Other causes of hypoglycaemia Flashcards
In addition to iatrogenic causes of hypoglycaemia related to diabetes, what are 5 further causes of hypoglycaemia?
- Addison’s disease
- Insulinoma
- Mesenchymal tumours (e.g. Non-Islet Cell Tumour Hypoglycaemia NICTH)
- Factitious hypoglycaemia
- Reactive hypoglycaemia
How can Addison’s disease cause hypoglycaemia?
- as there are many hyperglycemic hormones (glucagon, growth hormone, adrenaline), a cortisol deficiency is not likely to produce hypoglycemia unless fasting occurs or the person is stressed
- Cortisol is essential for proper mobilization of proteins for glucose production - under stress hypoglycaemia can therefore occur
What is Addison’s disease?
a primary adrenal insufficiency in which the levels of both mineralocorticoids (aldosterone) and glucocorticoids (cortisol) are usually extremely low
What is the most common cause of Addison’s disease in the developed world?
autoimmune adrenal deustruction (90% of cases)
Which gender is predominantly affected by Addison’s disease?
women (2-3:1 F:M)
What are 7 causes of Addison’s disease additional to autoimmune?
- Infections - tuberculosis commonest cause worldwide
- Adrenal haemorrhage/infarction (in sepsis: Waterhouse-Friderichsen syndrome)
- Metastatic carcioma (breast and lung)
- Infiltrative causes: sarcoidosis, amyloidosis and haemochromatosis
- Inherited disorders
- Iatrogenic - surgery, bilateral nephrectomies
- Trauma
What predominantly causes the symptoms and signs of Addison’s disease?
cortisol deficiency
What are 6 symptoms of Addison’s disease?
- Lethargy
- GI symptsom: abdominal pain, nausea, vomiting, diarrhoea
- Skeletal muscle weakness, fatigue
- Orthostatic dizziness (postural hypotension)
- Weight loss
- Increase in pigmentation
What causes increased skin pigmentation in Addison’s disease?
increased levels of ACTH due to adrenal insufficiency; the other product when the precursor of ACTH, pro-opiomelanocortin, is cleaved is beta-lipotrophin
beta-lipotrophin stimulates melanocytes to produce melanin
What is Addisonian crisis?
sudden-onset adrenal failure e.g. haemorrhage, or caused by increased cortisol requirements (concurrent infection, surgery, trauma)
leads to hypovolaemic shock, often with acidosis and hypoglycaemia
What are 7 key investigations in Addison’s disease and the likely findings?
- Serum cortisol concentration: low
- Adrenal autoantibodies: against 21-hydroxylase, in 50% of patients
- Serum ACTH: raised
- Serum electrolytes: hyponatraemia, hyperkalaemia, raised urea
- Glucose level: hypoglycaemia may occur
- Short and long synacthen tests: positive
- Screening for other autoimmune diseases e.g. thyroid
What is the definitive investigation in suspected Addison’s disease?
ACTH stimulation test: short synacthen test
plasma cortisol measured before and 30min after giving Synacthen 250 ug IM
What are the 4 key electrolytes abnormalities seen in Addison’s patients?
- Hyperkalaemia
- Hyponatraemia
- Hypoglycaemia
- Metabolic acidosis
What are the 3 key aspects of the management of Addison’s disease?
- Glucocorticoid and mineralocortoid replacement therapy:
- hydrocortisone, 20-30mg per day in 2-3 divided doses, most in first half of day
- fludrocortisone
- Patient education
- Management of intercurrent illness
What are 4 aspects of patient education in Addison’s disease?
- importance of not missing glucocorticoid doses
- consider MedicAlert bracelets/ steroid cards
- provide with hydrocortisone for injection with needles and syringes to treat an adrenal crisis
- discuss how to adjust the glucocorticoid dose during an intercurrent illness
In simple terms what is the management of Addison’s disease during intercurrent illness?
glucocorticoid dose should be doubled
What is an insulinoma?
neuroendocrine tumour deriving mainly from pancreatic islet of Langerhans cells. most common pancreatic endocrine tumour
What proportion of insulinomas are 1. malignant and 2. multiple at once occur?
- 10%
- 10%
Of patients with multiple insulinoma tumours, what proportion have MEN-1 (multiple endocrine neuroplasia type 1)?
50%
What are 4 key clinical features of insulinoma?
- hypoglycaemia: typically early in morning or just before meal e.g. diplopia, weakness, sweating, palpitations, confusion, grand mal seizures, tremor
- rapid weight gain
- high insulin, raised proinsulin: insulin ratio
- high C-peptide
What are 2 key investigations to make a diagnosis of insulinoma?
- Supervised, prolonged fasting (up to 72 h)
- CT pancreas
What are 4 key aspects of the management of insulinoma?
- Surgical removal - enucleation of single insulinoma, partial pancreatectomy for multiple
if not candidates for surgery:
- Diazoxide: inhibits insulin release, enhances glycogenolysis
- Lanreotide and octreotide - somatostatin analogues
- Streptozotocin - toxic to insulin-producing beta cells
What are 3 ways that factitious hypoglycaemia can arise?
- Intentionally as diagnostic tool
- Accidentally as complication of treatment of DM
- Consequence of poisoning either with insulin itself or with drugs e.g. sulfonylureas that stimulate insulin release
In children whenever severe hypoglycaemia occurs with documented hyperinsulinism, what diagnosis must be considered?
Munchausen syndrome by proxy
What possibiliy should be considered in the case of sudden onset hypoglycaemia in a previously healthy individual?
possibility of malicious administration of insulin or an oral sulfonylurea
What is the clue in the biochemistry pointing towards a diagnosis of factitious hypoglycaemia?
raised insulin level accompanied by normal C-peptide
What are 4 causes of reactive hypoglycaemia?
- Insulin-induced
- Drug-induced e.g. sulfonylreas
- Alcohol
- Dumping syndrome - accelerated gastric emptying following gastric resection e.g. gastric bypass for weight loss, may result in rapid absorption of large amounts of glucose with surge of insulin release
What is C-peptide?
pro-insulin molecule breaks up into insulin and C-peptide
What are 3 mechanisms of alcohol causing hypoglycaemia?
- Malnutrition
- Inhibition of gluconeogenesis
- Liver disease
What can help to minimise hypoglycaemia when caused by Dumping syndrome?
smaller, more frequent meals and avoidance of large amounts of sugars
