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Endocrinology Keys and Notes for PLAB 1
1ry Adrenal insufficiency (Addison’s disease):
- low Cortisol and Aldosterone.
- Presentation: a patient with postural hypotension, weakness, nausea, vomiting, hyperpigmentation on the skin and the mucous membranes.
- The commonest cause in the developed world (including the UK) --> Autoimmune.
- The commonest cause in the developing world --> TB.
- Hypotension, Hyponatremia, Hypoglycemia.
- The only hyper is K+ (Hyperkalemia) and Hyperpigmentation. + Metabolic Acidosis.
In Addison’s disease (1ry):
High ACTH --> Hyperpigmentation (So, there is no hyperpigmentation in 2ry adrenal insufficiency).
Low Aldosterone --> Hyponatremia and Hyperkalemia
Low Cortisol --> Postural hypotension and Hypoglycemia.
2ry adrenal insufficiency (mostly iatrogenic).
After a long period of steroids intake, a sudden cessation of steroids will lead to adrenal insufficiency (iatrogenic).
look for unexplained abdominal pain and vomiting / postural hypotension ‘’ dizziness’’.
DM type 2, (age 45 years with polyuria, polydipsia, weight loss) Starts with?
Initial: metformin (Biguanide).
**Important Notes on Hypoglycemics**
With bad kidneys (GFR<30), do not use MS (Metformin, Sulphonylureas).
The Heart has 4 chambers, so with Heart Failure (and pancreatitis), do not use DDP4 inhibitors (gliptins).
"The pie (pioglitazone) comes with the die" (Risk of bladder cancer). So, Pioglitazone has a risk for Bladder Cancer.
Hypoglycemics that cause weight gain are SPR (Sulphonylureas, Pioglitazone, Repaglinide). The rest cause weight loss except DDP4 inhibitor Which has no effect.
SPR without the P have a risk of hypoglycemia: Sulphonylureas and Repaglinide.
Osteoporosis: Ca: normal, Ph: Normal, Alk. Phosphatase: Normal
Paget’s disease: Ca: Normal, Ph: Normal, Alk. Phosphatase: High
Osteomalacia: Ca: Low, Ph: Low, Alk. Phosphates: High
Note: Ca=Calcium / Ph=Phospahte / Alk.Phosphatase=Alkaline Phosphatase
Hyperkalemia with ECG changes: Tall Tented T wave, Prolonged QRS -->
Firstly, protect the cardiac membrane by giving IV Calcium Gluconate (OR: Calcium Chloride).
Then, reduce the Serum Potassium by giving insulin with dextrose OR sometimes salbutamol inhalation.
Acromegaly: bitemporal hemianopia, spade like hands, enlarged nose and jaw.
- Initial (screening) test and F/U test --> IGF-1 (insulin like growth factors).
- The most definitive (confirmatory test) --> OGTT (Oral Glucose Tolerance Test) with serial GH "Growth Hormone" measurements.
In normal people, GH is suppressed by Glucose.
In acromegaly, GH is not suppressed by Glucose.
Hypercalcemia with Prostate cancer.
- Hypercalcemia manifestations: (thirst, confusion, depression, low mood, kidney stones, abdominal pain, constipation, bone pain) = (Moans, Groans, Stones, Bones).
In a prostate cancer patient with these manifestations, initially order serum calcium.
The main causes of hypercalcemia: 1ry hyperparathyroidism, Malignancy, Sarcoidosis, TB
Initial management: rehydration IV Normal Saline.
Then: Bisphosphonates (e.g. Alendronate, Risedronate).
Amenorrhea can occur with HYPOTHYROIDISM:
- Hypothyroidism Manifestations: decreased appetite but weight gain, intolerance to cold, lethargy, puffy face, hand and feet (myxoedema), bradycardia, dry coarse cold skin, constipation, hair loss.
N.B. initially menorrhagia followed by oligomenorrhea or amenorrhea.
- The Commonest cause of Hypothyroidism in the UK: Autoimmune hypothyroidism (Hashimoto thyroiditis).
