Endocrine Flashcards
What is the definition of diabetes mellitus?
A disease in which the body’s ability to produce or respond to the insulin is impaired, resulting in abnormal metabolism of carbohydrates and elevated levels of glucose in the blood
Briefly outline the pathology of type 1 diabetes
An insulin deficiency disease characterised by loss of beta cells due to autoimmune destruction
Briefly outline the pathology of type 2 diabetes
Inappropriately low insulin secretion and peripheral insulin resistance
Name 3 examples of endocrine causes of secondary diabetes.
Acromegaly
Cushing’s syndrome
Drug-induced diabetes
Give 3 subacute presentations of diabetes
Thirst, polyuria, weight loss and fatigue, hunger, blurred vision
Give 3 acute presentations of diabetes
Diabetic ketoacidosis - polyuria and polydipsia, abdominal pain, hyperventilation, hypotension, coma
What investigations are carried out for the diagnosis of diabetes?
Fasting plasma glucose >7mmol/L
HbA1c 48mmol/mol
C peptide decreases in type 1
How do we screen for neuropathy?
Sensation - 10mg monofilament
Vibration perception (tuning fork)
Ankle reflexes
What is a serious consequence of missing a type 1 diabetes diagnosis?
Formation of ketone bodies:
Reduced insulin leads to fat breakdown and formation of glycerol and free fatty acids.
These impair glucose uptake and are transported to the liver, providing energy for gluconeogenesis.
Oxidised to form ketone bodies which dissolve in the blood and release H+, causing acidosis
What are the complications of diabetes?
Diabetic retinopathy, nephropathy, peripheral vascular disease, stroke, CVD, diabetic peripheral neuropathy
What is a hyperglycaemic hyperosmolar state and how does it present?
Hyperglycaemic hyperosmolar state - a diabetic emergency glucose >30mmol/L
Dehydration, severe hyperglycaemia, weakness, leg cramps, vision problems, altered level of consciousness
LMWH prophylaxis, then rehydrate with IV saline
What is hypoglycaemia and how does it present?
Endocrine emergency - plasma glucose <3mmol/L
Sweating, anxiety, hunger, tremor, palpitations, dizziness, confusion, drowsiness, visual trouble, seizures, coma
Treat with quick-acting carb snack
How is type 1 diabetes managed?
BD Biphasic regimen - twice daily premixed insulins by pen
QDS regimen - before meals ultra-fast insulin + bedtime long-acting analogue
Once-daily before bed long-acting insulin
Awareness of blood glucose lowering effect of exercise
DAFNE - dose adjustment for normal eating
How is type 2 diabetes managed?
Lifestyle Modification - weight loss and exercise
Ramipril - control BP, statins control cholesterol
1st line - metformin - increases cell sensitivity to insulin (SE: diarrhoea, nausea, weight loss)
HbA1c > 53 add a sulfonylurea
HbA1c > 57 add isoprene insulin
DDP4 inhibitors - prevent breakdown of incretins
What are the 3 mechanisms for increased levels of thyroid hormone?
- Overproduction of thyroid hormone
- Leakage of preformed hormone from thyroid
- Ingestion of excess thyroid hormone
What are some causes of hyperthyroidism?
Grave’s disease, congenital, thyroiditis, toxic adenoma
Name 4 symptoms of hyperthyroidism
Weight loss, tachycardia, anxiety, heat intolerance, sweating, diarrhoea, menstrual disturbance
How is hyperthyroidism diagnosed?
Thyroid function tests
Diagnosis of underlying cause
Clinical history, physical signs
Thyroid antibodies
How is hyperthyroidism treated?
Antithyroid drugs e.g. thionamides
Radioiodine
Surgery (partial/ subtotal thyroidectomy)
Describe the pathology of Graves’ disease
Increased levels of TSH receptor stimulating antibody which causes excess thyroid hormone secretion
What is Graves’ disease?
An autoimmune disease affecting the thyroid that causes hyperthyroidism and results in an enlarged thyroid
Give 4 symptoms of Graves’ disease.
