Endocrinology Flashcards
Describe the aetiology of hyperthyroidism
Grave’s disease
Nodular thyroid disease
Iodine excess
Exogenous thyroid hormone
Thyroid carcinoma
Secondary causes:
-TSH secreting pituitary tumour
-Thyroid hormone resistance
Describe the pathophysiology of Grave’s disease
Autoimmune thyroiditis caused by the production of TSH receptor stimulating antibodies
These stimulate the thyroid to produce more T3/T4
Describe the presentation of hyperthyroidism
Heat intolerance and sweating
Hyperactivity/irritability/altered mood
Palpitations
Weight loss with increased appetite
Fatigue and weakness
Fine tremor
Muscle weakness and wasting
Pretibial myxoedema
Diffuse, symmetrical goitre
Hyperreflexia
Monorrhagia
AF
Palmar erythema
Sinus tachycardia
Eyelid retraction, peri-orbital oedema, proptosis (opthalmopathy)
Give the presentation of thyrotoxic storm
Marked fever
Seizures
Vomiting
Diarrhoea
Jaundice
Death
Give the management of thyrotoxic storm
Propranolol
Corticosteroids
Carbimazole (anti-thyroid)
Give the investigations for hyperthyroidism
TFTs:
-Primary: low TSH, high T3/T4
-Secondary: high TSH, high T3/T4
TSH receptor antibodies - diagnostic for Grave’s
Radionucleide scan (Tc-99m) - diffuse widespread uptake in Grave’s
Describe the management of hyperthyroidism
Propranolol - for symptoms
Carbimazole/propylthiouracil - anti-thyroid - decrease output of T3/T4
Block and replace: high dose carbimazole + levothyroxine
Subtotal thyroidectomy: once euthyroid
Describe the management of hyperthyroidism in pregnancy
First trimester - propylthiouracil
Second and third trimester - carbimazole
Monitor fetal heartbeat (carbimazole may have effect on fetus)
Describe the aetiology of a toxic multinodular goitre
Common in older women and associated with increased iodine uptake. Strong link with amiodarone (contains iodine)
Describe thyroiditis
Autoimmune destruction of the thyroid resulting in the release of the thyroxine within
Causes a brief thyrotoxicosis, followed by a transient period of hypothyroidism
Describe De Quervain’s Thyroiditis
AKA subacute thyroiditis
4 phases:
1. Painful goitre, hyperthyroidism
2. Euthyroid
3. Hypothyroidism
4. Normal thyroid structure and function
Investigation: reduced uptake of I-131
Management: self-limiting, aspirin and NSAIDs for pain
Give two causes of pituitary space occupying lesions
Prolactinoma
Craniopharyngioma
Describe the pathophysiology of hyperprolactinaemia
Prolactin mainly controlled by tonic inhibition by hypothalamic dopamine.
Prolactin acts to induce lactation but also has inhibitory effect on GnRH secretion and the action of LH.
Describe the presentation of hyperprolactinoma
Galactorrhoea
Oligo/amenorrhoea
Reduced libido
Gynaecomastia
Subfertility
Give the investigations for prolactinoma
Serum prolactin raised
MRI head - pituitary prolactinoma
Describe the management of prolactinoma
1st line: dopamine agonist (e.g. cabergoline/bromocriptine) - DO NOT USE ROPINIROLE, this is D2 selective and therefore mostly effective in Parkinson’s
2nd line: trans-sphenoidal surgery
Describe the pathophysiology of acromegaly
Excess growth hormone, usually due to a GH secreting pituitary adenoma
Describe the presentation of acromegaly
Prominent supraorbital ridge
Large tongue
Spade-like hands and feet
Tall stature
Menstrual irregularities
Galactorrhoea
Visual field defects (due to pituitary adenoma compressing optic chiasm)
Describe the investigations for acromegaly
Insulin-like growth factor-1 (IGF-1) levels + OGTT (if GH not suppressed by glucose then diagnose acromegaly)
MRI head
Pituitary function testing
Describe the management of acromegaly
1st line: trans-sphenoidal surgery + radiotherapy
2nd line: somatostatin analogue (e.g. octreotide) +/- dopamine agonist
3rd line: GH antagonist (e.g. pegvisomant)
Why is OGTT used in the diagnosis of acromegaly?
