Endocrine Flashcards
Type 1 Diabetes Mellitus definition
Metabolic autoimmune destruction of pancreatic beta cells leading to complete insulin deficiency
Type 1 diabetes epidemiology
5-15yrs
T1DM aetiology
HLA-DR and HLA-DQ provide protection from or increase susceptibility to diabetes. Environmental factors and viruses may trigger the destruction of beta cells
T1DM risk factors
geographic region (European > Asian), genetic predisposition, infectious agents, dietary factors
T1DM pathophysiology
Autoimmune destruction of beta cells in the Islets of Langerhans by autoantibodies -> insulin deficiency and continued breakdown of liver glycogen -> hyperglycaemia and glycosuria
T1DM key presentations
polyuria, polydipsia, blurred vision, fatigue or tiredness
T1DM signs
young age (<50), weight loss, low BMI, FHx of autoimmune disease, ketoacidosis
T1DM symptoms
thirst, dry mouth, lack of energy, blurred vision, hunger, weight loss
T1DM 1st line investigations
Random glucose tolerance test >11.1mmol/L
Fasting plasma glucose, 2-hour plasma glucose, plasma or urine ketones can all be measured
T1DM gold standard investigations
Glycated haemoglobin A1C test: average blood sugar for past 2-3 months, measures % glucose attached to Hb. >6.5% = diabetes
T1DM differential diagnosis
Type 11 DM, other diabetes subtypes
T1DM management
basal-bolus insulin; pre-meal insulin correction dose; amylin analogue; 2nd line: fixed insulin dose
Side effects of insulin
hypoglycaemia; weight gain; lipodystrophy
T1DM monitoring
Check BP at each visit and treat it to a goal of <140/90mmHg
T1DM complications
Microvascular - retinopathy, nephropathy, neuropathy
Macrovascular - CAD (coronary artery disease), cerebrovascular disease, PAD (peripheral artery disease)
T1DM prognosis
Untreated type 1 is fatal due to diabetic ketoacidosis.
Blindness, renal failure, foot amputations, MIs
Type 2 Diabetes Mellitus definition
progressive disease characterised by high blood sugar, insulin resistance and a relative lack of insulin
T2DM epidemiology
Around 90% of diabetes cases, around 6% of pop in England, around 10% of NHS expenditure
T2DM aetiology
genetic predisposition (near 100% concordance in identical twins)
T2DM risk factors
ageing, physical inactivity, overweight, obesity, M>F
T2DM pathophysiology
Impaired insulin action leads to: reduced muscle and fat uptake after eating, failure to suppress lipolysis and high circulating FFAs and abnormally high glucose output after a meal.
Excessive glucose production due to hepatic insulin resistance possible due to fat deposition in liver and pancreas. This causes hyperglycemia.
Glycosuria due to hyperglycaemic blood.
Insulin suppresses lipolysis so increased FFAs in blood.
Even low levels of insulin prevent muscle catabolism and ketogenesis so profound muscle wasting and gluconeogenesis are restrained and ketone production is rarely excessive.
T2DM signs and symptoms
usually asymptomatic (maybe glycosuria or high blood glucose) but can develop signs of hyperglycaemia (polyuria, polydipsia if severe)
T2DM 1st line investigations
HbA1c: usually every 3 months, 48mmol/mol (6.5%) or greater
Fasting plasma glucose: 8hr min fast. Confirm an elevated result with HbA1c and second fasting plasma glucose, >6.9mmol/L (>125mg/dL)
Random plasma glucose: convenient but less accurate. Used for rapid assessment of glucose. >11.1mmol/L (greater than or >200mg/dL)
T2DM gold standard investigations
2hr post-load glucose after 75g oral glucose: diabetes should be confirmed on separate occasion with another test. >11.1mmol/L (>200mg/dL)
Other T2DM investigations
Fasting lipid profile; urine ketones; random C-peptide; urinary albumin; serum creatinine and estimated GFR; ECG; ankle-brachial index; dilated retinal examination
T2DM differential diagnosis
pre-diabetes; T1DM; gestational diabetes; latent autoimmune diabetes in adults
T2DM management
Diet: low carbohydrates and reduced sugar. Remission may occur with significant sustained weight loss; moderate exercise and strength training.
Cardiovascular risk management: ACE inhibitors, Ca channel blocker, or thiazide diuretic if HTN present. Home BP monitoring.
T2DM complications
Microvascular: diabetic neuropathy (leg), diabetic retinopathy (eye), diabetic nephropathy (kidney).
