Endocrine Flashcards
Describe the hormones and feedback loops from the hypothalamus and pituitary (mnemonic)
Hypothalamus releases releasing hormones (CRH, TRH, GnRH, GHRH) other than dopamine that inhibits prolactin. Also makes oxytocin and ADH that are stored in posterior pituitary.
The anterior pituitary secretes (peptide): follicle SH, luteinizing H, adrenocorticotropic H, thyroid SH, prolactin, growth H (TP FLAG)
ACTH, FSH, LH, TSH all have negative feedback from their hormones at pituitary and hypothalamus. Prolactin and GH just have effect on hypothalamus (no secondary gland)
What is released by the posterior pituitary
ADH and oxytocin
What are the actions of insulin and glucagon
Insulin decreases amount of serum glucose. It suppresses hepatic glucose output (glycogenolysis and gluconeogenesis) and the breakdown of fat and muscle. It increases uptake into sensitive tissues: liver, muscle (glycogen + protein synthesis), fat (lipogenesis).
Glucagon increases hepatic insulin output, increases from glycogenolysis + gluconeogenesis (from lactic acid and amino acids), reduces peripheral glucose uptake, stimulates lipolysis + muscle breakdown
What are the complications of diabetes
Microvacular: retinopathy, nephropathy, neuropathy
Macrovascular: stroke, MI, renovascular, limb ischaemia + ulcers
Others like erectile dysfunction, frequent infections, poor healing of wounds, autonomic neuropahty
What are the symptoms of diabetes
Fatigue, polyuria + polydipsia, unintentional weight loss, opportunistic infections, slow wound healing
Long term: blurred vision, altered sensation in hands and feet, areas of darkened skin - acanthosis nigricans
What are the test result values to diagnose diabetes
HbA1c > 48 (6.5%) (repeat after 1m if no symptoms); > 42 prediabetes
Fasting plasma glucose >7
2 hours after 75g oral glucose > 11.1
Random glucose > 11.1
What is recommended by NICE to manage T2DM
Structured education program, low-glycaemic and high-fibre diet, exercise, healthy BMI, antidiabetic drugs, monitor and manage complications (regular checks)
What are the treatment targets for diabetics
HbA1c of 48 for new patients, 53 for patients requiring more than one medication
What class of drugs are second line in T2DM and why, when are they first line
SGLT2 inhibitors (dapagliflozin) protect against cardiovascular disease and CKD
To be offered alongside metformin when Qrisk >10%
Risk of UTI / thrush, risk of DKA
Describe the mechanisms of action of the different classes of antidiabetic drugs used
Metformin (biguanide): increases insulin sensitivity / peripheral glucose uptake, inhibits gluconeogenesis in liver + intestinal absorption
Sodium-glucose co-transporter-2 inhibitors (flozins): increased glucose excretion / reduced reabsorption in kidneys, lowers blood pressure; direct cardiac protection / improved function?