- The Commonest cause worldwide: iodine deficiency (in both causes, there is goitre)
Hyperprolactinemia (milk discharge in non-pregnant woman)
- MRI shows Pituitary Adenoma (pressing the optic chiasma), the visual defect is -->
* Remember: In pituitary adenoma and acromegaly --> bitemporal hemianopia.
* Remember: Hyperprolactinemia --> Amenorrhea (low FSH and LH) and Galactorrhea.
Diabetic patient suddenly collapsed and fell unconscious --> Measure Random Blood Glucose.
- If blood sugar is below 4 --> It is hypoglycemia.
- Other features: (tachycardia, sweating, confusion, altered mentation)
If conscious patient and can swallow: give 200 ml fruit juice.
If cannot swallow: administer 200 ml of 10% glucose IV (OR) 1 mg glucagon IM or SC.
If unconscious --> IV 75 ml of 20% Glucose.
- Causes of hypoglycemia: alcohol, liver failure (due to impaired gluconeogenesis), Excess paracetamol, aspirin, sulphonylureas (e.g. glibenclamide, gliclazide) intake.
- Note that Sulphonylurea is antihyperglycemic; however, it has a risk of hypoglycemia particularly in patients with renal impairment. It can also cause weight gain.
Glycosuria (glucose in the urine) is a NORMAL finding after Surgery. It occurs due to stress which increases the cortisol secretion and thus leads to hyperglycemia. This resolves in a few days post-op.
- Remember: High Stress --> High Cortisol --> High Glucose
SCC (squamous cell carcinoma) of the lung --> Hypercalcemia.
(This occurs due to the paraneoplastic effect, as SCC releases parathyroid like molecules (PTH) like molecules --> hypercalcemia. [High PTH --> High Calcium]
* Small cell lung cancer --> High ADH --> SIADH --> ‘’ dilutional’’ Hyponatremia and Hypokalemia.
It can also cause High ACTH --> (Cushing).
* SCC of the bronchus (lung) --> PTH like molecules --> Hypercalcemia.
Small cell lung cancer --> SIADH & Cushing
SCC of the lung --> Hypercalcemia
DM type 2 in an obese patient with impaired renal function --> What To Give?
Give insulin (OR):
Gliptins (DDP4 inhibitors) "as long as there is no risk of pancreatitis or HF".
The following medications are contraindicated for the explained reasons:
Biguanides (metformin): although it reduces weight and it is considered the first line hypoglycemic drug for DM type 2, it is contraindicated in renal impairment (GFR< 30) and the dose should be reduced if GFR<45.
Sulphonylureas (e.g. Glibenclamide, Gliclazide): is also contraindicated in renal impairment as it increases the risk of hypoglycemia + it also increases weight and the patient is obese.
Glitazones (Pioglitazone): it increases the weight.
SGLT-2 inhibitors: Contraindicated if GFR<60
Thyrotoxicosis (Hyperthyroidism) in pregnancy:
* Propylthiouracil is the preferred anti-hyperthyroidism drug preconception (before pregnancy if the woman is planning to get pregnant) and in the first trimester and postpartum.
Carbimazole is preferred in 2nd and 3rd trimesters.
* Carbimazole: risk of aplasia cutis and omphalocele in the fetus.
* Propylthiouracil: risk for hepatotoxicity in the mother.
* Both drugs can cross the placenta; so, use the lowest possible dose.
* Radioiodine therapy is contraindicated during pregnancy.
* If hyperthyroidism cannot be controlled by drugs --> partial thyroidectomy can be done in the 2nd trimester.
- A rare adrenal tumour secreting catecholamines (epinephrine and norepinephrine).
- The key word is (EPISODIC).
- Features: HTN (Hypertension), Headache, Sweating, Tremors, Palpitations, Anxiety.
Mnemonic: PHEochromocytoma: Palpitations, Headache, Hypertension, PH=F=Flushing (Sweating), E: Episodic (Paroxysmal)
Dx: 24 hours collection of urine metanephrines (not catecholamines).
* Rx of choice: surgical resection of the adrenal tumour.
