Endocrinology Flashcards
Describe the mechanism of action of water soluble hormones, giving some examples of them.
- They are synthesised + then stored in vesicles to be released when they’re required.
- They enter cells by binding to cell surface receptors.
- Peptide hormones like TRH, LH + FSH
Describe the mechanism of action of fat soluble hormones, giving some examples of them.
- They are synthesised + released on demand.
- Cell receptors are located in the cytoplasm.
- Steroid hormones like cortisol.
Describe the synthesis pathway of amine hormones and how they are broken down.
Phenylalanine > L-tyrosine > L-dopa > Dopamine > NAd + Ad.
- Broken down into normetadrenaline + metadrenaline by the enzymes MAO + COMT.
Give examples of hormones that act on nuclear cell receptors.
Thyroid, vitamin A + D and oestrogen.
What part of the trilaminar disc is the anterior pituitary gland derived from?
The ectoderm (Rathke’s pouch).
How do hormones travel from the hypothalamus to the anterior pituitary gland?
The hypothalamo-hypophyseal portal vessels.
Name the 6 hormones produced by the hypothalamus.
- Thyrotropin-releasing hormone (TRH).
- Corticotropin-releasing hormone (CRH).
- Gonadotropin-releasing hormone (GnRH).
- Growth hormone releasing hormone (GHRH).
- Somatostatin (inhibitor).
- Dopamine (inhibitor).
Name the 6 hormones produced by the anterior pituitary gland.
FLATPIG…
- Follicle stimulating hormone (FSH).
- Luteinising hormone (LH).
- Adrenocorticotropic hormone (ACTH).
- Thyroid stimulating hormone (TSH).
- Prolactin.
- Growth hormone (GH).
Describe the thyroid axis.
Hypothalamus > TRH > TSH > Thyroid > T3+4
- T3/4 have a -ve feedback effect on the hypothalamus + anterior pituitary gland.
Which has a longer half-life, triiodothyronine (T3) or thyroxine (T4) and so which is more metabolically active?
- T4 has a half-life of 5-7 days.
- T3 has a half-life of 1 day.
- T4 has the longer half-life + so T3 is more metabolically active.
What happens to T4 peripherally?
- It’s converted into T3, the more metabolically active form.
What is the function of T3/4 in the body?
- Food metabolism.
- Protein synthesis.
- Heat production.
- Increased sympathetic action like CO + HR.
- Needed for growth + development.
Describe the adrenal cortex axis.
Hypothalamus > CRH > ACTH > Adrenal cortex (zona fasciculata) > glucocorticoid synthesis e.g. cortisol.
- Cortisol has a -ve feedback effect on the hypothalamus + anterior pituitary gland.
What are the three zones of the adrenal cortex and what do they produce?
- All produce different types of steroids called corticosteroids, where cholesterol is the precursor.
- Zona glomerulosa, produces mineralocorticoids like aldosterone.
- Zona fasiculata, produces glucocorticoids like cortisol (+ small amounts of androgens).
- Zona reticularis, produces androgens (+ small amounts of cortisol).
What are the functions of cortisol in response to stress?
- Mobilises energy sources via lipolysis, gluconeogenesis + protein breakdown as it inhibits insulin + activates glucagon.
- Vasoconstriction.
- Suppresses inflammatory + immune responses.
- Inhibits non-essential functions like growth + reproduction.
Describe the gonadal axis.
Hypothalamus > GnRH > FSH/LH > ovaries/testes.
- FSH/LH has a -ve feedback effect on the hypothalamus + anterior pituitary gland.
- Inhibin + activin also acts on the anterior pituitary gland to regulate FSH levels.
What is the function of FSH/LH in females?
- FSH acts on granulosa cells to produce oestrogen from androgens using the aromatase enzyme.
- LH acts on theca cells to produce androgens that diffuse into granulosa cells to be converted into oestrogen.
What is the function of FSH/LH in males?
- FSH acts on sertoli cells to stimulate spermatogenesis + also produces Mullerian inhibition factor (MIF), inhibin + activin.
- LH acts on Leydig cells to produce testosterone.
