Module 3D Endocrine - Conditions Flashcards

Question

T2DM scenario --> first-line management (eg. metformin +/- SGLT-2-inhibitor) has not worked to control HbA1c levels (HbA1c is now > 58 mmol/l), what is the further management?

Answer 1

- GLP-1 mimetics mimic the action of the GLP-1 hormone to treat type 2 diabetes and obesity --> give if BMI > 35 g/m2 - insulin-based treatment --> human NPH insulin (isophane, intermediate-acting) taken at bed-time or twice daily according to need

Answer 2

You do not add another drug as she has not reached the threshold of 58 mmol/mol (7.5%)

Answer 3

- Hypertension --> ACE-inhibitors (eg. ramipril) (or ARB (eg. losartan) if black African) are first-line (Note: BP targets are same as normal --> see image) - Antiplatelets --> only offer if pt has existing CVD - Lipids --> offer a statin if Q-risk > 10% (atorvastatin 20mg)

Answer 4

- Diabetic retinopathy --> characterised by damage to the retinal vasculature, leading to microaneurysms, hemorrhages, and neovascularization - Diabetic nephropathy --> common cause of chronic kidney disease and end-stage renal disease, it is characterised by albuminuria, declining glomerular filtration rate (GFR), and eventually renal failure - Diabetic neuropathy --> peripheral neuropathy is most common form (pain/numbness/tingling in extremities --> increasing risk of foot ulcers and amputations), autonomic neuropathy affects autonomic NS leading to GI, cardiovascular, and genitourinary dysfunction

Answer 5

- Coronary artery disease (CAD) / MI / heart failure - Cerebrovascular disease (stroke / TIAs) - Peripheral arterial disease (PAD)

Answer 6

- Diabetic foot --> arise from a combination of neuropathy, PAD, and impaired wound healing --> can result in foot ulcers, infections, and ultimately amputations - Infections --> T2DM pts are more susceptible to infections due to immune dysfunction, impaired wound healing, and increased colonisation of pathogens --> common infections include UTIs, skin and soft tissue infections, and respiratory infections - Hyperglycaemic emergencies --> HHS is more common than DKA in T2DM pts

Answer 7

- DKA is a serious and potentially life-threatening complication of diabetes mellitus, characterised by hyperglycaemia, ketosis, and metabolic acidosis - It is more common in pts with T1DM - DKA results from an absolute or relative deficiency of insulin, leading to increased hepatic glucose production, decreased peripheral glucose utilisation, and enhanced lipolysis with subsequent ketone body formation - Prompt recognition, diagnosis, and treatment are crucial to prevent complications and improve patient outcomes

Answer 8

Risk factors: - Insulin deficiency --> inadequate insulin therapy or poor compliance with insulin treatment is the most common precipitating factor for DKA --> this may be due to financial constraints (socially deprived), fear of hypoglycaemia, or psychological issues (eg. depression, eating disorders) - Infection --> acute infections can increase insulin requirements by inducing a state of physiological stress --> common infections include pneumonia (Strep. pneumoniae) and UTIs (E.coli) - New-onset diabetes --> DKA may be the first presentation of T1DM - Certain medications --> eg. glucocorticoids, thiazide diuretics, atypical antipsychotics, and SGLT2 inhibitors can increase the risk of DKA by raising blood glucose levels or decreasing insulin sensitivity

Answer 9

- Insulin deficiency and hyperglycaemia - Gluconeogenesis and Glycogenolysis - Osmotic diuresis - Lipolysis and Ketoacidosis - Ketonuria - Respiratory compensation - Electrolyte imbalances

Answer 10

- Insulin deficiency and hyperglycaemia --> DKA begins with a severe deficiency of insulin, leading to decreased glucose uptake by peripheral tissues --> this results in hyperglycaemia as glucose remains in the bloodstream instead of being transported into cells for energy use - Gluconeogenesis and Glycogenolysis --> the lack of insulin triggers hepatic gluconeogenesis and glycogenolysis, further contributing to the elevated blood glucose levels (simultaneously, reduced inhibition of glucagon release leads to enhanced gluconeogenesis and glycogen breakdown)

Answer 11

- Lipolysis and Ketoacidosis --> in response to cellular starvation caused by a lack of glucose utilisation, lipolysis occurs in adipose tissue releasing free fatty acids (FFAs) --> these FFAs are converted into ketone bodies (acetoacetate, beta-hydroxybutyrate, and acetone) in the liver through a process called ketogenesis --> in high concentrations, these ketone bodies decrease the blood pH leading to metabolic acidosis (hence the name 'ketoacidosis') - Ketonuria --> ketone bodies are also excreted in the urine (ketonuria), which can further exacerbate dehydration and electrolyte imbalances --> the presence of ketones in urine is a key diagnostic feature of DKA

Answer 12

- Osmotic diuresis --> the resultant hyperglycemia causes osmotic diuresis as glucose is excreted in the urine along with water and electrolytes such as sodium and potassium --> this can lead to volume depletion, hypotension, and renal impairment if not promptly managed

Answer 13

- Kussmaul breathing = rapid, deep respirations characteristic of severe DKA - Respiratory compensation can occur in DKA --> in response to the metabolic acidosis, hyperventilation occurs as part of the body's compensatory mechanism to decrease CO2 lvls and increase blood pH --> leading to Kussmaul breathing

Answer 14

Due to electrolyte imbalances --> due to combination of osmotic diuresis and acid-base disturbance leads to significant electrolyte imbalances --> particularly hyponatraemia and hypokalemia (can cause cardiac arrhythmias)

Answer 15

- Hyperglycaemia, ketosis, and metabolic acidosis . - Polyuria, polydipsia, and profound weakness, with notable signs including Kussmaul breathing, dehydration, and a distinct acetone odour on the breath

Answer 16

- A blood pH of less than 7.3 with a bicarbonate level below 15 mmol/L typically indicates metabolic acidosis --> patients exhibit deep, rapid (Kussmaul) breathing as a compensatory mechanism to expel excess carbon dioxide

Answer 17

- Due to insulin deficiency, there is increased lipolysis, leading to the production of ketone bodies, which are acidic - Ketosis presents with a characteristic sweet, fruity, or acetone odour on the breath

Answer 18

- Blood-glucose (point of care finger prick sample) --> >11.1 mmol/L is a key diagnostic criterion for DKA - Ketones --> presence of ketones in blood (> 3 mmol/L) or urine (+2 or more on dipstick) confirms diagnosis (note: blood ketone testing is preferred over urine due to its greater sensitivity and specificity) - Venous blood gas (VBG) --> this will reveal metabolic acidosis (expect to find a low bicarbonate and low pH (< 7.3) - U&Es --> to assess renal function and identify any electrolyte imbalances that may need correction (particularly potassium levels)

Answer 19

- Blood glucose > 11 mmol/L or known diabetes mellitus - pH < 7.3 - Bicarbonate < 15 mmol/L - Ketones > 3 mmol/l or urine ketones ++ on dipstick

Answer 20

- HHS --> typically presents in pts with T2DM + usually more severe hyperglycaemia (> 33.3) + no ketonaemia or metabolic acidosis + pts will often have neuro signs - Alcoholic ketoacidosis (AKA) --> usually a hx of heavy drinking followed by poor oral intake + blood glucose lvls will be normal + often a concomitant metabolic alkalosis due to vomiting - Lactic acidosis --> can occur in diabetes patients due to biguanide use (eg. metformin), but also from critical illness or sepsis + both have high anion gap metabolic acidosis but lactic acidosis has no ketonaemia or glycosuria + elevated lactate lvls

