Endocrinology Flashcards
What is the cause of acromegaly?
- Excessive secretion of growth hormone.
- Usually due to pituitary adenomas.
Symptoms of acromegaly?
- Hands and feet enlargement
- Coarse facial features
- Macroglossia
- Enlargement of jaw (prognathism)
- DM2
- Hypertension
- Headaches
- Sweating
What is the investigation done in acromegaly?
Initial test and for monitoring
- Insulin growth insulin growth factor (IGF-1).
Confirmation of diagnosis
- Oral glucose test.
Others
- MRI scan of pituitary (adenomas).
What is the treatment of acromegaly?
- Trans-sphenoidal surgery
- GH receptor antagonist: Pegvisomant
- Somatostatin analogues: octreotide
- Radiotherapy
What is the physiology of Addison’s disease?
- AKA primary adrenal insufficiency;
- The adrenal gland (kidney) cannot produce adequate levels of cortisol (glucocorticoids) and aldosterone (mineralocorticoids) due to autoimmune destruction.
What is the cause of primary Addison’s disease?
- Autoimmune.
What are the symptoms of primary adrenal disease?
- Fatigue
- Weakness
- Weight loss
- Postural hypotension
- Hyperpigmentation (due to ACTH raised)
- Salt cravings
- Hypoglycaemia
What are the investigations done in primary Addison’s disease?
- Electrolytes: Hyponatraemia & Hyperkalaemia.
- Early morning cortisol: low
- ACTH: high
- Synacthem / ACTH stimulation test: cortisol does not rise.
What is the cause of SECONDARY adrenal insufficiency?
- Hypothalamic and pituitary failure.
- Long term steroid medication (suspension of hypothalamic-pituitary-adrenal axis)
What is the investigation of secondary adrenal insufficiency?
- ACTH: low
- Cortisol (early morning): low
- ACTH stimulation test / Synacthem: cortisol does not rise.
DDx between:
- Addison’s disease (primary adrenal insufficiency)
- Secondary adrenal insufficiency
Primary adrenal insufficiency
- Autoimmune destruction of adrenal gland, leads to low cortisol and low aldosterone.
- Low cortisol leads to negative feedback to the pituitary which leads to high levels of ACTH which leads to hyperpigmentation.
Low aldosterone leads to hyponatraemia and hyperkalaemia.
Secondary adrenal insufficiency
- Inadequate pituitary or hypothalamic stimulation, leads to low ACTH, which leads to low cortisol.
- Aldosterone levels are normal hence normal Na and K.
What is the DDx between:
- Conn’s syndrome
- Addison’s disease
Conn’s syndrome
- Hypernatraemia
- Hypokalaemia
- Hypertension
Addison’s disease
- Hyponatraemia
- Hyperkalaemia
- Hypotension
- Hypoglycaemia
What are the causes of Addisonian crisis?
- Withdrawal of chronic steroid therapy
- Infection or stress (corticosteroids needs will be raised)
What are the symptoms of Addisonian crisis?
- Shock: postural hypotension, tachycardia, oliguria
- Abdominal pain
- Hypoglycaemia
What are the investigations of Addisonian crisis?
- Cortisol
- ACTH levels
- Blood sugar
- FBC, U&Es, Cultures
What is the treatment of Addisonian crisis?
- IV hydrocortisone 100 mg
- IV fluids if shocked
- IV glucose if hypoglycaemia
- Improvement after 72h oral steroids
- If adrenal pathology identified: fludrocortisone.
What is the Rx for DM₂
?
First line:
- Metformin
Check HbA1c in 3-6 monthsIf HbA1c > 58 mmol/mol
- Reinforce lifestyle advice
- Add another drug.
If added cardiovascular risk:
- Metformin
AND
- SGLT-2 inhibitors
DM2
Describe the pharmacology
of Biguanides.
Example:
Metformin
Renal imparment adjustments- eGFR < 45:
reduce dose- eGFR < 30:
discontinue
DM2
Describe the pharmacology
of SGLT-2 inhibitors (AKA gliflozins).
Example:
- Dapagliflozin
- Canagliflozin
- Empagliflozin
Benefits
- Cardioprotective
- Renal protective
- Weight loss
Risks
- DKA at moderately raised glucose (< 14 mmol/L).
DM2
Describe the pharmacology
of Sulphonylurea.
Example:
- Gliclazide
Risks
- Hypoglycaemia
- Weight gain
Not to be given to lorry, ambulance, heavy machinery drivers due to hypoglycaemia.
DM2
Describe the pharmacology
of DDP4 inhibitors (AKA sitagliptin).
Example:
- Sitagliptin
Risks
- Pancreatitis
DM2
Describe the pharmacology
of Pioglitazone.
Contraindicated in:
- Heart failure
- Bladder cancer
- Fractures (women)
Risks
- Weight gain
DM2
Describe the pharmacology
of Repaglinide.
Risks
- Hypoglycaemia
- Weight gain
- Avoid in liver disease
DDx between:
- Osteoporosis
- Paget’s disease
- Osteomalacia
Osteoporosis
Calcium: Normal
Phosphate: Normal
Alkaline phosphatase: Normal
Paget's disease
Calcium: Normal
Phosphate: Normal
Alkaline phosphatase: High
Osteomalacia
Calcium: Low
Phosphate: Low
Alkaline phosphatase: High
Define what is Conn's syndrome / primary hyperaldosteronism
?
Condition due to excessive production of aldosterone by the adrenal glands.
What are the symptoms of Conn's syndrome / primary hyperaldosteronism
?
- Hypertension: Due to ⬆︎ aldosterone ➝ hypernatraemia which causes water retention.
- Hypokalaemia: causes muscles weakness.