* N.B. 7-10 days before the surgery, stabilize the Hypertension using Alpha-blockers (Phenoxybenzamine) followed by Beta-blockers (Propranolol) to prevent an intra-operative hypertensive crisis.
DM type 2 + Microalbuminuria + Mild HTN + Hypercholesterolemia --> give:
Metformin (To control blood glucose) +
ACE inhibitor (To reduce the BP and to slow the progression of the kidney damage ‘’evidenced by the microalbuminuria and DM type 2’’ +
Statin (for hypercholesterolemia).
Remember: DM type 2 + HTN --> always consider ACEi unless severe renal impairment.
DM type 2 + HTN + Microalbuminuria + NORMAL Cholesterol -->
ACE inhibitors (for the HTN and to slow renal impairment that is shown by the presence of the microalbuminuria) + lifestyle modification and diet control (if no hypoglycemic is in the options).
2ry amenorrhea (cessation of menstruation for >6 months after it has been established) that occurs with stress or excessive exercise or significantly low BMI --> Think of hypothalamic amenorrhea
* This is because hypothalamic failure occurs in these conditions).
* (In Hypothalamic Amenorrhea, all low except prolactin. i.e. low FSH, low LH, low Oestradiol, HIGH PROLACTIN).
Congenital Hypothyroidism Complication --> Jaundice
- It is rarely seen nowadays as there are screening tests used widely across the UK..
- If congenital hypothyroidism is not corrected early, complications:
Prolonged Physiological Jaundice (starts after 24 hrs and lasts for a long time)
FFT (failure to thrive), Short stature, Impaired mental development
Broad Flat nose, Widely set eyes, Protruding tongue.
DM type 1 with DKA presented unwell with an altered level of consciousness and tachycardia with signs of dehydration (Dry MM, hypotension, slow capillary refill).
- The initial investigation --> Capillary blood glucose, THEN --> Arterial Blood Gas.
Alcohol can cause HYPOGLYCEMIA.
Alcohol is the most common cause of hypoglycemia in the adults followed by treated diabetes.
Scenario Example: A young adult outside a local pub with semiconscious level, profuse sweating, sweaty skin, GCS 12/15, tachycardia, hypotension --> Hypoglycemia due to excess alcohol intake.
Dx of Hypoglycemia: Whipple’s Triad
Low plasma glucose
Symptoms of hypoglycemia: e.g. sweating, confusion, tachycardia, hypotension, altered mentation.
If blood glucose is corrected --> rapid resolution of symptoms.
Diabetic ketoacidosis: occurs mostly in DM type 1.
- Presentation: Abdominal pain, vomiting, Kussmaul breathing (deep hyperventilation), dehydration, glucose>11.
- Management: Initially: IV fluids followed by IV infusion of insulin + take arterial blood gases.
N.B. Sometimes, these options are not given, pick (measure capillary blood glucose) Obviously!
- Dx: (pH < 7.3) / ketonemia > 3 or ketonuria ++ / Glucose > 11 / Bicarb <15.
Hypokalemia + Hypertension --> Think of 1ry hyperaldosteronism (Conn’s syndrome).
* Think of Conn’s if: Hypertension + Hypokalemia OR Refractory hypertension despite 3 or more antihypertensive drugs OR Hypertension before the age of 40 years.
* Rx: give aldosterone antagonist (e.g. Spironolactone) before jumping to the surgery (Adrenalectomy).
* Conn’s: excess Aldosterone: Hypertension, Hypokalemia (might be normokalemia), normal Na+ or upper normal, headache, weakness + METABOLIC ALKALOSIS +/- Polyuria (due to aldosterone escape)
In Addison’s (low cortisol and aldosterone) --> Hyperkalemia, Hypotension and Metabolic Acidosis.
In Conn’s (high Aldosterone) --> Hypokalemia, Hypertension and Metabolic Alkalosis.
In PHEochromocytoma (high catecholamines) --> the first three letters (PHE) Palpitations, Headache, Hypertension, Flushing (sweating), Episodic.
Pre-op Management of DM type 2 (on hypoglycemics):
If major surgery: Stop oral hypoglycemic before surgery.