Answer 21

- Fluid replacement --> IV fluids (isotonic saline) - IV insulin infusion - Correction of electrolyte disturbance --> serum potassium often high on admission, this often falls following insulin treatment resulting in hypokalemia --> potassium may need to be added to fluids (potentially need cardiac monitoring) - Long-acting insulin should be continued, short-acting insulin should be stopped (note: slower infusion indicated in young adults (18-25 yrs) due to risk of cerebral oedema)

Answer 22

DKA resolution: - pH > 7.3 - blood ketones < 0.6 mmol/L - bicarbonate > 15.0 mmol/L . - Both the ketonaemia and acidosis should have been resolved within 24 hrs --> if not then need senior endocrinologist - If pt is eating and drinking --> switch them back to subcutaneous insulin - The patient should be reviewed by specialist nurse prior to discharge

Answer 23

- HHS is a severe complication of diabetes mellitus, predominantly T2DM, characterised by extreme hyperglycaemia and hyperosmolarity without significant ketosis

Answer 24

- Insulin deficiency and increased counter-regulatory hormones, leading to excessive hepatic glucose production and impaired renal excretion --> this results in elevated serum osmolality and triggers a shift of water from intracellular to extracellular space, causing cellular dehydration - Hyperglycaemia results in osmotic diuresis with associated loss of sodium and potassium - Severe volume depletion results in a significant raised serum osmolarity --> resulting in hyperviscosity of blood

Answer 25

- It typically presents with polyuria, polydipsia and profound dehydration due to osmotic diuresis - Neurological symptoms may also be present, ranging from lethargy to seizures or coma

Answer 26

A precise definition of HHS does not exist so use this as a guide to help differentiate from DKA: 1. Hypovolaemia 2. Marked Hyperglycaemia (>30 mmol/L) without significant ketonaemia or acidosis 3. Significantly raised serum osmolarity (> 320 mosmol/kg)

Answer 27

- DKA presents within hrs of onset, HHS comes on over many days --> consequently the dehydration and metabolic disturbances are more extreme

Answer 28

- Management includes aggressive fluid replacement, correction of electrolyte imbalances particularly potassium, and cautious insulin therapy - Concurrent illnesses often precipitate HHS --> hence identification and treatment of underlying conditions are integral parts of management. - HHS carries a high mortality rate; therefore vigilant monitoring for complications such as thromboembolic events, AKI or cerebral oedema is essential during treatment

Answer 29

- Excess levels of insulin causes hypoglycaemia --> most commonly this is from exogenous, injectable insulin used in the management of T1DM/T2DM --> ie. pt has injected too much insulin OR has used the same amount of insulin whilst not eating enough/skipping a meal - Sulfonylureas (eg. gliclazide) act by increasing the secretion of insulin from β-cells --> hypoglycaemia is a common adverse effect (esp. when starting this medication) - Hypoglycaemia more likely to occur in diabetics who have a viral illness, have drunk alcohol, or exercised more than usual . - Non-diabetic causes --> alcohol consumption is the most common non-iatrogenic cause of hypoglycaemia --> due to its inhibitory effects on gluconeogenesis and glycogenolysis - Rare cause --> insulinoma (neuroendocrine tumour of pancreas) which causes unregulated secretion of insulin

Answer 30

The brain is particularly sensitive to low glucose levels as it relies heavily on glucose for energy

Answer 31

The initial response to declining blood glucose involves the autonomic nervous system and counter-regulatory hormones. - As glucose levels drop, the pancreas reduces insulin secretion - Concurrently, there is an increase in glucagon release from pancreatic alpha cells --> glucagon promotes glycogenolysis and gluconeogenesis in the liver, elevating plasma glucose concentrations . - Adrenaline (epinephrine) is also released from the adrenal medulla, stimulating hepatic glycogenolysis and inhibiting insulin release further - This hormone additionally activates lipolysis in adipose tissue, providing free fatty acids as an alternative energy source for peripheral tissues, thereby sparing glucose for cerebral use . - Cortisol and growth hormone are secreted in response to prolonged hypoglycaemia --> cortisol enhances gluconeogenesis and decreases peripheral utilisation of glucose by antagonising insulin action at target tissues - Growth hormone similarly supports gluconeogenesis while promoting lipolysis

Answer 32

1. Autonomic symptoms --> sweating (due to increased sympathetic stimulation), tachycardia (due to adrenaline release), pallor (due to vasoconstriction caused by sympathetic activation), tremors, and hunger (polyphagia) 2. Neuroglycopenic symptoms --> cognitive impairment (due to reduced cerebral glucose supply), dizziness and weakness (due to lack of glucose within nervous system), vision changes (impaired function of neurons in retina and optic nerve), mood changes, and seizures (due to brain's increased excitability from lack of glucose) 3. Non-specific symptoms --> fatigue, nausea, paresthesias (note: presentation can vary widely)

Answer 33

1. Symptoms or signs of hypoglycaemia 2. Low blood glucose 3. Resolution of symptoms with the correction of blood glucose

Answer 34

- Stroke/TIA - MI - Sepsis --> altered mental status may be the only presenting feature of sepsis - Epilepsy

Answer 35

Management in community: - oral glucose (10-20g) should be given --> eg. sweets or liquid form (not chocolate!) - OR a quick-acting carbohydrate may be given --> GlucoGel or Dextrogel - OR a 'HypoKit' may be prescribed --> contains syringe and vial of glucagon for IM or SC injection at home . Management in hospital setting: - If pt alert --> quick-acting carbohydrate can be given in the form of a glucose gel on the buccal mucosa - If pt unconscious or unable to swallow --> subcut or IM injection of glucagon may be given - OR IV 20% glucose solution given IV Note: once blood glucose back to normal --> pt should consume slower-acting carbohydrates (eg. toast or biscuits) to prevent lvls from dropping again

Answer 36

- Recurrent episodes of hypoglycaemia lead to 'hypoglycaemic unawareness' where patients do not develop autonomic symptoms of low blood glucose --> this is more frequent in type II diabetes and increases the chance of neuroglycopenic complications of hypoglycaemia

Answer 37

- refers to diabetes triggered by pregnancy --> it is caused by reduced insulin sensitivity during pregnancy, and resolves after birth - after birth, women are at a higher risk fo developing T2DM

Answer 38

Shoulder dystocia

Answer 39

- Anyone with risk factors should be screened with an oral glucose tolerance test at 24 – 28 weeks gestation - Women with previous gestational diabetes also have an OGTT soon after the booking clinic

Answer 40

- Previous gestational diabetes - Previous macrosomic baby (≥ 4.5kg) - BMI > 30 - Ethnic origin (black Caribbean, Middle Eastern and South Asian) - Family hx of diabetes (first-degree relative)

Answer 41

- Fasting --> < 5.6 mmol/l - At 2 hrs --> < 7.8 mmol/l (results higher than these are used to diagnose gestational diabetes)

Answer 42

- 4 weekly USS scans to monitor the fetal growth and amniotic fluid volume form 28 to 36 weeks gestation . Initial management: - Fasting glucose < 7 mmol/l --> trial of diet and exercise for 1-2 weeks, followed by metformin, then insulin - Fasting glucose > 7 mmol/l --> start insulin +/- metformin - Fasting glucose > 6 mmol/l + macrosomia (or other complications) --> start insulin +/- metformin (Glibenclamide (a sulfonylurea) is suggested as an option for women who decline insulin or cannot tolerate metformin)

Answer 43

- Fasting --> 5.3 mmol/l - 1 hr post-meal --> 7.8 mmol/l - 2 hrs post-meal --> 6.4 mmol/l - in general --> avoiding levels of 4 mmol/l or below

Answer 44

Folic acid 5mg --> to reduce risk of neural tube defects and other developmental complications

Answer 45

- managed using metformin and insulin only --> other diabetic medications should be stopped

