Endocrinology Flashcards
What is the definition of type I diabetes mellitus?
Autoimmune destruction of pancreatic β cells
What is the aetiology of type I diabetes mellitus?
HLA-DR3 + HLA-DR4
What is the clinical presentation of type I diabetes mellitus?
Polyuria, polydipsia, weight loss
What are the investigations of type I diabetes mellitus?
o Random plasma glucose: >11.1 mmol/L
o Fasting plasma glucose: >7 mmol/L
o Plasma or urine ketones: medium or high quantity
o HbA1c: >48 mmol/mol (6.5%)
What is the treatment of type I diabetes mellitus?
Insulin
What are the complications of type I diabetes mellitus?
Diabetic ketoacidosis, hypoglycaemia, diabetic retinopathy, nephropathy and neuropathy, stroke, CVD, PVD
What is the definition of diabetic ketoacidosis?
Acute metabolic complication of diabetes characterised by hyperglycaemia, ketosis, and metabolic acidosis due to absolute insulin deficiency
What is the aetiology of diabetic ketoacidosis?
Idiopathic, infection, myocardial infarction, treatment errors, undiagnosed diabetes
What is the pathophysiology of diabetic ketoacidosis?
Insulin deficiency leads to fat breakdown and the formation of glycerol and free fatty acids. Free fatty acids are transported to the liver, where they are oxidised to ketone bodies
What is the clinical presentation of diabetic ketoacidosis?
Polyuria, polydipsia, nausea and vomiting, weight loss, hyperventilation, acetone scented breath
What are the investigations of diabetic ketoacidosis?
o Random plasma glucose: >11.0 mmol/L
o Venous/arterial blood gas: pH <7.3 or bicarbonate < 15 mmol/L
o Ketone testing: capillary blood ketone ≥ 3 mmol/L or urinary ketones +++ or above
What is the treatment of diabetic ketoacidosis?
IV fluids, insulin, potassium replacement
What is the definition of type II diabetes mellitus?
Impaired insulin secretion and insulin resistance leads to impaired glucose tolerance, hyperglycaemia, and increased free fatty acids
What is the clinical presentation of type II diabetes mellitus?
Polyuria, polydipsia, polyphagia, infections
What are the investigations of type II diabetes mellitus?
o Random plasma glucose: >11.1 mmol/L
o Fasting plasma glucose: >7 mmol/L
o HbA1c: >48 mmol/mol (6.5%)
What is the treatment of type II diabetes mellitus?
Lifestyle and risk factor modifications, glycaemic management with metformin (increase insulin sensitivity and decrease hepatic gluconeogenesis), sulfonylureas (stimulate insulin secretion), insulin therapy
What is the definition of hyperosmolar hyperglycaemic state?
Acute metabolic complication of diabetes characterised by hyperglycaemia, hyperosmolality, and hypovolaemia in the absence of ketoacidosis
What is the aetiology of hyperosmolar hyperglycaemic state?
Infection (UTI, pneumonia)
What is the pathophysiology of hyperosmolar hyperglycaemic state?
Decreased insulin and increased counterregulatory hormones results in increased gluconeogenesis, accelerated glycogenolysis, and impaired glucose utilisation by peripheral tissues
What is the clinical presentation of hyperosmolar hyperglycaemic state?
Altered mental status, polyuria, polydipsia, nausea and vomiting, dehydration, tachycardia, hypotension
What are the investigations of hyperosmolar hyperglycaemic state?
o Random plasma glucose: >30 mmol/L
o Serum osmolality: ≥320 mOsm/kg
o Ketone testing: capillary blood ketone < 3 mmol/L
What is the treatment of hyperosmolar hyperglycaemic state?
IV fluids, electrolyte replacement, treatment of precipitating events
What is the definition of hypoglycaemia?
Blood glucose concentration < 3.0 mmol/L
What is the aetiology of hypoglycaemia?
Excess insulin, growth hormone deficiency, adrenal insufficiency
What is the clinical presentation of hypoglycaemia?
- Autonomic Symptoms: Tremor, palpitations, anxiety, sweating, hunger, nausea, headache
- Neuroglycopenic Symptoms: Paraesthesia, dizziness, weakness, drowsiness, confusion, altered mental status, seizure
What are the investigations of hypoglycaemia?
Serum glucose: < 4.0 mmol/L
What is the treatment of hypoglycaemia?