If minor surgery: Continue the same routine.
Pre-op Management of DM type1 (on Insulin):
If major surgery: Start sliding scale IV insulin before surgery and continue until per-mouth diet is re-established.
If minor surgery: Omit insulin on the day of the surgery.
In all cases, restart the previous regimen when per mouth diet is re-established + Check Blood glucose 4 hourly.
Diagnosis of DM:
DM Symptoms (polyuria, polydipsia, Unexplained weight loss in DM 1) + One abnormal value. (OR):
Two Abnormal values without symptoms.
Abnormal values: FBG >= 7 mmol/L (OR) Hb1Ac >= 48 mmol/mol (>= 6.5%)
Pre-diabetes (Impaired Glucose Tolerance):
Fasting: 5.5-6.9 II 2-hour Post-Prandial: 7.8-11 II HbA1c: 42-47
Note: OGTT (Oral Glucose Tolerance Test) is the diagnostic test for gestational DM.
If a patient presents with polyuria, polydipsia, +ve glucose in urine --> measure FASTING Blood Glucose, NOT RANDOM.
* Alcohol can cause hypoglycemia (confusion, unable to speak, impaired GCS or even coma) à Check Blood glucose.
* Remember, the causes of hypoglycemia (Glucose<4):
- Drugs: sulphonylureas, excess paracetamol, aspirin,
- Alcohol intoxication,
- Liver failure (impaired gluconeogenesis),
- Addison’s disease (hypoglycemia due to low cortisol, hypotension, hyponatremia, hyperkalemia and Metabolic acidosis)
MODY (Maturity Onset Diabetes in the Young).
DM< 25 Y/O
Strong Family History (2 generations)
No need for insulin initially. Responds to Sulphonylureas.
Addison’s (Low Cortisol, Low Aldosterone) electrolytes: Low Na+, High K+
Remember: In Addison’s disease (1ry adrenal insufficiency), all are hypo except potassium: Hyponatremia, hypoglycemia, hypotension (Dizziness) + HYPERKALEMIA + N, V, Abd pain.
Another hyper is tanned skin (Hyperpigmentation) but it is only seen in 1ry not 2ry adrenal insufficiency.
High ACTH --> Hyperpigmentation
Low cortisol --> Hypoglycemia and arterial hypotension
Low Aldosterone --> Hyponatremia and Hyperkalemia
High K+ --> High H+ --> Metabolic Acidosis
Cushing syndrome Investigations.
The outpatient screening test --> 24 hours urinary free cortisol.
The best initial test to establish the Dx --> 1 mg Overnight Dexamethasone suppression test.
To localise the lesion (to differentiate between pituitary adenoma and ectopic source --> High dose dexamethasone suppression test.
Vomiting --> Metabolic Alkalosis
(due to the loss of H+ "the gastric hydrochloric acid" in the vomitus) --> body will keep CO2 "which is acid" to compensate (by hypoventilation) --> High pH, High PCO2
Hyperkalemia 2ry to Acute Kidney Injury (low eGFR) with ECG changes: Tall Tented T-wave and Widened QRS --> Protect the cardiac membrane before doing anything else by govong IV Calcium Gluconate or IV Calcium Chloride + Cardiac monitoring (as there are ECG changes and the Hyperkalemia is moderate (6.0-6.4).
The first thing to do in a patient with deep painless heel ulcer, polydipsia, polyuria, Wt loss, fatigue --> Measure blood sugar (As these are features of DM).
Stress Hyperglycemia: occurs in some diseases (e.g. Pneumonia, MI, Stroke) or post-op and resolves soon.
Understanding glucose levels
Severe post-op hyperkalemia (Could occur due to acute kidney injury 2ry to HF). Say that the K+ is >6.4 --> we need to push it intracellularly quickly as this may lead to life-threatening arrhythmia --> Give 10 units insulin in 50 ml of 50% glucose IV infusion over 30 minutes.
(N.B. if calcium gluconate is in the options, give it first to protect the heart)!