Answer 46

Retinopathy screening

Answer 47

after at least 6 weeks

Answer 48

- Neonatal hypoglycaemia --> baby becomes accustomed to a large supply of glucose during pregnancy, and after birth they struggle to maintain the supply they are used to with oral feeding alone - needs close monitoring (aim to keep blood glucose > 2 mmol/l) --> if falls then give IV dextrose by nasogastric feeding

Answer 49

- Hypothyroidism is a common endocrine disorder characterized by decreased thyroid hormone production - It affects approximately 5% of the population, with women being more commonly affected than men - The most common cause of hypothyroidism is autoimmune thyroiditis, also known as Hashimoto's thyroiditis --> other causes include iodine deficiency, thyroid surgery, and radiation therapy - Symptoms of hypothyroidism can be subtle and nonspecific, including fatigue, weight gain, constipation, and cold intolerance - Diagnosis is made through measurement of thyroid-stimulating hormone (TSH) and free thyroxine (T4) levels - Treatment involves replacement of thyroid hormone with levothyroxine, with regular monitoring of TSH levels to ensure adequate dosing

Answer 50

Primary hypothyroidism: - Hashimoto's thyroiditis (autoimmune thyroiditis) --> most common cause of hypothyroidism --> body produces antibodies that attack the thyroid gland, resulting in inflammation and impaired thryoid hormone production - Iodine deficiency (more common in developing world) --> iodine is essential for the synthesis of thyroid hormones - Surgical removal OR Radioactive iodine treatment --> these treatments for hyperthyroidism or thyroid cancer often result in hypothyroidism due to reduction or removal of functional thyroid tissue . Secondary hypothyroidism: - Pituitary disorders such as pituitary adenomas or hypopituitarism can lead to reduced production of thyrotropin-releasing hormone (TRH) --> leading to decreased stimulation of the thyroid gland and subsequent hypothyroidism . Tertiary hypothyroidism: - Hypothalamic disease can result in diminished secretion of TRH, leading to reduced stimulation of the pituitary gland and subsequently lowered release of thyroid-stimulating hormone (TSH)

Answer 51

- Female sex - Age --> > 60yrs - Family hx - Certain medications --> lithium and amiodarone - Radiation exposure --> head or neck

Answer 52

- The synthesis and secretion of thyroid hormones are primarily regulated by the hypothalamic-pituitary-thyroid (HPT) axis - In response to low circulating levels of thyroid hormones, thyrotropin-releasing hormone (TRH) is secreted from the hypothalamus --> this stimulates the anterior pituitary gland to release thyroid-stimulating hormone (TSH) - TSH then binds to receptors on the surface of thyroid follicular cells, stimulating endocytosis of thyroglobulin from the colloid, proteolysis and subsequent release of triiodothyronine (T3) and thyroxine (T4).

Answer 53

Iodide uptake into the follicular cells from plasma is an essential step for thyroid hormone synthesis. The sodium-iodide symporter (NIS), located on the basolateral membrane, mediates this process. Once inside the cell, iodide is transported to the apical membrane where it undergoes oxidation to iodine via thyroid peroxidase enzyme. Iodination of tyrosyl residues within thyroglobulin forms monoiodotyrosine (MIT) and diiodotyrosine (DIT). Coupling reactions between MIT and DIT yield T3 and T4.

Answer 54

- Middle-aged woman who presents with fatigue, weight gain, cold intolerance, and constipation - Other symptoms --> MSK, neuro (eg. cognitive impairment), skin (dry skin, hair loss), CVD (bradycardia is common finding), reproductive (menstrual irregularities and infertility, decreased libido and erectile dysfunction) (note: there are many ways that hypothyroidism can present as it affects multiple systems)

Answer 55

- Serum Thyroid-Stimulating Hormone (TSH) Test --> an elevated TSH level typically indicates primary hypothyroidism, due to decreased thyroid hormone production resulting in increased pituitary TSH secretion - Serum Free Thyroxine (FT4) Test --> if TSH levels are abnormal, this test should be performed next --> a low FT4 level alongside high TSH confirms primary hypothyroidism --> Normal FT4 with high TSH indicates subclinical hypothyroidism

Answer 56

- Serum Thyroglobulin (Tg) and Anti-Thyroglobulin Antibody (TgAb) Tests --> elevated lvls suggest Hashimoto's thyroiditis

Answer 57

- Pituitary adenoma (eg. prolactinoma) --> similar symptoms, but often presents with galactorrhoea (milk production) and menstrual irregularities in females or reduced libido and infertility in males + may cause secondary hypothyroidism (serum TSH lvls low/normal despite low free thyroxine (T4) lvls) - Cushing's syndrome --> similar symptoms, but will often presents with moon face, supraclavicular fat pads, and striae + lab findings will differ (eg. high cortisol) - Myxedema coma --> life-threatening form of hypothyroidism characterised by altered mental status (confusion/coma) and hypothermia, but other symptoms are similar + lab findings will show profound hypothyroidism with very low T4 lvls and significantly elevated TSH lvls

Answer 58

- Levothyroxine --> titrate up as necessary - thryoid function tests should be checked every 8-12 weeks - TSH lvl targets --> between 0.5-2.5 mU/l - women with established hypothyroidism who become pregnant should have their dose increased by at least 25-50 micrograms due to increased demands of pregannay

Answer 59

- hyperthyroidism --> due to over-treatment - reduced bone mineral density - worsening of angina - atrial fibrillation

Answer 60

iron --> absorption of levothyroxine reduced, give at least 2 hours apart

Answer 61

- cardiovascular --> can lead to increased LDL cholesterol, causing atherosclerosis and subsequent CAD - neuropsychiatric --> depression is common due to increased metabolic activity in the brain + cognitive impairment (eg. memory loss or decreased concentration) + myxedema coma (life-threatening condition causing slowing of function in multiple organs) - gastrointestinal --> can slow down gut motility leading to constipation - musculoskeletal --> adhesive capsulitis, carpal tunnel syndrome, and myopathy, presenting as muscle weakness and cramps - reproductive systems --> menstrual irregularities (menorrhagia) + infertility + pregnancy problems (miscarriage, pre-eclampsia, placental abruption, and postpartum haemorrhage)

Answer 62

- PCOS is a complex condition of ovarian dysfunction thought to affect between 5-20% of women of reporductive age - The aetiology is not fully understood - Both hyperinsulinemia and high levels of LH are seen in PCOS

Answer 63

- subfertility and infertility - menstrual disturbances --> oligomenorrhea and amenorrhoea - hirsutism + acne --> due to hyperandrogenism - obesity - acanthosis nigricans --> due to insulin resistance (see image)

Answer 64

- pelvic ultrasound --> multiple cysts on the ovaries - FSH, LH, prolactin, TSH, and testosterone are useful investigations --> raised LH:FSH ratio is a 'classical' feature but is no longer thought to be useful in diagnosis. Prolactin may be normal or mildly elevated. Testosterone may be normal or mildly elevated - however, if markedly raised consider other causes - check for impaired glucose tolerance

Answer 65

Two out of three of the following criteria are required to make the diagnosis: - Oligo- and/or anovulation --> ie. oligo- or amenorrhoea - Clinical and/or biochemical signs of hyperandrogenism --> e.g. hirsutism, acne, or elevated levels of total or free testosterone - Polycystic ovaries (by ultrasound) --> defined as the presence of 12 or more follicles (measuring 2-9 mm in diameter) in one or both ovaries and/or increased ovarian volume (greater than 10 cm3)