Sulfonylureas (glicazide): stimulates insulin release
DPP-4 inhibitors (alogliptin): prevents breakdown of GLP-1 and GIP hormones - increased insulin and decreased glucagon, do not cause hypos
Glucagon-like peptide-1 receptor agonist (semaglutide (ozempic)): enhances glucose dependent insulin secretion and suppressed glucagon release
What classes of drugs are used in diabetic patients with hypertension, CKD, neuropathic pain
HTN: ACE
CKD with albumin:creatinine >3 ACE; ACR > 30 dapagliflozin
Neuropathic: amitriptyline / dulozetine / gabapentin / pregabalin
Describe a hyperosmolar hyperglycaemic state
Similar to DKA without the ketones, enough insulin to prevent ketoacidosis but not enough to prevent hyperglycaemia. Usually a precipitating event like infection, glucose starts being excreted by kidneys, water follows leading to dehydration (osmotic diuresis). Large risk of cerebral oedema
Polyuria, polydipsia, dehydration, tachycardia, hypotension, confusion to coma / seizures
IV fluids, slow insulin infusion + potassium, VTE prophylaxis
Describe the bloods taken for a new diagnosis of T1DM
Baseline: glucose, HbA1c, U+Es, FBC, ketones
Other autoimmune: TFTs + TPO, anti-TTG
Abnormal presentation: C-peptide and specific T1DM autoantibodies
What in a history would make a patient more likely to be T1DM than T2DM
Peak age 10-14; suspect in child with normal diabetic symptoms
In adults: ketosis, rapid weight loss, age <50, BMI <25, personal / family history of autoimmune
Presenting with DKA: dehydration, n+v, abdo pain, tachypnoea, tachycardia, lethargy
T2DM in a child: strong family history, obese, black / asian, no insulin requirement, evidence of insulin resistance
Describe the different types of insulin and common regimes
Rapid acting - before meals (Humalog, novorapid). Isophane - cheap. Pre mixed - different % of short and long (NovoMix). Long acting analogues - bedtime
BD - twice premixed by pen (good for T2DM). QDS - rapid acting before meals and long acting overnight. Once daily before bed - initial in T2DM. Insulin pump - continuous infusion
What is the pathogenensis of diabetic ketoacidosis
Body has no available glucose or glycogen, fatty acids made into ketones as last resort
Kidneys can only compensate for acidosis for so long
Glucose in urine draws water with it causing dehydration (osmotic diuresis)
Lack of insulin means no potassium driven into cells
Cerebral oedema due to dehydration and hyperglycaemia (water extra - intracellular)
How is ketoacidosis monitored and treated
Venous blood gas, blood ketones (or urinalysis) + glucose, U+Es (measure potassium), FBC
Blood glucose >11.1, blood ketones >3, blood pH <7.3
Correct hydration over 48h (too fast - cerebral oedema), fixed rate insulin infusion, give dextrose and potassium, treat underlying cause, consider sodium bicarbonate and and VTE prophylaxis
What are the symptoms of hypoglycaemia
Start feeling hungry / shaky / sweaty, autonomic (trembling, palpitations), neuroglycopenic (confusion, drowsiness, seizures)
What are the causes of hyper and hypothyroidism
Hyperthyroidism / thyrotoxicosis (overproduction): Graves’ (Trab, TPO), toxic multi nodular goitre, toxic adenoma, thyroiditis
Hypothyroidism: primary 99% - Hashimoto’s (anti TPO, anti Tg, most common), atrophic hypothyroidism, iodine deficiency (most common global), thyroidectomy, lithium
What is the pathogenesis of Grave’s
Grave’s: autoimmune, genetic + environmental (smoking big precipitant), Abs mimic TSH causing goitre and hyperthyroidism, also receptors on orbital fibroblasts and adipocytes (inflammation, fibrosis, fat deposit)
What is the presentation and treatment of hyperthyroidism
Hyperthyroidism: heat intolerance, sweating, diarrhoea, weight loss, tachycardia, anxiety, light / infrequent periods, weakness, insomnia, brisk reflexes
Drugs, radioiodine, surgery
carbimazole blocks hormone synthesis (and immunosuppression), propylthiouracil stops conversion of T4 to T3; propranolol for symptom control only
(Carbimazole FL as propylthiouracil due to risk of severe liver injury; carbimazole is not to be used in pregnancy, risk of pancreatitis)