Bulging eyes - Graves' ophthalmopathy Thick, red skin on shins/top of feet - Graves' dermopathy Heat sensitivity Weight loss Fine tremor of hands
How is Graves’ disease diagnosed?
Physical exam - eye exam or enlarged thyroid gland
Blood sample - low TSH and high thyroid hormones
Ultrasound - to identify enlarged thyroid gland
How is Graves’ disease managed?
Radioactive iodine therapy to destroy the overactive thyroid cells over time
Beta blockers - provide rapid relief of irregular heartbeats, tremors, heat tolerance and muscle weakness
Thyroidectomy
What is primary hypothyroidism?
Absence/dysfunction of the thyroid gland - most cases due to Hashimoto’s thyroiditis
What is secondary hypothyroidism?
Pituitary/ hypothalamic dysfunction with isolated TSH deficiency
What are the causes for hypothyroidism in children?
Neonatal hypothyroidism
Resistance to thyroid hormone
Isolated TSH deficiency
Describe the pathophysiology of primary hypothyroidism
Disease associated with the thyroid - Antibodies bind and block TSH receptors leading to inadequate thyroid hormone production and secretion
Describe the pathophysiology of secondary hypothyroidism
Disease associated with the pituitary or hypothalamus - reduced release or production of TSH leading to reduced T3/T4 release
Describe the pathophysiology of tertiary hypothyroidism
Disease associated with treatment withdrawal - thyroid overcompensates until it can re-establish correct concentrations of thyroid hormone
Name 3 symptoms of hypothyroidism
Fatigue, lethargy Weight gain Cold intolerance Menstrual disturbances Decreased perspiration Dry skin
Name 3 signs of hypothyroidism
Weight gain, jaundice, slowed speech, pallor, loss of scalp, axillary or pubic hair, bradycardia, pericardial effusion
What is a differential diagnosis for hypothyroidism?
Chronic fatigue syndrome
How is hypothyroidism diagnosed?
Bloods - increased TSH, usually decreased T3/T4 (secondary/tertiary - TSH low)
Low pulse pressure and sinus bradycardia
How is hypothyroidism managed?
Replacement of thyroid hormone - levothyroxine
Requirements vary according to cause, dose is tired until TSH normalises
What is Hashimoto’s thyroiditis?
Hypothyroidism due to aggressive autoimmune destruction of thyroid cells
What are the risk factors for Hashimoto’s?
Sex - women Age - middle age Hereditary - family history Other autoimmune disease Radiation exposure
What can trigger Hashimoto’s?
Iodine, infection, smoking
Describe the pathophysiology of Hashimoto’s?
Antibodies bind and block TSH receptors leading to inadequate thyroid hormone production and secretion
How does Hashimoto’s present?
Fatigue, increased sensitivity to cold, constipation, dry skin, brittle nails, hair loss, muscle weakness, unexplained weight gain
How is Hashimoto’s diagnosed?
Based on signs and symptoms
Blood tests - low thyroid hormone but raised TSH
Antibody test - antibodies against thyroid peroxidase (TPO antibodies)
How is Hashimoto’s managed?
Synthetic hormones - synthetic thyroid hormone levothyroxine
Resection of obstructive goitre
What are the 4 types of thyroid cancer?
Papillary, follicular, medullary, anaplastic
How do thyroid cancers present?
Painless, palpable, solitary thyroid nodule
How is thyroid cancer diagnosed?
Fine-needle aspiration biopsy (FNAB)
Indirect laryngoscopy
Elevated serum calcitonin suggests medullary thyroid carcinoma
How is thyroid cancer managed?
Malignancies require surgical intervention
How is papillary thyroid cancer treated?
Total thyroidectomy to remove non-obvious tumour
Give levothyroxine to suppress TSH
How is follicular thyroid cancer treated?
Total thyroidectomy, T4 suppression, radioiodine ablation
How is medullary thyroid cancer treated?
Thyroidectomy and node clearance
How is anaplastic thyroid cancer treated?
Excision and radiotherapy - poor response to any treatment
How is lymphoma treated?
Chemotherapy
What is Cushing’s syndrome?