Answer 66

General: - weight reduction if appropriate - if a woman requires contraception then combined oral contraceptive (COC) pill may help regulate her cycle and induce a monthly bleed . Hirsutism: - COC pill (3rd gen) OR co-cyprindiol (anti-androgen action) - if no response to COC --> try topical eflornithine - spironolactone, flutamide, and finasteride may be used under specialist supervision . Acne: - COC pill (co-cyprindiol has the best anti-androgen effects) --> however, there is a risk of VTE - Other standard treatments for acne --> topical adapalene (retinoid), topical antibx (eg. clindamycin 1% with benzoyl peroxide 5%), topical azelaic acid 20%, and oral tetracycline antibx (eg. lymecycline) . Infertility: - weight loss is first step - specialist --> clomifene, laparoscopic ovarian drilling, IVF - metformin and letrozole may also help restore ovulation

Answer 67

Because the tongue is attached to the thyroglossal duct

Answer 68

G - Grave's disease (most common cause) I - Inflammation (thyroiditis) S - Solitary toxic thyroid nodule T - Toxic mulitnodular goitre . Others: - postnatal thyroiditis --> transient in nature, usually followed by a transient hypothyroid period

Answer 69

- Hyperthyroidism --> high lvls of thyroid hormones (overproduction of T3 and T4 by the thyroid gland) - Thyrotoxicosis --> refers to the clinical syndrome of hyperthyroidism Ie. A pt can present with thyrotoxicosis but not have hyperthyroidism

Answer 70

- Primary hyperthyroidism --> due to thyroid pathology (thyroid is producing excessive thyroid hormone) - Secondary hyperthyroidism --> due to pathology of hypothalamus or pituitary (pituitary gland produces too much TSH, stimulating the thyroid gland to produce excessive thyroid hormones - Subclinical hyperthyroidism --> T3 and T4 are normal, TSH is suppressed (low) - there may be mild or absent symptoms

Answer 71

- Grave's disease is an autoimmune condition resulting in the overproduction of thyroid hormones (T3 and T4) - This is due to the formation of antibodies to TSH, it is the most common cause of hyperthyroidism in developed countries - About 30% of pts with Grave's disease will display extrathyroidal manifestations --> orbitopathy, acropachy, and pretibial myxoedema (these only occur with Grave's and not other forms of hyperthyroidism)

Answer 72

- T1DM - Addison's disease - Pernicious anaemia

Answer 73

- autoimmune thyroid disease in which the body produces IgG antibodies to the thyroid-stimulating hormone (TSH) receptor - These antibodies bind to TSH receptors found on thyroid follicular cells within the thyroid gland, causing chronic stimulation --> hence, this is a type II hypersensitivity reaction . The follicular cells are responsible for the production of thyroid hormone --> therefore, this hyperstimulation results in: - Excessive production of thyroid hormone (T3 and T4) - Hypertrophy of the thyroid gland - Hyperplasia of thyroid follicular cells - Subsequent signs and symptoms of hyperthyroidism and the presence of a goitre

Answer 74

General hyperthyroidism signs and symptoms: **Metabolic**: - Heat intolerance: due to increased metabolism leading to higher body temperature. - Weight loss: caused by higher metabolic rate and accelerated metabolism. - Increased appetite: in 90% this is in the absence of weight gain. - Excessive sweating: must be differentiated from 'hot flushes' due to oestrogen deficiency in post-menopausal women. **Cardiac**: - Palpitations: this includes atrial fibrillation (20%) or other supraventricular tachycardias, especially in older patients. - Tachycardia - Atrial fibrillation: a cause of palpitations, especially in older patients. - Hypertension - Heart failure: thyrotoxic cardiomyopathy, especially in the elderly. **Excessive nervous stimulation**: - Anxiety: a feeling of nervousness and trembling. - Tremor: usually fine. **Other**: - Palpable thyroid: smooth, diffusely and uniformly enlarged thyrotoxic (excess production of thyroid hormone) goitre. - Oligomenorrhoea . **Extrathyroidal manifestations specific to Graves' disease**: - Eye disease (30%): upper eyelid retraction, exophthalmos, ophthalmoplegia, eye pain, tearing, diplopia, photophobia, blurred vision. - Pretibial myxoedema (3%): waxy, discoloured induration of the skin on the anterior aspect of the lower legs. - Thyroid acropachy (1%): clubbing of fingers and toes with soft tissue swelling due to sub-periosteal formation of new bone.

Answer 75

NICE say to test for thyroid dysfunction as step 1, then step 2 is to do further testing for Grave's disease . Step 1 - TFTs - TSH --> low - Free thyroxine (fT4) --> high - Free triiodothyronine (fT3) --> high Step 2 - specific tests for Grave's disease - TSH receptor antibodies (TRAbs) --> present in Grave's disease (very sensitive and specific test) - Technetium scan of thyroid gland --> considered if TRAvs are -ve

Answer 76

Imaging: - USS --> assess size, vascularity, and presence of nodules - Radioactive iodine scan --> uneven uptake indicates the presence of a nodule, diffuse and high uptake suggests Grave's, low uptake suggests thyroiditis

Answer 77

- Examine visual fields, acuity, and movements - MRI or CT scans --> can confirm diagnosis (esp. if subclinical)

Answer 78

- First-line definitive treatment --> radioactive iodine - Beta-blockers (eg. propanolol) --> for rapid control of symptoms (note: symptom control not treatment) - Anti-thyroid drugs (eg. carbimazole, propylthiouracil) --> 12 to 18 month course --> can do maintenance dose or "block and replace" (high dose which blocks all production and levothyroxine is used to replace) - Surgery --> total thyroidectomy (if concerns about compression or malignancy, or other treatments are not suitable) - pts become hypothyroid so replacement therapy required (levothyroxine)

Answer 79

- Carbimazole --> Acute pancreatitis - carbimazole and propylthiouracil --> agranulocytosis (dangerously low WBC count --. at risk of infections)

Answer 80

Recurrent laryngeal nerve

Answer 81

Thyroid storm (aka. thyrotoxic crisis) - sudden and significant rise in thyroid hormone lvls - results in fever, tachycardia, and delirium - requires admission --> supportive care (IV fluids, anti-arrhythmic medication, and beta-blockers) + normal thyrotoxicosis treatment

Answer 82

- a transient episode thought to occur following viral infection (temporary inflammation of the thyroid gland) and typically presents with hyperthyroidism . 1. Thyrotoxicosis 2. Hypothyroidism 3. Return to normal

Answer 83

- Very tender --> differs from other thyroid swellings (if thyroid is tender then likely to be subacute (De Quervain's) thyroiditis

Answer 84

- Excessive thyroid hormones - Thyroid swelling and tenderness - Flu-like illness (fever, aches and fatigue) - Raised inflammatory markers (CRP and ESR)

Answer 85

It is a self-limiting condition, symptomatic relief and inflammation control can be provided: - Analgesia --> NSAIDs (for pain + inflammation) - Corticosteroids (eg. prednisolone) --> in more severe cases (or NSAIDs are contraindicated) - Beta-blockers (eg. propranolol) --> for hyperthyroidism symptoms (palpitations, tremors, anxiety) - Levothyroxine --> for hypothyroidism symptoms

Answer 86

- a condition where multiple autonomously functioning nodules develop on the thyroid gland, these are unregulated by the thyroid axis and continuously produce excessive thyroid hormones --> resulting in hyperthyroidism - These nodules are often benign (however, non-functioning thyroid nodules can be malignant) - Iodine deficiency, head + neck irradiation and age > 50 yrs are risk factors

Answer 87

Pts may present with subclinical hyperthyroidism, accompanied by swelling of the thyroid gland - Pts can present with hyperthyrodiism symptoms --> hyperphagia, weight loss, heat intolerance, palpitations, anxiety, oligomenorrhoea, or hyperdefecation - The nodular nature of the goitre helps differentiate it from Grave's disease which is more diffuse

