Endocrinology Flashcards
What is primary adrenal insufficiency commonly known as?
Addison’s disease
Addison’s disease is characterized by destruction of the adrenal cortex, leading to deficiencies in cortisol and aldosterone.
What leads to the hyperpigmentation seen in Addison’s disease?
Increased CRH and ACTH production due to reduced cortisol levels
The feedback mechanism causes elevated levels of ACTH, which can stimulate melanin production.
What is the incidence of Addison’s disease?
3-4 million per year
The prevalence of Addison’s disease is estimated to be between 40-60 million per year.
What is the most common cause of primary adrenal insufficiency in the western world?
Autoimmune destruction of the adrenal cortex
This condition is more common in women, with autoantibodies targeting steroid biosynthesis enzymes.
Name three causes of primary adrenal insufficiency.
- Autoimmune destruction
- Tuberculosis
- Rare causes (e.g., adrenal hemorrhage, malignant metastasis)
Autoimmune destruction is the leading cause in the western world.
What are the clinical features of Addison’s disease?
- Weight loss
- Malaise
- Weakness
- Nausea and vomiting
- Abdominal pain
- Confusion
- Fainting
Symptoms can vary widely, leading to late diagnosis.
What is an Addisonian crisis?
A life-threatening presentation of Addison’s disease
It often occurs due to the sudden withdrawal of exogenous steroids.
What are common symptoms of an Addisonian crisis?
- Hypotension
- Dehydration
- Confusion
- Hyponatraemia
- Hypoglycaemia
These symptoms are critical and require immediate medical attention.
What are some signs of chronic Addison’s disease?
- Loss of weight
- General wasting
- Pigmentation (palmar creases, buccal mucosa)
- Postural hypotension
- Dehydration
Signs can be very subtle and may overlap with other conditions.
What blood test results may indicate adrenal insufficiency?
- Hyponatraemia
- Hyperkalaemia
- Elevated urea and creatinine
These abnormalities occur due to mineralocorticoid deficiency.
What is the purpose of the Synacthen test?
To assess adrenal function by measuring cortisol response to synthetic ACTH
A lack of cortisol response can indicate primary adrenal insufficiency.
What is the management for adrenal insufficiency?
- Mineralocorticoid replacement (fludrocortisone)
- Glucocorticoid replacement (hydrocortisone)
- IV hydrocortisone and fluid rehydration during Addisonian crisis
Hormone replacement is crucial for managing adrenal insufficiency.
What is secondary adrenal insufficiency primarily caused by?
Iatrogenic causes from long-term steroid therapy
This leads to suppression of the pituitary-adrenal axis.
True or False: Secondary adrenal insufficiency results in hyperpigmentation.
False
In secondary adrenal insufficiency, ACTH is not produced, hence no hyperpigmentation occurs.
What is the definition of Cushing’s syndrome?
Chronic glucocorticoid excess + loss of the normal feedback mechanisms of the HPA axis and loss of circadian rhythm of cortisol secretion.
What is the most common cause of Cushing’s syndrome?
Exogenous administration of steroids.
What are the rare endogenous causes of Cushing’s syndrome?
Endogenous causes are rare.
What is the annual epidemiology rate of Cushing’s syndrome?
3 million per year.
What are the two classifications of Cushing’s syndrome?
- ACTH-dependent
- ACTH-independent
What is Cushing’s disease?
A pituitary adenoma resulting in corticotrophs releasing excess ACTH.
What is ectopic ACTH production?
It manifests as a paraneoplastic syndrome in a number of malignancies such as small-cell lung cancer.
What are the primary causes of ACTH-independent Cushing’s syndrome?
- Primary cortisol secreting adrenal tumours (adenomas and carcinomas)
- Hyperplasia
What are common symptoms of Cushing’s syndrome?
- Tiredness
- Depression
- Weight gain (central)
- Easy bruising
- Back pain
- Amenorrhoea
- Reduced libido
What are the signs of Cushing’s syndrome?
- Acne
- Moon face (cushingoid facies)
- ‘Buffalo hump’
- Central obesity
- Hyperpigmentation (in ACTH dependent)
- Proximal muscle wasting
What is a key investigation for diagnosing Cushing’s syndrome?
24-hour urinary cortisol showing levels of 3 or 4 times normal.
What does a midnight cortisol test demonstrate?
The loss of the normal circadian pattern.
What is the purpose of the low-dose dexamethasone suppression test?
To demonstrate the loss of normal feedback on the pituitary gland and hypothalamus.
What should occur in a normal individual after administration of dexamethasone?
It should suppress the morning rise in serum cortisol.
What indicates a lack of suppression in patients with Cushing’s syndrome during the dexamethasone test?
A lack of suppression warrants further investigation.
What is a medical management option for Cushing’s syndrome?
Metyrapone, an inhibitor of 11-beta-hydroxylase.
What type of management is indicated when there is a tumor in Cushing’s syndrome?
Surgical management.
What is T1DM?
A condition caused by an inability to produce or secrete insulin.
In which age group does T1DM typically occur?
Children and adolescents.
How many adults in the UK are affected by T1DM?
About 370,000 adults.
What is the main factor leading to the destruction of beta-cells in T1DM?