Microvascular: storke, MI
T2DM prognosis
Risk of MI x2
T2DM diagnosed at 40yrs men lose an average of 5.8yrs of life and women lose 6.8
Ketoacidosis definition
an acute metabolic complication of diabetes. An absolute insulin deficiency. Most common acute hyperglycaemia complication of T1DM.
Triad of hyperglycaemia, ketonaemia and metabolic acidosis with rapid symptom onset
Ketoacidosis epidemiology
Increasing for T2DM in UK
Ketoacidosis aetiology
Reduction in net effective concentration of circulating insulin and elevation in counter-regulatory hormones (glucagon, catecholamines, cortisol). Common causes are MI, sepsis and pancreatitis
Ketoacidosis risk factors
Drugs affecting carbohydrate metabolism such as corticosteroids, thiazides, cocaine and cannabis.
SGLT2 inhibitors have been indicated.
Ketoacidosis pathophysiology
Complete absence of insulin -> unrestrained increased hepatic gluconeogenesis and decreased peripheral glucose uptake. Hyperglycaemia -> osmotic diuresis -> dehydration.
Peripheral lipolysis -> increased FFA -> oxidised to Acetyl CoA -> ketones
= ACIDOSIS
Ketoacidosis key presentations
emergency admission
Ketoacidosis signs and symptoms
nausea and vomiting, abdominal pain, dehydration, hyperventilation, reduced consciousness, acetone smell on breath
Ketoacidosis 1st line investigations
venous blood gas: (pH>7 indicated mild-moderate DKA, pH<7 severe) Blood ketones Blood glucose U&Es: mostly for potassium levels FBC: leukocytosis
Ketoacidosis other investigations
Urinalysis, ECG, pregnancy test, amylase and lipase, cardiac enzymes, creatinine kinase, CXR, LFTs, cultures
Keotacidosis differential diagnosis
- Hyperosmolar hyperglycaemic state (HHS)
- Lactic acidosis
- Starvation ketosis
- Alcoholic ketoacidosis
- Salicylate poisoning
- Ethylene glycol/methanol intoxication
- Uraemic acidosis
Ketoacidosis management
- Start IV fluids as soon as DKA confirmed
- IV potassium if hypokalaemic
- Fixed rate IV insulin infusion
- Continuous cardiac monitoring
Ketoacidosis monitoring
Hourly glucose and ketones, venous blood gas, CXR if SATS fall (pulmonary oedema)
Ketoacidosis complications
- Hypokalemia
- Hypoglycemia
- Arterial or venous thromboembolic events
- Cerebral oedema/brain injury
- Pulmonary oedema/acute respiratory distress syndrome (ARDS)
- Non-anion gap hyperchloremic acidosis
Ketoacidosis prognosis
Death is rare (0.67% mortality) prognosis is worse at extremes of age and in presence of coma and hypotension
Hyperosmolar hyperglycaemic state (HHS) definition
characterised by profound hyperglycaemia (glucose >30mmol/L) and volume depletion in the absence of significant ketoacidosis
HHS epidemiology
> 1% of diabetes-related admissions
HHS aetiology
Occurs mostly in older T2DM patients. Most common causes are infections such as pneumonia and UTIs, acute illness such as MI or stroke or trauma. Can be seen in post op patients.
HHS pathophysiology
insulin is often higher than in DKA patient. Thought to be enough to suppress lipolysis and ketogenesis but not to regulate hepatic glucose production and promote glucose utilisation. Hypernatraemia and hyperglycaemia and inadequate water intake and loss result in hypovolaemia.
HHS key presentations
acute cognitive impairment. Consider foot infection
HHS signs and symptoms
Polyuria, polydipsia, weight loss, nausea and vomiting, weakness, dry mucous membranes, tachycardia, hypotension
HHS 1st line investigations
blood glucose, ketones, venous blood gas, serum osmolality, U&Es and creatinine, FBC, ECG
HHS differental diagnosis
DKA, alcohol ketoacidosis, paracetamol overdose, salicylate overdose, seizures, stroke
HHS management
fluid replacement and fixed-rate intravenous insulin. Correction of serum osmolality, electrolytes and blood glucose. Prevention of venous thromboembolism, complications of tremens and foot ulceration. Treatment of underlying cause
HHS monitoring
blood glucose; SATS; cardiac monitoring
HHS complications
Insulin-related hypoglycaemia; treatment related hypokalemia; MI; stroke; PE
HHS prognosis
high mortality (5-15%)
Grave’s disease (hyperthyroidism) deifintion
most common cause of hyperthyroidism (75-80%) of cases. It is an autoimmune condition
Grave’s disease epidemiology
predominantly females (20-30 years old)
Grave’s disease aetiology
stimulation of the thyroid by TSH receptor antibodies. Caused mostly genetic but also environmental factors. Thyrotoxicosis is the clinical syndrome resulting from the effect of excess T3 and T4 in circulation. Overall is increased metabolic rate. Toxic adenoma is an example of another cause.
