Hypernatraemia (>145) 

Clinical Features

• Largely associated with cause (either excessive fluid loss, or excessive sodium gain)

Investigations

• Establish if secondary to fluid loss by taking a full history and examination
• Hypovolaemia can be due to diuretics, vomiting, diarrhoea, reduced intake, burns, excessive sweating, or diabetes insipidus
• Review fluid administration charts for records of excessive sodium containing fluid administration

Management

• Correct slowly, no faster than 0.5mmol/h
• If due to hypovolaemia, infuse isotonic crystalloid, slowly graduating to hypotonic fluid or enteral water (hypotonic fluid used initially does not remain in intravascular space)
• If due to excess sodium administration, change to hypotonic fluid such as dextrose saline
• Consider serial neurological examinations whilst correcting

 Complications

• Most serious complications are due to overly rapid correction
• Brain cells adapt to high sodium levels
• Rapid correction leads to cerebral oedema, seizures, and permanent neurological damage

Hyponatraemia (<135)

Question: What are the clinical features of hyponatraemia?

• Commonly incidental finding on blood tests
• Severe hyponatraemia can cause confusion, seizures, coma due to fluid shift into brain cells

Question: What are the investigations appropriate in hyponatraemia?

• Identify if the patient is hypovolaemic, normovolaemic, or hypervolaemic
• Low extra-cellular volume causes include diuretics, diarrhoea, salt losing renal disease or adrenal insufficiency. Review medications, stool charts, check renal function and for low aldosterone levels
• Normal extra-cellular volume causes include Syndrome of Inappropriate ADH production (SIADH), hypothyroidism, psychogenic polydipsia. Compare urinary to plasma sodium (SIADH causes excessive urinary sodium loss), check thyroid function, ask about fluid intake
• High extra-cellular volume hyponatraemia is most commonly due to excessive fluid administration but can also be caused by renal failure or TURP (trans urethral resection prostate) syndrome (bladder irrigation fluid is absorbed into the venous sinuses). Check fluid balance, renal function, review recent operation notes

Question: What is the management of hyponatraemia?

• Dependent on cause
• Review/stop diuretics
• Stop excessive fluid administration in high ECF volumes
• OR correct low ECF volume with 0.9% saline (slowly)
• Manage SIADH with fluid restrictions, or vasopressin antagonists (e.g. Tolvaptan) with endocrine advice
• Consider serial neurological examinations while correcting

Question: What are the complications of hyponatraemia?

• Metabolic encephalopathy due to cerebral oedema
• Irreversible demyelination of cerebral pontine cells due to overly rapid correction, do not correct faster than 6-8mmol per 24h

Diabetes Mellitis

Question: What are the major risks associated with diabetes and surgery?

• Increased perioperative risk due to co-morbidities, largely vascular

• Microvascular - nephropathy, retinopathy
• Macrovascular - increased rate of atherosclerosis

• Complex polypharmacy
• Increased risk of infective complications
• Risk of hyperglycaemia - normal metabolic response to surgical stress is lipolysis, glucose mobilization, and increased insulin production to maintain normoglycaemia. Diabetics have an absent/inadequate insulin response, leading to hyperglycaemia with or without ketoacidosis. This response is exaggerated in infection or sepsis

Question: How should diabetes be managed in the surgical patient?

• Approach depends on whether diet, tablet, or insulin controlled, magnitude of anticipated surgical stress, presence of sepsis, and starvation time:
• Elective patients
  1. Develop individual care plan based on local guidelines
  2. Manage lifestyle in advance - diet, exercise, alcohol intake
  3. Establish tight control prior to surgery
  4. Minimize starvation time
  5. Variable rate intravenous insulin infusion for patients missing more than one meal
  6. Hourly glucose monitoring during procedure and immediately afterward, aim 6-10mmol/L
  7. Enhanced recovery principles to return to normal eating and insulin/tablet regime early
• Emergency patients

• Measure HbA1c to establish degree of control
• Closely monitor glucose, if >10mmol/L initiate variable rate insulin infusion to continue until eating and drinking.
• Involve critical care and specialist diabetic team early

Diabetic ketoacidosis

Question: What is diabetic ketoacidosis?

• Insufficient insulin to allow glucose to enter cells, therefore they switch to breaking down fatty acids, with the byproduct of ketones
• Usually occurs in type 1 diabetics, rarely in insulin dependent type 2

Question: What are the symptoms of diabetic ketoacidosis?

• Vomiting
• Dehydration
• Deep, laboured (kussmaul) breathing, or tachypnoea
• Tachycardia
• Delirium
• Coma

 Question: What investigations should you do?

• Urinary and serum ketones
• Serum blood glucose - serial hourly measurement
• Arterial blood gases - for pH, anion gap, bicarbonate
• Serum electrolytes
• Full blood count (to look for precipitating infection)
• CT/MRI imaging if altered consciousness

Question: What is the management of DKA?