Describe the GH/IGF-1 axis.
Hypothalamus > GHRH (+) or somatostatin (-) > GH > Liver > IGF-1.
- IGF-1 + GH has a -ve feedback effect on the hypothalamus + anterior pituitary gland.
What is the function of IGF-1?
Induces cell division, cartilage + skeletal growth + protein synthesis.
What can inhibit GH production?
- High glucose levels.
Describe the prolactin axis.
Hypothalamus > dopamine (-) > inhibited prolactin.
Prolactin has a -ve feedback effect on the hypothalamus + anterior pituitary gland.
What does prolactin do?
Acts on the mammary glands to produce milk.
Where is the posterior pituitary gland derived from embryologically?
- The floor of the ventricles.
What are the two hormones synthesised in the posterior pituitary gland + where are they synthesised?
- Oxytocin = para-ventricular nucleus.
- Vasopressin/ADH = supra-optic nucleus.
What is the function of oxytocin?
Acts by stimulating milk secretion + uterine contractions.
What is the function of vasopressin/ADH?
Acts on the collecting ducts of the nephron + increases the insertion of aquaporin 2 channels to cause water retention.
TYPE 1 DIABETES MELLITUS
What is the pathophysiology of T1DM and the effect of this?
- Autoimmune destruction of the pancreatic beta cells.
- Causes severe insulin deficiency meaning that glycogenolysis/gluconeogenesis/lipolysis are NOT suppressed + there is reduced peripheral glucose uptake leading to hyperglycaemia + glycosuria.
TYPE 1 DIABETES MELLITUS
What genetics are associated in T1DM?
- HLA-DR3 + HLA-DR4 but triggered by one or more environmental antigens.
TYPE 1 DIABETES MELLITUS
What is the aetiology of T1DM?
Insulin deficiency from autoimmune destruction of the insulin-secreting pancreatic beta cells as they express HLA antigens.
TYPE 1 DIABETES MELLITUS
What is the clinical presentation of T1DM?
- Typically presents in childhood, before puberty + patients often slim.
- Polydipsia (fluid + electrolyte loss).
- Polyuria (osmotic diuresis).
- Weight loss.
- Ketosis.
TYPE 1 DIABETES MELLITUS
What is the diagnostic criteria for T1DM?
Signs of hyperglycaemia + one or more of…
- Ketosis.
- Rapid weight loss.
- Age of onset <5 y/o.
- BMI < 25kg/m^2.
- FHx of autoimmune disease.
TYPE 1 DIABETES MELLITUS
What are the 2 main complications with T1DM?
- Diabetic ketoacidosis (DKA).
- Hypoglycaemia.
TYPE 1 DIABETES MELLITUS
What happens in DKA?
- Occurs due to the absence of insulin, there is uncontrollable lipolysis which causes an increased production of free fatty acids.
- These free fatty acids are oxidised in the liver to form ketone bodies causing ketoacidosis to occur.
TYPE 1 DIABETES MELLITUS
Give some examples of ketone bodies.
- Acetoacetate.
- Acetone.
- Beta-hydroxybutyrate.
TYPE 1 DIABETES MELLITUS
What are the signs of DKA?
- HYPOtension.
- TACHYcardia.
- Kussmaul’s breathing (deep + laboured).
- Ketotic breath (fruity).
- Dehydration.
TYPE 1 DIABETES MELLITUS
How does hypoglycaemia present?
- Sweating.
- Palpitations.
- Confusion.
- Drowsiness.
- Seizures.
- Potentially comas.
TYPE 1 DIABETES MELLITUS
What is the most common cause of hypoglycaemia in patients with T1DM?
- Insulin therapy.
TYPE 1 DIABETES MELLITUS
How is hypoglycaemia diagnosed + managed?
- Plasma glucose ≤ 3mmol/L.
- Managed with glucose (food/IV infusion based on consciousness), glucagon + medication review.
TYPE 1 DIABETES MELLITUS
What is the general treatment for T1DM?
Education + lifestyle advice.