Autoimmunity.
What triggers the development of autoantibodies in genetically susceptible individuals?
An external trigger, such as a viral infection.
What percentage of T1DM patients have circulating autoantibodies?
Up to 85%.
Which antibody is most commonly identified in T1DM patients?
Anti-glutamic acid decarboxylase (anti-GAD) antibody.
What are counter-regulatory hormones to insulin?
- Glucagon
- Adrenaline
- Growth hormone
- Cortisol
What are the symptoms of insulin deficiency in T1DM?
- Polyuria
- Polydipsia
- Dehydration
- Electrolyte derangement
- Weight loss
What is a significant consequence of insulin deficiency?
A profound catabolic state may occur.
What happens to fatty acids in the absence of insulin?
They are converted into ketone bodies.
What condition can develop due to high circulating ketones?
Diabetic ketoacidosis (DKA).
What can severe acidosis lead to?
Failure of pH-dependent enzyme systems.
What are common clinical features of T1DM?
- Polyuria
- Polydipsia
- Polyphagia
- Glycosuria
- Weight loss
What signs may indicate dehydration in T1DM patients?
- Dry skin
- Dry mucous membranes
- BMI < 25
What are the potential presentations of diabetic ketoacidosis?
- Confusion
- Dehydration
- Vomiting
- Abdominal pain
- Decreased urine output
- Reduced GCS
- Coma
- Shock
- Kussmaul breathing
- Hyperkalaemia
How is T1DM diagnosed?
When classical clinical features are found in the presence of a raised random blood glucose level.
What is required for the management of T1DM?
- Life-long exogenous insulin
- Blood glucose monitoring at least 4 times a day
What class of oral hypoglycaemics blocks ATP-dependent potassium channels?
Sulphonylureas.
What is the mechanism of action of biguanides like metformin?
Increases peripheral uptake of glucose and decreases gluconeogenesis.
What do DPP4 inhibitors do?
Increase incretin levels, inhibiting glucagon release and decreasing blood glucose levels.
What is a common acute complication of T1DM?
Hypoglycaemia.
What are symptoms of hypoglycaemia?
- Sweating
- Tremor
- Anxiety
- Altered consciousness
What is hyperosmolar hyperglycaemic state (HHS)?
A state in which high blood sugar results in high osmolarity without significant ketoacidosis.
What is diabetic retinopathy?
Persistent damage to the retina leading to areas of ischaemia and new vessel formation.
What is the pathogenesis of diabetic nephropathy?
High blood glucose leads to hyaline deposits and thickening of the basement membrane.
What does diabetic neuropathy refer to?
A collection of conditions resulting from glucose-related damage to neurones.
What complications can arise from diabetic foot?
- Ulcers
- Secondary infection
- Skin necrosis
- Amputation
What macrovascular complication is associated with diabetes?
Atherosclerosis.
What is T2DM?
A condition caused by a combination of insulin resistance and deficiency.
What is insulin resistance?
The inability of cells to respond adequately to normal levels of insulin, primarily occurring in muscles, liver, and fat tissue.
What happens to glucose release in the liver during insulin resistance?
The liver inappropriately releases glucose into the blood.
What percentage of the risk for developing T2DM is due to obesity?
About 80%.
What is the genetic risk of developing T2DM if both parents have the condition?
As high as 75%.
List three environmental risk factors for developing T2DM.
- Obesity and inactivity
- Poor dietary habits
- Low birth weight
Which populations have a higher prevalence of T2DM?
- Asians
- Men
- Elderly (>40)
What initiates the uptake of glucose into cells during normal glucose homeostasis?
The release of insulin following ingestion.
What are the anabolic effects of insulin receptor activation?
- Inhibit proteolysis and lipolysis
- Inhibit hepatic gluconeogenesis
- Promote hepatic glycogen synthesis
What occurs during insulin resistance that leads to hyperglycaemia?
Failed uptake of glucose and catabolic effects on lipids, proteins, and hepatic tissue.
What is impaired glucose tolerance (IGT)?
Abnormal regulation of glucose following a meal in the post-prandial state.
What is impaired fasting glucose (IFG)?
High levels of glucose during the fasting state.
What is glucotoxicity?
The toxic effect of high glucose levels on beta cells, leading to a depletion in their cellular mass.
List three clinical features of T2DM.
- Lethargy
- Polyuria
- Polydipsia (thirst)
What is the major diagnostic tool for T2DM?
Measurement of glycated haemoglobin (HbA1c).
What HbA1c level indicates diabetes?
HbA1c > 48 mmol/mol.
What fasting plasma glucose level indicates diabetes?
> 7 mmol/L.
What random plasma glucose level indicates diabetes?
> 11.1 mmol/L.
What does an oral glucose tolerance test measure?
The ability of the body to deal with a glucose load over a two-hour period.
What are the main steps in the management of T2DM?
- Lifestyle modification
- Monotherapy with metformin
- Dual therapy if HbA1c rises
- Triple therapy or insulin-based therapy if no effect
What are the acute problems associated with T2DM?
Hypoglycaemia.
List two microvascular complications of T2DM.
- Retinopathy
- Nephropathy
What is a macrovascular complication of T2DM?
Atherosclerosis.