• Primary fluid management - isotonic saline, not too rapid unless circulatory collapse
• Early discussion with medical/diabetic team
• Insulin infusion - fixed rate or variable, depending on medical advice
• When serum glucose falls to 10-15mmol/L introduce glucose containing fluids (no more than 2L/24h) so that insulin infusion can continue
• Replace potassium (increased cellular uptake with insulin)
• Consider urinary catheter

Question: What are the complications of DKA?

• Drowsiness
• Confusion
• Coma
• Death 

Hyperglycaemic Hyperosmolar Non Ketotic Acidosis (HONK) / Hyperosmolar Hyperglycaemic State (HHS)

Question: What is HONK/HHS?

• Raised blood glucose (>30mmol/L) in type 2 diabetics can lead to a hyperosmotic state
• It can be due to not taking medications, illness/surgical insult, undiagnosed type 2 diabetes

What are the clinical features of HONK/HHS

• Extreme thirst
• Frequent need to urinate
• Nausea
• Disorientation

What is the management of HONK/HHS

• Frequent serum glucose monitoring
• Intravenous fluid (normal saline) is the primary intervention
• Fixed rate insulin infusion if glucose fails to normalise with fluid replacement alone
• Continue insulin until eating and drinking

Adrenal Disease

Hypoadrenalism

Question: What are the causes of adrenal insufficiency?

• inadequate secretion of cortisol and/or aldosterone
• causes can be secondary (withdrawal of suppressive glucocorticoid therapy, hypothalamic or pituitary disease
• Or primary

• Addison’s disease: auto-immune, tuberculosis, HIV/AIDS, metastatic carcinoma, bilateral adrenalectomy)
• Corticosteroid enzyme defects: congenital adrenal hyperplasia, drugs (e.g. ketoconazole)

Question: What are the clinical features of adrenal insufficiency?

• Glucocorticoid insufficiency (cortisol - haemostasis, cardiovascular, metabolic, immune response)

• weight loss, anorexia, malaise, weakness, nausea + vomiting, altered bowel habit, hypotension, shock, hypoglycaemia, hyponatraemia, hypercalcaemia
• Mineralocorticoid insufficiency (aldosterone - salt and water)
• weight loss, anorexia, malaise, weakness, nausea + vomiting, altered bowel habit, hypotension, shock, hypoglycaemia, hyponatraemia, hypercalcaemia
  Mineralocorticoid insufficiency (aldosterone - salt and water)

• hypotension, shock, hyponatraemia, hyperkalaemia
• ACTH excess (produced by the pituitary to stimulate glucocorticoid production from the adrenals) - pigmentation (palmar creases, scars, sun exposed and pressure areas)
• Androgen insufficiency - reduced body hair, reduced libido

Question: What are the investigations if suspecting hypoadrenalism?

• Random plasma cortisol - low or low end of normal range, in an unwell hypoadrenal patient
• Short synacthen ACTH stimulation test (give 250µg ACTH IM. Take blood at 0min and 30min for plasma cortisol)
• Serum electrolytes, renin and aldosterone levels
• Random dehydroepiandrosterone (DHEA) and androstenedione in women (in men the main source of testosterone is the testes)
• Adrenal autoantibodies
• CT/MRI of the adrenals
• CXR for tuberculosis, HIV test if history suggests risk
• If suspecting crisis - FBC, U+E, glucose, lipase, venous blood gas

 Question: What is the management of adrenal insufficiency?

• Do not wait for test results if patient is unwell
• Addisonian Crisis

• ABCDE
• IV saline resuscitation (but be aware that increasing plasma Na by > 8mmol/24h risks pontine demyelination)
• IV/IM hydrocortisone 100mg stat, then QDS for 12-24h/until well enough for oral replacement
• IV 10% glucose for hypoglycaemia, hourly glucose monitoring 
• Hyperkalaemia should normalise with volume replacement
• Monitor U+E at 4h, 12h, 24h
• Strict fluid input/output monitoring
• Treat any infection
• Call the endocrine team

Hyperadrenalism (Conns and Cushings)

Cushing’s Syndrome

Question: What causes Cushing’s Syndrome?

• Prolonged exposure to glucocorticoids
• Commonly iatrogenic due to steroid treatment (e.g. with prednisolone)
• Non iatrogenic causes are either excessive ACTH (pituitary adenoma, ectopic from neuroendocrine tumour (e.g. small cell lung cancer)) or secreting adrenal tumours (adenoma, carcinoma)
• pseudo-Cushing’s syndrome - alcohol excess, depression, obesity. Can mimic signs

Question: What are the clinical features of Cushing’s Syndrome?

• Thin hair, hirsutism, moon face, psychosis, cataracts, peptic ulcers, hyperglycaemia, menstrual disturbance, central obesity, hypertension, thin skin, bruising
• Wasting and weakness of limb muscles
• Osteoporosis, leading to fractures, loss of height (compressive wedge fractures)

Question: What investigations are appropriate in Cushings?