- Ensure patient understands benefits of exercise, eating healthily (less sat fats, sugars + more carbohydrates).
TYPE 1 DIABETES MELLITUS
What is the pharmacological treatment for T1DM and how is it administered?
Insulin.
- Usually administered by subcutaneous injection.
- Sometimes administered by insulin pump (continuous SC injection) when attempts to reach HbA1c goal with multiple daily injections hasn’t worked or caused disabling hypoglycaemia.
TYPE 1 DIABETES MELLITUS
What are the complications with insulin therapy?
- HYPOGLYCAEMIA.
- Lipohypertrophy at injection site (cycle injection sites).
- Insulin resistance.
- Weight gain.
- Lifestyle interference.
TYPE 2 DIABETES MELLITUS
What is the pathophysiology in T2DM?
- Beta cell mass is reduced to 50% of the normal mass resulting in an inappropriately low insulin secretion + peripheral insulin resistance causing impaired glucose tolerance.
- Impaired insulin secretion is thought to be as a result of lipid deposition in the pancreatic islets.
TYPE 2 DIABETES MELLITUS
What is the aetiology of T2DM?
- Genetic predisposition + environmental factors.
- NO HLA LINK.
TYPE 2 DIABETES MELLITUS
What are the risk factors for T2DM?
- Obesity.
- Physical inactivity.
- FHx.
TYPE 2 DIABETES MELLITUS
What is the clinical presentation of T2DM?
- Typically presents in Asians, men + has an older presentation.
- Often asymptomatic.
- Can present with signs of hyperglycaemia like polyuria + polydipsia if v severe.
TYPE 2 DIABETES MELLITUS
Impaired glucose tolerance can be an indicator of pre-diabetes and so insulin resistance. What would the Oral Glucose Tolerance Test (OGTT) show in someone with pre-diabetes?
7.8mmol/L ≤ 2-hour value < 11.1mmol/L.
TYPE 2 DIABETES MELLITUS
Impaired fasting glucose can be an indicator of pre-diabetes and so insulin resistance. What would the fasting plasma glucose (FPG) be in someone with pre-diabetes?
6.1mmol/L ≤ FPG < 7.0mmol/L.
TYPE 2 DIABETES MELLITUS
What 3 diagnostic criteria are needed to make a diagnosis of T2DM?
- Symptomatic + 1 abnormal glucose result.
- Asymptomatic + 2 separate abnormal glucose results.
- Abnormal HbA1c.
TYPE 2 DIABETES MELLITUS
When is a HbA1c test contraindicated for diagnosing T2DM?
- Pregnancy.
- T1DM.
- Children.
- Haemoglobinopathies.
TYPE 2 DIABETES MELLITUS
What are the symptoms of hyperglycaemia + so T2DM?
- Polyuria.
- Polydipsia.
- Unexplained weight loss.
- Lethargy, visual blurring.
TYPE 2 DIABETES MELLITUS What are the diagnostic values in T2DM for... i) Fasting plasma glucose. ii) Random plasma glucose. iii) OGTT 2-hour value. (iv) HbA1c
i) Fasting ≥7mmol/L
ii) Random ≥11.1mmol/L.
iii) OGTT 2-hour value ≥11.1mmol/L.
iv) HbA1c ≥48mmol/mol.
TYPE 2 DIABETES MELLITUS
What are the main complications associated with T2DM?
- Hyperglycaemia hyperosmolar state.
- Hypoglycaemia.
TYPE 2 DIABETES MELLITUS
Why is ketoacidosis not a feature of T2DM?
- Despite the impaired insulin secretion there are still some low levels of plasma insulin which is enough to prevent muscle catabolism + ketogenesis.
TYPE 2 DIABETES MELLITUS
What is hyperglycaemic hyperosmolar state caused by and how do patients present?
- Caused by insufficient oral hypoglycaemia agents.
- Presents with polydipsia, polyuria, nausea + dry skin.
- Plasma glucose can be ≥40mmol/L.
TYPE 2 DIABETES MELLITUS
What are the potential complications in the hyperglycaemic hyperosmolar state and how are these managed?
