Endocrinology Flashcards
What is sick euthyroid syndrome?
The sick euthyroid syndrome often occurs in individuals suffering from a systemic illness such as a myocardial infarction. The condition usually resolves upon treatment and resolution of the underlying condition. TSH, thyroxine and T3 are low; in most cases, the TSH level is often within the normal range.
What are expected renin and aldosterone levels in Conns syndrome?
High plasma aldosterone with suppressed renin
What is the mechanism of sitagliptin?
It inhibits DDP-4 (dipeptidyl peptidase-4).
DDP-4 is an enzyme that breakdowns incretins such as GLP-1.
By increasing incretin levels, there is an enhanced insulin release, reduced glucagon secretion and improved blood glucose control
What is pseudohypoparathyroidism?
Rare and genetic condition that occurs when there is a failure of cell response to PTH. PTH is hence elevated but calcium is low and phosphate is raised.
There are also other physical signs shortened metacarpals (especially fourth and fifth), a round face, short stature, calcified basal ganglia, and a low IQ
What is the difference between pseudohypoparathyroidism and pseudopseudohypoparathyroidism?
Pseudohypoparathyroidism will present with raised PTH, low calcium and raised phosphate + other physical features
Pseudopseudohypoparathyroidism has the same physical features as above but a normal biochemistry
What test has replaced the oral glucose tolerance test for acromegaly?
Insulin-like growth factor 1 (IGF-1) measurement
How do the following diabetes drugs work?
SGLT-2 inhibitors
Biguanides
Sulfonylureas
GLP-1 mimetics
DPP-4 inhibitors
SGLT-2 inhibitors (e.g. canagliflozin, dapagliflozin and empagliflozin) - reversibly inhibit sodium-glucose co-transporter 2 (SGLT-2) in the renal proximal convoluted tubule to reduce glucose reabsorption and increase urinary glucose excretion.
Biguanides (e.g. metformin) - decrease gluconeogenesis in the liver and increase insulin sensitivity
Sulfonylureas (e.g. gliclazide) - increase insulin release from beta-cells in the pancreas
GLP-1 mimetics (e.g. exenatide) - mimic incretin which is usually released in the gastrointestinal tract, and has the effect of increasing insulin production
DPP-4 inhibitors (e.g. sitagliptin) - block the action of DPP-4, an enzyme which breaks down incretin
Which diabetes drugs is recommended for patients with CVD and heart failure?
SGLT-2 inhibitors
What is a common cause of impaired hypoglycaemia awareness in T1DM?
Neuropathy of autonomic nervous system
*Certain drugs like beta blockers also blunt awareness.
What is the preferred first-line imaging when presenting with a thyroid nodule?
USS
It can detect lesions as small as 2 mm and provides information on their dimensions, shape, and parenchymal changes. Sonographic criteria are used to classify thyroid nodules, ranging from U1 (benign) to U5 (malignant), which helps to determine the need for further investigations.
If you suspect malignacny, you can then perform other tests such as fine needle aspiration
What is the usual presentation of maturity onset diabetes of the young (MODY)?
They present with persistent, asymptomatic hyperglycaemia without the typical features of T1DM or T2DM
Unlike Type 1 diabetes, patients with MODY usually do not present with diabetic ketoacidosis except under severe stress conditions, and unlike Type 2 diabetes, they are often of normal weight and do not exhibit signs of insulin resistance.
Why is insulin not given in hyperosmolar hyperglycaemic states?
Usually fluid replacement is sufficient to normalise serum glucose and improve patient symptoms.
Giving insulin in hyperosmolar hyperglycaemic state may provoke sudden and dramatic fluid shift between compartments, which may result in central pontine myelinolysis.
What class of diabetes medication has proven cardiovascular benefits?
SGLT-2 inhibitor (e.g. dapagliflozin)
What would the tests results (ACTH and Cortisol) suggest if you performed a high dose dexamethasone suppression test?
- ACTH suppressed, Cortisol not suppressed
- ACTH suppressed, Cortisol suppressed
- ACTH not suppressed, Cortisol not suppressed
- Cushing’s syndrome due to other causes (e.g. adrenal adenomas) *
- Cushing’s disease (i.e. pituitary adenoma –> ACTH secretion)
- Ectopic ACTH secretion
*ACTH is suppressed in high dose dexamethasone test in Cushing’s syndrome because cortisol release is ACTH-independent.