Grave’s disease risk factors
more common in females, smoking, genetic: HLA-DR3 association; 50% have a family history of autoimmune disorders
Grave’s disease pathophysiology
Grave’s thyroiditis. Caused by an auto-antibody of the IgG class which binds to thyroid epithelial cells (TSH-receptor) and mimics the stimulatory actions of TSH. This antibody is known as thyroid stimulation antibodies and its effect on the thyroid is a hypersensitivity reaction. Thyroid cell dysfunction is cytotoxic (CD8+) T cell-mediated. The antibodies stimulate the function and growth of thyroid follicular epithelium. Some of the antibodies block the effects of TSH and rarely cause hypothyroidism.
Grave’s disease key presentations
Diffuse goitre (equal swelling)
Grave’s disease signs and symptoms
General for hyperthyroidism: heat intolerance (due to increase metabolism); sweating, hair loss; weight loss; diarrhoea; palpitations inc AF and tachycardia; tremor; anxiety and agitation; orbitopathy; menstrual and sexual disturbances.
Specific to grave’s: Grave’s opthalmopathy-exophthalmos, ocular motor disturbances, lid lag and retraction. Pretibial myxoedema (less common)- non-paying oedema and firm plaques on shins.
Classic triad of grave’s: hyperthyroidism, opthalmopathy, pretibial myxedema.
Grave’s disease 1st line investigations
Serum TSH. Levels will be low in hyperthyroidism.
Serum free or total T4: normal level with low TSH is suggestive of subclinical hyperthyroidism or T3 toxicosis. Elevated level with low TSH indicates overt hyperthyroidism.
Serum free or total T3: elevated free T3 and suppressed TSH suggest hyperthyroid.
T3/T4 or FT3/FT4 ratio: high ratio suggestive of grave’s disease rather than thyroiditis.
Iodine uptake: diffuse uptake in Grave’s
Grave’s disease gold standard investigations
Measure TSH receptor antibodies
Grave’s disease differential diagnosis
TSH producing pituitary tumour; toxic neck goitre; gestational hypethyroidism; subacute thyroiditis; menopause
Grave’s disease management
First step is symptomatic treatment: beta blockers (propranolol first choice) to control tachycardia, sweating and tremors.
Antithyroid drugs: 12-18 month cause or to normalise levels before surgery. Includes carbimazole, thiamazole and propylthiouracil (PTU). Decrease synthesis of new thyroid hormone. PTU also inhibits T4 to T3 conversion. Do not treat underlying cause but immune modifying effects are seen (decreased IL-6).
Radioactive iodine therapy; surgery; immunosuppressive medication and steroids for opthalmopathy and pretibial myxoedema.
Grave’s disease monitoring
monitor TSH levels after thyroxine replacement therapy following surgery or radioactive iodine therapy
Grave’s disease complications
Thyroid storm - rare but dangerous exacerbation of hyperthyroidism. Need to use PTU, beta blockers, steroid (hydrocortisone) and potassium iodide
Bone mineral loss
AF
Congestive heart failure
Sight-threatening complications of Grave’s orbitopathy
Elephantiasic demopathy
Grave’s disease prognosis
excellent following therapy although there is a high degree of relapse
Hypothyroidism definition
underproduction og thyroid hormones thyroxine (T4) and triiodothyronine (T3)
Severe hypothyroidism is called Myxoedema
Hypothyroidism epidemiology
higher rates in white populations and in women (30-50yrs)
Hypothyroidism aetiology
can be congenital or acquired. Most common cause of congenital is iodine deficiency during pregnancy -> mental retardation and other defects
Most acquired hypothyroidisms are primary (95%) and due to Hashimoto’s (Autoimmune thyroiditis) in developed countries.
Iodine deficiency most common cause in developing countries
Other primary causes include absence/dysfunction of thyroid
Can be due to surgery or iodine therapy for Grave’s
Secondary/tertiary include pituitary/hypothalamic dysfunction
Consider drugs as cause (lithium and amiodarone)
Hypothyroidism risk factors
white, female, post-partum, iodine deficiency (much less common in the developed world)
Hypothyroidism pathophysiology
T4 is the main hormone produced by the thyroid. It is converted to T3 in target tissues. T3 stimulates cellular oxygen consumption and energy generation. Failure of the thyroid to produce T3 and T4 stimulates pituitary TSH production.
