Data interp. - Endo Flashcards
Spot diagnosis
Grave’s disease - the autoimmune condition causes the entire thyroid gland to be stimulated to actively take up iodine, resulting in a widespread increase in iodine uptake throughout the gland
Spot diagnosis
Toxic multinodular goitre - because these are regions of hyperfunctioning thyroid tissue within the gland, meaning only specific nodules or areas are actively producing excess thyroid hormone
- NOTE: can also be seen in hyperfunctioning adenomas (toxic adenoma)
Spot diagnosis
Thyroid cancers (abnormally low uptake) - cancerous cells do not actively take up iodine like normal thyroid tissue does
Spot diagnosis
Graves disease - diffuse uptake
Spot diagnosis
Normal thyroid gland
Spot diagnosis
Thyroiditis - inflamed thyroid gland is not actively taking up iodine, resulting in a low uptake across the entire gland because the inflammatory process disrupts the normal function of thyroid cells needed to absorb iodine
Spot diagnosis
Cold nodule - adenomas OR cancer
(most adenomas do not actively produce thyroid hormone and therefore do not readily absorb the radioactive iodine so appear as cold spots)
Spot diagnosis
Hot nodule - toxic adenoma
Spot diagnosis
Toxic multinodular goitre
TFTs - which hormones are measured to assess thyroid function?
- TSH and free T4 (fT4)
(fT3 is also measured but is less relevant as the thyroid releases T4 and T3 at a ratio of about 20:1 respectively, with T3 mainly being produced by peripheral conversion of T4)
How long would you have to wait to repeat TFTs if you are monitoring the impact of an intervention (eg. increasing a pt’s levothyroxine dose)?
several weeks - T4 has a half-life of about one week
Primary hypothyroidism location of pathology
Pathology affecting the thyroid gland itself - decreases the thyroid’s ability to release T4 and T3 or respond to TSH
Primary hypothyroidism TFTs and why
- TSH:
- T4:
- TSH: High
- T4: Low
.
1. Less T4 and T3 are produced due to thyroid’s reduced capacity to produce hormone or respond to TSH
2. As a result, there is reduced negative feedback on the pituitary and hypothalamus
3. The reduction in negative feedback results in increased production of TRH (which we don’t typically measure) and TSH
4. The end result is low T4 and T3, and a raised TSH
What is subclinical hypothyroidism?
condition where TSH levels are slightly elevated, but levels of free thyroxine (fT4) are normal
- causes mild symptoms
Causes of primary hypothyroidism
- Hashimoto’s thyroiditis (autoimmune thyroiditis) - 50%
(associated with anti-TPO and anti-Tg antibodies) - Iodine deficiency (developing world)
- Treatments of hyperthyroidism - carbimazole, propylthiouracil, radioactive iodine, thyroidectomy
Secondary hypothyroidism TFTs and why
- TSH:
- T4:
- TSH: Low
- T4: Low
.
1. Decreased production or secretion of TSH results in decreased stimulation of the thyroid gland.
2. The thyroid gland, therefore, produces less T3 and T4.
3. The low T3 and T4 would normally stimulate the pituitary gland to increase TSH production, however, they are unable to increase production.
4. The end result is low T4 and T3 and a normal/low TSH.
Causes of secondary hypothyroidism
- Pituitary adenoma: the most common cause.
- Pituitary surgery or radiotherapy which damages the pituitary tissue
- Sheehan’s syndrome (post-partum haemorrhage causes avascular necrosis of the pituitary gland)
Management of hypothyroidism (primary and secondary)
Oral levothyroxine - levothyroxine is a synthetic version of T4 and metabolises to T3 in the body
Primary VS Secondary hyperthyroidism - location of pathology
- Primary - excessive production of T3 and T4 by thyroid gland itself
- Secondary - excessive production of TSH by pituitary gland (or ectopic cause)
Primary hyperthyroidism TFTs and why?
- TSH
- T4
- TSH: Low
- T4: High
.
1. The thyroid produces excessive amounts of T4 and T3
2. The excessive T4 and T3 cause negative feedback on the pituitary and hypothalamus, resulting in decreased production of TRH and TSH
3. The end result is a raised T3 and T4 and a low TSH
Causes of primary hyperthyroidism
- Graves’ disease (75% of cases) - TSH receptor antibodies, produced by the immune system, stimulateTSH receptorson the thyroid
- Toxic multinodular goitre
- Toxic adenoma
Management of primary hyperthyroidism
- Carbimazole (or propylthiouracil in pregnancy)
- Propranolol (symptomatic relief)
- Radioactive iodine (definitive)
- Thyroidectomy
What is subclinical hyperthyroidism?