Answer 88

levator palpebrae muscle

Answer 89

- Radioactive iodine (RI) --> 1st-line in non-pregnant adults - Surgery (thyroidectomy) --> swelling of thyroid gland may obstruct breathing or swallowing which is an indication for surgery (or RI not worked) . - Beta-blockers (propranolol) --> for symptomatic relief . - Pregnant women --> MDT approach, commence anti-thyroid medication (carbimazole)

Answer 90

- aka. autonomously functioning thyroid nodules --> solitary hyperfunctioning nodules within the thyroid gland that autonomously produce thyroid hormones, leading to thyrotoxicosis - The nodules are usually benign adenomas

Answer 91

Dietary iodine deficiency

Answer 92

Toxic thyroid adenomas don't present with exopthalmos (extraocular muscle involvement) - (occurs in 25-30% of Graves' disease, but not in thyroid adenoma)

Answer 93

Blood tests: - TFTs --> TSH will be suppressed (if TSH normal then can rule out adenoma), fT3 and fT4 are elevated - TSH receptor and TPO antibodies --> to exclude Graves' disease (will be -ve in adenoma) - ESR --> to rule out thyroiditis Imaging: - Thyroid ultrasound --> 1st-line imaging of any thyroid nodule - Radioisotope scanning (99mtechnetium or 131iodine) --> shows a' hot' nodule which indicates autonomous activity

Answer 94

Hyperthyroidism is associated with atrial fibrillation --> so it is important to identify and anti-coagulate

Answer 95

- Graves' disease --> diffuse goitre rather than solitary nodule, expothalmos/eyelid retraction/extraocular muscle involvement, autoimmune mediated (+ve for antibodies) - Toxic multinodular goitre --> large, irregular goitre, usually older pts, radioisotope scan will show hot and cold areas - Thyroiditis --> usually transient and self-limiting, raised ESR, key risk factor is postnatal women, radioisotope scan shows little/no uptake - Thyroid cancer --> usually associated cervical lymphadenopathy, ultrasound shows suspicious features (eg. irregular hyperechoic mass)

Answer 96

- Radioactive iodine or surgery for definitive treatment - Symptomatic relief --> beta-blockers +/- anticoagulation (if pt has AF)

Answer 97

- Absolute contraindications --> Pregnant or lactating women - Relative contraindications --> children and adolescent pts

Answer 98

Papillary carcinoma

Answer 99

Most are asymptomatic and are detected incidentally on imaging studies or during physical examination - most common presenting symptom is a painless thyroid nodule/mass - associated cervical lymphadenopathy is often present

Answer 100

- characterised by inadequate production of cortisol and aldosterone by the adrenal cortex - autoimmune destruction is the most common cause (80%) - pts may present with an adrenal crisis which is a life-threatening condition

Answer 101

- Primary adrenal insufficiency (Addison's disease) --> refers to when the adrenal glands have been damaged, resulting in reduced cortisol and aldosterone secretion - Secondary adrenal insufficiency --> results from inadequate adrenocorticotropic hormone (ACTH) and a lack of stimulation of the adrenal glands (this is the results of loss or damage to the pituitary gland) - Tertiary adrenal insufficiency --> results from inadequate corticotropin-releasing hormone (CRH) release by the hypothalamus (usually the results of sudden withdrawal of long-term oral steroids and the hypothalamus hasn't "woke up" fast enough (hypothalamus has been suppressed)

Answer 102

Autoimmune adrenalitis --> involves autoimmune destruction of the adrenal cortex - Other causes --> infections (eg. TB), genetic disorders (CYP21A2 - congenital adrenal hyperplasia), metastatic infiltration - Adrenal haemorrhage --> can result in acute adrenal insufficiency (trauma, anticoagulation, and sepsis) - Medications --> eg. prolonged use of glucocorticoids (eg. ketoconazole) can suppress the HPA axis, leading to adrenal atrophy and insufficiency

Answer 103

Primarily cortisol and aldosterone, but also adrenal androgens: - Cortisol is crucial for marinating glucose homeostasis, immune function, and stress response --> insufficient cortisol production results in hypoglycaemia, increased susceptibility to infections, and an inadequate response to stressors - Aldosterone is responsible for regulating sodium and potassium balance --> insufficient aldosterone production leads to hyponatremia, hyperkalemia, and volume depletion (causing orthostatic hypotension and impaired renal function) - Adrenal androgens are involved in secondary sexual characteristics and libido --> deficiency may result in reduced body hair and reduced libido

Answer 104

- Symptoms --> fatigue, muscle weakness, muscle cramps, dizziness, thirst and 'salt-craving', weight loss . Signs: - Bronze hyperpigmentation of the skin --> elevated ACTH lvls result in melanocyte-stimulating hormone (MSH) production - Hypotension --> particularly postural hypotension - with a drop of more than 20 mmHg on standing

Answer 105

- ACTH stimulation test (short Synacthen test) - Biochemistry --> hyponatremia is a key finding (can also get hypoglycaemia, hyperkalemia) - Autoantibodies --> adrenal cortex antibodies, 21-hydroxylase antibodies - ACTH can be measured directly --> ACTH lvl high in primary adrenal insufficiency (as pituitary producing lots of ACTH without -ve feedback in absence of cortisol), ACTH lvl low in secondary adrenal failure - Early morning cortisol (9am) --> has a role but often falsely normal - Imaging (eg. CT or MRI) --> can be done but not routinely used - MRI of pituitary --> gives further info on pituitary pathology

Answer 106

Test of choice for diagnosis adrenal insufficiency: - a dose of Synacthen (synthetic ACTH) is given - blood cortisol is checked before and 30 and 60 mins after the dose - the synthetic ACTH will stimulate healthy adrenal glands to produce cortisol (cortisol lvl should at least double) --> a failure to double indicates either primary adrenal insufficiency (Addison's disease) or very significant adrenal atrophy (after a prolonged absence of ACTH in secondary adrenal insufficiency)

Answer 107

- Hydrocortisone (glucocorticoid) --> used to replace cortisol - Fludrocortisone (mineralocorticoid) --> used to replace aldosterone . - Pts are given a steroid card, ID tag, and emergency letter to alert emergency services that they depend on steroids for life - Pt education is important --> sick day rules + importance of not missing glucocorticoid doses - Pts and close contacts are taught to give IM hydrocortisone in an emergency (Adrenal crisis)

Answer 108

Glucocorticoid doses (hydrocortisone) are doubled during an acute illness to match the normal steroid response to illness - note: fludrocortisone dose stays the same

Answer 109

- an acute life-threatening condition characterised by severe hypotension, hypoglycaemia, altered mental status, and electrolyte imbalances (hyponatraemia and hyperkalemia) - may be initial presentation of adrenal insufficiency or triggered by an infection . Management: - ABCDE approach - IV hydrocortisone (100mg followed by infusion) - IV fluids - correct hypoglycaemia --> IV dextrose - correct electrolyte imbalances + monitor

Answer 110

- Osteoporosis --> long-term glucorticoid therapy increeases risk (give bisphosphonates and Adcal D3 as preventative measures) - Infections --> increased susceptibility to infections due to impaired immune function

Answer 111

where post-partum haemorrhage causes avascular necrosis of the pituitary gland --> a cause of secondary adrenal insufficiency

Answer 112

- Cushing's syndrome --> refers to features of prolonged high lvls of glucocorticoids in the body - Cushing's disease --> refers to a pituitary adenoma secreting excessive ACTH, which stimulates excessive cortisol release from the adrenal glands

Answer 113

- Glucocorticoids (eg. cortisol) --> the primary natural glucocorticoid hormone produced by the adrenal glands - Mineralocorticoids (eg. aldosterone)