An abnormal condition caused by chronic excess levels of corticosteroids in the body due to hyper function of the adrenal gland
What is Cushing’s disease?
A TUMOUR on the pituitary gland that CAUSES the gland to produce too much ACTH, leading to high levels of cortisol production
What are the symptoms of Cushing’s?
Weight gain, mood change, proximal weakness, gonadal dysfunction, acne
What are the signs of Cushing’s?
Central obesity, skin and muscle atrophy, purple abdominal striae, osteoporosis
How is Cushing’s diagnosed?
Overnight dexamethasone suppression test - 1mg dexamethasone at midnight, take serum cortisol at 8am. Normally should suppress to 50nmol/L, no suppression indicates Cushing’s syndrome
Test for plasma ACTH - if undetectable, a tumour is likely
How is Cushing’s managed?
Iatrogenic - stop causative medications
Cushing’s disease - selective removal of pituitary adenoma
What is the main cause of Cushing’s syndrome?
Corticosteroid medication
What is acromegaly?
The abnormal growth of hands, feet and face due to overproduction of growth hormone
Describe the pathophysiology of acromegaly?
Growth hormone stimulates growth of bone and soft tissue, through secretion of insulin-like growth factor-1
Name 3 symptoms of acromegaly
Acral enlargement, arthralgias, maxillofacial changes, excessive sweating, headache, backache, hypogonadal symptoms, acroparaesthesia, amenorrhoea
Name 3 signs of acromegaly
Coarsening face - wide nose, macroglossia, puffy lips, eyelids and skin, obstructive sleep apnoea
Name a differential diagnosis of acromegaly
Gigantism
How is acromegaly diagnosed?
GH >0.4ng/ml, 75mg glucose tolerance test, abnormal IGF-I
How is acromegaly managed?
Trans-sphenoidal surgery 1st line
Radiotherapy/ somatostatin analogues
What is Conn’s syndrome?
Excess aldosterone production (primary hyperaldosteronism) due to a solitary aldosterone-producing adenoma
What is primary hyperaldosteronism?
A disease of the adrenal glands involving excess production of aldosterone. (It can cause high BP)
What are the symptoms of Conn’s syndrome?
Often asymptomatic
Symptoms of hypokalaemia - weakness, cramps, paraesthesia, polyuria, polydipsia
What are the signs of Conn’s syndrome?
High blood pressure - causes headaches, blurred vision, dizziness
Low potassium - causes fatigue, increased urination and thirst
How is Conn’s syndrome diagnosed?
Investigate for suppressed renin and increased aldosterone, adrenal vein sampling, U&E - potassium may be low or normal
How is Conn’s syndrome managed?
Laparoscopic adrenalectomy
What is adrenal insufficiency?
A condition in which the adrenal glands do not produce adequate amounts of steroid hormone (cortisol)
Describe the pathophysiology of adrenal insufficiency
Autoimmune destruction of the entire adrenal cortex. Loss of cortex leads to reduction in ability to produce cortisol and/or aldosterone.
What is primary adrenal insufficiency and what are the causes?
Addison’s disease - destruction of the adrenal cortex leads to glucocorticoid (cortisol) and mineralocorticoid (aldosterone) deficiency
Caused by adrenal antibodies, very long chain fatty acids, genetics
What is secondary adrenal insufficiency and what are the causes?
Hypopituitarism/ long-term steroid therapy leading to suppression of the pituitary-adrenal axis
Caused by any steroids, imaging, genetic
What are the symptoms of Adrenal insufficiency?
Fatigue, weight loss, dizzy, faints, poor recovery from illness, headache, abdominal pain, diarrhoea, constipation
What is as an adrenal crisis?
Hypotension and cardiovascular collapse, fatigue, fever, hypoglycaemia, hyponatraemia and hyperkalaemia
What are the signs of adrenal insufficiency?
Pigmentation (primary) and pallor (secondary), hypotension
How is adrenal insufficiency diagnosed?
Family history of autoimmunity, any previous use of steroids
Low Na, high K, anaemia, borderline elevated TSH
How is adrenal insufficiency managed?
