up the fast acting carb, but the insulin will still be in the body **If unconscious, IV Glucose or IM Glucagon**

Answer 58

Hypoglycaemia.

Answer 59

3 types of HYPERparathyroidism - Primary, Secondary, Tertiary Just one Hypoparathyroidism - due to parathyroid damage) (No prim,sec,tert etc) *Primary Hyperparathyroidism and Hypercalcaemia of malignancy are the two main causes of Hypercalcaemia*

Answer 60

Increasaes Bone resorption Increased Ca2+ in kidney Increased Ca2+ absorption in gut, **through increased vit D** **Decreases phosphate reabsorption in kidney** All to increase serum calcium **RELEASED FROM CHIEF CELLS IN THE PARATHYROID**

Answer 61

Hypoparathyroidism - due to surgery/autoimmune/radiation @ parathyroid gland Vit D deficiency Alcohlism Hyperphosphatemia or Lots of Bisphosphate meds

Answer 62

c CHIMPANZEES- Calcium supplements, Hydrochlorothiazide, Iatrogenic/Immobilisation, Multiple myeloma/Medication (lithium), Parathyroid hyperplasia, Alcohol, Neoplasm, Zollinger ellison syndrome, Excessive Vit D, Excess Vit A, Sarcoidosis Also Thyrotoxicosis

Answer 63

Excessive can lead to a magnesium deficiency, as it promotes the excretion of it. Magnesium is needed for parathyroid hormone synthesis, so low magnesium can lead to low parathyroid hormone, which will in turn lead to hypocalcaemia.

Answer 64

Levels of albumin, what calcium binds to. If this is low, it might make calcium low. Adjust by looking at corrected calcium

Answer 65

CATS go numb: ● C - convulsions ● A - Arrhythmias ● T - Tetany (intermittent involuntary muscle contractions) ● S - spasms ● Numb - numbness Hypocalcemia causes prolonged QT Chvostek’s Sign _ Cause spasms of facial nerve Trousseau’s Sign Fill up blood pressure cough more than systolic pressure for 5 mins- aggravated Italian hands

Answer 66

Hypocalcaemia Prolonged ST Segment Prolonged QT interval

Answer 67

a) Tap over the facial nerve Look for spasm of facial muscles b)Inflate the blood pressure cuff to 20 mm Hg above systolic for 5 minutes - makes hand spasm upwards, like aggrivated italian sign with hands

Answer 68

- 7-dehydroxycholesterol is made directly from ingested chloresterol Which is converted into Vitamin D3, by UV radiation - Vitamin D3 is converted into Calcidiol in the Liver via the cytochrome P450 system) - Calcidiol is converted to Calcitriol (Vit D) in the presence of PTH in the Kidneys CALCITRIOL (VIT D) CAN GO ON AND PROMOTE GUT CALCIUM ION ABSORPTION

Answer 69

**DAMAGE TO PARATHRYOID GLAND!!** - WHAT WOULD CAUSE THIS: Surgery/Chemotherapy on the neck to target cancer, that damages the Parathyroid gland Genetic Autoimmune disesases *Magnesium Deficiency* Syndromes, like Di George - Developmental abnormality of third and fourth branchial pouches

Answer 70

Resistance to parathyroid hormone. It is a rare, hereditary condition * Short stature * Obesity * Round facies * Mild learning difficulties * Subcutaneous ossification * Short fourth metacarpal **A FORM OF HYPOCALCAEMIA** , Treat as such

Answer 71

Tourniquet on too long, which damages vessels IF sample has been left around for too long - calcium comes out of cells in blood sample

Answer 72

Thirst, polyuria * Nausea * Constipation (gut isnt working properly)

Answer 73

Malignancy (Lymphoma, bone mets) Primary Hyperparathyroidism ***^^^^Cause 90% of all hypercalcaemia*** Thiazides Diuretics (make you retain calcium)

Answer 74

Low PTH so Decreased Bone Resorption Decreased Ca2+ reabsorption Decreased Ca2+ absorption

Answer 75

Intravenous normal saline ==> *Reverses dehydration* (do first **IV bisphosphonates** (most effective,) *block osteoclastic bone resorption* ===> (slower acting though) **Calcitonin** interferes with renal tubular reabsorption of calcium, ==> more immediate. All to stop more calcium entering the blood, and to loose it in the Kidney!

Answer 76

Symptoms Painful *bones* Painful bone condition – typically **osteitis fibrosa cystica** Renal stones Calcium deposition in renal tubules causes **polyuria** and **nocturia** Can lead to **kidney stones** and kidney failure

Answer 77

**Psychiatric moans** – effects on nervous system - Fatigue - Depression **Abdominal groans** – GI symptoms - Nausea - Constipation - Indigestion - Polyuria - Polydipsia (thirst)

Answer 78

~1 in 1000 have mild asymptomatic hypercalcaemia Typically affects older women Eradication of underlying malignancy is crucial for continued maintenance of normocalcaemia.

Answer 79

If calcium is TOO HIGH, the QT interval gets SHORTER If calcium is TOO LOW, the QT interval gets LONGER

Answer 80

It's elevation of parathyroid hormone (PTH) due to hypocalcaemia.

Answer 81

Caused by **Insufficient vitamin D or chronic renal failure** ==> low absorption of calcium from the intestines, kidneys and bones, ==> Causes hypocalcaemia: ==> So parathyroid secretes More PTH, so Parathyroid glands become more bulky. **Serum Calcium and Phosphate will remain low but PTH will be high**

Answer 82

Serum Calcium Serum PTH 25-hydroxyvitamin D level Eradication of underlying malignancy is crucial for continued maintenance of normocalcaemia.

Answer 83

* Primary – excessive PTH secretion ○ Usually caused by single parathyroid adenoma

Answer 84

Development of parathyroid hyperplasia (more cells) after long-standing secondary hyperparathyroidism most commonly in renal disease So PTH will remain high even with calcium is high (phosphate is also high) Plasma calcium and PTH are both raised Treated by parathyroidectomy

Answer 85

by marked hyperglycaemia, hyperosmolality and mild/no ketosis Basically just mental dehydration

Answer 86

Hyperosmolarity = the loss of water making the blood more concentrated than usual. ==>blood has a high concentration of salt (sodium), glucose, etc ***draws the water out of the body's other organs, including the brain.*** *In the case of Hyperglycaemia, high blood glucose makes you wee loads, dehydrating you, and drawing water out of bodies organs*

Answer 87

HHS is seen most commonly in older people and, in the US, those of African-American ethnicity with diabetes. However, HHS is now being seen in younger adults and even in children/teenagers, often as the initial presentation of type 2 diabetes

Answer 88

Infection is the most common cause, ***mainly UTIs/pneumonia*** ***Diabetes that is uncontrolled*** Or any trauma that provokes the release of counter-regulatory hormones (catecholamines, glucagon, cortisol, and growth hormone) and/or compromises water intake - eg MI/ Stroke/Sepsis *In elderly patients, being bed-ridden and having an altered thirst response compromise access to water and water intake, leading to severe dehydration and HHS.*

Answer 89

Illness, bed ridden, diabetes, older age. Little access to water

Answer 90

HHS is extreme elevations in serum glucose concentrations and hyperosmolality , but **no ketosis.** Seen in T2DM, where insulin produced is *sufficient to suppress lipolysis and ketogenesis* but not enough to promote glucose regulation

Answer 91

Consider a diagnosis of hyperosmolar hyperglycaemic state (HHS) in any patient who is **unwell and has a raised blood glucose.** Look for - **Hypovolaemia** - **Marked hyperglycaemia** (≥30 mmol/L [≥540 mg/dL]) **without significant hyperketonaemia** (ketones ≤3 mmol/L) or significant acidosis - **High serum osmolality** (usually ≥320 mOsm/kg [≥320 mmol/kg]).