- Alert treatment: oral glucose load (Lucozade) and complex carbohydrate meal
- Coma treatment: IV glucose, glucagon
What is the definition of Graves’ disease?
Autoimmune hyperthyroidism
What is the aetiology of Graves’ disease?
HLA-DR3
What is the pathophysiology of Graves’ disease?
B lymphocytes produce stimulating IgG antibodies against the TSH receptors on the thyroid gland. The antibodies bind to the receptor and stimulate the release of T3 and T4
What is the clinical presentation of Graves’ disease?
Heat intolerance, sweating, weight loss, palpitations, tremor, hyperphagia, proximal muscle weakness, diarrhoea, anxiety, tachycardia, Graves ophthalmopathy, pretibial myxoedema
What are the investigations of Graves’ disease?
o TFTs: low TSH, high T3/4
o TSH receptor antibodies: positive
o Isotope uptake scan: diffuse uptake (irregular uptake with hot and cold areas in toxic multinodular goitre)
What is the treatment of Graves’ disease?
symptomatic treatment (propranolol), antithyroid medication (carbimazole and propylthiouracil (PTU), risk of agranulosis), radioactive iodine therapy, surgery
What is the definition of thyroid storm?
Potentially fatal result of untreated or undertreated hyperthyroidism
What is the aetiology of thyroid storm?
Thyroid surgery, exogenous iodine from contrast, discontinuation of medication, illness, infection, and other stress
What is the clinical presentation of thyroid storm?
Hyperpyrexia, tachycardia, hypotension, arrhythmia, volume depletion, sweating, diarrhoea, vomiting, severe agitation, anxiety
What are the investigations of thyroid storm?
TFTs: low TSH, high T3/4
What is the treatment of thyroid storm?
Symptomatic treatment (propranolol), external cooling, IV fluids, antithyroid medication and steroids
What is the definition of hypothyroidism?
Underproduction of the thyroid hormones T3 and T4
What is the aetiology of hypothyroidism?
Hashimoto’s disease (associated with HLA-DR3/4)
What is the pathophysiology of hypothyroidism?
B lymphocytes produce antibodies against TPO and thyroglobulin. There is lymphoid infiltration, autoimmune destruction, and inflammation
What is the clinical presentation of hypothyroidism?
Non-tender, painless rubbery goitre with symmetrical enlargement, dry or coarse skin, bradycardia, cold intolerance, constipation, weight gain, depression, menstrual irregularity
What are the investigations of hypothyroidism?
o TFTs: high TSH, low T3/4
o Anti-TPO antibodies: elevated in Hashimoto’s disease
o Isotope uptake scan: low uptake
What is the treatment of hypothyroidism?
moderate and severe hypothyroidism is treated with levothyroxine (synthetic T4, risk of atrial fibrillation with overtreatment)
What is the definition of myxoedema coma?
Life threatening complication of untreated or undertreated hypothyroidism
What is the aetiology of myxoedema coma?
Infection, surgery, trauma, illness
What is the clinical presentation of myxoedema coma?
Impaired mental status, hypothermia, hypoglycaemia, hypotension, myxoedema, elevated creatine kinase
What are the investigations of myxoedema coma?
TFTs: high TSH, low T3/4
What is the treatment of myxoedema coma?
IV levothyroxine and hydrocortisone, oxygen, gradual rewarming, glucose infusion
What is the definition of subacute granulomatous thyroiditis (De Quervain’s)?
Inflammation of the thyroid gland characterised by a triphasic course of transient thyrotoxicosis, followed by hypothyroidism and then a return to euthyroidism
What is the aetiology of subacute granulomatous thyroiditis (De Quervain’s)?
Usually follows an upper respiratory tract infection
What is the pathophysiology of subacute granulomatous thyroiditis (De Quervain’s)?
Cytotoxic T cell recognition of viral and cell antigens presentation leads to thyroid follicular cell damage and the formation of granulomas and fibrosis
What is the clinical presentation of subacute granulomatous thyroiditis (De Quervain’s)?
