Endocrinology Flashcards
Etiology of hypoglycaemia can be defined into two broad categories?
- Insulin-mediated
2. Insulin Independent
Ddx for insulin-mediated hypoglycaemia?
- Exogenous administration of insulin
- Insulin secretagogue use
- Insulin-secreting tumors (insulinomas, nesidioblastosis)
- Post-bariatric surgery hypoglycemia
- Insulin autoimmune hypoglycemia
What is an insulinomas
Insulinoma is a rare neuroendocrine tumor of insulin producing beta cells
What is an nesidioblastosis?
Nesidioblastosis is hypertrophy of insulin-producing beta cells in the pancreas.
Ddx for insulin independent hypoglycaemia?
- Malnutrition or starvation
- Cirrhosis/Hepatic Failure
- Sepsis
- End-stage renal disease
- Advanced heart failure
- Adrenal insufficiency
- Hormone deficiency (cortisol, glucagon and epinephrine in insulin-deficient DM)
- Non-islet cell tumours (typically the result of mesenchymal tumour overproduction of IGF-II)
- Inborn error of carbohydrate metabolism, glycogen storage disease, gluconeogenic enzyme
- Alcohol
- Drugs (e.g. quinine, indomethacin, gatifloxacin, lithium, ACE inhibitors, β-adrenergic receptor blockers)
How does pseudohypoglycemia occur?
Pseudohypoglycemia occurs when processing of blood specimens in untreated test tubes is delayed and cells, such as red blood cells and leukocytes (especially if increased, as in leukemia or polycythemia), consume glucose. Poor circulation to the digits can also cause erroneously low fingerstick glucose measurements.
What are the symptoms of hypoglycaemia?
- Autonomic nervous system activity – palpitations, sweating, tachypnea, tachycardia
- Neuroglycopenic symptoms – caused by decreased activity of CNS – dizziness, headache, clouding vision, mental dullness, fatigue, confusion, seizures
The surge in _______ in response to low plasma glucose typically occur first in hypoglycaemia
Autonomic activity
What is Whipple’s triad which suggest a patient’s symptoms are from hypoglycemia?
- serum glucose <4.0 mmol/L
- neuroglycopenic symptoms (confusion, sensation of warmth, weakness or fatigue, severe cognitive failure, seizure, coma)
- rapid relief provided by administration of glucose
Investigations of hypoglycaemia?
When the cause of hypoglycemia is not evident, screen for oral hypoglycemic agents and measure plasma glucose, serum ketones, insulin, pro-insulin, C-peptide, and insulin antibodies during a spontaneous hypoglycemic episode or a supervised fast of up to 72 h
What is C-Peptide?
A short peptide released into the circulation when proinsulin is cleaved to insulin
How can C-Peptide be used to distinguish between Exogenous and Endogenous source of hyperinsulinemia
o Increased = endogenous
o Decreased or normal = exogenous
Treatment for mild to moderate hypoglycemia (autonomic and neuroglycopenic symptoms)?
Rule of 15s:
- Ingestion 15g carbs (glucose tabs)
- Wait 15 mins - Check BG again
- If <4 repeat dose of carbs
Treatment for severe (unconscious) hypoglycemia?
Glucagon 1mg (IM or SC) or 1 amp D50W IV
After initial management of hypoglycaemia what are the next steps?
- Get them a complex snack afterward
2. Reduce their insulin dose
What is hypoglycemic unawareness?
Patient remains asymptomatic until severely hypoglycemic levels are reached
Etiology of hyperglycemia?
- Diabetes – impaired glucose tolerance, T1Dm, T2DM, gestational diabetes
- Endocrinopathy - Cause peripheral insulin resistance like Cushing syndrome, acromegaly, and pheochromocytoma
- Meds - corticosteroids, estrogen, beta blockers, epinephrine, thiazide diuretics, niacin, pentamidine
- Destruction of the pancreas from chronic pancreatitis, hemochromatosis, pancreatic cancer, and cystic fibrosis
- Total parental nutrition and dextrose infusion
- Critical Illness/Physiologic Stress – acute pancreatitis, post-stroke, post MI, shock, stress hyperglycemia (trauma, surgery, burns)
What are the causes of hypoglycemic unawareness?
- Decreased glucagon/epinephrine response
- History of repeated hypoglycemia or low HbA1c
- Autonomic neuropathy
What are the risk factors of hypoglycemic unawareness?
RFs: elderly, renal impairment, thin, missed meals, exercise, insulin, secretagogues
What is the treatment of hypoglycemic unawareness?
Tx: Get them to higher BG levels (>12) so their thermostat can reset and therefore notice their lows
Physical exam for hyperglycemia?
- General – ABCs
- Airway: GCS
- Breathing – monitor for Kussmaul breathing (rapid and deep respiration), fruity acetone breath (DKA)
- Circulation – postural BP and HR, assess JVP, mucous membranes, urine output and capillary BG - DERM – hyperpigmentation of the skin (r/o Addison’s disease)
- ABDO: abdominal tenderness (DKA)
- NEURO
Investigations for hyperglycemia?
Investigations: urinalysis/urine ketones, TSH, troponin, ABG, plasma glucose, lytes, Cr, bicarb, beta-hydroxybutyrate, CBC, urine/blood culture, amylase/lipase, plasma osmolality
- CXR
Describe the pathophysiology of diabetic ketoacidosis.
Insulin deficiency causes the body to metabolize triglycerides and amino acids instead of glucose for energy. Serum levels of glycerol and free fatty acids rise because of unrestrained lipolysis, as does alanine because of muscle catabolism. Glycerol and alanine provide substrate for hepatic gluconeogenesis, which is stimulated by the excess of glucagon that accompanies insulin deficiency.
Glucagon also stimulates mitochondrial conversion of free fatty acids into ketones. Insulin normally blocks ketogenesis by inhibiting the transport of free fatty acid derivatives into the mitochondrial matrix, but ketogenesis proceeds in the absence of insulin. The major ketoacids produced, acetoacetic acid and beta-hydroxybutyric acid, are strong organic acids that create metabolic acidosis.
The increase H is exchanged for potassium and thus causes hyperkalemia and eventually excreted. The potassium stores inside the body will therefore run low.
Causes of diabetic ketoacidosis?
Causes: insulin omission, infarction (MI, CVA), iatrogenic (steroids), new Dx, infection (stress increases release of epinephrine which releases glucagon which will result in increased blood glucose, loss of glucose in the urine and loss of water and therefore dehydration. You will also need alternative energy – generation of ketone bodies – ketoacidosis.