Answer 92

Polyuria Polydipsia Hypothermia Weakness Dehydration Acute cognitive impairment measure GCS Signs of the underlying cause. *- Common causes include myocardial infarction, sepsis, and stroke*

Answer 93

Blood glucose -- v high >30mmol/L Blood ketones - To make sure DKA is not involved Venous Blood gas Calculate Serum osmolality ECG Full blood count U and Es

Answer 94

Positive for HHS is >320 mOsm/L

Answer 95

A mild acidosis (pH >7.3, bicarbonate >15 mmol/L due to renal impairment secondary to dehydration. =====>Lactic acidosis may be present due to sepsis. Use a venous blood gas to monitor the patient’s biochemical progress (urea, electrolytes, glucose, serum osmolality, bicarbonate)

Answer 96

Urinalysis - looks for symptoms for UTI, and look for ketones to rule out DKA Cardiac enzyme test - Look for Troponin T or I if positive MI

Answer 97

Diabetic Ketoacidosis Latic Acidosis Alcohol Ketoacidosis

Answer 98

Start IV fluids as soon as you suspect hyperosmolar hyperglycaemic state (HHS) Requested Critical care support if you cant get IV access Give 1 L of 0.9% sodium chloride (normal saline) over 1 hour. Can give more rapidly if SBP is <90 mmHg Think about treating underlying cause!!! MI, Stroke/Sepsis

Answer 99

***Start intravenous fluids before giving insulin.*** If not, could cause CV collapse * Give 0.05 units/kg/hour if blood ketones >1 mmol/L and ≤3.0 mmol/L and the patient is not acidotic (venous pH ≥7.3 and bicarbonate >15.0 mmol/L),* * Give 0.1 units/kg/hour if blood ketones >3.0 mmol/L or ketonuria (2+ or more) with a pH <7.3 and bicarbonate <15 mmol/L (i.e. mixed diabetic ketoacidosis and HHS),* Think about treating underlying cause!!! - eg MI, Stroke/Sepsis

Answer 100

Hourly blood glucose for the first 24 hours hourly sodium, potassium, urea, and calculated serum osmolality for the first 6 hours, which can be reduced to every 2 hours after 6 hours if serum osmolality is decreasing by 3 to 8 mOsm/kg/hour (3-8 mmol/kg/hour) Continuous cardiac monitoring if necessary Vital signs including early warning score (EWS).

Answer 101

Insulin related Hypoglycaemia - Treatment related Hypokalaemia - due to all the insulin you're giving

Answer 102

Graves' disease Other causes are: - multinodular goiter, toxic adenoma - inflammation of the thyroid, - --eating too much iodine, -too much synthetic thyroid hormone. A less common cause is a pituitary adenoma.[

Answer 103

Graves Disease, makes up for 50-80% of cases

Answer 104

In iodine-sufficient parts of the world, the prevalence of overt hyperthyroidism around **1%** **6 times more common in women than men** *Any age can be affected*

Answer 105

Stimulation of the thyroid by **TSH receptor antibodies** Combination of genetic and environmental risk factors.

Answer 106

No specific genes but HLA linked. Complex pattern of inheritance. Defect in certain gene regions such as human leukocyte antigen (HLA)-DRB1*16:02 allele

Answer 107

Formation of **IgG** antibodies to the TSH receptors on the Thyroid Gland

Answer 108

HYPOTHALAMUS: Releases THYROTROPIN RELEASING HOROMONE ====> causes ANTERIOR PITUITARY GLAND TO RELEASE THYROID STIMULATING HOROMONE (THYOTROPIN) The binding of TSH to thyroid gland promotes every aspect of T3 and T4 production - *Iodine pumping, Thyroglobulin synthesis, releasing of thyroid hormone in the blood* T3 - NEGATVIE FEEDBAKC ON THE ANTERIOR PITIUARY TO STOP REALSING TSH Thyroxine = T4 (4 iodine) Triiodothronine = T3 (3 iodine)

Answer 109

Thyroxine = T4 (4 iodine) Triiodothronine = T3 (3 iodine) T3 is more active than T4 (half life of 1-2 days vs 6-8 days) **T4 is generally converted into T3** by enzymes known as deiodinases in target cells Thus its often said that **T3 is the major thyroid hormone**, despite the fact that the concentration of T4 in the blood is much higher than that of T3 *T4 can be thought of as a RESERVOIR for additional T3*

Answer 110

More Na/KATPases - seen in temperature homeostasis --> More heat produced - MORE Moving **Cholesterol from Plasma to cells** (so in Hypothyroidism there is high plasma cholesterol) -MORE Gluconeogenesis -MORE Bone resorption -MORE Fat Oxidation -Increase Heart Rate -Negative Feedback on TSH

Answer 111

* Female * Family History/Genetic – association with HLA-B8, DR3 and DR4 * Stress * Smoking Amiodarone

Answer 112

Serum **IgG antibodies called TSH receptor stimulating antibodies (TRAb)** bind to TSH receptors on the thyroid and stimulate T3/4 production This results in excess secretion, hyperplasia of the thyroid follicular cells, hyperthyroidism and goitre TSH receptor autoantibodies cause thyroid hormone hyperproduction as well as thyroid hypertrophy and hyperplasia of thyroid follicular cells. ===> Leads to clinical manifestations of hyperthyroidism

Answer 113

- **Tremor** - Tachycardia/AF - Goitre - **Hair loss/thin hair** - **Lid lag/retraction** - Hyperkinesia - increased muscle activity - **Exophthalmos** – bulging of the eye out of the orbit

Answer 114

**** Weight loss * Irritability * Heat intolerance*** * Insomnia * Diarrhoea * Sweats * Palpitations Anxiety ***Pretibial myxedema*** specific to Grave's

Answer 115

TSH levels test - it would be low, as lots of T3 and T4 being produced that is leading to the symptoms - so negative feedback.