Neck pain, tender, firm, enlarged thyroid, fever, palpitations
What are the investigations of subacute granulomatous thyroiditis (De Quervain’s)?
o TFTs: TSH is low in thyrotoxic phase and variable in hypothyroid and recovery phases, T3/4 is usually elevated due to the initial thyrotoxic phase
o CRP: elevated
What is the treatment of subacute granulomatous thyroiditis (De Quervain’s)?
o Hyperthyroid phase: analgesia for pain, beta blockers for symptom control, corticosteroids for thyrotoxicosis
o Hypothyroid phase: levothyroxine
What is the definition of Cushing’s syndrome?
Pathological hypercortisolism
What is the aetiology of Cushing’s syndrome?
Exogenous corticosteroid use, Cushing’s disease (ACTH-secreting pituitary adenoma), adrenal adenoma, ectopic tumours producing ACTH
What is the clinical presentation of Cushing’s syndrome?
Central obesity, moon facies, dorsocervical fat pads (buffalo hump), purple striae, diabetes mellitus, osteoporosis, thin skin, easy bruising, hypertension, weakness
What are the investigations of Cushing’s syndrome?
o 24-hour urinary free cortisol: elevated
o 1mg overnight dexamethasone suppression test: inadequate suppression of cortisol
o High-dose dexamethasone suppression test: adequate suppression shows Cushing disease, while no suppression shows ectopic ACTH secretion
What is the treatment of Cushing’s syndrome?
o Exogenous steroid use: dose taped down
o Tumour: surgical resection, or drugs to inhibit cortisol synthesis and secretion (metyrapone and ketoconazole)
What is the definition of acromegaly?
Excessive secretion of growth hormone
What is the aetiology of acromegaly?
Pituitary adenoma which secretes excess growth hormone
What is the clinical presentation of acromegaly?
Acral enlargement, arthralgias, maxillofacial changes, excessive sweating, headache, hypogonadal symptoms (excess periods, erectile dysfunction, loss of libido), giantism (in children if before fusion of epiphyseal plates)
What are the investigations of acromegaly?
o Random serum growth hormone: elevated
o Serum insulin-like growth factor-1: elevated
o Oral glucose tolerance test: growth hormone concentration will rise (usually falls)
What is the treatment of acromegaly?
Pituitary surgery, somatostatin analogues (octreotide), dopamine agonist (cabergoline), radiotherapy
What is the definition of primary aldosteronism?
Increased secretion of aldosterone autonomous to the RAAS
What is the aetiology of primary aldosteronism?
Bilateral adrenal hyperplasia, Conn’s syndrome (aldosterone producing adenoma)
What is the clinical presentation of primary aldosteronism?
Hypertension, hypokalaemia, nocturia, polyuria, lethargy
What are the investigations of primary aldosteronism?
o Plasma potassium: normal or low
o Plasma aldosterone: renin ratio: elevated
What is the treatment of primary aldosteronism?
Aldosterone antagonists (spironolactone) or adrenalectomy
What is the definition of adrenal insufficiency?
Decreased production of adrenocortical hormones due to destructive process, or interference with hormone synthesis
What is the aetiology of adrenal insufficiency?
Addison’s disease, tuberculosis (most common cause worldwide)
What is the pathophysiology of adrenal insufficiency?
Addison’s disease is an autoimmune condition with autoantibodies against 21-hydroxylase, which results in adrenal atrophy and destruction
What is the clinical presentation of adrenal insufficiency?
Fatigue, anorexia, weight loss, hyperpigmentation, salt craving, hypotension
What are the investigations of adrenal insufficiency?
o Morning serum cortisol: decreased
o Serum electrolytes: low sodium and high potassium
o Short synacthen test: little or no change in cortisol levels
o Adrenal autoantibody test: positive in Addison’s disease
What is the treatment of adrenal insufficiency?
Cortisol replacement with hydrocortisone, aldosterone replacement with fludrocortisone
What is the definition of adrenal crisis?
Sudden acute loss of adrenal function
What is the aetiology of adrenal crisis?
Stressful events
What is the clinical presentation of adrenal crisis?
Hypotension, hypovolaemic shock, acute abdominal pain, fatigue, fever, hypoglycaemia, hyponatraemia, hyperkalaemia
What is the treatment of adrenal crisis?
IV hydrocortisone, IV fluids
What is the definition of syndrome of inappropriate anti-diuretic hormone (SIADH)?
Impaired free water excretion, usually from excessive ADH release
What is the aetiology of syndrome of inappropriate anti-diuretic hormone (SIADH)?