- Hypernatraemia
- Metabolic alkalosis
Aldosterone acts on the convulted tubules to:
- ↑ Na⁺ reabsortion
- ↑ K⁺ excretion
- ↑ H⁺ excretion
What is the cause of Conn's syndrome / primary hyperaldosteronism
?
- Adrenal adenoma
- Adrenal hyperplasia
- Adrenal carcinoma
What are the investigations done in Conn's syndrome / primary hyperaldosteronism
?
Renim - Aldosterone ratio
- Renim: low
- Aldosterone: High
CT scan / MRI
- Searching for adenomas, carcinomas, etc.
Renim is low because:
- The kidneys juxtaglomerular cells are responsible for sensing the BP coming to the kidneys.
- If the BP is low, they release renim
- Renim converts angioteninogem (produced by the liver) into angiotensin I
- Angiotensin 1 is then converted (in the lungs) into angiotensin 2 (by angiotensin converting enzymes)
- Angiotensin 2 acts on the adrenal gland to produce aldosterone increasing the BP ➝ lowering renim
.
What is the treatment of Conn's syndrome / primary hyperaldosteronism
?
Aldosterone antagonist:
- Spironolactone
Surgery:
- Adrenalectomy
Define what is Cushing's syndrome
?
Condition caused by prolongued exposure of endogenous or exogenous glucorticoids
leading to excessive cortisol on the body.
Describe the adrenal axis physiology
.
- Hypothalamus releases CRH hormone
- CRH acts on the anterior pituitary gland
-
Anterior pituitary releases
ACTH hormone
-
ACTH acts on the
adrenal gland
-
Adrenal gland releases
cortisol
-
Cortisol does the following:
◆ Inhibits the immune system;
◆ Inhibits bone formation;
◆ ⬆︎ blood glucose
◆ ⬆︎ metabolism
◆ ⬆︎ alertness - ⬆︎ Cortisol sends a negative feedback to the anterior pituitary and to the hypothalamus, and they ⬇︎ the production of their hormones.
What are the causes
of Cushings syndrome?
◉ ACTH dependent disease
◆ Cushings disease: Pituitary adenoma;
◆ Ectopic ACTH: small lung carcinoma
◉ Non-ACTH dependent
◆ Adrenal adenoma/carcinoma
◆ Exogenous steroids
What are the symptoms
of Cushings syndrome?
◆ Round face
◆ Buffalo hump
◆ Abdominal obesity
◆ Purple abdominal striae
◆ Muscle weakness
◆ Osteoporosis
◆ Depression and insomnia
How is the diagnosis
of Cushings syndrome done?
Investigations done to diagnose it.
1. 24h urinary free cortisol
2. Dexamethasone suppression test (low dose)
Cushings syndrome
Explain how the low
dose dexa supression test is done and its clinical relevance
.
1. 1mg of Dexa is giving at midnight.
2. Cortisol (plasma) is measured the next day at 9 am.
➜ If positive for Cushings:
◆ 1mg of dexa won't be enough
to supress the hypothalamus (CRH) or the anterior pituitary (ACTH), as the body is used to ⬆︎ levels of cortisol.
➜ If negative for Cushings:
◆ Cortisol < 50 nmol/L.
◆ 1mg of dexa will be enough
to supress the hypothalamus and the anterior pituitary.
Cushings syndrome
After positive dexa supression test
(low dose), what is the next step?
◉ Differentiate the causes of Cushings by doing:
➜ High dose dexamethasone supression test.
Explain how the high
dose dexa supression test is done and its clinical relevance
.
✿This one is for that Deo that sat on the Uni’s floor in Shunde, hopeless, aimless.
✿This is for that Deo that decided to not cheat with everyone else on that final exam in Shunde, she was trying to find herself in the mist of it all.
◘ 8mg of dexa is administered.
➔ Cushing disease/pituitary adenoma:
◆ ACTH ⬇︎
◆ Cortisol ⬇︎
◆ 8 mg would supress the ACTH/adenoma
➔ Adrenal adenoma:
◆ ACTH ⬇︎
◆ Cortisol ⬆︎
◆ 8 mg would supress the pituitary but the source of the ↑ cortisol is on the kidney itself.
➔ Ectopic ACTH (lung carcinoma):
◆ ACTH ⬆︎
◆ Cortisol ⬆︎
◆ The source of the ↑ cortisol is elsewhere even though the pituitary is supressed.
✿This is for that Deo that sat on the lobby of ICOR, exhausted and scared.
✿This is for that Deo that worked unmotivated at HPM just repeating and copying daily tasks without really understanding the why’s.
✿This is for that Deo that in spite of everything
, still found hope and energy to pursue an amazing path.
Diabetes
Describe the Dawn phenomenom.
It is a rise in glucose levels in the early hours (2 - 8 AM) in diabetic patients.
Especially DM1.
Diabetes
What is the Rx of the Dawn phenomenom
?
⬆︎ night time dose of long acting insulin
.
What is the cause of diabetes insipidus
?
1. ⬇︎ production of ADH (antidiuretic hormone).
2. ⬇︎ response to ADH.
ADH is produced by the hypothalamus
and stored in the pitituitary
.
Diabetes insipidus
What is the function of ADH
(antidiuretic hormone)?
- Acts on the collecting ducts on the kidneys ⟶
Reabsportion of H₂O from urine
(urine becomes concentrated due to lack of water)
On diabetes insipidus:
- ⬇︎ ADH
- Prevents urine from becoming concentrating due to excessive water in urine
- Polyuria
(excessive amount of urine)
- Polydipsia
(thirst caused by blood being concentrated)
What are the symptoms of diabetes insipidus
?
- Polyuria: excessive amount of urine due to ⬆︎ water in the urine
- Polydipsia: thirst caused by blood being concentrated