Radioactive iodine (locally damages thyroid) - FL definitive for Grave’s and toxic multinodular goitre
What is the presentation of Graves’
Hyperthyroidism + retro orbital inflammation and swelling of extraocular muscles, discomfort, tear production, photophobia, eventually paralysis
Orbitopathy: upper eyelid retraction, exophthalmos, optic neuropathy, extraocular muscles
What is the presentation and treatment of hypothyroidism
Hypo: weight gain, fatigue, dry skin + coarse hair, fluid retention, heavy + irregular periods, constipation, bradycardia, depression, delayed reflexes
Thyroid hormone replacement - oral levothyroxine (monitor and stop when TSH normalises, in secondary will always be low)
What is the presentation and treatment of thyroid storm / thyrotoxic crisis
Thyroid storm: typically in established hyperthyroidism with a precipitating event (surgery, trauma, infection). Fever, tachycardia + hypertension, delirium; untreated will become life threatening
Emergency admission, carbimazole / propylthiouracil, IV propranolol, lugol’s solution (iodine), hydrocortisone. O2, IV fluids, sedation if required, paracetamol
What are the layers of the adrenal glands and what do they produce
(Outer)
Glomerulosa - Aldosterone
Fasciculata - Cortisol (and other glucocorticoids)
Reticularis - DHEA (and other androgens)
Medulla - adrenaline and noradrenaline
What are the effects of cortisol and Cushing’s
Cortisol: carbohydrate + protein + lipid metabolism, deposition of fat + glycogen, Na retention / K loss (HTN), lessened immune response, bone remodelling, inhibition of gonadotropins
Obese, moon face, mood change (depression, lethargy, irritability, psychosis), proximal weakness, gonadal dysfunction, muscle atrophy, bruising + purple striae, failure to grow, infections
What tests are used to diagnose Cushing’s
FL: pregnancy test, late night saliva cortisol
Overnight dexamethasone (1mg) (reduces ACTH and cortisol), cushing’s will have no suppression >50 nanomol/L. Alternatively urine free cortisol over 24h. No suppression: 48h dexamethasone test - oral *4 for 2 days, Cushing’s no cortisol suppression
Above positive, plasma ACTH: undetectable - adrenal tumour; detectable = pituitary / ectopic, give CRH if cortisol responds - Cushing’s. MRI of suspected area
What are the treatment options for Cushing’s
Cushing’s: surgical removal, transsphenoidal removal of adenoma, unlocatable / recurring - bilateral adrenalectomy
Adrenal adenoma / carcinoma - adrenalectomy (radiotherapy / chemo may be required)
Ectopic - surgery if located, drugs to inhibit cortisol synthesis: metyrapone, fluconazole
What is the presentation and compications of acromegaly
Acral (hand + feet) enlargement + paraesthesia, arthralgias, maxillofacial change
Amenorrhoea, decreased libido, headache, snoring, weight gain
Multisystem disease: diabetes, glucose tolerance, sleep apnea, hypertension, heart disease, colon cancer
Complications: diabetes, hypertension, LVH / cardiomyopathy / arrhythmias, increased risk of IHD and CVA, increased risk of colon cancer
What are the tests and treatment for acromegaly
IGF-1 FL (non pulsatile, long half life), glucose tolerance test / growth hormone suppression test, MRI pituitary, octreotide scan
Transsphenoidal surgical removal 1st line
Surgery fails: IM octreotide (somatostatin analogue), pegvisomant (GH receptor antagonist, most effective and expensive), cabergoline (dopamine agonist). Also radiotherapy for larger tumours
What is the pathogenesis and complications of Conn’s
Excess production of aldosterone due to adrenal adenoma, independent of RAA system, resulting in increased sodium (often normal or mildly elevated) and water retention (K loss to balance), metabolic alkalosis
Severe hypertension - cardiac, renal, retinal damage. Hypokalaemia - weakness, cramps, paraesthesia, polyuria, polydipsia
How is Conn’s diagnosed and treated
Aldosterone:renin (renin has to be low) then aldosterone suppression with fludrocortisone, U+Es (hypokalaemia + hypernatraemia), selective adrenal venous sampling for location, blood pressure
Laparoscopic adrenalectomy
Aldosterone antagonist - oral spironolactone