Malignancy, CNS disorders, tuberculosis, pneumonia, drugs
What is the pathophysiology of syndrome of inappropriate anti-diuretic hormone (SIADH)?
ADH binds to V2 receptors on the principal cells of the renal collecting tubules. Aquaporin-2 proteins are inserted into the apical membrane increased the permeability of the collecting duct. Water is reabsorbed from the renal collecting duct, decreasing the plasma osmolality
What is the clinical presentation of syndrome of inappropriate anti-diuretic hormone (SIADH)?
Euvolaemic, nausea and vomiting, altered mental status, headache, seizure, coma
What are the investigations of syndrome of inappropriate anti-diuretic hormone (SIADH)?
o Serum sodium: low
o Serum osmolality: low (<275 mOsmol/kg)
o Urine sodium elevated (>40 mmol/l)
o Urine osmolality: elevated (>100 mOsmol/kg)
What is the treatment of syndrome of inappropriate anti-diuretic hormone (SIADH)?
Fluid restriction, hypertonic saline, tolvaptan (ADH receptor antagonist), demeclocycline (reduces the responsiveness of the kidney to ADH)
What are the complications of syndrome of inappropriate anti-diuretic hormone (SIADH)?
Central pontine myelinolysis (demyelination of pontine, basal ganglion, and cerebellar regions)
What is the definition of diabetes insipidus?
Absolute or relative inability to concentrate urine, resulting in the production of large quantities of dilute urine
What is the aetiology of diabetes insipidus?
o Cranial (absolute or relative deficiency of ADH) – tumours, trauma, infections, idiopathic, genetic o Nephrogenic (renal insensitivity or resistance to ADH) – osmotic diuresis, drugs, chronic kidney disease, metabolic (hypercalcaemia, hypokalaemia)
What is the clinical presentation of diabetes insipidus?
Polyuria, polydipsia, nocturia
What are the investigations of diabetes insipidus?
o Urine osmolality: low (<300 mOsm/kg)
o Serum osmolality: normal or elevated
o Water deprivation test: plasma osmolality increases while urine osmolality remains constant
o Desmopressin stimulation test:
-Cranial diabetes insipidus: plasma osmolality will decrease, and urine osmolality will increase
-Nephrogenic diabetes insipidus: no response
What is the treatment of diabetes insipidus?
o Cranial diabetes insipidus: desmopressin
o Nephrogenic diabetes insipidus: maintenance of adequate fluid intake
What is the definition of hyperkalaemia?
An abnormally high concentration of potassium in the blood, >5.5 mmol/L
What is the aetiology of hyperkalaemia?
Increased intake of potassium in association with decreased renal excretion and decreased cellular entry of potassium or increased exit of potassium from cells
What is the pathophysiology of hyperkalaemia?
Increased plasma potassium concentration reduces the difference in electrical potential between the cardiac myocytes and serum
What is the clinical presentation of hyperkalaemia?
Asymptomatic, arrythmias, bradycardia, fatigue, weakness
What are the investigations of hyperkalaemia?
o Serum potassium: >5.5 mmol/l
o ECG: tall, tented T waves, wide QRS complex, small P waves
What is the treatment of hyperkalaemia?
Calcium gluconate (protects the myocardium), IV insulin and dextrose, nebulised salbutamol (activated beta-receptors to promote intracellular potassium shift)
What is the definition of hypokalaemia?
An abnormally low concentration of potassium in the blood, <3.5 mmol/L
What is the aetiology of hypokalaemia?
Decreased potassium intake, increased potassium entry into cells, increased potassium excretion, and in special situations such as during dialysis or plasmapheresis
What is the pathophysiology of hypokalaemia?
Increased leakage from intracellular fluid causing hyperpolarisation of the myocyte membrane decreasing myocyte excitability
What is the clinical presentation of hypokalaemia?
Asymptomatic, muscle weakness, hypotonia, hyporeflexia, palpitations, arrhythmia, nausea and vomiting, cramps
What are the investigations of hypokalaemia?
o Serum potassium < 3.5 mmol/L
o ECG: flat T waves, ST depression, prominent U waves, prolonged PR interval (U have no Pot and no T but a long PR and a long QT)
What is the treatment of hypokalaemia?
Oral or IV replacement
What is the definition of hypercalcaemia?
An abnormally high serum corrected calcium concentration in the blood, >2.6 mmol/L
What is the aetiology of hypercalcaemia?