Replace aldosterone with fludrocortisone
Hydrocortisone 2/3 times daily
Mineralocorticoids to correct postural hypertension
What is diabetes insipidus?
A rare metabolic disorder in which the patient produces large quantities of dilute urine and is constantly thirsty
Describe the pathology of diabetes insipidus
it is due to a deficiency of the pituitary hormone vasopressin (ADH), which regulates reabsorption of water in the kidneys. This means that the body can’t make enough concentrated urine and too much water is passed
What is cranial diabetes insipidus?
Not enough AVP in the body to regulate urine production. Caused by damage to the hypothalamus/ pituitary gland e.g. after infection, operation, tumour, injury
What is nephrogenic diabetes insipidus?
When there is enough AVP in the body, but the kidneys fail to respond to it. Caused by kidney damage or inherited as a problem
What are the symptoms of diabetes inspidus?
Polydipsia, polyuria, tiredness, irritability, difficulty concentrating
How is diabetes insipidus diagnosed?
Water deprivation test - no liquid for 8 hours - in DI the body will still pass large amounts of dilute urine instead of small amount of concentrated urine.
Vasopressin test - inject small dose AVP and if it stops urine production it’s cranial DI, if urine production continues it’s nephrogenic
How is cranial diabetes insipidus managed?
Desmopressin can be used to replicate the functions of AVP
How is nephrogenic diabetes insipidus managed?
Thiazide diuretics, which reduce the amount of urine the kidneys produce
What is syndrome of inappropriate secretion of ADH?
The hyponatraemia and hypo-osmolality resulting from inappropriate, continued secretion or action of the ADH arginine vasopressin (AVP) despite normal or increased plasma volume, which results in impaired water excretion
What are the causes of syndrome of inappropriate secretion of ADH?
Malignancy (lung small cell, pancreas, prostate, thymus, lymphoma)
CNS disorders - abscess, stroke
Chest disease - TB, pneumonia
Describe the pathophysiology of syndrome of inappropriate secretion of ADH
Ectopic production increases the amount of ADH produced, beyond mechanisms of control. This secretion results in enhanced water reabsorption, leading to hyponatreamia
What are the clinical presentations of syndrome of inappropriate secretion of ADH?
Nausea, irritability and headache with mild dilution hyponatraemia, fits and coma with severe hyponatraemia
Name a differential diagnosis of syndrome of inappropriate secretion of ADH
Cerebral salt-wasting syndrome (CSW) - excessive ADH secretion caused by stimulation of the hypothalamus after trauma or ischaemia
How is syndrome of inappropriate secretion of ADH diagnosed?
Diagnose by serum concentrations of sodium, potassium, chloride and bicarbonate
Hyponatraemia (>20mmol/L) with corresponding hypo-osmolality (>100mOsmol/kg)
How is syndrome of inappropriate secretion of ADH managed?
Treat the cause and restrict the fluid
Consider salt +/- loop diuretic if severe
Vasopressin receptor antagonists
Describe the clinical chemistry of syndrome of inappropriate secretion of ADH
Decreased sodium and plasma osmolality
Increased urine osmolality and urine sodium
What is hyperparathyroidism?
Excessive secretion of parathyroid hormone, usually due to a small tumour in one of the parathyroid glands.
What causes primary hyperparathyroidism?
A solitary adenoma, or occasionally hyperplasia of all glands
What causes secondary hyperparathyroidism?
Decreased vitamin D intake or chronic renal failure
What causes tertiary hyperparathyroidism?
Occurs after prolonged secondary hyperparathyroidism, causing glands to act autonomously after undergoing hyper plastic or adenomatous change
Briefly outline the pathophysiology of PTH.
Parathyroid hormone is normally secreted in response to low ionised Ca2+ levels, by 4 parathyroid glands situated posterior to the thyroid. The glands are controlled by negative feedback via Ca2+ levels
What are the symptoms of primary hyperparathyroidism?
Often asymptomatic, bones (osteoporosis), stones (kidney), groans (confusion), moans (abdominal - constipation)
What are the symptoms of secondary hyperparathyroidism?
Kidney disease, with skeletal or cardiovascular complications
What are the symptoms of tertiary hyperparathyroidism?