Answer 114

Cushing's disease --> adrenocorticotropic hormone (ACTH)-secreting pituitary adenoma

Answer 115

Zona fasciculata

Answer 116

- In a normally functioning HPA axis, rising cortisol lvls would suppress the release of CRH from the hypothalamus and ACTH from the pituitary --> thereby forming a negative feedback loop - However, the pituitary adenoma in Cushing's disease is often insensitive to this feedback inhibition --> resulting in a persistent state of ACTH hypersecretion

Answer 117

- Central obesity - Redistribution of adipose tissue --> moon facies, supraclavicular region, dorsocervical area ("buffalo hump") - Abdominal striae - Proximal myopathy --> leading to difficulty rising from a seated position - Osteopenia + osteoporosis - Thin skin with easy bruising and poor wound healing - Hirsutism (due to increased adrenal androgens) - Anxiety, depression, and insomnia - Hypertension --> due to cortisol-mediated sodium retention + potentiation of catecholamine action on blood vessels - T2DM --> due to cortisol-induced insulin resistance - Dyslipidaemia

Answer 118

- Exogenous steroids --> eg. pt taking long-term corticosteroids - Adrenal adenoma --> adrenal tumour secreting excess cortisol - Paraneoplastic syndrome --> when ACTH is released from a tumour somewhere other than the pituitary gland - ectopic ACTH - stimulating excessive cortisol release (small cell lung cancer is the most common)

Answer 119

- Low-dose overnight dexamethasone suppression test --> most sensitive test and used first-line to exclude Cushing's syndrome - 24hr urinary free cortisol --> two measurements required - Bedtime salivary cortisol --> two measurements required . - High-dose dexamethasone suppression test --> used to localise the issue

Answer 120

Dexamethasone suppression tests are used to diagnose Cushing's syndrome caused by a problem inside the body (no point if exogenous cause) - A normal response to dexamethasone is suppressed cortisol due to negative feedback --> dexamethasone causes -ve feedback on the hypothalamus (reducing the CRH output) --> causing -ve feedback on pituitary (reducing the ACTH output) --> the lower CRH and ACTH lvls result in a low cortisol output by the adrenal glands - A lack of cortisol suppression in response to dexamethasone suggests Cushing's syndrome . Low-dose overnight test: - dexamethasone (1mg) is given at night (usually 11pm), and the cortisol is checked at 9am the following morning - a normal result is that the cortisol lvl is suppressed --> failure of the dexamethasone to suppress the morning cortisol could indicate Cushing's syndrome and further assessment is required to localise the issue . Low-dose 48hr test: - 0.5mg taken every 6hrs for 8 doses (starting at 9am on first day) - cortisol is checked at 9am on day 1 and 9am on day 3 --> a normal result is that cortisol on day 3 is suppressed (failure of this suggests Cushing's syndrome) . High-dose 48hr test: - carried out same way as low-dose, but using 2mg instead of 0.5mg - this higher dose is enough to suppress the cortisol in Cushing's disease (pituitary adenoma), but not when it is caused by an adrenal adenoma or ectopic ACTH

Answer 121

- high in the morning, low at night

Answer 122

- ACTH is suppressed due to negative feedback on the pituitary when excess cortisol comes from an adrenal tumour (or endogenous steroids) - It is high when produced by a pituitary tumour or ectopic ACTH (e.g., small cell lung cancer)

Answer 123

- Trans-sphenoidal removal of pituitary adenoma (Cushing's disease) - Surgical removal of adrenal tumour - Surgical removal of tumour-producing ectopic ACTH (eg. small cell lung cancer), if possible . - Where removal of the cause is not possible --> bilateral adrenalectomy (removal of adrenal glands) is an option --> pt has to be placed on life-long steroid replacement therapy

Answer 124

- low/no endogenous cortisol following this procedure causes a massive increase in ACTH production by the pituitary gland (via negative feedback) --> this causes rapid pituitary enlargement --> this causes skin pigmentation (high ACTH)

Answer 125

- a severe, life-threatening form of hypothyroidism characterised by mental status changes and hypothermia --> often triggered by something (eg. infection) - While it shares many symptoms with typical hypothyroidism, the distinguishing feature is the altered mental status ranging from confusion to coma - Requires immediate treatment --> IV levothyroxine (T4) + supportive care (warm pt, fluids for hypotension) + treat underlying precipitating factors (eg. antibx for infection)

Answer 126

- a rare, but life-threatening condition characterised by a sudden and significant increase in thyroid hormone lvls - presents with fever, tachycardia, and delirium - Treatment is supportive --> fluids, anti-arrhythmic medication, and beta-blockers

Answer 127

- Primary hyperaldosteronism = an endocrine disorder caused by excessive secretion of aldosterone from the adrenal glands - Conn's syndrome = refers to an adrenal adenoma producing too much aldosterone

Answer 128

- Primary --> where the adrenal glands are directly responsible for producing too much aldosterone (serum renin will be low as the high blood pressure suppresses it) - Secondary --> caused by excessive renin stimulating the release of excessive aldosterone

Answer 129

Primary: - Bilateral adrenal hyperplasia - Adrenal adenoma secreting aldosterone (Conn's syndrome) . Secondary (excessive renin is released to disproportionately lower blood pressure in the kidneys), usually due to: - Renal artery stenosis - Heart failure - Liver cirrhosis and ascites

Answer 130

Zona glomerulosa - Aldosterone-producing adenoma --> benign tumour that originates from the outer layer of the adrenal gland - zona glomerulosa - Bilateral adrenal hyperplasia --> characterised by an enlargement of both adrenal glands due to an increased number of cells in the zona glomerulosa

Answer 131

1. Refractory hypertension --> stubborn hypertension due to excess aldosterone causing Na+ retention and K+ excretion, leading to an increase in blood volume and consequently blood pressure 2. Hypokalaemia --> due to excess K+ excretion (symptoms include muscle weakness, cramps, palpitations) 3. Metabolic alkalosis --> due to increased H+ secretion stimulated by aldosterone . (Note: a significant proportion of pts with primary hyperaldosteronism will be asymptomatic --> often identified when looking into refractory hypertension)

Answer 132

- Plasma aldosterone/renin ratio is first-line --> primary hyperaldosteronism should show high aldosterone lvls with low renin lvls (-ve feedback due to sodium retention from aldosterone) - High-resolution CT abdomen --> look for adrenal tumour/hyperplasia - Renal artery imaging (doppler, CT angiogram) --> to look for renal artery stenosis - adrenal vein sampling --> can distinguish between unilateral adenoma and bilateral hyperplasia (uses aldosterone lvls in blood to tell you which gland is producing more aldosterone)

Answer 133

- Percutaneous renal artery angioplasty --> via femoral artery to treat renal artery stenosis

Answer 134

- Surgery --> laparoscopic adrenalectomy (removal of the adenoma) is treatment of choice - Medical (if surgery contraindicated or bilateral disease) --> aldosterone antagonists (eg. eplerenone, spironolactone)

Answer 135

Hyperaldosteronism --> worth investigating if pt with hypertension isn't improving with hypertension medications and/or have a low potassium

Answer 136

- a tumour of the adrenal glands that secretes unregulated and excessive amounts of catecholamines (adrenaline) - to be more specific, it is a tumour of the chromaffin cells

Answer 137

- by chromaffin cell sin the adrenal medulla of the adrenal glands - adrenaline is a catecholamine hormone that stimulates the sympathetic nervous system and is responsible for the "fight or flight" response

Answer 138

About 30-40% of pts have a genetic cause: - multiple endocrine neoplasia type II (MEN 2) - neurofibromatosis type 1 - von Hippel-Lindau disease

Answer 139

- 10% bilateral - 10% cancerous - 10% outside the adrenal gland --> most common site is organ of Zuckerkandl, adjacent to the bifurcation of the aorta