How would you differentiate an adrenal adenoma from bilateral adrenal hyperplasia where both present with Cushing’s syndrome?
Adrenal vein sampling, where you can compare the aldosterone secretion
What are contraindications for prescribing metformin?
Patients at risk of lactic acidosis, including those with:
* diabetic ketoacidosis
* Estimated glomerular filtration rate (eGFR) less than 30 mL/minute/1.73 m2
* Risk of acute kidney injury, such as dehydration, prolonged fasting, severe infection, or shock
* Conditions that may cause tissue hypoxia, such as cardiac or respiratory failure, recent myocardial infarction, or shock
* Hepatic insufficiency, acute alcohol intoxication
What is the initial test to diagnose Cushing’s syndrome?
Low-dose (overnight) dexamethasone suppression test
Patients with Cushing’s syndrome do not have their morning cortisol spike suppressed
*You can also confirm Cushing’s with a 24 hr urinary free cortisol (two measurements are required) or bedtime salivary cortisol (two measurements are required)
What are the different thyroid cancers?
- Papillary (70%) - excellent prognosis
- Follicular (20%)
- Medullary (5%) - Cancer of parafollicular (C) cells, secrete calcitonin, part of MEN-2
- Anaplastic (1%) - Not responsive to treatment, can cause pressure symptoms
- Lymphoma (Rare) - Associated with Hashimoto’s thyroiditis
What is the distribution of diabetic neuropathy?
Sensory loss in a symmetrical ‘glove and stocking’ distribution, with the lower legs affected first
What are some causes of gynaecomastia?
- physiological: normal in puberty
- syndromes with androgen deficiency: Kallman’s, Klinefelter’s
- testicular failure: e.g. mumps
- liver disease
- testicular cancer e.g. seminoma secreting hCG
- ectopic tumour secretion
- hyperthyroidism
- haemodialysis
- drugs: see below
What drugs cause gynaecomastia?
- spironolactone (most common drug cause)
- cimetidine
- digoxin
- cannabis
- finasteride
- GnRH agonists e.g. goserelin, buserelin
- oestrogens, anabolic steroids
What are some side effects of thiazolidinediones (e.g. pioglitazone)?
- weight gain
- liver impairment
- fluid retention - heart failure + peripheral oedema
- bladder cancer
What is the ideal management of Grave’s disease?
- Symptomatic control - propanolol
- Anti-thyroid drugs (e.g. carbimazole, propylthiouracil)
- Radioiodine therapy
How is growth hormone administered and for what conditions?
It is given subcutaneously to:
* proven growth hormone deficiency
* Turner’s syndrome
* Prader-Willi syndrome
* chronic renal insufficiency before puberty
What are side effects of sulfonylureas?
Common:
* Hypoglycaemic events
* Weight gain - the glucose is stored as fat
Rare:
* Hyponatraemia secondary to SIADH
* Bone marrow suppression
* Hepatotoxicity (typically cholestatic)
* Peripheral neuropathy
What is liraglutide?
GLP-1 mimetic that can be given in obese patients (BMI >35) that are also pre-diabetic. It is given subcutaneously.
What electrolyte imbalance is seen in Cushing’s?
Hypokalaemic metabolic alkalosis
High cortisol –> sodium and water retention –> increased potassium excretion + increased hydrogen excretion
What is the treatment of phaeochromocytoma?
Surgery is the definitive management. The patient must first however be stabilized with medical management: alpha-blocker (e.g. phenoxybenzamine), given before abeta-blocker (e.g. propranolol)
What is Kallman’s syndrome?
X-linked recessive condition, causing failure of GnRH (gonadotropin-releasing hormone) secreting neurons migrating to the hypothalamus –> hypogonadotropic hypogonadism
It presents with delayed puberty and anosmia in a male, who are often average/ above average height. A hormone profile would show low testosterone with low (or inappropriately normal) luteinising hormone (LH) and follicle-stimulating hormone (FSH).
What is pseudo-Cushing’s?
Condition that mimics Cushing’s
Due to alcohol excess or severe depression
False positive dexamethasone suppression test or 24 hr urinary free cortisol
Insulin stress test may be used to differentiate
Would the following levels be raised or reduced in De Quervain’s thyroiditis?