Hashimoto’s thyroiditis is caused by infiltration of lymphocytes into the thyroid. (more info on Myles’ table)
Hypothyroidism key presentations
usually present with non specific symptoms of weakness, lethargy, depression and mild weight gain.
Up to half of patients have no symptoms or no specific or no specific symptoms.
Hypothyroidism signs and symptoms
Symptoms: weakness, lethargy, depression, fatigue, hoarseness, cold sensation, constipation, weight gain, brittle hair, menstrual problems, erectile dysfunction, decrease libido, puffy face
Signs: slow speech and movement, dry skin, eyelid oedema, bradycardia, diastolic hypertension, myopathy, hyporeflexia
Hypothyroidism 1st line investigations
Primary hypothyroidism - thyroid function test (TFTs)
Raised TSH (most sensitive marker) and usually low free T4 and free T3
T4/T3 may be low/normal in mild hypothyroidism
Positive titre of TPO antibodies in Hashimoto’s
Very low radio iodine uptake
Secondary/Tertiary Inappropriately low TSH for reduced T4/T3 levels
Hypothyroidism gold standard investigations
TFTs: TSH most sensitive
Hypothyroidism differential diagnosis
- Central or secondary hypothyroidism
- Depression
- Alzheimer’s
- Anaemia
Hypothyroidism management
Levothyroxine (synthetic T4)
Hypothyroidism monitoring
Measure TSH 4-6 weeks after starting therapy or dosage change
Stable patients with normal serum TSH should have TSH measured every 12 months
Hypothyroidism complications
Complications in pregnancy
Myxoedema coma (severe hypothyroidism triggered by infections, surgery, trauma, illness; generally in the elderly)
Osteoporosis
AF (overtreatment)
Resistant hypothyroidism
Angina
Non-Hodgkin lymphoma - constant infiltration of lymphocytes in any organ/tissue increases the risk that those become cancerous
Hypothyroidism prognosis
generally excellent
Thyroid nodules/cancers definition
Nodules are benign tumours, cancers are malignant
4 main types of nodule:
- Follicular Adenoma - most common; a benign tumour
- Toxic adenoma - an adenoma which can secrete thyroid hormone independent of TSH (toxic)
- Cysts - colloid filled sacks
- MNG - multiple nodules which can secrete thyroid hormone; can also cause hyperthyroidism
4 main types based on histology of cancer:
- Papillary carcinoma - most common
- Medullary carcinoma
- Follicular carcinoma
- Anaplastic carcinoma - very bad prognosis
Thyroid nodules/cancers epidemiology
most common in females (increases with age)
Nodules present in 50% of population, only palpable in 5-10%
5% of all thyroid nodules are cancerous
Thyroid nodules/cancers risk factors
ionising radiation esp. in childhood
Genetic predisposition
age
female
Thyroid nodules/cancers signs and symptoms
Asymptomatic nodule Nodule is firm and painless Neck lymph nodes may be swollen Tracheal deviation maybe present Late-stage signs - dysphagia, dyspnea, hoarseness, SVC syndrome - local infiltration and mass effects
Thyroid nodules/cancers 1st line investigations
TSH level is usually normal
Ultrasound findings - nodule with irregular margins and micro-calcifications
FNA - indicated if ultrasound findings are suspicious
Tumour markers - thyroglobulin and calcitonin (medullary carcinoma as C cells are affected)
Thyroid nodules/cancers management
Surgery followed by radioactive iodine ablation plus TSH suppression with Levothyroxine (to prevent further growth)
Cushing’s syndrome and Cushing’s disease definitions
Cushing’s syndrome is the clinical manifestation of pathological hypercortisolism (excess glucocorticoids) from any cause
Cushing’s disease is hypercortisolism caused by an adrenocorticotropic hormone (ACTH) - screwing pituitary adenoma
Cushing’s epidemiology
Relatively uncommon in general population.
Both more common in women
Cushing’s aetiology
Most common cause is exogenous corticosteroid exposure
A majority (70-80%) of endogenous Cushing’s syndrome is caused by ACTH- secreting pituitary adenomas, this is Cushing’s disease
Adrenal cortical neoplasms
Ectopic Cushing’s syndrome due to paraneoplastic syndrome such as small cell lung cancer producing ACTH
Cushing’s pathophysiology
Clinical manifestations result from excess tissue exposure to cortisol.