GH is suppressed by hyperglycaemia, but would not be suppressed by hyperglycaemia in acromegaly due to the underlying pituitary adenoma
Why are dopamine agonists used in the management of acromegaly?
Dopamine inhibits GH secretion
Describe Cushing’s syndrome
Clinical state of increased free-circulating glucocorticoid
Describe the aetiology of Cushing’s syndrome
Exogenous use (most common)
ACTH-producing pituitary tumour (Cushing’s disease)
Adrenal adenoma
Describe the presentation of Cushing’s syndrome
“Moon face”
Buffalo hump
Central obesity
Proximal muscle wasting
Abdominal striae
Describe the pathophysiology of Cushing’s disease
ACTH hypersecretion from the anterior pituitary resulting in excess glucocorticoid (cortisol) production (usually due to pituitary tumour)
Describe the presentation of Cushing’s disease
Cushing’s syndrome:
-“Moon face”
-Buffalo hump
-Central obesity
-Proximal muscle wasting
-Abdominal striae
Describe the investigations for Cushing’s disease
Aim to demonstrate inappropriate cortisol secretion which is not suppressed by exogenous steroids
48 hour low-dose dexamethasone suppression test (gold standard)
24 hour urinary cortisol/ACTH levels
Adrenal/pituitary MRI
Describe the management of Cushing’s disease
TSS - MUST CONTROL CORTISOL FIRST (usually with metyrapone)
Bilateral adrenalectomy (if treatment resistant)
How does metyrapone work?
It is an 11-beta-hydroxylase inhibitor
11-beta-hydroxylase normally acts to convert 11-deoxycortisol to cortisol
Define Nelson’s syndrome
Formation of an ACTH-secreting pituitary adenoma following bilateral adrenalectomy
Describe the management of Nelson’s syndrome
TSS with prior cortisol control
Describe the pathophysiology of pituitary apoplexy
Rapid loss of pituitary function due to a bleed into the gland or an impaired vascular supply
Vascular impairment may occur as a result of a rapidly expanding tumour or a massive haemorrhage in childbirth (Sheehan’s syndrome)
Describe the presentation and management of pituitary apoplexy
Severe headache, double-vision and visual field restriction
Management: hormone replacement
Describe empty-sella syndrome
All or most of the sella is devoid of pituitary tissue
Gland is normally flattened against the fossa wall and has normal function
Usually diagnosed incidentally but may be a sign of raised ICP
Describe the aetiology of primary hyperparathyroidism
Solitary adenoma
Parathyroid hyperplasia
Carcinoma
Describe the investigations for primary hyperparathyroidism
Raised serum calcium
Low serum phosphate
Raised PTH (may be inappropriately normal)
Hand and skull XR - osteolysis in phalanges and “pepper-pot” skull
Describe the presentation of hyperparathyroidism
Classically elderly lady with an unquenchable thirst and a raised PTH
Describe the management of primary hyperparathyroidism
Total parathyroidectomy - GOLD STANDARD
Cinacalcet (calcium mimetic) v- reduced PTH secretion
Why does primary hyperparathyroidism present with unquenchable thirst?