Answer 116

If serum TSH is normal or even (slightly) elevated in the presence of hyperthyroid symptoms and elevated free T4 level, consider other causes of hyperthyroidism such as a TSH-producing pituitary tumour and partial resistance to thyroid hormone

Answer 117

Where the **immune system attacks the thyroid** within 6 months after giving birth. So rise in T3 and T4 **(hyperthyroidism),** Followed by a decrease in T3 and T4, (hypothyroidism) *^^similar to De Quaverain* Will normally correct over 12 months, but may need treatment

Answer 118

Lithium (used to treat Bipolar) Amiodarone (used to treat arrhythmias - can cause either Hyper or Hypo) Interferons (used to treat cancer)

Answer 119

Measure TSH receptor antibodies (TRAb) not available in all places

Answer 120

Serum T4 or T3, thyroid isotope scan to see size, ultrasound of thyroid

Answer 121

Stimulates the release of it as it stimulates TSH receptors, which can lead to Gestational hyperthyroidism - resolves in second trimester

Answer 122

Toxic multinodular goitre (benign tumour on thyroid gland,) Gestational hyperthyroidism Iodine induced hyperthyroidism TSH producing pituitary adenoma

Answer 123

**Beta blockers** for rapid system control in attacks Decreases SNS activation ***Carbimazole*** – anti-thyroid drug decreases the synthesis new thyroid hormone **Potassium iodide** – to acutely block release of thyroid hormone from gland - Damage follicular cells (ionisation) **Thyroidectomy** – removal of the thyroid gland leaving a small remnant in order to maintain thyroid function

Answer 124

It should not be prescribed to pregnant women, as it can be toxic. Prescribe Propylthiouracil (a different Anti thyroid drug, also inhibits T4==> T3

Answer 125

* Carbimazole – anti-thyroid drug ○ Blocks thyroid hormone synthesis and also have immunosuppressive effects which affect Graves’ disease

Answer 126

Severe side effect is agranulocytosis --- a deficiency of granulocytes in the blood, causing increased vulnerability to infection. Due to the fact is depresses the activity of the bone marrow ***YOU MUST TELL THE PATIENTS THIS, AND THAT THEY MUST STOP THIS IF THEY GET SIGNS OF INFECTIONS EG SORE THROAT***

Answer 127

Thyroid crisis (Thyroid storm) Rare life threatening condition - Hyperpyrexia - Tachycardia - Extreme restlessness Delirium, Coma, death

Answer 128

monitor replacement thyroxine therapy with serum TSH at 6-week intervals until stable, then with serum TSH at least annually.

Answer 129

**Bone mineral loss** - if left untreated - in extreme cases, osteoporosis Atrial fibrillation - can lead to thromboembolic complications and stroke Congestive heart failure.

Answer 130

Primary - Problem with Thyroid Gland Central/Secondary - Problem with Pituitary Gland Primary has prevalence range between 0.2-5.3%. More common in women and white people. Incidence increases with age **Central accounts for less than 1% of hypothyroidism**. Affects population equally. 1 in 100,000

Answer 131

Primary: - Hashimoto's disease - most common cause of primary. - Iodine deficiency - common in developing world and mountainous areas - Sub-acute granulomatous (De Quervain's - Other infections - **Drug induced** Central: Pituitary adenomas (most common) Other infections Radiation

Answer 132

**Subacute Granulomatous disease** - caused by a virus eg mumps 1. First, T3 and T4 will lead out of colloid - Symptoms of Hyperthyroidism 2. Then, it will be used up and Thyroid Gland can't make more T3 and T4 - Symptoms of HYPOthyroidism eg **Caused by viruses like Mumps, Coxsaccie virus, Adenovirus**

Answer 133

Iodine deficiency, female, middle age, family history, treatment, - turners and down syndrome. - radiation therapy to head and neck, amiodarone and lithium use (both interfere with Thyroid hormone synthesis)

Answer 134

Amiodarone is structurally similar to thyroxine and also contains iodine, Amiodarone is an antiarrhythmic medication used to treat and prevent a number of types of irregular heartbeats (including atrial fibrillation which this lady has). It is known to cause thyroid problems, including both hyperthyroidism and hypothyroidism.

Answer 135

It is caused by autoimmune inflammation of the thyroid gland. It is associated with **antithyroid peroxidase (anti-TPO) antibodies** and **antithyroglobulin antibodies** Initially it causes a goitre after which there is atrophy of the thyroid gland.

Answer 136

Thyroid peroxidase stimulates MIT (Monoiodotyrosine) and DIT (Diiodotyrosine) binding forming T3 and T4. Thyroglobulin basically **acts a storage peptide in the colloid**, storing until T3 and T4 they are ready to be used

Answer 137

**Bradycardia** Unexplained weight gain **Slow reflexes, Ataxia** Round Puffy face **Immobile Ileus** - temporary arrest of Intestinal peristalsis **ASCITES** - fluid in abdomen

Answer 138

**Hoarse voice** Goitre - *lump or swelling on neck from thyroid gland* Weight gain **Constipation** **Cold intolerance** Menorrhagia – heavy periods **Tiredness** Lethargy Poor memory Puffy eyes Arthralgia/myalgia Symptoms of anaemia

Answer 139

Thyroid function test Measure Free T4 and TSH levels ○ Primary - High TSH, low free T4 ○ Secondary – inappropriately low TSH, low T3/T4 (since issue is in pituitary) In Hashimoto’s Thyroid antibodies ○ Thyroid antibodies (TPO) - **Look for Thyroperoxidases and Thyroglobulin antibodies** ***(TPO antibody more common than antithyroglobulin)***

Answer 140

Look for serum chloresterol and Blood glucose Serum Cholesterol would be high, *as T3 moves it from the blood* Fasting blood glucose may also be elevated (Hypothyroidism can be assosiated with T1DM)

Answer 141

Central hypothyroidism/Primary hypothyroidism, vice versa depending on what you are looking for Depression Anaemia

Answer 142

Thyroid hormone replacement agents such as **levothyroxine** Life long, oral, Start 25mcg (microgram) LEVOTHYROXINE IS SYNTHETIC T4 With primary, Primary – titrate dose *until TSH normalises* Aim is to get **TSH to >0.5** IN secondary, treat underlying pituitary issue!

Answer 143

Check TSH every 8 weeks after adjusting a dose - it takes that long for synthetic T4 to have an effect. Primary - Stable patients need TSH measured every 12 months Secondary – TSH will always be low, **monitor T4**

Answer 144

Angina Complications in pregnancy

Answer 145

Papillary Carcinoma 62% Follicular Carcinoma 17% Medullary Carcinoma Anaplastic is most deadly **PFM**

Answer 146

More common in women than in men. Most likely age to be diagnosed is 45-54.