Excess glucocorticoids have a catabolic effect on skeletal muscle (muscle wasting) as well as catabolic effects on the epidermic and connective tissue (striae, easy bruising)
Decreased bone material density due to glucocorticoids causing increased apoptosis of osteoblasts and osteoclasts
Increased hepatic gluconeogenesis, peripheral insulin resistance and direct suppression of insulin occur
Glucocorticoids lead to increased VLDLs and LDLs and decrease in HDLs
Cortisol causes high insulin leading to weight gain
Hypertension due to up-regulation of RAS system
Cushing’s signs and symptoms
Signs: weight gain (central obesity), purple abdominal striae, acne, hirsutism (facial and body hair in women), osteoporosis
Symptoms: mood change, proximal weakness, irregular menstruation, erectile dysfunction
Cushing’s 1st line investigations
Careful drug history (oral steroids)
24hr free cortisol - normal levels help exclude Cushing’s
Overnight dexamethasone suppression test - no cortisol suppression with Cushing’s syndrome but no suppression with ectopic ACTH producing cells or adrenal adenoma
Cushing’s differential diagnosis
May be difficult to distinguish between mild Cushing’s and metabolic syndrome (central obesity with insulin resistance and HTN)
Cushing’s management
Cushing’s disease: first line is surgery to remove pituitary adenoma
Ectopic ACTH or corticotropin-releasing hormone syndrome: surgery
Cushing’s complications
Adrenal insufficiency secondary to adrenal suppression Cardiovascular disease HTN DM Osteoporosis Central hypothyroidism
Cushing’s prognosis
Untreated has a 5 year survival of 50%
Acromegaly definition
Refers to the characteristic growth of extremities. It is a chronic, progressive, multi-systemic disease associated with significant morbidity and mortality.
Gigantism occurs in children with increase GH production, not adults
Acromegaly epidemiology
Pituitary adenomas occur in 15-20% of normal subjects
Growth hormone secreting tumours make up around 20% of pituitary tumours
Often recognised in middle-age but can occur at any age
NO difference between sexes
Acromegaly aetiology
Due to pituitary somatotroph (growth hormone producing cell) adenoma in 95-99% of cases
Rare cases due to hyperplasia eg ectopic GH-releasing hormone from a carcinoid tumour
Acromegaly pathophysiology
Growth hormone stimulates growth of bone and soft tissue through insulin-like growth factor 1
Acromegaly key presentations
Insidious (slow progression with few initial symptoms)
Acromegaly signs and symptoms
Acral enlargement - big hands and feet
Arthralgias (joint pain) and headaches
Facial features growth
Excessive swelling
Amenorrhea, decreased libido
Obstructive sleep apnoea (have they started snoring?)
Acroparenthesia (tingling in the extremities)
Acromegaly 1st line investigations
75g glucose tolerance test (if GH remains high after they receive glucose = diagnostic)
Serum insulin-like growth factor 1 (IGF-1)
Acromegaly gold standard investigations
Oral glucose tolerance test with 75g glucose
Acromegaly management
1st line: surgery
Somatostatin analogue - control GH and IGF-1 (somatostatin is also known as growth hormone inhibiting hormone (GHIH))
Dopamine agonists - cabergoline - used to control GH levels and IGF-1 GH antagonist
Acromegaly complications
Cardiac complications, HTN, sleep apnoea, osteoarticular complications, impaired glucose tolerance and diabetes, pre-concerous colon polyps, carpal tunnel syndrome
Conn’s syndrome definition
Primary aldosteronism (PA), aldosterone production exceeds the body’s needs
Conn’s syndrome epidemiology
accounts for at least 5% of HTN patients with most being normokalaemic
Conn’s syndrome aetiology
unknown for most forms. genetics
Conn’s syndrome risk factors
HTN, family history of PA, family history of early onset of HTN and/or stroke
Conn’s syndrome pathophysiology
Results in excessive Na+ reabsorption via amiloride-sensitive epithelial sodium channels in the distal nephron, leading to HTN and suppression of renin and angiotensin II. Urinary loss of K+ and H+, exchanged for sodium at distal nephron may result in hypokalaemia and metabolic alkalosis if severe and prolonged
Conn’s syndrome key presentations
often asymptomatic
Conn’s syndrome signs and symptoms
Signs of hypokalemia: - weakness, cramps - paraesthesia - polyuria and polydipsia - fatigue - constipations High BP, headaches, blurred vision, dizziness
Conn’s syndrome 1st line investigations
U&Es
- serum hypokalaemia (not always present)
- decreased renin and increased aldosterone (aldosterone/renin ratio)
ECG: hypokalaemia
- flat T waves and inversion
- prolonged PR interval