When TSH is low, but T4 (and T3) are normal
- causes mild symptoms
Secondary hyperthyroidism TFTs and why?
- TSH
- T4/T3
- TSH: High
- T4/T3: High
.
1. TSH production is increased by either the pituitary/hypothalamus or another source (known as ectopic production).
2. The excess TSH causes overstimulation of the thyroid gland, resulting in high levels of T3 and T4 production.
3. Normally a raised T3 and T4 level would cause negative feedback, decreasing TSH production, however, in this instance, the TSH production is not responsive to any negative feedback, resulting in continued excess production.
Main cause of secondary hyperthyroidism
TSH-secreting pituitary adenoma
Management of secondary hyperthyroidism (think about the main cause and how that would be treated)
Pituitary surgery often required to remove the TSH-secreting adenoma
note: Primary adrenal insufficiency is Addison’s disease
Why is a morning serum cortisol taken?
cortisol is at its highest in the morning 8/9am)
Explain how the ACTH stimulation test (Synacthen test) works and how it can diagnose Addison’s disease
ACTH stimulation test (Synacthen test) - exogenous ACTH is given to pt before measuring their cortisol lvls
- if cortisol lvls remain low - indicates that adrenal cortex is unresponsive to stimulation (diagnosis of Addison’s disease)
- if cortisol lvls increase to above normal range - this excludes diagnosis of Addison’s disease
.
(take baseline cortisol, then 30 mins after, then 60 mins after - should double)
Management of adrenal insufficiency
Oral hydrocortisone and fludrocortisone- to replace glucocorticoids and mineralocorticoids respectively
Adrenal insufficiency - sick day rules + steroid card
- mild stressors
- severe stressors
- Mild stress (illness) - double hydrocortisone (glucocorticoid dose) until recovery
(continue fludrocortisone (mineralocorticoid dose) at usual dose)
. - Severe stressors (acute illness or major trauma) - IV hydrocortisone +/- IV fluids, followed by continuous hydrocortisone treatment for 24hrs
(pts must carry a steroid card and keep an emergency supply of IM hydrocortisone)
Management of an Addisonian crisis (acute, severe presentation of Addison’s disease)
IV hydrocortisone + IV fluids
Main complication of treatment for adrenal insufficiency (eg. Addison’s disease)?
Cushing’s syndrome secondary to exogenous steroids
Causes of Cushing’s syndrome
- Exogenous glucocorticoids (eg. prednisolone, hydrocortisone) - most common
.
Endogenous- Pituitary adenomas (Cushing’s disease) - corticotropin-dependent
- Ectopic production of corticotropin (eg. small cell lung cancer) - corticotropin-dependent
- Adrenal adenomas and adrenal carcinomas - corticotropin-independent
Cushing’s syndrome VS Cushing’s disease
- Cushing’s syndrome is a general condition that results from too much cortisol in the body
- Cushing’s disease is a specific type of Cushing’s syndrome, caused by a tumour in the pituitary gland
- Cushing’s disease (pituitary adenoma) shows suppression on high-dose dexamethasone, as the pituitary still has some feedback sensitivity
(Plasma ACTH is slightly high due to the same reason of feedback sensitivity) - Adrenal causes (adenoma/carcinoma) and exogenous steroid use both have low ACTH due to negative feedback inhibition
Explain the low-dose dexamethasone suppression test
- Give 1 mg oral dexamethasone at 11 pm, then measure serum cortisol at 9am the following morning
- Normal result - cortisol suppression (< 50)
- Failure to suppress - suggests Cushing’s syndrome (need to do further tests)
Explain the high-dose dexamethasone suppression test
- Give 8mg oral dexamethasone at 11pm, then measure serum cortisol and plasma ACTH at 9am the following morning
. - < 50% suppression - Cushing’s disease (pituitary adenoma producing ACTH)
(pituitary adenomas retain some feedback sensitivity to glucocorticoids, so high-dose dexamethasone suppresses ACTH production) - No suppression (cortisol still high) - suggests ectopic ACTH syndrome (eg. small cell lung cancer) or adrenal Cushing’s
(ectopic ACTH-producing tumours lack feedback inhibition, so cortisol remains high)
Management of Cushing’s syndrome
- Exogenous
- Pituitary tumour
- adrenal tumour
- Exogenous Cushing’s - review pt’s current glucocorticoid treatments and reduce doses where possible (often with steroid-sparing immunosuppressive agents)
- Pituitary tumours - trans-sphenoidal surgery +/- radiotherapy
- Adrenal tumours - surgical removal (laparoscopic excision)
(Note: if you remove both adrenal glands you have to give replacement steroid hormones for life)
What test is used as a screening test for primary hyperaldosteronism?
aldosterone-to-renin ratio(ARR) - blood test
Management of hyperaldosteronism
Management:
- Eplerenone
- Spironolactone
.