Answer 147

Genetic alterations are thought to underlie thyroid cancers

Answer 148

Head and neck irradiation, female sex, Family history of thyroid cancer,

Answer 149

**THINK SIGNS OF TUMOUR ON THYROID GLAND** * Lymph node metastases * Thyroid nodule with history of progressive increase in size Enlarged lymph nodes **Tracheal Deviation Hoarse voice Dysphagia** ***Difficulty swallowing*** Weight loss

Answer 150

* Thyroid nodules – increased size, hardness and irregularity * Dysphagia * Hoarseness of voice – tumour pressing on recurrent laryngeal nerve Symptoms of Hyper/Hypothyroidism

Answer 151

**THINK -NEED TO LOOK AT THYROID GLAND, AND TREAT SYMPTOMS** * Fine needle aspiration cytology biopsy best for distinguishing between benign and malignant thyroid nodules * Thyroid ultrasound * Thyroid Function tests – hyper/hypothyroidism needs to be treated before surgery - Look for TSH

Answer 152

Free T3 and T4

Answer 153

Total thyroidectomy with neck dissection for local nodal spread Ablative radioiodine subsequently given – taken up by remaining thyroid tissue or metastatic lesions

Answer 154

Anaplastic and lymphoma: ○ External radiotherapy may produce brief respite ○ Otherwise treatment is largely palliative

Answer 155

Check to see if tumour has metastised

Answer 156

A Benign thyroid nodule

Answer 157

Airway obstruction, surgery related hypoparathyroidism, surgery related recurrent laryngeal nerve damage , secondary tumours

Answer 158

Adrenal glands consist of: **Outer cortex – steroids**(aldosterone, cortisol and androgens) Zona glomerulosa (G) – Mineralocorticoids e.g. aldosterone Zona fasciculata (F) – Glucocorticoids e.g. cortisol Zona reticularis (R) – Androgens (sex hormones) GFR – Makes Good Sex Inner medulla – catecholamines Under sympathetic control and secretes catecholamines e.g. adrenaline and noradrenaline

Answer 159

Follicle-stimulating hormone (FSH) Luteinising hormone (LH) Adrenocorticotrophic hormone (ACTH) Thyroid-stimulating hormone (TSH) **Prolactin (PRL) Growth hormone (GH)** FLAT PIG

Answer 160

It should not be prescribed to pregnant women, as it can be toxic. Prescribe Propylthiouracil (a different Anti thyroid drug, also inhibits T4==> T3 *Also can cause Agranulocytosis, more on that later*

Answer 161

Cushing’s Syndrome is used to refer to the **signs and symptoms that develop** after prolonged abnormal elevation of cortisol. *Cushing’s Disease causes a Cushing’s syndrome, but Cushing’s Syndrome is not always caused by Cushing’s Disease.*

Answer 162

Cushing’s Disease is used to refer to the **specific condition where a pituitary adenoma (tumour) secretes excessive ACTH.** *(Adrenocorticotropic hormone)* Responsible for 70-80% **ENDOGENOUS** of Cushing syndrome *Cushing’s Disease causes a Cushing’s syndrome, but Cushing’s Syndrome is not always caused by Cushing’s Disease.*

Answer 163

More Common in Women Age 20-50 is most likely diagnosis

Answer 164

Either ACTH *(Adrenocorticotropic hormone)* Dependant 1. adrenocorticotrophic hormone (ACTH)-secreting pituitary adenoma - Cushing's Disease 2. Ectopic Cushing’s Syndrome – coming from elsewhere Due to paraneoplastic syndrome e.g. small cell lung cancer producing ACTH or Non ACTH Dependant: 3. Exogenous - Oral Steroid Use **(Iatrogenic)** 4. An Adrenal adenoma or carcinoma, a tumour on the adrenal gland that releases Cortisol Think Tumours of various locations, and exogenous steroid use

Answer 165

Most common cause of Cushing's **Syndrome** is is exogenous therapeutic steroid use Then the second most common cause of Cushing’s syndrome is Cushing’s disease

Answer 166

exogenous corticosteroid use, pituitary or adrenal adenoma, or adrenal carcinoma.

Answer 167

○ Cataracts ○ Ulcers ○ Striae – purple strokes on skin ○ **Hypertension and hyperglycaemia (due to impaired glucose tolerance)** ○ Increased risk of infection – dampening of inflammatory response ○ Glucosuria - *due to the hyperglycaemia*

Answer 168

Truncal/central obesity Moon face - FACIAL PLETHORA Buffalo hump – fatty hump on upper back Acne Hirsutism – unwanted male pattern hair growth in women Thin skin/bruising - EASY BRUSING Osteoporosis

Answer 169

Late night salivary cortisol (would be elevated) Blood glucose (would be elevated) Urine pregnancy test (need to confirm not pregnant) 1 mg overnight dexamethasone suppression test morning cortisol Positive result : >50 nanomol/L

Answer 170

pituitary MRI CT scan of adrenals

Answer 171

Decreased Cortisol levels in blood, due to negative feedback that Dexamethasone would exert on the hypothalamus and the pituitary gland (so less ACTH and CRH as well) It would suppress the morning spike of cortisol that you see when you retest in the morning.

Answer 172

If they have Cushing's Disease, (Adenoma on Pituitary Gland), Then ACTH will still be high due to the tumour, so cortisol will not be suppressed. (Dexamethasone won't have made a difference) morning cortisol >50 nanomol/L

Answer 173

a) Low levels of ACTH, but high levels of Cortisol in the blood b) High levels of both ACTH and cortisol in the blood c) Low levels of Cortisol and low levels of ACTH -*as In Cushing’s Disease (pituitary adenoma) the pituitary still shows some response to negative feedback and 8mg of dexamethasone is enough to suppress cortisol.*

Answer 174

* Pseudo-Cushing’s syndrome ○ Caused by alcohol excess ○ Resolves after 1-3 weeks of alcohol abstinence Obesity Poorly controlled T2DM Metabolic Syndrome

Answer 175

Depends on the cause! If Exogenous, stop the steroids or surgery to remove relevant tumour on either Pituitary gland/ or Ectopic. **trans sphenoid removal** Remove adrenal glands (adrenalectomy) Give drugs

Answer 176

**Steroidogenesis inhibitor** (osilodrostat, ketoconazole, metyrapone, mitotane, etomidate), **Glucocorticoid receptor antagonist** (mifepristone) is occasionally used for mild hypercortisolism, or short term for severe hypercortisolism, before other therapies are undertaken

Answer 177

Nelson's Syndrome: removed Adrenal glands means No Cortisol so nothing to negatively feedback on ACTH from Pituitary, so too much ACTH ACTH can lead to: § causing a bronze pigmentation of the skin, visual disturbances and headache

Answer 178

Measure Cortisol - Patients with a postoperative morning cortisol of <55 nanomol/L (<2 micrograms/dL) are considered to be in remission and can transition into long-term follow-up Patients with Cortisol >138nanomol need further evaluation/therapy Recheck patients with Cortisol 55-138 nanomol the next morning.