Bones (osteoporosis), stones (kidney), groans (confusion), moans (abdominal - constipation)
Name a differential diagnosis of hyperparathyroidism
Cancers producing parathyroid hormone
How is hyperparathyroidism diagnosed?
Primary - raised Ca2+, PTH and ALP (bone resorption
Secondary - low Ca2+, raised PTH
Tertiary - raised Ca2+ and PTH
How is hyperparathyroidism managed?
Primary - surgical removal of adenoma
Secondary - calcium correction (underlying cause)
What is hypoparathyroidism?
Subnormal activity of the parathyroid glands, causing a fall in the blood concentration of calcium and muscular spasms
What are the causes of hypoparathyroidism?
Genetics, autoimmune, infiltration of the parathyroid glands by iron overload, surgery
Describe the pathology of hypoparathyroidism
PTH stimulates the activation of vitamin D, which facilitates intestinal calcium absorption, renal reabsorption of calcium as well as calcium release from bone
What are the symptoms of hypoparathyroidism?
Increased excitability of muscles and nerves. Numbness around the mouth/ extremities Cramps Tetany Convulsions
What is Chvostek’s sign (hyperparathyroidism)?
The twitching of the facial muscles in response to tapping over the area of the facial nerve
What is Trousseau’s sign (hyperparathyroidism)?
Carpopedal spasm caused by inflating the blood-pressure cuff to a level above systolic pressure for 3 minutes
What is pseudohypoparathyroidism?
A genetic defect that causes lack of response to parathyroid hormone.
What are the symptoms of pseudohypoparathyroidism?
Short stature, obesity, round faces, mild learning difficulties, short fourth metacarpals
What is hypercalcaemia of malignancy?
A higher-than-normal level of calcium in the blood due to a malignancy secreting parathyroid hormone-related protein
Which malignancies can cause hypercalcaemia and how?
Lung, oesophagus, skin, cervix, breast and kidney
The tumour secretes parathyroid hormone-related protein which results in increased calcium levels
How does hypercalcaemia of malignancy present?
Bones (osteoporosis), stones (kidney), groans (confusion), moans (abdominal - constipation)
Weight loss, anorexia, nausea, polydipsia, polyuria, constipation, abdo pain
What effect can a hypercalcaemia of malignancy seizure have on an ECG?
Short QT interval
How is hypercalcaemia of malignancy diagnosed?
Raised calcium and phosphate, decreased albumin, chloride and potassium
Alkalosis
How is hypercalcaemia of malignancy managed?
Aggressive rehydration, bisphosphonates, control of underlying malignancy
Whats is hypocalcaemia?
An abnormally low calcium concentration in the blood
What are the causes of hypocalcaemia?
HAVOC Hypoparathyroidism Acute pancreatitis Vit D deficiency Osteomalacia CKD
How does hypocalcaemia present?
SPASMODIC
Spasms, paraesthesiae, anxious, seizures, muscle tone increase, orientation impaired, dermatitis, impetigo herpetiformis, Chvostek’s sign
What effect can a hypocalcaemia seizure have on an ECG?
QT prolongation
Name 2 differential diagnoses of hypocalcaemia
Hypoparathyroidism, acute kidney injury
What are the complications of hypocalcaemia?
Dysphagia, wheezing, syncope, congestive heart failure, angina
How is hypocalcaemia diagnosed?
Measure serum albumin levels (rule out hypoalbuminaemia)
Chvostek’s/Trousseau’s sign
eGFR to look for CKD
PTH and vit D levels
How is hypocalcaemia managed?
Treat with calcium (oral/IV)
CKD - alfacalcidol
Respiratory alkalosis - correct alkalosis
What is hyperkalaemia?
An abnormally high concentration of potassium in the blood, usually due to a failure of the kidneys to secrete it
What are the causes of hyperkalaemia?
Renal impairment, metabolic acidosis, Addison’s disease, burns
How does hyperkalaemia present?
Dyspnoea, paraethesia, a fast, irregular pulse, chest pain, weakness, palpitations
What is a differential diagnosis for hyperkalaemia?