• Difficult to confirm due to cyclical nature of cortisol release
• 24h urinary cortisol
• Overnight dexamethasone suppression test (dexamethasone suppresses ACTH and therefore cortisol secretion. Suppression is incomplete in Cushing’s patients). Can be low dose or high dose
• MRI for pituitary adenomas (Cushing’s disease)
• CT/MRI for adrenal tumours

Question: What is the management of Cushing’s Syndrome?

• Usually surgical for non-iatrogenic causes
• Trans-sphenoidal excision of pituitary adenoma
• Laparoscopic/open adrenalectomy - high recurrence rates. Reduced with adjuvant radio and chemo therapy
• Excision of ectopic ACTH producing tissue (e.g. bronchial tumour)
• Withdraw glucocorticoids slowly, replace with weaning doses to avoid addisonian crisis

 Conn’s Syndrome (Mineralocorticoid excess)

 Question: What is the cause of Conn’s Syndrome?

• High renin and high aldosteronism (secondary)
  • inadequate renal perfusion (diuretics, cardiac failure, liver failure, renal artery stenosis)
  • renin secreting renal tumour (rare)
  • low renin, high aldosterone (primary)
    • adrenal adenoma
    • idiopathic adrenal hyperplasia
    • renin and aldosterone low
      • ectopic ACTH syndrome
      • Liquorice excess
      • Liddle’s syndrome (autosomal dominant, causes hypertension)

Question: What are the clinical features of Conn’s syndrome?

• Often asymptomatic
• Hypernatraemia (sodium retention) can lead to oedema, hypertension
• Hypokalaemia may cause muscle weakness 

Question: What investigations should be done?

• Serum electrolytes, renin and aldosterone (after discontinuing antihypertensives, which alter results)
• CT/MRI for adrenal adenomas

Question: What is the management?

• Mineralocorticoid receptor antagonists (spironolactone, eplerenone)
• Amiloride (inhibits sodium reabsorption in the distal convoluted tubules)
• Adrenalectomy for adenoma

Phaeochromocytoma

 Question: What is a phaeochromocytoma?

• Neuroendocrine tumour that may secrete catecholamines (adrenaline, noradrenaline)
• Can be benign or malignant
• ~ 30% associated with inherited disorders

 Question: What are the clinical features of Phaeochromocytoma?

• Hypertension
• Pallor, flushing, headache, palpitations, anxiety
• Abdominal pain, vomiting, constipation
• Weight loss

 Question: What are appropriate investigations?

• Plasma or urine metanaphrine and normetanaphrine (can have false positives if unwell/under strain, tricyclic antidepressants)
• Genetic testing
• MRI/CT to visualise
• PET scan can help confirm malignancy

Question: What is the management of Phaeochromocytoma?

• Surgical excision
• 6 weeks of medical therapy with alpha blockers (+/- beta blockers) prior to surgery
• Postoperatively may need volume expansion
• Metastatic tumours may be surgically debulked, or respond to radionuclide therapy, tyrosine kinase and angiogenesis inhibitors

Thyroid disease

Hyperthyroidism

Question:What causes hyperthyroidism?

• Pituitary adenoma
• Grave’s disease - stimulation of the thyroid by circulating thyroid receptor antibodies
• Toxic multinodular goitre - nodule(s) secreting independently to TSH levels
• Malignant tumours of the thyroid

Question: What are the clinical features of hyperthyroidism?

• skin - heat intolerance, excessive sweating
• cardiovascular - tachycardia, arrhythmias
• gastrointestinal - weight loss, increased motility
• eyes - lid retraction, exopthalmos (Grave’s)

Question: What investigations should be done?

• Serum T3, T4, and TSH
• Technetium sestemibi scan to identify active nodule 

Question: What is the management of hyperthyroidism?

• Carbimazole (blocks synthesis of T3 and T4)
• Radioactive iodine (targets thyroid cells. Should not be used in pregnancy/patients with young children)
• Thyroidectomy/hemithyroidectomy (risk of damage to recurrent laryngeal nerve)

Hypothyroidism 

Question: What are the cause of hypothyroidism?

• Autoimmune - Hashimoto’s thyroiditis
• Iatrogenic - following radioactive iodine, thyroidectomy, medication (e.g. carbimazole, lithium)
• Iodine deficiency - uncommon in the UK
• Congenital - thyroid aplasia
• Infiltrative - amyloidosis, sarcoidosis, Riedel’s thyroiditis
• Transient - de Quervain’s thyroiditis, postpartum thyroiditis

Question: What are the clinical features of hypothyroidism?

• Weight gain
• Hoarse voice
• Face - malar flush, periorbital oedema, loss of lateral eyebrows
• Anaemia
• Sinus bradycardia, hypotension
• Delayed relaxation of reflexes
• Dermal myxoedema (deposition of mucopolysaccharides in the dermis) 

Question: What investigations should be performed?

• Serum T4 and TSH
• ECG for bradycardia, low voltage complexes
• Thyroid peroxidase antibodies

Question: What is the management of hypothyroidism?

• Levothyroxine replacement as a single daily dose
• Start at 50µg/day and titrate up slowly according to TSH measurements over several weeks