Causes a reversible nephrogenic diabetes insipidus due to degredation of aquaporin-2 channels, leading to dehydration
Describe the pathophysiology of secondary hyperparathyroidism
Physiological compensatory hypertrophy of the parathyroid glands in response to hypocalcaemia
Describe the aetiology of secondary hyperparathyroidism
CKD and vit. D deficiency
Failing kidneys do not convert enough Vit. D to it’s active metabolite or excrete enough phosphate
This results in the formation of insoluble CaPO4 - removing calcium from the circulation
PTH therefore rises but calcium remains low
Describe the management of secondary hyperparathyroidism
Treat underlying cause, reduce dietary phosphate, Vit. D supplementation
Describe the pathophysiology of tertiary hyperparathyroidism
Autonomous increased release of PTH whilst in a hypercalcaemic state following longstanding secondary hyperparathyroidism - common in CKD
Describe the management of tertiary hyperpararthyroidism
Parathyroidectomy
Would see raised calcium and phosphate on bloods
Describe the pathophysiology of hungry bone syndrome
High pre-op PTH provides constant osteoclast stimulation
This creates a constant hypercalcaemic state due to bone demineralisation
Parathyroidectomy causes sudden drop in PTH and osteoclast activity subsequently diminishes quickly.
Bones rapidly remineralise with rapid depletion of serum calcium phosphate stores
Describe the management of hungry bone syndrome
Calcium supplementation and PTH replacement
Describe the pathophysiology and management of primary hypoparathyroidism
Decreased PTH secretion resulting in a low calcium and high phosphate
Management: alfacalcidol
Describe the pathophysiology and presentation of pseudo-hypoparathyroidism
End-organ resistance to PTH due to mutation in PTH-G gene
Presentation:
-Low IQ
-Short stature
-Shortened 4th/5th metacarpals
-Low calcium, high phosphate
Describe the investigations and anagement for pseudo-hypoparathyroidism
cAMP and phosphate levels following PTH infusion - in hypoparathyroidism they would both increase
Management: calcium/vit. D supplementation
Describe the hormones produced by the adrenal cortex
Steroid hormones! (mineralocorticoids, glucocorticoids, androgens)
Zona glomerulosa: aldosterone (m)
Zona fasciculata: cortisol (g)
Zona reticularis: androstenedione
Describe the hormones produced by the adrenal medulla
Adrenaline!
Describe the pathophysiology of Addison’s disease
Primary hypoadrenalism with destruction of the entire adrenal cortex, resulting in reduced steroid hormone production
Reduced cortisol drives increased CRH and ACTH
Describe the aetiology of Addison’s disease
Autoimmune
Describe the presentation of Addison’s disease
Addisonian adrenal destruction works from outside in:
First: zona glomerulosa - low aldosterone - hypotension, hyponatraemia, hyperkalaemia, salt craving
Second: zona fasciculata - low cortisol - tiredness, immunocompromised, hypermigmented, abdo pain
Third: zona reticularis - low androgen - reduced libido, loss of pubic/axillary hair
Describe the investigations for Addison’s disease
Short synacthen test - stimulates adrenal glands to produce cortisol and tests how they respond
Describe the management of Addison’s disease
Steroid replacement: PO hydrocortisone
In extreme exercise or if ill, double dose!
Describe the pathophysiology of congenital adrenal hyperplasia
Autosomal recessive deficiency of 21-hydroxylase (normally in cortisol synthesis pathway) causing an increased testosterone
Leads to reduced cortisol and subsequently increased ACTH - hyperstimulating the adrenals and causing hyperplasia
Describe the presentation of congenital adrenal hyperplasia
Sexual ambiguity
Adrenal failure
Hirsutism
Describe the investigations for congenital adrenal hyperplasia
Adrenocortical profile before and after ACTH administration
Describe the management of congenital adrenal hyperplasia
Steroid replacement
Describe the pathophysiology of primary hyperaldosteronism
5-10% of cases of HTN
Disorder of the adrenal cortex leading to excessive aldosterone production, commonly due to bilateral adrenal hyperplasia
Causes sodium retention, hypertension and hypokalaemia
Describe the pathophysiology of Conn’s syndrome
Adrenal adenoma causing a primary hyperaldosteronism - presents as HTN +/- hypokalaemia
Describe the pathophysiology of secondary hyperaldosteronism
Renal artery stenosis causing renin excess
Describe the investigations for primary hyperaldosteronism
Aldosterone:renin - shows high aldosterone and low renin
CT abdo
Adrenal vein sampling
Describe the management of primary hyperaldosteronism
Adenoma –> surgical resection
Hyperplasia –> aldosterone receptor blocker (e.g. spironolactone). If not tolerated may use CCB to control HTN (do not use ACEi, ARB or beta blocker)
How does renal artery stenosis cause increased renin secretion?