- increased amplitude and width of P wave
- ST depression
- prominent U waves
- Long QT
Conn’s syndrome differential diagnosis
Essential HTN
Secondary HTN
Thiazide induced hypokalemia in patient with essential HTN
Conn’s syndrome management
Laparoscopic adrenalectomy
Aldosterone agonist eg oral spironolactone 4 weeks pre op to control BP and K+
Conn’s syndrome complications
AF, heart failure, MI, stroke
Adrenal insufficiency definition
insufficient production of steroid hormones (primarily cortisol) by the adrenal glands
adrenal insufficiency epidemiology
most common in middle aged females
adrenal insufficiency aetiology
Primary - mostly Addison’s disease (autoimmune), idiopathic, congenital adrenal hyperplasia or adenoma of the adrenal gland
Secondary - hypopituitarism
TB is the most common cause worldwide
adrenal insufficiency pathophysiology
Addion’s
Decreased production of adrenocortical hormones; mineralocorticoids (aldosterone), glucocorticoids (cortisol). Caused by destruction of the layers of the adrenal cortex (glomerulosa, fasciculate and reticular) or disruption of hormone synthesis. TB or metastasis can also cause destruction of the adrenal medulla
adrenal insufficiency key presentations
usually non-specific such as fatigue, weight loss and weakness
adrenal insufficiency signs and symptoms
Signs: pigmentation (not with secondary) and pallor, hypotension
Symptoms: fatigue, weight loss, poor recovery from illness, headache
adrenal insufficiency 1st line investigations
U&Es: low Na, high K
FBC: eosinophilia (high eosinophils), anaemia is common
Morning cortisol and ACTH
- low cortisol consistent with AI
- High ACTH indicates primary
- Low ACTH indicates secondary renin/aldo
- elevated renin in primary
adrenal insufficiency differential diagnosis
Adrenal suppression due to corticosteroid therapy (may have Cushingoid appearance, no hyperpigmentation, low ACTH due to hypothalamic-pituitary-adrenal axis suppression)
Haemochromatis
Hyperthyroidism
Anorexia nervosa
adrenal insufficiency management
oral glucocorticoid and mineralocorticoid on diagnosis
Adrenal crisis should be immediately treated with IV hydrocortisone
adrenal insufficiency monitoring
monitor plasma renin and potassium
glucocorticoid adjustments made according to signs and symptoms
long term over-replacement of glucocorticoids may be associated with lower bone density
adrenal insufficiency complications
secondary Cushing’s syndrome
Osteopenia/osteoporosis
Treatment-related HTN
adrenal insufficiency prognosis
therapy for life, good compliance
diabetes insipidus definition
diabetes insipidus (DI) is a metabolic disorder characterised by an absolute or relative inability to concentrate urine, resulting in the production of large quantities of dilute urine
diabetes insipidus aetiology
Two types: central diabetes insipidus (DI), due to reduced synthesis or release of AVP from hypothalamo-pituitary axis; and nephrogenic DI, due to renal insensitivity to AVP
diabetes insipidus risk factors
Central: pituitary surgery, craniopharyngioma, traumatic brain injury, hypothalamus-pituitary defects, autoimmune disorders
Nephrogenic: lithium therapy, CKD, chronic hypercalcaemia or hypokalemia
Genetic mutations responsible for inherited forms
diabetes insipidus pathophysiology
AVP is the key regulator of renal water loss. Lack of AVP (or its effects) leads to increased diuresis and water loss
diabetes insipidus key presentations
polyuria
polydipsia
dehydration
diabetes insipidus 1st line investigations
water deprivation test - used to confirm DI. Patient deprived of fluids for 8 hrs. Result is inappropriately low urine osmolality with corresponding high serum osmolality (failure to concentrate urine in response to dehydration).
Desmopressin stimulation test - used to distinguish between central and nephrogenic DI following water deprivation. Patients with central DI respond to desmopressin with a reduction in urine output and increased urine osmolality. Patients with nephrogenic DI do not respond to desmopressin with no or little urine reduction and no increase in urine osmolality
Diabetes insipidus management
Central DI: desmopressin
Nephrogenic DI: Bendroflumethiazide (thiazides can create mild hypovolemia which can encourage salt and water uptake in the proximal tubule), NSAIDs (can reduce urinary frequency)
Diabetes insipidus complications
Hypernatraemia
Syndrome of inappropriate secretion of ADH (SiADH) definition
Syndrome of inappropriate antidiuretic hormone (SIADH) is defined as euvolemic, hypotonic hyponatremia secondary to impaired free water excretion, usually from excessive arginine vasopressin (AVP) release.