Answer 140

Features are typically episodic - relating to periods when the tumour is secreting adreanlaine: - Hypertension (in 90% of cases) - Diaphoresis (sweating) - Tachycardia

Answer 141

- Plasma free metanephrines - 24hr urinary collection of metanephrines (measuring the serum catecholamine or adrenaline level is unreliable as the levels fluctuate and have a very short half-life of only a minute or so --> metanephrines (a breakdown product of adrenaline) have a longer half-life with more stable levels) - CT or MRI --> can be used to localise tumour - Genetic testing of pt +/- relatives

Answer 142

- Surgery --> definitive management - Medical --> alpha-blocker (eg. phenoxybenzamine) given before a beta-blocker (eg. propranolol) (Note: patients have their symptoms controlled medically before surgery to reduce the anaesthesia and surgery risks) (alpha-blockers given before beta-blockers to reduce vasoconstriction and normalise blood pressure, beta-blockers are then added to control tachycardia or arrhythmias)

Answer 143

- Primary --> caused by excess secretion of PTH by a tumour of the parathyroid glands resulting in hypercalcaemia - Secondary --> where there is insufficient vitamin D or CKD reduces calcium absorption from the intestines, kidneys, and bones --> this results in hypocalcemia --> this causes parathyroid glands to increase PTH production --> so calcium lvls are low/normal and PTH lvls are high

Answer 144

Primary hyperparathyroidism

Answer 145

Pts with primary hyperparathyroidism are most commonly asymptomatic (raised calcium lvls picked up incidentally) - Stones --> increased risk of kidney stones - Bones --> bone pain + osteoporosis - Abdominal groans --> constipation, nausea, vomiting - Psychiatric moans --> fatigue, depression, psychosis

Answer 146

- Serum calcium --> hypercalcaemia (primary) - PTH lvls --> elevated or normal PTH with hypercalcemia supports diagnosis of primary hyperparathyroidism - Kidney function tests (eGFR) --> CKD can lead to secondary/tertiary hyperparathyroidism - Vitamin D lvls (25-hydroxyvitamin D) --> low vit D lvls can stimulate PTH secretion (leading to secondary hyperparathyroidism)

Answer 147

- 25-hydroxyvitamin D is more stable and reliable indicator of vitamin D within the body - 25-hydroxyvitamin D acts as the primary store of vitamin D

Answer 148

- Familial Hypocalciuric Hypercalcaemia (FHH) --> autosomal dominant disorder characterised by lifelong stable mild hypercalcaemia + reduced urinary calcium excretion (usually increased in primary hyperparathyroidism) - Malignancy-associated Hypercalcaemia --> PTH lvls usually suppressed + likely to be other symptoms - Secondary hyperparathyroidism --> calcium lvls will be low/normal +/- reduced eGFR +/- low vit D

Answer 149

- Parathyroidectomy for most pts --> high cure rates (98%) . Medical (when surgery not acceptable): - Calcitonin --> inhibits bone and kidney resorption of calcium - Cinacalcet --> acts to reduce serum Ca2+ conc. while not affecting bone density or urinary calcium conc. - Denosumab --> impairs Ca2+ resorption - Bisphosphonates

Answer 150

- Osteoporosis and fragility fractures - Kidney stones and kidney injury - Hypertension and heart disease - GI problems --> peptic ulcers, pancreatitis, gall stones

Answer 151

- Damage to recurrent or superior laryngeal nerves - Post-operative hypocalcemia (if removal of too much parathyroid tissue)

Answer 152

- Post-surgical --> inadvertent damage or removal of parathyroid glands during neck surgery (esp. thyroidectomy)

Answer 153

Low calcium lvls - PTH stimulates osteoclast activity leading to bone resorption and the release of calcium into the bloodstream --> low PTH means less Ca2+ being released into the bloodstream - PTH also acts on the kidneys to promote Ca2+ reabsoprtion from the glomerular filtrate --> low PTH leads to more calcium being excreted in the urine (exacerbating the hypocalcemia) . High phosphate lvls: - PTH reduces renal tubular phosphate reabsorption, leading to increased phosphate excretion --> reduced PTH action causes phosphate retention

Answer 154

The hallmark of hypoparathyroidism is hypocalcaemia, which presents with neuromuscular irritability: - Symptoms --> mild numbness or tingling of extremities and around mouth + muscle cramps + fatigue - Signs --> Chvostek's sign (twitching of facial muscles in response to tapping over facial nerve) + Trousseau's sign (carpopedal spasm induced by occluding the brachial artery with a blood pressure cuff

Answer 155

Diagnosis is made based off hypocalcaemia (+low PTH lvls) + hyperphosphataemia - ECG may show prolonged QT interval due to hypocalcemia - magnesium lvls should also be checked --> risk of magnesium deficiency

Answer 156

We want to maintain a slighlty low/low-normal serum calcium to avoid hypercalciuria and renal complications: - Oral calcium supplements (eg. calcium carbonate) + active vitamin D analogues (calcitriol or alfacalcidiol) - Monitor for hypocalcemia symptoms + phosphate and magnesium lvls + renal function and urinary calcium excretion

Answer 157

- an endocrine disorder caused by excessive secretion of growth hormone (GH)

Answer 158

produced by the anterior pituitary gland

Answer 159

- Pituitary adenoma (95% of cases) --> this can be microscopic or large enough to cause compression of local structures - Paraneoplastic syndrome (rare) --> acromegaly can be secondary to cancer --> the tumour secretes ectopic growth hormone-releasing hormone (GHRH) or growth hormone (GH)

Answer 160

- Gigantism results from excessive GH seceretion before epihyseal closure during childhood, leading to increased linear growth (height) - acromegaly occurs post-puberty resulting in enlargement of extremities rather than height

Answer 161

- Coarse facial appearance (frontal bossing), spade-like hands, increase in shoe size, increase in ring size (good measure of severity) - Large tongue (macroglossia), large protruding jaw (prognathism), interdental spaces - Excessive sweating and oily skin --> caused by sweat gland hypertrophy - Features of pituitary tumour --> hypopituitarism, headaches, bitemporal hemianopia - Raised prolactin in 1/3 cases (galactorrhoea)

Answer 162

Bitemporal hemianopia - the optic chiasm sits just above the pituitary gland - the optic chiasm is where the optic nerves from the eyes cross over to the opposite side of the head before traveling to the visual cortex in the occipital lobe - a pituitary tumour of significant size can press on the optic chiasm

Answer 163

Need to think of acromegaly --> comes up in exams apparently?

Answer 164

- Inuslin-like growth factor-1 (IGF-1) --> first-line + used to monitor - Growth hormone suppression test (or OGTT) --> used to confirm diagnosis if IGF-1 raised --> the glucose should suppress GH (failure to do so indicates acromegaly) - MRI of pituitary --> may localise a pituitary tumour (note: testing GH directly is unreliable as it fluctuates throughout the day)

Answer 165

- Trans-sphenoidal surgery --> first-line + definitive . Medical: 1. Somatostatin analogues (eg. octreotide) --> blocks GH release 2. Dopamine agonists (eg. bromocriptine) --> block GH release 3. Pegvisomant (GH receptor antagonist) --> given OD by subcut injection - Radiotherapy sometimes has a role in treatment . (if ectopic cause --> surgical removal of that tumour ideally)

Answer 166

- Somatostatin is also known as growth hormone-inhibiting hormone - it is normally secreted by the brain, gastro-intestinal tract and pancreas in response to complex triggers - one of the functions of somatostatin is to block growth hormone release from the pituitary gland

Answer 167

a type of pituitary adenoma that results in the overproduction of prolactin hormone --> it is the most common type of pituitary tumour