Primary hyperparathyroidism and hypercalcaemia of malignancy
What is the pathophysiology of hypercalcaemia?
Primary hyperparathyroidism results in increased parathyroid hormone secretion, while hypercalcaemia of malignancy increases serum calcium through osteolytic metastasis, PTH-related protein, and increased 1,25-dihydroxyvitamin D production
What is the clinical presentation of hypercalcaemia?
Renal stones, bone pain, polyuria, abdominal pain and psychiatric features (stones, bones, thrones, abdominal groans and psychiatric moans), nausea and vomiting
What are the investigations of hypercalcaemia?
o Corrected serum calcium: > 2.6 mmol/l
o ECG: short QT interval
o Serum PTH: elevated in primary hyperparathyroidism and decreased in hypercalcaemia of malignancy
What is the treatment of hypercalcaemia?
Oral or IV fluids, bisphosphonates and calcitonin can be considered in severe cases
What is the definition of hypocalcaemia?
An abnormally low serum corrected calcium concentration in the blood, <2.2 mmol/L
What is the aetiology of hypocalcaemia?
Chronic kidney disease, vitamin D deficiency, hypoparathyroidism, pseudohypoparathyroidism (PTH resistance)
What is the clinical presentation of hypocalcaemia?
Paraesthesia, muscle spasms, arrhythmia, hyperreflexia, Trousseau’s sign, Chvostek’s sign
What are the investigations of hypocalcaemia?
o Corrected serum calcium: < 2.2 mmol/L
o ECG: prolonged QT interval
What is the treatment of hypocalcaemia?
o Mild: oral calcium supplements, vitamin D and magnesium replacement if deficient
o Severe: intravenous calcium gluconate
What is the definition of prolactinoma?
Benign adenoma with secretes excess prolactin
What is the pathophysiology of prolactinoma?
: Secondary hypogonadism via its inhibitory effects on gonadotropin-releasing hormone and stimulation of milk production by the mammary gland
What is the clinical presentation of prolactinoma?
Amenorrhea or oligomenorrhea, infertility, galactorrhoea, loss of libido, erectile dysfunction, visual deterioration
What are the investigations of prolactinoma?
Serum prolactin: elevated
What is the treatment of prolactinoma?
Dopamine agonists (cabergoline)
What is the definition of pheochromocytoma?
A tumour of the adrenal medulla which secretes excess catecholamines (adrenaline, noradrenaline, and dopamine)
What is the clinical presentation of pheochromocytoma?
Headache, palpitations, diaphoresis, hypertension, hypertensive retinopathy, pallor, impaired glucose tolerance and diabetes mellitus
What are the investigations of pheochromocytoma?
o 24-hour urine collection for catecholamines, metanephrines, normetanephrines, and creatine: elevated
o Serum free metanephrines and normetanephrines: elevated
o CT or MRI of the abdomen and pelvis
What is the treatment of pheochromocytoma?
α and β blockers, surgical resection
What is the definition of carcinoid syndrome?
Release of serotonin and other vasoactive peptides from a carcinoid tumour
What is the clinical presentation of carcinoid syndrome?
Diarrhoea, flushing
What are the investigations of carcinoid syndrome?
Urinary 5-hydroxyindoleacetic acid: elevated
What is the treatment of carcinoid syndrome?
Surgical resection (tumour appears yellow), somatostatin analogues (octrotide)
What is the aetiology of thyroid cancer?
Radiation exposure, iodine deficiency (follicular)
What is the clinical presentation of thyroid cancer?
Painless, palpable, solitary thyroid nodule
What are the investigations of thyroid cancer?
o Fine-needle aspiration biopsy
o Indirect laryngoscopy
o Serum calcitonin (elevated suggests medullary)
What is the treatment of thyroid cancer?
Surgical resection
What are the features of papillary thyroid cancer?
Younger patients; spreads to lymph nodes and lungs; treatment with total thyroidectomy and levothyroxine to supress TSH
What are the features of follicular thyroid cancer?
Middle age; spreads early via the blood (bone, lung), treatment with total thyroidectomy, levothyroxine to supress TSH and radioiodine ablation
What are the features of medullary thyroid cancer?
MEN syndrome; treatment with thyroidectomy and node clearance
What are the features of anaplastic thyroid cancer?
Three times more common in females, elderly patients; poor response to any treatment