Characterised by hypotonic hyponatremia, concentrated urine and a euvolemic state
SiADH aetiology
Excess ADH (AVP) leads to increased water reabsorption in the collecting tubule. Resulting concentrated urine with free water intake in excess of what can be excreted leads to hyponatremia
SiADH key presentations
cerebral oedema (associated with nausea, vomiting, headache, altered mental status, seizure and coma)
Concentrated urine
Weight loss and confusion
SiADH 1st line investigations
Serum osmolality: SiADH presents with hypotonic hypernatremia (low serum sodium and osmolality)
Urine osmolality: high osmolality in presence to low serum sodium and low serum osmolality
Serum urea: usually low due to mild volume expansion
Serum sodium: hyponatremia
Pseudohyponatremia can occur due to hyperglycaemia-induced water shift
SiADH management
Treat underlying cause
Fluid restriction
Vasopressin receptor antagonist (captains such as conivaptan or tolvaptan)
Hyperkalemia definiton
Significant hyperkalemia defined at serum potassium >6.0mmol/L
Moderate hyperkalemia defined as serum potassium 5.0-6.0mmol/L
Hyperkalemia aetiology
Intake issues: hyper due to excessive consumption at a fast rate - IV fluids
Excretion issues:
- low secretion due to low aldosterone (adrenal insufficiency)
- ACE inhibitor (block the binding of aldosterone to receptor)
- acute kidney injury (declined filtration rate so more K+ maintained in blood)
Combination of ACE inhibitors with potassium sparing diuretics or NSAIDs is particularly dangerous in causing hyperkalemia
Hyperkalemia pathophysiology
Insulin and beta-agonists facilitate the cellular entry of K+. Insulin deficiency and beta blockers can be followed by a rise in serum potassium values.
Metabolic acidosis can be marked by a shift of potassium from an intracellular to an extracellular location un exchange for H+ ions.
Hyperkalemia key presentations
Severe hyperkalemia often present with muscle weakness and evident on ECG. Usually asymptomatic if mild.
Detailed history important
Hyperkalemia signs and symptoms
Hyper ‘everything speeds up’
- cramping
- weakness/flaccid paralysis due to over contraction of muscles which become drained of energy
- arrhythmias and arrest
Hyperkalemia 1st line investigations
U&Es
ECG
Hyperkalemia management
Non-urgent: polystyrene sulphonate resin = binds K+ in gut decreasing uptake
Urgent:
- calcium gluconate = decreases VF risk in the heart
- insulin with glucose = drives K+ into cells
Hypokalemia definition
Defined as serum potassium <3.5mmol/L
Moderate hypokalemia defined as 2.5-3.0mmol/L
Severe hpokalemia defined as <2.5mmol/L
Hypokalemia aetiology
Intake issues: - fasting, anorexia - vomiting Excretion issues: - high excretion due t high aldosterone
Hypokalemia pathophysiology
Too much K+ follows insulin into cell Alkalosis H+ out and K+ into cell B2 agonists (SABA/LABA) increases B2 pumping of K+ into cell Low K+ into serum (ECF) causes a water concentration gradient out of the cell (ICF). Increased leakage from the ICF causing hyperpolarization of the myocyte membrane decreasing myocyte excitability
Hypokalemia key presentations
Usually asymptomatic
Hypokalemia signs and symptoms
Hypo-everything slows
Constipation
Weakness/cramps
Arrhythmias and palpitations
Hypokalemia 1st line investigations
U&Es
ECG
- U have no POT (K+) and not Tea but long PR and a long QT
U wave present, no T waves/inversion, long PR and long QT
- Associated with increased ectopic beats
Hypokalemia management
Mild: dietary improvement or oral K+
Severe: IV K+
Pheochromocytomas definition
Adrenal medullary tumour that secretes catecholamines
Pheochromocytomas epidemiology
Very rare
Pheochromocytomas aetiology
Occur in certain familial syndromes:
- multiple endocrine neoplasia (MEN) syndrome
- neurofibromatosis
- Von-Hippel Lindau disease
Pheochromocytomas risk factors
family history
Pheochromocytomas pathophysiology
Pheochromocytomas synthesise and secrete catecholamines namely: adrenaline, noradrenaline and rarely dopamine. These are converted into metanephrines and normetanephrines. Symptoms caused are due to tumour hypersecretion of catecholamines and increased stimulation of alpha and beta-adrenergic receptors