Answer 168

- Microprolactinomas --> smaller than 10mm - Macroprolactinomas --> larger than 10mm

Answer 169

Excess prolactin in women: - amenorrhoea (absence of menstruation) - infertility - galactorrhoea (excess milk production) - osteoporosis . Excess prolactin in men: - impotence - loss of libido +/- erectile dysfunction - galactorrhoea

Answer 170

- Headaches - Bitemporal hemianopia - hypopituitarism signs and symptoms

Answer 171

- prolactin lvls + imaging studies - eg. MRI to view pituitary tumour . - Dopamine agonists - cabergoline OR bromocriptine

Answer 172

- a rare, but life-threatening clinical syndrome characterised by acute haemorrhagic infarction of the pituitary gland (typically within an existing pituitary adenoma) - Presentation --> abrupt onset of severe headache, visual disturbances, ophthalmoplegia due to cranial nerve palsies, altered mental status, and endocrine dysfunction (adrenal insufficiency or hypopituitarism) - Investigation --> MRI (identifies hemorrhagic transformation and oedema within the sella turcica) + lab investigations (to assess anterior pituitary hormonal function) - Management --> high-dose glucocorticoid therapy + surgical decompression via transspehnoidal approach +/- fluids

Answer 173

- Coxsackie B - Enterovirus

Answer 174

- The initial presentation of type 1 diabetes - An existing type 1 diabetic who is unwell for another reason, often with an infection - An existing type 1 diabetic who is not adhering to their insulin regime

Answer 175

- Only used if there is doubt between T1DM and T2DM - (Autoantibodies in T1DM --> anti-islet cell antibodies, anti-GAD antibodies, anti-insulin antibodies) - Serum C-peptide measures levels of endogenous insulin --> tells us about whether insulin production is high or low

Answer 176

Subcutaneous injection --> injection sites should be rotated regularly to avoid lipodystrophy

Answer 177

A basal-bolus regime of insulin involves a combination of: - Background, long-acting insulin injected once a day - Short-acting insulin injected 30 minutes before consuming carbohydrates (e.g. at meals)

Answer 178

- Injecting into the same spot can cause lipodystrophy, where the subcutaneous fat hardens - Areas of lipodystrophy do not absorb insulin properly from further injections - For this reason, patients should cycle their injection sites - If a patient is not responding to insulin as expected, ask where they inject and check for lipodystrophy

Answer 179

- A pancreas transplant involves implanting a donor pancreas to produce insulin - The original pancreas is left in place to continue producing digestive enzymes - The procedure carries significant risks, and life-long immunosuppression is required to prevent rejection - Therefore, it is reserved for patients with severe hypoglycaemic episodes and those also having kidney transplants . - Islet transplantation involves inserting donor islet cells into the patient’s liver - These islet cells produce insulin and help in managing diabetes - However, patients often still need insulin therapy after islet transplantation

Answer 180

- SIADH refers to the increased release of antidiuretic hormone (ADH) from the posterior pituitary - This increases water reabsorption from the urine, diluting the blood and leading to hyponatraemia (low sodium)

Answer 181

- Antidiuretic hormone (ADH) is produced in the hypothalamus and secreted by the posterior pituitary gland --> it is also known as vasopressin - ADH stimulates water reabsorption from the collecting ducts in the kidneys

Answer 182

- Increased secretion by the posterior pituitary - Ectopic ADH, most commonly by small cell lung cancer

Answer 183

- Excessive ADH results in increased water reabsorption in the collecting ducts, diluting the blood - This excess water reduces the sodium concentration (hyponatraemia) - The extra water is not usually significant enough to cause fluid overload. SIADH results in euvolaemic hyponatraemia - Euvolaemic means normal (eu-) volume (-vol-) of blood (-aemic) . - The urine becomes more concentrated as the kidneys excrete less water --> therefore patients with SIADH have high urine osmolality and high urine sodium

Answer 184

- The symptoms of SIADH relate to low sodium (hyponatraemia) . Depending on the sodium level and how rapidly it occurs, they may be asymptomatic or present with non-specific symptoms: - Headache - Fatigue - Muscle aches and cramps - Confusion . - Severe hyponatraemia can cause seizures and reduced consciousness

Answer 185

- Post-operative after major surgery - Medications (e.g., SSRIs and carbamazepine) - Malignancy, particularly small cell lung cancer

Answer 186

1. Admission if symptomatic or severe 2. Treat underlying cause (eg. stop causative medication or treat infection) 3. Fluid restriction (to correct the hyponatraemia) 4. Vasopressin receptor antagonist (eg. tolvaptan)

Answer 187

Block ADH receptor - cause a rapid rise in sodium

Answer 188

Osmotic demyelination - can lead to encephalopathy and if persists then demyelination of the neurons (particularly in pons) - note: prevention of osmotic demyelination is important as once it occurs, treatment is only supportive and pt will be left with neuro deficit

Answer 189

- Diabetes insipidus is a condition characterized by large amounts of dilute urine and increased thirst . Diabetes insipidus occurs due to: - A lack of antidiuretic hormone (cranial diabetes insipidus) - A lack of response to antidiuretic hormone (nephrogenic diabetes insipidus)

Answer 190

- Polyuria (excessive amounts of urine) - Polydipsia (excessive thirst) (Primary polydipsia is when the patient has a normally functioning ADH system but drinks excessive amounts of water, leading to excessive urine production (polyuria). This is not diabetes insipidus)

Answer 191

Nephrogenic diabetes insipidus is when the collecting ducts of the kidneys do not respond to ADH

Answer 192

Cranial diabetes insipidus is when the hypothalamus does not produce ADH for the pituitary gland to secrete

Answer 193

- Polyuria (producing more than 3 litres of urine per day) - Polydipsia (excessive thirst) - Dehydration - Postural hypotension (Primary polydipsia is when the patient has a normally functioning ADH system but drinks excessive amounts of water, leading to excessive urine production (polyuria). This is not diabetes insipidus)

Answer 194

Investigations show: - Low urine osmolality (lots of water diluting the urine) - High/normal serum osmolality (water loss may be balanced by increased intake) - More than 3 litres on a 24-hour urine collection . - The water deprivation test is the test of choice for diagnosing diabetes insipidus.

Answer 195

- The water deprivation test is also known as the desmopressin stimulation test . 1. The patient avoids all fluids for up to 8 hours before the test (water deprivation) 2. After water deprivation, urine osmolality is measured --> if the urine osmolality is low, synthetic ADH (desmopressin) is given 3. Urine osmolality is measured over the 2-4 hours following desmopressin . - In primary polydipsia, water deprivation will cause urine osmolality to be high - Desmopressin does not need to be given - A high urine osmolality after water deprivation rules out diabetes insipidus. . - In cranial diabetes insipidus, the patient lacks ADH - The kidneys are still capable of responding to ADH. Initially, the urine osmolality remains low as it continues to be diluted by the excessive water lost in the urine - After desmopressin is given, the kidneys respond by reabsorbing water and concentrating the urine - The urine osmolality will be high . - In nephrogenic diabetes insipidus, the patient is unable to respond to ADH - The urine osmolality will be low both before and after the desmopressin is given

Answer 196

- The underlying cause should be treated (e.g., stopping lithium) - Mild cases may be managed conservatively . - Desmopressin (synthetic ADH) can be used in cranial diabetes insipidus to replace the absent antidiuretic hormone - The serum sodium needs to be monitored, as there is a risk of hyponatraemia (low sodium) with desmopressin . Nephrogenic diabetes insipidus is less straightforward to treat. Management options include: - Ensuring access to plenty of water - High-dose desmopressin - Thiazide diuretics - NSAIDs

Answer 197

most commonly a type IV hypersensitivity reaction