Causes reduced renal perfusion, stimulating juxtaglomerular cells to release renin.
They are “tricked” into thinking the BP is low
Why can ACEi and ARBs not be used in the management of hyperaldosteronism?
Block constriction of efferent glomerular vessels - those with renal artery stenosis rely on this to maintain GFR.
Describe the diagnostic criteria for DKA
Glucose > 11
pH < 7.3
Bicarb < 15
Ketones > 3 (or urine ketones ++)
Describe the causes of DKA
Infection
MI
Missed insulin doses
Describe the presentation of DKA
Abdo pain
Thirst, polyuria, dehydration
Kussmaul respiration - fast, deep breaths in an attempt to blow off CO2
Ketotic breath (pear drops)
Describe the management of DKA
FLUIDS - normal saline regime. If hypotensive give 500ml boluses first
INSULIN - fixed rate IV insulin 0.1 units/kg/hr, plus K+!
Define the resolution criteria for DKA
pH > 7.3
Ketones < 0.6 AND bicarb > 15
Should resolve within 24 hours
Describe the aetiology of thyroid storm
Stress
Infection
Surgery
Describe the presentation of thyroid storm
Rapid deterioration in hyperthyroidism
Hyperpyrexia
Severe tachycardia
Restlessness
Cardiac failure
Liver dysfunction
Describe the management of thyroid storm
IV propranolol - controls HR and failure
Carbimazole - anti-thyroid
Potassium iodide
Corticosteroids (e.g. hydrocortisone)
Describe thyrotoxic cardiomyopathy
Ischaemic changes on ECG
Resolves completely once the patient is euthyroid
Describe the pathophysiology of Addisonian crisis
Severe hypotension and dehydration caused by illness or trauma
Hypovolaemic shock
Vomiting
Fever
Abdo pain
Give the management of Addisonian crisis
IV hydrocortisone
IV fluids
Describe myxoedema
Accumulation of mucopolysaccharides in the SC tissue
Describe myxoedema coma
Seen in hypothyroidism
Extreme version of myxoedema in which patients have hypothermia, cardiac failure, hypoventilation, hyponatraemia, hypoglycaemia, psychosis
Describe the management of myxoedema coma
IV levothyroxine
IV hydrocortisone
Describe the aetiology of hypercalcaemia
Most commonly in palliative care!
Hyperparathyroidism or bone mets
Describe the presentation of hypercalcaemia
“Stones, bones, groans and psychic moans”:
Renal stones
Bone pain
Abdo pain
Depression
Polydipsia, polyuria, dehydration, pancreatitis
Describe the management of hypercalcaemia
IV fluids and bisphosphonates
Treat underlying cause
Give 1 important side effect of carbimazole
Agranulocytosis
What is the minimum HbA1c for diagnosis of T2DM
48
Give 1 condition which cause gynaecomastia
Goserelin - GnRH agonist used in the management of prostate cancer
What is the most common thyroid cancer?
Papillary (70%) - seen in young females and has excellent prognosis
What is the second most common thyroid cancer?
Follicular
What is the management of thyroid cancer?
total thyroidectomy
followed by radioiodine (I-131) to kill residual cells
yearly thyroglobulin levels to detect early recurrent disease
Which drug may cause psychosis?
Steroids
Describe the aetiology of hypothyroidism
Primary:
-Autoimmune - e.g. Hashimoto’s thyroiditis, atrophic thyroiditis
-Congenital
-Iodine deficiency
Secondary:
-Hypopituitarism
-Post-surgery
Describe the epidemiology of hypothyroidism
Much more common in women
Mean age of onset = 60
Classically middle aged women
Which hormone is released by the hypothalamus which forms a part of the hypothalamic-pituitary-axis?