Pheochromocytomas signs and symptoms
Symptoms:
- headache
- profuse sweating (diaphoresis)
- palpitations
- tremor
Signs:
- HTN
- Postural hypotension
- Tremor
- Hypertensive retinopathy
- Pallor
Pheochromocytomas 1st line investigations
Plasma metanephrines and normetanephrines (raised)
24 hr urinary total catecholamines (raised)
CT - look for tumour
Pheochromocytomas differential diagnosis
Symptomatic phases are are episodic rather than situational
Hyperthyroidism is an important DDx
Carcinoid syndrome: this is associated with dry skin flush rather than pallor
Pheochromocytomas management
Without HTN crisis:
- 1st line: alpha blockers: phenoxybenzamine
- Most patients will get tumour removed and then managed medically
With HTN crisis:
- 1st line: antihypertensive agents: phentolamine
Pheochromocytomas prognosis
Very good if benign tumour, bad if metastatic
Hypercalcaemia definition
Calcium levels >2.6 mmol/L
Hypercalcaemia epidemiology
Hypercalcaemia much more common than hypo
Hypercalcaemia occurs in 20-30% of cancer patients
Hypercalcaemia aetiology
Malignancies (not in the parathyroid) Primary hyperparathyroidism (adenoma of the parathyroid gland(s)) (main cause) Drugs: thiazides, over-the-counter antacids, large doses of vitamin D
Hypercalcaemia pathophysiology
Serum calcium levels are mainly controlled by parathyroid hormone (PTH) and vitamin D.
Malignancies secreting parathyroid hormone related peptide (PTHrP), bony metastases promoting osteoclast differentiation and function, calcitriol secretion by lymphoma cells
Hypercalcaemia key presentations
Mild is usually asymptomatic
Hypercalcaemia signs and symptoms
Bones, stones, moans, groans
Bone pain, osteoporosis
Kidney stones
Abdominal moans (pain, constipation, acute pancreatitis)
Psychic groans (confusions, insomnia, anxiety, cognitive dysfunction)
Weakness, fatigue, muscle symptoms, polyuria, polydipsia
Hypercalcaemia 1st line investigations
Bloods: raised Ca++, decreased K+, alkalosis, decreased Cl-, decreased albumin
24hr urinary Ca++
Malignancy causes - low albumin, low PTH (tumour secreting PTHrP not PTH)
Hypercalcaemia management
Acute severe hypercalaemia is a medical emergency
Aggressive rehydration - IV 0.9% saline
Bisphosphates (pamidronate)
Oral prednisolone
Hypocalcaemia aetiology
Renal failure is the most common cause (due to increased phosphate levels)
Hypocalcaemia after thyroid or parathyroid surgery (usually short lasting)
Hypocalcaemia signs and symptoms
Tetany (muscle spasms) Neuropsychiatric signs (convulsions, psychosis, anxiety)
Hypocalcaemia 1st line investigations
Serum and urine creatinine (renal disease)
PTH levels - absent or low in hypoparathyroidism, high in other causes 25-hydroxyvitamin D levels for suspected vitamin D deficiency
Hypocalcaemia management
Vitamin D derivatives (alpha-hydroxylates are preferred)
Treat underlying cause
Carcinoid syndrome definition
Groups of symptoms due to release of seritonin and other vasoconstriction peptides into systemic circulation from carcinoid tumour. Carcinoid tumours are neuroendocrine tumours often in the midgut
Carcinoid syndrome aetiology
Caused by carcinoid tumours. Very common in patients with liver metastasis
Carcinoid syndrome pathophysiology
increased serotonin and other products go directly into systemic circulation and cause the symptoms
Carcinoid syndrome signs and symptoms
Symptoms:
- diarrhoea
- flushing
Signs:
- palpitations
- abdonimnal cramps
- signs of right heart failure
- bronchospasm
Carcinoid syndrome 1st line investigations
High volume of urinary 5-hydroxyindoleacetic acid (breakdown product of serotonin)
Metabolic panel and LFTs
Liver ultrasound: confirm metastases
Carcinoid syndrome differential diagnosis
IBC
Crohn’s
Menopause
In all of these there will be a normal 5-hydroxyindoleacetic acid
Carcinoid syndrome management
Local disease: surgical resection + peri-operative octreotide infusion
Metastases: above + additional radiofrequency ablation