Rhabdomyolysis (muscle injury- death of muscle fibres that release their contents into the bloodstream)
How is hyperkalaemia diagnosed?
Plasma potassium >6.5mmol/L
ECG: tall tented T waves, small P waves, wide QRS complex and ventricular fibrillation
How is hyperkalaemia managed?
Treat underlying cause, polystyrene sulfonate resin - binds K+ in the gut preventing absorption and bringing K+ levels down over a few days
Dietary potassium and loop diuretic
What is hypokalaemia?
Abnormally low levels of potassium in the blood (occurs in dehydration)
Describe the pathology of hypokalaemia
Gi fluid loss -> less chloride -> increase in aldosterone -> decreased potassium reabsorption
How does hypokalaemia present?
Muscle weakness, hypotonia, hyporeflexia, cramps, tetany, palpitations, light-headedness, constipation
Name a differential diagnosis for hypokalaemia
Bartter syndrome (inherited defect that causes low potassium levels)
How is hypokalaemia diagnosed?
ECG: T wave inversion, prominent U wave
Serum potassium levels
Urine potassium, sodium and osmolality
How is hypokalaemia managed?
Potassium (oral/ IV)
Withdraw harmful medication, normalise magnesium and potassium
What are the 3 vital signs of presentation for diagnosing tumours?
- Pressure on local structure e.g. optic nerves
- Pressure on normal pituitary - hypopituitarism
- Functioning tumour e.g. prolactinoma
Which inherited conditions increase your chance of developing a neuroendocrine tumour/
Multiple endocrine neoplasia type 1
Neurofibromatosis type 1
Von Hippel-Lindaeu syndrome
What is a prolactinoma?
Lactotroph cell tumour of the pituitary
How do proclactinomas present?
Local effect of tumour - headache, visual field defect
Effect of prolactin - amenorrhoea
Loss of libido
How are prolactinomas diagnosed?
Ultrasound, CT, MRI, PET
How are prolactinomas managed?
Dopamine agonists e.g. cabergoline
What is a pheochromocytoma?
A catecholamine (adrenaline) secreting tumour - tumours of the chromaffin cells of the medulla (these produce catecholamine)
How do pheochromocytomas present?
Episodic, headaches, palpitations, sweating, tremor, anxiety and nausea, hypertension, tachycardia, pallor
How are pheochromocytomas diagnosed?
24 hour urine collection for urinary catecholamines and metabolites
How are pheochromocytomas managed?
Surgery preceded by alpha and beta blockers to stagger adrenaline loss
What is a carcinoid tumour?
Neuroendocrine tumours that particularly affect the small bowel, large bowel or appendix.
Common sites: appendix, ileum, rectum
Describe the pathophysiology of carcinoid tumours
Carcinoid tumours are a group of tumours of enterochromaffin cell origin, capable of producing 5HT. They secrete bioactive compounds e.g. serotonin and Kallikrein which cause carcinoid syndrome
(only with liver metastasis)
How do bowel tumours present?
Stomach pain, diarrhoea, constipation, nausea, vomiting, rectal bleeding
How do lung tumours present?
Cough, wheezing, SOB, chest pain, tiredness
How do stomach tumours present?
Pain, weight loss, tiredness, weakness
What is carcinoid syndrome?
The collection of symptoms some people get when a neuroendocrine tumour (usually hepatic involvement) releases hormone such as serotonin into the blood stream
How does carcinoid syndrome present?
Bronchoconstriction, diarrhoea, skin flushing, carcinoid crisis
What is a carcinoid crisis and how is it treated?
When a tumour outgrows its blood supply, mediators flow out causing life threatening vasodilation, hypotension, tachycardia and bronchoconstriction.
Treated with octreotide and management of fluid balance
How are carcinoid tumours diagnosed?
CXR + chest/pelvis MRI/CT to locate primary tumours
Echocardiography - carcinoid heart disease
Liver ultrasound - confirm metastasis
How are carcinoid tumours managed?
Loperamide for diarrhoea
Tumour resection is only cure for carcinoid tumours - vital to find primary site