Answer 179

Adrenal Insufficiency secondary to adrenal suppression Cardiovascular disease Hypertension Diabetes Mellitus **imunosuppression** - as high levels of cortisol lead to immunosuppression

Answer 180

Acromegaly is a rare, chronic disease caused by excessive secretion of growth hormone (GH), usually due to a pituitary somatotroph adenoma.

Answer 181

Acromegaly = excessive production of growth hormone **occurring in adults after fusion of the epiphyseal plates** Gigantism = excessive production of growth hormone occurring **in children before fusion of the epiphyses of long bones** - gonna grow lots

Answer 182

Acromegaly is often recognised in middle-aged men or women but can occur at any age. **The disease is equally distributed between both sexes.** Global prevelance is 5.9 cases per 100,000 people

Answer 183

Due to a **pituitary somatotroph adenoma** in 95-99% of cases. Prolactin co-secreted in 25% of cases . Activating mutation in the **GNAS1 gene** is shown in 30% to 40% of somatotroph adenomas

Answer 184

Dysregulation of *hormones transcription factors growth factors* that all act on the pituitary can promote tumour development. Pituitary somatotroph adenomas chronically secrete excessive GH, **which stimulates insulin-like growth factor 1 production** Function of GH: * Direct – acts on tissues such as liver, muscles, bones and fat to **induce metabolic changes**

Answer 185

* Indirect – IFG-1 ○ Stimulate growth by protein synthesis and cell division ○ Increases lipolysis and calcium retention ○ Decrease blood glucose ○ *Stimulate hypertrophy and hyperplasia of bone, skeletal muscle etc.*

Answer 186

* Morphological facial changes: frontal bossing, enlarged nose, prognathism (protuding jaw) and separation of teeth, macroglossia (massive tongue), large ears and nose * Thick skin, *+ Skin tags* * **Obstructive sleep apnoea** * Deep voice * **Hypertension** * **HF** Visual field defect (“bitemporal hemianopia”) Elevated IGF-1, elevated GH

Answer 187

**Sweating** **Headaches, due to pressure locally** Increase in hands and feet (Show and ring size) **Oligo/amenorrhea** Joint pain Development of **Skin Tags** Fatigue *More GH ==> Body works harder, so increase in Temperature/Sweat. Also, increased GH leads to more oil and sweat glands*

Answer 188

Serum GH and Serum IGF-1

Answer 189

* Oral glucose tolerance test ○ Normally a rise in blood glucose *will suppress GH levels* ○ Give glucose and then test GH levels – **if they remain high** this is diagnostic for acromegaly

Answer 190

* 1st line - Transphenoidal surgical resection to remove the adenoma and correct compression of surrounding structures e.g. optic chiasm ○ Complications § Hypopituitary § Infection § Diabetes Insipidus

Answer 191

* Somatostatin analogues e.g. **IM octreotide/lanreotide** – inhibit GH secretion § Given by s/c or IM injection

Answer 192

Monitor GH and IGF-1 levels. Monitor for complications of acromegaly, ie cardiac complications

Answer 193

Cardiac complications Hypertension **Sleep apnoea** Osterartiucalr complications ie arthritis **Impaired glucose tolerance and diabetes mellitus**

Answer 194

Prolactin-secreting pituitary adenomas (Prolactinomas) *Prolactinomas are the most common type of pituitary adenoma, constituting about 50% of these tumours*

Answer 195

There are three vital points when assessing a tumour: Pressure on local structures: e.g. optic nerves Pressure on the normal pituitary (🡪 hypopituitary) Functioning tumour (🡪 Prolactinoma, acromegaly or cushings)

Answer 196

Headaches (due to stretching of the Dura) Visual field defects Cranial Nerve palsy Hydrocephalus - *accumulation of cerebrospinal fluid (CSF) within the brain* Pressure on Hypothalamic centres - so increased thirst, obesity, early puberty in children (precocious) Cerebrospinal fluid rhinorrhoea (downward extension through the pituitary fossa) 🡪 CSF dripping out of the nose

Answer 197

dopamine, so tumours inhibiting dopamine can cause hyperprolactinaemia.

Answer 198

In patients with hypothyroidism, an increase in prolactin is due to **compensatory increase** in the discharge of central hypothalamic TRH as a result of low thyroxine ==> **Can lead to Hyperprolactinaemia**

Answer 199

Prolactin-secreting adenomas are more frequent in women between 20 and 50 years old, mainly during the child-bearing years, with an estimated ratio of frequency between women and men of 10:1. **SO WOMEN ARE 10 X MORE LIKELY TO GET IT THAN MEN** 30-60 years is when men are most likely to get it

Answer 200

oestrogen therapy (Also, Primary Hypothyroidism due to high levels of TRH)

Answer 201

Increased prolactin ==> increased milk production in the breast (also **galactorrhoea)** Menstruation stops **(amenorrhoea)** *Infertility/ reduced fertility* Visual deterioration - temporal hemianopia

Answer 202

as prolactin inhibits GnRH (Gonadotrophic releasing Hormone)

Answer 203

* Decreased libido, erectile dysfunction* Visual deterioration - temporal hemianopia

Answer 204

Serum prolactin - *would be elevated* Pituitary MRI Computerised visual field examination

Answer 205

Dopamine agonist **(inhibits Prolactin)**– CABERGOLINE or BROMOCRIPTINE

Answer 206

Visual field impairment, **Anterior pituitary failure/diabetes insipidus** Hypopituitarism

Answer 207

Cushing's Disease - PA = too much ACTH = too much cortisol Acromegaly - PA - Too much growth hormone = too much IGF-1 Prolactinoma - PA - Too much prolactin produced Secondary Hyperthyroidism - Too much TSH - Too much Thyroxine

Answer 208

Aldosterone acts on the kidneys Extracellular volume goes up Renal blood pressure goes up More Na+ and water retention K+ excretion Decreased Extracellular fluid of K+

Answer 209

Conn’s syndrome refers ONLY to **PRIMARY Aldosterone producing adenoma** A tumour in the adrenal gland!!