T4
ESR
Uptake of iodine-131
T4: raised
ESR: raised
Uptake of iodine-13: reduced
What are precipitating factors for thyroid storms?
- Thyroid or non-thyroidal surgery
- Trauma
- Infection
- Acute iodine load e.g. CT contrast media
What is the management of thyroid storm?
- Symptomatic treatment e.g. paracetamol
- Treatment of underlying precipitating event
- Beta-blockers: typically IV propranolol
- Anti-thyroid drugs: e.g. methimazole or propylthiouracil
- Lugol’s iodine
- Dexamethasone - e.g. 4mg IV qds - blocks the conversion of T4 to T3
What is the medical treatment for patients with a parathyroid adenoma?
Calcimimetics such as cinacalcet. These mimic the action of calcium on tissues by allosteric activation of the calcium-sensing receptor –> increases the sensitivity of calcium receptors on parathyroid cells, reducing PTH levels and resulting in a decrease in serum calcium levels.
What are the mechanism of actions of:
* Metformin
* Sulfonylurea
* SGLT-2 Inhibitors (e.g. empagliflozin)
* Thiazolidinedione (e.g. pioglitazone)
* DPP-4 Inhibitors (gliptins)
* GLP-1 Mimetics (e.g. exenatide)
- Metformin - increase insulin sensitivity and decrease glucose production
- Sulfonylurea - stimulates insulin release from pancreas
- SGLT-2 Inhibitors - reduces reabsorption of glucose in proximal tubules
- Thiazolidinedione - increase insulin sensitivity and decrease glucose production
- DPP-4 Inhibitors & GLP-1 Mimetics - increase incretin activity (increase insulin secretion + inhibit glucagon production + slow absorption by the gastrointestinal tract)
Each one of the following is a feature of subacute thyroiditis, except:
- Good prognosis
- Increased iodine uptake on scan
- Painful goitre
- Hyperthyroidism
- Elevated ESR
Increased iodine uptake on scan
*In De Quervain’s thyroiditis there is globally reduced uptake of iodine-131 during thyroid scintigraphy
What is the clinical picture of subacute (De Quervain’s) thyroiditis?
Thyrotoxicosis with tender goitre
*Grave’s would usually not present with tender goitre
What should every person being treated with insuline have?
A glucagon kit for emergencies where the patient is not able to orally ingest a short-acting carbohydrate
What should you do when someone is experiencing gastrointestinal side effects of metformin (immediate release)?
Change them to modified release (which is taken once a day)
What is subclinical hypothyroidism?
TSH raised but T3, T4 normal + no obvious symptoms
Significance:
* risk of progressing to overt hypothyroidism is 2-5% per year (higher in men)
* risk increased by the presence of thyroid autoantibodies
What is the management of subclinical hypothyroidism?
If TSH is > 10mU/L and the free thyroxine level is within the normal range, consider offering levothyroxine if the TSH level is > 10 mU/L on 2 separate occasions 3 months apart.
If TSH is between 5.5 - 10mU/L and the free thyroxine level is within the normal range:
* if < 65 years consider offering a 6-month trial of levothyroxine if: the TSH level is 5.5 - 10mU/L on 2 separate occasions 3 months apart, and there are symptoms of hypothyroidism
* in older people >80, offer “watch and waiting”
* if asymptomatic, observe and repeat thyroid function in 6 months
What investigation is used to confirm Addison’s disease?
Short ACTH test
Plasma cortisol is measured before and 30 minutes after giving Synacthen 250ug IM
In which conditions can you see lower-than-expected levels of HbA1c?
*Due to reduced red blood cell lifespan
Sickle-cell anaemia
GP6D deficiency
Hereditary spherocytosis
Haemodialysis
In which conditions can you see higher-than-expected levels of HbA1c?
*Due to increased red blood cell lifespan
Vitamin B12/folic acid deficiency
Iron-deficiency anaemia
Splenectomy
What are the criteria for diagnosis of diabetes using plasma glucose?
If symptomatic:
* fasting glucose greater than or equal to 7.0 mmol/l
* random glucose greater than or equal to 11.1 mmol/l (or after 75g oral glucose tolerance test)
If asymptomatic:
* Same as above but must be demonstrated on two separate occasions