Reduce sodium in diet
Describe the symptoms due to the different hormone deficiencies in adrenal insufficiency
Cortisol deficiency: fatigue, weakness, weight loss, susceptible to infections (overactive immune response), hypotension, abdominal pain / GI disturbance
Aldosterone deficiency: hyponatraemia (weakness, confusion, nausea), hyperkalaemia (cramps, arrhythmias), volume depletion / hypotension / dizziness
Androgen deficiency (females, men in testicles): loss of axilla / pubic hair, decreased libido
Increased ACTH: hyperpigmentation (stimulates melanocytes)
What tests are used to diagnosed Addison’s / adrenal insufficiency
Serum cortisol (8-9am), U+Es (hyponatraemia and hyperkalameia)
(Also: low blood glucose, mild hypercalcaemia, anaemia, raised liver transaminases (ALT+AST), raised TSH, raised urea + albumin, raised raised renin)
Secondary care: plasma renin, elevated plasma ACTH, ACTH stimulation (synacthen) test with inadequate cortisol response
Adreno-cortical antibodies in autoimmune adrenalitis
TB: abdominal film, CXR
How addison’s / adrenal insufficiency treated
Seriously ill on presentation - IV hydrocortisone, saline, glucose infusion
Fluid resuscitation with saline, calcium gluconate for hyperkalaemia
Hydrocortisone (cortisol) + fludrocortisone (aldosterone) replacement 3* a day, double dose for infection / trauma / surgery. Also increase in pregnancy and before strenuous exercise
What are the causes and symptoms of SIADH
Large range of causes: post operative, tumours (posterior pituitary, small cell lung), pulmonary lesions (pneumonia, TB, abscess), alcohol withdrawal, CNS (meningitis, injury, subdural haematoma, SLE), drugs (SSRI, carbamazepine)
Symptoms due to hyponatraemia: nausea and vomiting, weakness, confusion + drowsiness, fatigue, irritability, seizures, coma
How do you diagnose and treat SIADH
Clinical diagnosis: euvolaemia, hyponatraemia, low serum + high urine osmolality, high urine sodium. Distinguish from salt / water depletion, will not respond to saline
Exclude other causes: synacthen test, no diuretics, no hypokalaemia, no CKD, no heart failure or liver disease
Treat underlying cause, restrict fluid intake to 0.5-1L
Hypertonic saline if very symptomatic (salt stops brain swelling)
Oral demeclocycline daily (induces nephrogenic diabetes, inhibits action of ADH on kidneys), vasopressin antagonist tolvaptan (water excretion with no loss of electrolytes), salt and loop diuretics (furosemide)
What is the pathogenesis of diabetes insipidus
Cranial DI, reduced ADH secretion from the posterior pituitary. Idiopathic, genetic, disease of hypothalamus, tumour, infiltrative disease
Nephrogenic DI, impaired response of the kidney ADH. Mostly acquired, build resistance due to low concentration. Hypokalaemia, hypercalcaemia, drugs, renal tubular acidosis, sickle cell, prolonged polyuria (any cause), genetics
What is the presentation of diabetes insipidus
> 3L of urine per day, polydipsia, hypernatraemia (lethargy, weakness, irritability), no glycosuria
How do you diagnose and treat diabetes insipidus
Measure urine volume, water deprivation test (measure plasma osmolality, rises abnormally, healthy will stay the same and urine will rise)
Nephrogenic vs cranial, give IM vasopressin and cranial will have concentrated urine
Bloods (glucose for DM), MRI of hypothalamus, renal + pituitary function
Cranial: oral desmopressin, treat cause
Nephrogenic: treat cause, thiazide diuretics, lots of water, ibuprofen
Thiazide diuretics used as actually decrease urine volume, reduce sodium reabsorption
What is the pathogenesis of hyperparathyroidism
Primary hyperparathyroidism: parathyroid tumour causes uncontrolled PTH secretion
85% single adenoma, 15% multigland. Presentation is hypercalcaemia or asymptomatic
Secondary: vitamin D deficiency or chronic kidney disease, low calcium absorption - hypocalcaemia and reactive increase in PTH secretion (low calcium, high PTH)
Tertiary: long term secondary, hyperplasia of glands and increased PTH secretion, secondary treated but now left with increased PTH production (high PTH, high calcium)
What are the symptoms and causes of hypercalcaemia