Treatment of underlying cause:
- Surgical removalof theadrenaladenoma
- Percutaneous renal artery angioplastyvia the femoral artery to treatrenal artery stenosis
What is a phaeochromocytoma + what is it associated with?
Adrenal tumour causing excessive amounts of catecholamines (adrenaline)
- associated with MEN 2
Investigations for a phaeochromocytoma
- Plasma-free metanephrines (breakdown product of adrenaline) - longer half-life therefore more stable lvls —> more reliable
- 24-hour urine catecholamines - gives idea of how much adrenaline is being secreted by the tumour over 24hrs
.
(measuring serum catecholamine (adrenaline) level is unreliable as lvls fluctuate and have very short half-life - 1 minute)
Management of a phaeochromocytoma
- Alpha-blockers (eg. phenoxybenzamine or doxazosin)
(Beta-blockers - once established on alpha-blockers) - Surgical removal of tumour - adrenalectomy
Main cause of acromegaly
- excessive GH produced in theanterior pituitary gland (most commonly occurs secondary to apituitary adenoma)
.
(rare cause of acromegaly - secondary to cancer (paraneoplastic) that secretes ectopic GNRH or GH)
Visual field defect seen in pituitary gland tumours
bitemporal hemianopia (sits close to optic chiasm)
Investigations in acromegaly
- Serum IGF-1: raised because GH increases glucose lvls
.
Growth hormone suppression test (OGTT): - pt consumes a 75g glucose drink with GH tested at baseline and 2hrs following the drink
- the glucose should suppress the GH lvl - failure to suppress GH indicates acromegaly
.
(further investigations - visual fields, MRI of pituitary)
Management of acromegaly
Surgical:
- Pituitary tumour - trans-sphenoidal surgery
- Other tumour (ectopic) - surgical removal
.
Medical:
- Pegvisomant - GH receptor antagonist
- octreotide - somatostatin analogue (blocks GH release)
- bromocriptine - dopamine agonists (blocks GH release)
Young women with fertility issues or irregular menstruation, what condition should you suspect
hyperprolactinaemia
Where is prolactin secreted?
Prolactin is secreted by lactotroph cells in theanterior pituitary gland
Causes of hyperprolactinaemia
- Physiological - stress, pregnancy, lactation, exercise
- Drug-related - antipsychotics, antidepressants, and certain antiemetics (domperidone, metoclopramide)
- Pathological - prolactinomas are tumours originating from lactotroph cells of the ant. pituitary gland
(microprolactinomas: <10mm, macroprolactinomas: >10mm)
Investigations in hyperprolactinaemia
- Serum prolactin: raised (diagnostic)
- Pregnancy test: to exclude pregnancy (common cause of hyperprolactinaemia)
Management of hyperprolactinaemia
- address underlying cause
- Prolactinomas - dopamine agonists 1st-line (cabergoline, bromocriptine)
Secondary:
- reduced calcium absorption form the intestines, kidneys, and bones —> resulting in hypocalcemia (low blood calcium)
- parathyroid glandsreact to thelow serum calciumby excretingmore PTH
- serum calcium levelwill below or normal,but theparathyroid hormonewill behigh
Explain tertiary hyperparathyroidism
occurs when secondary hyperparathyroidism continues for an extended time, leads to hyperplasia of the parathyroid glands as they adapt to producing a higher lvl of PTH
- Then, when underlying cause of secondary hyperparathyroidism is treated, the baseline PTH production remains inappropriately high
- This high PTH lvl leads to inappropriately high absorption fo calcium in the intestines, kidneys, and bones - causing hypercalcaemia
Type 1 diabetes VS Type 2 diabetes - pathophysiology
T1DM:
- Chronic autoimmune disease, causes immune-mediated destruction of insulin-producing pancreatic beta cells
- Results in an absolute insulin deficiency and subsequent hyperglycaemia
.