Answer 210

2.6% Incidence is rising

Answer 211

30% Unilateral forms - Treat with Laparoscopic adrenalectomy 70% Bilateral forms - treat with aldosterone antagonistic medicines

Answer 212

family history of Primary aldersosteronism and family history of early onset (e.g., <40 years) hypertension and/or stroke

Answer 213

* **Excess production of aldosterone, independent of RAAS causes** ○ **Increases K+ loss, Na+ and water retention** 🡪 raised BP ○ Decreased renin release *○ Hypokalaemia*

Answer 214

Hypertension Increased risk of cardiac arrhythmias, particularly in patients with cardiac disease Symptoms **Polyuria, Nocturia** Lethargy/tiredness Muscle weakness Paraesthesia Headaches Mood disturbance

Answer 215

Plasma potassium - Low in approx. 20% of patients with PA

Answer 216

Aldosterone : Renin ratio Positive result would be **>70 for aldosterone** in picomol/L *(High aldosterone, low renin, as primary)*

Answer 217

Essential hypertension Thiazide induced hypokalaemia in a patient with essential hypertension Renal artery stenosis Secondary hyperaldosteronism (too much renin and aldosterone)

Answer 218

* Laparoscopic adrenalectomy Prescribe * **Oral spironolactone** – *aldosterone antagonist* (K+ sparing diuretic)

Answer 219

* BP, plasma electrolytes, and aldosterone and renin levels should be monitored every 6 to 12 (after adrenalectomy) Look for any delveloping hyperkalaemia

Answer 220

Renin is produced by *Juxtaglomerular cells* in Kidney, in response to **Decreased renaal perfusion at the Juxtaglomerular apparatus** ***(aka Low Blood pressure*** Renin is inhibited by Atrial natriuretic peptide (ANP), released by stretched atria in response to increases in blood pressure.

Answer 221

Renin cleaves **angiotensinogen** into angiotensin 1, *Angiotensin 1* becomes *Angiotensin 2* by **Angiotensin converting enzyme ACE**, This reaction happens in the lungs, where ACE is made.

Answer 222

- ALDOSTERONE SECRETION FROM THE ADRENAL CORTEX (zona Glomerulosa) - ADH (vasopressin) from the Posterior Pituitary Gland - More sympathetic activity, ○ Increased release from noradrenaline Arteriolar vasoconstriction

Answer 223

Acts on the **Principle cells of the collecting duct** Causes vasoconstriction *(greater in the efferent arteriole)* **Increased Na+ and Cl- reabsorption AND INCREASED K+ SECRETION INTO URINE , and H2O retention** **Increases Na+ reabsorption in exchange for K+**

Answer 224

Occurs when there is excessive **Renin** (and hence angiotensin II) which stimulates the adrenal glands to produce more **aldosterone**

Answer 225

**Renal artery Stenosis** Renal artery obstruction Heart Failure Which leads to *Blood pressure in the kidneys being* ***disproportionately lower than the blood pressure in the rest of the body, from decreased renal perfusion*** ===> Too Much Renin Released, leading to too much aldosterone release *(hyperaldosteronism)*

Answer 226

High aldosterone and low renin

Answer 227

High aldosterone and high renin indicates secondary hyperaldosteronism

Answer 228

Stroke, MI, heart failure, AF, impaired renal function, *aldosterone antagonist induced hyperkalaemia* - if you give too much treatment or Hypokalaemia, if it is left untreated. Monitor for these!

Answer 229

Adrenal glands have been damaged, resulting in reduced **secretion of cortisol and aldosterone.** Also called **primary adrenal insufficiency.**

Answer 230

Worldwide = TB In UK = Autoimmune adrenalitis

Answer 231

Problem with the pituitary gland means not enough ATCH is secreted, so not enough Cortisol is secreted from the adrenal glands. Either due to Surgery, Congenital deformation, infection Or long term steroid use being suddenly stopped, HPA axis hasn't "woken up" and started making its own steroids again. ( End of Use) ABCDE Drug reaction

Answer 232

Due to **inadequate CRH** Being released from the Hypothalamus *Corticotropin-releasing hormone*

Answer 233

Normally because people get taken off steroids too quickly, and not enough time for Hypothalamus to *wake up again* and start releasing CRH

Answer 234

○ Addison’s - autoimmune adrenalitis (90% of cases) **most common in the UK** ○ Adrenal TB - **most common worldwide** ○ Surgical removal of adrenal glands

Answer 235

1. **Female sex,** 2. adrenocortical autoantibodies *ie 21 Hydroxylase antibody enzyme adrenal haemorrhage, autoimmune diseases, coeliac disease Adrenalectomy??

Answer 236

Destruction of Entire adrenal cortex resulting in reduced glucocorticoid (cortisol), mineralocorticoid (aldosterone) and androgen production **Adrenal antibodies – 21-hydroxylase** - *involved in biosynthesis of aldosterone and cortisol.* Leads to symptoms, and Increased CRH and ATCH levels

Answer 237

Hyperpigmentation of the skin

Answer 238

* Postural hypotension caused by salt and water loss **Lacking aldosterone** * Bronzed Hyperpigmentation caused by excess ACTH in primary hypoadrenalism * Vitiligo and loss of body hair in females due to dependence on adrenal androgens * Hypoglycaemia - Steroids can increase blood sugar REMEMBER – Tanned, Tired, Toned and Tearful

Answer 239

**Lethargy** Lack of steroids Feeling faint - LOW BP due to low Aldosterone Dehydration - Due poor water retention due to Poor aldosterone **Weight Loss - due to lack of steroids** Abdominal Pain Depression/tearfullness * Impotence Amenorrhoea - stopped period - due to lack of Androgens

Answer 240

Presentation of Severe Addison's, *where the absence of steroid hormones* result in a life threatening presentation. Very unwell!! They present with: Reduced consciousness/confusion Hypotension Hypoglycaemia, **hyponatraemia and hyperkalaemia** Muscle cramps Hypovolemic Shock

Answer 241

Urgently! Give IV Fluids, and IV Hydrocortisone Correct any hypoglycaemia

Answer 242

Morning Serum cortisol - less than <140 nanomols/L Look at ATCH levels - ○ **HIGH ACTH with low or normal cortisol** confirms primary hypoadrenalism ○ **LOW ACTH and cortisol** indicate secondary or tertiary hypoadrenalism

Answer 243

* **Short ACTH stimulation test** (Synacthen test) ○ Take baselines cortisol ○ Give ACTH (synACTHen) then measure cortisol level – § In Addison’s – ***cortisol remains low after giving ACTH*** * Adrenal antibodies – **21-hydroxylase** - *involved in biosynthesis of aldosterone and cortisol.

Answer 244

In addisons, would have high plasma renin , low sodium, high potassium) due to low aldosterone

Answer 245

Hyperthyroidism Adrenal suppression due to drugs Central (secondary or tertiary) adrenal insufficiency (pituitary or hypothalamic lesions)

Answer 246

* Glucocorticoids - oral **Hydrocortisone**/prednisolone to replace cortisol Mineralocorticoids - **fludrocortisone** to replace aldosterone

Answer 247

Evaluate annually to judge adequacy of glucocorticoid and mineralocorticoid replacement. Look at serum electrolytes measurement to monitor mineralocorticoid replacement. **Sick day rules are really important in anyone taking long term steroids - patients must double the dose when they are sick!**

Answer 248

Long QT interval

Answer 249

As a **Concentration** so high serum or urine osmolarity means **high concentration** of Solutes in the serum or urine A Low Urine osmolarity would be low concentration of solutes in urine, as seen in Diabetes Insipidus

Answer 250

Commonest type of monogenic diabetes (~1% diabetes) Diagnosed <25y Autosomal dominant Non-insulin dependent Single gene defect altering beta cell function Tend to be non-obese **Monogenic - caused a mutation of one gene only**