- Causes hyperviscosity of the blood + so a risk of stroke/MI.
- Managed with low molecular weight heparin prophylaxis, fluids + insulin if v severe.
TYPE 2 DIABETES MELLITUS
How does hypoglycaemia present and what is the most common cause of it in T2DM?
- Presents as sweating, palpitations, confusion, drowsiness, seizures + potentially comas.
- Most common cause in T2DM is sulfonylurea treatment.
TYPE 2 DIABETES MELLITUS
How is hypoglycaemia diagnosed + managed?
- Plasma glucose ≤ 3mmol/L.
- Managed with glucose (food/IV infusion based on consciousness), glucagon + medication review.
TYPE 2 DIABETES MELLITUS
What is the first-line treatment for pre-diabetes and T2DM?
Lifestyle modification advice + risk factor reduction.
- Control diet, weight + exercise more.
TYPE 2 DIABETES MELLITUS
What drug is used first for monotherapy in T2DM?
- Metformin.
TYPE 2 DIABETES MELLITUS
What drugs other than Metformin are used to treat T2DM?
- Sitagliptin.
- Glitazone.
- Gliclazide.
- Empagliflozin.
- Insulin (last resort).
TYPE 2 DIABETES MELLITUS
Describe the pharmacology of Metformin.
- Biguanide.
- Increases insulin sensitivity, reduces gluconeogenesis in the liver + helps weight.
- SIde effects can include nausea, diarrhoea + abdominal pain.
- Does NOT cause hypoglycaemia.
TYPE 2 DIABETES MELLITUS
Describe the pharmacology of Sitagliptin.
- DPP4-inhibitor/gliptin.
- Inhibits DPP4 + increases the effect of incretins which stimulate insulin secretion.
- Does NOT affect weight.
TYPE 2 DIABETES MELLITUS
Describe the pharmacology of Glitazone.
- Pioglitazone.
- Enhances uptake of fatty acids + glucose.
- Side effects can include HYPOGLYCAEMIA, WEIGHT GAIN + fluid retention.
TYPE 2 DIABETES MELLITUS
Describe the pharmacology of Gliclazide.
- Sulfonylurea.
- Stimulates beta cells to secrete insulin.
- Side effects can include HYPOGLYCAEMIA + WEIGHT GAIN.
TYPE 2 DIABETES MELLITUS
Describe the pharmacology of Empagliflozin.
- Selective sodium-glucose co-transporter-2 inhibitor (SGLT-2i).
- Blocks the reabsorption of glucose in the kidneys + promotes excretion of excess glucose in the urine.
DIABETES MELLITUS
What is the main risk factor for diabetic complications?
Poor glycaemic control.
DIABETES MELLITUS
What can acute and chronic hyperglycaemia cause?
- Acute = DKA + hyperosmolar coma.
- Chronic = micro/macrovascular tissue complications.
DIABETES MELLITUS
Give 3 examples of microvascular diabetic complications.
- Diabetic retinopathy.
- Diabetic nephropathy.
- Diabetic peripheral neuropathy.
DIABETES MELLITUS
What is the pathophysiology of diabetic retinopathy?
Micro-aneurysms lead to pericyte loss + protein leakage resulting in occlusion + subsequent ischaemia.
DIABETES MELLITUS
What are the types of diabetic retinopathy?
- R1 grade = non-proliferative/background retinopathy.
- R2 grade = pre-proliferative.
- R3 grade = proliferative.
DIABETES MELLITUS
What is seen in R1 grade retinopathy?
- Micro-aneurysms (dots).
- Haemorrhages (blots).
- Hard exudates (lipid deposits).
DIABETES MELLITUS
What is seen in R2 grade retinopathy?
Signs of ischaemia…
- Cotton-wool spots (e.g. infarcts).
- Haemorrhages.
- Venous beading.
DIABETES MELLITUS
What is seen in R3 grade retinopathy?
New vessel formation.
DIABETES MELLITUS
What are the risk factors for diabetic retinopathy?
- Poor glycaemia control + long-term DM.
- HTN.
- High HbA1c.
- Insulin therapy.