Thyrotropin releasing hormone
Which hormone is released by the anterior pituitary which forms a part of the hypothalamic-pituitary-axis?
Thyroid stimulating hormone
Which hormone is released by the thyroid which forms a part of the hypothalamic-pituitary-axis?
T3 and T4
(only 25% of circulating \T3 is produced by the thyroid, the rest is produced from T4 in peripheral tissues)
Describe the pathophysiology of primary hypothyroidism
Thyroid unable to produce sufficient T3/T4 despite a high TSH
Describe the pathophysiology of secondary hypothyroidism
Insufficient TSH produced by the anterior pituitary, so the thyroid produced less T3/T4
OR
Thyroid has been removed/damaged during surgery
Describe the pathophysiology of atrophic thyroiditis
T-cell mediated auto-reactive cytotoxicity to follicular cells
DOES NOT PRODUCE A GOITRE!
Describe the pathophysiology of Hashimoto’s thyroiditis
Autoimmune hypothyroidism
Thyroid attacked by T-cells resulting in lymphocyte infiltration and fibrosis - resulting in a GOITRE
Very high levels of thyroid peroxidase antibodies, resulting in insufficient iodide for T3/T4 production
May be initial transient hyperthyroidism followed by period of hypothyroidism
Describe the pathophysiology of post-partum thyroiditis
May involve hypo- or hyper-thyroid pathology
Usually seen transiently after pregnancy
B-HCG acts on TSH receptors, including to induce the production of more T3/T4, resulting in hyperthyroidism
Usually self-limiting
Describe myxoedema
Skin and tissue disorder associated with hypothyroidism
Skin and subcutaneous tissue thickening due to accumulation of mucopolysaccharides in the subcutaneous tissue, resulting in a “coarse” appearance
Describe the presentation of hypothyroidism
Puffy eyes
Dry skin
Overweight
Dry, brittle, unmanageable hair
Thin hair, loss of eyebrows
Deep voice
Goitre (Hashimoto’s)
Pretibial myxoedema
Cold intolerance
Fatigue/tiredness/malaise/headache
Poor memory/slow thoughts/depression
Bradycardia/peripheral oedema/hypertension/decreased exercise tolerance
Poor libido/infertility/oligomenorrhoea/menorrhagia
Describe the TFT results in primary hypothyroidism
High TSH
Low T4
Describe the TFT results in subclinical hypothyroidism
High TSH
Normal T4
Describe the TFT results in secondary hypothyroidism
Normal/low TSH
Low T4
Describe the TFT results in primary hyperthyroidism
Low TSH
High T4
Describe the TFT results in subclinical hyperthyroidism
Low TSH
Normal T4
Describe the confirmatory investigation for autoimmune hypothyroidism
TPO antibodies
(also do FBC due to risk of B12 deficiency of autoimmune cause, e.g. pernicious anaemia, atrophic gastritis)
Give the management of hypothyroidism
Levothyroxine - oral T4 supplementation
Give the management of hypothyroidism in pregnancy
Levothyroxine - if already taking then increase dose by 25%
Low TSH in mother can lead to cognitive impairment in the child
Describe the management of depression in hypothyroidism
Levothyroxine! Depression will usually resolve within a few weeks of starting levothyroxine
What ABG findings are seen in Addisonian crisis?
hyperkalaemic metabolic acidosis
Describe the TFT findings in sick euthyroid syndrome
In sick euthyroid syndrome it is often said that everything (TSH, thyroxine and T3) is low. In the majority of cases however the TSH level is within the normal range (inappropriately normal given the low thyroxine and T3).
Sick euthyroid is where there are decreased values but no underlying pathology - associated with stress (e.g. acute illness)
What can result in a falsely high HbA1c?
Splenectomy