Answer 251

Positive for HHS is >320 mOsm/kg

Answer 252

Continued secretion of ADH despite plasma being very dilute 🡪 water retention, excess blood volume and hyponatraemia Too much ADH

Answer 253

Malignancy eg Cancer tumours that secrete Ectopic ADH Drugs Head Injury, Meningitis

Answer 254

lead to ectopic secretion of ADH. Seen in ***Small cell carcinomas of the lungs, Prostate and Pancreatic**

Answer 255

Opiates, Carbamazepine (anti epileptic) . Chlorpropamide (to treat diabetes) SSRIs Thiazide diuretic

Answer 256

The listed causes *(Malignancy, Drugs, Head Injury)* Also Recovering from major surgery Including age >50 years, nursing home residence, Presence of a postoperative state, Pulmonary conditions (e.g., pneumonia), CNS *(eg MS)* disease Trauma

Answer 257

a) Excess ADH ==> insertion of aquaporin 2 increases ==> water retention ==> **Dilution of Blood plasma** . ***This in itself can lead to hyponatraemia*** ADH acts on the collecting ducts and distal convoluted tubules of the Nephron

Answer 258

But more water means **less RAAS so les Aldosterone released**, so more **Na+ secretion and loss into urine** (body is removing sodium from blood that already has a low concentration of sodium) ==> NORMOVOLAEMIC yet HYPONATRAEMIC *The excessive water reabsorption is not usually significant enough to cause a fluid overload, therefore you end up with a* ***“euvolaemic hyponatraemia"***

Answer 259

Not usually. The excessive water reabsorption is not usually significant enough to cause a fluid overload, therefore you end up with a *“euvolaemic hyponatraemia”* You See low serum osmolarlty and High urine osmolartity - concentrated sodium

Answer 260

Need to have an absence of hypovolaemia and hypervolemia No signs of **adrenal insufficiency or hypothyroidism** You also need to rule out Hyponatraemia in order to diagnose SIADH

Answer 261

* Concentrated urine * Mild dilutional hyponatraemia – could lead to fits and coma

Answer 262

* Reduction in GCS and confusion with drowsiness * Irritability * Headaches * Anorexia * Nausea/Vomiting

Answer 263

Test by giving with 1-2L of 0.9% saline – sodium depletion WILL respond, SIADH will NOT

Answer 264

Diagnostic Criteria for SIADH: - Hyperosmolar Urine - Hypo osmolar Serum - No hyper or hypovolaemia - Hyponatraemia Adrenal, Thyroid and renal function all normal

Answer 265

Serum Sodium - will be low Serum Osmolality - Will be low Serum urea Urine osmolality will be high Urine sodium will be high

Answer 266

* Treat underlying cause * Restrict fluid – to increase Na+ concentration

Answer 267

Demeclocycline – inhibits action of vasopressin on kidney * Vasopressin receptor antagonists (vaptans) – V2 blocker ○ Tolvaptan – used for treatment of hyponatraemia secondary to SIADH as promotes water excretion with no loss of electrolytes Oral furosemide – salt and loop diuretics if severe and to prevent circulatory overload

Answer 268

Maintaining the resting potentials in all muscles in the body, involving the heart

Answer 269

**Hypo - Everything Slows** a) Constipation b) Weakness/Cramps c) Arrhythmias and Palpitations

Answer 270

a) Smooth - Cramping b) Skeletal - Weakness/Flaccid Paralysis *(Due to over contraction of muslces, become totally drained of energy) c) Cardiac- Arrhythmias and arrest.

Answer 271

Uptake of K+ into cells Renal excretion – mainly controlled by aldosterone Extrarenal losses e.g. GI

Answer 272

The amount in the blood determines the excitability of nerve and muscle cells including the heart muscle (myocardium) When K+ levels in blood rise, this reduced the difference in electrical potential between cardiac myocytes and outside of the cells 🡪 **threshold for action potential significant decreased** 🡪 abnormal action potential 🡪 arrhythmias 🡪 cardiac arrest

Answer 273

Low levels of aldosterone in kidneys – adrenal insufficiency - as it gets rid of K+ in the urine Certain Drugs AKI - decreased filtration rate so more K+ is maintained in the blood

Answer 274

ACE inhibitors – block the binding of aldosterone to receptor Diuretics that spare K+ NSAIDs Heparin

Answer 275

Typically, asymptomatic until high enough to cause cardiac arrest Muscle weakness Flaccid paralysis Chest pain Light-headedness

Answer 276

Metabolic acidosis causing Kussmaul’s respiration – low, deep, sighing inspiration and expiration Tachycardia ECG abnormalities

Answer 277

U and Es ECG

Answer 278

Tall tented T waves *(Normally smaller secondary wave)* Wide, flat P waves *(Tiny initial wave)* Wide QRS complex *(Big main wave)* Look up a picture

Answer 279

Over 5.5mmol/L = hyperkalaemic Over 6.5mmol/l = MEDICAL EMERGENCY

Answer 280

Treat underlying cause Restrict Dietary potassium Restriction of drugs causing hyperkalaemia Loop diuretics e.g. **furosemide – increase urinary K+ excretion**

Answer 281

**Calcium gluconate** – decreases VF risk in the heart and protects myocardium by reducing excitability of cardiac myocytes **Insulin and dextrose** – drives K+ into the cells **Polystyrene sulphonate resin** – binds K+ in the gut decreasing uptake

Answer 282

Less K+ in the blood means that there a greater will be a greater-than-normal stimulus required for depolarization of the membrane to initiate an action potential. (The membrane is said to be **Hyperpolarised**) In heart, therefore the excitability of the myocyte decreases

Answer 283

Fasting, Anorexia High levels of ***ALDOSTERONE*** Increased renal excretion, bu Thiazides diuretics e.g. Bendroflumethiazide Loop diuretics e.g. furosemide GI losses – vomiting, severe diarrhoea and laxative abuse

Answer 284

Because the Majority of K+ excretion is through the kidneys **Aldosterone stimulates secretion of K+** Seen in Cushing’s and Conn’s

Answer 285

Usually asymptomatic Muscle weakness Cramps Tetany – intermittent muscle spasms Palpitations Constipation Some of those are also seen with Hypocalcaemia?

Answer 286

Serum K+ < 3.5mmol/L = hypokalaemia Serum K+ < 2.5mmol/L = MEDICAL EMERGENCY

Answer 287

U waves Small or inverted T waves Depressed ST segments Prominent U Wave Long PR Long QT Rhyme – You have no Pot (K+) and no Tea (T Wave) but a Long PR and a Long QT, FOR YOU (Prominent U wave)

Answer 288

Mild – Oral K+ e.g. oral Sando-K and spironolactone (K+ sparing) Severe- IV K+

Answer 289

A Carcinoid tumour is a **slow-growing** type of neuroendocrine tumour originating in the cells of the neuroendocrine system. Carcinoid syndrome is a paraneoplastic syndrome comprising the signs and symptoms that occur secondary to carcinoid tumours.