Hypercalcaemia: (kidney) stones, bones, abdominal groans, psychiatric moans
Bone pain, osteopenia / osteoporosis, fractures
Groans: abdo pain, constipation, n+v. (excitable GI smooth muscles)
Moans: fatigue / weakness, depression, psychosis, irritability
Mild adjusted 2.6-3 mmol/L, moderate 3-3.4, severe >3.4
Severe: arrhythmias, short QT, confusion, coma, cardiac arrest. Neuromuscular weakness and hyporeflexia
Calcium: accelerates the repolarisation phase and reduces the automaticity of SA node. Also increases the threshold potential of nerves, less depolarisation
Causes: parathyroidism, malignancy (parathyroid, bone, multiple myeloma), medications (lithium, thiazides), chronic renal failure (secondary hyperparathyroidism), Paget’s, familial hypocalciuric hypercalcaemia, MEN
Malignancy vs parathyroid: decreased albumin / chloride, alkalosis, increased phosphorus + ALP
How do you investigate hypercalcaemia and hyperparathyroidism
Ix: serum calcium / adjusted calcium (albumin), PTH, 25-hydroxyvitamin D, ALP, phosphorus, 24h urinary calcium, DXA
Neck US / CT / MRI, technetium99 sestamibi scan / SPECT
How do you treat hyperparathyroidism and hypercalcaemia
Symptomatic parathyroidism: parathyroidectomy, vitamin D. consider bisphosphonates, cinacalcet
Indications for surgery: ca >2.85 / 0.25 mmol/L, osteoporosis, kidneys affected, age <50
Hypercalcaemia: IV fluids, bisphosphonates, calcitonin if available, treat cause (chemo, steroids). Severe needs hospital admission
What are the causes and the presentation of hypocalcaemia
Hypoparathyroidism, vit D deficiency, CKD, acute pancreatitis, medications, hyperphosphataemia, osteoblastic bone mets, severe burns, hypoalbuminaemia, hungry bone D (parathyroidectomy)
(Meds: loop diuretics, bisphosphonates, calcimimetics)
Hypocalcaemia: paraesthesia, muscle cramps, tetany, numbness, seizures, confusion, coma
(Reduces threshold potential required for neuronal depolarisation (spontaneous firing), required for proper muscle contraction, long QT (calcium repolarises))
How do you treat hypocalcaemia
Mild: oral calcium gluconate, cholecalciferol / calcitriol. Severe: IV CG +/- IV dextrose
CKD: alfacalcidol (active vit D)
What is the presentation and investigations for thyroid cancer
Sx: neck lump, hoarse voice, dys / odyno phagia, dyspnoea, stridor. General: fatigue, weight loss, diarrhoea
Exam: firm, fixed, regional lymphadenopathy, goitre, stridor
Ix: TFTs, US + fine needle aspiration; TSH usually normal; US size, solid / cystic, scoring, nodes; FNA (if >1cm or highly suspicious US) Bethesda system
What are the treatment options for thyroid cancer
If very low risk, active surveillance with US for 6-12m
Lobectomy if 1-4cm and no extra thyroidal extension (papillary, follicular, Hurthle)
Total thyroidectomy + hormone replacement +- central neck dissection +- TSH suppression (levothyroxine) +- radioactive iodine (i.e. still abnormal TFTs post surgery)
Following surgery radioiodine scan
Recurrent / metastatic: radiotherapy, thermal ablation, kinase inhibitors (sorafenib, lenvatinib)
Anaplastic / primary thyroid lymphoma - chemo
Describe neuroendocrine tumours
NET: neuroendocrine cells (capable of producing hormones), slowly progressive, functional (symptomatic) in 40%; in children most commonly: appendix, lungs; adults most commonly: digestive tract (48%) / pancreas, lungs
Digestive tract: pain, n+v, diarrhoea, constipation, jaundice, blood in stool, confusion
Lungs: sob, chest pain, wheeze, haemoptysis, infections
Pancreas has several types: gastrinoma (^acid, ulcers), glucagonoma (hyperglycaemia), insulinoma (hypoglycaemia), somatostatinoma, VIPoma (chronic diarrhoea)
Describe phaeochromocytomas
Tumour of adrenal glands that secretes excessive catecholamines (adrenaline) by chromaffin cells
35% genetic, 10% rule: 10% bilateral, 10% cancerous, 10% outside adrenals
Anxiety, sweating, headache, tremor, palpitations, hypertension, tachycardia
Plasma free metanephrines, 24h urine catecholamines. CT / MRI, genetic testing
Doxazosin (or phenoxybenzamine, alpha blockers), beta blockers once established on alpha, surgical removal of tumours
