Endocrinology I & II: Diabetes Mellitus and Acromegaly

• What is glucagon?

  Peptide from alpha cells in Islets of Langerhans

  
  

  Secreted in response to lowered glucose levels

  
  

  Action is to oppose insulin
• What are hypoglycaemic and hyperglycaemic hormones?

  Hypoglycaemic: Hormone that drops glucose levels e.ginsulin

  Hyperglycaemic: Hormone that encourages increase in glucose levels e.gGlucagon, cortisol, catecholamines and growth hormone
• What are catecholamines?

  Secreted by adrenal medulla in response to stress which raises blood glucose levels
• What is glucocorticoid?

  Cortisol which promotes gluconeogenesis, gyconeolysis and protein catabolism
• What is diabetes Mellitus?

  Group of conditions characterised by chronic hyperglycaemia resulting from reactive insulin deficiency, peripheral tissue resistance or both.

  
  

  Is usually primary and classified as insulin dependent (type 1)
• Compare type I vs type II diabetes

  
• What values suggest someone has diabetes mellitus (glucose tolerance test)?

  >6.7 mmol/l fasting

  >10 mmol/l two hours after glucose
• What is the treatment for diabetes?

  Type I - insulin such as actrapid, monotard, mixtard

  
  

  Diet - fat reduced to 30% of total energy intake

  
  

  Drugs - sulphonylureas, gibenclamide, tolbutamide, biguanides (metformin)

  
• How do you measure the control of blood glucose levels?

  Fingerprick glucose

  Urine dipstick

  Lab serum glucose

  Glycosylated Hb

  
• What is acute hypoglycaemia?

  Blood glucose is less than 2.2 mmol/l

  (dental emergency)

  
• What are the signs and symptoms of acute hypoglycaemia?

  Increased sympathetic tone causes hunger, sweating, pallor and tachycardia

  
  

  Later changes include aggression and peripheral tingling and altered sensations

  
  

  Fits, hemiparesis and ultimately coma
• What is the treatment of acute hypoglycaemia?

  If patient is conscious, rapid ingestion of sugar (IV glucose, 50ml 50% dextrose or glucagon, 1mg IM)

  
  

  If unconscious or depressed, gag reflex then
• What is diabetic ketoacidosis (DKA)?

  A condition where raised metabolism is required to fight illness which needs more insulin.

  
  

  Reduced doses kill by causing relative hypoglycaemia
• What is the pathophysiology of DKA?

  Insulin deficiency leads to uncontrolled catabolism (cells cannot access glucose)

  
  

  High blood sugar levels produces glycosuria, osmotic diuresis and dehydration

  
  

  Tissues that can't get sugar from the blood start to break down into acidic ketones.
• What are the clinical features of DKA?

  Profound dehydration due to renal water and electrolyte losses

  
  

  Low BP and air hunger to compensate for metabolic acidosis
• What are the complications of diabetes?

  Heart disease

  Peripheral vascular disease

  Atheroma

  Stroke

  Increased risk of UTI and skin infections

  Macrovascular:accelerated atheroma leading to stroke, ischaemic heart disease or ischaemic limbs

  Microvascular:diabetic retinopathy can lead to blindness, diabetic nephropathy can lead to renal failure, diabetic neuropathy can lead to loss of sensation
• What are the two parts of the adrenal gland and what are their functions?

  Medulla- catecholamine production

  Cortex- steroid hormone production
• What is Cushing's syndrome?

  Persistent raised plasma cortisol levels

  
  

  Mostly from exogenously supplied steroid (different to Cushing's disease)
• Whats cushing's disease?

  Glucocorticoid excess secondary to inappropriate ACTH secretion only
• What are the clinical features of Cushing's syndrome?

  Obesity- fat centrally distributed (trunk, abdomen, buffalo hump on neck)

  Plethoric complexionandthin skinwhich easily bruises (protein catabolic effect)

  Moon face

  Purple striaeon abdomen, breasts and thighs

  Pigmentation(melanin)
• What are the investigations of Cushing's syndrome?

  -Surgical removal of pituitary

  
  

  -Metyrrapone inhibits cortisol release in cases not amenable to surgery

  
  

  -Pituitary irradiation as salvage for impossible or failed surgery.

  
  

  -Iatrogenic Cushing's disease responds to reduction/cessation of steroid if possible.

  
• What is Addison's disease?

  Hypoadrenalism-underfunction of adrenal gland

  
  

  (Disease is rare but syndrome is more common)
• What is Addison's syndrome?

  Endogenous steroid production is suppressed by exogenous therapeutics

  
  

  Far more common
• What are the clinical signs of Addison's disease?

  Lethargy

  
  

  Anorexia and weight loss

  
  

  Hypotension (usually postural)

  
  

  Hyperpigmentation of buccal mucosa, skin creases and scars

  
  

  Can present as crisis (in disease and syndrome) which involves: abdominal pain, low Na, high K, hypoglycaemia and hypovolaemic shock with no bleeding
• What is the management of Addison's disease?


  Supplementation for life using hydrocortisone twice daily or fludrocortisone
• What is an Addisonian crisis?


  Patient on steroid excess treatment has had the drug withdrawn too quickly

  
  

  Patient cannot produce adequate cortisol to go along with the adrenaline in stressful situations so must receive supplementation to facilitate adrenaline's action to maintain blood pressure
• What is the supplementation for Addisonian crisis?

  100-200mg hydrocortisone if pre short procedure (multi uses if long operation)

  
  

  IV access is mandatory during procedures
• What are mineralocortcoids?

  Steroid hormones that promote renal sodium reabsorption and K excretion

  
  

  e..g aldosterone
• What are the features of aldosterone?

  Driven primarily by renal renin-angiotensin system

  
  

  Increased by low plasma Na or low blood pressure

  
  

  High K stimulates aldosterone secretion directly
• What is Conn's syndrome?

  Hyperaldosteronism which drives excess fluid retention, low K (hypokalaemia) and secondary hypertension
• What are the endocrine causes of hypertension?

  Excess renin production

  Excess aldosterone production

  Adrenal adenoma or hyperplasia

  Excess production of other steroid

  Excess catecholamines

  Oral contraceptive pill
• What is the management of Conn's syndrome?

  Surgical resection of an adenoma

  
  

  Hypertension from hyperplasia can be combatted using spironolactone (aldosterone antagonist)
• What is the growth hormone?

  Substance secreted by the adenohypophysis (anterior pituitary)

  
  

  Effects mediated via insulin like growth factor synthesised in liver

  
  

  GH deficiency in childhood produced a pituitary dwarf

  
  

  Excess GH in childhood leads to gigantism
• What is acromegaly?

  Growth hormone excess that happens in adulthood typically from a benign anterior pituitary acidophil adenoma
• What are the clinical features of acromegaly?

  Enlarging head, hands and feet

  Chin enlarges- dentures too small

  Cranial nerves pinched in bony foraminae
• What is the management of acromegaly?

  Surgery

  Radiotherapy

  Drugs- octreotide (long acting somatostatin analogue) or bromocriptine (elderly)
• What is thyroid disease?

  Hyper or hypo thryoidism
• What is hypothyroidism?

  Typically a primary disease of the thyroid tissue where thyroid gland produces too little thyroid

  
• What are the clinical features of hypothyroidism?

  Normocytic/Macrocytic anaemia

  
  

  Hypercholesterolaemia

  
  

  Hyponatraemia

  
  

  Hard to diagnose in elderly
• What is the management of hypothyroidism?

  Lifelong replacement therapy with thyroxine (T4)

  
  

  Assess efficacy and adjust dose on clinical resolution of symptoms and thyroid function tests