T2DM:
- Chronic metabolic disorder characterised by insulin resistance and impaired insulin secretion, leading to hyperglycaemia
- Multifactorial aetiology - genetic, environmental (obesity, sedentary lifestyle, and poor diet), and other factors like age, ethnicity, and smoking
- Progressive pancreatic beta-cell dysfunction and insulin resistance in target tissues
T1DM symptoms
Presents in childhood/adolescence
- Polyuria / Polydipsia / Weight loss
- OR critically unwell with DKA
Investigations done for type 1 diabetes
Blood glucose testing (capillary blood glucose):
- Fasting plasma glucose: > 7.0 mmol/L
- Random plasma glucose: > 11.1 mmol/L
.
Glycated Hb (HbA1c) - overview of blood sugar lvls over past 2-3 months
- HbA1c ≥ 48 mmol/mol (6.5%) on two separate tests indicates diabetes
.
Urine dipstick - glucosuria and ketonuria are common findings
.
Autoantibody testing - can confirm diagnosis
- GAD antibodies
- Islet antibodies
.
C-peptide - co-released with insulin from beta cells in pancreas (direct measure of endogenous insulin production)
- low lvls + hyperglycaemia suggest T1DM - due to beta-cell destruction
Criteria for diagnosis of diabetes mellitus (WHO)
- Random plasma glucose
- Fasting plasma glucose
- OGTT (plasma glucose after 75g glucose oral load)
- HbA1c
- Random plasma glucose ≥ 11.1 mmol/L + symptoms of hyperglycaemia
OR - Fasting plasma glucose ≥ 7.0 mmol/L
OR - Plasma glucose lvl ≥ 11 mmol/L 2 hours after a 75g oral load (OGTT)
OR - HbA1c ≥ 48 mmol/mol (≥ 6.5%) - note HbA1c can be unreliable if pt has condition affecting RBC survival
Once diabetes mellitus has been diagnosed, how can we identify T1DM as the cause?
- Clinical history is important - age, symptoms, ketosis
- Autoantibodies - supports diagnosis
- C-peptide: low/undetectable
Management options for type 1 diabetes mellitus
- Monitor HbA1c every 3-6 months - aiming for ≤ 48 mmol/mol (≤ 6.5%)
.
Regular self-monitoring of blood glucose (eg. 4 times a day) - 5-7 mmol/l on waking
- 4-7 mmol/l rest of day
.
MDIs (basal-bolus) regimens - Basal (long-acting) - Determir BD OR Glargine OD
- Bolus (short-acting) - NovoRapid, Humalog, Apidra
. - Insulin pump therapy (continuous subcutaneous insulin infusion)
.
Hybrid closed-loop system (eg. artificial pancreas) - adjusts insulin delivery on real-time glucose levels
How is T2DM usually diagnosed?
Usually asymptomatic (”silent disease”) and is picked up on routine screening
note: if pt asymptomatic, then criteria must be met on 2 separate occasions
T2DM - impaired fasting glucose (IFG) VS impaired glucose tolerance (IGT)
- Impaired fasting glucose (IFG): fasting glucose ≥ 6.1 but < 7.0 mmol/l (ie. 6.1-6.9 mmol/l)
- Impaired glucose tolerance (IFT): fasting plasma glucose < 7.0 mmol/l and OGTT 2-hour value ≥ 7.8 mmol/l but less than 11.1 mmol/l
.
Diabetes UK say: ‘People with IFG should then be offered an oral glucose tolerance test to rule out a diagnosis of diabetes. A result below 11.1 mmol/l but above 7.8 mmol/l indicates that the person doesn’t have diabetes but does have IGT.’
Management of type 2 diabetes mellitus
- Lifestyle advice - lose weight (5-10% initially), healthy diet (high fibre, low glycaemic index carbs, low fat (saturated fats esp.)
In a patient with T2DM, when should a statin be offered?
only patients with a 10-year cardiovascular risk > 10% (using QRISK2)
What is gestational diabetes?
Glucose intolerance fist diagnosed in pregnancy (typically 2nd/3rd trimester), due to insulin resistance
Investigations for gestational diabetes
- which measure of blood glucose is not used?
(note: HbA1c not used!)
.
OGTT at 24-28 weeks
- 2-hour post-75g glucose ≥7.8 mmol/L
OR
- fasting glucose ≥5.6 mmol/L
Management of gestational diabetes
- Lifestyle - diet, exercise
- Metformin (1st-line)
- (Insulin if metformin ineffective or fasting glucose ≥ 7.0 mmol/l)
- screen for T2DM postpartum