Answer 290

GI tract Can also be in lung, and can metastisise elsewhere eg Liver *Carcinoid syndrome generally does not occur until the disease is so advanced that it overwhelms the liver's ability to metabolize the released serotonin*

Answer 291

serotonin and kallikrein Serotonin is involved with initiating peristalsis, and plays a role in bronchoconstriction *In Carcinoid Syndrome, Serotonin can cause fibrous of heart valves, especially on the the right hand side.* Kallikrein - leads to formation of bradykinin, one of the most potent vasodilators known. Therefore has great effect on Blood flow **(can cause flushing)**

Answer 292

**Flushing: The most important clinical finding is flushing of the skin**, usually of the head and the upper part of thorax. - *Due to vasodilation* - Abdominal pain, due to Hepatomegaly , or bowel obstruction or bowel ischaemia, - Diarrhoea - due to abdominal cramping, and abnromal peristalsis - Carcinoid Heart disease - Serotonin leads to fibrous of right hand side heart valves Bronchoconstriction, due to serotonin/histmaine, leads to Flushing, sneezing, and SOB

Answer 293

- **24 hr urine 5-hydroxyindoleacetic acid:** show increased levels - *(its a major metabolite of 5-HT/serotnin)* GOLD STANDARD - **Chest X-ray/ chest or pelvis MRI/ CT:** to identify location - **Ostreoscan:** injected radiolabelled somatostatin analogue, octreotide, to bind to the increased number of somatostatin receptors on tumour cells.

Answer 294

Somatostatin analogues, which decreases the secretion of serotonin by the tumour Will also decrease the breakdown product of serotonin Surgery to remove the tumour

Answer 295

a lack of antidiuretic hormone (ADH) or a lack of response to ADH

Answer 296

Cranial Diabetes Insipidus - Too little ADH from Posterior Pituitary Gland Nephrogenic Diabetes Insipidus - Kidney not responding to ADH.

Answer 297

a) made in the Hypothalamus b) Stored in the posterior pituitary gland, ready for secretion.

Answer 298

Drugs, particularly lithium used in bipolar affective disorder, and Demeclocycline Mutations in gene that codes for the ADH receptor - so **Familial** Kidney disease Electrolyte disturbance (hypokalaemia and hypercalcaemia) Renal Tubular Acidosis

Answer 299

No, as ADH can still “leak” from the damaged end of the intact neurone

Answer 300

Brain tumours Head injury Brain infections (meningitis, encephalitis and tuberculosis) Brain surgery or radiotherapy Pituitary Tumour

Answer 301

Polyuria/Nocturia Polydipsia Dehydration

Answer 302

The water deprivation test - main one Also Look at Serum and Urine Osmolarity MRI of Hypothalamus Plasma biochemistry

Answer 303

It aims to determine whether kidneys continue to produce dilute urine despite dehydration. You restrict fluid for 8 hours, and measure Urine osmolarity, which can check for Diabetes insipidus. Then, give **Synthetic ADH** *(Desmopressin)* and recheck the urine osmolarity to distinguish between Cranial DI and Nephrogenic DI

Answer 304

a) Concentrated/high, but in normal ranges b) Still low, (lots of urine produced) despite dehydration

Answer 305

a) Cranial - High urine osmolarity (as kidneys are still capable of responding to ADH) b) Nephrogenic - Still low Urine osmolarity, as problem is not with the lack of ADH but the lack of response in the kidneys to it.

Answer 306

a) Desmopressin - **Synthetic ADH** b) Bendroflumethiazide Diuretic - **(Causes more Na+ secretion), so more water lost so body responds by reducing GFR)** Treat underlying cause!

Answer 307

Adrenaline is produced by the “chromaffin cells” in the adrenal medulla of the adrenal glands.

Answer 308

A phaeochromocytoma is a tumour of the chromaffin cells that secretes unregulated and excessive amounts of adrenaline.

Answer 309

MEN 2a (or 2B) MEN = Multiple Endocrine Neoplasia, autosomal dominant

Answer 310

*The Adrenaline tends to be secreted in bursts, giving periods of worse symptoms followed by more settled periods*

Answer 311

24 hour urine catecholamines Plasma free metanephrines Measure over 24 hours to get a better picture of how much adrenaline is secreted. ***Metanephrines*** are a breakdown product of adrenaline and have a longer half life -so more reliable to diagnose with

Answer 312

a1- Vasoconstriction, increased BP, Increased closure of internal sphincter of the bladder, pupil dilation a2 - Inhibits NA release, and inhibits Ach release. Also inhibits Insulin release

Answer 313

a) Chronotropic and inotropic effects on heart *(tachycardia and increased contractility)* b) Relaxes smooth muscle (seen in labour/asthma) **bronchodilation**, inhibits labour, **causes insulin and glucagon** to be secreted) c) Enhances lipolysis relaxes bladder detrusor (urine retention)

Answer 314

**Symptoms of Adrenaline release!** Anxiety Sweating Headache Hypertension Palpitations, tachycardia and paroxysmal atrial fibrillation *Signs and symptoms tend to fluctuate with peaks and troughs relating to periods when the tumour is secreting adrenaline.*

Answer 315

Alpha blockers (i.e. phenoxybenzamine) Beta blockers once established on alpha blockers *^^To control the symptoms* Adrenalectomy to remove tumour *Patients should have symptoms controlled medically prior to surgery to reduce the risk of the anaesthetic and surgery.*

Answer 316

High aldosterone and low renin

Answer 317

Conns, primary aldosteronism

Answer 318

Diabetes insipidus

Answer 319

Cushing's disease

Answer 320

Graves disease, iodine induced hyperthyroidism

Answer 321

Amiodarone is structurally similar to thyroxine and also contains iodine, Amiodarone is an antiarrhythmic medication used to treat and prevent a number of types of irregular heartbeats (including atrial fibrillation which this lady has). It is known to cause thyroid problems, including both hyperthyroidism and hypothyroidism.

Answer 322

Glucagon - First ot be secreted Cortisol and Glucagon can also raise blood sugar

Answer 323

Gliclazide Sitagliptin Dapagliflozin

Answer 324

pituitary MRI CT scan of adrenals

Answer 325

Flat P wave Prolonged PR interval Tall, Peaked T wave Wide QRS Go, Go long, Go tall, Go wide

Answer 326

ST Depression, Flat, inverted T wave presence of a U Wave U Wave Comes after T wave, - *'U' waves are thought to represent repolarization of the Purkinje fibres.*

Answer 327

The U wave is a small (0.5 mm) deflection immediately following the T wave, its polarity is the same as the T wave, meaning that they will both be in the same direction **may be a sign of hypokalemia or drug effect or toxicity**

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