- Pregnancy.
DIABETES MELLITUS
What is the treatment for diabetic retinopathy?
- Offered annual screening to assess visual acuity.
- Laser therapy used to treat neovascularisation.
DIABETES MELLITUS
What is the hallmark of diabetic nephropathy?
- Development of proteinuria + progressive decline in renal function.
- Microscopically, there is thickening of the glomerular basement membrane as a result of hyperglycaemia.
DIABETES MELLITUS
What are the differences in presentation with diabetic nephropathy?
- T1DM = microalbuminuria develops 5-10 years AFTER diagnosis.
- T2DM = microalbuminuria PRESENT AT diagnosis.
DIABETES MELLITUS
What is the treatment for diabetic nephropathy?
- Glycaemic + BP control.
- Inhibition of RAAS system with an ACEi or ARB even when normotensive will protect kidney.
- Spironolactone (K-sparring diuretic) may help.
DIABETES MELLITUS
What is the commonest form of diabetic peripheral neuropathy?
Distal symmetrical polyneuropathy.
DIABETES MELLITUS
What are the clinical consequences of diabetic peripheral neuropathy?
Pain…
- Described as burning, paraesthesia w/ nocturnal exacerbation.
Autonomic neuropathy…
- Loss of cerebrovascular autoregulation for functions like BP, HR, bowel/bladder emptying.
Insensitivity…
- Can lead to foot ulceration causing infection w/ ?amputation.
DIABETES MELLITUS
What are the signs of autonomic neuropathy in diabetic peripheral neuropathy?
- HYPOtension.
- HR affected.
- Diarrhoea or constipation.
- Incontinence.
- Erectile dysfunction.
- Dry skin.
DIABETES MELLITUS
What is the pattern of insensitivity in diabetic peripheral neuropathy?
- Starts in the toes + moves proximally.
- Glove + Stocking distribution, symmetrically.
DIABETES MELLITUS
What are the risk factors for diabetic peripheral neuropathy?
- Poor glycaemic control + long-term DM.
- HTN.
- Smoking.
- High HbA1c.
- Being overweight.
DIABETES MELLITUS
What are the treatments for diabetic peripheral neuropathy?
- Improve glycaemic control.
- Tricyclic anti-depressants (amitriptyline).
- Pain relief (paracetamol).
Podiatrist. - MDT foot clinics.
DIABETES MELLITUS
Give examples of macrovascular complications of DM.
- Cardiovascular disease + stroke.
- Vascular disease is the chief cause of death.
- MI more likely to be silent + women are at high risk as DM removes the vascular advantage of females.
DIABETES MELLITUS
What are the signs of acute ischaemia in macrovascular DM complications?
- Pulseless.
- Pale.
- Perishing cold.
- Pain.
- Paralysis.
- Paraesthesia.
DIABETES MELLITUS
What are the treatments of macrovascular DM complications?
- Address other risk factors like diet, smoking + HTN.
- ?Statins (atorvastatin).
- Prophylactic aspirin 75mg (secondary prevention).
THYROTOXICOSIS
What is the pathophysiology of thyrotoxicosis and what are the mechanisms involved?
Clinical effect of excess thyroid hormone, usually from gland hyperfunction.
3 mechanisms…
- Overproduction of thyroid hormone.
- Leakage of pre-formed hormone from thyroid.
- Ingestion of excess thyroid hormone.
THYROTOXICOSIS
What is the epidemiology of thyrotoxicosis?
- Females»_space; males.
- Presentation mainly 20-40 y/o.
THYROTOXICOSIS
What is the aetiology of thyrotoxicosis?
- 2/3 cases = Graves’ disease.
- Toxic multinodular goitre.
- Toxic adenoma.
- Exogenous iodine excess.
THYROTOXICOSIS Explain how the following cause thyrotoxicosis... i) Toxic multinodular goitre. ii) Toxic adenoma. iii) Exogenous iodine excess
i) Nodules secrete excess thyroid hormones.
ii) Solitary nodule produces T3/4.
iii) Food contamination or drugs like lithium + amiodarone.