* Remember: crackles at lungs, sacral oedema --> think of Heart Failure (Do not give IV fluid)! He is already overloaded!
* Remember: Insulin with Glucose will move K+ inside the cells temporarily (for 2-6 hours). Therefore, IV Normal Saline needs to be given (if not overloaded patient!) if well hydrated, start or increase the dose of loop diuretics (Furosemide) OR give Calcium Resonium.
N.B. In Acute Renal failure + Anuria + severe Hyperkalemia (especially if >=7.5) --> Hemodialysis.
Breast cancer --> bone metastasis --> hypercalcemia (Drowsiness and increased thirst)
N.B. Fluoxetine like all other SSRI (for depression) can cause Hyponatremia; however, excessive thirst presents with hypercalcemia, not with hyponatremia.
So, in a patient with Hx of breast cancer and presents with increased thirst --> Think of hypercalcemia (due to bone metastasis).
Addison’s disease: low Na+ but high K+.
Remember, in Addison’s (high ACTH, low cortisol, low aldosterone): HypOnatremia, HypOglycemia, HypOtension, HypeRkalemia + Metabolic acidosis, N, V, Abd pain. + Hyperpigmented skin.
Cushing’s disease is not the same as Cushing’s syndrome.
In Cushing disease (e.g. pituitary adenoma), excess ACTH is released from the pituitary and travels to BOTH adrenal glands making them secrete large amounts of cortisol. So, Bilateral (NOT UNILATERAL) adrenal hyperplasia would occur.
Remember: in Cushing’s disease: ACTH is suppressed by low (Overnight) or high dose of dexamethasone.
Remember: Cushing patients have: hypertension that requires>2 antihypertensive agents, Truncal obesity, Hyperglycemia, moon face, striae, cardiac hypertrophy, osteoporosis…etc.
Cushing’s syndrome features.
Toxic nodular goitre.
A lump on the front of the neck moves on swallowing + manifestations of hyperthyroidism --> Think of Toxic nodular goitre.
Some S&S of hyperthyroidism:
Palpitations, tachycardia, intolerance to heat, wt loss (unintentional weight loss despite having a good appetite), restlessness, nervousness, sweating.
Panic attacks + Palpitations + Hypertension + Tremors --> Think of Pheochromocytoma
PHEochromocytoma: Palpitations, Headaches, Hypertension, Flushing, EPISODIC + Tremors and Anxiety.
It is a rare catecholamine-secreting tumours (adrenal).
10% bilateral, 10% malignant, 10% extra-adrenal, 10% familial, 10% without HTN.
Ix: 24-hour urine collection of metanephrines.
Surgical removal of the tumour is required, but 1-week pre-op, stabilize the Hypertension by alpha-blockers (phenoxybenzamine) followed by beta-blockers (propranolol).
Subacute thyroiditis (De Quervain’s Thyroiditis):
Tender (itis), no thyroid enlargement and negative thyroid Abs
Since Negative thyroid Antibodies --> it is Not (graves), and Not (Hashimoto).
Subacute thyroiditis usually follows URTI (Viral).
Initially: Hyperthyroidism (Hight T3 and T4, and low TSH, perspiration-sweating-, palpitations) followed by hypothyroidism.
Remember: in Graves (Hyper) and Hashimoto (Hypo) --> +ve thyroid Abs.
Rx: self-limited (NSAIDs) can be used. Also, Beta-Blockers (e.g. Propranolol) to control arrhythmia and palpitations.
Thyroid storm (Thyroid crisis) can be precipitated by an infection (e.g. chest pneumonia):
- ill patient with low GCS, palpitations, tremors, tachycardia, feeling warm --> (thyrotoxicosis)
+ Coughing, High temperature (chest infection)
+ AF on ECG 2ry to thyrotoxicosis.
What to give to manage palpitations? --> Beta-Blockers (Propranolol Oral or IV).
N.B. Commence broad-spectrum IV Antibiotics as well.
Eye signs of Grave’s disease, what to do?
--> TFT (Thyroid function tests are superior to Autoantibodies as we need to establish the diagnosis of hyperthyroidism before looking for its aetiology).